Medstar Pediatrics - 2nd Edition

CLINICAL GUIDE
AND SYNOPSIS
Prepared By
The graduating class of 2015 e.c (2022/23)
Jimma University, ethiopia.
MEDSTAR
Clinical guide and synopsis
2ND EDITION
PEDIATRICS
December, 2022
JIMMA, ETHIOPIA
PREFACE
Welcome to the 2nd edition of Medstar. We are proud to present this book to you as a
result of the hard work and dedication of our team.
As once clinical year students ourselves, we understand the challenges and obstacles
you will face in your studies. That is why we have worked tirelessly to compile a
comprehensive collection of knowledge and advice to help you navigate your clinical
year and beyond.
Our team has spent countless hours researching, writing, and reviewing the
information contained within these pages. We have drawn upon our own experiences,
as well as the expertise of our faculty and mentors, to provide you with a valuable
resource that will support you in your medical education and career.
We hope that this book will serve as a useful and practical guide for you as you
embark on your journey in the medical field. We wish you the best of luck in your
studies and in your future as a healthcare provider.
Your feedback and suggestions are welcome Email address:

MEDSTARcomment@gmail.com
The contributors
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EDITOR’S NOTE
We are pleased to present the 2nd edition of Medstar. This edition has been thoroughly
revised and updated to ensure that it reflects the latest advances in the field.
One of the major improvements in this edition is the organization of the content. We
have reorganized the chapters and sections to improve the flow and logical
progression of the material. We have also added new sections and chapters to cover
emerging topics in medical practice.
In addition to the organizational changes, we

have also focused on improving the quality of
the images and illustrations in the book. We
have sourced high-resolution images and
updated all of the figures to ensure that they
are clear and accurate
Finally, we have also revised and expanded the

tables and charts throughout the book to
provide more comprehensive and detailed information. These changes will make it
easier for readers to understand and retain the material covered in the book.
We hope Medstar will be a treasured resource for your clinical year studies and
beyond. Good luck on your journey!!
Dr. Nahom Asnake

Editor-In-Chief of MedStar Pediatrics
Cover page designer of Medstar Series
@nAxBiTw
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ACKNOWLEDGMENT
The contributors of Medstar clinical guide and synopsis of pediatrics wish to
acknowledge the help and support of Dr. Temam Kedir (MD, pediatrician), Dr. Lealem
Atlabachew (MD, Pediatrics R-3), Dr. Hunde Ahmed (MD, Pediatrics R-3) and Dr. Aniso
Mohammed (MD, Pediatrics R-3) whose comments and suggestions for some of the
cases became invaluable for this book.
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CONTRIBUTORS
Dr Nahom Asnake Dr. Jordan Ashenafi
EDITOR IN CHIEF CHIEF EDITOR OF 1ST EDITION
COVER PAGE DESIGNER ASSISTANT EDITOR
CONTRIBUTOR OF CONTRIBUTOR OF
SECTIONS NEONATOLOGY (BREASTFEEDING GROWTH AND DEVELOPMENT, APPROACH
AND BIRTH INJURY), APPROACH TO CARDIAC TO WHEEZE, APPROACH TO STRIDOR AND
PATIENT, DIABETES MELITUS, BLEEDING CHILDHOOD ASTHMA
DISSORDERS
Dr. Meghfira Abrar Dr Dereje Gondol

CONTRIBUTOR OF
CONTRIBUTOR OF
APPROACH TO BODY WEAKNESS AND
MALARIA, MEASLES, ALTERED MENTAL
DISSCUSSION OF DIFFERENTIALS OF BODY
STATUS, PHYSICAL EXAMINATION IN
WAKNESS
NEUROLOGIC PATIENT
Dr. Betelhem Birhanu

Dr Oliyad Yadeta
CONTRIBUTOR OF
CONTRIBUTOR OF CHILDHOOD TUBERCLOSIS AND PERTUSIS
NEPHROLOGY
Dr. Benti Shentema

Dr Kassa Kebede
SECTIONS OF NEONATOLOGY GENTETIC DISORDERS AND DYSMORPHIC
FEATURES
Dr. Dinaol Dinagde Dr Meron Biable

CONTRIBUTOR OF
CONTRIBUTOR OF
DERMATOLOGY
CARDIAC EVALUATION (SHORTNESS OF
BREATH), RHEUMATIC HEART DISEASE,
INFECTIVE ENDOCARDITIS AND
Dr. Minase Getachew Dr Kirubel Misganaw

CONTRIBUTOR OF
CONTRIBUTOR OF
APPROACH TO FEVER, TORCH INFECTIONS
CNS INFECTIONS (MENINGITIS BEYOUND
NEONATAL AGE AND BRAIN ABSCESS)
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Dr. Negussu Legesse Dr Lemi Sheferaw
ONCOLOGY (SOLID TUMORS IN CHILDREN AND CARDIOLOGY (FETAL TO NEONATAL
ONCOLOGIC EMERGENCIES) CIRCULATORY TRANSITION AND CONGENITAL
HEART DISEASES).
Dr. Mulat Alemu

Dr Eyasu Girma
CONTRIBUTOR OF
CONTRIBUTOR OF ACUTE COUGH, PNEUMONIA AND
DIARRHEA, ACUTE GASTROENTERITIS AND HEMATOLOGIC MALIGNANCIES
FLUID MANAGEMENT
Dr. Natnael Alemu Dr. Elsabeth Sisay

BODY FLUID COMPOSITION AND PEDIATRICS HIV/AIDS
ELECTROLYTE DISTURBANCES
Dr Hermela Zewge Dr Nardos Befekadu

CONTRIBUTOR OF
CONTRIBUTOR OF
APPROACH TO ANEMIA
CAUSES OF UPPER AIRWAY OBSTRUCTION
Dr. Fasika Solomon Dr Fikraddis Cheru

APPROACH TO ABNORMAL BODY MOVEMENT IMMUNIZATION
Dr. Kinfegabriel Wagaye Dr Martha Fisseha

CONTRIBUTOR OF
CONTRIBUTOR OF
PEDIATRICS HISTORY TAKING AND
APPROACH TO BODY SWELLING AND SAM
NEONATOLOGY
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MedStar – Pediatrics
2nd Edition
CONTENTS
CHAPTER 1 – INTRODUCTION TO PEDIATRICS
PEDIATRICS HISTORY TAKING..................................................................... 2
IMMUNIZATION...................................................................................... 6
GROWTH AND DEVELOPEMENT ................................................................. 12
GROWTH .................................................................................. 12
DEVELOPMENT ............................................................................ 15
CHAPTER 2 - NUTRITION
APPROACH TO BODY SWELLING ................................................................ 23
MALNUTRITION ................................................................................... 25
MANAGEMENT PRINCIPLES .............................................................. 32
CHAPTER 3 - FLUID AND ELECTROLYTE DISTURBANCES
FLUID COMPOSITION AND FLUID THERAPY.................................................... 42
ELECTROLYTE DISORDERS ....................................................................... 45
SODIUM DISORDERS ...................................................................... 45
POTASSIUM DISORDERS .................................................................. 50
CALCIUM DISORDERS ..................................................................... 54
DIARRHEA AND DEFICIT THERAPY .............................................................. 59
ACUTE GASTROENTERITIS............................................................... 64
CHAPTER 4 - NEONATOLOGY
HISTORY AND PHYSICAL EXAMINATION OF NEONATES ...................................... 74
BREASTFEEDING .................................................................................. 85
NEONATAL SEPSIS ................................................................................ 88
PERINATAL ASPHYXIA ............................................................................ 93
PREMATURITY AND ITS COMPLICATIONS ...................................................... 99
NEONATAL JAUNDICE (HYPERBILIRUBINEMIA) ............................................... 107
NEONATAL SEIZURE ............................................................................. 117
METABOLIC DISORDERS OF THE NEWBORN .................................................. 120
HYPOGLYCEMIA ......................................................................... 121
HYPOTHERMIA ........................................................................... 124
BIRTH TRAUMAS ................................................................................. 127
CHAPTER 5 - INFECTIOUS DISEASES
APPROACH TO FEVER ........................................................................... 131
FEVER WITHOUT A FOCUS IN THE NEONATE AND YOUNG INFANT (AGE-GROUP
0-3 MONTHS) ............................................................................ 132
FEVER IN THE OLDER CHILD ........................................................... 136
CLASSIFICATION OF FEVER ............................................................. 141
FEVER OF UNKNOWN ORIGIN (FUO) .................................................. 142
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TORCH: CONGENITAL AND PERINATAL INFECTIONS ........................................ 144

CONGENITAL TOXOPLASMOSIS ....................................................... 145
CONGENITAL RUBELLA ................................................................ 150
CONGENITAL SYPHILIS ................................................................. 152
NEONATAL HERPES .................................................................... 155
CYTOMEGALOVIRUS (CMV) ............................................................ 157
CONGENITAL CMV INFECTION ........................................................ 158
PEDIATRICS HIV/AIDS ........................................................................... 160
PERTUSSIS ........................................................................................ 173
MEASLES .......................................................................................... 181
MALARIA .......................................................................................... 189
CHAPTER 6 - PULMONOLOGY
COUGH............................................................................................ 202
ACUTE COUGH ................................................................................... 203
PNEUMONIA .............................................................................. 204
CHRONIC COUGH ................................................................................ 214
TUBERCULOSIS .......................................................................... 215
APPROACH TO WHEEZE ........................................................................ 244
CHILDHOOD ASTHMA ................................................................... 254
ACUTE BRONCHIOLITIS ................................................................. 276
STRIDOR AND UPPER AIRWAY OBSTRUCTION ................................................ 282
MANAGEMENT OF CROUP .............................................................. 288
DISCUSSION OF CAUSES OF UPPER AIRWAY OBSTRUCTION ................................ 291
CHAPTER 7 - CARDIOLOGY
EVALUATION OF THE CARDIOVASCULAR SYSTEM ........................................... 299
WORK-UPS IN CARDIAC EVALUATION ......................................................... 312
THE FETAL TO NEONATAL CIRCULATORY TRANSITION ..................................... 317
CONGENITAL HEART DISEASES ................................................................ 320
DISCUSSION OF SOME COMMON CHD ................................................. 324
ACQUIRED HEART DISEASES .................................................................... 340
RHEUMATIC HEART DISEASES ...................................................... 340
RHEUMATIC HEART DISEASE (RHD) .............................................. 351
INFECTIVE ENDOCARDITIS .............................................................. 356
CHAPTER 8 - HEMATOLOGY
ANEMIA ........................................................................................... 363
APPROACH TO A PATIENT WITH ANEMIA ..................................................... 364
HEMOSTASIS AND BLEEDING DISORDERS ..................................................... 375
DISORDERS OF PRIMARY HEMOSTASIS ........................................................ 376
IDIOPATHIC (AUTOIMMUNE) THROMBOCYTOPENIC PURPURA ..................... 378

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VON WILLEBRAND DISEASE (VWD) .................................................... 380

DISORDERS OF SECONDARY HEMOSTASIS .................................................... 382
HEREDITARY CLOTTING FACTOR DEFICIENCIES ..................................... 383
CHAPTER 9 - ONCOLOGY
HEMATOLOGIC MALIGNANCIES ................................................................ 386
THE LEUKEMIA`S ................................................................................ 386
LYMPHOMA ....................................................................................... 392
SOLID TUMORS IN CHILDREN ................................................................... 399
CENTRAL NERVOUS SYSTEM TUMORS ......................................................... 399
NEUROBLASTOMA ............................................................................... 408
WILMS TUMOR ................................................................................... 413
RETINOBLASTOMA ............................................................................... 417
BONE TUMOR .................................................................................... 421
OSTEOSARCOMA ......................................................................... 422
EWING SARCOMA ........................................................................ 424
ONCOLOGIC EMERGENCIES ..................................................................... 427
CHAPTER 10 - NEPHROLOGY
INTRODUCTION .................................................................................. 441
RENAL FAILURE .................................................................................. 442
GLOMERULAR DISEASES ........................................................................ 453
ACUTE NEPHRITIC SYNDROME ................................................................. 456
NEPHROTIC SYNDROME ......................................................................... 469
CHAPTER 11 - DIABETES MELLITUS
INTRODUCTION .................................................................................. 479
TYPE 1 DIABETES MELLITUS .................................................................... 479
COMPLICATIONS OF DIABETES ................................................................. 482
TREATMENT OF DIABETES ...................................................................... 485
TYPE 2 DIABETES MELITUS ..................................................................... 489
OTHER CAUSES OF POLY SYMPTOMS ......................................................... 491
CHAPTER 12 - NEUROLOGY
APPROACH TO BODY WEAKNESS .............................................................. 495
APPROACH TO ABNORMAL BODY MOVEMENT................................................ 498
APPROACH TO PATIENT WITH ALTERED MENTAL STATUS ................................. 502
PHYSICAL EXAMINATION OF NEUROLOGIC PATIENT ........................................ 515
SPECIAL DIAGNOSTIC PROCEDURES ........................................................... 522
CNS INFECTIONS ................................................................................. 527
ACUTE BACTERIAL MENINGITIS BEYOND THE NEONATAL PERIOD ................ 527
BRAIN ABSCESS .......................................................................... 534
12.7. DIFFERENTIAL DIAGNOSIS FOR BODY WEAKNESS .................................... 539

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POLIOMYELITIS .......................................................................... 539

GUILLAIN-BARRE SYNDROME (GBS) ................................................... 550
TRANSVERSE MYELITIS .................................................................. 555
MYASTHENIA GRAVIS.................................................................... 556
CEREBRAL PALSY ........................................................................ 557
RABIES .................................................................................... 559
INFANTS BOTULISM ..................................................................... 561
FOODBORNE BOTULISM................................................................. 562
INFANT BOTULISM....................................................................... 562
CHAPTER 13 - GENETIC DISORDERS AND DYSMORPHIC FEATURES
CHROMOSOMAL DISORDERS .................................................................... 566
DOWN SYNDROME ....................................................................... 566
EDWARD SYNDROME (TRISOMY 18) ................................................... 576
TURNER SYNDROME (45, X) ............................................................ 578
NEURAL TUBE DEFECTS ........................................................................ 583
HYDROCEPHALUS ................................................................................ 588
CLEFT LIP AND PALATE ......................................................................... 592
CHAPTER 15 - DERMATOLOGY
INTRODUCTION .................................................................................. 595
DISCUSSION OF SELECTED CASES.............................................................. 597
REFERENCES ................................................................................... 612
ANNEXES ........................................................................................ 613
NEW WHO GROWTH STANDARDS...................................................... 614
GROWTH CURVE FOR PATIENTS WITH DOWN SYNDROME ......................... 632

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CHAPTER 1 - INTRODUCTION
1. Pediatrics History taking
2. Immunization
3. Growth and Development
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1.1. PEDIATRICS HISTORY TAKING
COMPONENTS OF PEDIATRICS HISTORY

1. IDENTIFICATION
• Name • Date of admission
• Age • Mode of arrival
• Sex • Referral
• Address • Source of History
• Hospital, ward and bed no
• Pediatric age group
o Neonate Birth- 1month
o Infant Up-to 1yr
o Toddler 1-3 yrs
o Preschool aged 4-6 yrs
o School aged 7-12 yrs
o Adolescent 13-18 yr
2. PREVIOUS ADMISSION
• Specify when, where, why (what was the illness), treatment & outcome.
• If the patient P/A has direct relation with the current complaint, it should be
included in HPI. So you can say P/A is included in
SAMPLE
• Date and time of clerking: Tuesday 07/02/2023 at 2:00 PM
• Identification
• This is Rufael Endashaw a 4 years old preschool aged male child from Jimma
zone, Mana Woreda admitted to JUMC, Pediatrics level one ward, bed no. 3, 4
days back after being referred from a local health center. The source of history
is his mother with no language barrier.
• Previous Admission
• No History of previous admission
HISTORY OF PRESENT ILLNESS

• The main reason the patient is seeking a medical attention.
N.B Patient may have more than one complaint but don’t forget to take the main
complain he came to hospital so that you can build your differential diagnosis around
the chief complaint and reach on diagnosis.

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• A child may come with
o Shortness of breath o Altered mental status
o Cough o Yellowish discoloration of
o Wheeze eye/skin
o Diarrhea o Abdominal pain
o Generalized body swelling o Fever
o Abnormal Body Movement o Body weakness etc…
• Characterization of the chief complaint and ruling in/out the differential
diagnosis is discussed under each chapter of the book with sample history for
each so you can refer them depending on your patient chief complaint.
NUTRITIONAL HISTORY
• Current nutrition:
o Staple food, type of food and composition of food (Eg. Enjera made of
tef or bread made of wheat..)
o Amount and frequency of meals per day
o Does the child finish his dish and does he share dishes with siblings.
• Previous nutrition: (important for all children under 2 and as indicated)
o Breast feeding History: Initiation of breast feeding, duration of exclusive
breast feeding (EBF), frequency of breast feeding, switching of breasts,
and total duration of breast feeding.
o Complementary feeding: Time of initiation, food type, and frequency.
• Sunshine exposure:
o Normally the child must be exposed in the early morning sun undressed,
with no oil/petroleum application for 20-30min till the child is able to
get sunshine by himself.
DEVELOPMENTAL HISTORY (SEE GROWTH AND DEVELOPMENT)

• All of the four developmental milestones should be assessed. If there is any
developmental delay or regress then try search at which age of the child the
development began to deviate from normal by tracing back to earlier age.
• For example, if a 3 years old child has developmental delay
o then assess his developmental milestone at the age of 2yr, 1yr, 9mo go
back to get when the development began to delay.
IMMUNIZATION HISTORY
• Has the child completed the EPI schedule? Does he have the yellow certificate
card?
• If not vaccinated, why?

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• In most of pediatrics diseases Nutritional, Immunization, and Developmental
histories are a pertinent, so include them in HPI.
PAST MEDICAL & SURGICAL HISTORY
• Childhood illnesses like measles, chicken pox, mumps

• Previous History of same illness
• History of medication and drug allergy
• History of surgery and trauma
PERSONAL, FAMILY & SOCIAL HISTORY

• Personal History: birth place, growth, parents name and occupation, academic
life, current achievement and how the illness affects his personal life
• Family History: family size; birth order, siblings’ health status; maternal
health; mother & father living together or separated, family income
• Social History:
o Housing and no. of people per room (WHO Crowding Criteria)
o Animals, pet, poultry living together
o Kitchen in the same house -exposure to domestic smoke.
o Waste disposal system: diarrheal diseases are usually associated with
poor personal and environmental hygiene.
REVIEW OF SYSTEM
• Helps you to pick up what u have missed to ask.
VITAL SIGNS
• Vital Signs: Normal range of vital signs for specific age group
Table 1 Vital signs by age
Age Heart rate Respiratory rate Blood pressure
(beats/min) (breath/min) (mmhg)
Premature 120-170 40-70 55-75/35-45
0-3 month 100-150 35-55 65-85/45-55
3-6month 90-120 30-45 70-90/50-65
6-12month 80-120 25-40 80-100/55-65
1-3 years 70-110 20-30 90-105/55-70
3-6years 65-110 20-25 95-110/60-75
6-12years 60-95 14-22 100-120/60-75
12+ 55-85 12-18 110-135/65-85
SYSTOLIC BLOOD PRESSURE CALCULATION

• Systolic blood pressure calculation in children over 1 year old:

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o Median SBP = 90 mmHg + (2 x Age in years)
o Minimum SBP = 70 mmHg
PHYSICAL EXAMINATIONS RELATED TO EACH SYSTEM ARE MENTIONED IN THEIR

CHAPTERS.

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1.2. IMMUNIZATION
• Vaccination is the administration of any vaccine or toxoid for prevention of
disease.
• Immunization is the process of inducing immunity artificially.
• It can be active or passive
o Active immunization involves stimulating the immune system to produce
antibodies and a cellular immune response against infectious agent
through the use of a urine vaccine or toxoid.
o Passive immunization provides temporary protection through the
administration of exogenous antibody or maternal antibody transfer to
the fetus.
DETERMINANTS OF THE IMMUNE RESPONSE

• The nature and magnitude of the response to a vaccine or toxoid depend on the
following factors:
1. Age
▪ presence of high concentration of maternal antibody and
immature response to some vaccines in the first four months of
life impair immunization. The measles vaccine is given at 9
months of age to reduce this effect.
2. Route of administration.
▪ Vaccines given orally induce mucosal secretary IgA
▪ e.g. OPV vaccine
▪ Using an improper route to administer the vaccine may reduce the
immune response e.g. where BCG is administered IM rather than
intradermal
3. Nature of vaccine
▪ Live attenuated vaccines induce immunity with a single dose
which lasts longer than inactivated ones
4. Genetic
▪ Individuals genetically vary in their ability to respond to the same
vaccine.
5. Potency
▪ Ensuring the potency of a vaccine, especially live attenuated,
requires keeping the cold chain.

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Table 2 The main antigenic preparations
Type of antigen Vaccine example

Living organism Natural Small pox vaccine.
Attenuated * Polio (Sabin) OPV, Measles,
Mumps, Rubella, BCG
Intact but non Virus Polio (Salk)
living organisms
Bacteria Pertussis
Sub cellular Capsular disaccharide Meningococcal
Fragments Surface antigen Hepatitis B.
Toxoids Tetanus, diphtheria
• Live attenuated vaccines, particularly viral ones like measles, confer life long
protection after a single immunizing dose, since they closely simulate natural
infection and contain the greatest number of microbial antigens. Their
drawbacks are:
o Reversion to wild type can lead to disease
o They can cause severe disease in immunocompromised children
o Some people exhibit hypersensitivity to viral antigens.
Table 3 Administrations of Vaccines
VACCINE DOSE ROUTE OF SITE OF
ADMINISTRATION ADMINISTRATION
BCG Infants: 0.05 Intradermal Right deltoid region of the
ml0.1ml for arm
children>1yr
DTP 0.5ml Intramuscular Upper, outer portion of the
thigh
Polio 2 drops, or Oral Mouth
Measles 0.5 ml Subcutaneous Outer, upper part of left
arm
Tetanus 0.5 ml Intramuscular Deltoid region of the upper
Toxoid arm

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TYPES OF VACCINATION
1. ROUTINE IMMUNIZATION
• The Expanded Programme on immunization in Ethiopia
• The Expanded Programme on Immunization (EPI) was established by the World
Health Organization in 1974 to control vaccine preventable diseases.
• EPI in Ethiopia covers
o BCG(Bacillus-Calmette- o Pertussis
Guerin) o PCV (Pneumococcal
o Diphtheria Conjugated Vaccine)
o Hib (Hemophilus influenza o Oral polio virus
type B) o Rotavirus
o Hepatitis B o Tetanus
o Measles
Table 4 Immunization Schedule
Vaccination for infants
Age Visit Antigen
Birth 1 BCG, OPV-O
6 weeks 2 Pentavalent (DPT + Hep B + Hib), OPV1, PCV1,
rotavirus
10 weeks 3 Pentavalent2, OPV2, PCV2, rotavirus
14 weeks 4 Pentavalent3, OPV3, PCV3
9 months 5 Measles 1
1 year and 3 mo 6 Measles 2
2. CATCH-UP VACCINATION
For children below 5yr but not vaccinated in the first one year (catch-up vaccination)
the following should be administered:
Table 5 Catch up vaccination
Visit Vaccination
1st visit Pentavalent, Rota virus, OPV
Measles (if not exposed, age greater than 9
month),
Mantoux test - BCG if test negative in 3 days
2nd visit (1 month after 1st visit) Pentavalent, Rotavirus, OPV, Measles 2
3rd visit (1month after 2nd visit) Pentavalent, OPV
4th visit (1 year later) Pentavalent, OPV
5th visit (4 years later) (Adult type)
3. OUTREACH (MOBILE SCHEDULE FOR REMOTE AREAS)

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• This service gives coverage for people living within 20 km radius of the health
facility.
4. MASS CAMPAIGNS:
• National immunization days (NIDs) for polio (currently active) and measles.
SIDE EFFECTS OF VACCINES

BCG
• Kochs phenomenon – self-limiting acute inflammatory reaction four days after
vaccination.
• Indolent ulcer – ulcer persisting 12 wk. after vaccination or ulcer more than
10mm, mainly resulting from deep injection or secondary infection.
• Deep abscess – abscess at site of injection or draining lymph nodes due to
subcutaneous or deep injections.
• Disseminated disease with BCG – 1 per million vaccines results in BCG causing
active disease especially in immunosuppressed children.
OPV:
• Paralytic polio from vaccine strain poliovirus
Table 6 Minimum intervals between vaccine
Antigen Minimum Minimum Minimum Minimum Comments
age at interval interval interval
first dose between doses between between
1 and 2 doses 2 and doses 3 and
3 4
BCG Birth Give at earliest
opportunity after birth.
Hepatitis B 6 weeks 4 weeks 4 weeks
(excluding
birth dose)
DTP- 6 weeks 4 weeks 4 weeks 6 months
containing (If >1 year, (and >1 year
vaccine leave at least of age)
6 months
between dose
2 and 3)
Hib* 6 weeks 4 weeks 4 weeks If >1 year, only 1 dose is
needed.
Not recommended for >5
years, if healthy.

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Polio OPV 6 weeks 4 weeks 4 weeks 4 weeks
(excluding
birth dose) *
Rotavirus 6 weeks 4 weeks 4 weeks Not recommended >2
(If using a 3- years.
dose
schedule)
PCV* 6 weeks 4 weeks 4 weeks If 1-5 years, only 2 doses
needed.
Measles 9 months 4 weeks
DPT:
• The major side effect is from the pertussis component
• Superficial injection can cause injection site abscess a week later.
• Encephalopathy (0.3 – 3/100,000 vaccines)
• Convulsion (0.3 – 90/100,000)
• Shock like state or collapse (hypotonic – hypo responsiveness episode) (0.5 –
30/100,000)
• Permanent brain damage (0.2 – 0.6/100,000)
MEASLES:
• May have mild reaction likes low grade fever irritability and allergic reactions.
• Major side effects include (per 100,000 vaccinations):
o Encephalopathy (0.1)
o Convulsions (0.02 – 100)
o Sub acute sclerosing panencephalitis (0.01 – 0.05)
CONTRAINDICATION
• The general contraindications for all vaccines include:
o Anaphylactic reaction
o Moderate to severe illness
o Live-attenuated vaccines for severely immunosuppressed patient
(exception is measles) Not contraindications
o Moderate fever after prior vaccine dose
o Moderate local reaction after injectable vaccine
o Mild acute illness
o Prematurity (same dose as for full-term infants)
o Severe malnutrition (rather strong indication)
o Penicillin allergy (personal or family)

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THE CONTRAINDICATIONS FOR SPECIFIC VACCINES INCLUDE:

• BCG: Symptomatic AIDS
• OPV:
o Severe immune suppression
o Diarrhea is not contraindication. Give OPV without registering it and
repeat OPV 4 weeks later.
• DPT:
o Encephalopathy within 7 days of Previous dose not attributable to
another cause
o Seizures if poorly controlled or new onset, defer until control.
COLD CHAIN
• “Cold Chain” refers to the process used to maintain optimal conditions during
the transport, storage, and handling of vaccines starting at the manufacturer
and ending with the administration to the patient or client.
• As vaccines are sensitive, their potency and effectiveness may be negatively
impacted if they are exposed to freezing temperatures, Heat or direct sunlight
Table 7 Recommended Storage Temperature of EPI
Types of vaccine Storage temperature
Most sensitive to heat Oral polio -15oC to – 25oC
Measles (freeze dried) -15oC to – 25oC
DPT 2oC to 8oC
Least sensitive BCG (freeze dried) 2oC to 8oC
to heat
Tetanus toxoid 2oC to 8oC
• In addition, protection from light is a necessary condition for some
vaccines.

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1.3. GROWTH AND DEVELOPEMENT

• Growths is as the increase in the size of a cell, organ or person.
o It is purely physical.
o It’s is characterized quantitatively (using measurements).
• Development refers to the functional process where a person can develop
regarding his/ her physical, mental, social, emotional, language, etc.
o it is both Quantitative & Qualitative in Nature.
STAGES OF GROWTH AND DEVELOPMENT

• Infancy
o Neonate - Birth to 1 month
o Infancy - 1 month to 1 year
• Early Childhood
o Toddler - 1-3 years
o Preschool - 3-6 years
• Middle Childhood
o School age - 6 to 12 years
• Late Childhood
o Adolescent - 13 years to approximately 18 years
1.3.1. GROWTH
• Diseases tend to have more impairment when they occur during period of rapid
growth.
• Deviation of child's own pattern of growth and development is more significant
than deviation from standard growth chart.
• Rate of growth is more important than actual size. So serial measurement of
growth is best indicator of health.
A. WEIGHT
• Best index of nutrition and growth (especially in acute illnesses)
• 1 kg = 2.2 Ib (pound)
Table 8 Weight by age groups
Age Weight
At birth 3.2 kg / 7 Ibs
Birth - 10th day 10% of BW lost because of loss of meconium, Loss of
• At 10th day urine, loss of physiologic edema, less intake
• BW is regained at day 10
1 - 3 months increases by 200 g/wk

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3 - 12 months increases by 150 g/wk
• 6 months • Doubles the BW
• 1 year • Triples the BW
2 years 4 times the BW
2 yr - puberty Increases by 5 Ibs / year
• 7 years • 7 times the BW
• 10 years • 10 times the BW
Puberty Growth spurt - rapid weight gain
• Formulas for approximate average weight
Table 9 Formulas for approximate average weight
Age Weight (kg)
3 – 12 months 𝒂𝒈𝒆 (𝒎𝒏) + 𝟗
𝟐
1 - 6 years (𝒂𝒈𝒆(𝒚𝒓) ∗ 𝟐) + 𝟖
7 – 12 years (𝒂𝒈𝒆 (𝒚𝒓) ∗ 𝟕) − 𝟓

𝟐
B. HEIGHT
• Affected by chronic illnesses
Age Height
At birth 50 cm
1 year 75 cm
2 years 85 cm (Half of the adult's height)
3 years 90 cm
4 years 100 cm
up to puberty increases by 5 cm / year
At puberty growth spurt - increases by 9 - 10 cm /yr for 2-3 years
Formulas for approximate average height
Age Height (cm)
2 – 12 years (𝒂𝒈𝒆(𝒚𝒓) ∗ 𝟔) + 𝟕𝟕
C. HEAD CIRCUMFERENCE
• Estimate of brain growth
• HC is larger than chest circumference at birth; and equals at 1 year.
• HC rapidly increases during infancy.
• Small brain indicates:

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o Abnormal brain growth
o Craniosynostosis (premature closure of sutures)
Table 10 Head circumference by age
Age HC
At birth 35 cm
3 mn 41 cm
6 mn 44 cm
9 mn 46 cm
1 year 47 cm
2 years 49 cm
3 years 50 cm
5 years 51 cm
Up to puberty (12 years) in Increases by 0.5 cm / year
12 years 54/55 cm
D. DENTITION
• First eruption - at 6 months of age
• Last eruption - at 2.5 year (by now has 20 teeth in total)
• First shedding of deciduous teeth - at 6 years
• Last shedding (completed) - at 12 year
• Delayed eruption - considered when there are no teeth by approximately 13
mo of age.
• Common causes include:
o Hypothyroid
o Rickets
o Hypoparathyroidism
o Familial
o Idiopathic (the most common)
o Mechanical blockage (crowding, gum fibrosis)
CHRONOLOGY OF HUMAN DENTITION OF PRIMARY (DECIDUOUS) AND SECONDARY

(PERMANENT) TEETH
• For Primary teeth
o Age at eruption:
▪ 5 – 7 months old – Mandibular central incisors
▪ 6 – 8 months old – Maxillary central incisors
▪ 7 – 10 months old – Mandibular lateral incisors
▪ 8 – 11 months old – Maxillary lateral incisors
▪ 10 – 16 months old – Maxillary and mandibular 1st molars
▪ 16 – 20 months old - Maxillary and mandibular canines

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▪ 20 – 30 months old - Maxillary and mandibular 2nd molars
o Age at shedding:
▪ 6 – 7 years old - Mandibular central incisors
▪ 7 – 8 years old –
• Maxillary central incisors and
• Mandibular lateral incisors
▪ 8 – 9 years old - Maxillary lateral incisors
▪ 9 – 11 years old - mandibular canines
▪ 10 – 12 years old –
• maxillary and mandibular 1st molars
• maxillary 2nd molars
▪ 11 – 12 years old – maxillary canines
▪ 11 – 13 years old - mandibular 2nd molars
• For permanent teeth:
• Mandibular central incisors
• maxillary and mandibular 1st molars
• Maxillary central incisors and
• Mandibular lateral incisor
▪ 8 – 9 years old - Maxillary lateral incisors
▪ 9 – 11 years old - mandibular canines
▪ 10 – 11 years old – Maxillary 1st premolars
▪ 10 – 12 years old –
• Mandibular 1st premolars
• Maxillary 2nd premolars
▪ 11 – 12 years old – maxillary canines
▪ 11 – 13 years old – Mandibular 2nd premolars
▪ 12 – 13 years old - maxillary and mandibular 2nd molars
▪ 17 – 22 years old – Maxillary and mandibular 3rd molars
1.3.2. DEVELOPMENT
• A child’s development represents the interaction of heredity and the
environment on the developing brain.
• There is variation in the pattern of development between children.

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Child’s development
Affected by interaction of heredity and
environment.
Environment
influences the extent to which that
Heredity
potential is achieved
determines the potential of Env’t has to meet 2 needs for child’s dev’t:
the child
Needed for school age children

Needed for infants from their parents
Figure 1 Factors affecting Child's Development
• There are four fields of developmental skills:

o Gross motor
o Vision and fine motor
o Hearing, speech and language
o Social, emotional and behavioral.
• Developmental milestones - the age of acquisition of important developmental
skills.
• The median age - the age when half of a standard population of children
achieve that level; it does not tell us if the child’s skills are outside the normal
range.
• Limit ages - the age by which the developmental milestones should have been
achieved.
o Major evaluating steps when analyzing a young child’s developmental
progress.

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1. Questioning - consider the child’s age and then focus your questions on the
areas of likely current developmental progress (shortcut approach)
2. Equipment - offer the child suitable toys to find out about skills through play
3. Observation - observe how the child uses the toys and interacts with people.
Development is in a cephalo-caudal direction.
The age when there is the most rapid emergence of skills in each developmental
field:
• The first year of life - gross motor development
• 1 year of age onwards - vision and fine motor development
• 18 months of age onwards - hearing, speech and language
• 2.5 years of age onwards - social, emotional and behavioral development
Then make a focused questioning considering the age of the child. Thus, for a
child aged:
• less than 18 months – ask first gross motor abilities -> acquisition of vision and
hearing skills ->
questions about fine motor
• 18 months to 2.5 years – ask first acquisition of speech and language -> fine
motor skills -> only brief gross motor skills
• 2.5 to 4 years – ask speech and language -> social, emotional, and behavior
development.
• When evaluating a child’s development, consider:
o Each skill field separately
o The sequence of developmental progress
o The stage the child has reached for each skill field
o If progress is similar in each skill field
o Only at the end, the child’s overall developmental profile and how that
relates to the child’s age.
CAUSES OF ABNORMAL DEVELOPMENT

PRENATAL
Genetic –
⚫ Chromosome/DNA disorders, e.g. Down syndrome, fragile X syndrome,
chromosome microdeletions or duplications.
⚫ Cerebral dysgenesis, e.g. microcephaly, absent corpus callosum, hydrocephalus,
neuronal migration disorder
Cerebrovascular - Stroke – haemorrhagic or ischaemic
Metabolic - Hypothyroidism, phenylketonuria
Teratogenic - Alcohol and drug abuse
Congenital infection - Rubella, cytomegalovirus, toxoplasmosis, HIV

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Neurocutaneous syndromes - Tuberous sclerosis, neurofibromatosis, Sturge–Weber,
Ito syndrome
PERINATAL
⚫ Extreme prematurity - Intraventricular hemorrhage /periventricular leukomalacia
⚫ Birth asphyxia - Hypoxic-ischemic encephalopathy
⚫ Metabolic - Symptomatic hypoglycemia, hyperbilirubinemia
POSTNATAL
⚫ Infection - Meningitis, encephalitis
⚫ Anoxia - Suffocation, near drowning, seizures
⚫ Trauma - Head injury – accidental or non-accidental
⚫ Metabolic - Hypoglycemia, inborn errors of metabolism.
⚫ Cerebrovascular - Stroke
⚫ Nutritional deficiency - Maternal deficiency (breast fed), food intolerance,
restrictions
⚫ Other
Unknown (about 25%): chronic illness, physical abuse, emotional neglect.
⚫ Developmental problems often present at an age when a specific area of
development is most rapid and prominent. Therefore:
✓ Motor problems - during the first 18 months of age,
✓ Speech and language problems - between 18 months and 3 years,
✓ Social and communication disorders - between 2–4 years of age
Adjusting for prematurity

✓ If a child has been born preterm, the anticipated developmental skills of a 9-
month-old preterm baby (chronological age) born 3 months early (at 28 weeks’
gestation) are more like those of a 6-month-old baby (corrected age).
DEVELOPMENT (MEDIAN AGES)

Table 11 Developmental Milestones
Neonate 3 months 6 months 9 months 1 year
Gross ✓ Head lag ✓ Lifts head ✓ Lifts head and ✓ Riches for ✓ Walk with support
motor ✓ Tonic neck ✓ Sits supported chest objects ✓ Stands independently
reflex ✓ Roll from ✓ Sits without ✓ Pulls to stand
✓ Walk reflex stomach to support ✓ Cruises
back ✓ Rolls over both ✓ Crawls
way
Fine motor ✓ Fisted ✓ Grasps rattle ✓ Palmar grasp ✓ Pincer grasp ✓ Turns pages of book
hands ✓ Follow ✓ Follow objects all ✓ stacks 2 blocks
✓ Pupillary objects 180° directions
reflex ✓ Transfers object
hand to hand

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Speech and ✓ cries ✓ coos ✓ Monosyllabic ✓ Polysyllabic ✓ Says “mama” or “Dada” (10
language ✓ startle to ✓ turns to babble babble months)
loud noise nearby voice ✓ Inhibits to ✓ Speaks first real word
“no”
Social and ✓ Mostly ✓ Loughs ✓ Everything to ✓ Stranger ✓ Waves bye bye

behavior sleeps ✓ Anticipate mouth fear ✓ Points to desired objects
✓ Primitive food on site ✓ Friendly with ✓
reflexes strangers
✓ Social smile
(4-6 wk)
18 months 2 years 3 years 4 years 5 years

Gross ✓ Walk alone steady ✓ Runs well ✓ stands ✓ Hops on 1 foot ✓ skips
motor ✓ walks upstairs (1 step ✓ walks up and momentarily on 1 ✓ throws ball ✓ walks backward
at a time) down stairs, 1 foot overhand ✓ run stairs
✓ Throws ball step at a time ✓ walk stairs ✓ uses scissors to
✓ jumps alternating feet cut out pictures
✓ climb on ✓ Rides tricycle ✓ climbs well
furniture
Fine ✓ stacks 3 blocks ✓ stacks 6 blocks ✓ stacks 9 blocks ✓ copy cross and ✓ copy triangles
motor ✓ imitates scribbling ✓ scribbles ✓ copy circle square
✓ makes a line with ✓ copy line ✓ draws a man with
crayon 2-4 parts besides
head
Speec ✓ Speaks 10-15 words ✓ speak 2-3 word ✓ gives full name ✓ speech is ✓ Names 4 colors
h and ✓ names pictures sentences ✓ knows age and sex intelligible to ✓ Counts up to 10
langua ✓ identifies 1 or more strangers ✓ Define nouns
ge parts of body ✓ tell a story
Social ✓ Feeds self ✓ Handles spoon ✓ helps in dressing ✓ Plays with several ✓ Dresses and
and well (unbuttons clothing children undresses alone
behavi ✓ helps to undress and puts on shoes) ✓ goes to toilet ✓ asks questions
or ✓ washes hands alone (toilet about meaning of
trained) words
✓ engages in
domestic role-
playing
RED FLAGS (LIMIT AGES)

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TANNER STAGING (SEXUAL MATURITY RATINGS)

• For females:
Table 12 Tanner Staging (Females)
SMR Pubic hair Breasts
stages
1 preadolescent preadolescent
2 Sparse, lightly pigmented, Breast and papilla elevated as small
straight, medial border of labia mound; areola diameter increased
3 Darker, beginning to curl, Breast and areola enlarged, no
increased amount contour separation
4 Coarse, curly, abundant (but less Areola and papilla form secondary
than in adult) mound
5 Adult feminine triangle, spread Mature, nipple projects, areola part of
to medial surface of thighs general breast contour
• For males
Table 13 Tanner Staging (Males)
SMR Pubic hair Penis Testes
stages
1 None preadolescent Preadolescent
2 Scanty, long, slightly Minimal enlargement Enlarged scrotum,
pigmented pink, texture altered

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3 Darker, starting to curl, Lengthens Larger
small amount
4 Coarse, curly, resembles Larger; glans and Larger, scrotum dark
adult type (but less breadth increase in
quantity) size
5 Adult distribution, spread Adult size Adult size
to medial surface of
thighs

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CHAPTER 2 - NUTRITION
1. Approach to Body Swelling
2. Malnutrition

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2.1. APPROACH TO BODY SWELLING

• BODY SWELLING:
o is a compliant of a patient that may suggest the presence of edema
(accumulation of excess interstitial fluid).
o Can be localized or generalized
o For localized swelling consider: inflammation, lymph edema, DVT, mass,
as differentials.
GENERALIZED BODY SWELLING

• Patho-physiology: when the forces maintaining fluid exchange b/n intravascular
and interstitial compartments are lost; these are intra capillary hydrostatic
pressure, plasma oncotic pressure, and interstitial oncotic pressure. Or when
there is excess salt and water retention.
CONDITIONS AND DIFFERENTIALS

• Increased hydrostatic pressure
o Volume expansion
▪ Acute glomerulo-nephritis
▪ Acute tubular necrosis
▪ Acute and chronic renal failure
▪ Heart failure
o Venous insufficiency
▪ Cardiac failure(low output and high output)
▪ Constrictive pericarditis
o Reduced plasma oncotic pressure
▪ Nephrotic syndrome
▪ Chronic liver failure, fulminant hepatitis
▪ Protein losing enteropathy
▪ Severe acute malnutrition(edematous)
▪ Severe burns
o Increased interstitial oncotic pressure
▪ Hypothyroidism
o Damage to capillary endothelium
▪ Vasculitis (SLE, anaphylactoid,….)
▪ Sepsis
APPROACH TO THE PATIENT

HISTORY

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1. CHARACTERIZE THE SWELLING
• Duration and onset
• Pattern of the swelling:
o If from face downward may suggest renal diseases
o If from leg upwards may suggest cardiac diseases or SAM
o If from abdomen downward to legs may suggest liver diseases
2. WEIGHT GAIN
• Usually precedes overt GBS, patient may complain of difficulty putting shoes
and cloths particularly in the evening (why?)
3. ASSOCIATED SYMPTOMS:
• SOB, fatigue, jaundice, abdominal distention, urinary complaints, diarrhea,
symptoms of hypothyroidism; cold intolerance, constipation,
4. PREVIOUS HISTORY
• Previous history of renal, cardiac, liver diseases and their risk factors
5. DETAILED HISTORY ON NUTRITION
PHYSICAL EXAMINATION
• Do all P/Es but focus based on the history obtained and the most likely
differentials suspected.
• Lab investigations: based on history and physical findings we may consider;
CBC, LFT, U/A, RFT, ECHO, abdominal U/S.

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2.2. MALNUTRITION
GENERAL CONCEPTS
MALNUTRITION
• Encompasses the full continuum of under-nutrition and over-nutrition of both
macro and micronutrients.
• The greatest risk of under-nutrition occurs in the first 1000 days of life and this
early damage to growth and development can have adverse consequences.
• Many poor nutritional outcomes begin in uterus and are manifest as low birth
weight (LBW, <2,500 g).
MALNUTRITION (UNDER-NUTRITION)
PREVALENCE
• Rates of LBW are highest (26%) in southern Asia, and are twice those of sub-
Saharan Africa.
• Globally, in 2011; 16% of children <5 yr of age were underweight (weight for-
age <−2 SD).
• According to the 2014EDHS, the prevalence of GAM at national level is
estimated to be at around 9%.
• And prevalence of stunting was stated to be 40%.
• Fetal growth restriction together with suboptimal breastfeeding, stunting,
wasting and deficiency of vitamin A and zinc jointly contribute to 45% of global
child deaths (3.1 million deaths/yr), and many more are disabled or stunted for
life.
CAUSES OF UNDER-NUTRITION
• Nutritional status is determined by three factors:
o Immediate cause: act on the individual, these are inadequate food
intake and infection with their vicious cycle.
o Underlying cause: influence the households and the community; these
are drought, flooding, household food insecurity…
o Basic cause: influence communities and society these include the
country’s economy and political status.
• Consequences of Under-nutrition
o The most profound consequence of under-nutrition is premature death.
o For girls, under-nutrition is passed on to the next generation when
undernourished women give birth to LBW babies.

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o LBW and low weight gain in the first 2 yrs of life are associated with an
increased risk of hypertension, stroke, and type 2 diabetes in adults.
o Stunting before the age of 3 yr is associated with poorer motor and
cognitive development and altered behavior in later years.
o Iodine and iron deficiencies also lead to loss of cognitive potential.
ASSESSMENT OF NUTRITION
• We can use the ABCDs to assess nutritional status of an individual;
Anthropometry, Biochemistry, Clinical, Dietary.
CLASSIFICATIONS
• There are two ways of classifying malnutrition; these are community survey
and clinical.
COMMUNITY SURVEY CLASSIFICATION OF MALNUTRITION

Table 14 Assessment based on Community survey
CLASSIFICATION INDEX GRADING
Gomez (underweight) Weight For Age
Combined wasting and 90-75% of median Grade 1 (mild)
stunting 75-60% Grade 2 (moderate)
<60% Grade 3 (severe)
Waterlow (wasting) Weight For Height
Acute malnutrition 90-80% of median Mild
<70% Severe
Waterlow (stunting), Height for age
Chronic malnutrition 95-90% of median Mild
90-85% Moderate
<85% Severe
WHO (wasting) Weight for height
Acute (new onset) -2SD to -3 SD Moderate
malnutrition <-3SD Severe
WHO (stunting) Height for age
Chronic malnutrition <-2SD to -3 SD Moderate
<-3SD Severe

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WHO (wasting) MUAC
(For age group 6-59 mo) 115mm to 125 mm Moderate
<115 mm Severe
(For age group 5-9 yrs) ≥140mm Normal

≥130mm to < 140 mm Moderate
< 130 mm Severe
(For age group 10-14 yrs) 180mm≥ Normal

≥ 160 to < 180 mm Moderate
< 160 mm Severe
(for age group 15-17.9) ≥190mm Normal

≥17mm to <190mm Moderate
<170mm Severe
• The WHO further classifies SAM as complicated and non complicated based on
the presence or absence of possible complications
CLINICAL ASSESSMENT
WELCOMES CLASSIFICATION.
• Marasmus: severe wasting; severe weight loss and muscle mass leaving ‘skin
and bones.
• Kwashiorkor: characterized by edema (nutritional edema) that is a clinical
indicator for SAM.
• Marasmic-kwash: severe wasting + edema; combination of kwashiorkor and
marasmus.
• Severe Acute Malnutrition (SAM) is severe wasting (MUAC<11.5cm for
children aged 6-59monthes, weight for height<-3SD) and/or bilateral
edema.
CLINICAL PRESENTATION
• Two clinical syndromes of malnutrition (under-nutrition) are well recognized,
these are kwashiorkor and marasmic- kwashiorkor (edematous SAM) and
marasmus (non-edematous SAM) with their own patho-physiology and
presentations.
PATHO-PHYSIOLOGY

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• Physiologic and metabolic changes take place in an orderly progression to
conserve energy and prolong life. The process is called reductive adaptation
i.e. reduced body homeostasis in order to survive on limited macro and micro-
nutrients intake.
• Different organs in the body become atrophic and become less functional.
o The functions of different organs are preserved more in non-edematous
SAM than edematous.
o And the compensatory breakdown of muscle proteins in non-edematous
SAM makes the reduction in serum proteins to be less extent.
HISTORY
• Age at presentations is 12-36 months for kwashiorkor. It usually occurs at the
time of weaning, when the diet is suddenly changed to that of the adult diet,
which is high in CHO but low in protein.
• Severe protein and essential amino acid deprivation in association with
adequate caloric intake.
• For marasmus, age at presentation is usually 6-12 mo (“infantile marasmus”)
when the amount of breast milk is markedly reduced, or more frequently in
those who are artificially fed.
• Marasmus is also seen in older children living on inadequate diets for prolonged
periods. This is described as “late marasmus” and is similar to chronic
starvation in adults.
SYMPTOMS DIRECTLY RESULTING FROM UNDER-NUTRITION:

• KWASHAKOR
O Generalized body swelling staring from the legs.
O Loss of appetite, vomiting, diarrhea(mal-absorption), abdominal
distention
O Growth retardation and mental changes together with GBS are the three
essential features of kwashiorkor.
O Symptoms of anemia; vertigo, easy fatigability, light headiness, tinnitus,
pica (craving for non-edible matters; feature of iron deficiency)
• MARASMUS
O Growth retardation; failure to gain weight is the earliest manifestation.
O Irritability, continuously crying b/c of hunger
O Good appetite, unlike kwashiorkor.
O Diarrhea and symptoms of micronutrient deficiencies are also present.
• MARASMIC-KWASHIORKOR
O These children will have the clinical features of both marasmus and
kwashiorkor

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O Edema appears in a child who is chronically undernourished and has not
been growing well for weeks or months.
O Generally, the muscles of the upper limbs are wasted while the lower
limbs appear swollen.
SYMPTOMS RESULTING FROM THE COMPLICATIONS OF UNDER-NUTRITION

• Infection:
o Has a vicious relationship with malnutrition, in that it can cause
malnutrition as an immediate cause and it can also be a result of low
immunity seen in malnutrition.
o Prognosis is often poor owning to young age of the patients, severity of
the infection and presence of complications.
o Bronchopneumonia and gram-negative septicemia (translocation of
bacteria? b/c bacterial over growth and GI mucosal atrophy) are
common infections.
o Systemic symptoms of inflammation; fever, chills, malaise… may not be
apparent b/c low immune response.
o And different symptoms depending on the focus of infection; R/S (cough,
fast breathing…) and GIT (diarrhea, vomiting…) being most common.
GUT (dysuria, frequency, urgency...), ear and eye, skin, etc…
• Hypoglycemia:
o Mostly seen in marasmus and is not common to be symptomatic.
o It is often associated with septicemia.
o In severe cases, twitching and convulsions may occur and the child
becomes unconscious.
o Early and adequate feeding usually avoids this complication.
• Hypothermia:
o It is one of the medical emergencies in malnourished patients.
o It occurs more often in severely wasted children and is associated with
high mortality.
o Results from Impairment of thermoregulatory control and decreased
energy stores.
o In addition, the loss of thermal insulation b/c of emaciation.
o Patient may Shiver and be drowsy.
• Shock:
o Feared emergency complication seen in SAM
o Immediate diagnosis and management is critical
o Patient may be lethargic or unconscious
• Others: dehydration, corneal ulceration, severe anemia, skin lesions, and etc.

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RISK FACTORS
• Inadequate food intake: infection or chronic illnesses, economic status
• Decreased absorption of nutrients: HIV, intestinal TB, parasites, cow’s milk
intolerance,
• In many of these cases the child may present with failure to thrive and chronic
or persistent diarrhea.
• Increased daily nutritional requirements: physiologically children and
adolescents have more nutritional requirements.
• Others: infection, Parasites, especially hookworms, Schistosomes, malaria,
cause blood loss, which increases nutrient needs.
PHYSICAL FINDINGS (SIGNS)

• G/A
o moon face and apathy (kwashiorkor), simian face (marasmus, visible
wasting
• V/S:
o BP; hypotension b/c shock is one complication,
o PR; bradycardia or tachycardia,
o RR; tachypnea b/c of pneumonia,
o T◦; fever T◦≥37.5◦c (for axillary) due to infection or hypothermia T◦<35◦c
(for axillary) b/c low energy for heat production.
• Anthropometry: wt, ht/length for <2yrs
o BMI: < -2SD (thinness), b/n +1SD and +2SD (overweight) and >+2SD
(obesity).
o WFH/WFL: is an indicator of acute malnutrition ;( see WHO
classification)
o WFA: easy to measure but doesn’t differentiate b/n stunting and
wasting. (See Gomez classification)
o HFA/LFA: is a measure of linear growth, deficit represents the
cumulative impact of adverse events, usually in the first 1,000 days from
conception (critical period for child growth) which shows stunting. (See
WHO classification)
o MUAC: for community level screening (see above).
• HEENT
o Head: craniotabes, frontal bossing, delayed fontanel closure (vit D)
▪ N:B- skeletal changes seen in rickets may not be present in
children with SAM b/c rickets is disease of growing bone and
children with SAM are in reductive adaptation… (From ward)

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o Eyes: dry eyes, pale conjunctiva, icteric sclera, periorbital edema
(kwashiorkor), broom stick eyelashes
▪ Sunken eye balls (marasmus), due to atrophy of retro-orbital
tissue also seen in dehydration b/c vasoconstrictions of orbital
Veinous plexus.
▪ Bitot spot, xeropthalmia or keratomalacia (Vit A),
o Ear: signs of otitis media, tragus and ante-tragus tenderness.
o Nose: bleeding nasal mucosa,
o Mouth and throat: dry oral mucosa and oral trash, angular cheilosis,
glotitis (Vit B2), spongy bleeding gums (vitamin C), parotid enlargement,
enamel mottling, delayed eruption (Vit D).
• LGS
o There may be a Significant LAP: may be present b/c infection.
▪ NB: lymphatic organs; thymus, spleen, LN, atrophy in SAM
patients
• R/S:
o visible wasting, costo-chondral bead (Vit C; sharp and vit D dull),
Harrison’s groove and signs of pneumonia.
• CVS:
o Bradycardia, hypotension, reduced cardiac output, small vessel
vasculopathy, slow capillary refill>3sec, shock
• Abdomen: Distended (port belly), hepatomegaly with fatty liver is only seen in
kwashiorkor. fluid thrill and shifting dullness
• Musculoskeletal: Edema characterizes as pitting or non-pitting, and grade 1-3.
o Muscle wasting (Buttocks giving baggy pant appearance) and thighs
o Sign of hypocalcemia Chvostek sign (twitching of the face while striking
on jaw angle) and trousseau sign (flexion of metacarpophalangeal joint
and extension of inter phalangeal joints.
o Skeletal deformities (Vit D, Vit C and calcium deficiencies).
• Integumentary
o Skin: cold and clammy skin; shock, loose and wrinkled (marasmus),
shiny and edematous (kwashiorkor), dry follicular hyperkeratosis, patchy
hypo-and hyper-pigmentation (crazy paving/flaky paint dermatosis),
erosion and poor wound healing, Pallor, petechiae.
o Hair: brownish discoloration (flag sign), easily pluck-able, dull, sparse,
broom stick eyelashes, alopecia.
o Nails: koilonychia, thin and soft nail plates, fissure and ridges.
• Neurologic: lethargic, apathy, irritable, weak reflexes, impaired memory.
INVESTIGATIONS

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• The diagnosis of SAM is clinical but we may order some labs to look for
complications depending on the evidences we have from history and physical
examination. But basic investigations include:
o CBC, RBS, Stool Examination, PICT, Organ Function Tests (OFT) , Serum
Electrolyte, Chest X-ray.
MANAGEMENT PRINCIPLES
• Two steps of treatment; stabilization and rehabilitation.
• For patients with shock and other emergency conditions like hypoglycemia,
severe dehydration, very severe anemia (Hb< 4g/dl) and corneal ulceration
Emergency treatment must be priority before stabilizing.
• The stabilization phase repair cellular function, correct fluid and electrolyte
imbalance, restore homeostasis, and prevent death from the interlinked triad
of hypoglycemia, hypothermia, and infection.
• The rehabilitation phase restores wasted tissues (i.e., catch-up growth).
• It is essential that treatment proceeds in an ordered progression and that the
metabolic machinery is repaired before any attempt is made to promote weight
gain or correction of deficiencies.
o E.g. iron should not be given to severely malnourished child who can’t
make Hb since the reductive adaptation, in order to prevent the
accumulation of iron in excess.
MANAGEMENT (SAM GUIDELINE OF ETHIOPIA, 2020)

ADMISSION CRITERIA
• Young infants (0-6mo): if any one of these is present.
o WFL<-3SD
o Visible wasting
o Nutritional edema on both feet and complications.
• Age group 6-59mo: if any one of these is present.
o WFL/H<-3SD or MUAC <11.5cm and any medical complications or failed
appetite test
o Grade 1-2 edema and any medical complication or failed appetite test
o Grade 3 edema
o Marasmic- kwashiorkor (WFH/L<-3SD with bilateral edema or
MUAC<11.5cm with bilateral edema.
• Age group 5-18: if any one of these is present.
o WFL/H < -3Z score
o MUAC in severe category
o BMI for age <-3SD

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o Edema of both feet (+, ++), PLUS any one of the medical complications ,
or Failed appetite test
o Grade 3 edema
o Marasmic Kwashiorkor (WFL/H < -3SD with edema, OR MUAC in severe
category with edema).
MANAGEMENT OF SAM IN STABILIZATION CENTRE

• Phase 1: treatment is always given in an in-patient setting. During this phase,
o Life-threatening medical complications are treated
o Routine drugs (vitamins, folic acid, antibiotics, de-worming) are given to
correct specific deficiencies
o Feeding with F-75 milk (low caloric and sodium) is begun
• Transition phase: Here the patients are going to be prepared for phase 2 and
F75 in phase 1 is changed to F100 or RUTF
• Phase 2: can be given both in inpatient and out patient
o Phase 2 inpatient: when treating the patient in outpatient is not
reasonable; no capable care giver, no enough supply of RUTF
o Phase 2 outpatient: when there is capable care giver, enough RUTF,
OTP program is near to home.
o N: B F100 is never given in outpatient care.
SEVERE ACUTE MALNUTRITION MANAGEMENT

• Initial management focus on preventing or treating life threatening
complications of malnutrition
HYPOGLYCAEMIA
• Definition: RBS<54mg/dl
• Prevention: feeding appropriate amount of F 75(check reference card) Q 2hrs
especially in the first 24 hrs.
• Treatment: 10% glucose
o If the child is awake: 50ml of bolus orally or by NGT if the child is unable
to drink
o If the child is lethargic, unconscious or convulsing: 5ml/kg of 10%
glucose by IV then 50ml of 10% bolus by NGT
o Continue giving F75 30min after giving glucose solution and every 30min
(1/4th of the 2 hr feed) thereafter for the first 2 hrs
HYPOTHERMIA
• Definition: rectal temperature<35.5°c, or axillary temperature<35°c

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• N.B. It can be the result of hypoglycemia or infection therefore always check
RBS and check for other evidences of infection in hypothermic patients
• Prevention: feeding, avoid heat loss, keep them dry, sleep with the
mother(skin to skin), room T° 28°c-32°c
o Monitor T° Q 30 min while rewarming
DEHYDRATION
• Diagnosis:
o Mainly depending on history, watery diarrhea and vomiting with recent
change in appearance
o Excessive weight loss for edematous SAM; >2% of body weight per day
o Look for other sign and symptoms if dehydration
o Special rehydration solution: ReSoMal, rehydration solution for
malnutrition
o Best solution in malnutrition over ORS, with less sodium, more sugar and
potassium.
o Exception is dehydration caused by cholera; use ORS
• Modifying ORS to ReSoMal
o MIX WHO standard 1 litter packet ORS in 2 litters of water
o Add 50g of sugar
o Add 40ml of mineral mix or 1 scoop of CMV (combined mineral mix) - use
5 tablets of 600mg (8MEq) KCL for our setup.
• Prevention Clinical Tip!!
o Replace loss with: It’s very important to follow
o 50-100ml/loss for non-edematous SAM below age SAM patients who present
with dehydration and replace
2yrs
their loss (Vomiting, diarrhea)
o 100-200ml/loss for non-edematous SAM above age appropriately since
2yrs neglecting to do so could lead
o 30ml/loss for edematous SAM of all ages to deterioration rapidly.
o
MANAGEMENT
DEHYDRATION WITHOUT SHOCK
Table 15 Management of Dehydration in SAM patients
Frequency Amount
Every 30 min for the 1st 2 hrs 5ml/Kg
Alternate hours for the next 10 hrs 5-10ml/Kg
• Target weight is always pre diarrheal weight

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• If pre diarrheal weight is unknown, target weight = current weight x 1.05,
considering 5% loss
SHOCK (LETHARGIC OR UNCONSCIOUS)

• Diagnosis: cold hands, with slow capillary refill and weak fast feeble or absent
pulses
• IV fluid: RL or 0.45% NS with 5% dextrose.
o NB: RL and 0.45% saline are the preferred fluids for management of
shock in malnutrition b/c of their low sodium concentration as compare
to NS.
• Amount: 15ml/Kg over 1hr, reassess response
• If improving repeat 15ml/Kg over 1 hr
• If not improving consider septic shock and put on maintenance 4ml/kg/hr and
look for cross matched blood, 10 ml/kg slowly over 3 hours or packed RBC in
case of heart failure
• Evaluate the patient further to identify the cause
• Follow patients with V/S, wt, input output, liver size,
ANEMIA
• Mild: Hgb<age-appropriate value, >9g/dl
• Moderate: Hgb≤9g/dl, >7g/dl
• Severe: Hgb≤7g/dl
• Very severe anemia: Hgb<4g/dl; transfusion threshold for malnutrition
• Investigate other possible causes such as malaria and intestinal parasites (for
example, hookworm).
• Do NOT give iron during stabilization phase as it can damage cell
membranes and make infections worse.
• Pseudo-anemia: dilutional anemia on 2-14 days of treatment due to movement
of fluids from to tissue to vascular space transient and normally resolves
spontaneously after 2 or 3 days when kidney function recovers, and excess
fluids can be eliminated.
• For these reasons, transfusion is not recommended between 48 hours and day
14 days unless there is heart failure and the cause is other than dilution
anemia.
BLOOD TRANSFUSION
• Give blood transfusion in the first 48 hours if:
o Hgb is < 4 g/dl, (Hct is < 12 %), or

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o Hgb 4 to 6 g/dl (Hct 12 to 18%) and respiratory distress
o Stop all oral intake and IV fluids during the transfusion.
• Look for signs of congestive heart failure such as fast breathing, respiratory
distress, rapid pulse, engorgement of the jugular vein, cold hands and feet,
cyanosis of the fingertips and under the tongue.
o Furosemide (1 mg/kg, given by IV)
• If no signs of congestive heart failure, transfuse whole fresh blood at 10 ml/kg
slowly over 3 hours.
• If signs of heart failure, give 5-7 ml/kg packed cells over 3 hours instead of
whole blood.
• Diuretics should never be used to reduce edema in children with Severe
Malnutrition. The purpose of giving a diuretic before a blood transfusion is to
prevent congestive heart failure from overloading the circulation with the
transfusion.
EMERGENCY EYE CARE FOR CORNEAL CLOUDING AND ULCERATION

• Corneal clouding: is haziness of the surface of the cornea (eye surface)
• Corneal ulceration is: a break in the surface of the cornea. The eye may be
extremely red or bleeding,
• Corneal clouding and ulceration are dangerous conditions that may lead to loss
of vision if not treated urgently.
• Give vitamin A and atropine eye drops immediately for corneal ulceration
o If the child has corneal clouding and ulceration, give vitamin A
immediately as in the table below.
Table 16 Dosage of Vitamin A
• one drop atropine (1%) into the

affected eye(s) to relax the eye and
prevent the lens from pushing out.
• Tetracycline eye drops and
bandaging are also needed but may
wait until later in the day.
• All severely malnourished children with eye signs need vitamin A on Day 1, and
many may need additional eye care which can wait until later in the day.
MANAGING HEART FAILURE
DIAGNOSIS
• Physical deterioration with weight gain,

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• Sudden increase in liver size,
• Tenderness of the liver,
• Crackles in lungs,
• Prominent superficial and neck veins,
• Engorgement of the neck veins when the abdomen (right upper quadrant) is
pressed, (hepatojugular reflex)
• Heart failure and pneumonia may be difficult to tell apart as they can be
clinically similar. When weight gain precedes or is associated with signs of
respiratory distress, heart failure should be the first diagnosis. If there is loss of
weight, consider pneumonia instead.
• Note: Children with edema do not necessarily present with weight gain during
heart failure if the expanded circulation is due to mobilization of edema fluid
from the tissues to vascular space.
TREATMENT
• Stop all intakes of oral or IV fluids. No fluid or therapeutic feeds should be
given until heart failure has improved (even if this takes 24 to 48 hours). Small
amounts of sugar-water can be given orally to prevent hypoglycemia.
• Give Furosemide (1 mg/kg) single dose, repeat if necessary.
• If it is due to severe anemia, manage the anemia as above.
TREAT INFECTIONS
• Antibiotics is indicated for all malnourished patients.
• Selection of antibiotics depends on the Presence or Absence of complications
• Complications include
o septic shock,
o hypoglycemia,
o hypothermia,
o skin infections or dermatosis (+++ with raw skin/fissures),
o Respiratory or urinary tract infections, or
o lethargic/sickly appearance.

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Table 17 Summary of Antibiotics for malnourished child
If: Give:
No complications Amoxicillin oral: 25 mg/kg every 12 hours for 5-7 days
Complications (shock, Gentamycin IV or IM (7.5 mg/kg), once daily for 7 days, plus:
hypoglycaemia, hypothermia,
dermatosis with raw skin/fissures,
respiratory or urinary tract
infections, or lethargic/sickly
appearance)
Ampicillin IV or IM (50 mg/kg), Followed by amoxicillin oral: 25
every 6 hours for 2 days mg/kg, every 12 hours for 5 days
If resistance to amoxicillin and See details of drug on standard treatment guideline
ampicillin, and presence of medical In the case of sepsis or septic shock: IM ceftriaxone (for
complications: children/
infants beyond 1 month: 50 mg/kg every 8 to 12 hours) + oral
ciprofloxacin (5–15 mg/kg 2 times per day)
If suspected staphylococcal infections: add Cloxacillin (12.5–50
mg/
kg/dose 4 times a day, depending on the severity of the
infection)
If HIV-positive or HIV Exposed Child Treat of medical complications should be like any SAM patient
without HIV-infection or exposure. Give Cotrimoxazole
prophylaxis
as well in addition to antibiotic selected. Medical treatment
and
care should follow the National Guidelines for Comprehensive
HIV
Prevention, Treatment and Care.
If a specific infection requires an Specific antibiotics as directed in the standard treatment
additional antibiotic, also give: guideline
a. If the child is not passing urine; Gentamicin may accumulate in the body and
cause renal failure and deafness. Do not give the second dose until the child is
passing urine.
b. If amoxicillin is not available; give Ampicillin, 50 mg/kg orally every 6 hours for
5 days.
c. If ciprofloxacin bioavailability decreases when given with the milk, so should be
given 2 hours after the milk is given.

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MANAGEMENT OF ABDOMINAL DISTENSION WITH ABSENT BOWEL SOUNDS
• Abdominal distension can occur because of reduced gastrointestinal motility
due to electrolyte disturbance (Hypokalemia).
MANAGEMENT
• Gentamicin IV once daily plus Ampicillin IV every 6 hours
• Consider adding Ceftriaxone IV
• Stop all other drugs that may be causing toxicity (such as metronidazole)
• Give a single IM injection of magnesium sulphate (2ml of 50% solution).
• Pass an NG-tube and aspirate the contents of the stomach, then “irrigate” the
stomach with isotonic clear fluid (5% dextrose or 10% sucrose –the solution does
not need to be sterile). Do this by introducing 50ml of solution into the
stomach and then gently aspirating all the fluid back again. This should be
repeated until the fluid that returns from the stomach is clear.
• Put 5 ml/kg of sugar-water (10% sucrose solution) into the stomach and leave it
there for one hour. Then aspirate the stomach and measure the volume that is
retrieved. If the volume is less than the amount that was introduced, then
either a further dose of sugar-water should be given or the fluid returned to
the stomach.
• There is frequently gastric and esophageal candidiasis: give oral nystatin
suspension or fluconazole.
• Keep the child warm.
• If the child’s level of consciousness is poor give intravenous glucose,
• Do not put up a drip at this stage. Monitor the child carefully for 6 hours,
without giving any other treatment
• Improvement is measured first by a change in intestinal function (decrease in
the distension of the abdomen, visible peristalsis seen through the abdominal
wall, return of bowel sounds, decreasing size of gastric aspirates) and second
by improvement in the general condition of the child.
IF THERE IS INTESTINAL IMPROVEMENT, THEN;

• Start to give small amounts of F-75 by NG tube (half the quantities given in the
feeding table – subsequently adjust by the volumes of gastric aspirated).
IF THERE IS NO IMPROVEMENT AFTER 6 HOURS, THEN:

• Consider putting up an IV drip. It is very important that the fluid given contains
adequate amounts of potassium. Sterile Potassium Chloride (20mmol/l) should
be added to all solutions that do not contain potassium. Use Ringer-Lactate in
5% dextrose or half-strength saline in 5% dextrose. The drip should be run VERY

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SLOWLY – the amount of fluid that is given should be NO MORE THAN 2 to 4
ml/kg/h.
• When the gastric aspirates decrease so that one half of the fluid given to the
stomach is absorbed, discontinue the IV treatment and continue with oral
treatment only.
MANAGEMENT OF SAM IN TB AND HIV INFECTED CHILDREN

• Longer time to recover
• Treatment failure is common
• The treatment of severe acute malnutrition in children with HIV/ AIDS should
be the same as for HIV-negative children.
• Increased rate of drug toxicities and non-adherence to malnutrition
management
• Neither TB nor HIV is rapidly fatal illnesses. Thus, it is better to treat first
severe malnutrition in all patients and to delay introduction of ARVs or Anti-TB
drugs for one or two weeks until the liver, pancreas and intestine have
recovered sufficiently to metabolize the drugs safely.
• TB, HIV and SAM are linked and frequently appear in the same patient. Thus,
children with SAM should be particularly screened for TB and HIV.
COMPLICATIONS IN MANAGING SAM

RE-FEEDING SYNDROME
• It may follow overly aggressive enteral or parenteral alimentation.
• When excessive carbohydrates are administered, the resultant increase in
serum insulin levels may produce hypokalemia, hypophosphatemia, and
hypomagnesemia.
• The hallmark of this condition is hypophosphatemia (≤0.5 mmol/L ) and
clinically weakness, rhabdomyolysis, neutrophil dysfunction, cardio-respiratory
failure, arrhythmias, seizures, altered level of consciousness, or sudden may
occur.

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CHAPTER 3 - FLUID AND ELECTROLYTE

DISORDERS
1. Fluid composition and Fluid therapy
2. Electrolyte Disorders
3. Diarrhea and Deficit therapy

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3.1. FLUID COMPOSITION AND FLUID THERAPY

FLUID COMPOSITION
• Total body water (TBW) as a percentage of body weight varies with age.
o The fetus has very high TBW, which gradually decreases to
approximately 75% of birth weight for a term infant. TBW
decreases to approximately 60% of body weight and
basically remains at this level until puberty.
• TBW is divided between 2 main compartments:
o Intracellular fluid (ICF) and
o Extracellular fluid (ECF) which is further divided into the
▪ Plasma water and the
▪ Interstitial fluid.
• There is a delicate equilibrium between the intravascular fluid
and the interstitial fluid is regulated by The balance between Figure 2 Compartments of
o Hydrostatic and the TBW
o Oncotic forces
• An imbalance in these forces may cause expansion of the interstitial volume at
the expense of the intravascular volume.
o For example, in children with hypoalbuminemia, the decreased oncotic
pressure of the intravascular fluid contributes to the development of
edema.
o In contrast, with heart failure, there is an increase in venous hydrostatic
pressure from expansion of the intravascular volume, which causes fluid
to move from the intravascular space to the interstitial space.
FLUID BALANCE
Table 18 Body fluid balance
Typical Amount
Fluid Normal Food Variable
Input Drinks Variable
Normal Metabolism Variable
Abnormal/Iatrogenic IV Fluids Variable
Blood Transfusion Variable
Fluid Normal Urine Variable
Output Stool Variable
Sweat and Respiratory 300ml x BSA
(Insensible)
Abnormal/Iatrogenic Diarrhea Variable

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Vomiting Variable
Other GI loss (Stoma, Variable
Fistula)
Blood Loss Variable
Burn Depend on %TBSA
MONITORING AND ASSESSING FOR FLUID BALANCE

• Daily Fluid balance - Registering and monitoring for
measurable fluid inputs and out puts. Positive Fluid-Balance – Gain of
fluid.
• Daily weight monitoring - For hospitalized patients
Zero Fluid-Balance – No loss or
daily weight monitoring is reliable measure for fluid gain of fluid.
status. Incorporate daily weight monitoring as part of Negative Fluid-Balance – Loss of
vital signs. fluid.
CLINICAL ASSESSMENT
• Physical examination indicating volume depletion
o Vital signs: Low BP, postural hypotension (drop in systolic BP by 20,
increase in PR by 10), tachycardia and tachypnea
o Weight: daily weight monitoring is a very sensitive measurement.
o Delayed capillary refill time: > 2seconds
o Skin and mucosa: dried oral mucosa, decreased skin turgor
o Extremities: cold in state of shock
• Physical examination indicating volume overload states
o Weight gain: Daily weight measurement
o Lungs: Lower lung zone crackles (also called crepitation or rales)
o JVP and neck vessels: raised JVP and full neck veins
o Liver: enlarged liver
o Lower extremities: edema
FLUID THERAPY
INDICATIONS
• Indications for IV fluid therapy: 3R’s
a) Resuscitation: Rapid correction of shock using rapid boluses of IV fluids
b) Replacement: Replacement of lost fluid until signs of hypovolemia
improve and continual replacement if there is ongoing loss
c) Routine maintenance: Providing the daily fluid and electrolyte needs
using IV fluid. (Maintenance Fluid only provides 10-20% of daily calorie
requirements)

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Table 19 Maintenance Fluid Calculation
Weight Amount (ml per kg)
First 10kg 100ml/kg
Second 10kg 50ml/kg
Over 20kg 20ml/kg
E.g., For a child weighting 27kg, to calculate MF over 24hrs we use
Maintenance Fluid (MF) = (10 X 100ml) + (10 X 50ml) + (7 X 20ml) = 1640ml
TYPE AND COMPOSITION OF COMMON IV FLUIDS
Table 20 Compositions of common IV fluids

Fluid Na Cl K Glucos Ca Buffer Comment
e
Type (mmol/ (mmol/ (mmol/ (mmol/
L) L) L) (mg/dl L)
)
Plasma 135-145 95-105 3.5-5.5 70-140 2.2-2.6 24-32
NS 154 154 0 0 0 0 The highest concentration
of Na and no K or Carbonate
RL 130 109 4 0 1.35 28 Contains lactate that gets
(lactate converted to bicarbonate; it
) contains more K and less Na
5%DW 0 0 0 50 0 0 Electrolyte free.
Can’t be used for
resuscitation
DNS 154 154 0 50 0 0
Table 21 Preferred fluid for resuscitation
Clinical Disorder Preferred Fluid for resuscitation

Hemorrhage Whole or Packed Blood
Diarrhea RL
Vomiting NS
Burn RL
DKA RL

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3.2. ELECTROLYTE DISORDERS
ELECTROLYTE COMPOSITION
• The composition of the solutes in the ICF and ECF are very different.
• Sodium and chloride are the dominant cation and anion, respectively, in the
ECF. The sodium and chloride concentrations in the ICF are much lower while
potassium is more abundant. This difference — is a result of the activity of the
Na+-K+ ATPase pump.
• Proteins, organic anions, and phosphate are the most plentiful anions in the
ICF. The dissimilarity between the anions in the ICF and the ECF is largely
determined by the presence of intracellular molecules that do not cross the
cell membrane.
3.2.1. SODIUM DISORDERS
HYPERNATREMIA
• Hypernatremia is defined as plasma
sodium concentration of >145mmol/l.
ETIOLOGY
• Hypernatremia can be classified based on Figure 3 Sodium level and their interpretation
the volume status of the body into
o Hypovolemic Hypernatremia
o Euvolemic Hypernatremia
o Hypervolemic Hypernatremia
Table 22 Causes of Hypernatremia
Hypovolemic Euvolemic Hypervolemic
Gastrointestinal losses Diabetes Insipidus Excess Sodium Intake
− Diarrhea − Central − Ingestion of
− Emesis/nasogastric − Nephrogenic seawater or sodium
suction Increased insensible chloride
− Osmotic cathartics losses − Intravenous
(lactulose) − Premature hypertonic saline
Cutaneous losses infants − Hyperaldosteronism
− Burns − Radiant − Improperly mixed
− Excessive sweating warmers formula
Renal losses − Phototherapy − Excess sodium
bicarbonate

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− Osmotic diuretics − Inadequate
(mannitol) intake:
− Diabetes mellitus − Ineffective
− Chronic kidney disease breastfeeding
(dysplasia and − Child neglect
obstructive uropathy) or abuse
− Polyureic phase of acute − Adipsia (lack
tubular necrosis of thirst)
− Post obstructive diuresis
CLINICAL MANIFESTATIONS
• Clinical manifestation of hypernatremia depends on degree of hypernatremia
and speed (acuity) of development.
• Generally, in hypernatremia patients CNS sign and symptoms and
manifestations of dehydration dominate than any other systems.
Table 23 Clinical Manifestations of Hypernatremia
Dehydration Signs like Central nervous system (CNS) symptoms
• sunken eyeball like
• slow doughy skin pinch • restless,
• Lethargy/irritability • irritability
• Severe thirst • weakness
• lethargy
• high-pitched cry
• and hyperpnea are present
N.B. Even though dehydration is invariably present in hypernatremia symptomatically it
is less than expected than the degree of dehydration because of the shift of water
from intracellular space to extracellular space.
COMPLICATIONS
• Brain hemorrhage occurs as the extracellular osmolality increases, water moves
out of brain cells, leading to a decrease in brain volume. This decrease can
result in tearing of intracerebral veins and bridging blood vessels as the brain
moves away from the skull and the meninges. Patients may have subarachnoid,
subdural, and parenchymal hemorrhages.
• Thrombotic complications occur in severe hypernatremia dehydration; they
include stroke, Dural sinus thrombosis, peripheral thrombosis, and renal vein
thrombosis. This is secondary to dehydration and possibly hypercoagulability
associated with hypernatremia.

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TREATMENT
• Treatment principles are
1. Correction of water deficit and restoration of serum tonicity
2. Avoid rapid correction.
3. Detection and treatment of the underlying cause
1. CORRECTION OF WATER DEFICIT AND RESTORATION OF The following formula is

SERUM TONICITY often cited for calculating
the water deficit:
• The main stay of treatment for hypernatremia is water (free
water) given orally (preferred) but management depends on Water deficit = 0.6 × Body
the severity of hypernatremia and the patient’s volume weight × 1-145 /[current
state. sodium]
• Hypovolemic Hypernatremia: Intravenous RL/NS (NS
preferred) until hypovolemia improves.
• Euvolemic Hypernatremia: Correct water deficit using either oral free water
(if patient can take oral fluids) or 0.45% Saline (if available) or 5%DW (in our
setup)
• Hypervolemic Hypernatremia: Use 0.45% Saline (if available) or 5%DW (in our
setup) along with diuretics.
2. AVOID RAPID CORRECTION

• The goal is to decrease the serum sodium by <12 mEq/L every 24 hrs., a rate of
0.5 mEq/L/hr.
• As hypernatremia develops, the brain generates idiogenic osmoles to increase
the intracellular osmolality and prevent the loss of brain water. If the serum
sodium concentration is lowered rapidly, there is movement of water from the
serum into the brain cells to equalize the osmolality in the 2 compartments.
The resultant brain swelling manifests as seizures or coma.
3. DETECTION AND TREATMENT OF THE UNDERLYING CAUSE
HYPONATREMIA
• Hyponatremia is a serum sodium level <135 mEq/L.
• Hyponatremia is caused by an imbalance in the body's handling of water,
resulting in a relative deficit of effective plasma osmolality (tonicity) to total
body water.
ETIOLOGY

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• Hypovolemic Hyponatremia – is caused by fluid loss and associated with an
appropriate elevation in ADH, which in the setting of excess free water
repletion leads to water retention and a drop of plasma sodium.
• A history of fluid loss (eg, vomiting, diarrhea, profound bleeding, diuretic
therapy) and
• Signs of extracellular volume depletion (eg, decreased skin turgor, tachycardia,
or orthostatic or persistent hypotension) are indicative of hypovolemia.
HYPERVOLEMIC HYPONATREMIA— is typically seen in conditions associated with
reduced effective circulating volume (ECV) despite having total body volume overload
like Nephrotic syndrome, Cirrhosis, Heart Failure and renal failure.
• A history or physical finding of edema and ascites.
• The following mechanisms are thought to be involved in development of
a) Reduced ECV ➔ ADH release ➔ free water retention
b) Decreased renal perfusion ➔ stimulation of the RAAS ➔ Low urinary sodium
excretion
NORMOVOLEMIC HYPONATREMIA—Mostly is due to inappropriate excess of ADH

activity with the exception of primary polydipsia.
• Look for causes of syndrome of inappropriate ADH secretion (SIADH), such as
brain injury or infection, and pulmonary disease suggests this type of
hyponatremia.
Table 24 Causes of Hyponatremia
Hypovolemic Euvolemic Hypervolemic
Gastrointestinal losses Syndrome of inappropriate ADH Nephrotic
secretion medications -- Syndrome
− gastroenteritis
− secretory or increasing sensitivity of ADH
− osmotic diarrheas, o Chemotherapy Cirrhosis
− enteric fistulas, and (cyclophosphamide,
− ostomies vincristine, and platinum-
Diuretic-induced based agents)
o antiepileptic agents
Cutaneous losses Heart Failure
o valproate
− Excessive sweating o carbamazepine,
− Renal salt wasting o oxcarbazepine
Primary polydipsia
Reset osmostat
TREATMENT
• Objectives of treatment

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o Restore plasma tonicity
o Prevent serious CNS complications
o Avoid rapid correction
o Detect and correct the underlying cause
NON-PHARMACOLOGIC TREATMENT
• Free water restriction – for euvolemic and hypervolemic causes
• Encourage table salt intake-if not hypervolemic
PHARMACOLOGIC TREATMENT
• Hypovolemic hyponatremia - Normal saline, IV infusion-volume depending on
the estimated fluid deficit.
• Hypervolemia hyponatremia – Furosemide (or other N.B If NaCl is an available
diuretic), dose depending on the underlying disease and we can prepare an oral
previous response, when the hypervolemia corrects, the substitution for 3% NaCl, by
hyponatremia corrects by itself. adding 2 and a ½ tsp
• Euvolemic hyponatremia: if it is severe or symptomatic teaspoon of table salt in
o 3% NaCl (513mmol of Na/L), 1-2 ml/kg IV per hour 500ml of water and giving
o Should elevate the serum Na approximately 1-2mmol the solution PO at 1-
per hour 2ml/kg/hr.
o Raising the serum Na 4-6mmol/L over 2-3 hours is
enough to prevent serious neurologic complications
o Subsequently, the rate of correction should be less than 10mmol/L per
24 hours.
AVOID RAPID CORRECTION

• Rapid correction of severe hyponatremia that has been
present for more than two to three days may result in Memorization sidenote for
neurologic complications collectively called osmotic Rapid correction of sodium
demyelination syndrome (ODS) - formerly called central abnormalities
pontine myelinolysis or (CPM)
o Clinical manifestations of ODS : usually occur two From high to Low– The brain
to six days after overly rapid elevation of the will blow. (Brain edema)
From Low to High – The Pons
serum sodium concentration. Symptoms are
will die (Central Pontine
usually irreversible.
Myelinolysis)
o The symptoms dysarthria, dysphagia, paraparesis
or quadriparesis, behavioral disturbances,
movement disorders, seizures, lethargy,
confusion, disorientation, obtundation, and coma.
o The mechanism by which a rapid fall in brain volume results in
demyelination has not been established.

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3.2.2. POTASSIUM DISSORDERS

• The intracellular concentration of potassium is much higher than the plasma
concentration, majority of which is contained in muscle. Because most
potassium is intracellular, the plasma concentration does not always reflect the
total body potassium content.
• The normal distribution of
potassium between cells and the
extracellular fluid is primarily
maintained by the Na-K-ATPase
pump in the cell membrane. Figure 4 Serum Potassium level
• Insulin, Nonselective (e.g., epinephrine) and selective (e.g., salbutamol) beta-

adrenergic agents promotes intracellular potassium movement by increasing
the activity of the Na-K-ATPase pump.
• Alkalosis—Promotes intracellular potassium movement as hydrogen ions exit the
cell in response to the increase in extracellular pH. Acidosis has the opposite
effect.
HYPERKALEMIA
• Hyperkalemia is defined as serum potassim level >5.5mmol/L.
• Because of the potential for lethal arrhythmias—is one of the most alarming
electrolyte abnormalities.
ETIOLOGY
• Hyperkalemia can be caused by 4 main mechanisms
o Increased intake
o Transcellular shifts
o Decreased excretion
o False laboratory value
Table 25 Causes of Hyperkalemia
INCREASED INTAKE TRANSCELLULAR SHIFTS DECREASED EXCRETION
Intravenous or oral Acidosis Renal failure
potassium Rhabdomyolysis • Primary adrenal disease:
supplementation Tumor lysis syndrome Hyporeninemic hypoaldosteronism:
Hemolysis • Urinary tract obstruction
Blood transfusions GI bleeding • Kidney transplant
Drugs • Lupus nephritis
− Succinylcholine

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− Digitalis intoxication Renal tubular disease:
− Fluoride intoxication • Pseudohypoaldosteronis
− β-Adrenergic blockers • Urinary tract obstruction
Exercise • Kidney transplant
Hyperosmolality Medications:
Insulin deficiency • Angiotensin-converting enzyme
inhibitors
• Angiotensin II blockers
• Potassium-sparing diuretics
• Nonsteroidal anti-inflammatory drugs
• Trimethoprim
• Heparin
• FALSE LABORATORY VALUE – is the leading cause of hyperkalemia in clinical
practice
o Excessive/Tight tourniquet during blood drawing(due to hemolysis and
tissue ischemia)
o Thrombocytosis
o Leukocytosis
• The most important effects of hyperkalemia are a result of the role of
potassium in membrane polarization especially on cardiac conduction system
and skeletal muscles.
CARDIAC MANIFESTATIONS
• Symptoms of cardiac conduction abnormalities –
palpitations, syncope, or asystole.
• The easiest way to pick up cardiac conduction
problems is to see if there are any ECG changes
like –
o Tall peaked T-waves (earliest sign)
o Prolonged PR interval, Figure 5 ECG of Hyperkalemia
o decreased or absent P waves

o widening of QRS complex (most severe)
MUSCULAR SYMPTOMS
• Paresthesia, fasciculations, weakness, and even an ascending paralysis
• Muscle weakness or paralysis – Muscle weakness is usually flaccid and
ascending, beginning in the legs and progressing to the trunk and arms.

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TREATMENT
• The plasma potassium level, the ECG, and the risk of the problem worsening
determine the aggressiveness of the therapeutic approach.
• Severe hyperkalemia with potassium level greater than >7 and the presence of
ECG changes require urgent and aggressive medical treatment usually under
continuous cardiac monitoring.
PRINCIPLES OF TREATMENT OF HYPERKALEMIA ARE

1. Stop intake of extra potassium: The first action in a child with hyperkalemia is
to stop all sources (foods, drinks or IV fluids) of additional potassium and to
stop drugs that increase plasma potassium levels.
2. Stabilize the heart to prevent life-threatening arrhythmias : Using Calcium
infusion— Calcium gluconate (10 percent solution) is given at a dose of
0.5mL/kg by IV infusion over ten minutes.
3. Treating the hyperkalemia
a) To shift extracellular potassium into the intracellular compartment—
▪ The combination of IV insulin and glucose is the preferred method to
shift extracellular potassium into the cell. Insulin administration drives
extracellular potassium into the cells by enhancing the activity of the
Na-K ATPase pump in skeletal muscles. Glucose is given concomitantly to
prevent hypoglycemia.
▪ Regular insulin (dose of 0.1 units per kg, maximum dose of 10 units) is
given along with a dextrose (glucose) dose of 0.5g/kg over 30 minutes.
▪ Give 10 percent dextrose (100mg/mL)at a dose of 5mL/kg.
b) Therapies removing potassium from the body—
▪ The three available modalities for potassium removal in children are
diuretics, cation exchange resin, and dialysis.
▪ Diuretics - Loop and thiazide diuretics can be used. (Furosemide 1
mg/kg IV)
Table 26 Food Rich in Potassium
Food Rich in potassium Amount (mg per set of serving)
Potatoes (with skin) 900mg
Sweet Potatoes (with skin) 500mg
Beans 600mg
Seafood/Fish (Salmon, mackerel, halibut) 500mg
Bananas 422mg
Avocado 365mg
Spinach and other green leafy vegs. 400mg

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HYPOKALEMIA
• Hypokalemia is defined as a serum or plasma potassium that is less than
3.5mmo/l.
ETIOLOGY
• Gastrointestinal loss
• Transcellular shifts
• Increased urinary loss
Table 27 Causes of Hyperkalemia
Gastrointestinal Transcellular Shift Increased urinary losses
Increased losses Alkalosis Increased delivery of
− diarrhea, Increased insulin sodium to distal nephron
− vomiting (not activity − Diuretics
important cause, Beta-adrenergic − Mannitol,
since there is small agents − Hyperglycemia
amount of potassium − Salbutamol − Non-reabsorbed
in gastric fluid) − Epinephrine anions
Decreased intake − Dopamine − Tubular injury
− anorexia, bulimia Hyperthyroidism (Cisplatin)
Other Drugs Types I and II renal tubular
− Barium acidosis
− Antipsychotic Increased
drugs mineralocorticoid activity
− Chloroquine
• Clinical manifestations vary depending on the severity and acuity of
hypokalemia.
• Symptoms are unlikely to occur in most healthy children until serum potassium
is below 3 mEq/L.
o Muscle weakness and paralysis - typically starts in the proximal muscles of
the lower extremities and progresses upwards to the trunk and upper
extremities. It might also involve respiratory muscles, which may result in
respiratory failure and death.
o Smooth muscle weakness, which is manifested as ileus resulting in
abdominal distension, anorexia, nausea, vomiting and/or constipation.
o Cardiac arrhythmias and electrocardiogram (ECG) changes
▪ Premature atrial and ventricular beats,

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▪Sinus bradycardia,
▪paroxysmal atrial or junctional
tachycardia,
▪ Atrioventricular block, and
▪ Ventricular tachycardia or Figure 6 ECG of hypokalemia
fibrillation.
o Renal abnormalities: polyuria and polydipsia due to impaired urinary
concentrating ability.
TREATMENT
• The acuity and degree of the hypokalemia influence the clinical approach to
therapy.
PRINCIPLES OF MANAGEMENT
1. JUDICIOUS POTASSIUM SUPPLEMENTATION
• In symptomatic patients (arrhythmias, marked muscle weakness, or paralysis),
rapid IV potassium supplementation is needed
o KCL 40mEq/L is given at a rate not to exceed 0.5 to 1 mEq/kg/hr. The goal
is to raise the potassium level by 0.3 to 0.5 mEq/L.
• In asymptomatic patients Oral therapy with PO KCL is preferred and IV
supplementation should be reserved for those who are unable to take oral
medications.
o Patients should be encouraged to eat food rich in potassium.
2. IDENTIFYING AND, IF POSSIBLE, TREATING THE UNDERLYING CAUSE OF

HYPOKALEMIA (EG, HYPOMAGNESEMIA)
3.2.3. CALCIUM DISORDERS

• Normal calcium homeostasis depends on parathyroid hormone (PTH) and
vitamin D.
o Parathyroid hormone
▪ Mobilizing calcium from the bone – via stimulation of osteoclastic bone
resorption and release of calcium from a rapidly exchangeable calcium
pool.
▪ Stimulating 1-alpha-hydroxylase in the kidney – thereby converting 25-
hydroxyvitamin D to 1,25-dihydroxyvitamin D (the active form of vitamin
D), which directly increases intestinal calcium absorption.
▪ Directly increasing calcium reabsorption in the distal renal tubule
o Vitamin D

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▪ promotes calcium and phosphorus absorption from the gastrointestinal
tract.
▪ Lesser effects on calcium reabsorption from the renal tubules.
HYPOCALCEMIA
•Hypocalcemia is defined as serum Total Calcium level below 8.5 mg/dL (2.12
mmol/L) or Ionized Calcium level below 4.65 mg/dL(1.2 mmol/L).
ETIOLOGY
Table 28 Causes of hypocalcemia
Low PTH (hypoparathyroidism) Impaired Synthesis or Secretion Of PTH
Genetic
− DiGeorge Syndrome
− Autosomal Dominant Disorders Of PTD Production
− Autosomal Recessive Disorders Of PTH Production
Autoimmune
Parathyroid or thyroid gland surgery
Infiltration of parathyroid gland (eg, iron overload)
High PTH Hypovitaminosis D (impaired vitamin D intake or synthesis)
− Insufficient dietary intake and/or sun exposure
− Decreased gastrointestinal absorption
− Defects in vitamin D metabolism or action
− Liver disease (including some
− Drugs
◦ anticonvulsants,
◦ isoniazid, and
◦ rifampin).
− Renal disease
− 25-hydroxylase deficiency
Vitamin D "dependent" rickets
Miscellaneous Hungry bone syndrome
hypoparathyroidism after parathyroidectomy leading to reductions
in bone reabsorption and increases in bone formation, leading to an
increased influx of calcium into bone and hypocalcemia.
Osteopetrosis
Sepsis or acute severe illness
Hyperphosphatemia
Alkalosis
Intravenous products with citrate/lactate
Pancreatitis

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Hypomagnesemia
ACUTE MANIFESTATIONS
(1) Tetany
• Acute hypocalcemia directly increases peripheral neuromuscular irritability and
hyperexcitability.
• Tetany is manifested clinically by sensory, muscular and automomic
dysfunction
• Sensory Symptoms - perioral and acral paresthesias
• Motor Symptoms - stiffness and clumsiness, myalgia, and
muscle spasms and cramps. carpopedal spasm and spasm of
the respiratory muscles and of the glottis other
manifestations.
• Trousseau's sign — It is the induction of carpopedal spasm by
inflation of a sphygmomanometer above systolic blood
pressure for three minutes
• Carpopedal spasm, as indicated above, is characterized by Figure 7 Trousseau's sign
adduction of the thumb, flexion of the metacarpophalangeal

joints, extension of the interphalangeal joints, and flexion of
the wrist
• Chvostek's sign — Chvostek's sign is contraction of the
ipsilateral facial muscles elicited by tapping the facial nerve
just anterior to the ear. The response ranges from twitching of
the lip to spasm of all facial muscles
• Autonomic symptom - diaphoresis, bronchospasm, and biliary
colic.
(2) Seizures — Both generalized and focal seizures can occur
Figure 8 Chvostek's sign
(3) Cardiovascular — Hypotension may complicate acute
hypocalcemia
CHRONIC MANIFESTAIONS
• Ectopic calcification (basal ganglia)
• Extrapyramidal signs
• Parkinsonism
• Abnormal dentition
TREATMENT
SEVERE ACUTE AND/OR SYMPTOMATIC HYPOCALCEMIA

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• Initially, IV calcium gluconate should be given at 0.5mL/kg by IV infusion over
ten minute
• Then a 1000ml calcium gluconate should be prepared to give 0.5 to 1.5 mg/kg
of elemental calcium per hour.
ASYMPTOMATIC, MILDLY SYMPTOMATIC OR CHRONIC HYPOCALCEMIA

• Oral calcium supplementation is preferred.
HYPERCALCEMIA
•Hypercalcemia is defined as serum Total Calcium level above 10.5 mg/dL (2.62
mmol/L) or Ionized Calcium level above 5.25 mg/dL (1.3 mmol/L).
ETIOLOGY
Table 29 Causes of Hypercalcemia
Parathyroid mediated Primary hyperparathyroidism (sporadic)
Inherited variants
• Multiple endocrine neoplasia (MEN)
syndromes
• Familial isolated
hyperparathyroidism
• Hyperparathyroidism-jaw tumor
syndrome
Familial hypocalciuric hypercalcemia
Tertiary hyperparathyroidism (renal
failure)
Non-parathyroid mediated Hypercalcemia of malignancy
Vitamin D intoxication
Medications Thiazide diuretics
Lithium
Teriparatide
Abaloparatide
Excessive vitamin A
Theophylline toxicity
Miscellaneous Hyperthyroidism
Acromegaly
Pheochromocytoma
Adrenal insufficiency
Immobilization
Parenteral nutrition
Milk-alkali syndrome

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• Renal: Polyuria, Polydipsia, Nephrolithiasis, Nephrogenic Diabetes insipidus
• GI: Anorexia, Nausea, Vomiting, Constipation, Pancreatitis
• Musculoskeletal: Weakness, Bone Pain, Memory note for hypercalcemia symptoms
Osteopenia Psychiatric moans
• Neurologic: Decreased concentration, Abdominal groans
confusion, stupor, coma Renal stones
• CVS: Bradycardia and Hypertension Painful bones

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3.3. DIARRHEA AND DEFICIT THERAPY

DEFINITION
• Diarrhea is best defined as excessive loss of fluid and electrolyte in the Stool.
o Subjectively, Diarrhea is the passage of loose or watery stools at least
three times in a 24-hour period.
o Objectively, diarrhea is defined as stool volume of more than 20
grams/kg/day in infants and toddlers (<10 kg), or more than 200
grams/day in older children or teenagers
o Diarrhea is an increased volume, fluidity, or frequency of stool relative
to the usual pattern of individual. (WHO).
PATHOPHYSIOLOGY
• The basis of all diarrheas is disturbed intestinal solute transport and water
absorption.
• Disorders that interfere with absorption in the small bowel tend to produce
voluminous diarrhea,
• whereas disorders compromising colonic absorption produce lower-volume
diarrhea.
• The explanations for the pathogenesis are:
1. SECRETORY DIARRHEA
• Occurs when solute transport system is in an active state of secretion by:
o a secretagogue - gastrointestinal peptides (such as vasoactive
intestinal peptide and gastrin),
o cholera toxin
• Decreased absorption
• Persists during fasting
• On Stool Examination
o no stool leukocytes
o Watery, normal osmolality with ion gap <100 mOsm/k
• Example
o Cholera, toxigenic Escherichia coli; carcinoid, VIP, neuroblastoma,
congenital chloride diarrhea, Clostridium difficile, cryptosporidiosis
(AIDS)
2. OSMOTIC DIARRHEA
• occurs after ingestion of a poorly absorbed solute. The solute can be:
o Not well absorbed (magnesium, phosphate, lactulose, or sorbitol)
o not well absorbed due to the disorder of the small bowel (lactose
with lactase deficiency, glucose with rotavirus diarrhea)

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o lesser volume than a secretory diarrhea and stops with fasting.
• On stool examination
o no stool leukocytes
o Watery, acidic, reducing substance and increased osmolality with ion
gap >100 mOsm/kg.
3. MOTILITY DISORDER
• Can be increased or decreased motility
• Increased: the diarrhea is due to decreased transit time.
o Loose to normal appearing stool, stimulated by gastrocolic reflex
o Ex: Irritable bowel syndrome, thyrotoxicosis, postvagotomy dumping
syndrome.
• Decreased: the diarrhea is due to Defect in neuromuscular unit(s) stasis
(bacterial overgrowth)
o Loose to normal appearing stool
o Pseudo obstruction, blind loop
4. DECREASED SURFACE AREA
• The diarrhea is due to Decreased functional capacity
• The diarrhea is watery in consistence
o Ex: Short bowel syndrome, celiac disease, rotavirus enteritis
5. MUCOSAL INVASION
• The diarrhea is due to Inflammation, decreased colonic reabsorption, increased
motility
• Blood and increased WBCs in stool
o Example: Salmonella, Shigella infection; amebiasis; Yersinia,
Campylobacter infection.
CLASSIFICATION
• Based on onset and duration diarrhea is classified as:
1. ACUTE DIARRHEA:
• is defined as sudden onset of excessively loose stools of >10 mL/kg/day in
infants and >200 g/24 hr in older children, which lasts <14 days.
• Normally in young infant ~ 5 mL/kg/day of stool and ~ 200 g/24 hr in an adult.
Dysentery is a term for small volume, frequent bloody stools with mucus, tenesmus,
and urgency. It is the predominant symptom of colitis.
2. CHRONIC DIARRHEA
• last >14 days with gradual onset.

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• typically associated with serial enteric infections and malnutrition;
• comorbid conditions, such as HIV/AIDS, malaria, or tuberculosis, result in
malnutrition that impairs the child’s immune response, thereby potentiating
the likelihood of prolonging diarrhea or acquiring another enteric infection.
• Example:
o E. coli and Giardia lamblia
o Clostridium difficile or cytomegalovirus (opportunistic agents in
oncologic patients and in inflammatory bowel diseases)
o Cryptosporidium (in AIDS patients)
3. PERSISTENT DIARRHEA
• lasts > 14days but starts as acute diarrhea. Further classified as:
o Severe persistent diarrhea (with any kind of dehydration) and
o Persistent Diarrhea (without dehydration).
Dehydration: is majorly a complication of acute diarrhea. Is classified as no
dehydration, some dehydration, and severe dehydration.
APPROACH TO PATIENT WITH DIARRHEA

HISTORY
SYMPTOMS
• Characterize the diarrhea: its duration (acute or chronic), frequency, and
character (if bloody or not)
• Associated symptoms like
o abdominal cramps, and
o vomiting
o nausea and vomiting (nonspecific symptoms) - upper intestine infection
o Fever - inflammatory diarrhea and also dehydration or coinfection (e.g.
urinary tract infection, otitis media)
o Severe abdominal pain and tenesmus - the large intestine and rectum.
Nausea and vomiting and absent or low-grade fever with mild to moderate
periumbilical pain and watery diarrhea - small intestine involvement and reduce the
likelihood of a serious bacterial infection.
RISK FACTORS
• Poverty (ask family income)
• Poor personal and environmental hygiene (ask personal experience of washing
hand after toilet and washing of food preparing materials and hands properly
before preparing food)
• Malnutrition –

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o NB: There is a vicious cycle relation between diarrhea and malnutrition.
(So, ask properly to know which one is the cause for the other, meaning
whether the diarrhea (infection) or the edema (malnutrition) comes
first?)
• Bottle feeding
• Lack of immunization (rota virus).
• Assessment of a child with acute diarrhea should include evaluation of the
following:
• G/A - Acute sick looking (Abdominal pain, Dehydreated)
• V/S
o Temperature — Fever is common in diarrheal illness.
▪ fever or hypothermia with watery diarrhea should raise clinical
suspicion of a comorbid illness. (Example, malaria in endemic
area)
o Pulse rate — weak pulse, tachycardia (due to dehydration and
hypovolemia)
o Respiratory rate — tachypnea
o Blood pressure — decreased (sign of dehydration and then hypovolemic
shock)
• HEENT - Sunken Eyeball (sign of dehydration)
• R/S — Tachypnea can be a sign of pneumonia in the setting of cough or
difficulty breathing.
o Children with dehydration should be reassessed for pneumonia following
initial rehydration.
• ABDOMEN — cylindrical abdominal mass is palpable (in the case of
Intusseception)
• IS - check for skin pinch (sign of dehydration)
• CNS —
o Irritability (in moderate dehydration)
o lethargy and coma (in severe dehydration)
o Encephalopathy or seizures - in Shigella and Salmonella.
The differential diagnosis of seizures in a child with diarrhea includes hypoglycemia,
hyponatremia, hypernatremia, encephalopathy, meningitis and febrile seizures.
CAUSES OF DIARRHEA

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Table 30 Causes of Diarrhea
Cause Infants and young children Older children and
adolescents
Gastrointestinal Viruses Viruses
infections Bacteria Bacteria
Parasites Parasites
Non-gastrointestional Otitis media Systemic infections
infections (parenteral Urinary tract infections
diarrhea) Other systemic infections
Anatomic Intussusception Appendicitis

abnormalities Hirschsprung disease (± Partial obstruction
toxic megacolon) Blind loop syndrome
Partial bowel obstruction
Blind loop syndrome
Intestinal lymphangiectasis
Short gut syndrome
Inflammatory bowel Ulcerative colitis (± toxic

disease megacolon)
Crohn's disease (± toxic
megacolon)
Malabsorption or Cystic fibrosis Celiac disease

increased secretion Celiac disease Disaccharidase deficiency
Disaccharidase deficiency Acrodermatitis enteropathica
Acrodermatitis Secretory neoplasms
enteropathica
Immunodeficiency Severe combined Human immunodeficiency
immunodeficiencies and virus infection (HIV)
other genetic disorders
Human immunodeficiency
virus infection (HIV)
Endocrinopathy Congenital adrenal Hyperthyroidism

hyperplasia Hypoparathyroidism
Miscellaneous Antibiotic-associated
diarrhea Irritable bowel syndrome
Pseudomembranous colitis Psychogenic disturbances
Toxins
Hemolytic uremic
syndrome
Neonatal drug withdrawal

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3.3.1. ACUTE GASTROENTERITIS

DEFINITION
• It is an infection of the gastrointestinal tract caused by bacterial, viral, or
parasitic pathogens
Diarrheal disorders are more commonly used to denote infectious diarrhea, although
several noninfectious causes with vomiting and/or diarrhea are well recognized.
EPIDEMIOLOGY
• Accounts 9% of childhood deaths, with an estimated 0.71 million deaths per
year globally, making it the second most common cause of child deaths
worldwide.
• Preventive rotavirus vaccination, improved case management of diarrhea, and
improved nutrition of infants and children have decreased diarrheal mortality
(However, no significant changes in incidence)
TRANSMISSION
• By person-to-person contact (those that are infectious by small inoculum):
Shigella, enterohemorrhagic Escherichia coli, Campylobacter jejuni,
noroviruses, rotavirus, Giardia lamblia, Cryptosporidium parvum, Entamoeba
histolytica.
• By contaminated food or water supply: cholera.
ETIOLOGY
• Differ by age group, geographic region and type of diarrhea.
• Rota virus, Cryptosporidium, Shigella, enterotoxigenic Escherichia coli are
common organisms in children causing diarrhea.
• Rota virus is the most common pathogen among children under 2 years old.
• Cryptosporidium 2nd most common pathogen among children under 1 year old
and it is uncommon above 2yrs old children.
• Cryptosporidium common among children with RVI.
• Shigella is the most common pathogen among children 2-5 years old.
• E coli is common in older children
• V. cholerae is important bacterial cause in endemic areas.
• Shigella is the most common etiology of invasive or bloody diarrhea in
resource limited countries. Other causes for invasive bloody diarrhea are
salmonella enterica, campylobacter spp, enterohemorrhagic e.coli and
Entamoeba histolytica.
• VIRAL CAUSES
o rotavirus o sapoviruses
o noroviruses o enteric adenoviruses

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o astroviruses.
• BACTERIAL CAUSES
o Salmonella o Shigella
o Clostridium perfringens o Cryptosporidium
o Campylobacter o Yersinia
o Staphylococcus aureus o Listeria
o E. coli o Vibrio
o Clostridium botulinum o Cyclosporaspecies
CLINICAL ASSESSMENT
• The assessment of the child with diarrhea can be divided into four components
to guide clinical management:
o Classification of the type of diarrheal illness
o Assessment of hydration status
o Assessment of nutritional status
o Assessment of co-morbid condition
1. Classification Of Diarrhea — as acute, chronic, persistent or dysentery.
2. Hydration Status — The degree of dehydration should be assessed at presentation
based on physical signs and symptoms.
• The World Health Organization (WHO) has issued recommendations for
assessing dehydration based on four clinical signs. (see table below).
3. Nutritional Status — Because, recurrent diarrhea in childhood is associated with
malnutrition, which contributes to delays or irreversible deficits in physical and
cognitive development.
NB: Children with acute diarrhea and malnutrition are at increased risk for developing
fluid overload and heart failure during rehydration.
4. Diagnostic Studies — Most children with acute diarrhea do not require laboratory
testing, although in complex cases some laboratory studies may be useful:
o Glucose And Electrolyte Assessment – if with seizures or altered
consciousness
o Relevant Investigations - for suspected pneumonia, sepsis, meningitis,
urinary tract infection or HIV infection
o Imaging Studies - for patients with acute abdominal findings on physical
examination.
o Microscopy - for presumptive diagnosis of two important causes of
gastroenteritis:
▪ Cholera (using dark field microscopy to detect motile Vibrios, which
appear as "shooting stars")

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Amoebic dysentery (using direct microscopy to detect Entamoeba
▪
trophozoites containing red blood cells).
o Microbiology laboratory evaluation - for invasive diarrhea (dysentery) who
do not respond to empiric antibiotic therapy.
Table 31 Classification of Dehydration
COMPLICATION
• Dehydration
• Hypovolemic shock
• Malnutrition
• Secondary infection
• Micronutrient deficiency (iron, zinc, vitamin A)
• Based on the pathogen different extraintestinal manifestations.
TREATMENT
PRINCIPLE OF MANAGEMENT
1. Fluid therapy
2. Enteral feeding and diet selection
3. Zinc supplementation
4. and additional therapies such as probiotics.

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1. FLUID THERAPY (KNOW IN DEPTH)

• Fluid management consists of two phases: Replacement and Maintenance.
A. REPLACEMENT THERAPY
• is to replenish deficits in water and electrolytes lost and replacement of the
ongoing losses.
• Continued until all signs and symptoms of diarrhea are absent and the patient
has urinated; ideally this is achieved during the first four hours of therapy.
• The deficit is calculated based on the dehydration status
• No dehydration,
• Some dehydration 5%,
• Severe dehydration 10%) by estimating target weight.
▪ Target weight = Current Weight + % of dehydration X (Current
Weight).
The approach to fluid and electrolyte management depends on the degree of

dehydration and the goal is to reach target weight.
NO SIGNS OF DEHYDRATION;
• Treatment plan a: home therapy to prevent dehydration and malnutrition
o Rule 1: Give the child more fluids than usual, to prevent dehydration.
o Rule 2: Give supplemental zinc (10 - 20 mg) to the child, every day for
10 to 14 days.
o Rule 3: Continue to feed the child, to prevent malnutrition.
o Rule 4: Take the child to a health worker if there are signs of
dehydration or other problems.
SOME DEHYDRATION
• Treatment Plan B: oral rehydration therapy for children with some dehydration
o 75 ml/kg ORS solution is given within the first 4 hrs
o Check hydration status while giving the fluid (dehydration or
overhydration).
o Replace ongoing loss.
o After completion check for the target weight
o Give supplemental zinc
o Except for breastmilk, food should not be given during the initial four-
hour rehydration period.
SEVERE DEHYDRATION
• Treatment Plan C: for patients with severe dehydration
o Manage urgently with IV fluids in a hospital setting.

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o The goal of rehydration with intravenous fluids is to stabilize the
circulation immediately.
o Give 100 ml/kg Normal saline or Ringer's Lactate Solution divided as
follows:
▪ For infants it is given over 6 hrs as
− 30 ml/kg over the first 1 hrs
− Then 70ml/kg over the next 5 hrs.
▪ For older children it is given over 3 hrs,
− 30 ml/kg over the first 30 min
− Then 70ml/kg over the next 2 and ½ hrs.
o Reassess the patient every 1-2 hours. If hydration is not improving, give
the IV drip more rapidly.
o After six hours (infants) or three hours (older patients), evaluate the
patient using the assessment chart.
▪ Then choose the appropriate Treatment Plan (A, B or C) to
continue treatment.
• NB: Crystalloid fluids such as Ringers’ Lactate solution or normal saline are
used. Colloids, blood products, or hypotonic fluids can be harmful and should
NOT be administered since these may cause fluid shifts which exacerbate fluid
loss in the cellular compartment.
• Rehydration for Malnourished children - refer on SAM management
REPLACEMENT OF ONGOING LOSSES
• GI losses are often associated with loss of potassium, leading to hypokalemia.
• Because of the high bicarbonate concentration in stool, children with diarrhea
usually have a metabolic acidosis, which may be accentuated if volume
depletion causes hypoperfusion and a concurrent lactic acidosis.
• Emesis or losses from an NG tube can cause a metabolic alkalosis.
• Ongoing loss replacement is based on an estimated composition of water and
electrolyte. Thus, it is different for diarrhea and vomiting.
• 1 ml loss should be replaced by 1 ml of the following solution accordingly.
REPLACEMENT FLUID FOR DIARRHEA
• Average composition of diarrhea
o Sodium: 55 mEq/L
o Potassium: 25 mEq/L
o Bicarbonate: 15 mEq/L
• Approach to replacement of ongoing losses
o Solution: 5% Glucose with NS (D5NS) + 30 mEq/L Sodium Bicarbonate +
20 mEq/L KCI
o Replace stool mL/mL every 1-6 hr

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REPLACEMENT FLUID FOR EMESIS OR NASOGASTRIC LOSSES
• Average composition of gastric fluid
o Sodium: 60 mEq/L
o Potassium: 10 mEq/L
o Chloride: 90 mEq/L
• Approach to replacement of ongoing losses
o Solution: normal saline + 10 mEq/L KCI
o Replace output mL/mL every 1-6 hr
B. MAINTENANCE THERAPY
• Replacement of the obligatory daily water losses. These losses are both
measurable (urine, stool) and not measurable (insensible losses from the skin
and lungs).
• Sources of Water Loss
o Urine: 60%
o Insensible losses: 35% (skin and lungs)
o Stool: 5%
Table 32 Calculation for maintenance fluid
Body Weight Method for Calculating Daily Maintenance Fluid Volume
BODY WEIGHT FLUID PER DAY
0-10 kg 100 mL/kg
11-20 kg 1,000 mL + 50 mL/kg for each kg >10 kg
>20 kg 1,500 mL + 20 mL/kg for each kg >20 kg*
*The maximum total fluid per day is normally 2,400 mL.
Hourly Maintenance Water Rate

For body weight of 0-10 kg: 4 mL/kg/hr
For body weight of 10-20 kg: 40 mL/hr + 2 mL/kg/hr x (wt - 10 kg)
For body weight of >20 kg: 60 mL/hr + 1 mL/kg/hr x (wt - 20 kg)*
*The maximum fluid rate is normally 100 mL/hr.
SELECTION OF FLUIDS (SEE COMPOSITIONS OF FLUIDS ABOVE)

• The usual choices for maintenance fluid therapy in children are half-normal
saline (1/2 NS) and NS. These solutions are available with 5% dextrose (D5) or
without dextrose.
• A normal plasma osmolality is 285-295 mOsm/kg.
• Infusing an intravenous solution peripherally with a much lower osmolality can
cause water to move into red blood cells, leading to hemolysis.
• Thus, intravenous fluids are generally designed to have an osmolality that is
either close to 285 or greater (fluids with moderately higher osmolality do not
cause problems).

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• Maintenance fluids usually contain D5, which provides 17 calories/100 mL and
nearly 20% of the daily caloric needs. This level is enough to prevent ketone
production and helps minimize protein degradation, but the child will lose
weight on this regimen.
• Children with volume depletion the preferred fluid composition for
maintenance fluid is D5 NS + 20 mEq/L KCl.
TIPS ON MAINTENANCE FLUID

• Recommended fluid composition for maintenance fluid is different based on
clinical conditions.
• D5 1/2NS + 20 mEq/L KCl is recommended in the child who is NPO and does not
have volume depletion or risk factors for Nonosmotic ADH production.
• D5 NS + 20 mEq/L KCl is recommended in Children with volume depletion,
baseline hyponatremia, or at risk for Nonosmotic ADH production (lung
infections such as bronchiolitis or pneumonia; central nervous system
infection).
• Fever increases evaporative losses from the skin. These losses are somewhat
predictable, leading to a 10-15% increase in maintenance water needs for
each 1°C (1.8°F) increase in temperature above 38°C (100.4°F). These
guidelines are for a patient with a persistent fever; a 1 hr fever spike does not
cause an appreciable increase in water needs.
2. NUTRITION
• The goal of nutritional management for patients without malnutrition is to
encourage sufficient feeding both during and after the diarrheal illness episode
to prevent development of malnutrition and chronic enteropathy.
o FOR INFANTS WITH DIARRHEA, once rehydration is completed:
▪ Breastfeed or,
▪ If they are not breastfed, encourage them to continue to take
undiluted formula at least every three hours, in addition to ORS.
o FOR CHILDREN WITH DIARRHEA, encourage them to take solid foods
immediately after initial dehydration is corrected.
▪ AS LONG AS DIARRHEA PERSISTS, foods high in energy content and
micronutrients should be offered at frequent intervals (at least six
meals a day).
▪ AFTER DIARRHEA RESOLVES, at least one extra meal per day
should be continued for a minimum of two weeks, or until the
patient regains normal weight-for-height.
• In children with severe malnutrition, refer on SAM management.

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3. VITAMINS AND MINERALS
ZINC SUPPLEMENTATION
• Several studies have demonstrated that zinc supplementation reduces the
severity and duration of diarrhea and reduces the incidence of subsequent
episodes of diarrhea for several months.
• Based on these studies, the WHO recommends zinc for children under 5 years
of age with diarrhea (10 mg/day for under 6 months and 20 mg/day for 10 days
for 6 months to 5 years).
VITAMIN A SUPPLEMENT —
• Because children with diarrhea in developing countries are at high risk of
vitamin A deficiency.
• If patients with signs of xerophthalmia, severe malnutrition, or a history of
measles (a three-dose series of repeated treatments)
4. ANTIBIOTICS
• are not indicated for most children with acute watery diarrhea; suspected
cholera is an important exception in which antibiotic therapy is useful.
DYSENTERY TREATMENT
• Includes correction of fluid and electrolyte losses, appropriate nutritional care,
and treatment of the underlying cause of illness.
• The management of fluids and nutrition is as described in the preceding
sections.
• Empiric antibiotic therapy for acute bloody diarrhea should be targeted against
Shigella species. It reduces the duration of fever and diarrhea, decreases the
duration of bacterial shedding, and the risk of life-threatening complications of
infection (bacteremia).
NB
• Sodium loss
o Fluid loss in acute watery diarrhea can be isonatremic, hyponatremic, or
hypernatremic.
o Corrected by ORS gradually (has advantage of reducing the risk of the
neurologic complications due to rapid shifts in osmolarity that may occur
with IV fluids)
• Potassium loss
o Stool potassium losses commonly result in hypokalemia.
o manifests with muscle weakness, paralytic ileus or arrhythmia.
o replaced using ORS

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PREVENTION
• WHO recommendations to prevent diarrhea include:
o Exclusive breastfeeding until age six months, and continued
breastfeeding with complementary foods until 2 years of age.
o The consumption of safe food and water. Boiling water.
o Handwashing after defecating, disposing of a child's stool, and before
preparing meals.
o The use of latrines; these should be located more than 10 meters and
downhill from drinking water sources.
o Immunizations — WHO strongly recommended rotavirus vaccine in
countries where diarrheal deaths account for ≥10 percent of mortality
among children aged <5.

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CHAPTER 4 - NEONATOLOGY
1. History and Physical examinations of Neonates
2. Breastfeeding
3. Neonatal sepsis
4. Perinatal Asphyxia
5. Prematurity
6. Neonatal Jaundice
7. Neonatal Seizure
8. Hypothermia
9. Birth trauma

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4.1. HISTORY AND PHYSICAL EXAMINATION OF NEONATES
HISTORY TAKING
IDENTIFICATION
• This is baby a hr (if <72hr) or day up to 1month,
gender of neonate born from _______ years old, para___ Mother, from Address
He/ She was admitted ____ days back to ward and bed number, source of
history and referral (if there is any referral note)
o Example… This is Baby Jaware a 16hr old female neonate born to a 24yrs
old parous mother. She come from Serbo, Jimma zone and admitted to
JUMC, pediatric department, neonatal ICU, room number 2 bed number
4 ,2days back with referral letter from Serbo Health center. The source
of history is mother without language barrier.
CHIEF COMPLAINT(C/C)
• The main complaint why the neonate presented to health facility. Like
o Fast breathing,
o Failure to suck
o Yellowish discoloration of skin …etc.
HPI
• This is a___ age ___sex neonate born from para__ mother who is amenorrheic
for the past____ month (if she doesn’t remember exact date of LNMP;
o if she remembers her LNMP write as ‘whose LNMP was on__).
• Maternal history
• Prior pregnancies, deliveries, and associated complications
o History of siblings with congenital defects or genetic disorders
• Complications during pregnancy
o Gestational diabetes
o Hypothyroidism
o malaria
o Hypertensive diseases of pregnancy
• Social behaviors (tobacco use, illicit drug use, alcohol use)
• Preventative care during pregnancy:
o Adherence to routine prenatal care
o Vaccination for tetanus,
o Rhogam administration, if applicable
• Results of screening tests, including:
o Genetic screenings
o Glucose tolerance test (gestational diabetes screening)
o HIV and other sexually transmitted infection (STI) screening

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• Labor and delivery
o duration of labor,
o duration of ROM,
o route of delivery,
o complication during labor and delivery.
• APGAR score (if it is documented) or assess indirectly as
o crying after delivery, bluish discoloration, any movement seen etc. and
treatment given (TTC and VK)
• Feeding pattern (interruption, unable or good) and breast problem.
• Lastly What are the current complaints (describe current compliant well)
o Any risk factors
o Rule in/Rule out
• Note: for further clarification see sample history under each topic.
PHYSICAL EXAMINATION OF NEWBORNS

QUICK EXAMINATION
• The initial examination of a newborn infant should be performed as soon as
possible after delivery.
o Value: To detect life threatening insults
• Apgar scoring → done at 1, 5 minutes.
Table 33 APGAR score - Components and scoring as follows
Sign Score 0 Score 1 Score 2
Activity Flaccid Some flexion Well flexed
Pulse Absent <100 per minute >100 per minute
Grimace No response Grimace Cough or sneeze
Appearance Pale/Blue Blue extremities Completely pink
Respiration Absent Weak Good cry
• Three levels of score
o Low APGAR score 0-3
o Moderate APGAR score 4-6
o Normal APGAR score 7-10

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SYSTEMIC DETAILED EXAMINATION

GENERAL APPEARANCE
• Mental status, Color, Respiratory distress, Activity.
• Level of consciousness:
o Normal newborn is conscious, active, alert.
o Disturbed consciousness as lethargy, coma or weak suckling may indicate
cerebral lesion or severe infection.
• Color:
o Normal newborn is pinkish in color.
o Abnormal appearance of the newborn may be:
▪ Pallor (anemia or shock)
▪ Cyanosis
▪ Jaundice.
• Signs of respiratory distress –
o grunting
o head nodding
o IC/SC retraction
o lower chest indrawing
o labored breathing…. etc.
VITAL SIGNS
• Heart rate
o (120- 160 beat/minute) …Normal
o < I00 beat/minute … Bradycardia.
o > 160 ...tachycardia.
• Respiratory rate
o (30 - 60 /minute) …Normal
o > 60 …tachypnea (RD)
o <30…. bradypnea
• Temperature
o (36.5- 37.2°C) …. Normal
o < 36.5…. Hypothermia (see classification of hypothermia under
metabolic disorders)
o > 37.5…. Fever.
ANTHROPOMETRY
• Weight: 2500g -3999gm
o Below the 10th percentile is small for gestational age (SGA).
o Above the 90th percentile is large for gestational age (LGA).
• Length:48-53 cm (average: 50cm)
o Head circumference: 33-38cm

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HEENT
Scalp swelling like
o caput succedaneum
o subgaleal hemorrhage,
o cephalohematoma
Sutures (Palpate for symmetry),
o Temporary asymmetry from passage through the birth canal is normal
(sutures overlap to allow passage through the birth canal).
o Persistent asymmetry may indicate Craniosynostosis
▪ early closure of the sutures leading to an abnormal head shape.
Figure 9 Sagittal craniosynostosis (left) and lambdoidal craniosynostosis (right)
Fontanel:
Figure 10 Fontanels
o Anterior fontanel (normal size ranges from 0.6-4cm with mean of 2cm)
o Posterior fontanel (normally less than 1cm at time of birth)
• Note: Posterior fontanel usually closes by age of 1 or 2months.it may be
already closed at birth.
• Abnormally: Opened > 1cm or not closed within 4 months
o Causes:
▪ Prematurity
▪ Increased intra cranial tension (e.g., hydrocephalus)

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▪ Mongolism
▪ Cretinism
• Anterior fontanel usually closes between 9 and 18 months.
• Anterior fontanel: Clinical value
1. Assessment of growth
▪ At birth → 3 fingers (~ 3-4cm).
▪ At 6 months → 2 fingers.
▪ At 12 months → 1 finger.
▪ At 18 months → Closed.
2. Size
▪ Large fontanel (delayed closure) in: (MACRO HIP)
− Mongolism
− Achondroplasia Note: Fontanel size calculated by
− Cretinism (Width+Length)/2
− Rickets
− Osteogenesis imperfecta
− Hypopituitarism
− Increased intra cranial tension
− Premature
▪ Small fontanel (premature closure; before 6 months) in:
− Craniosynostosis
− Microcephaly
− Congenital hyperthyroidism
− Hypercalcemia
3. Surface: normally smooth & continuous with skull bones.
▪ Bulging: in increased intra cranial tension e.g.
− CNS infections; meningitis, encephalitis
− Hydrocephalus
− Intra cranial hemorrhage.
▪ Depressed: in dehydration & shock.
Eyes
o Note the spacing, symmetry, and positioning of the eyes.
▪ Hypotelorism and hypertelorism (narrowly and widely spaced
eyes) are often associated with genetic disorders.
o Check for red reflex
▪ Present in all infants
▪ Absent in one or both eyes in:
• Retinoblastoma
• Congenital cataracts
• Retinopathy of prematurity

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o Ophthalmia neonatorum
▪ Infection of the eye
▪ Associated with periocular
swelling, conjunctival injection
and discharge.
▪ May require antimicrobials
Figure 11 Abnormal red reflex
MOUTH
• Visualize and palpate the palate for the presence or
absence of a cleft palate.
o Palpation is important because submucosal cleft
palates are not visible.
o Look for bifid or lateralized uvula as these may be a
sign of cleft palate
NECK
• Observe the neck’s range of motion.
o Congenital torticollis is a common finding due to
birth trauma and is treated with physical therapy
• Look for neck mass, asymmetry and any abnormalities
o Medial masses may indicate a thyroglossal duct
Figure 12 Six-month-old girl before going into
cyst. surgery to have her unilateral complete cleft
o Lateral masses may indicate a branchial cleft cyst. lip repaired.
o Neck webbing and cystic hygromas are associated pretty perfect
with Down's and Turner syndromes.

CHEST EXAMINATION
• Inspect for chest wall symmetry, spacing of the nipples, and any visible
deformations.
o Wide-set nipples may indicate Turner syndrome
o Accessory nipples may also be observed.
• Check for signs of respiratory distress, breathing pattern, respiratory rate, air
entry to the lungs
• AP diameter and symmetry of the chest,
• Auscultation for wheezes, crepitations, and any added breath sounds.
o Bowl sound in the chest may indicate diaphragmatic hernia.
CARDIOVASCULAR SYSTEM
• Apex beat: Normally in Left 4th space just outside mid clavicular line.
• Murmurs: Most of murmurs in early neonatal period are transient
• The 2nd heart sound may not be splited in the 1st day of life
ABDOMINAL EXAMINATION
• Shape of abdomen - full normally

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o Grossly distended (suspect intestinal obstruction)
o Scaphoid abdomen (suspect Diaphragmatic hernia)
• Examine for the presence of any noticeable deformities (omphalocele or
gastroschisis) or abdominal distension.
• Movement with respiration - If not suspect peritonitis
• Check for organomegaly
o Liver may be palpable 2 cm in neonates
o Spleen is usually difficult to palpate.
o Both kidneys should be palpable in the 1st day of life
• Check for patency of anal of opening (suspecting Anorectal malformations)
EXTERNAL GENITALIA
In Males
• Assess the penis location of the urethral meatus
o Epispadias: Urethra opens on the dorsal surface of
the penis.
o Hypospadias: Urethra opens ventrally on the glans
or the shaft of the penis.
• Scrotum - Look for “bifid scrotum” or signs of ambiguous
genitalia.
o Palpate for both testes. Can sometimes be palpated
in the inguinal canal Figure 13 A child with undescended testes
o Should descend within the first 6 months of life showing nonpalpable left testicle and
prepubertal right testicle in scrotal position
In Female
• Verify the presence of the labia, urethral meatus, and
vaginal opening.
o Term female infants have prominent labia majora.
o Preterm female infants have prominent labia
minora.
o A small amount of vaginal discharge and bleeding Figure 14 Ambiguous genitalia with bifid
scrotum and microgenia
associated with withdrawal from maternal
estrogens is normal.
• Note any signs of virilization (fused labia, clitoromegaly).
MUSCULOSKELETAL

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• Use Ortolani and Barlow maneuvers to assess hip
stability.
o The Ortolani and Barlow maneuvers are physical
examination tests that are used to diagnose
developmental dysplasia of the hip (DDH) in
infants.
o DDH is a condition in which the hip joint is not
properly formed and can result in dislocated hips.
o The Ortolani maneuver involves gently abducting
the infant's affected leg, while the Barlow
maneuver involves adducting the leg and applying
pressure on the thigh.
o These maneuvers help to determine the stability Figure 15 Ortolani and Barlow maneuvers
of the hip joint and can indicate the presence of
DDH.
• Look for other Fractures and birth injuries,
• limb defects (clubfoot, syndactyly, polydactyly)
• Spinal bifida
• Malformations.
SKIN
• Meconium staining • Jaundice, Figure 16 A child with syndactyly
• Edema • Pallor,
• rash, • Cyanosis,
Note: Acral (extremity) cyanosis is a normal finding in newborns
NEUROLOGICAL EXAMINATION
• Level consciousness.
• Muscle tone (normally flexed all limbs).

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NEONATAL REFLEXES (KNOW IN DEPTH)
• Moro reflex:
o The infant is placed in a semi-upright position.
The head is momentarily allowed to fall
backwards, followed with immediate support by
the examiners hand.
o A complete response consists of abduction of the
upper limbs at the shoulder, extension of the
forearms at the elbow and extension of the fingers
followed by adduction and flexion. Usually
followed by the infant crying.
o Check for completeness and symmetry
o Absent or weak Moro response indicate serious
CNS disturbance.
o Asymmetries occur with Erb palsy and clavicular
fractures.
o This reflex disappears by 4 to 6 months of age.
• Rooting reflex
o Stimulating one corner of the mouth or the lower
lip causes the infant to turn towards the touch
and open his/her mouth.
o This reflex disappears by 4 to 7 months of age.
• Grasp reflex (arm and plantar)
o is elicited by placing a finger in the open palm of
each hand; normal infants grasp and hold the
object.
o This reflex diminishes by 3 to 4 months of age.
• Sucking reflex
o When an object is placed in the infant’s mouth or
touches the lips, a sucking reflex is elicited.
o Reflex disappears by 12 months of age
o Check for its absence or presence
CLASSIFICATION OF THE NEWBORN

Figure 17 Neonatal reflexes
1. Based on the gestational age, a newborn could be
classified in to:
o Preterm: less than 37 Completed weeks
o Term: 37- 42 weeks
o Post term: more than 42 weeks

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• Gestational age estimation - could be estimated by one of the following
methods
o Based on last menstrual period (LMN)
o Ultrasound estimation: gestational age estimate during the first
trimester is ultrasonography can be accurate within +/- 5-7 days.
o Based on Ballard score
▪ The New Ballard has two components,
1. Neuromuscular and
2. Physical maturity scoring
▪ The accuracy is within a range of +/- two weeks.
Figure 18 Neuromuscular maturity (Lt) and Physical maturity

(Rt) assessment of new born
• Example: if calculated score is 23 the gestational age is between 32 and 34

weeks.
• Note: Ballard score only calculated when neonate presented within 72hr
2. Classifications of the newborn based on the birth weight:
o Macrosomia: birth weight of 4000 gram and
above
o Normal weight: 2500 – 3999 grams
o Low birth weight: 1500 – 2499 grams
o Very low birth weight: 1000 – 1499 grams
o Extremely low birth weight: less than 1000
grams.
3. A newborn can also be classified with respect to birth
weight and gestational age as follows:
o Appropriate for Gestational Age (AGA): if the Figure 19 Birth weight and Gestational age
birth weight is between 10-90%.

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o Large for Gestational Age (LGA) if birth weight is greater than 90%.
o Small for Gestational Age (SGA) if birth weight is less than 10%.
BASIC DEFINITIONS
• Neonatal period: a period from birth to 28 completed days of life.
• Early neonatal period: this is a period from birth to 7 completed days of life
• Late neonatal period: A period from 8 to 28 completed days of life
• Perinatal period: This period includes from 28 completed weeks of gestation to
7 days after birth.
• Gestational age: this is the time counted (in weeks) from the first day of the
woman’s last menstrual period to the day of delivery (or current date if baby
not yet born).
• Chronologic age: this is the age of the baby counted from the time of birth
• Corrected age: this is the age of the baby which is counted by reducing the
chronological age from the number of weeks born before 40 weeks of gestation

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4.2. BREASTFEEDING
• It is recommended that infants be exclusively breastfed up to the age of 6
months.
• Breastfeeding plays an important role in mother-child bonding.
• Important recommendations regarding breastfeeding
o Initiate of breastfeeding within 1 hour of birth.
o Exclusive breastfeed for 6 months of life.
o To continue with breastfeeding up to 2 years and beyond.
PHYSIOLOGY OF LACTATION
• Prolactin from the anterior pituitary:
o leads to stimulation of continued lactogenesis (milk production) and
o disruption of pulsatile GnRH secretion (causing lactational amenorrhea).
• Oxytocin from the posterior pituitary: leads to stimulation of milk ejection
(letdown) and uterine contractions.
BREAST MILK COMPOSITION

• Breast milk contains all the required nutrients (except vitamin D and vitamin
K) for infants up to 6 months of age.
• Colostrum: the first milk produced during late pregnancy until 3–4 days (up to
a week) postpartum;
o Rich in immunoglobulins (first immunization to the newborn)
o Low in quantity but have higher proteins and electrolytes than mature
milk
• Transitional Milk
o Produced after 2nd week.
o Its protein and immunologic content is relatively lower than colostrum
but higher than mature milk
o Better quantity when compared with colostrum
o Color become more whiter than colostrum
• Mature milk is composed of:
o Proteins, lactose and oligosaccharides, fats, minerals, trace elements,
and vitamins
o Proteins and cells that provide passive immunity in neonates
o Immunoglobulins (secretory IgA), lactoferrin, lysozymes
o Lymphocytes, macrophages
o Bifidobacterium that contributes to the neonate's gastrointestinal flora.
• Premature milk
o produced by mother who delivered preterm

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o It consists of increased protein and electrolytes (Na, Cl, Mg) than mature
milk.
Table 34 Contents of Mature milk and Cow's milk
Mature milk (from the 14th day) Cow's milk
g/100 mL g/100 mL
Proteins 1.1 – 1.3 3.4
Carbohydrates 6.8 4.6
Fat 3.8 - 4.5 3.7
Calories (kcal) 67 65
Unsaturated fatty acids 1.6 1.3
Salts/minerals 0.2 0.8
BENEFITS OF BREASTFEEDING
• Infant benefits
o Decreased risk of middle-ear, respiratory, gastrointestinal, and urinary
tract infections
o Breast milk immunoglobulins (especially IgA) and white blood cells
provide passive immunity for the child
o Better gastrointestinal function and motility
o Lower risk of asthma, allergies, obesity, and diabetes mellitus
• Maternal benefits
o Faster uterine involution and post-partum weight loss
o Lower risk of ovarian and breast cancers
o Postpartum contraception (lactational amenorrhea)
o Improved bonding with the infant
o Reduced costs
POSITIONING AND ATTACHMENT

GOOD ATTACHMENT AND POSITIONING
• Good attachment means:
o The baby’s mouth
should wide open
o Lower lips everted out
o More areola seen on
upper part of breast
o Chin of baby should
Figure 20 Breastfeeding positions a. Cross-cradle position b. Supine position c. Football
touch the breast hold
OPTIMAL BREASTFEEDING PRACTICE

• Newborn is fed 2-3 hourly intervals day and night
• Baby is dry, not too cold or not too warm and is hungry

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• Should be fed day and night and fed at any time on demand
• Must be fed exclusively with no water or fluid or any solid is added.
• Nothing else is given per oral except medication ordered by his doctor.
• Avoid pacifiers, dummies, bottle
• Let baby complete one breast before switching to the other breast
• Start next feeding on the breast that was fed on last in the preceding feeding
• This exclusively feeding is continued till 1st 6 months of baby life and is
adequate to support growth.
• Explain and encourage her to start semi-solid or solid complementary diet at 6
months with breast feeding continued.
CLUES FOR ADEQUATE BREAST-FEEDING INCLUDE

• At least 3-5 strong suckling before pausing for breath or rest
• Dimpling of cheeks may be seen while suckling
• Hearing of swallowing gurgle
• Milk may be seen around the mouth leaking out when it is excess
WELL AND ADEQUATELY FED BABY WILL BE SATISFIED AND

•Go asleep for 2- 4 hours between each feeding
•Will have frequent wet diapers (at least 6 times) indicating that baby has
adequate urine.
• Increase weight daily after 7 postnatal days (20 – 30 gm/kg/day). In the 1st 7
postnatal days baby tend to lose 10% of birth weight. This is normal physiology.
CONTRAINDICATIONS TO BREASTFEEDING
• Absolute
o Maternal factors: HIV infection (in developed counties only).
o Infant factors: galactosemia
• Temporary (relative)
o Maternal factors
▪ Infections: human T-cell lymphotropic virus, brucellosis,
tuberculosis, active herpes simplex on the breasts
▪ Current recreational substance use
▪ Use of substances that are excreted in milk (e.g., tetracycline,
chloramphenicol, chemotherapy agents, lithium, alcohol, illicit
drugs)
▪ Infant factors: phenylketonuria, and maple syrup urine disease

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4.3. NEONATAL SEPSIS

DEFINITION
• is defined as a clinical syndrome manifested with systemic signs and symptoms
of infection in the first 4 weeks of life.
o Neonates are uniquely prone to invasive disease because of their lack of
fully responsive innate immunity.
o Attenuated immune responses often result in minimal or nonspecific
clinical manifestations.
INCIDENCE AND EPIDEMIOLOGY

• Up to 10% of infants have infections in the 1st mo. of life.
• Newborn infection is more common in areas with limited access to healthcare
• The overall incidence of neonatal sepsis ranges from 1 to 5 cases per 1,000 live
births.
• Neonatal sepsis is one of top three causes of neonatal death and accounts for
approximately 15% of all neonatal deaths.
CLASSIFICATION
• Classified as:
A. Early-onset neonatal sepsis (EONS) (Birth to 7 days)
B. Late-onset neonatal sepsis (LONS) (8 to 30 days)
C. Very-late-onset infections or sepsis (LOS) (onset after 1 month of life)
EARLY ONSET NEONATAL SEPSIS

• occur from birth to 7 days, usually less than 72
hrs.
• is usually due to vertical transmission by
o ascending contaminated amniotic fluid or
o during vaginal delivery from bacteria
colonizing or infecting the mother's lower
genital tract.
• the risk for sepsis increases from 1 to 4 percent
in neonates born to mothers with
chorioamnionitis. Figure 21 Pathways of ascending or
intrapartum infection
• Meningitis present with Early-onset sepsis in 30%
of cases.
LATE-ONSET NEONATAL SEPSIS

• occur between 8- 30 days.
• can be acquired by the two following mechanisms:

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a. Maternal vertical transmission, resulting in initial neonatal colonization
that evolves into later infection.
b. Horizontal transmission from direct contact with care providers or
environmental sources.
▪ Disruption of the intact skin or mucosa, which can be due to
invasive procedures (e.g., intravascular catheter), increases the
risk of late-onset infection.
• In late onset sepsis meningitis is present in 75% of case.
ETIOLOGY
• The commonest organisms in EONS are (in order of decreasing frequency):
o Group B Streptococcus
o Escherichia coli (E. coli),
o Streptococci other than Group B
o Staphylococcus aureus
o Hemophilus influenza
o Listeria monocytogenes
o Gram negative anaerobes
o Fungi
o Chlamydia trachomatis
o Some viral causes are: - CMV, HSV, enteroviruses, and HIV.
• The commonest organisms in LONS are (in order of decreasing frequency):
o Coagulase negative Staphylococcus
o Staphylococcus aureus
o Klebsiella
o Group B streptococcus
o Enterobacter
o Escherichia coli,
o Enterococcus / group D Streptococcus
o Pseudomonas,
o Other Gram negatives
o Candida albicans
RISK FACTORS
• Risk factors for early onset sepsis
o Maternal fever (temp >38ºC) during labor or within 24 hours after
delivery (chorioamnionitis), meconium-stained liquor
o Maternal urinary tract infection in current pregnancy or bacteriuria
o Duration of membrane rupture > 18 hours before delivery
o Prolonged labor(>24hr)

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o Unclean Per Vaginal examination
o Foul smell vaginal discharge
o Birth weight <2kg or prematurity
o Home delivery
o poor cord care
o Congenital anomaly (gastroschisis, omphalocele, myelomeningocele
o Poor aseptic technique in handling baby
• Risk factors for late onset neonatal sepsis: -
o Use of forceps during delivery
o Invasive intrauterine monitoring which penetrates the neonatal
defensive epithelial barriers of the skin and mucosa
o Neonatal resuscitation
o Catheterization
o IV Cannulation
o Intubation
o Bottle feeding
• HISTORY
o Fever o Yellowish discoloration of
o Failure to suck eye and skin
o Change in behavior o Staring
o Fast breathing o Abnormal body movement
o Poor feeding and vomiting o Loss of consciousness….
o Diarrhea etc.
o High pitched cry
• Physical Examination (Pertinent findings)
o General appearance
▪ respiratory distress ▪ lethargy etc.
o Vital signs: -
▪ tachycardia or ▪ tachypnea or apnea
sometimes ▪ hypothermia or
bradycardia fever
o HEENT: -
▪ Bulging fontanel ▪ pale conjunctiva
▪ icteric sclera
o Respiratory system:
▪ irregular breathing ▪ grunting
▪ nasal flaring ▪ IC/SC retractions
▪ cyanosis ▪ lower chest indrawing

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▪ use of accessory
muscles
o Abdomen: -
▪ Distended abdomen ▪ hepatosplenomegaly
▪ Tender abdomen (if
peritonitis)
o Genitourinary system: -oliguria
o Integumentary system: -
▪ cold, clammy skin ▪ petechiae, purpura
▪ molting ▪ bleeding
▪ pallor ▪ edema
▪ jaundice
o Nervous system: -
▪ irritability ▪ hyporeflexia
▪ poor Moro reflex ▪ seizure
▪ hypotonia
Table 35 Clinical Criteria for the Diagnosis of Sepsis in the International Setting
IMCI AND WHO CRITERIA FOR SEVERE INFECTIONS IN CHILDREN
Neurologic: convulsions, drowsy or unconscious, decreased activity, bulging fontanel
Respiratory: respiratory rate >60 breaths/min, grunting, severe chest indrawing,
central cyanosis
Cardiac: poor perfusion, rapid and weak pulse
Gastrointestinal: jaundice, poor feeding, abdominal distention
Dermatologic: skin pustules, periumbilical erythema or purulence Musculoskeletal:
edema or erythema overlying bones or joints
Other: temperature >37.7°C (99.9°F; or feels hot) or <35.5°C (95.9°F; or feels cold)
CARDIAC
Congenital: hypoplastic left heart syndrome, other structural disease, persistent
pulmonary hypertension of the newborn (PPHN)
Acquired: myocarditis, hypovolemic or cardiogenic shock, PPHN
GASTROINTESTINAL
Necrotizing enterocolitis
Spontaneous gastrointestinal perforation
Midgut volvulus
Hepatic failure (inborn errors of metabolism, neonatal iron storage disease)
HEMATOLOGIC
Neonatal purpura fulminans
Immune-mediated thrombocytopenia
Immune-mediated neutropenia
Severe anemia
Malignancies (congenital leukemia)

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Langerhans cell histiocytosis
Hereditary clotting disorders
Familial hemophagocytosis syndrome
METABOLIC
Hypoglycemia
Adrenal disorders: adrenal hemorrhage, adrenal insufficiency, congenital adrenal
hyperplasia Inborn errors of metabolism: organic acidurias, lactic acidosis, urea
cycle disorders, galactosemia
NEUROLOGIC
Intracranial hemorrhage: spontaneous, caused by child abuse
Hypoxic-ischemic encephalopathy Neonatal seizures
Infant botulism
RESPIRATORY
Respiratory distress syndrome
Aspiration pneumonia: amniotic fluid, meconium, or gastric contents
Lung hypoplasia
Tracheoesophageal fistula
Transient tachypnea of the newborn
DIAGNOSTIC WORKUP
1. CBC (Complete Blood Count with differential): Concern for sepsis if:
o Total WBC is abnormal (<5,000 or >20,000)
o Differential with granulocytes >70%.
o Anemia
o Thrombocytopenia
2. Micro-ESR or CRP
3. Culture (blood, CSF and urine)
4. U/A: -for >1wk
5. LP: -Consider lumbar puncture if concern for meningitis (lethargy, irritability,
convulsions, bulging fontanel, meningismus
• A diagnosis of meningitis should be made based on clinical evidence
(abnormal neurological exam: seizures, abnormal tone and full fontanels)
and risk of infection for babies less than 72 hours of age, for babies age
greater than 72 hours of age diagnosed with sepsis CSF analysis should be
done to rule out meningitis despite absence of overt signs of meningitis.
• CSF analysis suggestive of meningitis:
o Identification of organism on gram stain or culture (70-80
o WBC count greater than or equal to 15 cells/mm3 in term and 30 cell in
preterm
o Low glucose (less than two third of serum value-70%) or 30mg/dl
o Protein greater than 150 mg/dl in term and 175mg/dl in preterm infant
6. CXR: -Consider chest x-ray if respiratory distress or oxygen desaturation

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TREATMENT
• Treatment of neonatal sepsis include:
1. General Supportive Measures:
o Assess airway, breathing, saturation and provide oxygen if needed.
o Provide maintenance iv fluid for the first 12hr, give blood if hemoglobin
is <12g/dl.
o Treat convulsion if present. (See neonatal seizure)
o Treat hypoglycemia and hypothermia if present.
2. Antibiotic treatment: -
o For early onset (less than 7 days)
▪ Antibiotic – Ampicillin and Gentamycin
▪ Duration: If positive cultures – minimum 7 days
• If negative cultures, and clinically well, with normal CRP or
ESR – stop after 48 hours
• If negative cultures, but not clinically well, abnormal CXR
or elevated CRP – treat as confirmed sepsis.
• If no improvement after 48 hours, or worsens, after
repeating blood cultures (if possible) and considering
further investigations, consider changing to:
o Ceftriaxone and gentamicin
o For late onset (7-30 days)
▪ Antibiotic – Ampicillin and Gentamicin
• In certain cases, where patient is critically sick or
staphylococcal infection is likely (pustular skin rash,
osteomyelitis…)
o start with triple antibiotics (cloxacillin, ampicillin
and gentamycin)
▪ If no improvement after 48 hours, or the infant’s condition
worsens. Consider changing antibiotics to:
• Cloxacillin, ceftriaxone and gentamicin or vancomycin and
gentamicin.
3. Treatment of neonatal sepsis with meningitis
o Antibiotics the same as for sepsis but with higher dose and prolonged
duration (Gentamycin for two weeks the rest for three weeks).
4.4. PERINATAL ASPHYXIA

IMPORTANT TERMINOLOGIES
• Anoxia is a term used to indicate the consequences of complete lack of oxygen
as a result of a number of primary causes.

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• Hypoxemia refers to decreased arterial concentration of oxygen.
• Hypoxia refers to a decreased oxygenation to cells or organs.
• Ischemia refers to blood flow to cells or organs that is insufficient to maintain
their normal function.
DEFINITION
PERINATAL ASPHYXIA
• WHO defines as
o failure to initiate and sustain breathing at birth or it is 5th minute Apgar
score of 0-3.
o It can also be defined as placental or pulmonary gas exchange
impairment leading to hypoxemia and hypercarbia.
• AAP and ACOG Criteria for diagnosis of perinatal asphyxia
o An arterial cord pH < 7.0 and base deficit more than 12
o Apgar score of less than 7 at 5 minutes.
o Evidence of altered neurological status (altered level of consciousness,
seizures, hypotonia, obtundation).
• This definition using APGAR score is not applicable in
o Preterm babies
o Babies with birth trauma
o Congenital neurologic abnormalities.
EPIDEMIOLOGY
• Perinatal asphyxia is the second commonest cause of neonatal mortality only
preceded by infection and the commonest cause of disability in surviving
newborns.
Diarrhea
1% Mortality (%)
Congenital Others
Anomaly 4%
6%
Preterm
complications
Severe 37%
Infections
24%
Intrapartum
related
28%
Figure 22 Causes of mortality among Neonates

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PATHOPHYSIOLOGY
Note: Perinatal asphyxia results from compromised placental or pulmonary gas
exchange. This lead to
Hypoxia and hypercarbia
Anaerobic glycolysis and lactic acid production
Hypoxia and acidosis
depress myocardial function, leading to hypotension and ischemia
further compromise, specifically to CNS and kidney
RISK FACTORS
• Asphyxia can occur before, during, or after birth and a variety of maternal,
obstetric, and neonatal conditions predispose the fetus and newborn to
asphyxia.
• Antepartum cause (20%)
o Maternal hypotension of any cause usually APH
o Severe anemia
o Cardiopulmonary diseases
o Maternal hypertension
o Preeclampsia/eclampsia
o Maternal diabetes
• Intrapartum cause (70%)
o Cord compression (E.g., Cord prolapses)
o Meconium aspiration
o Prolonged labor (maternal/ fetal causes)
• Postpartum cause (10%)
o Prematurity
o Cardiovascular abnormalities

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o Pulmonary malformations
o Neurologic abnormalities
o Severe infections
o Bleeding, shock
o Congenital heart disease
CLINICAL PICTURE
• Depends on duration & severity of asphyxia
A. In the fetus: Fetal monitoring shows:
▪ Slow, weak, irregular heartbeats (type II deceleration)
▪ Scalp pH less than 7.2
▪ Action: Intrapartum resuscitation
− give mother high oxygen concentration and
− Position change
− prepare for immediate delivery.
B. After delivery:
▪ Meconium staining of the newborn, amniotic fluid and vernix
caseosa
▪ Decreased consciousness with failure of spontaneous breathing.
▪ Low Apgar score with cyanosis and flaccidity.
C. Later manifestations of perinatal asphyxia:
▪ Hypoxic-ischemic encephalopathy (HIE)
▪ Cardiac: - Heart failure, hypotension
▪ Respiratory: - Meconium aspiration, persistent pulmonary
hypertension of newborn, respiratory distress.
▪ Renal: - Acute tubular necrosis, hematuria, oliguria (<
0.5ml/kg/hr
▪ GIT: -Necrotizing enterocolitis and intestinal perforation
▪ Metabolic: -Hypoglycemia, hypocalcemia, hypomagnesemia,
hyponatremia lactic acidosis and syndrome of inappropriate
secretion of ADH
• ORGAN INVOLVEMENT
o The commonly affected organ in PNA is:
▪ Kidney (50%)
▪ CNS (28%)
▪ CVS (25%)
▪ Pulmonary (23%)
▪ GIT
HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)

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• Hypoxia from PNA impair cerebral perfusion that progressively result in Na-K
ATPase impairment, cell swelling and cell death. HIE result in focal or diffused
cerebral injury. The commonly affected area includes periventricular area,
thalamus and parasagittal superomedial cortex.
• At birth, affected infants is usually depressed and fail to initiate and sustain
breathing spontaneously.
• During the ensuing hours, they may remain hypotonic or change from a
hypotonic to a hypertonic state, or their tone may appear normal.
• Pallor, cyanosis, apnea, a slow heart rate, and unresponsiveness to stimulation
are also signs of HIE.
Note: Cerebral edema may develop during the next 24 hr and result in profound
brainstem depression.
• During this time, seizure activity may occur; it may be severe and refractory to
the usual doses of anticonvulsants.
Note: Though most often a result of the HIE, seizures in asphyxiated newborns may
also be a result of hypocalcemia, hypoglycemia, or infection.
• In addition to CNS dysfunction, systemic organ dysfunction is noted in up to 80%
of affected neonates; heart failure and cardiogenic shock, persistent
pulmonary hypertension, RDS, gastrointestinal perforation, and acute kidney
injury are associated with perinatal asphyxia secondary to inadequate
perfusion.
Table 36 Clinical spectrums of HIE includes mild, moderate or severe according to
Signs STAGE 1 STAGE 2 STAGE 3
Level of consciousness Hyper alert Lethargic Stuporous, coma
Muscle tone Normal Hypotonic Flaccid
Posture Normal Flexion Decerebrate
Tendon reflexes/clonus Hyperactive Hyperactive Absent
Myoclonus Present Present Absent
Moro reflex Strong Weak Absent
Pupils Mydriasis Miosis Unequal, poor light reflex
Seizures None Common Decerebration
Electroencephalographic Normal Low voltage changing Burst suppression to
findings to seizure activity isoelectric
Duration <24 hr if 24 hr-14 days Days to weeks
progresses;
otherwise, may
remain normal.
Outcome Good Variable Death, severe deficits

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CLINICAL MANIFESTATIONS OTHER THAN CNS
• Renal failure: Oliguria - • Shock
Respiratory distress, • Necrotizing enterocolitis /Bloody
• Tachycardia stool
• Cardiomegaly • Hypoglycemia
• Hepatomegaly • Hypocalcemia
LABORATORY EVALUATION
• CBC • Echocardiography as needed
• RBS • Serum electrolytes
• Urine analysis • EEG
• Stool for blood • CXR
• Renal function • Brain imaging
• Liver function test
MANAGEMENT OF ASPHYXIA
A. Keep NPO for severe PNA (because of risk of necrotizing enterocolitis, it can
be for 48 hours).
o Start feeding (with 5 to 10ml) when the neonate is passing meconium,
clear gastric content, normoactive bowel sound and then advance as
tolerated
B. Fluid Management- two third of the maintenance fluid (avoid both overload
and inadequate circulating volume)
C. Oxygenation it should be maintained in the normal range (Saturation between
90-95%)
D. Maintain normal temperatures
o Cooling therapy is the standard treatment for hypoxic ischemic
encephalopathy. However, it is not available in Ethiopian setup.
E. Correction of Metabolic States-
o Blood glucose has to be kept in the normal range.
▪ Hypoglycemia is often seen in asphyxiated newborns. It increases
energy deficit. It has to be treated with 2ml/kg of 10% dextrose
4ml/kg (in the presence of seizure) followed by maintenance.
o Hypocalcemia (can cause seizure and decreased cardiac contractility)
administer 1-2ml/kg of 10% calcium gluconate QID or add in to the
maintenance fluid.
F. Seizure Treatment (see on neonatal seizure)
G. Management of other organ system dysfunctions
o Congestive heart failure – diuretics, dopamine or dobutamine
o Acute renal failure – dopamine

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o Gastrointestinal – delay oral feeding
o Hematologic failure – blood component replacement
H. Parent counseling has to be the integral part of management
I. Follow up
o Perinatal Asphyxia Follow up chart include:
▪ V/S, ▪ mental status,
▪ Wt., ▪ tone,
▪ HC, ▪ neonatal reflex,
▪ Capillary refill, ▪ seizure,
▪ Gastric content, ▪ remarked (RBS,
▪ bowel sound, U/A, serum
▪ bloody stool, electrolyte)
▪ pupillary reflex,
PROGNOSIS OF HIE
• Stage I (mild HIE) 98- 100% of newborns will have a normal neurological
outcome and < 1% mortality
• Stage II (moderate HIE) 20-37% of them die or have abnormal
neurodevelopmental outcome.
• Stage III (Severe HIE) death is more likely survivors would have one or more
major neurodevelopmental disability such as Cerebral palsy, intellectual
disability, visual impairment or epilepsy.
4.5. PREMATURITY AND ITS COMPLICATIONS

DEFINITION
• A newborn delivered before a gestational age of completed 37 weeks (259
days).
• Complications of preterm birth are the leading cause of death in children < 5
years of age worldwide.
EPIDEMIOLOGY
• They have a higher morbidity and mortality when compared to full term
newborns.
• Preterm delivery accounts for 75-80% of all neonatal morbidity and mortality.
• It is most common cause of under-five mortality accounting for 16%.
CLASSIFICATION
A. Late preterm: a newborn delivered at gestational age of 34-37wk.
B. Early preterm: a newborn delivered at gestational age of less than 34 wk.
RISK FACTORS

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• Prematurity is associated with the following conditions:
o Low socioeconomic status
o Acute or chronic maternal illnesses
o Multiparty >4 children
o Previous history of prematurity
o Multiple pregnancy
o Maternal age less than 20 or greater than 35
o Obstetrics factors (hypertensive disorders, Antepartum hemorrhage,
cervical incompetence, uterine anomalies)
o Maternal physical stress
o Trauma
COMMON PROBLEMS OF PREMATURITY

• Most of the problems of prematurity are related to difficulty in extra uterine
adaptation due to immaturity of organ systems. Common problems as follows:
• Respiratory
o Respiratory distress syndrome (RDS)
o Apnea of prematurity
• Neurologic
o Respiratory center depression
o Intra cranial hemorrhage
• Cardiovascular
o Hypotension (due to hypovolemia, sepsis, cardiac problems)
o Patent ductus arteriosus (PDA)
• Hematologic
o Anemia of prematurity
o Hyperbilirubinemia
• Nutritional and Gastrointestinal
o Necrotizing enterocolitis (NEC)
• Metabolic
o Hypo or hyperglycemia
o Fluid and electrolyte imbalance
• Renal – low glomerular filtration rate and inability to handle water and solute
loads
• Temperature regulation
• Immunologic – immature immune defenses
• Ophthalmologic – retinopathy of prematurity (ROP).
RESPIRATORY DISTRESS SYNDROME (RDS)

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DEFINITION
• Neonatal respiratory distress syndrome is caused by impaired synthesis and
secretion of surfactant.
• Also called Hyaline membrane disease (RDS type 1)
EPIDEMIOLOGY
• Most cases of hyaline membrane disease occur in babies born before 37 weeks
of gestation.
• Incidence is inversely related to gestational age and birth weight.
o Less than 28 weeks 60 – 80%,
o 32-36 weeks 15-35% in
o >37 weeks 5%.
• Uncomplicated course characterized by peak severity at 1-3 days. Onset of
recovery is at 72 hrs.
RISK FACTORS:
• Prematurity (about 60%)
• Male predominance
• Maternal diabetes
• Perinatal asphyxia
• Elective caesarian section
NB: The risk of RDS is reduced in pregnancies with chronic or pregnancy-associated

hypertension, maternal heroin use, prolonged rupture of membranes, and Antenatal
corticosteroid prophylaxis.
PATHOPHYSIOLOGY
• Surfactant is a mixture of phospholipids and proteins
o Produced by type II alveolar cells.
o It reduces alveolar surface tension, preventing the alveoli from
collapsing.
• Surfactant deficiency is most likely to occur in preterm infants, because:
o Surfactant production begins at approximately 20 weeks gestation.
o Distribution throughout the lungs begins at 28-32 weeks' gestation and
does not reach sufficient concentration until 35 weeks gestation.
• Surfactant deficiency will lead to hypoxemia and hypercapnia since there will
be
o increased alveolar collapse → atelectasis → decreased lung compliance
and functional residual capacity.

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• Respiratory distress (Grunting, flaring, retraction, tachypnea)
• Characteristic expiratory grunting
o Affected infants exhale through a partially closed glottis, limiting
alveolar collapse in an effort to increase intrapulmonary pressure.
• Auscultatory findings – markedly decreased air entry
bilaterally
• Cyanosis
INVESTIGATION
• CBC
• Chest X-ray
o Interstitial pulmonary edema with perihilar
streaking
o Diffuse, fine, reticulogranular (ground-glass)
densities with low lung volumes and air
bronchograms Figure 23 Xray of a Neonate with
respiratory distress syndrome
o Atelectasis
• If possible, blood gas analysis,
o Evaluate acidosis
o Evaluate for partial respiratory failure or global respiratory failure
• Septic work up,
PREVENTION
• PRENATAL TESTING OF NRDS: screening for markers of fetal lung immaturity
o Lecithin-sphingomyelin ratio < 1.5 (≥ 2 is considered mature)
▪ The amount of sphingomyelin in the amniotic fluid remains
relatively consistent during pregnancy.
▪ The amount of lecithin, which is the major component of
surfactant, starts increasing after week 26 of gestation.
▪ The lower the lecithin-sphingomyelin ratio, the more likely it is
that the lungs are immature.
o Foam stability index < 0.48
▪ A semi-quantitative test used to assess fetal lung maturity
▪ Amniotic fluid is mixed with ethanol until foam formation ceases
to occur
▪ The index refers to the highest quantity of ethanol that can be
added to amniotic fluid still permitting the formation of foam.
o Low surfactant-albumin ratio
• Antenatal corticosteroids (at least 24-48 hrs. before delivery) given to
pregnant women < 34 weeks of gestational period.

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• Prevention of preterm delivery
MANAGEMENT
• Nasal CPAP with continuous monitoring
o Physiologic O2 saturation in neonates is around 90%. A saturation of 100%
is considered toxic for neonates!
• Fluid and metabolic management
• Surfactant substance administration
COMPLICATION AND PROGNOSIS

• Air leaks (pneumothorax, pneumomediastinum)
• Intracranial bleeding, pulmonary hemorrhage
• Bronchopulmonary dysplasia
• Retinopathy of prematurity
NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE VENTILATION (NCPAP)

• Indications:
a. Mild to moderate respiratory distress as a result of: • RDS-for those <32
weeks, TTN, MAS
b. Apnea of prematurity
c. Atelectasis (and also small lung volume)
• Contraindications
a. Upper airway abnormalities
b. Severe cardio-respiratory instability
c. Essential intubation and mechanical
ventilation
• Dangers
o Nasal obstruction as a result of
secretions or displaced nasal prongs
o Nasal prongs displacement
o Nasal decannulation
o Water accumulates in circuit and nose Figure 24 nCPAP
o Pneumothorax
o CO2 retention, impaired pulmonary blood flow
o Abdominal distension
APPLICATION OF NCPAP
1. Palace baby supine in overhead radiant heater bed with small rolled up nappy
under the shoulders
2. Keep baby NPO initially with orogastric tube on open drainage
3. Begin intravenous infusion

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4. Put snug-fitting woolen cap on baby’s head
5. Choose correct size of nasal prongs so as to fit comfortably into nostrils. insert
without pressing on nasal septum.
6. Connect correct size of nasal prongs to the nosepiece and place in baby’s
nostrils. The prongs should fit smugly without pressing on the nasal septum.
7. Tie the tapes of the nosepiece to the woolen cap with sticking plaster
8. Check that there is sterile water in the humidifier
9. Commence initial oxygen flow of 6-8litres/minute or 4-5cm H2O pressure
10. Adapt oxygen concentration (FiO2) according to saturation.
11. Observe baby and document saturation
APNEA
DEFINITION
• It is a disorder of respiratory control characterized by
o absence of air flow for ≥20 seconds or
o less than that if it is accompanied by bradycardia (heart rate <100/min)
or cyanosis.
• It is classified in to three Classification
1. Central – no airflow, no respiratory efforts
2. Obstructive – no airflow, despite respiratory efforts
3. Mixed – often begins as central and later becomes obstructive
EPIDEMIOLOGY
• It commonly occurs in premature newborns due to immaturity of brain
functions and generally begins 1 or 2 days after birth. In term newborns, it
occurs in association with serious identifiable causes.
ETIOLOGY
• Prematurity, infection, metabolic abnormalities
• Hypoxemia, anemia, hypo or hyperthermia
• Gastroesophageal reflux
• Upper airway malformations (TEF)
PREVENTION
• Maintain normal hematocrit, electrolytes and PaO2
• Avoid neck flexion and abdominal distension
• Kangaroo Mother Care (KMC)
MANAGEMENT

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• Methylxanthines o Aminophylline - Loading dose 8mg/kg IV infusion over 30
minutes.
o Maintenance – 1.5 to 3mg/kg IV every 8 to 12 hours.
o Caffeine – loading dose 20 to 25mg/kg IV Slow Push every 24 hrs.
• CPAP
• Kangaroo mother care
• Maintain normal hematocrit, electrolytes and PaO2
• Avoid neck flexion and abdominal distension
• Treat underlying etiology
NECROTIZING ENTEROCOLITIS (NEC)

DEFINITION
• NEC is an acute intestinal necrosis syndrome of unknown etiology. Prematurity
is the single greatest risk factor (90% of NEC).
EPIDEMIOLOGY
• It is a most common serious surgical disorder among newborns and is a
significant cause of neonatal morbidity and mortality.
• Premature newborns tend to get NEC later compared with full terms.
• The most commonly affected part is the terminal ileum and proximal colon
parts of intestine.
• Commonly the onset of NEC is related with gestational age and is as follows:
o In <31 weeks onset is 23rd day
o >31 weeks – 11 days
o Full term – 3rd day
RISK FACTORS
• It has multifactorial associations listed as follows the final result being
activation of an inflammatory cascade:
o Feeding (Trophic phase should always be considered)
o Prematurity: immature host defense, immature regulation of circulation
o Formula feeding: 90 to 95% affected neonates had been fed formula,
decreased risk with breast milk
o Intestinal ischemia
o Abnormal bacterial colonization: reduced number of bacterial species
after antibiotic therapy

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• Abdominal distention, feeding intolerance, vomiting, blood in stool, loose stools,
abdominal wall erythema, systemic instability
INVESTIGATIONS
• CBC (Leucopenia, thrombocytopenia)
• Serum Electrolytes (Hyponatremia, hypokalemia, metabolic acidosis)
• Coagulation profile - Disseminated intravascular coagulopathy (DIC)
• RBS
• Plain abdominal X-ray (prone with lateral or decubitus) Pneumatosis
intestinalis, dilated loops, thickened bowel wall, ileus, pneumoperitoneum
Table 37: Management of NEC Bell staging criteria
Diagnosis Management (usual attention to respiratory, cardiovascular and
hematologic resuscitation presumed)
Stage I Clinical signs and

•NPO with IV fluids
(suspect) symptoms •Nasogastric drainage
Non-diagnostic • CBC, electrolytes, Serial Abdominal x-ray
radiograph • Blood culture
• Stool heme test and Clinitest
• Ampicillin and gentamicin × 48 hours
Stage II Clinical signs and • NPO with parenteral nutrition (by CVL once sepsis ruled out)
(definite) symptoms • Nasogastric drainage
Pneumatosis • CBC, electrolytes, Abdominal x-ray, Blood culture
intestinalis on • Stool heme test and Clinitest
radiograph • Ampicillin, gentamicin and clindamycin × 14 days
• Surgical consultation
Stage III Clinical signs and • NPO with parenteral nutrition (by CVL once sepsis ruled out)
(Advanced) symptoms • Nasogastric drainage
Critically ill • CBC, electrolytes, Abdominal x-ray Stool heme test and
Pneumatosis Clinitest
intestinalis or • Ampicillin, gentamicin, and clindamycin × 14 days
pneumoperitoneum • Surgical consultation with intervention, if indicated:
on radiograph • Resection with enterostomy or primary anastomosis
• In selected cases (usually <1,000 g and unstable), bedside
drainage under local anesthesia
AP = anteroposterior; CBC = complete blood count, CVL = central venous line; NPO = nothing by
mouth.
INTRAVENTRICULAR HEMORRHAGE (IVH)

• Bleeding into the ventricles from the germinal matrix,
• a highly vascularized region within the subventricular zone of the brain from
which cells migrate out during brain development.
RISK FACTORS

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• Birth weight < 1500 g and delivery before 32 weeks' gestation
o due to the fragility of the germinal matrix and/or
o impaired autoregulation of blood pressure
• Maternal chorioamnionitis
• Hypoxia during or after birth
CLINICAL FEATURES
• Most infants are asymptomatic, but may manifest early or late (after several
days.)
• Usually occurs within the first days of life (up to day 5).
• Lethargy, hypotonia, irregular respirations, seizures, bulging anterior
fontanelle
• Cranial nerve abnormalities (e.g., pupils react sluggishly to light) and changes
in eye movement (e.g., roving eye movements).
DIAGNOSTICS
• Cranial ultrasound: allows grading of IVH based upon the location and extent to
assess severity.
o Grade I: bleeding confined to germinal matrix and ≤ 10% of the
ventricular area
o Grade II: 10–50% of the lateral ventricle volume occupied by germinal
matrix and IVH
o Grade III: > 50% of the lateral ventricle volume occupied by germinal
matrix and IVH, ventricular distortion
• Since most patients are asymptomatic, screening ultrasounds are routinely
performed in infants with
o a birth weight < 1500 g and
o delivery before 30 weeks' gestation.
TREATMENT
• Treatment is mainly supportive
• Lumbar puncture, diuretics, and/or ventriculoperitoneal shunt could benefit in
severe IVH.
4.6. NEONATAL JAUNDICE (HYPERBILIRUBINEMIA)

DEFINITION
• Neonatal jaundice: is a yellowish discoloration of the skin and or sclera due to
bilirubin deposition.
• In newborns, jaundice appears when total bilirubin (TB) is more than 7 mg /dl

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o 97 % healthy full-term babies have biochemical hyperbilirubinemia
(1.5mg/dl) and
o 65% has clinical jaundice(>7mg/dl).
• Hyperbilirubinemia with a TB >25 to 30 mg/dL (428 to 513 micromole/L) is
associated with an increased risk for Bilirubin-Induced Neurologic Dysfunction
(BIND), which occurs when bilirubin crosses the blood-brain barrier and binds to
brain tissue.
• The term "Acute Bilirubin Encephalopathy" (ABE) is used to describe the acute
manifestations of BIND,
• while the term "Kernicterus" is used to describe the chronic and permanent
sequelae of BIND.
BILIRUBIN METABOLISM
Knowledge of the basic steps in bilirubin metabolism is essential to the understanding
of the pathogenesis of neonatal hyperbilirubinemia.
• Bilirubin is a product of heme catabolism.
• Approximately 80 to 90 percent of bilirubin is produced during the breakdown
of hemoglobin from red blood cells or from ineffective erythropoiesis.
• The remaining 10 to 20 percent is derived from the breakdown of other heme-
containing proteins, such as cytochromes and catalase.
• Bilirubin is formed in two steps.
• The enzyme Heme Oxygenase (HO), located in the spleen and liver as well as
all nucleated cells, catalyzes the breakdown of heme, resulting in the
formation of equimolar quantities of carbon monoxide (CO) and biliverdin.
• Biliverdin is converted to bilirubin by the enzyme biliverdin reductase and
bilirubin is excreted from body by the following process:
o Hepatic uptake – Circulating bilirubin, which is bound to albumin, is
transported to the liver. Bilirubin dissociates from albumin and is taken
up by hepatocytes, where it is processed for excretion.
o Conjugation – In hepatocytes, uridine diphosphogluconurate-
glucuronosyltransferase (UGT) catalyzes the conjugation of bilirubin with
glucuronic acid, producing bilirubin diglucuronides and, to a lesser
degree, bilirubin monoglucuronides. Conjugated bilirubin, which is more
water-soluble than unconjugated bilirubin, is excreted in bile.
o Biliary excretion – Conjugated bilirubin is secreted into the bile in an
active process that depends upon canalicular transporters, and then
excreted into the digestive tract. Conjugated bilirubin cannot be
reabsorbed by the intestinal epithelial cells. It is broken down in the
intestine by bacterial enzymes and, in the adult, it is reduced to urobilin
by bacterial enzymes. But at birth the infant's gut is sterile and,

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subsequently, infants have far fewer bacteria in the gut, so very little, if
any, conjugated bilirubin is reduced to urobilin. Infants have beta-
glucuronidase in the intestinal mucosa, which deconjugates the
conjugated bilirubin. The unconjugated bilirubin can now be reabsorbed
through the intestinal wall and recycled into the circulation;
▪ A process known as the "Enterohepatic Circulation of Bilirubin".
CLASSIFICATION
• Physiologic vs Pathologic jaundice
No Features Physiologic Pathological
Jaundice Jaundice
1 Clinical onset of jaundice (after >24 hrs <24 hrs
birth)
2 Jaundice still clinically visible (day Term < 8 days Term ≥8 days
after birth) Preterm < 14 days Preterm > 14 days
3 Peak Total Serum Bilirubin (TSB) Term < 12 mg/dl Term > 12 mg/dl
Preterm < 15 mg/dl Preterm > 15 mg/dl
4 Rise in TSB < 5mg/dl/24 hrs > 5mg/dl/24 hrs
5 Conjugated serum bilirubin level <2mg/dl >2mg/dl or 15 % of
TB
ETIOLOGY
• During the neonatal period, metabolism of bilirubin is in transition from the
fetal stage, during which the placenta is the principal route of elimination of
the lipid-soluble, unconjugated bilirubin, to the adult stage, during which the
water-soluble conjugated form is excreted from hepatic cells into the biliary
system and gastrointestinal tract.
• In general, the common causes of jaundice are:
o Physiologic jaundice o Breast milk

o Hemolytic o Breast feeding jaundice
o Sepsis o Cigler Najjar
o Internal hemorrhage o Gilbert syndrome
o TORCHS infection o Biliary atresia
• The cause of jaundice categorized based metabolism of bilirubin
o Increased production: -The most common cause of pathologic indirect
hyperbilirubinemia is increased bilirubin production due to hemolytic
disease processes that include the following:
▪ Isoimmune-mediated hemolysis (e.g., ABO or Rh(D)
incompatibility).
▪ Inherited red blood cell membrane defects (e.g., hereditary
spherocytosis and elliptocytosis).

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▪Sepsis is a known cause of hemolysis. The mechanism is not
known; however, one theory suggests that increased oxidative
stress due to sepsis damages neonatal red blood cells that are
susceptible to cell injury.
▪ Other causes of increased bilirubin production due to increased
red blood cell breakdown include polycythemia or sequestration
of blood within a closed space, which occurs in
cephalohematoma.
▪ Macrocosmic infants of diabetic mothers (IDM) also have
increased bilirubin production due to either polycythemia or
ineffective erythropoiesis.
o Decreased clearance: Inherited defects in the UGT1A1 gene, which
catalyzes the conjugation of bilirubin with glucuronic acid, decrease
bilirubin conjugation. This reduces hepatic bilirubin clearance and
increases TB levels. These disorders include Cigler-Najjar syndrome
types I and II and Gilbert's syndrome
▪ Cigler-Najjar syndrome: it can be relative or absolute UGT
deficiency. Although some affected children develop severe
jaundice, the hyperbilirubinemia often responds to phenobarbital
treatment. CN-II usually is inherited in an autosomal recessive
manner, although autosomal dominant transmission occurs in
some cases.
▪ Gilbert's syndrome: - Gilbert's syndrome is the most common
inherited disorder of bilirubin glucuronidation. It is a mutation in
the promoter region of the UGT1A1 gene that causes a reduced
production of UGT, leading to unconjugated hyperbilirubinemia.
BREAST MILK JAUNDICE:

• is defined as the persistence of physiologic jaundice beyond the first week of
age.it is estimated to be occur in 2% of breast feed term baby. It typically
begins after the first three to five days of life and its maximal concentrations
become as high as 10-30mg/dL reached during the 2nd-3rd wk.
• If breastfeeding is continued, the bilirubin gradually decreases but may persist
for 3-10 wk. at lower levels.
• If nursing is discontinued, the serum bilirubin level falls rapidly, reaching
normal range within a few days.
• With resumption of breastfeeding, bilirubin seldom returns to previously high
levels. Photo therapy may be of benefit. Although uncommon, kernicterus can
occur in patients with breast milk jaundice.

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• Breast milk jaundice appears to be caused by a factor, which has not yet been
identified, in human milk that promotes an increase in intestinal absorption of
bilirubin.
• Beta-glucuronidase is one proposed substance as it deconjugates intestinal
bilirubin, increasing its ability to be absorbed (i.e., increasing enterohepatic
circulation).
BREAST FEEDING JAUNDICE

• It is a benign condition that occurs within the first seven days of life, which is
caused by decrease intake resulting in excessive weight and fluid loss.
• Breastfeeding compared to formula feeding is associated with an increased risk
of jaundice and kernicterus.
• The primary mechanism for the increased likelihood of kernicterus and
jaundice with breast versus formula feeding is the failure to successfully
initiate breastfeeding rather than a direct effect of breast milk itself, as is
seen in breast milk jaundice.
• Breastfeeding failure jaundice typically occurs within the first week of life as
lactation failure leads to inadequate intake with significant weight and fluid
loss resulting in hypovolemia.
• This causes hyperbilirubinemia (jaundice) and in some cases, hypernatremia
defined as a serum sodium >150 mEq/L.
• Decreased intake also causes slower bilirubin elimination and increased
enterohepatic circulation that contribute to elevated TB.
Note: A root cause analysis identified the following as predictors of lactation
failure in infants with kernicterus
• Inadequate education from clinicians and lactation consultants
• Inadequate documentation of infant latching
• Inadequate measurement of milk transfer
• Inadequate recording of urine output and stool pattern changes
• In addition, maternal breastfeeding complications, such as engorgement,
cracked nipples, and fatigue, and neonatal factors, such as ineffective suck,
may not be properly addressed prior to hospital discharge and result in
ineffective breastfeeding.
INTESTINAL OBSTRUCTION
• Ileus or anatomic causes of intestinal obstruction increase the enterohepatic
circulation of bilirubin and result in jaundice. TB levels are frequently higher
with small bowel than with large bowel obstruction. As an example, jaundice
occurs in 10 to 25 percent of infants with pyloric stenosis when vomiting
begins.

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CAUSE OF JAUNDICE BASED ON DURATION
1. In the 1st 24hr
o Hemolysis secondarily to Rh and ABO incompatibility and hereditary
hemolysis
o Sepsis
o Con-sealed hemorrhage
o TORCH infection
o Cigler Najjar syndrome
o Drug (oxytocin, diazepam and sulphonamide)
2. Between 24-72h
o It is time for physiologic jaundice but can be aggravated by prematurity,
hypothermia, hypoglycemia, hematoma, drug, breast feeding and PNA
3. Between 3-14 day
o Sepsis
o Breast milk and breast feed jaundice
o Torch infection
o Bile duct abnormality
o Metabolic disease (galactosemia, CF)
o HPS
o Hypothyroidism
BHUTANI NOMOGRAM
o The Bhutani nomogram defines age-specific percentile curves to
evaluate the risk of developing pathological neonatal jaundice.
o Depending on the measured serum bilirubin value, several risk zones are
defined. Neonates in the high-risk zone must be evaluated for
pathological jaundice!
Figure 25 BHUTANI NOMOGRAM

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• Jaundice usually appears during the early neonatal period, depending on
etiology.
• Jaundice usually becomes apparent in a cephalocaudal progression, starting on
the face and progressing to the abdomen and then the feet, as serum levels
increase.
• Dermal pressure may reveal the anatomic progression of jaundice (face, ≈ 5
mg/dL; mid-abdomen, ≈ 15 mg/dL; soles, ≈ 20 mg/dL), but clinical examination
cannot be depended on to estimate serum levels.
• Jaundice to the mid-abdomen, signs or symptoms, high-risk factors that suggest
non physiologic jaundice, or hemolysis must be evaluated.
KERNICTERUS, OR BILIRUBIN ENCEPHALOPATHY

• is a neurologic syndrome resulting from the deposition of unconjugated
(indirect) bilirubin in the basal ganglia and brain stem nuclei.
• The pathogenesis of kernicterus is multifactorial and involves an interaction
between unconjugated bilirubin levels, albumin binding and unbound bilirubin
levels, passage across the blood-brain barrier, and neuronal susceptibility to
injury.
• Disruption of the blood–brain barrier by disease, asphyxia, and other factors
and maturational changes in blood–brain barrier permeability affect risk.
• The precise blood level above which indirect-reacting bilirubin or free bilirubin
will be toxic for an individual infant is unpredictable, but in a large series,
kernicterus occurred only in infants with a bilirubin >20 mg/dL.
• Ninety percent of the infants in whom kernicterus developed were in previously
healthy, predominantly breastfed term and near-term infants.
• The duration of exposure to high bilirubin levels needed to produce toxic
effects are unknown.
• The more immature the infant is, the greater the susceptibility to kernicterus
Clinical Manifestations
• Signs and symptoms of kernicterus usually appear 2-5 days after birth in term
infants and as late as the 7th day in preterm infants, but hyperbilirubinemia
may lead to encephalopathy at any time during the neonatal period.
• The early signs may be subtle and indistinguishable from those of sepsis,
asphyxia, hypoglycemia, intracranial hemorrhage, and other acute systemic
illnesses in a neonate.
• The common initial signs are:
o Lethargy
o Poor feeding, and

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o loss of the Moro reflex
• Subsequently, the infant may appear
o gravely ill and prostrate,
o with diminished tendon reflexes and respiratory distress.
o Opisthotonos with a bulging fontanel,
o twitching of the face or limbs, and
o a shrill high-pitched cry may follow.
• Note: In advanced cases, convulsions and spasm occur, with affected infants
stiffly extending their arms in an inward rotation with the fists clenched.
• Many infants who progress to these severe neurologic signs die; the survivors
are usually seriously damaged but may appear to recover and for 2-3 mo. show
few abnormalities.
• Later in the 1st yr, opisthotonos, muscle rigidity, irregular movements, and
convulsions tend to recur.
• In the 2nd yr, the opisthotonos and seizures abate, but irregular, involuntary
• movements, muscle rigidity, or, in some infants, hypotonia increase
steadily.
• By 3 yr of age, the complete neurologic syndrome is often apparent.
ACUTE BILIRUBIN ENCEPHALOPATHY HAS THREE PHASES
• Phase – 1 (1st – 2 days of age)
o Poor motor reflex o Lethargy,
o High pitched cry, o Poor feeding
o Decreased tone,
• Phase - 2 (middle of 1st week of age):
o Hypertonia, o opisthotonos posturing,
o seizure and depressed o paralysis of upward
sensorium, gazing.
o fever,
• Phase - 3 (after 1 week of age):
o Hypertonia decreases, o poor feeding,
o Hearing and visual o Athetosis and seizure may
abnormality, also occur
CHRONIC FORM OF BILIRUBIN ENCEPHALOPATHY (KERNICTERUS)
• It is seen after 1 year of age and manifests with: -
o Choreoathetoid cerebral palsy
o Upward gaze palsy
o Sensorineural hearing loss
o The intellect may be spared with severe physical handicap
DIAGNOSTIC APPROACH

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• Assess important risk factor for pathologic jaundice and do the following
investigation:
o Serum total and direct bilirubin
o CBC
o RPI or reticulocyte count
o Maternal and neonate BG
and Rh
o Peripheral morphology
o Liver function test and
abdominal ultrasound if
conjugated bilirubin is
elevated
o Coombs test
▪ Indirect Coombs test
(i.e., determination
of antibodies in the
plasma)
▪ it is a technique used
to know if maser is
sensitized for Rh
antigen and produced
Figure 26 Diagnostic approach to Jaundice
anti Rh antibody.
In summery for jaundice present in the 1st weak serum bilirubin, BG/Rh, direct
Coombs test, CBC, reticulocyte count, peripheral morphology, septic screen and torch
screening is mandatory. TFT and galactosemia screening may be done.
MANAGEMENT OF JAUNDICE
• Principles of treatment include
o Any factor that makes the CNS more affected should be corrected
(hypoglycemia, hypothermia and hypoxia)
o Avoid drug interfere with metabolism of bilirubin
o Drug therapy like phenobarbital to increase conjugation
o Improving the frequency and efficacy of breastfeeding or supplementing
inadequate breastfeeding with formula
o Lowering serum bilirubin by
▪ Phototherapy
▪ Exchange transfusion
PHOTOTHERAPY
• Phototherapy is the primary treatment in neonates with unconjugated
hyperbilirubinemia.

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• Indications
o For infants born ≥ 35 weeks gestation, threshold bilirubin levels for
treatment are based on the Phototherapy Nomogram (Available at
NICU).
• Procedure
o Exposure to blue light (non-UV, wavelength: 420–480 nm)
▪ Photoisomerization (major mechanism) and
▪ Photooxidation (minor mechanism) of unconjugated
(hydrophobic) bilirubin in skin to water-soluble forms → excretion
of water-soluble form in urine and/or bile
o Continued until total bilirubin levels < 15 mg/dL
• Side effects
o Changes in skin hue (bronzing) and skin rashes
o Bronze baby syndrome (rare)
▪ Occurs in infants with elevated direct bilirubin (conjugated
bilirubin > 2mg/dL) following phototherapy
EXCHANGE TRANSFUSION
• Most rapid method for lowering serum bilirubin concentrations
• Indications
o Threshold in a 24-hour-old term baby is a total serum bilirubin value > 20
mg/dL
o Inadequate response to phototherapy
o Acute bilirubin encephalopathy
o Hemolytic disease, severe anemia
• Procedure
o Use ABO-matched and Rh-negative erythrocyte concentrate
IV IMMUNOGLOBULIN
• Indications: used in cases with immunologically mediated conditions, or in the
presence of Rh, ABO, or other blood group incompatibilities that cause
significant neonatal jaundice.

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4.7. NEONATAL SEIZURE

INTRODUCTION
• Neonatal seizures are one of the few neonatal neurologic conditions that
require immediate medical attention.
• They are usually brief and subtle in clinical appearance.
EPIDEMIOLOGY
• The most common cause of neonatal seizure is
1. HIE
2. CNS infection
3. Hypoglycemia
4. Hypocalcemia
ETIOLOGY OF SEIZURES
1. HYPOXIA AND TRAUMA
o Hypoxic encephalopathy
o Intracranial hemorrhage
o IVH
2. METABOLIC
o Hypoglycemia in neonates of IUGR, Prematurity, asphyxia, IDM, E.tc
o Hypocalcemia in neonates of Prematurity, asphyxia, IDM, E.tc
o Hypomagnesaemia
o Hypo-/hypernatremia
o Pyridoxine deficiency/dependency
3. CNS INFECTION
o Bacterial meningitis- e.g.-group B strep, E coli…etc.
o Viral meningoencephalitis
o TORCH infections (See Under infectious diseases)
o Perinatal stroke
4. CNS MALFORMATION
CLINICAL DIAGNOSIS OF NEONATAL SEIZURE

• The clinical manifestations of neonatal seizures differ in many ways from those
in older patients.
• They are not generalized seizures like adults or older infants because of the
incomplete Myelination of neonatal brain.
CLINICAL SEIZURE SUBTYPES

• Clinical seizure types in newborn may be categorized broadly into four groups:
1. Subtle seizures:

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o are the most common subtype, comprising about 50% of all seizures in
term and preterm.
o Subtle seizure includes a broad spectrum of behavioral phenomena.
i. Ocular phenomena are common and include tonic eye deviation,
nystagmus eye movement, and sudden sustained eye opening with
visual fixation.
ii. Oro-Bucco-lingual movements include chewing, sucking, or lip-
smacking movements, and are often associated with a sudden
increase in drooling.
iii. Limb movements including pedaling, boxing, rowing, or swimming
movements have been described.
iv. Autonomic phenomena, including sudden changes in skin color,
tachycardia initially, and bradycardia if sustained.
N.B Subtle seizures are not usually associated with EEG seizure and as well poorly
respond to conventional anticonvulsant medications.
2. Clonic Seizure:
o Clinic seizure are stereotypic and repetitive biphasic movements with a
fast contraction phase and a slower relaxation phase.
o It can be univocal, multifocal, or generalized.
o Clonic seizures that remain unifocal are usually not associate with loss of
consciousness.
o The most common cause for clonic seizures that remain unifocal is
neonatal stroke.
3. Tonic Seizure:
o Have a sustained period (seconds) of muscle contraction without
repetitive features.
o It can be generalized or focal. Over all, the prognosis of tonic seizure is
very poor.
4. Myoclonic Seizure:
o Myoclonic seizure is distinguished from clonic seizures by their lightning-
fast contractions and non-rhythmic characters. It can occur in a
multifocal or generalized pattern.
o It is associated with diffuse and usually serious brain dysfunction
resulting from etiologies such as PNA, inborn errors of metabolisms,
major brain trauma, etc.
o Myoclonic seizures are usually associated with a poor long-term
outcome.
N.B
o In many cases, more than one type seizures occur in a new born over time.

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o In the newborn it may be difficult to distinguish between normal immature
behaviors (e.g., non-nutritive sucking), abnormal but no epileptic behaviors
(e.g., jitteriness), and true epileptic manifestations.
INVESTIGATIONS
• CBC • Blood culture
• Serum electrolyte e • Urine analysis and culture
• Blood glucose a • Cranial ultrasound, EEG, MRI
• CSF analysis and culture
COMPLICATIONS
• Cerebral palsy • Learning disability
• Hydrocephalus • Mental retardation
• Epilepsy
MANAGEMENT OF NEONATAL SEIZURES

INITIAL MANAGEMENT (ABC OF LIFE)
• Ensure air way: -place the baby in semi prone position and clean oropharyngeal
secretions.
• Ensure satisfactory breathing and circulation.
ARREST THE SEIZURES WITH THE FOLLOWING ORDERS
1. Hypoglycemia: if RBS shows hypoglycemia or if there is no facility to test blood
sugar, immediately 4 ml/kg of 10% glucose should be given by bolus followed by
maintenance.
2. Hypocalcemia: if hypoglycemia has been treated or excluded as a cause of
seizures, the neonate should receive 2 ml/kg of 10% calcium gluconate IV over 10
minutes, under strict cardiac monitoring. If ionized calcium levels are suggestive
of hypocalcemia the new born should receive calcium gluconate at 8 ml/ kg/d in
four divided doses for 3 days.
3. Anticonvulsants
• Phenobarbital: preferred initial drug. An initial IV loading dose of 20 mg/kg may
be followed by increments of 10 mg/kg IV to a total of 40 mg/kg, with higher
doses associated with improved efficacy. Maintenance dose should be started at 5
mg/kg/day divided twice daily.
− If there is no IV, use oral dose as above. Advantages of Phenobarbitone
include reduction of cerebral metabolic rate and free radical scavenger.
• Phenytoin: it is the second agent selected when Phenobarbitone fails. Loading
dose is 20 mg/kg; maintenances dose is 4-6 mg/kg daily.

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• Diazepam: used only when immediate cessation of seizure activity is required. It
should be administered after dilution of 0.2 ml of diazepam with 0.8 ml of normal
saline. Initial dose is 0.1 -0.3 mg/kg slowly IV until seizures stop.
− Disadvantage: It contains sodium benzoate which interferes with binding of
bilirubin to albumin leads to jaundice. It has short anticonvulsant effect
but prolonged respiratory suppressant effect
• Lorazepam: the current recommended dose is 0.05 mg/kg/dose over 2-5 minute
4. Pyridoxine deficiency /dependency: is diagnosed by giving pyridoxine 100 mg IV.
Seizures will cease within minutes if pyridoxine dependency or deficiency is
causing
5. Maintenance therapy is given for life at 10 to 100 mg daily in case of dependency
and 5 mg daily in case of deficiency.
FOLLOW UP ANTICONVULSANT MEDICATIONS

• If the neonate takes more than one anticonvulsant medication, phenobarbitone
will be the last one to be tapered and discontinue.
• Discontinuation of drugs before discharge from the NICU is generally
recommended. However, newborns with congenital or destructive brain lesions
on neuroimaging or those with persistently abnormal findings on neurologic
examination at the time of discharge may require a slower taper off medication
over several weeks or months.
INDICATIONS FOR DISCONTINUATIONS OF ANTIEPILEPTIC DRUGS

• Normal findings on examinations
• Absence of recurrent seizure
• Non-epileptic EEG
PROGNOSIS
• Long-term squeal in infants with neonatal seizures, including cerebral palsy and
intellectual disabilities, still occur at a high rate of up to 30% to 35%, with post
neonatal seizures occurring in up to 20%.
• The most important factor affecting outcome for infants with neonatal seizures
is the underlying etiology.
4.8. METABOLIC DISORDERS OF THE NEWBORN

• Hypoglycemia
• Hyperglycemia
• Thermoregulation
• Hypocalcemia

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HYPOGLYCEMIA
DEFINITION
• Hypoglycemia could be defined as blood glucose level less than 40mg/dl.
EPIDEMIOLOGY
• Hypoglycemia is common metabolic problem in NICUs.
• Some neonates are symptomatic whereas most are asymptomatic despite very
low blood glucose levels. This variability is due to number of factors including:
• Gestational age
• Birth weight
• Post-natal age
• Feeding status
• Presence or absence of associated illnesses
CLASSIFICATION
• There are two types of neonatal hypoglycemia
o Transient hypoglycemia: most neonates will have transient
hypoglycemia, which responds to treatment and is associated with good
prognosis.
o Persistent hypoglycemia
CAUSES OF HYPOGLYCEMIA
• Transient hypoglycemia could be:
o Related with changes in maternal metabolism
▪ Intrapartum glucose administration
▪ Diabetes in pregnancy-infant of diabetic mother
▪ Maternal drugs (tocolytics, propranolol, thiazide diuretics)
o Related with neonatal problems
▪ Intrauterine growth ▪ Birth asphyxia
retardation ▪ Infection
▪ Prematurity ▪ Post exchange
▪ Large for transfusion
gestational age ▪ Hypothermia
(LGA) ▪ Delayed feeding
▪ Delayed onset of ▪ Polycythemia
feeding ▪ Erythroblastosis
fetalis

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• The clinical manifestations of neonatal hypoglycemia are non-specific and they
may confuse with other disorders of the newborn.
• History
o Abnormal crying (weak or high-pitched cry).
o Poor feeding, vomiting,
o Loss of consciousness,
o Abnormal body movement
• Physical Examination
o G/A irritability, RD, cyanosis
o V/S tachypnea, tachycardia, Hypothermia
o R/S Apnea, Grunting
o CNS Seizures, lethargy or coma, hypotonia
DIAGNOSIS IS BASED ON
• Supportive perinatal history (risk factors).
• Signs and symptoms of hypoglycemia.
• Whole blood glucose less than 40mg/dl.
N.B
•Glucometers measure whole blood glucose, which is 15% lower than plasma
glucose levels.
• Newborns with persistent or recurrent hypoglycemia need additional testing
including hormone analysis and imaging studies.
MANAGEMENT PRINCIPLES (KNOW IT WELL)
• The overall management of neonatal hypoglycemia should include:
1) Anticipation and prevention in those who are at high risk.
2) Correction of hypoglycemia in those who are symptomatic and
3) Investigation and treatment of the cause of hypoglycemia, when it is
possible to identify the cause.
TREATMENT OF ASYMPTOMATIC HYPOGLYCEMIA

▪ Feeding
• Feeding is the initial treatment in an asymptomatic term
infant,
• Immediately offer breast-feeding.

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• Check blood glucose 30 minutes after feeding and repeated
blood glucose is > 40mg/dl continue to offer feedings at 2-
3hours interval.
• Indications of IV infusions in asymptomatic hypoglycemia
(use same infusion as symptomatic hypoglycemia)
o Blood glucose < 25mg/dl.
o Blood glucose remains < 40mg/dl after one attempt
of feeding
o If infant becomes symptomatic
o If oral feeding is contraindicated
TREATMENT OF SYMPTOMATIC HYPOGLYCEMIA

• Many neonates have asymptomatic (chemical) hypoglycemia.
• The incidence of symptomatic hypoglycemia is highest in small for gestational
age infants.
• Immediate treatment
o Secure IV line
o Give 2ml/kg of 10% glucose IV bolus over one minute if signs other than
seizure
o Give 4 ml/kg of 10% glucose as a bolus over one minute if seizure is
present.
• How do we prepare 10% glucose?
o 10% dextrose for IV bolus can be prepared using one part of 40% dextrose
and three parts of distilled water.
▪ E.g., 8ml 10% dextrose prepared from 2ml of 40% dextrose and
6ml of Normal saline.
o 10% dextrose for IV bolus can also be prepared using 15% of 40% dextrose
and 85% of DNS.
▪ E.g., 100ml of 10% glucose can be prepared from 85ml of DNS and
15ml of 40% dextrose.
o You can choose the cheaper alternative from these.
• Continuous therapy
o Put on 10% glucose infusion at glucose infusion rate (GIR) of
6mg/kg/minutes (~ 90ml/kg/day) as maintenance.
o Recheck blood glucose after 30 minutes and if it remains above 40mg/dl
frequency of checking can be decreased to one hourly then every six
hours.
o If blood glucose remains <40mg/dl, increase the GIR by 2mg/kg/minutes
every 30 minutes until repeat values are above 40mg/dl.

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o Once the blood glucose values stabilize above 40mg/dl for 24 hours, the
GIR can be tapered off at 2 ml/kg/min every six hourly with proportional
increment of oral feeds.
o If the neonate requires GIR > 12mg/kg/minutes, persistent hypoglycemia
should be considered.
o Glucose infusion rate (GIR) can be calculated using the following formula
GIR in mg/kg/min
▪ Example: for an infant taking 10% D/W at 100ml/kg/day, the GIR
will be = 6.9 mg/kg/min (~ 0.07 ml/kg/min).
• PRACTICAL POINTS
o Do not use > 12 % dextrose infusion through a peripheral vein due to the
risk of thrombophlebitis.
o Do not stop an IV infusion of glucose abruptly, severe rebound
hypoglycemia may occur.
PROGNOSIS
• The prognosis is good in asymptomatic neonates with hypoglycemia of short
duration.
• The major long-term sequelae of severe, prolonged hypoglycemia are
o Cognitive impairment
o Recurrent seizure activity
o Cerebral palsy
o Autonomic dysregulation.
HYPOTHERMIA
DEFINITION
• Hypothermia is defined as skin (axillary) temperature less than 36.50C.
• The normal body temperature of a newborn is between 36.50C -37.5 0C.
CLASSIFICATION
• Based on its severity hypothermia could be:
o Mild (cold stress) = 360C -36.40C
o Moderate = 320C -35.9 0C and
o Severe (neonatal cold injury) < 320C
PATHOPHYSIOLOGY
• Newborns may lose heat by the following mechanisms:
1. Convection – where heat is lost from the skin to moving air.

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2. Radiation – where heat is dissipated from the baby to a colder object in
the surrounding like to the floor, wall or window.
3. Conduction – where the baby loses heat to the surface on which he or
she lies.
4. Evaporation – major cause of heat loss immediately after birth where
water is evaporated from wet infants’ skin like evaporation from boiling
water.
Figure 27 Mechanisms of physical heat loss
RISK FACTORS
• In general, newborns and premature and LBW babies in particular are at risk of
hypothermia because of:
o large surface area for small body mass for the following reasons:
o Highly permeable skin which increases epidermal water loss
o Deficient subcutaneous fat with less insulation
o Deficient stores of brown fat
o Immature central thermoregulation
o Poor caloric intake
o Poor oxygen consumption because of associated pulmonary problems
CAUSES OF HYPOTHERMIA
• Cold environment/room • Early bath
• Wet or naked baby • Sepsis
• Cold linen • Prematurity
• Transportation without proper • Hypoglycemia
precaution • Hypoxia
• Procedures without thermal
protection

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• Congenital defects
(gastroschisis, omphalocele,
neural tube defects etc.…)
• Bluish discoloration of extremities (acrocyanosis)
• Cold and mottled extremities
• Sluggish and inactive neonate
• Unsatisfactory weight gain and slow increase in head size
NEWBORNS WITH SEVERE HYPOTHERMIA MAY PRESENT WITH

• Hypoglycemia
• Failure to suckle
• Bradycardia
• Disseminated intravascular coagulation
• Irregular and slow breathing
• Shock
PREVENTION
BEFORE DELIVERY
• Warm delivery room (Thermo-neutral environment)
• Organize newborn corner with adequate heat source
AT DELIVERY
• Deliver the baby on mother’s abdomen
• Dry the baby thoroughly immediately after birth and remove wet clothes.
• Use cap to prevent significant heat loss through the scalp
• Keep the newborn in skin-to-skin contact with the mother
• Keep the newborn under pre heated radiant warmer or a pre-warmed rice bag –
if need for resuscitation
• Cover weighing scales with warm towel
• Initiate early breast feeding
• Identify and treat cause of hypothermia (disease process and environmental
conditions)
• Put hypothermic infants on KMC, in incubators or under radiant warmer.
• Warm the new born slowly
o Monitor axillary temperature every 30 minutes till newborn temperature
becomes stable

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o Monitor environmental temperature
MANAGEMENT OF NEWBORNS WITH SEVERE HYPOTHERMIA

• Warm the baby using a pre warmed radiant warmer.
• Remove cold or wet cloths.
• Cover the baby with warm clothes and hat.
• Treat for sepsis, if present
• Measure blood glucose and treat if hypoglycemic.
• Keep IV fluid under the radiant warmer to warm the fluid.
• Measure the baby’s temperature every hour.
• If the baby’s temperature is increasing at least 0.5 °C per hour in the 1st three
hours, re warming is successful.
• Then measure the baby’s temperature every two hours.
• If the baby’s temperature does not rise or is rising more slowly than 0.5 °C per
hour, check and reset temperature of the warmer.
• Once the baby’s temperature is normal, measure the temperature every three
hours for 12 hours and then every 12 hours.
• Monitor for complications and manage accordingly
• Look for respiratory problems
o Monitor vital signs
o Monitor urine output
o Monitor blood sugars
o Look for signs multi organ failure.
4.9. BIRTH TRAUMAS

• are injuries to the newborn caused by mechanical forces during birth.
RISK FACTORS
• Macrosomia or anatomical abnormalities
• Extremely premature infants; low birth weight
• Abnormal fetal presentation
o Breech presentation
o Shoulder dystocia
• Forceps-assisted delivery or vacuum delivery
• Prolonged or rapid labor
• Small maternal stature.
SOFT TISSUE INJURIES OF THE SCALP IN INFANTS

• are mostly caused by shearing forces during vacuum or forceps delivery.
HEAD MOLDING

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• Transient deformation of the head into an elongated shape due to external
compression of the fetal head as it passes through the birth canal during labor
• Typically resolves within a few days after the birth
CAPUT SUCCEDANEUM
• benign edema of the scalp tissue that extends across the cranial suture lines
• Firm swelling; pits if gentle pressure is applied
• No treatment required; resolves within hours or days
CEPHALOHEMATOMA
• subperiosteal hematoma that is limited to cranial suture lines
• Complications: calcification of the hematoma, secondary infection
• No treatment required; resolves within several weeks or months
SUBGALEAL HEMORRHAGE
• Rupture of the emissary veins and bleeding between the periosteum of the
skull and the aponeurosis that may extend across the suture lines
• Associated with a high risk of significant hemorrhage and hemorrhagic shock.
Figure 28 SOFT TISSUE INJURY TO THE SCALP
NEONATAL BRACHIAL PLEXUS PALSY

• Excessive lateral traction on the neck during delivery → injury to the upper
trunk of the brachial plexus → Erb palsy (most common iatrogenic brachial
plexus injury during delivery)
o Hyperextension of the C5 to C7 spinal nerve roots
o Forearm is medially rotated, and the hand pronated (“waiter's tip”)

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• Excessive traction on the arm during delivery → injury to the lower trunk of
the brachial plexus → Klumpke palsy
o Injury to the distal portions of C8 and T1
o Paralysis of the entire arm with areflexia
• Prognosis: approx. 25% of affected infants experience persistent functional
impairment
• Brachial plexus injury is associated with shoulder dystocia which can cause Erb
palsy more commonly than Klumpke palsy.

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CHAPTER 5 - INFECTIOUS DISEASESES

1. Approach To Fever
2. TORCH infections
3. HIV/AIDS
4. Pertussis
5. Measles
6. Malaria

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5.1. APPROACH TO FEVER

• Body temperature is controlled by the hypothalamus.
• In a neutral temperature environment, core body temperature is maintained in
the range of 36.5–37.5°C.
• FEVER is defined as an elevation of body temperature that exceeds the
normal daily variation and occurs in conjunction with an increase in the
hypothalamic set point. (Axillary temperature greater than 37.5).
• A fever of >41.5°C is called hyperpyrexia.
• It can develop in patients with severe infections but most commonly occurs in
patients with CNS hemorrhages.
FEVER VS HYPERTHERMIA
• Hyperthermia (Heat stroke) is characterized by an uncontrolled increase in
body temperature that exceeds the body’s ability to lose heat.
• In contrast to fever in infections, hyperthermia does not involve pyrogenic
molecules.
• Exogenous heat exposure and endogenous heat production are two mechanisms
by which hyperthermia can result in dangerously high internal temperatures.
• Hyperthermia is often diagnosed on the basis of the events immediately
preceding the elevation of core temperature.
o e.g., heat exposure or treatment with drugs that interfere with
thermoregulation.
• The clinical manifestations (C/Ms) of hyperthermia reflect a total loss of
thermoregulatory function.
o These include: tachypnea, various tachycardias, hypotension, and a
widened pulse pressure.
• The historical and physical triad of
o exposure to a heat stress,
o CNS dysfunction, and
o a core temperature >40.5°C helps establish the preliminary diagnosis of
hyperthermia.
• Antipyretics do not reduce the elevated temperature in hyperthermia, whereas
in fever—and even in hyperpyrexia—adequate doses of either aspirin or
acetaminophen usually result in some decrease in body temperature.
• Fever has four major etiologies:
1. Infectious,
2. Inflammatory,
3. Neoplastic, and
4. Miscellaneous

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• Most common causes of acute fever (fever lasting 7 days or less) are:
o Viral infections (like common cold, gastroenteritis) and
o Uncomplicated bacterial infections (otitis media, pharyngitis, sinusitis).
• Fever in pediatrics is broadly classified as:
o Fever in neonates and young infants and
o Fever in older children.
▪ Approach and management differ in these two categories.
o Finally, there is also Fever of Unknown Origin (FUO).
I. FEVER WITHOUT A FOCUS IN THE NEONATE AND YOUNG

INFANT (AGE-GROUP 0-3 MONTHS)
• For this age-group, fever without a focus refers to a rectal temperature of
≥38°C, without other presenting signs or symptoms.
• The etiology and evaluation of fever without a focus depend on the age of the
child. Three age groups are typically considered:
o Neonates 0-28 days,
o Young infants 29-90 days, and
o Children 3-36 months.
• There is a difficulty in distinguishing between a serious infection (bacterial or
viral) and a self-limited viral illness.
• Serious Bacterial Infection (SBI) occurs in 7% to 13% of neonates and young
infants with fever.
• In this group, the most common SBIs are:
o UTI (5–13%),
o Bacteremia (1–2%) and
o Meningitis (0.2–0.5%).
• E. coli is the most common organism causing SBI, followed by GBS.
• Increased screening of pregnant women and use of intrapartum antibiotic
prophylaxis has led to the decrease in GBS infections.
• Other, less common organisms include Klebsiella spp., Enterococcus spp., S.
pneumoniae, N. meningitidis, and S. aureus. Listeria monocytogenes is a rare
cause of neonatal infections.
• In well appearing infants, viral illnesses are much more common than bacterial
or serious viral infections.
• The most common viruses include RSV, enteroviruses, influenza viruses,
parainfluenza viruses, human metapneumovirus, adenovirus, par echoviruses,
and rhinovirus.
• HSV infections should also be considered in febrile neonates <28 days old.
• Most of these infections are caused by HSV type 2.

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• Neonates with disseminated disease and skin, eye, and mouth (SEM) disease
typically present at 5-12 days of life.
• Neonates with CNS disease generally present at 16-19 days.
• Perinatally acquired HSV may occasionally manifests beyond 28 days of age,
although some of these later onset cases may represent postnatal acquisition.
APPROACH TO THE PATIENT

• Diagnosing serious illness can be a challenge because bacterial and viral
infections can present with isolated fever or nonspecific symptoms.
• Some neonates and young infants will have signs of systemic illness at
presentation, including:
o Abnormal temperature (hypothermia <36°C, fever ≥38°C),
o Abnormal respiratory examination (tachypnea >60 bpm, respiratory
distress, apnea),
o Abnormal circulatory examination (tachycardia >180 bpm, delayed
capillary refill >3 sec, weak or bounding pulses),
o Abnormal abdominal examination,
o Abnormal neurologic examination (lethargy, irritability, alterations in
tone), or
o Abnormal skin examination (rash, petechiae, cyanosis).
DIAGNOSIS
• Protocols were developed to identify infants at lower risk of SBI, so that they
can be managed outside the hospital setting.
• The 3 most widely used are the Rochester, Philadelphia, and Boston criteria.
• These protocols were initially developed for use in the emergency department.
• And, keep in mind that these criteria apply only to the well-appearing child.
• Infants and young children appearing critically ill (septic) require prompt
evaluation, resuscitation, and empirical antibiotic therapy (within 1 hr.).

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Table 38 Boston Criteria
BOSTON CRITERIA Low-Risk Criteria
1. Febrile infants 0-27 days 1. Normal examination and well-appearing
a. Empirical 2. Caregiver available by telephone
antimicrobials 3. No antimicrobials, no DTaP vaccine in
b. Admit to hospital previous 48 hours
4. Meets all laboratory/radiographic criteria
2. Febrile infants 28-89 days: a. Peripheral blood: WBC count <20,000 per
Non–low risk mm3
a. Empirical b. Urine
antimicrobials − UA with <10 WBCs per hpf
b. Admit to hospital − Dipstick negative for leukocyte esterase
c. CSF: WBC count <10 per mm3
3. Febrile infants 28-89 days: d. Chest radiograph: No infiltrate on chest
Low risk radiograph (only obtained if signs of
a. One dose of IV respiratory illness).
Ceftriaxone
b. Discharge to home
with follow-up in 24
hrs.
c. Risk of SBI 5.4%
N.B.
• All neonates ≤28 days old should:
o undergo a complete evaluation for serious infections
o receive empirical antimicrobials, and
o be hospitalized.
• Young febrile infants ≥29 days old who appear ill (with signs of systemic illness)
require complete evaluation for SBI, including antimicrobials and
hospitalization.
• Well-appearing infants can be managed safely as outpatients using low-risk
criteria of one of the 3 widely used protocols.
ASSOCIATION OF UTI AND BACTERIAL MENINGITIS IN THIS AGE GROUP:

• Traditionally, infants with abnormal findings on urinalysis (UA) would undergo
complete evaluation for infection, including LP.
• However, in well-appearing infants >28 days old with an abnormal UA the risk
of bacterial meningitis is extremely low, <0.5%.
• For neonates 0-28 days, the risk of concomitant bacterial meningitis with UTI is
1–2%.
• CSF pleocytosis in the absence of bacterial meningitis (i.e., sterile pleocytosis)
has been reported in infants with UTI. The cause is uncertain.

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LABORATORY DIAGNOSIS
1. CBC:
o The WBC count alone can NOT accurately predict SBI risk. It should be
combined with other factors, eg. WBC with differentials.
2. Blood Culture:
o A negative blood culture does not eliminate the risk of bacterial
meningitis.
o Don’t forget that approximately 35% of infants with bacterial meningitis
do not have a positive blood culture.
3. Urine Analysis
4. CSF Analysis:
5. HSV Testing (includes surface cultures of the mouth, conjunctiva, nasopharynx,
rectum, and any vesicles; CSF PCR (sensitivity: 75–100%); whole blood PCR; and
serum levels of ALT)
o Historical and clinical features that should raise concern for HSV include:
▪ exposure to individuals infected with HSV, particularly mothers
with primary HSV infections or first-time genital infections,
▪ seizure or abnormal neurologic
examination,
▪ vesicular rash,
▪ ill appearance,
▪ apnea,
▪ hypothermia,
▪ petechial rash,
▪ excessive bleeding, or
Figure 29 Herpes simplex virus (HSV) in
▪ a history of a scalp electrode.
neonates
o However, neonates with HSV can present
without any high-risk clinical or historical features, particularly with
early isolated CNS disease.
6. Inflammatory markers such as C-reactive protein (CRP) and serum procalcitonin
(PCT), particularly in the diagnosis of SBI and, more specifically invasive
bacterial infection, IBI (bacteremia and meningitis).
TREATMENT
ANTIMICROBIALS
• Commonly used regimens include:
A. A third-generation cephalosporin (typically cefepime),
B. A third-generation cephalosporin and ampicillin, or
C. An aminoglycoside and ampicillin.

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• Ampicillin is the preferred treatment of GBS and covers L. monocytogenes and
many Enterococci spp.
• For neonates 0-28 days, options 2 or 3 have been recommended, given the risk
of L. monocytogenes.
• For young infants >28 days, option 1 (third-generation cephalosporin:
ceftriaxone) can be a reasonable choice.
• For ill-appearing infants or those with positive CSF Gram stains, additional
antibiotics may include vancomycin or broad-spectrum antibiotics such as
carbapenems.
• Neonates with concern for HSV should be empirically treated with high-dose
acyclovir (60 mg/kg/day).
• Treatment duration and route of antimicrobial administration depend on the
infection.
PROGNOSIS
• Most infection related mortality and long-term morbidity results from HSV
infection and bacterial meningitis.
• The mortality of bacterial meningitis varies by pathogen, but ranges from 4–
15%.
• In one study of children who had meningitis as infants, 84% had normal
development at age 5 yr.
II. FEVER IN THE OLDER CHILD

• History & Physical Examination are reliable to establish a diagnosis in this age
group.
• Occult infections (like UTI) may be present, and screening for such infections
should be guided by age, gender, and degree of fever.
DIAGNOSIS
• Potential causes of fever in older infants and children can be categorized into:
o infectious causes mainly, viral and bacterial, which can be further
organized by body region, like:
▪ CNS infections (meningitis, brain abscess)
▪ Respiratory tract infections,
▪ Bone & joint infections (Osteomyelitis, Septic arthritis,
▪ Protozoan infections, like Malaria etc.);
o Inflammatory (ARF, SLE, IBD, HSP, etc.);
o Oncologic (leukemia, lymphoma, solid tumors);
o Endocrine (e.g., thyrotoxicosis); and
o Medication-induced causes (e.g., Salicylate toxicity).

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2. Viral Infections: are the most common cause of fever, and the prevalence of
specific viral infections varies by season.
• Bacterial Infections: Common bacterial infections include acute otitis media
and streptococcal pharyngitis (strep throat).
• Look for signs in each body system, e.g.:
o Focal auscultatory findings i.e., crackles can suggest LRTI, bronchiolitis.
o Neck pain or drooling may indicate a deep neck infection such as a
retropharyngeal abscess (in infants and young children), or a
peritonsillar abscess, typically affects older children.
o Skin and soft tissue infections such as cellulitis and abscess may also
present with fever, with the buttock a common area for abscesses in
young children etc.
• IBIs, including sepsis and bacterial meningitis, must be considered.
• These infections are potentially life-threatening and require prompt
recognition and treatment.
• Ill appearance, lethargy, and tachycardia are typically present among children
with severe sepsis.
• Petechiae may be an early finding among children with meningococcemia or
other invasive bacterial diseases.
• Children with fever who are immunosuppressed are at higher risk for IBI.
OCCULT BACTERIAL INFECTIONS

• Infants and children age 2-24 mo merit special consideration because they have
limited verbal skills, are at risk for occult bacterial infections, and may be
otherwise asymptomatic except for fever.
OCCULT URINARY TRACT INFECTION

• Among children 2-24 mo old without Sx or PHYSICAL EXAMINATIONfindings that
identify another focal source of infection, the prevalence of UTI may be as high
as 5–10%.
• The highest risk of UTI occurs in females and uncircumcised males, with a very
low rate of infection (<0.5%) in circumcised males.
Table 39 Risk Factors for UTI

FEMALE MALE
White Race Uncircumcised boys
Age <1 yr Nonblack race
Temperature ≥39°c Temperature ≥39°C
Fever duration ≥2 days Fever duration >1 day
No obvious source of infection No obvious source of infection

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OCCULT BACTEREMIA
• Definition: a positive blood culture for a pathogen in a well appearing child
without an obvious source of infection.
• Currently, the prevalence of occult bacteremia is <1% in febrile, well-appearing
young children.
• Unimmunized and incompletely immunized young children remain at higher risk
for occult bacteremia because of pneumococcus.
• Subsequent serious invasive infection may rapidly follow bacteremia caused by
Hib or meningococcus.
GENERAL APPROACH
A. OVERALL APPEARANCE AND VITAL SIGNS
• Children who are ill or appear toxic or who have abnormal V/S (e.g.,
tachycardia, tachypnea, hypotension): focused P/E to evaluate for the
presence of an IBI.
• Detailed history and P/E can be performed in the well-appearing child.
B. SYMPTOMS
I. Characterization (degree & duration) of fever is important.
o For children with prolonged fever, determine whether the fever has
been episodic or persistent.
o Patients with prolonged fever may harbor:
▪ Occult infections,
▪ UTI,
▪ Bone or soft tissue infections,
▪ Have an inflammatory or oncologic condition, or
▪ Kawasaki disease
II. Look for the presence of symptoms that may indicate an etiology for the fever,
• Using systemic approach (HEENT, LGS, R/S, CVS, Abdomen, etc.)
o E.g.: Symptoms of common viral infections such as rhinorrhea, cough,
vomiting, and diarrhea.
• Symptoms should be elicited for each body system: e.g.
o HEENT: headache, ear pain, sore throat, neck pain or swelling,
o R/S: difficulty breathing, chest pain,
o GIT: abdominal pain,
o GUT: the presence of dysuria, urinary frequency, or back pain
o IGS: rash or changes in skin color,
o MSS: extremity pain or difficulty with ambulation (including refusal
to bear weight in a young child), and overall activity level.

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• Presence of weight loss or night sweats may indicate leukemia, lymphoma,
or tuberculosis.
• A thorough social history should be performed, inquiring about attendance
at daycare, any travel, and any sick contacts at daycare, school, or in the
household.
• N.B: Assessment of oral intake and urine output is also critical, because
DHN may accompany common childhood.
C. PHYSICAL EXAMINATION
• Vital signs.
• careful evaluation of each body system.
o E.g.: Erythema and exudate of the tonsils with palatal petechiae suggest
streptococcal pharyngitis.
o focal crackles or decreased breath sounds suggest pneumonia.
o petechiae may suggest meningococcal or other IBI,
o viral exanthems are typically associated with a blanching macular or
maculopapular rash.
• N.B.: Assessment of neck pain and mobility is also
significant, but it may be limited in children with
meningitis.
• Check for the presence of lymphadenopathy, which may be
present with infectious as well as oncologic causes of
fever.
D. LABORATORY TESTS
• The decision to perform laboratory testing should be
guided by:
o The overall appearance
o Vital signs of the child,
o The presence of specific Sx or P/E findings, and
o age.
• Rapid lab evaluation should be done in children who are:
o Ill or appear toxic, or
o who have V/S abnormalities indicative of an IBI Figure 30 Algorithm for evaluation and
management of fever in infants and children
(tachycardia, hypotension). >2 mo of age
• CBC and culture (blood and possibly urine), and CSF
cultures should be performed in these children.
• Children who are immunosuppressed should receive prompt antimicrobial
therapy, given their higher risk of IBI.

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• Viral testing may also be useful with prolonged fever to identify a source of the
fever.
• Children with 2 or 3 of the risk factors for UTI, particularly females and
uncircumcised males, should undergo evaluation with UA.
• Females and uncircumcised males 2-6 mo old with high fever or fever that lasts
≥2 days, may undergo urine testing even in the presence of respiratory tract
infection, given the higher risk of UTI in this younger group.
• Who have V/S abnormalities indicative of an IBI (tachycardia, hypotension).
• Rapid strep testing of the oropharynx is indicated for:
o Children ≥3 yr old with signs of streptococcal pharyngitis on
examination, and
o Children <3 yr old, if they have:
▪ signs of strep throat on exam PLUS
▪ a household contact with streptococcal pharyngitis.
E. IMAGING
• In the febrile child with P/E findings suggestive of pneumonia, presumptive
antibiotic treatment for pneumonia based on clinical grounds should be
initiated.
• CXR is indicated for admitted children to assess for complicated pneumonia,
like empyema.
• Otherwise, the performance of imaging should be dictated by P/E findings.
o E.g.: lateral radiograph or CT of the soft tissue of the neck may be
performed in a child with high clinical suspicion of RPA.
F. MANAGEMENT
GENERAL PRINCIPLES
• Supportive care, like antipyretics and adequate hydration, for all children with
fever.
• Children with viral infections generally require supportive care only, except for
children at higher risk of severe or complicated disease with influenza virus.
• Antibiotics should be reserved for children with evidence of bacterial infection
on P/E.

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CLASSIFICATION OF FEVER
Fever, for the sake of ease, can also be classified as:
Figure 31 Classification of fever
Fever lasting less than 7 days Fever lasting more than 7 days
Meningitis Abscess
Otitis media Salmonella infection (non-typhoidal)
Mastoiditis Infective endocarditis
Osteomyelitis Rheumatic fever
Septic arthritis Miliary TB
Acute rheumatic fever Brucellosis
Skin and soft tissue infection
Pneumonia
• Fever can also be classified as: fever with and without rash.
FEVER WITH RASH

• Bacterial and viral infections are frequently associated with a rash and fever in
children.
• Most exanthems are self-limited and resolve in 7 to 10 days and only
symptomatic treatment is needed.
• Vaccinations have significantly decreased the incidence of measles, rubella,
varicella, and their congenital complications.
IMPORTANT TO REMEMBER:
• Association of Fever and Heart Rate:
o Normally, HR increases by 10 bpm/1°C rise in T° for children >2 months
of age.
• Relative Tachycardia:
o Is when PR increases disproportionately to the temperature.
o is usually caused by noninfectious diseases or infectious diseases in
which a toxin is responsible for the clinical manifestations.
• Relative Bradycardia:
o is when PR remains low in the presence of fever.
o It can accompany the following diseases:
▪ Typhoid fever
▪ Brucellosis
▪ Leptospirosis
▪ Drug fever

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• Bradycardia in the presence of fever also may be a result of a conduction
defect resulting from cardiac involvement with acute rheumatic fever, Lyme
disease, viral myocarditis, or infective endocarditis.
• The following table helps in the evaluation of fever in an older child in our set
up:
Table 40 Evaluation of fever in an older child

Diagnosis of fever In favor
Measles - Typical rash, Cough, runny nose, red eyes,
Mouth ulcers, Corneal clouding
- Recent exposure to a measles case
- No documented measles immunization
Viral infection - Mild systemic upset
- Transient non-specific rash
Meningococcal infection - Petechial or purpuric rash Bruising
- Shock Stiff neck (if meningitis)
Relapsing fever - Petechial rash/ skin hemorrhages
- Jaundice
- Tender enlarged liver and spleen
- History of relapsing fever
- Positive blood smear for Borrelia
Typhus - Epidemic of typhus in region
- Characteristic macular rash
III. FEVER OF UNKNOWN ORIGIN (FUO)

• Definition:
o children with a temperature >38°C documented by a healthcare provider
and for which the cause could not be identified after at least 8 days of
evaluation.
• Whereas, Fever without a source (FWS)
o is fever where the source has not yet been identified and is
differentiated from FUO by the duration of the fever.
ETIOLOGY
• The many causes of FUO in children are:
o Infectious,
o Rheumatologic (connective tissue or autoimmune),
o Auto-inflammatory,
o Oncologic,
o Neurologic,
o Genetic,
o Factitious, and

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o Iatrogenic processes.
• Drug fever can also be a cause.
• Drug fever is usually sustained and not associated with other symptoms.
• Discontinuation of the drug is associated with resolution of the fever, generally
within 72 hr, although certain drugs, such as iodides, are excreted for a
prolonged period, with fever that can persist for as long as 1 mo after drug
withdrawal.

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5.2. TORCH: CONGENITAL AND PERINATAL INFECTIONS

• Congenital, a.k.a. intrauterine infections: are those transmitted across the
placenta.
• Perinatal infections: are those transmitted from the mother to the fetus or
newborn infant during the birth process.
• Congenital infections include a well-known group of fungal, bacterial, and viral
pathogens:
o toxoplasmosis, rubella, CMV, HSV, congenital syphilis,
o VZV, parvovirus, HIV, hepatitis B, Zika virus,
o Neisseria gonorrhoeae, Chlamydia, and Mycobacterium tuberculosis.
• Generally well-known by the acronym TORCH infection.
GENERAL APPROACH
• DDx of congenital and perinatal infections should include infectious as well as
noninfectious processes, such as underlying CHD, genetic disorders, and inborn
errors of metabolism.
• Because maternal infection is a prerequisite for infection in the fetus, a
thorough history is
• essential to assess the mother for her symptoms, travel, diet, medication use,
occupational exposures, and any STIs during pregnancy.
• Laboratory testing and/or radiologic imaging is often required to confirm the
diagnosis.
Table 41 Common manifestations of TORCH infections
IUGR Jaundice • This group of infections may present in

Nonimmune HSM the neonate with similar clinical and
hydrops laboratory findings, hence the usefulness
Anemia chorioretinitis of the TORCH concept.
Thrombocytopenia Congenital • Many of the clinical manifestations of
malformations
congenital infections are similar (See
table)
• Evaluation of patients thought to have a congenital infection should include

attempts to:
o isolate the organism by culture (for Rubella, CMV, HSV, gonorrhea, and
M. tuberculosis),
o Identify the antigen of the pathogen (for hepatitis B and C.
trachomatis),
o Identify the pathogen’s genome with PCR, and

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o Identify specific fetal production of antibodies (IgM or increasing titer of
IgG for Toxoplasma, syphilis, parvovirus, HIV, or Borrelia).
• Treatment depends on the specific pathogen and can range from
symptomatic management with close follow-up for long-term sequelae to
targeted antimicrobial therapy.
• However, treatment may not be always available, specific, or effective
(e.g. in the case of CMV infection).
• The route and timing of infection can provide helpful clues as to the
potential infectious etiology.
o E.g.: 1st TM infection may alter embryogenesis and result in
malformations of the heart and eyes, as seen in congenital rubella
syndrome.
o 3rd TM infection (e.g., congenital toxoplasmosis) can result in active
infection with signs of hepatomegaly, splenomegaly, and generalized
lymphadenopathy at birth.
o Infections that occur late in gestation (e.g., congenital syphilis) may
lead to a delay in C/Ms until weeks to years after birth.
• Intrauterine infection from CMV, T. pallidum, T. gondii , rubella virus, VZV,
and human parvovirus B19 may cause Minimal or no symptoms in the mother
but still may be transmitted across the placenta to the fetus.
• Regardless of the mother's immune status, the placenta may act as a
barrier, and the fetus may or may not be infected.
• If infection occurs, signs may or may not be noted in the fetus during
pregnancy.
• Infection can result in:
In general, the earlier in
o spontaneous abortion,
pregnancy a TORCH infection
o congenital malformation, occurs, the more severe the
o IUGR, complications.
o premature birth,
o stillbirth,
o acute or delayed disease in the neonate, or
o asymptomatic persistent infection with sequelae later in life.
• In this chapter, we’ll be discussing just the five of them.
1. CONGENITAL TOXOPLASMOSIS
• T. gondii is a coccidian parasite which is ubiquitous in nature and is one of the
most common latent infections of humans throughout the world.
• The vast majority of cases are a result of acquired maternal acute primary
infection during pregnancy by trans-placental transfer of the organism;
• Placental infection occurs and persists throughout gestation.

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• Transmission from an acutely infected mother to her fetus occurs in about 30-
40% of cases.
• In contrast to congenital rubella, risk of infection transmission to the fetus is
directly related with gestational age.
• The later in pregnancy that infection is acquired, the more likely is
transmission to the fetus:
o 1st TM = 17%
o 2nd TM = 25%, and
o TM = 65% transmission.
• Rarely, a parasite may be transmitted via an infected placenta during
parturition.
• However, infections transmitted earlier in gestation are likely to cause more
severe fetal effects (abortion, stillbirth, or severe disease with teratogenesis).
• Those transmitted later are more apt to be subclinical mostly with no overt
disease at birth;
• The classic findings of:
o Obstructive hydrocephalus,
o chorioretinitis, and
o intracerebral calcifications suggest the diagnosis of congenital
toxoplasmosis.
• Almost all congenitally infected individuals who are not treated manifest signs
or symptoms of infection, such as chorioretinitis, by adolescence.
CLINICAL MANIFESTATION
• Most often, maternal infection is asymptomatic or The 4 Cs of congenital
without specific S/Sx. toxoplasmosis:
• Lymphadenopathy is the most commonly identified • Cerebral calcifications,
• Chorioretinitis,
physical finding.
• HydroCephalus, and
• Congenital toxoplasmosis may be manifested as: • Convulsions.
o clinical neonatal disease,
o disease in the first few months of life,
o late sequelae or relapsed infection of a previously undiagnosed and
untreated infection later in infancy or even later in life, or
o subclinical disease.
A. CLINICAL DISEASE
• From 25% to >50% of infants with clinically apparent disease at birth are born
prematurely.
• IUGR, low Apgar scores, and temperature instability (including hypothermia)
are common.

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• Congenital infection may present as a mild or severe neonatal disease.
• These can be as severe as from hydrops fetalis and perinatal death, or can be
milder manifestations like:
o SGA
o Persistent jaundice (direct hyperbilirubinemia)
o Prematurity
o Mild thrombocytopenia
o Peripheral retinal scars
o CSF Pleocytosis
• Affected infants tend to:
o have HSM, and
o present with a generalized maculopapular rash
• Infection in the fetus or neonate usually involves disease in one of two forms:
o Infection of the CNS or the eyes, or
o Infection of the CNS and eyes with disseminated infection.
• The characteristic triad of congenital toxoplasmosis is mentioned above.
• In addition, toxoplasmosis has also been associated with other abnormalities
like:
o various endocrinopathies (which may be secondary to hypothalamic or
pituitary effects),
o end-organ involvement,
o congenital nephrosis,
o isolated mental retardation.
I. NEUROLOGIC MANIFESTATIONS OF CONGENITAL TOXOPLASMOS IS

• Vary from massive acute encephalopathy to subtle neurologic syndromes.
• Toxoplasmosis should be considered as a potential
cause of any undiagnosed neurologic disease in
children <1 yr old, especially if retinal lesions are
present.
A. Hydrocephalus may be the sole clinical neurologic
manifestation of congenital toxoplasmosis.
B. Microcephaly usually reflects severe brain damage,
but those treated may have normal cognitive
function.
Figure 32 Hydrocephalus due to congenital
▪ Untreated congenital toxoplasmosis. that is toxoplasmosis.
symptomatic in the 1st yr of life can cause
substantial diminution in cognitive function and developmental
delay.

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▪ Seizures and focal motor defects may become apparent after the
newborn period
C. Calcifications occur throughout the brain.
▪ MRI and contrast-enhanced CT brain scans are useful for detecting
active inflammatory lesions.
D. CSF abnormalities occur in at least 50% of infants with congenital
toxoplasmosis.
▪ A CSF protein level >1 g/dL is characteristic of severe CNS
toxoplasmosis. and is usually accompanied by hydrocephalus.
II. OCULAR MANIFESTATIONS OF CONGENITAL TOXOPLASMOSIS

• Almost all untreated congenitally infected infants
develop chorioretinal lesions by adulthood and may
have severe visual impairment.
• T. gondii causes a focal necrotizing retinitis in
congenitally infected individuals and retinal detachment
may even occur.
• Any part of the ocular structure can be involved.
• Other manifestations include:
▪ Strabismus, Figure 33 Macular scar secondary to
▪ visual impairment, congenital toxoplasmosis. Visual acuity of
the patient is 20/400.
▪ nystagmus, and
▪ microphthalmia.
III. CUTANEOUS MANIFESTATIONS OF CONGENITAL TOXOPLASMOSIS

• Include rashes and jaundice and/or petechiae secondary to thrombocytopenia,
• but ecchymoses and large hemorrhages secondary to thrombocytopenia also
occur.
• Macular rashes involving the entire body including the palms and soles,
exfoliative dermatitis, and cutaneous calcifications have been described.
• Jaundice with hepatic involvement and/or hemolysis,
• Cyanosis due to interstitial pneumonitis from congenital infection, and
• Edema secondary to myocarditis or nephrotic syndrome may be present.
• Jaundice and conjugated hyperbilirubinemia may persist for months.
IV. AUDITORY MANIFESTATION OF CONGENITAL TOXOPLASMOSIS

• Sensorineural hearing loss, both mild and severe, may occur.
B. DISEASE IN THE FIRST FEW MONTHS OF LIFE, AND LATE SEQUELAE OR

RELAPSED INFECTION.
• 70% to 90% of infants with congenital infection are asymptomatic at birth.

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• However, visual impairment, learning disabilities, or mental impairment
becomes apparent in a large percentage of children months to several years
later.
• Late sequelae are primarily related to ocular or CNS disease.
• Seizures are common.
• These infants are at increased risk for long-term neurological and
neurodevelopmental complications.
DIAGNOSIS
• Prenatal diagnosis
o Fetal U/S examination, performed every 2 week during gestation,
beginning at diagnosis of acute acquired infection in a pregnant woman,
o PCR analysis of amniotic fluid.
• Diagnosis of acute Toxoplasma infection can be established by a number of
methods:
o isolation of T. gondii from blood or body fluids;
o identification of tachyzoites in sections or preparations of tissues and
body fluids, amniotic fluid, or placenta;
o identification of cysts in the placenta or tissues of a fetus or newborn;
and
o characteristic lymph node histologic features.
• Serological tests are the primary means of diagnosis.
• IgG-specific antibodies achieve a peak concentration 1-2 months after infection
and remain positive indefinitely.
• For infants with seroconversion or a 4x increase in IgG titers, specific IgM
antibody determinations should be performed to confirm disease.
• Especially for congenital infections, measurement of IgA and IgE antibodies can
be useful to confirm the disease.
• PCR is useful to identify T. gondii DNA in CSF and amniotic fluid.
TREATMENT
• For symptomatic and asymptomatic congenital infections, initial therapy should
include pyrimethamine (supplemented with folic acid) combined with
sulfadiazine.
• Duration of therapy is often prolonged, even up to 1 year.
• Optimal dosages of medications and duration of therapy should be determined
in consultation with appropriate specialists.
• Prevention: Pregnant women should avoid eating raw meat or raw eggs and
avoid exposure to cat litter boxes or cat feces.

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2. CONGENITAL RUBELLA
• Maternal viremia is a prerequisite for placental infection, which may or may
not spread to the fetus.
• After infecting the placenta, the virus spreads through the vascular system of
the developing fetus and may infect any fetal organ.
• The most important risk factor for severe congenital defects is the stage of
gestation at the time of infection.
• Maternal infection during the first 8 week of gestation results in the most
severe and widespread defects.
• The occurrence of congenital defects approaches 85% if infection is acquired
during the first 4 weeks of gestation; close to 40% spontaneously abort or are
stillborn.
• Defects occurring after 16 week of gestation are uncommon, even if fetal
infection occurs.
• Infection after 4 months’ gestation does not seem to cause disease.
• The most distinctive feature of congenital rubella
CCC-Triad of congenital
is chronicity. rubella syndrome:
• Once the fetus is infected early in gestation, the Cataracts,
virus persists in fetal tissue until well beyond Cochlear defects,
delivery. Cardiac abnormality
• Infants with congenital rubella are chronically and
persistently infected and tend to shed live virus in
urine, stools, and respiratory secretions for 1 year.
• Persistence suggests the possibility of ongoing tissue damage and reactivation,
most notably in the brain.
• Infants should be isolated while in the hospital and kept away from
susceptible pregnant women when sent home.
• Placental or fetal infection may lead:
o resorption of the fetus,
o fetal infection from multisystem disease,
o spontaneous abortion,
o congenital anomalies,
o stillbirth or
o inapparent infection
• The most common characteristic abnormalities associated with congenital
rubella include:
o Auditory (Sensorineural hearing loss),

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▪ Nerve deafness is the single most common finding among infants
with Congenital Rubella Syndrome (CRS).
o Ophthalmologic (Cataracts, Retinopathy, and
Glaucoma),
▪ Unilateral or bilateral cataracts are the most
serious eye finding, occurring in about a third of
infants.
▪ Retinal findings described as salt-and-pepper
retinopathy are the most common ocular
Figure 34 Morgagnian (hypermature)
abnormality but have little early effect on cataract
vision. Slit-lamp photography
o Cardiac (PDA and peripheral pulmonary artery
stenosis),
▪ PDA is the most frequently reported cardiac defect, followed by
lesions of the pulmonary arteries and valvular disease.
o Neurological (behavioral disorders, meningoencephalitis, and
developmental delay) conditions.
▪ Meningoencephalitis is present in 10–20% of infants with CRS and
may persist for up to 12 mo.
• Most infants have some degree of IUGR.
• Interstitial pneumonitis leading to death in some cases has
been reported.
• In addition, infants can present with:
o Growth retardation
o Early-onset jaundice
o HSM
o Radiolucent bone disease
o Early-onset jaundice
o Purpuric skin lesions (“blueberry muffin” appearance
Figure 35 Blueberry muffin syndrome
from dermal erythropoiesis)
• More than one half of all newborns with congenital rubella are normal at birth;
however, the majority later develop one or more signs and symptoms.
• A variety of late-onset manifestations of CRS have been recognized.
• In addition to Progressive Rubella Panencephalitis (PRP), they include diabetes
mellitus (20%), thyroid dysfunction (5%), psychomotor retardation, autism and
glaucoma and visual abnormalities associated with the retinopathy, which had
previously been considered benign.
DIAGNOSIS

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• Serologic studies are the mainstay of rubella diagnosis, but the disease itself
may cause immunologic aberrations and delay the infant's ability to mount IgM
or IgG responses.
• Detection of rubella-specific IgM antibody usually indicates recent infection.
• Measurement of rubella-specific IgG over several months can be confirmatory.
• Rubella virus can be isolated from blood, urine, CSF, and throat swab
specimens.
TREATMENT
• There is no specific treatment available for either acquired rubella or CRS.
• Long-term follow-up is needed secondary to late-onset symptoms.
PREVENTION
• Prevention consists of vaccination of the susceptible population (especially
young children).
• Vaccine should not be given to pregnant women.
• Because they may excrete the virus in respiratory secretions up to 1 yr of age,
children with congenital rubella should be considered contagious until they are
at least 1 year old, unless nasopharyngeal and urine cultures are repeatedly
negative for rubella virus.
3. CONGENITAL SYPHILIS
• Syphilis is a chronic systemic sexually or vertically (mother to child)
transmitted infection caused by the bacteria Treponema.
• Treponemas appear able to cross the placenta at ANY time during pregnancy,
thereby infecting the fetus.
• Congenital syphilis results from trans-placental Hutchinson triad: Interstitial
transmission of spirochetes or occasionally by keratitis, sensorineural hearing
intrapartum contact during passage through the loss, Hutchinson teeth.
birth canal.
• Syphilis can cause preterm delivery, stillbirth
(30-40% of fetuses with congenital syphilis are stillborn), congenital infection,
or neonatal death, depending on the stage of maternal infection and duration
of fetal infection before delivery.
• Untreated infection in the first and second trimesters often leads to significant
fetal morbidity, whereas with third-trimester infection many infants are
asymptomatic.
• Virtually all infants born to untreated women with primary and secondary
syphilis have congenital infection; 50% are clinically symptomatic.

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• The mortality rate may be as high as 54% in infected infants.
• Early congenital syphilis is when clinical manifestations occur before 2 years of
age; late congenital syphilis is when manifestations occur at >2 years of age
appearing gradually during the first 2 decades.
CASE CLASSIFICATION
PROBABLE CASE
1. A condition affecting an infant whose mother had untreated or inadequately
treated* syphilis at delivery, regardless of signs in the infant OR
2. An infant or child who has a reactive non-treponemal test for syphilis (Venereal
Disease Research Laboratory [VDRL], rapid plasma reagin [RPR], or equivalent
serologic methods) AND any one of the following:
a. Any evidence of congenital syphilis on physical examination (see Clinical
description)
b. Any evidence of congenital syphilis on radiographs of long bones
c. A reactive cerebrospinal fluid (CSF) venereal disease research laboratory
test (VDRL) test
d. In a non-traumatic lumbar puncture, an elevated CSF leukocyte (white
blood cell, WBC) count or protein (without other cause):
- Suggested parameters for abnormal CSF WBC and protein values:
I. During the first 30 days of life, a CSF WBC count of >15
WBC/mm3 or a CSF protein >120 mg/dl is abnormal.
II. After the first 30 days of life, a CSF WBC count of >5
WBC/mm3 or a CSF protein >40 mg/dl, regardless of CSF
serology. The treating clinician should be consulted to
interpret the CSF values for the specific patient.
* Adequate treatment is defined as completion of a penicillin-based regimen, in
accordance with CDC treatment guidelines, appropriate for stage of infection,
initiated 30 or more days before delivery.
CONFIRMED CASE
A case that is laboratory confirmed.
• Generally, neonates do not have signs of primary syphilis from in
utero acquired infection.
• Two thirds show no clinical signs of infection at birth and are
identified by routine prenatal screening.
• Their manifestations are systemic and similar to those of adults Figure 36 Hutchinson's Teeth
resulting from congenital syphilis
with secondary syphilis.

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• There is a higher chance of CNS involvement.
• The most common findings in the neonatal period
include:
o HSM,
o jaundice, and
o osteochondritis.
• Other signs include:
o generalized lymphadenopathy,
o pneumonitis,
o myocarditis, Figure 37 Skin alterations in congenital syphilis
o Rash (vesicobullous, especially on the palms Pemphigus syphiliticus on the plantar surfaces of the feet in a
newborn with congenital syphilis. The formation of blisters on the
and soles), soles of the feet are difficult to identify in this image. Source: ©
o hemolytic anemia (normocytic or IMPP
normochromic), and
o hemorrhagic rhinitis (snuffles).
• Late congenital syphilis manifests by:
o Hutchinson's teeth,
o healed retinitis,
o eighth nerve deafness,
o saddle nose,
o mental retardation,
o arrested hydrocephalus, and
o saber shins.
Figure 38 Newborn with
• Other clues to the diagnosis of congenital syphilis include congenital syphilis
placentomegaly and congenital hydrops.
DIAGNOSIS
1. Nonspecific reagin antibody tests (NTA)
i. VDRL slide test
ii. Rapid plasma regain test
2. Specific treponemal tests (STA)
o verify a diagnosis of current or past infection.
o should be performed if NTA test results are positive.
o are useful for diagnosing a first episode of syphilis and for
distinguishing a false-positive result of NTA tests.
o do not correlate with disease activity and are not quantified.
TREATMENT
A. Treated mother

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o Infants born to mothers who received adequate penicillin treatment for
syphilis during pregnancy are at minimal risk.
o The infant should be treated if maternal treatment was inadequate,
unknown, or given during the last 4 weeks of pregnancy or if a drug
other than penicillin (eg, erythromycin) was used.
o In a pregnant woman who has been treated for syphilis, quantitative NTA
tests should be done monthly for the duration of the pregnancy.
o Appropriate treatment should result in a progressive decrease in titer.
B. VDRL-positive infant
o May only be an indication of maternal transfer of IgG.
o These infants should be treated if adequate follow-up cannot be
obtained.
C. Definitive treatment
o Current treatment guidelines recommend treating all infants with
congenital syphilis with:
- aqueous crystalline penicillin G, 100,000-150,000 units/kg/24 h
IV, or
- alternately 50,000 units/kg/day of procaine penicillin IM; the
duration of therapy should be 10-14 days in both instances.
D. Isolation procedures
o Precautions regarding drainage, secretions, and blood and body fluids
are indicated for all infants with suspected or proven congenital syphilis
until therapy has been given for 24 h.
E. Follow-up care
o The infant should have repeated quantitative NTA tests at 3, 6, and 12
months.
o Most infants will have a negative titer with adequate treatment.
o A rising titer requires further Ix and retreatment.
4. NEONATAL HERPES
• Neonatal herpes is an uncommon but potentially fatal infection of the fetus or
more likely the newborn.
• Two serologic subtypes: HSV-1 (orolabial) and HSV-2 (genital).
• 75% of neonatal herpes infections are secondary to HSV-2.
• HSV-1, however, is the cause of 7-50% of primary genital herpes infections.
• HSV infection of the neonate can be acquired at one of three times:
o Intrauterine,
o Intrapartum, or
o Postnatal.

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• Most infections (80%) are acquired in the intrapartum period as ascending
infections with ruptured membranes or by delivery through an infected cervix
or vagina.
• 4-6 h is considered a critical period for ascending infection to occur.
• However, acquisition can also occur even with cesarean delivery with intact
fetal membranes.
• The usual portals of entry for the virus are the skin (breaks or abrasions
occurring with forceps delivery or scalp electrode monitoring), eyes, mouth,
and respiratory tract.
• Once colonization occurs, the virus may spread by contiguity or via a
hematogenous route.
• The incubation period is from 2-20 days.
• Three general patterns of neonatal HSV are disease:
o localized to the skin, eyes, and mouth (SEM);
o CNS involvement (with or without SEM involvement); and
o Disseminated disease (which also may include signs of the first 2 groups).
• Around 20% present between 5 and 9 wk of age.
• 33 to 50% of infants born vaginally to mothers with a primary infection will
themselves have HSV compared with only 3-5% of those born to mothers with
recurrent infection.
• Maternal antibody is not necessarily protective in the fetus.
• Neonatal HSV infection is thought to never be asymptomatic.
• Infants with intrauterine infection typically have:
o Skin vesicles or scarring,
o Eye findings, and
o Microcephaly or hydranencephaly that are present at delivery.
• Only few infants with neonatal herpes survive without therapy, and those who
do generally have severe sequelae.
• Infants with SEM disease generally present at 5-11 days of life.
• If untreated, SEM disease in infants may progress to encephalitis or
disseminated disease.
• Infants with encephalitis typically present at 8-17 days of life.
• They have clinical findings suggestive of bacterial meningitis, including
irritability, lethargy, poor feeding, poor tone, and seizures.
• Fever is relatively uncommon.
• Skin vesicles occur in only approximately 60% of cases.
• If untreated, 50% of infants with HSV encephalitis die and most survivors have
severe neurologic sequelae.

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• Infants with disseminated HSV infections generally become ill at 5-11 days of
life.
• Their clinical picture is similar to that of infants with neonatal sepsis.
• Common presenting features include: hyperthermia or hypothermia,
irritability, poor feeding, and vomiting.
• They may also have respiratory distress, cyanosis, apneic spells, jaundice,
purpuric rash, and evidence of CNS infection.
• Seizures are common.
• Skin vesicles are seen in around 75% of cases.
• If untreated, the infection causes shock and DIC, killing approximately 90% of
infants, and most survivors have severe neurologic sequelae.
• Infants with neonatal herpes whose mothers received antiherpes antiviral drugs
in the weeks prior to delivery may present later than their untreated
counterparts.
APPROACHES TO NEONATAL HSV

• Evaluation of the neonate with suspected HSV infection should include:
o Cultures of suspicious lesions, also eye and mouth swabs and
o PCR of both CSF and blood.
• Most HSV diagnostic tests take at least a few days to complete, therefore
treatment should not be withheld but rather initiated promptly so as to ensure
the maximum therapeutic benefit.
MANAGEMENT PRINCIPLE:
1. Testing and empirical treatment of all neonates <21 days old who are
evaluated for infection,
2. Testing and empirical treatment of neonates with the presence of high-risk
clinical features for HSV, and
3. Testing and empirical treatment for all neonates with high-risk features plus
testing the CSF of all neonates <21 days old while deferring empirical acyclovir
in those without high-risk features, unless the CSF HSV PCR test is positive.
• All infants with proven or suspected neonatal HSV infection should be treated
immediately with high-dose intravenous acyclovir (60 mg/kg/day divided every
8 hr IV).
• These neonates receiving the therapy should be monitored for neutropenia.
• SEM disease should be treated for 14 days.
• Those with disseminated or CNS disease should receive 21 days of therapy.
5. CYTOMEGALOVIRUS (CMV)

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• Human CMV is ubiquitous in the population, and individuals who become
infected remain persistently infected for life, with intermittent shedding of
infectious virus from mucosal surfaces.
• CMV infections are acquired through several settings:
a. community exposure,
b. nosocomial transmission, and
c. intrauterine infection.
• Our focus in this chapter will be on Congenital CMV infection.
CONGENITAL CMV INFECTION

• Possible transmission routes for CMV: transplacental, at delivery (with cervical
colonization), via breast milk, and via transfusion of
Congenital toxoplasmosis
seropositive blood to an infant whose mother is
may manifest with
seronegative.
symptoms resembling
• 10 to 30% of pregnant women have cervical colonization congenital CMV infection.
with CMV.
• CMV is capable of penetrating the placental barrier as
well as the blood-brain barrier.
• Both primary and recurrent maternal CMV can lead to transmission of virus to
the fetus.
• However, transmission rate is much higher with primary maternal infection
occurring during pregnancy.
• The risk does not appear to vary significantly with gestational age at time of
maternal infection.
• More than 90% of infants born with CMV have subclinical infection.
• Symptomatic infants are usually born to women with primary infection and
they have a mortality rate of 20 - 30%.
• The primary target organs are the CNS, eyes, liver, lungs, and kidneys.
• Risk factors include: lower socioeconomic status, drug abuse, sexual
promiscuity in the mother, prematurity, and transfusion with unscreened
blood.
1. Subclinical infection
o is 10 times more common than clinical illness.
2. Low birth weight
o Maternal CMV infection is associated with LBW and SGA infants even
when the infant is not infected.
3. Classic CMV inclusion disease consists of:
o IUGR,

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oHSM with jaundice,
oabnormal LFTs,
othrombocytopenia with or without purpura,
osevere CNS disease (including microcephaly,
intracerebral calcifications, most characteristically
in the subependymal area),
o chorioretinitis, and
o progressive sensorineural hearing loss.
o Other symptoms include hemolytic anemia and
pneumonitis. Figure 39 An infant with congenital CMV
4. Late sequelae.
o With subclinical infection, late sequelae such as mental retardation,
learning disability, and sensorineural hearing loss have been attributed
to CMV.
o By 2 years of age, 5-15% of infants who are asymptomatic at birth may
experience serious sequelae, such as hearing loss or ocular
abnormalities.
DIAGNOSIS
• Laboratory studies
o Gold Standard: urine or saliva culture.
o PCR
• Radiologic Studies
o Skull films or CT scans of the head may demonstrate characteristic
intracranial calcifications.
TREATMENT
• Currently, there are no recommendations for the treatment of infants with
congenital CMV infection.
• Under life-threatening circumstances, a dose of 5-6 mg/kg IV Ganciclovir every
8 h can be considered.
• Efforts are focused primarily on the development of a safe vaccine.
• Affected infants may excrete the virus for months to years and are often a
concern to personnel caring for them.
• Standard precautions, especially good hand washing after diaper changes, is
particularly important for pregnant personnel.

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5.3. PEDIATRICS HIV/AIDS
ETIOLOGY
• There are two types of HIV:
I. HIV-1
▪ Which is found worldwide and is responsible for the worldwide
pandemic.
▪ HIV-1 has many subtypes, often varying in transmissibility and
virulence, as well as other characteristics.
II. HIV-2
▪ Which is found mainly in West Africa, Mozambique and Angola
▪ HIV-2is less pathogenic and makes little or no contribution to
pediatric AIDS.
LIFECYCLE
• The HIV life cycle in the host cell can be divided into several steps;
1. Binding; HIV binds to cells via interaction between the HIV envelope
glycoprotein (gp120) and the host cell receptors (CD4 molecule) and co-
receptors.
2. Fusion; binding results in the insertion of the trans-membrane
glycoprotein (gp41) into the cell membrane of the host cell, with fusion
of the two membranes.
3. Entry; Thevirus particleleavesits membrane behind(uncoating) and the
core of the virus is released into the cytoplasm of the host cell.
4. Reverse transcription; for the virus to multiply, the viral (single strand)
RNA must first be converted into (double-strand) DNA by reverse
transcriptase.
5. Integration and replication; the viral DNA is then able to enter the host
nucleus and the viral enzyme integrase is used to insert the viral DNA
into the host cell’s DNA.
6. Budding; newly formed immature viral particles gather at the
membraneoftheCD4cellsandpushthroughthecellmembrane by budding.
7. Maturation; The gp160, embedded in the cell membrane, is cleaved by
the enzyme protease to produce functional gp41 and
gp120toformamaturevirus, which is then ready to infect a new cell.
TRANSMISSION
• Sexual contact
• Parenteral exposure to blood

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• Vertical transmission from mother to child. It is primary route of infection in
the pediatric population.
Table 42 Vertical transmission from mother to child
Pregnancy Labor and delivery Breast feeding
• Viral, bacterial, or • Rupture of membranes for more • Any exposure to breast milk
parasitic placental than 4 hours • Duration of breastfeeding
infections, such as • Invasive delivery procedures that • Mixed feeding (giving water,
malaria increase contact with mother’s other liquids, or solid foods in
• Sexually transmitted infected blood or body fluids addition to breastfeeding)
infections (STIs) (episiotomy, artificial rupture of • Breast abscesses, nipple
• History of past and membranes) fissures, mastitis
current multiple sexual • Chorioamnionitis (from untreated • Oral disease in the baby
partners STI or other infection) (thrush or sores)
• Preterm delivery
• Low birth weight
NATURAL HISTORY
• Children prenatally infected with HIV fit in to one of three categories:
a. Category 1 (25–30%): Rapid progressors, who die by the age of one and
who are thought to have acquired the infection in utero or during the
early perinatal period.
b. Category 2 (50–60%): slow progressors Children who develop symptoms
early in life, followed by a downhill course and death by the age of three
to five.
c. Category 3 (5–25%): Long-term survivors, who live beyond the age of
eight.
• In young infants the earliest clinical signs and symptoms may be nonspecific,
such as:
o failure to thrive,
o acute respiratory infections, and
o diarrhea.
• Clinical manifestations found more commonly in children than adults with HIV
infection include recurrent bacterial infections, chronic parotid swelling,
lymphocytic interstitial pneumonitis (LIP), and early onset of progressive
neurologic deterioration.
1. INFECTION
• Approximately 20% of AIDS-defining illnesses in children are recurrent bacterial
infections caused primarily by encapsulated organisms such as Streptococcus
pneumonia and Salmonella as a result of disturbances in humoral immunity.

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• The most common serious infections in HIV –infected children are bacteremia,
sepsis, and bacterial pneumonia, accounting for more than 50% of infections in
these patients.
• Otitis media, sinusitis, and skin and softtissue infections, are very common and
may be chronic with atypical presentations.
• Opportunistic infections are generally seen in children with severe depression
of the CD4 count. Infants <1yr of age have a higher incidence of developing
stage 3–defining opportunistic infections and mortality rates compared with
older children and adults even at higher CD4 counts, reflecting that the CD4
count may over predict the immune competence in young infants.
2. RESPIRATORY SYSTEM
• Recurrent upper respiratory tract infections such as otitis media and sinusitis
are very common. Although the typical pathogens (S. pneumoniae, H.
influenzae, Moraxella catarrhalis) are most common, unusual pathogens such as
P. aeruginosa, yeast, and anaerobes may be present in chronic infections and
result in complications such as invasive sinusitis and mastoiditis.
A. LIP (LYMPHOCYTIC INTERSTITIAL PNEUMONIA)

• is the most common chronic lower respiratory tract abnormality chronic
process with nodular lymphoid hyperplasia in the bronchial and bronchiolar
epithelium, often leading to progressive alveolar capillary block over months to
years.
• LIP is a lymphoproliferative response to a primary Epstein-Barr virus infection
in the setting of HIV infection.
• There is an insidious onset of tachypnea, cough, and mild to moderate
hypoxemia with normal auscultatory findings or minimal rales accompanied by
digital clubbing which usually resolves with oral corticosteroid therapy
pneumonia.
• Most symptomatic HIV –infected children experience at least one episode of
pneumonia during their disease. S. pneumonia is the most common bacterial
pathogen, but P. aeruginosa and other Gram-negative bacterial pneumonias
may occur in end-stage disease and are often associated with acute respiratory
failure and death Pneumocystis pneumonia is the most common opportunistic
infection,
• The peak incidence of Pneumocystis pneumonia occurs at age 3-6mo clinical
features.
• The classic clinical presentation of Pneumocystis pneumonia includes an acute
onset of fever, tachypnea, dyspnea, and marked hypoxemia.
DIAGNOSIS

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• The diagnosis is established by demonstration of P. jiroveci with appropriate
staining of induced sputum or bronchoalveolar fluid lavage; rarely, an open
lung biopsy is necessary chest x-ray interstitial infiltrates or diffuse alveolar
disease.
TREATMENT
• The first-line therapy for Pneumocystis pneumonia is trimethoprim
sulfamethoxazole (TMP-SMX) (15-20mg/kg/day of the TMP component divided
every 6hr intravenously) with adjunctive corticosteroids for moderate to severe
disease, usually defined as if the PaO2 is <70mm Hg while breathing room air.
After improvement, therapy with oral TMP-SMX should continue for a total of
21 days while the corticosteroids are weaned.
B. TUBERCULOSIS
• The burden of TB in children depends on the burden of the disease in the adult
population. These children are at increased risk of developing primary
progressive TB because of the associated severe immune suppression resulting
from their young age and HIV.
• Extrapulmonary TB is seen more often in HIV-infected children.
CLINICAL FEATURE
HISTORY
• Unexplained weight loss or failure to grow normally Co-administration of
rifampin and single PIs
• Unexplained fever, especially if more than 14 days (except ritonavir) or
• Chronic cough (more than 14 days) NNRTIs can accelerate
• Failure to respond to appropriate antibiotic treatment of clearance of these drugs
resulting in sub
presumed bacterial pneumonia or meningitis therapeutic levels of these
• Exposure to an adult with probable or definite pulmonary drugs.
infectious TB Both anti TB drugs and
ARVs have overlapping
PHYSICAL EXAMINATION; toxicities especially
hepatotoxicity therefore
• Fluid on one side of chest (dullness to percussion, reduced children require close
air entry) clinical monitoring.
• Enlarged, non-tender lymph nodes or abscess, especially in
the neck
• Signs of meningitis, especially if subacute and developing over several days
• Abdominal swelling, with or without palpable lumps
• Progressive swelling or deformity of a bone or joint, including the spine
DIAGNOSIS

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• Xpert MTB/RIF should be used rather than conventional microscopy, culture
and drug susceptibility testing (DST) as the initial diagnostic test. (WHO).
• Gastric washing from young children and sputum in older children should be
sent for AFB smear (and culture if possible) (NATIONAL PEDIATRIC GUIDLINE)
• The absence of bacteriologic evidence or failure to obtain a sample should not
deter diagnosis of TB in a child not responding to or deteriorating despite
adequate treatment for non-tuberculosis infections.
TREATMENT
• When faced with a child with HIV-associated TB disease the priority is to treat
TB, and restore immune function by providing ART whilst minimizing toxicity
from medications.
• All children with HIV-associated TB disease should be on prophylactic
cotrimoxazole therapy.
• Directly observed therapy short course (DOTS) is recommended for treatment
of tuberculosis in children.
C. GI SYSTEM
Oral Lesions
• Erythematous or pseudomembranous candidiasis; The most common oral
condition in HIV-infected children is candidiasis, which may be oropharyngeal
or esophageal. Oral candidiasis is strongly predictive of HIV infection if it is
recurrent, persistent and occurs outside the neonatal period without prior
antibiotic treatment. It is characterized by white or yellow plaques on the
buccal mucosa, palate, and/or tongue
• DIAGNOSIS: Candidiasis is diagnosed by its clinical appearance and by detection
of organisms on smears.
• TREATMENT: Most commonly used is nystatin 100,000 units/ml suspension: 1-2
ml into the mouth 4-6 times daily for 7 days; using cotton wool or a piece of
cloth to paint the mouth with nystatin may even be better. Use fluconazole 3
mg/kg daily orally for 7-14 days for recurrent refractory oral candidiasis. In
cases of suspected esophageal candidiasis extend treatment for 21 days.
OTHER ORAL LESIONS;

HERPES SIMPLEX;
• Primary herpetic gingivostomatitis commonly occurs in children and young
adults and may be followed by frequent recurrences. Tender submandibular
lymphadenopathy and superficial painful ulcers in the gingiva and oral mucosa
characterize primary herpetic gingivostomatitis.

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• DIAGNOSIS: Appearance of typical ulcers and vesicles around the mouth and
nose.
• TREATMENT: HIV-infected children with symptomatic disease should be treated
with acyclovir at a dose of 20mg/kg/dose by mouth, administered 3 times per
day for 7-14 days. Periodontal disease (e.g. ulcerative gingivitis or
periodontitis), salivary gland disease (i.e. swelling, xerostomia),
LOWER GI PROBLEMS
• Diarrhea the most common symptoms of gastrointestinal disease are chronic
or recurrent diarrhea with malabsorption, abdominal pain, dysphagia, and
failure to thrive.
o Acute diarrhea is one of the most common causes of morbidity and
the leading cause of death in HIV-infected children during the first
year of life.
o Diarrhea in HIV-infected children tends to be prolonged and is usually
complicated by dehydration and malnutrition.
• The infectious causes of diarrhea in HIV-infected children are similar to the
common causes in non-infected children. The leading cause of diarrhea is
rotavirus (RV), followed by bacterial causes that include Enterobacter,
Escherichia coli, Shigella species, Salmonella species, Campylobacter jejuni,
Giardia lamblia, Entamoeba histolytica, and Candida albicans.
o In HIV-infected children, other infectious causes of diarrhea include
AIDS-defining illnesses such as cryptosporidiosis, isosporiasis,
cytomegalovirus (CMV) infection, atypical Mycobacteria species, HIV
enteropathy, and parasitic infections, including Strongyloidiasis
stercoral is and Tricuris tricuria.
• The wasting syndrome, defined as a loss of > 10% of body weight, is not as
common as failure to thrive in pediatric patients, but the resulting
malnutrition is associated with a grave prognosis.
HEPATOBILIARY
• Chronic liver inflammation evidenced by fluctuating serum levels of
transaminases with or without cholestasis is relatively common, often without
identification of an etiologic agent.
• Cryptosporidial cholecystitis is associated with abdominal pain, jaundice, and
elevated γ-glutamyltransferase. In some patients, chronic hepatitis caused by
CMV, hepatitis B, hepatitis C or MAC may lead to portal hypertension and liver
failure.

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• Several of the antiretroviral drugs or other drugs such as didanosine, protease
inhibitors, nevirapine, and dapsone may also cause reversible elevation of
transaminases.
D. NERVOUS SYSTEM
OPPORTUNISTIC INFECTIONS
CRYPTOCOCCAL MENINGITIS
• Cryptococcal meningitis is an AIDS defining fungal CNS infection caused by the
organism Cryptococcus neoformans.
• CLINICAL MANIFESTATION: Intermittent fever is the most common clinical
manifestation. Headache is present in patients with CNS infection but
meningeal signs may be absent and focal neurological signs are seldom seen.
• CNS cryptococcus may be rapidly be complicated by increased ICP and cortical
blindness may ensue if untreated. It may also occur as part of IRIS.
• DIAGNOSIS: Lumbar puncture: measure opening pressure; CSF India ink and
cryptococcus antigen test; fungal culture.
• TREATMENT: High dose fluconazole 12 mg/kg/day in two divided doses
(maximum dose 400mg/day) for 10 weeks.
CNS TOXOPLASMOSIS
• Toxoplasma encephalitis (TE) is caused by the protozoa Toxoplasma gondii.
• CLINICAL MANIFESTATION: Toxoplasma encephalitis is the most frequent cause
of focal neurological lesions such as hemi paresis, hemiplegia, hemi-sensory
loss in HIV-infected persons.
• DIAGNOSIS Presence of Ig M antibody is proof of acute infection as is raising
titer of Ig G. Ring enhancing lesions are seen on CT scan.
• TREATMENT fansidar is used i.e pyrimethamine + sulfadoxine; loading dose of 2
tabs bid for 2 days followed by 1 tab daily plus folinic acid 5–15 mg daily.
o Lifelong suppressive therapy is indicated after treatment to prevent
recurrence.
OTHER MANIFESTATIONS
HIV encephalopathy
• HIV encephalopathy is an encephalopathy caused by HIV infection of the brain.
• It manifests clinically with various neurodevelopmental, cognitive, motor, and
behavioral abnormalities.
o Failure to attain or loss of developmental milestones or loss of
intellectual ability
o Impaired brain growth or acquired microcephaly

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• Acquired symmetrical motor deficit manifested by two or more of the
following: paresis, pathological reflexes, ataxia, or gait disturbances
• DIAGNOSIS is mainly clinical and depends on the presence of least two of the
following for at least two months.
• Cerebrospinal fluid is normal or has non-specific findings and CT scan shows
diffuse brain atrophy
• SEIZURES may result from:
o Space-occupying lesions (most often cerebral toxoplasmosis or
tuberculoma)
o Meningitis (most often cryptococcal)
o Metabolic disturbances
o No identified cause other than HIV infection
E. INTEGUMENTARY SYSTEM
• Skin disorders in HIV-infected children tend to be recurrent, disseminated and
respond less consistently to conventional therapy than in HIV-uninfected
children.
• Non-specific generalized papular dermatitis is the commonest dermatological
manifestation in children living with HIV/AIDS. Viral, bacterial and fungal skin
infections are also common including;
o Impetigo
o Dermatophytosis
o Scabies
o Molluscum Contagiosum Virus
o Herpes simplex
HIV EXPOSED INFANTS (HEI)
INTRODUCTION
• HEI is infants born to HIV positive pregnant women. These infants can be
infected with HIV during pregnancy, labor or after birth through breast feeding.
• All HEI (infected and non-infected) will test antibody positive during the first
few months of life.
• HIV infected infants are susceptible to many opportunistic infections including
PCP, TB and other bacterial infections that are associated with high rates of
mortality. In the provision of care for these children, we use the national HIV
exposed follow-up card.
COMPONENTS OF CLINICAL CARE FOR THE HEI

1. History

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2. Physical examination
3. Growth assessment Children with HIV infection are at high risk for poor growth
so, growth should be monitored closely for all HIV exposed and infected
infants.
4. Developmental assessment: Use developmental check list to assess growth &
development.
5. Infant feeding: Nutrition and feeding history should be assessed regularly.
6. Immunization: All HEI should be immunized according to EPI.
7. ARV infant prophylaxis
• For infants born to HIV infected mothers and on breastfeeding;
✓ Initiate ART for the mother.
✓ Infant prophylaxis with daily NVP for 6 weeks.
✓ Collect specimen for DNA PCR testing at 6 weeks of age.
✓ For infants born to HIV infected mothers but not breast feeding:
✓ initiate ART for the mother.
• If the infant is brought within 72 hours of birth provide NVP prophylaxis for
6 weeks; otherwise, there is no need to provide NVP syrup for the infant.
✓ Collect specimen for DNA PCR testing at 6 weeks of age.
✓ High-risk infants are defined as those infants born to women with
established HIV infection who have received less than four weeks of
ART at the time of delivery; OR
✓ Born to women with established HIV infection with viral load >1000
copies/mL in the four weeks before delivery, if viral load
measurement available; OR
✓ Born to women with incident HIV infection during pregnancy or
breastfeeding (incident HIV infection is new HIV diagnosis in
pregnancy or breastfeeding woman with a prior negative HIV test
during pregnancy); OR
✓ Those identified for the first time during the postpartum period, with
or without a negative HIV test prenatally.
8. Co-trimoxazole preventive therapy (CPT): Using pediatric co-trimoxazole in ALL
HIV EXPOSED INFANTS significantly reduces the rate of PCP and other bacterial
infections.
9. TB risk assessment: At each visit the infant should be evaluated for
Tuberculosis.
10. Determination and evaluation of infection status
• One of the goals of follow-up of HEI is to identify and treat the HIV infected
ones early. All HEI should have virologic testing at 6 weeks of age or at
earliest opportunity thereafter.
11. Current assessment and plan based on above assessment

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• Follow-up visits and schedule of HEI monthly for the first six months of life
then every 3 months until infection status is determined.
Table 43 WHO PAEDIATRIC CLINICAL STAGING OF INFANTS AND CHILDREN WITH ESTABLISHED HIV INFECTION (WHO 2010)
STAGE Manifestations
1 - Asymptomatic
- Persistent generalized lymphadenopathy (PGL)
2 - Unexplained persistent hepatosplenomegaly
- Extensive wart virus infection; facial, more than 5% of body area or disfiguring
- Papular pruritic eruptions
- Fungal nail infections
- Lineal gingival erythema
- Extensive human papilloma virus (HPV) or molluscum contagiosum (>5% of body area/face)
- Recurrent oral ulcerations (>2 episodes/6 months)
- Unexplained persistent parotid enlargement
- Herpes zoster
- Recurrent or chronic upper respiratory tract infection (URTI): otitis media, otorrhea,
sinusitis, tonsillitis (with at least 1 episode in the last 6 months)
3 - Unexplained moderate malnutrition (-2 SD or Z score) not adequately responding to standard
therapy
- Unexplained persistent diarrhea (≥14 days)
- Unexplained persistent fever above 37.5 °C (intermittent or constant) for longer than 1 month
- Persistent oral candidiasis (after first 6 weeks of life)
- Oral hairy leukoplakia
- Lymph node TB
- Pulmonary tuberculosis
- Severe recurrent presumed bacterial pneumonia (current episode plus 1 or more episodes in
previous 6 months)
- Acute necrotizing ulcerative gingivitis/periodontitis
- Symptomatic lymphoid interstitial pneumonitis (LIP)
- Chronic HIV-associated lung disease including bronchiectasis
- Unexplained anemia
4 - Extrapulmonary tuberculosis
- Kaposi’s sarcoma
- Esophageal candidiasis (or candida of trachea, bronchi or lungs)
- CNS toxoplasmosis (after the neonatal period)
- HIV encephalopathy
- Cytomegalovirus (CMV) infection; retinitis or CMV affecting another organ with onset at age
over 1 month
- Extrapulmonary cryptococcosis, including meningitis
- Any disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
- Chronic cryptosporidiosis with diarrhea
- Chronic isosporiasis
-Disseminated non-tuberculous mycobacterial infection
- Acquired HIV-associated rectal fistula

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- Cerebral or B cell non-Hodgkin’s lymphoma
- Progressive multifocal leukoencephalopathy (PML)
- HIV-related cardiomyopathy or nephropathy
DIAGNOSIS OF HIV INFECTION

Laboratory assays: There are two types of laboratory tests:
1. Antibody tests are the most widely used HIV diagnostic tests and provide
reliable evidence of HIV infection in adults and children who are older than 18
months.
• The HIV antibody test is less reliable in infants aged less than 18 months
because they may still be carrying HIV-specific antibodies acquired from
the mother in utero.
INTERPRETATION OF TEST RESULTS

• In children more than 18 months of age:
o HIV infection can be confirmed in those with positive antibody
results.
o HIV infection can be excluded in those with negative antibody
results.
o HIV-exposed children who continue to breast feed should be
provided with cotrimoxazole prophylaxis and
re tested a minimum of six weeks after
All infants born to HIV-
complete cessation of breastfeeding before infected women should
HIV infection can be excluded. In addition, have DNA PCR at six weeks
the child should be retested at any stage of age. If the test is
during breastfeeding should features of HIV positive, the infant is
infection occur. presumed to be HIV
• In children less than 18 months of age: infected and should be
o A positive antibody test (mother’s or of a referred for care and
child less than 18 months old) should be a treatment.
trigger for virologic testing.
o DNA or RNA PCR is considered best for infant diagnosis.
• All infants born to HIV-infected women should have DNA PCR at six
weeks of age. If the test is positive, the infant is presumed to be HIV
infected and should be referred for care and treatment.
2. Virology tests
• In order to make a definitive diagnosis of HIV in infants less than 18
months, assays that detect the virus or its components (virological tests)
are required. Interpretation of test results.

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• A negative test in a non-breastfed infant, ≥4–6 weeks old excludes HIV
infection.
• A positive test confirms HIV infection.
• HIV-exposed infants who continue to breast feed should be provided with
cotrimoxazole prophylaxis and should be re tested a minimum of six
weeks after complete cessation of breastfeeding before HIV infection
can be excluded. In addition, the infant should be re tested at any stage
during breastfeeding if features of HIV infection occur.
MANAGEMENT
• Start ART as early as possible to all children living with HIV regardless of their
WHO clinical stages and CD4 counts/percentage. Infants and young children
infected with HIV have exceptionally higher morbidity and mortality. Up to 52%
and 75% of children die before the age of two and five years respectively in the
absence of any intervention.
• For HIV infected infants diagnosed with the first DNA PCR result, initiate ART
and take dried blood spot specimen for confirmatory DNA PCR. Continue ART if
the second DNA PCR confirms; whereas if the second DNA PCR turns negative,
without holding the ART, make the 3rd DNA PCR test.
Figure 40 Algorithm for testing of HIV Exposed Infants <18 months
Table 44 First line and alternative drug regimens

Age Preferred first-line Alternative first-line
regimens regimens

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Adolescents (10 to 19 TDF + 3TC + DTG (FDC)* AZT + 3TC + EFV
years) weight ≥35 kg OR AZT + 3TC + NVP
(Including those with TDF + 3TC + EFV (FDC)* TDF + 3TC + NVP
TB/HIV co infection ABC + 3TC + EFV
Children 3 years to less AZT or ABC + 3TC + EFV AZT + 3TC + NVP
than TDF + 3TC + EFV
10 years and adolescents TDF + 3TC + NVP
weight <35 kg ABC + 3TC + NVP

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5.4. PERTUSSIS
• Pertussis is an acute respiratory tract infection; the term pertussis means
“intense cough” and is preferable to whooping cough, because most infected
individuals do not “whoop.”
PERTUSSIS CASE DEFINITION:
• Cough of ≥14 days’ duration with at least 1 associated symptom of paroxysms,
whoop, or post tussive vomiting.
ETIOLOGY
• Organism: Bordetella pertussis & Bordetella parapertussis (G-negative
coccobacilli)
• Route of infection: Droplet infection (mainly in child< 5y.)
PATHOGENESIS
• Bordetella organisms colonize only ciliated epithelium.
• Only B. pertussis expresses Pertussis Toxin (PT), the major virulence protein.
• PT has numerous proven biologic activities:
o histamine sensitivity
o insulin secretion
o leukocyte dysfunction
• Tracheal cytotoxin- it causes respiratory epithelial damage
• Adenylate cyclase toxin- it impairs host immune-cell function
• Dermonecrotic toxin- it may contribute to respiratory mucosal damage
• After aerosol acquisition, filamentous hemagglutinin, some agglutinogens
(especially fimbriae [Fim] types 2 and 3), and the 69-kDa pertactin (Prn)
protein are important for attachment to ciliated respiratory epithelial cells
• Tracheal cytotoxin, dermonecrotic factor, and adenylate cyclase are
responsible for the local epithelial damage that produces respiratory symptoms
and facilitates absorption of PT.
• Classically, pertussis is a prolonged disease, divided into catarrhal, paroxysmal,
and convalescent stages
1. Catarrhal stage (1-2 weeks)
• Begins insidiously after an incubation period ranging from 3-12 days
• With nondistinctive symptoms of -congestion and rhinorrhea
o variably accompanied by low-grade fever
o sneezing, lacrimation, and conjunctival suffusion
2. Paroxysmal Stage (2-6 Weeks)

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• As initial symptoms wane, coughing marks the onset of the paroxysmal stage
• The cough begins as a dry, intermittent, irritative hack and evolves into the
inexorable paroxysms (uninterrupted cough on a single exhalation)
• During the attack; chin and chest held forward, tongue protruding maximally,
eyes bulging and watering, face purple, until coughing ceases
• Aloud whoop follows as inspired air traverses the still partially closed airway.
• Posttussive emesis is common, and exhaustion is universal.
• No abnormal signs on chest examination.
3. Convalescent stage (≥2weeks),
• Gradual decline in the number, severity, and duration of episodes of paroxysm
but cough may last for month
• Infants <3 mo old do not display the classic stages
o The catarrhal phase lasts only a few days or is unnoticed,
o And then, after the most insignificant startle from a draft, light, sound,
sucking, or stretching, a well-appearing young infant begins to choke,
gasp, gag, and flail the extremities, with face reddened
o Apnea and cyanosis can follow a coughing paroxysm
o The paroxysmal and convalescent stages in young infants are lengthy.
o Paradoxically, in infants, cough and whooping may become louder and
more classic in convalescence.
o “Exacerbations” of paroxysmal coughing can occur throughout the 1st yr.
of life with subsequent respiratory illnesses; these are not a result of
recurrent infection or reactivation of B. pertussis.
• Adolescents and previously immunized children have foreshortening of all
stages of pertussis.
o Adults have no distinct stages.
o Classically they describe a sudden feeling of strangulation followed by
uninterrupted coughs, feeling of suffocation, bursting headache,
diminished awareness, and then a gasping breath, usually without a
whoop.
o Posttussive emesis and intermittency of paroxysms separated by hours of
well-being are specific clues to the diagnosis.
DIAGNOSIS
• Clinical: Pertussis should be suspected in:
o Complaint of cough in absence of fever, malaise or myalgia, exanthem
or enanthem sore throat, hoarseness, tachypnea, wheezes, and rales.
o Cough of ≥14 days’ duration with at least 1 associated symptom of
paroxysms, whoop, or posttussive vomiting

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o In older children whose cough illness is escalating at 7-10 days and
whose coughing is not continuous, but rather comes in bursts
o Apnea or cyanosis in infants less than 3 months
• CBC: leukocytosis with absolute lymphocytosis
o Leukocytosis (15,000-100,000 cells/μL) caused by absolute lymphocytosis
is characteristic in the catarrhal stage
o Absolute increase in neutrophils suggests a different diagnosis or
secondary bacterial infection
o A severe course and death are correlated with rapid-rise and extreme
leukocytosis (median peak white blood cell count in fatal vs nonfatal
cases, 94,000 vs 18,000/μL, respectively)
o A severe course and death are correlated with thrombocytosis (median
peak platelet count in fatal vs nonfatal cases, 782,000 vs 556,000/μL,
respectively).
• Chest radiographic finding
o Showing perihilar infiltrate or edema and variable atelectasis.
o Parenchymal consolidation suggests secondary bacterial infection.
o Pneumothorax, pneumomediastinum, and subcutaneous emphysema can
be seen occasionally.
• Nasopharyngeal swab and:
o Microscopic examination.
o Culture on Regan - Lowe charcoal agar
o PCR
DIFFERENTIAL DIAGNOSIS: FROM OTHER CAUSES OF CHRONIC COUGH

1. Adenovirus infection; associated with fever, sore throat and conjunctivitis.
2. Chlamydia trachomatis infection; associated with staccato cough, purulent
Conjunctivitis, wheezes and rales.
3. Bronchial asthma:
− Recurrent wheezy chest
− Related to allergens or exercise
− Respond to bronchodilators
− Relatives with asthma
4. Foreign body inhalation
5. Pulmonary tuberculosis
6. Mycoplasma pneumonia
7. Suppurative lung syndromes e.g. Cystic fibrosis , immunodeficiency
COMPLICATIONS

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• Are more frequent in infants and young children.
1. Respiratory
− Otitis media
− Bronchopneumonia & pneumonia caused mainly by S. aureus, S.
pneumoniae
− Activate latent T.B focus
− Apnea & cyanotic attacks in infants < 6 months
− Atelectasis
− Bronchiectasis
2. Convulsions; may be due to:
− Brain damage (due to hypoxemia) but hyponatremia from excessive
secretion of ADH during pneumonia can occur.
− Intracranial hemorrhage and ischemic necrosis.
− Tetany (severe vomiting, alkalosis)
3. Mechanical: with severe paroxysms due to increased intrathoracic and
intraabdominal pressure during coughing
− conjunctival and scleral hemorrhage, petechiae on the upper body,
epistaxis and intracranial hemorrhage
− Pneumothorax and subcutaneous emphysema
− Umbilical or inguinal hernias
− Rectal prolapse
− Laceration of the lingual frenulum
4. Malnutrition due to anorexia, vomiting , and faulty food restriction
5. Pulmonary hypertension and cardiogenic shock with fatal outcome are
associated with extreme elevation of lymphocyte and platelet counts.
− Preterm birth and young maternal age are associated with fatal
pertussis.
− Neonates with pertussis have longer hospitalizations, greater need for
oxygen, and for mechanical ventilation
− Apnea or bradycardia result from
✓ Apparent laryngospasm
✓ Vagal stimulation just before a coughing episode
✓ obstruction during an episode
✓ hypoxemia following an episode.
− Progressive pulmonary hypertension in very young infants and secondary
bacterial pneumonia are severe complications of pertussis and are the
usual causes of death.
TREATMENT

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1. CASES: (ADMIT YOUNG INFANTS).
• Admission criteria
o Infants <3 mo old with suspected pertussis usually are hospitalized, as
are many 3-6 mo old, unless witnessed paroxysms are not severe
o patients of any age if significant complications occur
o Children with significant underlying cardiopulmonary or neuromuscular
disorders
• The specific, limited goals of hospitalization are to
o assess progression of disease and likelihood of life-threatening events at
peak of disease
o to maximize nutrition
o to prevent or treat complications
o To educate parents in the natural history of the disease and in care that
will be given at home
o Typical paroxysms that are not life threatening have the following
features
▪ Duration <45sec
▪ Red but not blue color change
▪ Tachycardia, bradycardia (not <60 beats/min in infants)
▪ Oxygen desaturation that spontaneously resolves at the end of the
paroxysm
▪ Whooping or strength for brisk self-rescue at the end of the
paroxysm
▪ Self-expectorated mucus plug; and posttussive exhaustion but not
unresponsiveness
DISCHARGE CRITERIA
• If over 48 hours:
o disease severity is unchanged or diminished
o intervention is not required during paroxysms
o nutrition is adequate, no complication has occurred, and parents are
adequately prepared for care at home.
GENERAL MANAGEMENT
• Isolation for 5 days after starting antibiotics or 3 weeks after start of paroxysm
• Bed rest
• Symptomatic treatment; avoid triggers of cough.
• Care of feeding: small frequent feeds or tube feeding

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ANTIBIOTICS
• Values: Reduction of infectivity period and possible clinical improvement.
• An antimicrobial agent always is given when pertussis is suspected or confirmed
to decrease contagiousness and to afford possible clinical benefit.
• Azithromycin is the drug of choice in all age-groups, for treatment or
postexposure
PROPHYLAXIS
• Infantile hypertrophic pyloric stenosis (IHPS) is associated with macrolide use
in young infants, especially in those <14 days old, with highest risk in those
receiving erythromycin vs azithromycin
• The FDA also warns of risk of fatal heart rhythms with use of azithromycin in
patients already at risk for cardiovascular events, especially those with
prolongation of the QT interval.
• Trimethoprim-sulfamethoxazole (TMP-SMX) can be used as an alternative
agent to macrolides in patients ≥2 mo old who are allergic to macrolides, who
cannot tolerate macrolides, or who are infected with a rare macrolide-resistant
strain of Bordetella pertussis
Table 45 Recommended Antimicrobial Treatment and Postexposure Prophylaxis for Pertussis
AGE GROUP PRIMARY AGENTS ALTERNATE AGENT
Azithromycin Erythromycin Clarithromycin TMP-SMX
<1 mo Recommended agent Not preferred Not Contraindicated for infants
10 mg/kg/day in asingle Erythromycin is recommended <2 mo of age (risk for
dose for 5 days substantially (safety data kernicterus
associated with unavailable)
infantile
hypertrophic pyloric
stenosis.
Use if azithromycin
is unavailable; 40-
50mg/kg/day in 4
divided doses for 14
days.
1-5 mo 10 mg/kg/day in a single 40-50 mg/kg/day in 15 mg/kg/day in Contraindicated at age <2
dose for 5 days 4 2 divided doses mo
divided doses for 14 for 7 days For infants age ≥2 mo:
days TMP 8 mg/kg/day plus SMX
40 mg/kg/day in 2
divided doses for 14
days

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Infants 10 mg/kg in a single 40-50 mg/kg/day 15 mg/kg/day in TMP 8 mg/kg/day plus SMX
age ≥6 dose on day 1 (max 500 (max 2 2 divided doses 40mg/kg/day in 2 divided
mo and mg), then 5 mg/kg/day g/day) in 4 divided (max 1 g/day) doses (max TMP: 320
children (max 250mg) on days 2-5 doses for 7 days mg/day) for 14 days
for 14 days
Adults 500 mg in a single dose 2 g/day in 4 divided 1 g/day in 2 TMP 320 mg/day–SMX
onday 1, then 250 doses for 14 days divided doses for 1600 mg/day in 2 divided
mg/day on days 2-5 7 days doses for 14 days
CONTACTS
• Azithromycin should be given promptly to all household contacts and other
close contacts, such as those in daycare, regardless of age, history of
immunization, or symptoms
• The same drugs and age-related doses used for treatment are used for
prophylaxis.
• In close contacts <7 yr old who have received <4 doses of DTaP, DTaP should be
given to complete the recommended series.
• Children <7 yr old who received a 3rd DTaP dose >6 mo before exposure, or a
4th dose ≥3 yr before exposure, should be given a booster dose.
• Individuals ≥9 yr old should be given Tdap
PREVENTION
• Universal immunization of children with pertussis vaccine, beginning in infancy

with reinforcing dose(s) through adolescence and adulthood, is central to the
control of pertussis
• Prevention of pertussis mortality in young infants depends on universal
maternal immunization during each pregnancy and focused full immunization of
contacts, both children and adults of all ages
DTaP VACCINES
• Several diphtheria and tetanus toxoids combined with acellular pertussis
vaccines (DTaP ) or combination products currently are licensed in the United
States for children <7 yr old
• Acellular pertussis vaccines all contain inactivated PT and 2 or more additional
antigens (filamentous hemagglutinin, Prn, and Fim 2 and 3)
• Clinical effectiveness immediately at completion of the 5-dose series is
approximately 80% for illness defined as “paroxysmal cough” for >21 days
• Four doses of DTaP should be administered during the 1st 2 yr of life, generally
at ages 2, 4, 6, and 15-18 mo

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• In high-risk settings, infants may be given DTaP as early as 6 wk of age, with
monthly doses through the 3rd dose
• The 4th dose may be administered as early as 12 mo of age, provided that 6 mo
have elapsed since the 3rd dose.
• When feasible, the same DTaP product is recommended for all doses of the
primary vaccination series. The 5th dose of DTaP is recommended for children
at 4-6 yr of age; a 5th dose is not necessary if the 4th dose in the series is
administered on or after the 4th birthday
TDAP VACCINES
• Tdap (Two tetanus toxoid, reduced-diphtheria toxoid and acellular pertussis
antigen vaccine)
• The preferred age for Tdap vaccination is 11-12 yr.
• All adolescents and adults of any age (including ≥65 yr) who have not received
Tdap should receive a single dose of Tdap promptly, regardless of interval since
Td, or at least in place of one Td booster at the 10 yr interval, or when
indicated during wound management.
• Pregnant women should be given Tdap during every pregnancy to provide
passive antibody protection to the infant until administration of DTaP.
• Tdap can be given at any time during pregnancy, optimal administration is
early in the period between 27 and 36 wk of gestation to maximize antibody
concentration at birth.
• Safety of Tdap during pregnancy and effectiveness in reducing fatal pertussis in
infants are proven.
• There is no contraindication to concurrent administration of any other
indicated vaccine.
• When Td is indicated and only Tdap is available, a previously Tdap-immunized
person can be given Tdap.
• A single dose of Tdap is recommended for children 7-10 yr old who had
incomplete DTaP vaccination before age 7 yr.
• Another dose of Tdap can be given in adolescence

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5.5. MEASLES
INTRODUCTION
• Measles is a highly contagious infectious disease.
• Caused by single-stranded, lipid-enveloped RNA virus.
TRANSMISSION
• is through the respiratory tract or conjunctivae.
• Patients are infectious from 3 days before to up to 4-6 days after the onset of
rash.
• 90% of exposed susceptible individuals experience measles.
PATHOLOGY
• Measles virus Is epitheliotropic and lymphotropic and causes
o necrosis of the respiratory tract epithelium
o small vessel vasculitis on the skin and on the oral mucous membranes.
o intracellular edema and dyskeratosis
o lymphoid hyperplasia
o immunosuppression (infects CD4 cells)
o Fusion of infected cells results in multinucleated giant cells, the
Warthin-Finkeldey giant cells that are pathognomonic for measles
PATHOGENESIS
• initial targets for measles virus are alveolar macrophages, dendritic cells, and
lymphocytes
• Measles infection consists of 4 phases: incubation period, prodromal illness,
exanthematous phase, and recovery.
1) Incubation period
o 8-12 days
o The first viremia- after the virus replicates locally and spread to
regional lymphatic tissues, it disseminates to other reticuloendothelial
sites via the blood stream.
o The second viremia- the virus spreads to body surfaces. and it signals
the beginning of prodromal phase
2) Prodromal phase
o 2-4 days
o associated with epithelial necrosis and giant cell formation in body
tissues
o Virus shedding begins
3) Exanthematous phase
o antibody production begins, and viral replication subsides

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• Classical measles infection
1. Incubation period-
o asymptomatic period
2. Prodromal phase-
o begins with mild fever, malaise, anorexia followed
by
✓ the three Cs of measles
▪ Conjunctivitis
▪ Coryza
▪ A prominent cough (lasts the longest, up
to 10 days),
✓ Increasing fever
✓ Koplik spots-
▪ represent the enanthem
▪ pathognomonic sign of measles, Figure 41 Koplik Spots
▪ occur 50-70%
▪ appear 1-4 days prior to the onset of
the rash.
▪ 1-3 mm whitish, grayish, or bluish
elevations with an erythematous
base
▪ Typically seen on the buccal mucosa
opposite to the molar teeth.
▪ Described as “grains of salt on red
background” Figure 42 Rash of measles
3. Exanthomatous period
o Symptoms begin to subside (fever usually subsides 2 days after the onset
of the rash)
✓ Exanthem-
▪ Erythematous, maculopapular, blanching rash (on
the early stage) then become non blanching
▪ Begins on the forehead (around the hair line),
behind the ears, and on the upper neck and then
spreads cephalocaudal and centrifugal
▪ frequently becomes confluent on the face and
upper trunk
▪ fades over about 7 days in the same progression
as it evolved
✓ Lymphadenopathy (cervical and occipital are more
prominent).
Figure 43 Rash of measles

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MODIFIED MEASLES INFECTION
•Occurs in individuals with pre-existing nonprotective measles immunity
o trans placental transfer- is generally cleared by 3-9 months of age
o Receipt of immunoglobulin
o Vaccination that result in lower antibody titers
o Prior history of measles
• has milder clinical manifestations and prolonged incubation period
• individuals with modified measles are not highly contagious
ATYPICAL MEASLES INFECTION
• Occurs in individuals immunized with the killed virus vaccine
• The killed vaccine sensitizes the recipient without providing full protection.
• Characterized by
o higher and more prolonged fever
o Rash that begins on the extremities that can be vesicular, petechial,
purpuric or urticarial
o Severe illness with respiratory distress
o Chest radiography typically demonstrates bilateral pulmonary nodules
and hilar lymphadenopathy
o Higher and rapid rise in antibody titer
• Individuals with atypical measles are not contagious
DIAGNOSIS
CASE DEFINITION
Table 46 Case definition of Measles
Suspected measles A suspected case is one in which a patient with fever and maculopapular
case (non-vesicular) rash, or in whom a health care worker suspects measles.
Laboratory- A suspected case of measles that has been confirmed positive by testing in a
confirmed measles proficient laboratory, and vaccine-associated illness has been ruled out.
Epidemiologically A suspected case of measles that has not been confirmed by a laboratory,
linked measles but was geographically and temporally related with dates of rash onset
occurring 7–23 days apart from a laboratory-confirmed case or another
epidemiologically linked measles case.
Clinically A suspected case with fever and maculopapular rash and at least one of
compatible measles cough, coryza or conjunctivitis, but no adequate clinical specimen was
taken, and the case has not been linked epidemiologically to a laboratory-
confirmed case of measles or other communicable disease.
Non-measles A suspected measles case that has been investigated and discarded as non-
discarded case measles through:

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▪ Negative laboratory testing in a proficient laboratory on an adequate
specimen collected during the proper time after rash onset;
▪ Epidemiological linkage to a laboratory-confirmed outbreak of another
communicable disease that is not measles, i.e. confirmation of another
etiology;
▪ Failure to meet the clinically compatible measles case definition.
Measles outbreak A single laboratory-confirmed measles case should trigger an aggressive
public health investigation and response in an elimination setting. An
outbreak is defined as two or more laboratory-confirmed cases that are
temporally related (with dates of rash onset occurring 7–23 days apart) and
epidemiologically or virologically linked, or both.
CRITERIA FOR EPIDEMIOLOGICAL LINKAGE INCLUDE

• Being a known contact,
• Being in the same physical setting as the case during their infectious period for
any length of time (shared enclosed air space such as at home, school, health
facility waiting room, transport or workplace). Note, the virus remains
contagious in the air or on infected surfaces for up to 2 hours;
Diagnosis is clinical but in the absence of outbreak, confirmation is recommended.

1) Serologic confirmation
o IgM antibody appears 1-2 days after the onset of the rash and remains
detectable for about 1 mo. In high prevalent regions
o a 4-fold rise in IgG antibodies in acute and convalescent specimens
collected 2-4 wk. apart
2) viral culture
3) PCR
COMPLICATIONS
• largely attributable to the pathogenic effects of the virus on the respiratory
tract and immune system
• one or more complications occur in ~30% of cases
• factors associated with increased risk of complication
o individuals younger than 5 year of age (esp. <1 yr) and > 20 yr.
o Crowding (larger inoculum doses after household exposure)
o Severe malnutrition
o Lower serum retinol level
o Immune compromised state

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• Occurrence of fever beyond 3rd to 4th day of rash suggests complication
• Acute otitis media and diarrhea are the most common complications.
IMMUNE SUPPRESSION AND SECONDARY INFECTION

• IMMUNE SUPPRESSION- includes
o T cell lymphopenia with depletion of T dependent areas of lymph nodes
and spleen
o Diminished T cell proliferation
o Diminished antibody production
• SECONDARY INFECTIONS- may include
o Bacteremia, Pneumonia, Gastroenteritis, TB reactivation
o Pulmonary
▪ Pneumonia-
• The most common cause of measles-associated deaths in
children
• May manifest as giant cell pneumonia (in
immunocompromised) caused directly by the viral infection
or
• as superimposed bacterial infection
• Occur in ~ 6%
▪ Croup
▪ Bronchiolitis
o Gastrointestinal
▪ Diarrhea
▪ Gingivostomatitis
▪ Oral ulcer- severe ulcer precluding feeding is an indication to
admit
▪ Gastroenteritis
▪ Hepatitis
▪ Mesenteric lymphadenitis
▪ Appendicitis (due to lymphoid hyperplasia)
NEUROLOGIC COMPLICATIONS
ENCEPHALITIS
• is a post infectious, immunologically mediated process and in
immunocompromised patients results from direct damage to the brain by
the virus
• Clinical onset begins during the exanthem

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• Symptoms include fever, headache, vomiting, stiff neck, meningeal
irritation, drowsiness (46%), convulsions (56%)and coma (28%)
• CSF analysis shows pleocytosis (85%) predominantly lymphocytes, elevated
protein concentration and a normal glucose concentration.
• ~20-40%% have neurodevelopmental sequelae, ~15% die
ACUTE DISSEMINATED ENCEPHALOMYELITIS

• Is a post infectious autoimmune demyelinating disease
• Occurs during the recovery phase typically within two weeks of exanthem
• Manifestations include fever, headache, neck stiffness, seizure, mental
status change, ataxia, myoclonus, choreoathetosis and sign of myelitis
• 10-20% mortality rate
SUBACUTE SCLEROSING PAN ENCEPHALITIS

• Is a fatal, progressive degenerative disease of the CNS
• Result from a persistent infection with an altered virus
• Usually occurs 7-13 yrs after the natural infection
• Risks for SSPE include
o Measles infection at an early age, (50% had primary measles before 2 yr.
of age, and 75% had measles before 4 yr. of age)
o immunocompromised patients
• SSPE is divided into-
o Stage I
▪ Subtle changes in behavior or school performance appear,
including irritability, reduced attention span, and temper
outbursts.
o Stage 2
▪ Massive myoclonus-hallmark of this stage,
▪ worsening dementia and long tract motor or sensory disease
▪ usually lasts 3-12 months
o Stage 3
▪ involuntary movements disappear
▪ choreoathetosis, immobility, dystonia, and lead pipe rigidity
▪ sensorium deteriorates into dementia, stupor, and then coma
o Stage 4
▪ loss of critical centers that support breathing, heartrate, and
blood pressure
• Diagnosis of SSPE
o clinical course and at least 1 of the following
1. Measles antibody detected in CSF,

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2. Characteristic EEG finding- seen in stage 2
3. Typical histologic findings in and/or isolation of virus or viral
antigen from brain tissue
• Management is usually supportive and most patients die withn1-3 yrs.
OTHER COMPLICATIONS
• Ocular- keratitis and corneal ulceration
• Cardiac- myocarditis, pericarditis
MANAGEMENT
• Is supportive because there is no specific antiviral therapy approved for
treatment of measles
• Prophylactic antimicrobial therapy to prevent bacterial infection is not
indicated
Table 47 Management of measles
Symptom Treatment
Fever Treat fever with paracetamol
Nutrition Monitor child’s weight daily and their intake.
Encourage breastfeeding for infants and small frequent meals for children.
Consult Dietician.
Treat malnutrition if present
Mouth ulcer Wash mouth with clean, salted water at least four times a day. Avoid giving
child spicy foods. If mouth ulcers appear superinfected with bacteria, treat
with antibiotics.
Eye care For mild conjunctivitis, clear and watery discharge, no treatment is
necessary. Monitor for change in discharge quality, if pus present, then treat
for bacterial conjunctivitis.
If eye has more than just clear watery discharge, such as pus or cloudy
discharge, then treat for superinfection with bacteria with bacterial
ointment, such as tetracycline ointment, applied three times a day for 7 days.
Clean the eye carefully using clean cloth dipped in clean water or sterile
gauzes.
Consult with eye specialist as needed. Do not usesteroid ointment on infected
eyes.
Skin care Ensure skin is kept clean and dry. Monitor for signs of infection, such as
cellulitis or other more severe soft tissue infections.
VITAMIN A
• Deficiency leads to delayed recovery and increases risk of complication
• Falls during measles infection
• Supplementation reduce severity and risk of complication
• therapy is indicated for all patients with measle
o administered once daily for 2 days at doses of

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o 200,000 IU for children 12 mo. of age or older;
o 100,000 IU for infants 6-11 mo. of age; and
o 50,000 IU for infants <6 mo. of age.
• In children with signs and symptoms of vitamin A deficiency, a 3rd age-
appropriate dose is recommended 2-4 wk. after the 2nd dose.
PREVENTION
• Exposure of susceptible individuals to patients with measles should be avoided
during infectious period
• Immunocompromised patients with measles will shed virus for the duration of
the illness, so isolation should be maintained throughout the disease.
• To disrupt broad transmission herd immunity must be maintained above 85-95%
VACCINE
• most effective and safe prevention strategy
• current recommendations include a 1st dose at 12-15 mo. of age, followed by a
2nd dose at 4-6 yr of age. (The 2nd dose can be given any time after 30 days
following the 1st dose).
• WHO recommends 1st dose at the age of 9 month for infants in developing
areas.
• Seroconversion is slightly lower in children who receive the 1st dose before or
at 12 mo. of age because of persisting maternal antibody
• For children who have not received 2 doses by 11-12 yr of age, a 2nd dose
should be provided
• Infants who receive a dose before 12 mo. of age should be given 2 additional
doses at 12-15 mo. and 4-6 yr of age
• Live vaccines should not be administered to pregnant women or to
immunodeficient or immunosuppressed patients
POST EXPOSURE PROPHYLAXIS

• vaccine administration or with Ig
• The vaccine is effective in prevention or modification of measles if given within
72 hr. of exposure.
• Ig may be given up to 6 days after exposure to prevent or modify infection
• Ig is indicated for susceptible household contacts of measles patients,
especially infants younger than 6 mo. of age, pregnant women, and
immunocompromised persons.

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5.6. MALARIA
DEFINATION
• Malaria is an acute illness characterized by paroxysms of fever, chills, sweats,
fatigue, anemia, and splenomegaly.
• Is one of the leading causes of morbidity and mortality worldwide.
• Malarial deaths in areas of high malaria transmission occur primarily in children
<5 year of age, but in areas of low transmission, a large percentage of deaths
may occur in older children and adults.
ETIOLOGY
• Malaria is caused by intracellular Plasmodium protozoa, P. falciparum,
P. malariae, P. ovale, P. vivax, and P. knowlesi.
• Mode of transmission
o Female Anopheles mosquitoes.
o Blood transfusion
o use of contaminated needles and
o Trans-placentally from a pregnant woman to her fetus
EPIDEMIOLOGY
• Malaria is a major worldwide problem, occurring in 95 countries that comprise
approximately half the world’s population.
• The principal areas of transmission are Africa, Asia, and South America.
• P. falciparum and P. malariae are found in most malaria endemic areas.
• P. ovale is the least-common species and is transmitted primarily in Africa.
PATHOGENESIS
• Plasmodium species have two reproductive cycles
o Asexual cycle
▪ Occur In human host in a 2-step process. 1st phase in hepatic cells
(exoerythrocytic phase) and the 2nd phase in the RBCs
(erythrocytic phase).
o Sexual cycle
▪ Also called sporogenic cycle.
▪ Occur in the female anopheles mosquito.
• Infection with all species leads to
o Fever, caused by the host immune response when erythrocytes rupture
and release merozoites into the circulation, and

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o Anemia, caused by hemolysis, RBC sequestration and bone marrow
suppression.
• Physiology and pathogenesis in malaria
differ according to species.
o Severe malaria is more common
in P. falciparum due to:-
▪ Higher-density parasitemia
(60%),
▪ This may lead to
excessive production of
proinflammatory
cytokines.
▪ Is due to P. falciparum
affinity for both mature
and immature
erythrocytes Figure 44 Life cycle of Malaria
▪ Cytoadherence of P. falciparum-infected erythrocytes to the

vascular endothelium which can lead to
▪ Obstruction of blood flow and capillary damage, with resultant
vascular leakage of blood, protein, and fluid and
▪ Tissue anoxia and
▪ Polyclonal activation, resulting in both hypergammaglobulinemia and
the formation of immune complexes.
o Tissue schizonts of P. ovale and P. vivax can remain dormant in the liver
cell for weeks, months, or as long as 5 year before releasing merozoites
and causing relapse of infection.
IMMUNITY
• Is incomplete (prevent severe infection but allow future infection) because the
parasite has developed a number of immune evasive strategies, such as
o Intracellular replication,
o Vascular cytoadherence that prevents infected erythrocytes from
circulating through the spleen,
o Rapid antigenic variation, and
o Alteration of the host immune system resulting in partial immune
suppression.
• The human host response to Plasmodium infection includes
o Natural immune mechanisms that prevent infection by other Plasmodium
spp.,
o Several alterations in erythrocyte physiology that prevent or modify
malarial infection.

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▪Erythrocytes containing hemoglobin S (sickle erythrocytes) resist
malaria parasite growth,
▪ Erythrocytes lacking Duffy blood group antigen are relatively
resistant to P. vivax, and
▪ Erythrocytes containing Hemoglobin F (fetal hemoglobin) and
ovalocytes are resistant to P. falciparum.
• In hyper endemic areas, newborns rarely become ill with malaria, because of
o passive maternal antibody and
o High levels of fetal hemoglobin.
• Children 3 months to 2-5 year of age have little specific immunity to malaria
species and therefore suffer yearly attacks of debilitating and potentially fatal
disease.
RISK FACTOR
Risk factors for malarial infection include: -
• Environmental risk assessment
o Presence of Bushes
o Presence of stagnant water
o Rainfall season (major transmission season)
▪ Sept to December
▪ April to May
o Low altitude(<2000m)
o High temperature area
o Use of protective factor
▪ ITN (insecticide treated net)
▪ IRS (indoor residual spraying)
o Living in malaria endemic area
Figure 45 Stagnant water
• History of previous malarial attack
o Recrudescence
▪ Occur from the survival of erythrocyte forms in the blood
stream
o Long term relapse
▪ Release of merozoites from an exoerythrocytic source in the liver
(hepatocyte schizont) P. ovale and P. vivax.
HISTORY
• Children and adults are asymptomatic during the initial phase of infection, the
incubation period. The usual incubation periods are

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o 9-14 days for P. falciparum,
o 12-17 days for P. vivax,
o 16-18 days for P. ovale, and
o 18-40 days for P. malariae. The incubation period can be as long as 6-12
months for P. vivax and can also be prolonged for patients with partial
immunity or incomplete chemoprophylaxis.
• A prodrome lasting 2-3 days is noted in some patients which includes headache,
fatigue, anorexia, myalgia, slight fever, and pain in the chest, abdomen, and
joints.
• Children with malaria often lack the typical paroxysms in adults (high fever,
followed by shaking chills and then diaphoresis) and may have nonspecific
symptoms, including fever (often >40°C), headache, drowsiness, anorexia,
nausea, vomiting, and diarrhea.
• Rupture of schizonts occurs
o Every 48 hour with P.vivax and P. ovale (fever every other day) and
o Every 72 hour with P. malariae (fever every 3rd day)
o Periodicity is less apparent with P. falciparum, and mixed infections and
may not be apparent early on in infection.
• Patients with primary infection, such as travelers from non-endemic regions,
also may have irregular symptomatic episodes for 2-3 days before regular
paroxysms begin, so most travelers presenting with malaria lack a classic
malaria fever pattern.
• Recrudescence after a primary attack may occur from the survival of
erythrocyte forms in the bloodstream.
• Long-term relapse is caused
o By release of merozoites from an exoerythrocytic source in the liver,
which occurs with P. vivax and P. ovale, or
o From persistence within the erythrocyte, which occurs with P. malariae
and rarely with P. falciparum
CONGENITAL MALARIA
•Is acquired from the mother prenatally or perinatally.
•Usually occurs in the offspring of a non-immune mother with P. vivax or P.
malariae infection.
• The first sign or symptom typically occurs between 10 and 30 days of age.
• Signs and symptoms include fever, restlessness, drowsiness, pallor,
jaundice, poor feeding, vomiting, diarrhea, cyanosis, and
hepatosplenomegaly.
• Distinctive physical signs may include

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o Splenomegaly (common),
o Hepatomegaly, and
o Pallor as a consequence of anemia.
DIAGNOSIS
A. CLINICAL DIAGNOSIS
• Is made when
o A patient from malaria endemic area has fever or history of fever in the
last 48 hours or
o If a patient from non-malaria endemic area has fever or history of fever
in the last 48 hours and has a history of travel to malariaendemic areas
within the last 30 days and spending at least one night.
• Is not recommended
• The health worker examining a suspected malaria case should look for other
causes of fever (e.g. typhoid fever, relapsing fever, acute respiratory tract
infections, meningitis, schistosomiasis, visceral leishmaniasis) and manage the
case accordingly and malaria should still be considered, even if the individual
has another obvious cause for the fever.
B. PARASITOLOGICAL DIAGNOSIS
1) IDENTIFICATION OF ORGANISMS ON GIEMSA-STAINED SMEARS OF
PERIPHERAL BLOOD
• P. falciparum is most likely to be identified from blood just after a febrile
paroxysm.
• At least 3 negative blood smears is recommended to rule out malaria in
children in whom malaria is strongly suspected.
o Diagnostic stages of the species and infected
RBCs can be seen –
▪ Trophozoites, both immature (ring
stage) and mature
▪ Schizont
▪ Gametocyte
▪ Schüffner dots and ovoid shaped
infected RBCs
• Thick smear -concentration of erythrocytes
Figure 46 Ring stage of P. falciparum
is 20-40 times that on a thin smear and is used to
quickly scan large numbers of erythrocytes.
o Can be very sensitive detecting 5 parasites per microliter of blood
• Is recommended
• Thin smear allows

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o For positive identification of the malaria species
o Determination of the percentage of infected erythrocytes and
o Is useful in following the response
to therapy.
o Can detect 20 parasites per microliter of blood
2) RAPID IMMUNOCHROMATOGRAPHIC ASSAY (RAPID DIAGNOSTIC TEST).

• The BinaxNOW Malaria test -Immunochromatographic test for P. falciparum
histidine-rich protein (HRP2) and aldolase is approved for testing for P.
falciparum and P. vivax.
o Sensitivity and specificity for P. falciparum (94–99% and 94–99%,
respectively) and P. vivax (87–93% and 99%, respectively) are good, but
sensitivity for P. ovale and P. malariae is lower.
o The test is simple to perform and can be done in the field or laboratory in
10 min.
• PCR is more sensitive than microscopy but is technically more complex.
o Can be useful for confirmation and for diagnosis of multiple species of
malaria, but the time delay in availability of results generally precludes its
use for acute diagnosis of malaria.
COMPLICATIONS OF PLASMODIUM FALCIPARUM MALARIA

• WHO has identified 10 complications of P. falciparum malaria that define
severe malaria.
Table 48 WHO Criteria for Severe Malaria, 2000
WHO Criteria for Severe Malaria, 2000
Impaired consciousness Hemoglobinuria
Prostration Abnormal bleeding
Respiratory distress Severe anemia
Multiple seizure Circulatory collapse
Jaundice Pulmonary edema
Figure 47 Complications of Malaria by Age
Note that: Seizure and Anemia are more common in pediatrics age group.

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MANIFESTATIONS OF SEVERE FALCIPARUM MALARIA BY AGE

• The most common complications in children are
▪ Severe anemia,
▪ Impaired consciousness (including cerebral malaria),
▪ Respiratory distress (a result of metabolic acidosis),
▪ Multiple seizures, prostration, and jaundice.
• Severe malarial anemia (hemoglobin level <5 g/dL)
▪ Is the most common severe complication of malaria in children and is the
leading cause of anemia leading to hospital admission in African children.
▪ Anemia is associated with
▪ Hemolysis,
▪ Removal of infected erythrocytes by the spleen and
▪ Impairment of erythropoiesis
▪ The primary treatment for severe malarial anemia is blood transfusion.
▪ Low mortality (approximately 1%).
• Cerebral malaria
▪ Is defined as the presence of coma in a child with P. falciparum
parasitemia and an absence of other reasons for coma.
▪ Is most common in children in areas of midlevel transmission and in
adolescents or adults in areas of very low transmission.
▪ Often develops after the patient has been ill for several days but may
develop precipitously.
▪ Has a fatality rate of 15–40% and is associated with long-term cognitive
impairment in children.
▪ Repeated seizures are frequent in children with cerebral malaria.
▪ Hypoglycemia is common, but children with true cerebral malaria fail to
arouse from coma even after receiving a dextrose infusion that normalizes
their glucose level.
▪ Physical findings
▪ May include high fever, seizures, muscular twitching, rhythmic
movement of the head or extremities, contracted or unequal pupils,
retinal hemorrhages, hemiplegia, absent or exaggerated deep tendon
reflexes, and a positive Babinski sign.
▪ Lumbar puncture reveals
▪ Increased pressure and mildly increased cerebrospinal fluid protein,
typically with no CSF pleocytosis and a normal CSF glucose.
▪ Funduscopic findings of malaria retinopathy
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▪ Retinal hemorrhages,
▪ Peripheral whitening,
▪ Macular whitening,
▪ Vessel changes are relatively specific for cerebral malaria, so children
with cerebral malaria who do not have malaria retinopathy should be
carefully assessed for other causes of coma. (However, they should
still be treated for cerebral malaria).
▪ Treatment of cerebral malaria other than antimalarial medications is
largely supportive
▪ Cerebral edema with increased ICP is the leading cause of death in
children with cerebral malaria
• Respiratory distress
▪ Is a poor prognostic indicator in severe malaria and appears to be caused
by metabolic acidosis rather than intrinsic pulmonary disease.
• Seizures
▪ Are common complications of severe malaria, particularly cerebral
malaria
▪ Benzodiazepines are first-line therapy for seizures, and intrarectal
diazepam has been used successfully in children withmalaria and seizures.
▪ Many seizures resolve with a single dose of diazepam.
▪ For persistent seizures, phenobarbital or phenytoin is the standard
medications used.
• Hypoglycemia
▪ Is a complication of malaria that is more common
▪ In children,
▪ Pregnant women, and
▪ Patients receiving quinine therapy.
▪ Any child with impaired consciousness and malaria should have a glucose
level checked, and if glucometers are not immediately available, an
empirical bolus of dextrose should be given.
▪ Hypoglycemia is associated with increased mortality and neurologic
sequelae.
• Circulatory collapse (algid malaria)
▪ Is a rare complication that manifests as
▪ Hypotension, hypothermia, rapid weak pulse, shallow breathing,
pallor, and vascular collapse.
▪ Is most likely caused by bacterial superinfection, since up to 15% of
children in endemic areas with severe malaria may have concurrent
bacteremia.

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▪ Death may occur within hours.
▪ Any child with severe malaria and hypotension or hypo perfusion should
have a blood culture obtained and should be treated empirically for
bacterial sepsis.
• Long-term cognitive impairment
▪ occurs in
▪ 25% of children with cerebral malaria
▪ Children with repeated episodes of uncomplicated disease.
▪ Prevention of attacks in these children may improve educational
attainment.
• Hyperreactive malarial splenomegaly (HMS)
▪ Is a chronic complication of P. falciparum malaria in which massive
splenomegaly persists after treatment of acute infection.
▪ Major criteria include
▪ splenomegaly(>10 cm),
▪ IgM > 2 SD above local mean,
▪ High levels of antibodies to a blood-stage P. falciparum antigen, and
▪ A clinical response to an antimalarial drug.
▪ HMS occurs exclusively in children in endemic areas with repeated
exposure to malaria and
▪ Is thought to be caused by an impaired immune response to P. falciparum
antigens.
▪ Prolonged antimalarial prophylaxis (for at least 1 yr, typically with
chloroquine, quinine, or mefloquine) is required to treat this syndrome if
the child remains in a malaria-endemic area.
▪ Spleen size gradually regresses on antimalarial prophylaxis but often
increases again if prophylaxis is stopped.
• Other complications in children include acute kidney injury and jaundice, both
of which are associated with a worse outcome and prostration.
• Prostration
▪ Is defined as the inability to sit, stand, or eat without support, in the
absence of impaired consciousness.
▪ Has been associated with increased mortality in some studies
INVESTIGATION
• Other than diagnostic investigation, laboratory evaluation for assessing
complications is needed.
▪ Full blood count ▪ Algid
▪ Anemia malaria(leukocytosis)

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▪ Thrombocytopenia ▪ LFT
▪ RBS ▪ Chest x-ray
▪ Blood group and cross match ▪ Arterial blood gas analysis
▪ Coagulation profile ▪ Abdominal ultrasound
▪ Lumbar puncture ▪ CT or MRI
▪ Blood culture
MANAGEMENT
▪ Includes general supportive management and chemotherapy
▪ General management
▪ Antipyretics
▪ Nutritional support
▪ Management of complications
▪ Chemotherapy
▪ Uncomplicated malaria- a patient who presents with symptoms of
malaria and a positive parasitology test but with no feature of severe
malaria.
Table 49 Treatment of Uncomplicated Malaria in Malaria Endemic Areas
Regimen
All Plasmodium Artemether-lumefantrine, 1.5 mg/kg–9 mg/kg twice daily for 3
falciparum malaria days with food or milk
Artesunate, 4 mg/kg daily for 3 days, and mefloquine, 25 mg base
per kg (8 mg/kg/daily for 3 days*)†
Dihydroartemisinin-piperaquine, 2.5 mg/kg–20 mg/kg daily for 3
days
Sensitive P. falciparum Artesunate, 4 mg/kg daily for 3 days, and a single dose of
Malaria sulfadoxinepyrimethamine, 25 mg/kg–1.25 mg/kg
Artesunate, 4 mg/kg, and amodiaquine*, 10 mg base per kg daily
for 3 days
Chloroquine-sensitive Chloroquine, 10 mg base per kg immediately, followed by 10
P. vivax, ‡, P. mg/kg at 24 hr and 5 mg/kg at 48 hr
malariae, ‡ P. ovale, ‡
P. knowlesi. ‡
• ‡ Any of the artemisinin combination treatments can be given except for
artesunate-sulfadoxine-pyrimethamine where P. vivax is resistant.
• Patients with P. vivax or P. ovale infections should also be given a 14-day
course of primaquine to eradicate hypnozoites (radical cure). However, severe
glucose-6-phosphate dehydrogenase deficiency is a contraindication because a
14-day course of primaquine can cause severe hemolytic anemia in this group.

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Table 50 Treatment of Severe Malaria in Adults and Children in Malaria-Endemic Areas
Artesunate, 2.4 mg/kg by intravenous or intramuscular* injection, followed by 2.4 mg/kg at
12 hr and 24 hr; continue injection once daily if necessary†
Artemether, 3.2 mg/kg by immediate intramuscular* injection,followed by 1.6 mg/kg daily
Quinine dihydrochloride, 20 mg salt per kg infused during 4 hr, followed by maintenance of 10
mg salt per kg infused during 2-8 hr every 8 hr (can also be given by intramuscular injection*
when diluted to 60-100 mg/mL)
• Artesunate is the treatment of choice in severe malaria. Artemether should
only be used if artesunate is unavailable. Quinine dihydrochloride should be
given only when artesunate and artemether are unavailable.
• Intramuscular injections should be given to the anterior thigh.
PREVENTION
• Malaria prevention consists of
o Reducing exposure to infected mosquitoes and
o Chemoprophylaxis.
PREVENTIVE MEASURES
• Insecticide-treated bed nets (which have decreased all-cause mortality in
children <5 yr old in several highly malaria endemic areas by approximately
20%),
• Indoor residual spraying with long-lasting insecticides,
• The use of artemisinin-combination therapy for first-line malaria treatment.
• Intermittent prevention treatment
o Sulfadoxine-pyrimethamine given to infants at the 2nd and 3rd doses of the
diphtheria, tetanus toxoid, and pertussis vaccine is safe and relatively
effective.
o Has also been given to pregnant women; 3 doses of sulfadoxine-
pyrimethamine have resulted in a reduction of low-birthweight infants.
• Mosquito repellent applied to thin clothing and exposed areas of the skin
o 25–35% N, diethyltoluamide (DEET) (not >40%).
o Picaridin
• Chemoprophylaxis
o Person who travels to malaria-endemic area are at risk of acquiring
malaria

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Table 51 Chemoprophylaxis of Malaria for Children
Area Drug Description
Chloroquine Mefloquine*† Once weekly dosing
resistant Children going to malaria endemic area for ≥4 wk
Area
Doxycycline‡ Cannot give to children <8 yr and pregnant women
Must take with food or causes stomach upset
Atovaquone/pro Children going to malaria endemic area for <4 wk
guanil§ Not recommended in pregnant women, children weighing
(Malarone) <5 kg, and women breastfeeding infants who weigh <5 kg.
Contraindicated in individuals with severe renal
impairment (creatinine clearance <30 mL/min).
Chloroquine Chloroquine Once weekly dosing
susceptible phosphate
Area
▪ Chloroquine and mefloquine should be started 1-2 wk prior to departure
and continued for 4 wk after last exposure
▪ ‡Doxycycline should be started 1-2 days prior to departure and continued
for 4 wk after last exposure
▪ Atovaquone/proguanil (Malarone) should be started 1-2 days prior to
departure and continued for 7 days after last exposure.

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CHAPTER 6 – PULMONOLOGY
1. Cough
2. Acute Cough
− Pneumonia
3. Chronic cough
− Tuberculosis
4. Approach to Wheeze
− Asthma
− Bronchiolitis
5. Upper airway obstruction and Stridor

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6.1. COUGH
• Cough is an explosive expiration that provides a normal protective mechanism
for clearing the tracheobronchial tree of secretions and foreign material
o It Is an important defense mechanism of the lungs and is a common
symptom.
o The duration of the symptoms
▪ Determines the level of concern and
▪ Degree of workup that is warranted.
o An acute cough, lasting < 2 weeks, is frequently related to an
infectious illness and is often self-limited.
o A chronic cough, a cough that persists for ≥ 2 weeks and suggests a
potentially more serious underlying cause.
MECHANICS OF COUGH
• Three Phases
1. Inspiratory phase - air inhalation lengthens the expiratory muscles
(favorable length-tension relation).
2. Compressive phase - Contraction of expiratory muscles against a closed
glottis leads to an increase in intrathoracic pressure.
3. Expiratory phase - Opening of the glottis results in high expiratory flow
and audible coughs.
APPROACH
If a patient present with a compliant of cough, we approach through taking
appropriate History, doing Physical examination and investigating them as indicated.
HISTORY
• QUESTIONS TO ASK
o Duration of cough - Acute (less than 2 weeks) or Chronic cough (more
than two weeks)
o Nature of cough - Watch "Different types of cough sounds" on YouTube
here https://youtu.be/YizKqqN8SWQ
▪ Barking/brassy cough (Laryngotracheobronchitis) - Watch "What
croup Cough sounds like and how to treat it - Home Remedies" on
YouTube https://youtu.be/O7fZDEBJ7TM
▪ Staccato cough (Chlamydia in infant) Watch "Staccato Baby" on
YouTube https://youtu.be/qdexsh6Ejmk
▪ Honking or Goose-like (Psychogenic)

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Whooping cough (Pertussis) - What Whooping Cough Sounds Like -
▪
Toddler with the "whoop" sound - https://youtu.be/zuK4honWVsE.
o Time of the day the cough worsens
▪ Asthma (worsen during night and early morning)
o Type of exposure that triggers the cough
▪ Seasonal aero allergens
▪ Noxious odor (perfumes)
o The cough aggravator and reliever
▪ Asthma aggravated by exposure to allergen
▪ Pets or animal contact
• Any Associated symptoms like
o Shortness of breath (dyspnea)
o Vomiting (post-tussive emesis) like in Pertussis
o Evidence of fevers – May suggest infectious causes
o Failure to thrive or weight loss, loss of appetite and Night sweating -
Tuberculosis or Malignancy (Immunocompromising)
o Child exposure to smoke (tobacco, wood burn)
o History of choking - foreign objects in airway
o Prenatal and neonatal history – Look for risk factors for pneumonia
o Family history of atopy (eczema, allergies, asthma).
6.2. ACUTE COUGH

DIFFERENTIAL DIAGNOSIS FOR ACUTE COUGH
• Upper respiratory infection • Asthma (details under
o Rhinitis wheezing disorders)
o Sinusitis, especially • Inhalation of irritants
maxillary (environmental, occupational)
• Gastroesophageal reflux • Smoke/smog
• Bacterial and other infections • Noxious fumes
• Croup (details under stridor) • Extremely hot or cold air
• Bronchiolitis (details under • Pulmonary embolism
wheezing disorders) • Acute pleural, pericardial,
• Pneumonia (see below) mediastinal, or diaphragmatic
• Bordetella pertussis inflammation
• Aspiration pneumonia • External or middle ear disease
• Foreign body aspiration
• Laryngeal inflammation

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PNEUMONIA
• Pneumonia is an inflammation of the parenchyma of the lungs.
EPIDEMIOLOGY
• Is a substantial cause of morbidity and mortality in childhood (particularly
among children <5 yr of age) throughout the world.
• Developed countries……. incidence of 0.026 /child-year
• Developing countries…...incidence of 0.28 /child-year
• Viral pneumonia……. peaks b/n 2 & 3 yrs., decreasing slowly thereafter.
ETIOLOGIES
• Although most cases of pneumonia are caused by microorganisms,
noninfectious causes include:
o Aspiration of food or gastric acid,
o Foreign bodies,
o Hydrocarbons, and lipoid substances,
o Hypersensitivity reactions, and
o Drug- or radiation-induced pneumonitis.
• Viral pathogens are a prominent cause of lower respiratory tract infections
in infants and children <5 yr of age, influenza virus and respiratory syncytial
virus are the major pathogens, especially in children <3 yr of age.
o S. pneumoniae, H. influenzae, and S. aureus are the major causes of
hospitalization and death from pneumonia among children in developing
countries,
• The age of the patient may help identify possible pathogens. (See table)
PATTERNS OF PNEUMONIA
• There are five patterns of bacterial pneumonia:
1. Lobar pneumonia: involvement of a single lobe or segment of a lobe; this is
the classic pattern of S. pneumoniae pneumonia
2. Bronchopneumonia: primary involvement of airways and surrounding
interstitium; this pattern is sometimes seen in Streptococcus pyogenes and
Staphylococcus aureus pneumonia.
3. Necrotizing pneumonia: - associated with aspiration pneumonia and
pneumonia resulting from S. pneumoniae and S. aureus.
4. Caseating granuloma (as in tuberculosis pneumonia).

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5. Interstitial and peribronchiolar with secondary parenchymal infiltration: this
pattern typically occurs when a severe viral pneumonia is complicated by
bacterial pneumonia.
Table 52 Causes of Pneumonia in different age group.

AGE GROUP COMMON PATHOGENS* (IN
APPROXIMATE ORDER OF
FREQUENCY
Neonates (up to 1 Group B streptococcus, Escherichia coli, other gram-negative bacilli,
month of age Streptococcus pneumonia
1 to 3 months
Febrile Respiratory syncytial virus, other viruses (parainfluenza viruses, influenza
pneumonia viruses, adenoviruses), S. pneumoniae, H. inflenzae (type b, & non
typable)
Afebrile Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum,
pneumonia CMV, Bordetella pertussis
3 months to 5 RSV, other respiratory
years viruses (parainfluenza viruses, Influenza viruses,
Human metapneumovirus, adenoviruses),S. pneumoniae, H. inflenzae
(type b,& nontypable)
5 to 18 years M. pneumoniae, S.
pneumoniae, C. pneumoniae,
≥18 years M. pneumoniae, S.pneumoniae, C. pneumoniae,
H. inflenzae (type b, nontypable), inflenza viruses, adenoviruses,
• There are two patterns of viral pneumonia:
1. Interstitial pneumonitis
2. Parenchymal infection with viral inclusions
PATIENT APPROACH
HISTORY
• Symptoms can be helpful in determining: -
o the etiologic agent,
o the likelihood of infection with an organism that is resistant to antibiotics,
and
o The severity of illness.

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Table 53 Approach to patient with pneumonia
Historical feature Possible significance
Age of the child Viral etiologies are most common in infants and preschool children
Atypical bacterial pathogens are more common in school-age
children
Recent viral upper respiratory May predispose to bacterial superinfection with Streptococcus
tract infection pneumoniae or Staphylococcus aureus
Associated symptoms Mycoplasma pneumoniae is often associated with extrapulmonary
manifestations (eg, headache,
photophobia, rash)
Cough, chest pain, shortness of "Classic" features of pneumonia, but nonspecific
breath, difficulty breathing
Increased work of breathing in Suggestive of severe pneumonia
the absence of stridor or
wheezing
Fluid and nutrition intake Difficulty or inability to feed suggests severe illness
Choking episode May indicate foreign body aspiration
Duration of symptoms Chronic cough (>4 weeks) suggests etiology other than acute
pneumonia (refer to UpToDate topic on causes of chronic cough in
children)
Previous episodes Recurrent episodes may indicate aspiration, congenital or acquired
anatomic abnormality, cystic fibrosis, immunodeficiency, asthma,
missed foreign body
Immunization status Completion of the primary series of immunizations for Haemophilus
influenzae type b, S. pneumoniae, Bordetella pertussis, and
seasonal influenza decreases, but does not eliminate, the risk of
infection with these organisms
Previous antibiotic therapy Increases the likelihood of antibiotic-resistant bacteria
Maternal history of chlamydia May indicate Chlamydia trachomatis infection
during pregnancy (for infants
<4 months of age)
Exposure to tuberculosis May indicate Mycobacterium tuberculosis infection
Ill contacts More common with viral etiologies
Animal exposure May indicate histoplasmosis, psittacosis, Q fever
Day care center attendance Exposure to viruses and antibiotic-resistant bacteria

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Classification
Cough or difficulty in breathing with: Severe
• Oxygen saturation < 90% or central cyanosis Pneumonia
• Severe respiratory distress e.g. grunting, severe chest
indrawing
• Signs of pneumonia with
o a general danger sign (inability to breastfeed or
drink, lethargy or reduced level of consciousness,
convulsions)
Fast breathing Pneumonia
• ≥ 60 breaths/minute in a Child aged <2 months;
• ≥ 50 breaths/ minute in a child aged 2–11 months
• ≥ 40 breaths/minute in a child aged 1–5 years
OR
• Chest indrawing
• Definite chest findings on auscultation
DIAGNOSIS
The diagnosis of pneumonia is clinical.
• Baseline investigations
o CBC (Leukocytosis)
o ESR and CRP (raise)
• Diagnostic investigation
• Chest Xray - Confirms the diagnosis of pneumonia and may indicate a
complication such as a pleural effusion or empyema.
o Viral pneumonia is usually characterized by:
▪ hyperinflation with bilateral interstitial infiltrates and
▪ peribronchial cuffing.
o Confluent lobar consolidation is typically seen with pneumococcal
pneumonia.
o Indications
▪ Severe disease, as defined above.
▪ Confirmation of the diagnosis when clinical findings are
inconclusive.
▪ Exclusion of alternate explanations for respiratory distress (eg,
foreign body aspiration, heart failure), particularly patients with
underlying cardiopulmonary or medical conditions.
▪ Assessment of the presence of complications, particularly in
children whose pneumonia is prolonged and unresponsive to
antimicrobial therapy
▪ Exclusion of pneumonia in:

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•
Young children (3 to 36 months) with fever >39ºC and
leukocytosis (≥ 20,000 WBC/microL) and
• Older children (<10 years) with fever >38ºC, cough, and
leukocytosis (≥ 15,000 WBC/microL)
• Pleural fluid analysis
Table 54 Pleural fluid analysis
Differentiation of pleural fluid
Transudate Exudate Complicated
empyema
Appearance Clear Cloudy Purulent
Cell count <1000 >1000 >5000
Cell type Lymphocytes, PMNs PMNs
monocytes
LDH <200 U/L >200 U/L >1000 U/L
Pleural/serum LDH <0.6 >0.6 >0.6
ratio
Protein>3 g Unusual Common Common
Pleural/serum <0.5 >0.5 >0.5
protein ratio
Glucose* Normal Low Very low* (<40
mg/dL)
pH* Normal(7.40–7.60) 7.20–7.40 <7.20
Gram stain Usually positive >85% positive
Negative unless patient
received prior
antibiotics
COMPLICATIONS OF PNEUMONIA
• Local complications These complications are more
o Pleural effusion, common with staph and
o Empyema and Klebsiella pneumonia
o Lung abscess
o Pneumatoceles.
o Septic emboli in pulmonary veins
• Systemic complications
o Septicemia is the most common pneumonia complication and occurs
when the bacteria causing pneumonia spreads into the blood stream
o The spread of bacteria can lead to septic shock or metastatic secondary
infections like meningitis especially in infants, peritonitis, and
endocarditis especially in patients with valvular heart disease or septic
arthritis.

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o Metastatic abscesses
1. SUPPORTIVE CARE
• Bed rest.
• With severe respiratory distress- humidified O2 inhalation & restricted I.V.
fluids
• Symptomatic treatment e.g., antipyretics for Fever.
• Treatment of complications.
o Chest tube drainage for massive effusion or empyema.
2. ANTIBIOTIC THERAPY
• Bacterial pneumonia => Antibiotics Choice:
o As suggested by clinical picture & chest X-ray.
o According to culture & sensitivity if available.
o Antibiotic combination if the cause cannot be detected.
• Viral pneumonia:
o Antibiotics may be used as coexisting bacterial infection exists in 30% of
cases
o Antiviral (for immunodeficient):
▪ Ribavirin for RSV.
▪ Amantadine for influenza A virus
Table 55 Choice of antibiotics for pneumonia
Age group Empiric regimen
1 to 6 months
Bacterial Infants <3 to 6 months of age with suspected bacterial pneumonia should be
(not hospitalized
Chlamydia
trachomatis)
C. Refer to UpToDate topic on C. trachomatis infections in the newborn

trachomatis
6 months to 5
years
Typical Amoxicillin 90 mg/kg per day in 2 or 3 divided doses (MAX 4 g/day), or

bacterial* ¶

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Amoxicillin-clavulanate 90 mg/kg per day of the amoxicillin component in 2 or 3

divided doses (MAX 4 g/day amoxicillin
component)
For children with mild reactions to a penicillin and no features of an IgE-mediated

reaction :
Δ
Amoxicillin 90 mg/kg per day in 2 or 3 divided doses (MAX 4 g/day), or
Amoxicillin-clavulanate 90 mg/kg per day of the amoxicillin component in 2 or 3

divided doses (MAX 4 g/day
amoxicillin component), or
A third-generation cephalosporin, such as cefdinir 14 mg/kg per day in 2 divided

doses (MAX 600 mg/day) in
communities with a low rate of pneumococcal resistance to penicillin
For children with IgE-mediated or serious delayed reaction to a penicillin:
Levofloxacin 16 to 20 mg/kg per day in 2 divided doses (MAX 750 mg/day), or

◊
Clindamycin 30 to 40 mg/kg per day in 3 or 4 divided doses (MAX 1.8 g/day), or
Linezolid 30 mg/kg per day in 3 divided doses (MAX 1.8 g/day)
In communities with a high rate of pneumococcal resistance to penicillin:
Levofloxacin 16 to 20 mg/kg per day in 2 divided doses (MAX 750 mg/day), or

◊
Linezolid 30 mg/kg per day in 3 divided doses (MAX 1.8 g/day)
>5 years
Mycoplasma Azithromycin 10 mg/kg on day 1 followed by 5 mg/kg daily for 4 more days (MAX 500
pneumoniae mg on day 1 and 250 mg
or thereafter), or
Chlamydia
pneumoniae Clarithromycin 15 mg/kg per day in 2 divided doses (MAX 1 g/day), or
Erythromycin 40 to 50 mg/kg per day in 4 divided doses (MAX 2 g/day as base, 3.2
g/day as ethylsuccinate), or
Doxycycline 4 mg/kg per day in 2 divided doses (MAX 200 mg/day), or

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Levofloxacin 8 to 10 mg/kg once daily for children 5 to 16 years (MAX 500 mg/day);
500 mg once daily for children
≥16 years, or
Moxifloxacin 400 mg once daily (≥18 years)
Typical Amoxicillin 90 mg/kg per day in 2 or 3 divided doses (MAX 4 g/day)

bacterial*
reaction :
Amoxicillin 90 mg/kg per day in 2 or 3 divided doses (MAX 4 g/day), or
A third-generation cephalosporin, such as cefdinir 14 mg/kg per day in 2 divided

doses (MAX 600 mg/day)
For children with IgE-mediated or serious delayed reaction to a penicillin:
750 mg once daily for
children ≥16 years, or
Clindamycin 30 to 40 mg/kg per day in 3 or 4 divided doses (MAX 1.8 g/day), or
Linezolid 30 mg/kg per day in 3 divided doses (MAX 1.8 g/day) for children <12
years; 20 mg/kg per day divided in
2 doses (MAX 1.2 g/day) for children ≥12 years
In communities with a high rate of pneumococcal resistance to penicillin:
750 mg once daily for
children ≥16 years, or
Linezolid 30 mg/kg per day divided in 3 doses (MAX 1.8 g/day) for children <12
years; 20 mg/kg per day divided in
2 doses (MAX 1.2 g/day) for children ≥12 years
Community- Amoxicillin-clavulanate 40 to 50 mg/kg per day in 2 or 3 divided doses (MAX 1.75

acquired g/day amoxicillin component)

reaction:
Amoxicillin-clavulanate 40 to 50 mg/kg per day in 2 or 3 divided doses (MAX 1.75
g/day amoxicillin component)

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For children with IgE-mediated or serious delayed reaction to amoxicillin:
Clindamycin 30 to 40 mg/kg per day divided in 3 or 4 doses (MAX 1.8 g/day)
Moxifloxacin 400 mg once daily (for ≥18 years)
Parenteral empiric antibiotics for inpatient treatment of pediatric community-

acquired pneumonia
Table 56 Parenteral empiric antibiotics for inpatient treatment
Age group and Suggested parenteral Comments
suspected pathogens empiric agent(s)
1 to 6 months
Bacterial (not One of the following: If CA-MRSA is suspected, ADD one of the
Chlamydia trachomatis Ceftriaxone following:
or Cefotaxime Vancomycin or clindamycin
Staphylococcus aureus) Ceftaroline* (alternative)
C. trachomatis Azithromycin
≥6 months
Uncomplicated One of the following: Cefotaxime and ceftriaxone are reserved for:
bacterial (not Ampicillin or penicillin G Children with incomplete Hib or
Mycoplasma (preferred) Streptococcus pneumoniae
pneumoniae, Cefotaxime immunizations, or
Chlamydia Ceftriaxone Communities with substantial prevalence of
pneumoniae, or S. penicillin-resistant S. pneumoniae (eg,
aureus) ≥25%)
M. pneumoniae or C. One of the following:
pneumoniae Azithromycin
Erythromycin
Levofloxacin
Clinical syndrome (any Suggested empiric Comments
age) parenteral agent(s)
Severe pneumonia Combination therapy with Children with severe infection may benefit
one of the following: from
Ceftriaxone broad-spectrum therapy that addresses both
Cefotaxime typical and atypical pathogens
PLUS one of the following: If S. aureus is a consideration, either:
Azithromycin ADD vancomycin or clindamycin, OR
Erythromycin Provide therapy with ceftaroline* PLUS
Doxycycline azithromycin

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Severe pneumonia Combination therapy with: If S. aureus is likely:

requiring ICU Vancomycin ADD nafcillin , OR
admission PLUS one of the following: SUBSTITUTE linezolid for vancomycin and
Ceftriaxone nafcillin, OR
Cefotaxime Use ceftaroline* PLUS azithromycin PLUS
PLUS: antiviral treatment for influenza if the child
Azithromycin is hospitalized during influenza season
PLUS:
Antiviral treatment for
influenza if the child
is hospitalized during
influenza season
Complicated Combination therapy with Potential pathogens include S. pneumoniae,

pneumonia (eg, one of the following: S.
effusion/empyema, Ceftriaxone aureus, and Streptococcus pyogenes
necrotizing process, Cefotaxime Vancomycin is an alternative to clindamycin
abscess ) PLUS: for
Clindamycin if S. aureus or children with allergy to clindamycin or high
anaerobic prevalence of clindamycin resistance in the
infection is a consideration community
Monotherapy with ceftaroline is an
alternative if
S. aureus is a consideration
ADMISSION CRITERIA
• Age <6 mo • Dehydration
• Sickle cell anemia with acute • Vomiting
chest syndrome • No response to appropriate oral
• Multiple lobe involvement antibiotic therapy
• Immunocompromised state • Noncompliant parents
• Toxic appearance
• Severe respiratory distress
• Requirement for supplemental
oxygen

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6.3. CHRONIC COUGH

COMMON CAUSES OF CHRONIC COUGH ARE
• Respiratory system
o Tuberculosis
o Asthma (Discussed under wheeze)
o Pertussis (Discussed under Childhood Infections)
o Foreign body aspiration (Discussed under Acute Airway obstruction)
o Tracheobronchomalacia
o Dyskinetic cilia
• Cardiovascular system
o Congenital heart disease
o Heart failure
• Gastrointestinal system
o Gastoesophageal reflux disease
• Systemic
o Measles
o Human immunodeficiency virus (PCP)
IN THIS SECTION WE WILL DISCUSS TUBERCULOSIS

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TUBERCULOSIS
• Tuberculosis is a chronic infectious disease caused by Mycobacterium
tuberculosis
• TB in children is mainly due to failure of TB control in adults
ETIOLOGY
• M. tuberculosis complex: - M. tuberculosis, (the most important cause in
humans), M. bovis, M. africanum, M. microti and M.Canetti
• Mycobacterium tuberculosis
o Non-spore-forming, non-motile, Acid fast, obligate aerobes
o Mycobacteria grow slowly, their generation time being 12–24 h
EPIDEMIOLOGY
• The World Health Organization (WHO) estimates that since 2015, tuberculosis
has surpassed (HIV/AIDS) as the leading cause of death from an infectious
disease worldwide
• It infects almost one third of the world's population(The highest numbers of
cases are in Asia, Africa, and the eastern Mediterranean region)
• Approximately 95% of TB cases occur in the developing world
• The global burden of tuberculosis is influenced by several factors, including:
o the HIV pandemic;
o the development of multidrug-resistant(MDR) tuberculosis and
o the disproportionately low access of populations in low-resource settings
worldwide to both diagnostic tests and effective medical therapy.
MODE OF TRANSMISSION
• Inhalation: - pulmonary tuberculosis
o Infectious droplet nuclei can be spread into the air by:
▪ Coughing (single coughing Can produce 3000 droplet nuclei)
▪ Talking
▪ Sneezing
▪ Spitting and singing
o Most important source is smear positive coughing adult
• Ingestion (raw milk): - intestinal Tuberculosis
• Wound contamination: - cutaneous tuberculosis
• Hematological spread form primary Tuberculosis focus

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PATHOGENESIS
• Primary infection occurs in persons without previous exposure to tubercle
bacilli
• Pulmonary infection occurs when TB bacilli, contained in a small infectious
aerosol droplet, reaches a terminal airway and succeeds in establishing
infection
• A localized granulomatous inflammatory process occurs within the lung and this
is called the PRIMARY (GHON) FOCUS
• From the Ghon focus, bacilli drain via lymphatics to the regional lymph nodes
• The Ghon focus with associated tuberculous lymphangitis and involvement of
the regional lymph nodes is called the primary (Ghon) complex
• The development of the primary complex is asymptomatic
• From the regional lymph nodes bacilli enter the systemic circulation directly or
via the lymphatic duct
• This occult haematogenous spread occurs during the incubation period, before
adequate immune responses contain the disease
• After dissemination, bacilli may survive in target organs for prolonged periods
• The future course of the disease at each of these sites depends on the dynamic
balance between host immunity and the pathogen
NATURAL HISTORY
• In 90-95% of persons infected with M. Tuberculosis, the immune system either
kills the bacilli or perhaps more often, keeps them suppressed (silent focus)
resulting in a latent TB infection (LTBI).
• In immunocompetent individuals, only 5-10% of infected persons develop active
disease in their lifetime
• Individuals with latent TB infection do not have symptoms as there is no tissue
destruction by the bacilli and are not infectious
• Active TB disease may arise from:
o progression of the primary lesion after infection
o from endogenous reactivation of latent foci, which remained dormant
since the initial infection
o from exogenous re-infection
• The progression from LTBI to TB disease may occur at any time, from soon to
many years later
• Post primary TB usually affects the lungs after hematogenous and/or lymphatic
spread of the bacilli

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CLINICAL STAGES
There are 3 major clinical stages of tuberculosis: exposure, infection, and disease
1. EXPOSURE MEANS
• A child has had significant contact with an adult or adolescent with infectious
tuberculosis but lacks proof of infection
• In this stage, the tuberculin skin test (TST) or interferon-γ release assay (IGRA)
result is negative
• The chest radiograph and physical examination is normal
• The child lacks signs or symptoms of disease
• However, the child may be infected and develop TB disease rapidly, since there
may not have been enough time for the TST or IGRA to turn positive
2. TUBERCULOSIS INFECTION (TBI):

• It occurs when the individual inhales droplet nuclei containing M. tuberculosis,
which survive intracellularly within the lung and associated lymphoid tissue
• The hallmark of TBI is a positive TST or IGRA result
• In this stage the child has no signs or symptoms
• A normal physical examination, and the chest radiograph is either normal or
reveals only granuloma or calcifications in the lung parenchyma
3. DISEASE
• occurs when signs or symptoms or radiographic manifestations caused by M.
tuberculosis become apparent
• Not all infected individuals have the same risk of developing disease
• An immunocompetent adult with untreated TBI has approximately a 5–10%
lifetime risk of developing disease An infected child <1 yr old has a 40% chance
of developing TB disease within 9 months
RISK FACTORS FOR TUBERCULOSIS INFECTION

• Children exposed to high-risk adults
• Foreign-born persons from high-prevalence countries
• Homeless persons
• Persons who inject drugs
• Present and former residents or employees of correctional institutions,
homeless shelters, and nursing homes
• Healthcare workers caring for high-risk patients (if infection control is not
adequate

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RISK FACTORS FOR PROGRESSION OF TUBERCULOSIS INFECTION TO
TUBERCULOSIS DISEASE
• Infants and children ≤4 yr old, especially those <2 yr old
• Adolescents and young adults
• Persons co-infected with human immunodeficiency virus
• Persons with skin test conversion in the past 1-2 yr
• Persons who are immunocompromised, especially in cases of malignancy and
solid-organ transplantation,
• Immunosuppressive medical treatments including anti–tumor necrosis factor
therapies, diabetes mellitus, chronic renal failure, silicosis, and malnutrition
RISK FACTORS FOR DRUG-RESISTANT TUBERCULOSIS

• Personal or contact history of treatment for tuberculosis
• Contacts of patients with drug-resistant tuberculosis
• Birth or residence in a country with a high rate of drug resistance
• Poor response to standard therapy
• Positive sputum smears (acid-fast bacilli) or culture ≥2 months after initiating
appropriate therapy.
Time between initial infection and clinically apparent disease:

• Disseminated and meningeal tuberculosis are early manifestations (2–6 months)
• Significant lymph node or endobronchial tuberculosis (within 3–9 months)
• Lesions of the bones and joints take several years to develop
• Renal lesions (decades after infection)
PRIMARY PULMONARY DISEASE
• The hallmark of primary tuberculosis in the lung is the relatively large size of
the regional lymphadenitis compared with the relatively small size of the initial
lung focus
• As delayed-type hypersensitivity develops, the hilar lymph nodes continue to
enlarge in some children, especially infants, compressing the regional bronchus
and causing obstruction.
• The usual sequence is hilar lymphadenopathy, focal hyperinflation, and then
atelectasis. The resulting radiographic shadows have been called collapse-
consolidation or segmental tuberculosis
• Up to 50% of infants and children with radiographically moderate to severe
pulmonary tuberculosis have no physical findings.
• Infants are more likely to experience signs and symptoms.

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• Nonproductive cough and mild dyspnea are the most common symptom
• Systemic complaints occur less often
PROGRESSIVE PRIMARY PULMONARY DISEASE

• A rare but serious complication of tuberculosis in a child occurs when the
primary focus enlarges steadily and develops a large caseous center
• Liquefaction can cause formation of a primary cavity associated with large
numbers of tubercle bacilli.
• The enlarging focus can slough necrotic debris into the adjacent bronchus,
leading to further intrapulmonary dissemination
• Significant signs or symptoms (High fever, severe cough with sputum
production, weight loss, and night sweat ) are common in locally progressive
disease
REACTIVATION TUBERCULOSIS
• It is rare in childhood but can occur in adolescence
• Children with a healed TBI acquired when they were <2 yr old rarely develop
chronic reactivation pulmonary disease, which is more common in those who
acquire the initial infection when they are >7 yr old
• The most common pulmonary sites are the original parenchymal focus, lymph
nodes, or the apical seedings (Simon foci) established during the hematogenous
phase of the early infection.
• This form of TB disease usually remains localized in the lungs, because the
established immune response prevents further extrapulmonary spread.
• The most common radiographic findings are extensive infiltrates and thick-
walled cavities in the upper lobes
• Older children and adolescents are more likely to experience fever, anorexia,
malaise, weight loss, night sweats, productive cough, hemoptysis, and chest
pain than children with PTB
• This form of tuberculosis may be highly contagious if there is significant sputum
production and cough
1. PULMONARY TUBERCULOSIS
• It refers to any bacteriologically confirmed or clinically diagnosed case of TB
involving the lung parenchyma or the tracheobronchial tree. A patient with
both pulmonary and extrapulmonary TB should be classified as a case of PTB
• Pulmonary TB is uncommon in childhood
• Symptoms of Pulmonary tuberculosis:

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o Persistent cough for two or more weeks, (cough of any duration for HIV
positives)
o Fever for more than 2 weeks
o Night sweats
o Unexplained weight loss
2. EXTRA PULM ONARY TUBERCULOSIS

• It refers to any bacteriologically confirmed or clinically diagnosed case of TB
involving organs other than the lungs, e.g. pleura, lymph nodes, abdomen,
genitourinary tract, skin, joints and bones, meninges.
• Extrapulmonary manifestations are more common in children than adults and
develop in 25–35% of children with tuberculosis.
TYPES OF EXTRA-PULMONARY TUBERCULOSIS ARE
LYMPHOHEMATOGENOUS (DISSEMINATED) DISEASE

• Tubercle bacilli are disseminated to distant sites, including liver, spleen, skin,
and lung apices, in all cases of TBI
• The clinical picture subsequent to lymphohematogenous dissemination depends
on:
o The burden of organisms released from the primary focus to distant sites
and
o The adequacy of the host's immune response
• Although the clinical picture may be acute, more often it is indolent and
prolonged
• Multiple organ involvement is common:
o Leading to hepatomegaly, splenomegaly, lymphadenitis in superficial or
deep nodes, and papulonecrotic tuberculoid appearing on the skin
o Bones and joints or kidneys also can become involved
o Meningitis occurs only late in the course of the disease
o Early pulmonary involvement is mild, but diffuse involvement becomes
apparent with prolonged infection
MILIARY TUBERCULOSIS
• The most clinically significant form of disseminated tuberculosis is military
disease
• It Occurs when massive numbers of tubercle bacilli are released into the
bloodstream, causing disease in 2 or more organs
• Is most common in infants and malnourished or immunosuppressed patients

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• Clinical picture
o The onset is insidious with early systemic signs, including anorexia,
weight loss, and low-grade fever
o The lesions are usually smaller than 2–3 mm in diameter, then coalesce
to form larger lesions
o Generalized lymphadenopathy and hepatosplenomegaly in about 50%
of cases
o Signs or symptoms of meningitis or peritonitis are found in 20–40% of
patients with advanced disease
o Choroid tubercles occur in 13–87% of patients and are highly specific for
the diagnosis of miliary tuberculosis
• Diagnosis
o It can be difficult and a high index of suspicion by the clinician is
required
o Often the patient presents with fever of unknown origin
o Chest imaging shows miliary pattern in two-thirds of patients that assist
in the diagnosis of military TB
o Early sputum or gastric aspirate cultures have a low sensitivity
o Biopsy of the liver or bone marrow with appropriate bacteriologic and
histologic examinations more often yields an early diagnosis
o The most important clue is usually history of recent exposure to an adult
with infectious TB.
o The resolution of miliary tuberculosis is slow, even with proper therapy:
o Fever usually declines within 2-3 wk of starting chemotherapy
o the chest radiographic abnormalities might not resolve for many months
o The prognosis is excellent with early diagnosis and adequate
chemotherapy.
TUBERCULOUS LYMPHADENOPATHY
o TB of Superficial LNs (Scrofula) is most common form of EPTB
o Common sites are cervical lymph node, occasionally axillary and intra-
abdominal LN may be involved
o Initially cervical lymph nodes are discrete, firm and non-tender may
later be matted together and become fluctuant
o The overlying skin may breakdown with the formation of abscesses and
chronic discharging sinuses, which heal with scarring
• Diagnosis
o The TST is usually reactive, but the chest radiograph is normal in 70% of
cases

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o It is usually diagnosed by (FNA) of the lymph node
o A definitive diagnosis of tuberculous adenitis usually requires:
▪ histologic or bacteriologic confirmation, which is best
accomplished by FNA for culture, stain, and histology
▪ Culture of lymph node tissue yields the organism in only
approximately 50% of cases
DIFERENTIAL DIAGNOSIS
• Nontuberculous mycobacteria (NTM)
• Cat scratch disease (Bartonella henselae)
• Tumor
• Branchial cleft cyst
• Cystic hygroma, and
• Pyogenic infection
• Treatment
• It responds well to antituberculosis therapy
TUBERCULOUS PLEURAL EFFUSION

• It is uncommon in children <6 yr old and rare in children <2 yr old
• Effusions are usually unilateral but can be bilateral
Clinical picture
• most often present as sudden onset of low to high fever, shortness of breath,
chest pain on deep inspiration, and diminished breath sounds
• The prognosis is excellent but radiographic resolution often takes months
Diagnosis
• CXR shows unilateral, uniform white opacity,, ultrasound can confirm the
presence of fluid in the pleural space in case of doubt
• examination of pleural fluid and the pleural membrane
• The pleural fluid:
o is usually yellow and only occasionally tinged with blood
o The specific gravity is usually 1.012–1.025
o the protein level is usually 2–4 g/dL, and
o the glucose concentration may be low although it is usually in the low-
normal range (20-40 mg/dL)
o The white cell count is usually high with an early predominance of
polymorphonuclear leukocytes (PMNs) followed by a high percentage of
lymphocytes

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• Acid-fast smears of the pleural fluid are rarely positive
• The TST is positive in only 70–80% of cases
• Cultures of the fluid are positive in only <30% of cases
• Biopsy of the pleural membrane is more likely to yield a positive acid-fast stain
or culture, and granuloma formation usually can be demonstrated.
PERICARDIAL TB
• The most common form of cardiac tuberculosis is TB pericarditis
• It is rare, occurring in 0.5–4% of TB cases in children
• Pericarditis usually arises from direct invasion or lymphatic drainage from
subcarinal lymph nodes
o None specific symptoms like low-grade fever, malaise, weight loss
o Chest pain is unusual in children
o A pericardial friction rub or distant heart sounds with pulsus paradoxus
may be present
• Diagnosis
o Acid-fast smear of the fluid rarely reveals the organism
o cultures are positive in 30–70% of cases
o The pericardial fluid is typically serofibrinous or hemorrhagic
o ADA levels are elevated in TB pericarditis
o The culture yield from pericardial biopsy may be higher, and the
presence of granulomas often suggests the diagnosis.
TB OF CNS
• TB meningitis and intracranial tuberculoma are the two most common forms
• Is the most serious complication in children and is fatal without prompt and
appropriate treatment
• complicates about 0.3% of untreated tuberculosis infections in children
• most common in children between 6 mo and 4 yr of age
• Due to lymphohematogenous dissemination of the primary infection
• The combination of vasculitis, infarction, cerebral edema, and hydrocephalus
results in the severe damage
• The brainstem is often the site of greatest involvement, which accounts for the
commonly associated dysfunction of cranial nerves III, VI, and VII
• The sixth nerve involvement being the most common
• Clinical feature
o The clinical progression of tuberculous meningitis may be rapid or slowly
progressing

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o Mostly slow progression and have 3 stages
THE 3 STAGES OF TB MENINGITIS

• 1st stage
o lasts 1–2 weeks
o characterized by nonspecific symptoms(fever, headache, irritability,
drowsiness, and malaise)
o Focal neurologic signs are absent
o Infants can experience a stagnation or loss of developmenta milestones
• 2nd stage
o usually begins more abruptly
o The most common features are:
▪ Lethargy, nuchal rigidity, seizures positive Kernig or Brudzinski
signs, hypertonia
▪ vomiting, cranial nerve palsies, and other focal neurologic signs
▪ signs of encephalitis, such as disorientation, movement disorders,
or speech impairment.
• 3rd stage
o it is marked by coma, hemiplegia or paraplegia, hypertension,
decerebrate posturing, deterioration of vital signs, and eventually
death.
• Diagnosis
o Identifying an adult in contact with the child who has infectious
tuberculosis.
o The tuberculin skin test is nonreactive in up to 50% of cases
o 20–50% of children have a normal chest radiograph.
o The most important laboratory test for the diagnosis of tuberculous
meningitis is examination and culture of the lumbar CSF
o The CSF Analysis
▪ Leukocyte count -10 to 500 cells/mm3
▪ Glucose <40 mg/dL
▪ Protein - 400–5,000 mg/dL
▪ AFB and culture yield depends on volume (if 5-10ml: AFB is
positive in 30%, culture positive in 50-70%)
• Prognosis
o The majority of patients in the 1st stage have an excellent outcome
o most patients in the 3rd stage who survive have permanent disabilities
including
▪ blindness
▪ deafness

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▪ paraplegia
▪ diabetes insipidus, or
▪ mental retardation.
o The prognosis for young infants is generally worse than for older children
TUBERCULOMA
• A tumor-like mass resulting from aggregation of caseous tubercles that usually
presents clinically as a brain tumor
• Tuberculomas account for up to 30% of brain tumors in some areas of the world
• The most common symptoms are headache, fever, focal neurologic findings,
and convulsions.
• In adults, tuberculomas are most often supratentorial, but in children they are
often infratentorial
• The tuberculin skin test is usually reactive, but the chest radiograph is usually
normal
• Surgical excision is often necessary to distinguish tuberculoma from other
causes of brain tumor
• Surgical removal is not necessary because most tuberculomas resolve with
medical management.
• Corticosteroids are usually administered during the 1st few weeks of treatment
or in the immediate postoperative period to decrease cerebral edema
• On CT or MRI of the brain, tuberculomas usually appear as discrete lesions with
a significant amount of surrounding edema
• Contrast medium enhancement is often impressive and can result in a ringlike
lesion
BONE AND JOINT TB

• TB can affect any bone but most commonly affects the vertebral column
• The classic manifestation of tuberculous spondylitis is progression to Pott
disease, in which destruction of the vertebral bodies leads to gibbus deformity
and kyphosis
• In many cases more than one intervertebral disc is involved
• Involvement of the intervertebral disc occurs by spread of a lesion from the
vertebral body
• Tuberculous bone lesions may resemble pyogenic and fungal infections, or bone
tumors
Clinical feature

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• It is characterized by loss of bone density and slow bone erosion, with the disc
space being maintained for a long time (differentiating it from pyogenic
infections)
• Involvement of the thoracic vertebrae causes:
o localized back pain
o deformity of the spine and
o in extreme cases an angulated kyphosis (Gibbus)
o Spread may occur into the soft paravertebral tissue to form a so-called
“cold abscess”
SPINAL TUBERCULOSIS
• The typical appearance is erosion of the anterior edges of the superior and
inferior borders of adjacent vertebral bodies. The disc space is narrowed
• The sites most commonly involved are the lower thoracic, lumbar and
lumbosacral areas
Diagnosis
• Plain X-ray of the spine is usually diagnostic of spinal TB
• A bone biopsy is essential to confirm the diagnosis
ABDOMINAL AND GASTROINTESTINAL DISEASE

• TB of Oral cavity or pharynx is rare
• Esophageal Tb is rare (may be associated with traceesophageal fistula in
infants)
• Intestinal tuberculosis is due to:-
o Ingested tuberculosis bacilli in milk
o Swallowed sputum from T.B lesions in the lungs
TUBERCULOSIS ENTERITIS
• Caused by hematogenous route or swallowing of bacilli from their own lungs or
ingestion of raw milk (M. bovis)
• Most common sites of involvement; ileum and jejunum near Peyer patches &
appendix
• The typical findings are shallow ulcers that cause pain, diarrhea or
constipation, and weight loss with low-grade fever
• Mesenteric adenitis is usually complicates the infection
• Enlarged nodes may cause intestinal obstruction or erode through the omentum
to cause generalized peritonitis

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• The ileocecal region is most common site due to relative stasis and abundant
lymphoid tissues in this region.
• The macroscopic appearance of intestinal lesions categorized as follows
o Ulcerative (60%): characterized by multiple superficial ulcers
o hypertrophic (10%): characterized by scarring, fibrosis, and
pseudotumor lesions
o ulcerohypertrophic (30%): characterized by an inflammatory mass
around ileocecal valve with thickened and ulcerated intestinal walls. It
is more commonly observed in ileocecal disease.
TUBERCULOUS PERITONITIS
• Uncommon in adolescents and rare in children
• Generalized peritonitis may arise from subclinical or miliary hematogenous
dissemination.
• Localized peritonitis is caused by direct extension from an abdominal lymph
node, intestinal focus, or genitourinary tuberculosis.
• typical manifestations
o Abdominal pain or tenderness,
o ascites,
o anorexia, and
o low-grade fever
• The tuberculin skin test is usually reactive
• The diagnosis can be confirmed by paracentesis with appropriate stains and
cultures.
GENITOURINARY DISEASE
RENAL TUBERCULOSIS
• Renal TB is rare in children
• Tubercle bacilli usually reach the kidney during lymphohematogenous
dissemination
• It is often clinically silent in its early stages, marked only by sterile pyuria and
microscopic hematuria
• As the disease progresses, dysuria, flank or abdominal pain, and gross
hematuria develop
• Hydronephrosis or ureteral strictures can complicate the disease.
Diagnosis
• Urine cultures for M. tuberculosis are positive in 80–90% of case

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• Acid-fast stains of large volumes of urine sediment are positive in 50–70% of
cases
• The TST is nonreactive in up to 20% of patients.
• A pyelogram or CT scan often reveals mass lesions, dilation of the proximal
ureters, multiple small filling defects, and hydronephrosis if ureteral stricture
is present
• Disease is most often unilateral
GENITAL TRACT TUBERCULOSIS

• Uncommon in prepubescent boys and girls
• originates from lymphohematogenous spread, or by direct spread from the
intestinal tract or bone
• Genital tract tuberculosis in adolescent girls:
o It can develop during the primary infection
o The fallopian tubes are most often involved (90–100% of cases), followed
by the endometrium (50%), ovaries (25%), and cervix (5%)
o The most common symptoms are lower abdominal pain and
dysmenorrhea or amenorrhea
o Systemic manifestations are usually absent
o the chest radiograph is normal in the majority of cases, The TST is
usually reactive
• Genital tuberculosis in adolescent boys:
o It causes epididymitis or orchitis
o The condition usually manifests as a painless, unilateral nodular swelling
of the scrotum
o Involvement of the glans penis is extremely rare
o Genital abnormalities and a positive TST in an adolescent boy or girl
suggest genital tract tuberculosis
TB IN PATIENTS WITH ESPECIAL CONDITIONS
PREGNANCY AND THE NEWBORN

• Pulmonary and particularly extrapulmonary tuberculosis other than
lymphadenitis in a pregnant woman is associated with increased risk for:
o prematurity,
o fetal growth retardation,
o low birthweight, and perinatal mortality.
• Congenital tuberculosis is rare because the most common result of female
genital tract tuberculosis is infertility

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o Primary infection in the mother just before or during pregnancy is more
likely to cause congenital infection than is reactivation of a previous
infection.
o Congenital transmission usually occurs from a lesion in the placenta
through the umbilical vein, when tubercle bacilli infect the fetal liver,
where a primary focus with periportal lymph node involvement can
occur.
o Organisms pass through the liver into the main fetal circulation and
infect many organs
o The bacilli in the lung usually remain dormant until after birth, when
oxygenation and pulmonary circulation increase significantly.
o Congenital tuberculosis can also be caused by aspiration or ingestion of
infected amniotic fluid
o However, the most common route of infection for the neonate is
postnatal airborne transmission from an adult with infectious pulmonary
tuberculosis.
PERINATAL DISEASE
o Symptoms of congenital tuberculosis may be present at birth but usually
begin by the 2nd or 3rd wk of life.
o The most common signs and symptoms are respiratory distress, fever,
hepatic or splenic enlargement, poor feeding, lethargy or irritability,
lymphadenopathy, abdominal distention, failure to thrive, ear drainage,
and skin lesions
o Generalized lymphadenopathy and meningitis occur in 30–50% of patients
o The clinical presentation of tuberculosis in newborns is similar to that
caused by bacterial sepsis and other congenital infections, such as
syphilis, toxoplasmosis, and cytomegalovirus
• Diagnosis
o The diagnosis should be suspected in an infant with signs and symptoms
of bacterial or congenital infection whose response to antibiotic and
supportive therapy is poor and in whom evaluation for other infections is
unrevealing
o The most important clue for rapid diagnosis of congenital tuberculosis is
a maternal or family history of tuberculosis. Often, the mother's disease
is discovered only after the neonate's diagnosis is suspected
o The infant's TST is negative initially but can become positive in 1-3
months

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o A positive acid-fast stain of an early-morning gastric aspirate from a
newborn usually indicates tuberculosis
o Direct acid-fast stains on middle ear discharge, bone marrow, tracheal
aspirate, or tissue biopsy (especially liver) can be useful.
o The CSF should be examined, cultured, and sent for PCR testing
o The mortality rate of congenital tuberculosis remains very high because
of delayed diagnosis
o Many children have a complete recovery if the diagnosis is made
promptly and adequate chemotherapy is started
DISEASE IN HIV-INFECTED CHILDREN

• HIV increases susceptibility to infection with M. tuberculosis
• HIV increases the risk of progression of M. tuberculosis infection to TB disease
• Tuberculosis in HIV-infected children is often more severe, progressive, and
likely to occur in extrapulmonary sites
• Nonspecific respiratory symptoms, fever, and weight loss are the most common
complaints.
Table 57 Lifetime risk of developing TB disease
HIV status Life time risk of developing TB
Negative 5-10%
Positive 50%
• Radiographic findings are similar to those in children with normal immune
systems, but lobar disease and lung cavitation are more common
• Recurrent disease and relapse occur more frequently in HIV-infected children
• Rates of drug-resistant tuberculosis tend to be higher in HIV-infected adults
and probably are also higher in HIV-infected children
• The prognosis generally is good if TB disease is not far advanced at diagnosis
and appropriate antituberculosis drugs are available
• The mortality rate of HIV-infected children with tuberculosis is high, especially
as the CD4 lymphocyte numbers decrease
• In adults the host immune response to TBI appears to enhance HIV replication
and accelerate the immune suppression caused by HIV
• Increased mortality rates are attributed to progressive HIV infection rather
than tuberculosis
• Therefore, HIV-infected children with potential exposures and/or recent
infection should be promptly
• evaluated and treated for tuberculosis
• Conversely, all children with TB disease should be tested for HIV infection

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• Children with HIV infection who are given (HAART) are at high risk of
developing immune reconstitution inflammatory syndrome (IRIS)
• IRIS should be suspected in patients:
o who experience a worsening of TB symptoms during antituberculosis
therapy (Paradoxical IRIS) or
o who develop new-onset TB symptoms and radiographic findings after
initiation of HAART (Unmasking IRIS)
• The most common clinical manifestations of IRIS in children are:
o Fever, cough, new skin lesions, enlarging lymph nodes in the thorax or
neck, and appearance or enlargement of tuberculomas in the brain, with
or without accompanying meningitis
INVESTIGATIONS (DIAGNOSTIC TOOLS)

1. BACTERIOLOGICAL METHODS
MICROSCOPIC EXAMINATION
• The most specific confirmation is isolation of M.tuberculosis
• Spot sputum smear examination with two sample; the second taken 30-60
minutes after the first one
• Early morning gastric aspirate (young age)
CULTURE
• It is the gold standard
• Negative culture never exclude pulmonary TB
2. MOLECULAR TEST
• Gene Xpert
o It is a new and rapid DNA test for TB and it can detect Rifampin
resistance
o currently preferred first line diagnostic test
o Indicated for diagnosis of TB in high MDR-TB and TB/HIV
o For diagnosis of TB in children and Extra pulmonary TB
• Line Probe Assay (LPA)
o Identify specific mutations on the genes of TB bacilli responsible for
Isoniazid and Rifampicin resistance
o It is rapid and accurate test to identify MDR-TB
3. HISTO-PATHOLOGICAL EXAMINATION
PLEURAL FLUID ANALYSIS

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• Color: Yellow with blood tinged
• Chemical: Protein (2-4gm/dl,
• glucose (20-40 mg/dl)
• Cells: lymphocyte predominance
CSF ANALYSIS (TB MENINGITIS)

• White Blood Cell(10-500mg/dl)
• Glucose less than 40mg/dl
• AFB and culture yield depends on volume (if 5-10ml:AFB is positive in 30%,
culture positive in 50-70%)
• Fine needle aspiration (TB lymphadenitis)
• Tissue biopsy (bronchial, pleural, pericardial, peritoneal, liver tissue)
• Shows characteristic granulomatous lesion
4. RADIOLOGIC EXAMINATION
CHEST X-RAY
• Upper lobe infiltration
• Enlarged hilar and mediastinal lymph nodes and opacification in lung tissue
• Cavitation (common with older children), pleural effusion, emphysema,
collapse
• Miliary mottling in lung tissue
X-RAY OF BONES
• Narrowing of disc space
• Collapse of vertebral body, Extensive destruction with kyphosis (pott disease)
CT/MRI
• Diffuse brain edema and lepto-meningeal inflammation, meningeal
enhancement (TB meningitis)
• Discrete lesions with significant surrounding edema and ring enhancement
(Tuberculoma)
5. TUBERCULIN SKIN TESTING (TST)

• It detects delayed hypersensitivity reaction to tuberculosis protein
• MANTOUX TEST: the intradermal injection of 0.1 mL purified protein derivative
stabilized with Tween 80

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• T cells sensitized by prior infection are recruited to
the skin, where they release lymphokines that induce
induration through local vasodilation, edema, fibrin
deposition, and recruitment of other inflammatory
cells to the area
• Interpretation: measure induration after 48-72 hours
• Tuberculin sensitivity develops 3 wk to 3 mo (most
often in 4-8 wk) after inhalation of organisms.
Figure 48 TUBERCULIN SKIN TESTING (TST)
FALSE POSITIVE TST
• Hypersensitivity to constituents
• Cross-sensitization to Antigens of NTM (usually below 10mm)
• Previous vaccination with BCG can cause reaction:
o If 2 BCG vaccinations given
• 50% of the infants who receive a BCG vaccine never develop a reactive TST
• Reactivity usually wanes in 2-3 yr in those with initially positive TST
• Prior vaccination with BCG is never a contraindication to TST
FALSE NEGATIVE TST

• Very young age
• Severe PEM
• Infections (measles, mumps, varicella)
• Vaccination with live-viruses’ vaccines (within 6wks)
• Overwhelming TB
• Immunosuppression by disease or drugs (HIV, Steroids).
Table 58 Definitions of Positive Tuberculin Skin Test (TST) Results in Infants, Children, and Adolescents
Criteria for positive Tuberculin skin test
Reaction Population
1. Induration • Children in close contact with known or suspected contagious people with
≥5 mm tuberculosis disease
• Children suspected to have tuberculosis disease:
– Findings on chest radiograph consistent with active or previously
tuberculosis disease
– Clinical evidence of tuberculosis disease
• Children receiving immunosuppressive therapy or with immunosuppressive
conditions, including HIV infection
2. Induration • Children at increased risk of disseminated tuberculosis disease:
≥10 mm – Children <4 yr old

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–Children with other medical conditions, including Hodgkin disease,
lymphoma, diabetes mellitus, chronic renal failure, or malnutrition
• Children with increased exposure to tuberculosis disease:
– Children born in high-prevalence regions of the world
– Children often exposed to adults with HIV infection, homeless, users of
illicit drugs, residents of nursing homes, incarcerated or institutionalized,
or migrant farm workers
– Children who travel to high-prevalence regions of the world
3. Induration • Children ≥4 yr old without any risk factors
≥15 mm
DIANGOSIS OF TUBERCULOSIS IN CHILDREN

• Characteristic presentations of TB in Children
o TB most commonly occurs in less than 5 years of age
o Pulmonary TB is the commonest form though up to 30-40% may have
EPTB
o Infants and young children (especially those under 2 years) are at
greatest risk of developing severe, disseminated disease and the time
between infection and disease can be shorter than in older children
• Key risk factors for development of TB in children include:
o Household contact or other close contact with pulmonary TB cases
o Child’s age younger than 5 years
o HIV infection; and
o Severe malnutrition.
APPROACH TO DIAGNOSE TB IN CHILDREN

EVALUATION OF A CHILD WITH PRESUMPTIVE TB
• Who should be evaluated for TB disease?
o A child with symptoms suggestive of TB, with history of exposure to an
infectious pulmonary TB patient;
o A child with pneumonia, pleural effusion, or a cavitary or mass lesion in
the lung that does not improve with standard antibiotic therapy;
o Patients with fever of unknown origin, failure to thrive, significant
weight loss; severe malnutrition and/or other immunosuppressive
conditions (such as measles in the previous 3 months, whooping cough,
HIV, being on medication like steroids), or unexplained
lymphadenopathy.

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APPROACHES TO DIAGNOSE TB IN CHILDREN:
• Careful history (including history of TB contact and symptoms consistent with
TB)
• Clinical assessment (including growth assessment)
• Diagnostic tests
o Bacteriologic confirmatory tests (AFB microscopy, Xpert MTB/RIF assay &
culture)
o Chest X-ray
o HIV testing
o Histopathology, mainly for suspected EPTB
DIAGNOSIS OF TUBERCULOSIS IN HIV NEGATIVE CHILDREN

A. Diagnosis of TB based on bacteriologic confirmation
− Bacteriologic confirmation of TB is reached if the TB bacilli are detected
by m WRDs (e.g., Xpert MTB/RIF), AFB microscopy or culture from
biologic specimen.
B. Clinical diagnosis of TB based Algorithmic Approach
− By combining the evidences from clinical features of TB, contact
information and supportive evidences from investigations
C. Clinical diagnosis of TB can also be made if the child has either:
− Radiological picture of Miliary pattern;
− Histopathological findings compatible with TB; or
− Presence of clinical features suggestive of TB, documented contact
history and decision to treat TB with help of experienced clinician
DIAGNOSIS OF TUBERCULOSIS IN HIV POSITIV E CHILDREN

• The approach to diagnosing TB in children living with HIV is essentially the
same as for diagnosis in HIV-negative children
• Bacteriologic confirmation of TB is first step for investigation.
TB SCREENING IN INFANTS AND CHILDREN:

• Children living with HIV who have any one of the following symptoms –poor
weight gain, fever, current cough or contact history with a TB case – may have
TB and should be evaluated for TB and other conditions
• Children living with HIV and who do not have poor weight gain, fever or current
cough are unlikely to have active TB.
DEFINITION OF TERMS AND PATIENT REGISTRATION

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CLASSIFICATION OF TB
• Bacteriologically confirmed or clinically diagnosed cases of TB cases are also
classified according to:
I. Anatomical site of disease
II. History of previous treatment
III. Drug Resistance, and
IV. HIV status of the patient
I. CASE DEFINITION BY SITE AND RESULT OF SPUTUM SMEAR FOR PTB
PULMONARY TUBERCULOSIS (PTB):

• refers to any bacteriologically confirmed or clinically diagnosed case of TB
involving the lung parenchyma or the tracheobronchial tree. A patient with
both pulmonary and extrapulmonary TB should be classified as a case of PTB.
EXTRA-PULMONARY TUBERCULOSIS (EPTB):

• refers to any bacteriologically confirmed or clinically diagnosed case of TB
involving organs other than the lungs, e.g. pleura, lymph nodes, abdomen,
genitourinary tract, skin, joints and bones, meninges
SMEAR POSITIVE CASE:

• At least 2 sputum smears positive for AFBs or
• 1 sputum smear positive and X-ray abnormality consistent with TB
SMEAR NEGATIVE CASE

• At least 2 (preferably3) sputum smear negative for AFB and
• Chest X-ray consistent with TB
II. HISTORY OF PREVIOUS TREATMENT:

• New case (N): a patient who has never taken treatment for TB or has been on
anti-TB treatment for less than one month
• Relapse(R): a patient who has been declared cured or treatment completed of
any form of TB in the past, but who reports back to the health service and is
found to be AFB smear-positive or culture positive
• Treatment failure(F): a patient who, while still on treatment remains smear-
positive or comes again sputum smear-positive 5 months or more after starting
treatment
• Return after default (D): a patient who has previously been recorded as
defaulted from treatment (completed at least one month of treatment and

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interrupted for at least 2 months) and returns to the health service with smear-
positive sputum
• Transfer in (T): a patient registered for treatment in one district and is
transferred to another.
• Chronic case (C): a patient who remains smear-positive after completing a
supervised re-treatment regimen. This is usually seen in adults and is rare in
childhood but may occur in adolescents
• Other (O): a patient who does not easily fit into one of the above case
definitions (e.g., a smear-negative PTB who returns after default).
III. DRUG RESISTANCE

RIFAMPICIN RESISTANT TB:
• resistance to Rifampicin detected using phenotypic or genotypic methods, with
or without resistance to other anti-TB drugs
MULTIDRUG-RESISTANCE (MDR):
• Resistance to at least Isoniazid and Rifampicin
EXTENSIVELY DRUG-RESISTANT TB (XDR-TB):

• Is TB that is resistant to any fluoroquinolone and to at least one of three
second-line injectable drugs (capreomycin, kanamycin and amikacin), in
addition to multidrug resistance.
• The current definition of XDR-TB is likely to change, given the phasing out of
injectables, the likelihood of patterns of resistance that are more relevant to
current and future regimens, and advances in diagnostic methods and DST.
IV. HIV STATUS OF A PATIENT

• HIV-positive TB.
• HIV-negative TB
• HIV status unknown TB
TREATMENT OF DRUG SUSCEPTIBLE TB

• The aims of treatment of Tuberculosis are:
o To cure the patient from TB
o To prevent death from TB disease and its late effects
o To prevent relapse of TB
o To prevent the development of acquired drug resistance, and
o To decrease TB transmission
TUBERCULOSIS TREATMENT PRINCIPLES

• Antituberculosis drugs

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• Nutritional rehabilitation
• Screening of family members and and/or other suspected index cases: for
prevention and treatment
• Follow up for (Adherence, response to treatment, drug side effect).
Drug Dosage Daily Twice Maximum Adverse reactions
forms dosage weekly dose
(mg/kg) dosage
(mg/kg/dose)
Ethambutol Tablets: 20 50 2.5g Optic neuritis, decreased red-green
100mg, color, discrimination, gastrointestinal
400mg tract disturbances, hypersensitivity
Isoniazid Tablets: 10-15 20-30 Daily: Mild hepatic enzyme elevation,
100mg, 300 mg Hepatitis, Peripheral neuritis,
300mg Twice hypersensitivity
Syrup: weekly:
10mg/mL 900 mg
Pyrazinamide Scored 30-40 50 2g Hepatotoxic effects, hyperuricemia
tablets: , arthralgias, gastrointestinal tract upset
500 mg
Rifampin Capsules: 15-20 15-20 600mg Orange discoloration of secretions,
150mg, vomiting, hepatitis, thrombocytopenia,
300mg, pruritus, Oral contraceptives may be
Syrup ineffective
formulated
from
capsules
Table 59 Commonly Used Drugs for Treatment of Tuberculosis in Infants, Children, and Adolescent
NB: Patients treated with isoniazid for mycobacterium tuberculosis: pyridoxine (25_50
mg/day po) is given for prevention of peripheral neuropathy.
STANDARDIZED TB TREATMENT
• The daily dosage of First line TB treatment is standardized based on patients’
weight band ranges
• It is used to facilitate procurement, distribution and administration of
treatment to patient
Table 60 First line TB Treatment Pediatric Dosing Chart Using Body Weight Bands.
Table 61 Treatment regimen and doses based on Weight
Child’s Weight Treatment regimen and doses

Intensive phase: 2 (RHZ)E Continuation
phase: 4(RH)
RHZ 75/50/150 E 100mg RH75/50
4-7kg 1 1 1

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8-11kg 2 2 2
12-15kg 3 3 3
16-24kg 4 4 4
25+kg Adult dosages recommended
Table 62 First line TB Treatment Adult Dosing Chart Using Patient’s Body weight Bands
Patients weight band(kg) Treatment regimen and dose

Intensive phase 2(RHZE) Continuation phase 4(RH)
20-29 1½ 1½
30-39 2 2
40-54 3 3
≥55 4 4
PHASES OF CHEMOTHERAPY AND DAILY DOSING FREQUENCY
INTENSIVE PHASE
• Reduces bacterial load( makes patient noninfectious)
• Prevent emergence of drug resistant strains
• Treatment with two months of RHZE
CONTINUATION PHASE
• To ensure the patient is permanently cured and no relapse after completion of
treatment
• To clear dormant bacilli
• Treatment with Four months of RH (exceptions are Osteoarticular TB and TB
meningitis for which the recommended duration is 9 to 12 months
DOSING FREQUENCY:
• Daily administration of all doses of the six month TB treatment should be
implemented under DOT in Ethiopia. Intermittent dosing frequency is not
recommended
DIRECTLY OBSERVED TREATMENT

• DOT means that an observer watches the patient swallowing their tablets, in a
way that is sensitive and supportive to the patient's needs
• This ensures that a TB patient takes the right anti-tuberculosis drugs, in the
right doses, at the right intervals
• National TB program recommends supervision of treatment to be made by a
trained health worker, Health extension worker or a trained TB treatment
supporter.

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TREATMENT OF DRUG SUSCEPTIBLE TB IN CHILDREN
• In Treatment of children for TB:
o Children receiving treatment must be weighed at least every month.
o Treatment doses should be adjusted as soon as a child changes weight
band.
o Monitor nutritional status/response during treatment using growth chart
o Administer pyridoxine for children with severe malnutrition, or taking
ART (Pyridoxine 25_50 mg po /day for prevention of peripheral
neuropathy).
o Adverse events are less common in children than in adults.
Table 63 Anti-TB regimen

TB patient TB cases Regimen
type Intensive Continuation
phase phase
New • New smear positive, negative 2(RHZE) 4(RH)
pulmonary TB and extra
pulmonary TB
• TB meningitis, Tuberculoma 2(RHZE) 10(RH)
• Osteoarticular TB (vertebral
bones, joint and osteomyelitis)
Previously Previously treated smear positive 2(RHZE) 4(RH)
treated pulmonary TB:
• Relapse
• Treatment after default
INDICATIONS FOR TREATMENT WITH STEROIDS

• TB meningitis/ tuberculoma
• TB pericarditis
• TB pleural effusion and shift of the mediastinum (when large with severe
symptoms)
• Endobronchial TB with localized emphysema
• Hypoadrenalism (TB of adrenal glands)
• TB laryngitis (with life-threatening airway obstruction)
• Spinal TB with neurologic deficit
• The most commonly used regimen is
o Prednisone ,1-2 mg/kg/day in 1-2 divided doses orally for 4-6 wk,
followed by a taper.

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MONITORING TREATMENT RESPONSES
I. CLINICAL MONITORING OF TB PATIENTS

• During scheduled visit, a patient receiving TB treatment should be checked for:
o Persistence or reappearance of clinical feature of TB, including weight
monitoring (Weight is a useful indicator of clinical improvement)
o Treatment adherence by reviewing the “treatment supporter card” or
UNIT TB register
o Risk for developing acquired drug resistance, and need for DST screening
o Occurrence of Adverse drug reaction, and
o Development of TB complications
• Unsatisfactory response to treatment beyond two months of treatment should
alarm the possibility of drug resistance or alternative diagnoses
II. BACTERIOLOGIC MONITORING OF BACTERIOLOGICALLY CONFIRMED

PULMONARY TB PATIENTS
• bacteriologically confirmed pulmonary TB patients (i.e. those diagnosed by
identification of bacilli by smear microscopy, Xpert MTB/RIF assay or culture)
need their sputum to be checked using AFB microscopy
• TB Care Provider should request sputum for AFB microscopy at the end of 2nd,
5th and 6th months of therapy
• Xpert MTB/RIF assay cannot be used to monitor treatment response
• Xpert MTB/RIF may give false positive result as it identifies genetic material of
dead bacilli

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Sputum AFB Follow-up for Bacteriologically Confirmed PTB Patients
Bacteriologically confirmed
PTB1
Baseline Sample for Xpert MTB RIF Test, start Intensive phase of treatment TB
treatment
AFB Smear at end of 2nd month
Negative
v Positive
Send Sputum Sample for Xpert MTB RIF

Start continuation and FL-LPA2; and Start continuation phase
Phase
If DST result shows susceptibility to RIF If DST result shows resistance

and INH (No RR-TB, No Hr-TB), Continue to either Rifampicin or INH or
with 4 RH both3 (either RR/MDR-TB or
Hr-TB)
Do AFB Smear at end of

5th month
Negative -Stop First line TB Rx;
v -Assign “Moved to MDR” as
Smear at end of 6th v outcome, and
month Positiv
-Refer/Link patient to MDRTB
center
e
-Initiate appropriate Treatment
Negativ v v Regimen (RR/MDR TB Regimen or
e Declare Failure Hr-TB Regimen
Do DST at least for RIF and
Declare
INH, CXR, Chest CT-Scans, for
Cure/complet retreatment evaluation
e
1 Bacteriologicallyconfirmed TB patients include those diagnosed by positive result on
either AFB microscopy, Xpert MTB/RIF Assay or culture;
2 DST may be performed from one sputum sample using Xpert MTB/RIF, LPA or
convention al DST based on availability. Information on Rifampicin may be enough to

decide on Next Action.
3 if DST result shows resistance to INH but susceptible to Rifampicin; treat with Hr-TB
Regimen
III. MANAGEMENT OF ADVERSE REACTION TO FIRST LINE ANTI-TB DRUGS

• regularly monitor for occurrence of side effects of the Anti-TB drugs
administered to the patient

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TB PREVENTION
• Case finding and treatment

• Searching for index case and treatment
• Isoniazid prophylaxis
• TB screening in infants and children who have contact with adult case
• BCG vaccine
o BCG is 50% effective in preventing pulmonary tuberculosis in adults and
children
o The protective effect for disseminated and meningeal tuberculosis
appears to be slightly higher, with BCG preventing 50–80% of cases

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6.4. APPROACH TO WHEEZE

EPIDEMIOLOGY
• One in three children experience at least one acute wheezing illness before
the age of three years.
• A large worldwide study looking at older children showed a global prevalence
of wheezing of 11.6 percent in children aged 6 to 7 years and 13.7 percent in
children between 13 to 14 years of age.
DEFINITION
• Wheeze is a musical continuous sound that originates in narrowed airways
heard on expiration as a result of airway obstruction.
MECHANISM
• Wheeze is produced by the oscillation of opposing walls of an airway narrowed
almost to the point of closure.
• It requires sufficient airflow to generate airway oscillation and produce sound
in addition to narrowing or compression of the airway.
• It can occur during inspiration, expiration or both.
NB: Infants are more likely to wheeze than are older children, as a result of:
• Airway size (small-caliber peripheral airways)
• Chest wall compliance is also quite high (Differences in tracheal cartilage and
airway smooth muscle tone, and inward pressure produced in normal
expiration) subjects the intrathoracic airways to collapse
• Marginal additional narrowing, such as that caused by inflammation, is then
more likely to result in wheezing
DIFFERENTIAL DIAGNOSIS
• Wheezing can be divided clinically according to the acuity of its onset, the
mechanism of airway narrowing and age of onset of wheezing.
• According to the mechanism of airway narrowing:
1. INFECTIONS: - viral: Respiratory syncytial virus, Human
metapneumovirus, Parainfluenza, Adenovirus, Influenza, Rhinovirus,
Bocavirus, Coronavirus, Enterovirus
▪ Others: Chlamydia trachomatis, Tuberculosis, Histoplasmosis,
Papillomatosis, pneumonia
2. ASTHMA
3. ANATOMIC ABNORMALITIES:

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▪ Central Airway Abnormalities –
• Malacia of the larynx, trachea, and/or bronchi, Laryngeal
or tracheal web, Tracheoesophageal fistula (specifically H-
type fistula), Laryngeal cleft (resulting in aspiration)
▪ Extrinsic Airway Anomalies Resulting in Airway Compression
• Vascular ring or sling, Mediastinal lymphadenopathy from
infection or tumor, Mediastinal mass or tumor, Esophageal
foreign body
▪ Intrinsic Airway Anomalies
• Airway hemangioma, other tumor, Congenital pulmonary
airway malformation (cystic adenomatoid malformation),
Bronchial or lung cyst, Congenital lobar emphysema,
Aberrant tracheal bronchus, Sequestration, Congenital
heart disease with left-to-right shunt (increased pulmonary
edema), Foreign body
4. IMMUNODECIENCY STATES
▪ Immunoglobulin A deficiency, B-cell deficiencies, AIDS,
Bronchiectasis
5. MUCOCILIARY CLEARANCE DISORDERS
▪ Cystic fibrosis, Primary ciliary dyskinesia, Bronchiectasis
6. ASPIRATION SYNDROMES
▪ Gastroesophageal reflux disease (GERD), Pharyngeal/swallow
dysfunction
7. OTHERS
▪ Bronchopulmonary dysplasia, Eosinophilic granulomatosis with
polyangiitis, Interstitial lung disease (ILD), including bronchiolitis
obliterans, Heart failure, Anaphylaxis, Inhalation injury—burns
ACCORDING TO ACUITY
Acute (hours to days) • Tracheo-bronchomalacia* • Cystic fibrosis
• Asthma • Vascular compression/rings* • Immunodeficiency
• Bronchiolitis* • Tracheal stenosis/webs* • Primary ciliary dyskinesia
• Bronchitis • Tumors/lymphadenopathy • Bronchopulmonary dysplasia
• Laryngotracheobronchitis¶ • Cardiomegaly • Retained foreign body
• Bacterial tracheitis • Vocal cord dysfunction Δ (trachea or esophagus)
• Foreign body aspiration¶ Functional abnormalities • Bronchiolitis obliterans
• Esophageal foreign body • Asthma • Pulmonary edema
Chronic or recurrent • Gastroesophageal reflux
• Structural abnormalities • Recurrent aspiration

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• The age of onset of wheezing can also help determine the etiology: …… (*up-to-
date)
o * - These disorders tend to present in infancy.
o ¶ - These disorders are more commonly seen in young children (toddlers
and preschoolers).
o Δ - These disorders are more commonly seen in teenagers.
APPROACH TO WHEEZING CHILD

1. TAKE A HISTORY
I. Characterize the chief complaint (if wheeze)
II. List your differential diagnoses
III. Ask the associated symptoms, risk factors, complications of your top
differentials
IV. write your HPI
2. DO PHYSICAL EXAMINATION
3. ORDER AN INVESTIGATION FOR YOUR SUSPECTED DIAGNOSIS
4. TREAT THE PATIENT
I. CLINICAL HISTORY
1. CHARACTERIZE WHEEZE
• https://www.youtube.com/watch?v=T4qNgi4Vrvo (hear the sound)
• IS IT WHEEZING? — What the child/parents actually experiencing or hearing?
(The word "wheezing" is used as a general term to describe noisy breathing that
is primarily due to upper airway noises, including snoring, congestion, rattling,
gurgling noises, or stridor)
• AGE AT ONSET —
o since birth - a congenital abnormality
o During infancy and early childhood - Structural abnormalities, virus-
induced wheezing and foreign body aspiration (FBA) is seen.
o in later childhood to adolescence - Other disorders, such as vocal cord
dysfunction (VCD)
• SPEED OF ONSET AND PERSISTENCE — whether the onset of wheezing was acute
or gradual and whether the wheezing is intermittent or persistent.
o Acute onset or Persistent wheezing with sudden onset - FBA (particularly
if there is a history of choking)
o Slowly progressive onset – extra-luminal bronchial compression by a
growing mass or lymph node.

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o Persistent wheezing - a congenital or structural abnormality (particularly
if it presents very early in life).
o Paroxysmal or Intermittent wheezing – Asthma (particularly if it has
triggering factors like; upper respiratory infections, weather changes,
exercise, or allergens and has seasonal variation)
• GOOD RESPONSE TO BRONCHODILATORS - Asthma. It can also be seen with
other conditions that may lead to inflammation and bronchoconstriction, such
as bronchopulmonary dysplasia [BPD], cystic fibrosis [CF], and aspiration.
2. ASSOCIATED SYMPTOMS
• COUGH – characterize it:
o Wet cough - mostly due to infection or inflammation
o Dry cough – due to structural causes (eg, airway malacia or compression,
foreign body, vascular ring).
NB: Asthma - either a dry or wet cough depending on the degree of airway obstruction
and the amount of mucus produced (mucus production can vary from one patient to
another and can vary at different times in the same patient).
• Shortness of breath and chest tightness (if older children) – Asthma
• Sneezing and clear rhinorrhea (nasal discharge) – bronchiolitis
• Fever – infections (bronchiolitis, pneumonia…)
Symptoms vary with position
• Regurgitation or vomiting – GERD change - malacia or vascular
• Choking – FBA rings
• Difficulty of swallowing – swallowing disorder, esophageal Symptoms (shortness of
foreign body breath, cough or wheeze)
• Dysphonia (change or hoarseness of voice), throat worsen at night-time or early
tightness, choking sensation – VCD morning. – Asthma
• Poor Weight Gain – immunodeficiency, ciliary diseases,

cystic fibrosis
• Stridor – malacia, vascular ring, VCD (Vocal Cord Dysfunction)
5. PAST MEDICAL AND SURGICAL HISTORY
• Allergy history:
o Eczema
o Persistent rhinitis (apart from acute upper respiratory tract infection-
URTI)
o To allergens like food, dusts, pollen.
• Medical history:
o Recurrent ear infection (ear discharge), upper and lower respiratory
tract infections (nasal discharge, sneezing) – CF, immunodeficiency,
ciliary dyskinesia

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o Neurologic disease – swallowing disorders
o Any comorbid conditions like congenital heart disease - (cardiac wheeze)
o Asthma diagnosis or long-term treatment for asthma
• Surgical history – lung transplantation and hematopoietic cell transplantation –
Bronchiolitis obliterans (rare disease)
6. PERSONAL, FAMILY AND SOCIAL HISTORY
• Family history of:
o Asthma and atopy/allergy in 1st degree relatives:
▪ Paternal asthma is a risk factor for persistent wheeze in boys
▪ Maternal asthma was a risk factor for persistent wheeze in girls
and boys
o Cystic fibrosis
o Immunodeficiency
• Social history:
o Second hand tobacco and other smokes exposure – RF for bronchiolitis +
asthma
o Living room not separated from kitchen (coal smoke exposure) – RF for
bronchiolitis + asthma
o Day care exposure – RF for bronchiolitis
o Number of siblings or older family members (siblings) with even minor
URTI (cold) – RF for bronchiolitis
o Crowded living conditions – RF for bronchiolitis + pneumonia
o Pets in the house – trigger for Asthma
o Home environment – dust mite, construction dust, heating and cooling
technique, mold, cockroaches – trigger for Asthma
o Any lapse in supervision of the child – RF for FBA
7. IMMUNIZATION HISTORY –
• if unvaccinated – RF for pneumonia and bronchiolitis
8. NUTRITIONAL HISTORY
• bottle feed in bed or crib especially in propped position – RF for GER
• not breastfed – RF for bronchiolitis
9. DEVELOPMENTAL HISTORY –
• if failure to thrive - immunodeficiency, ciliary diseases, cystic fibrosis
10. BIRTH HISTORY

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• Gestational age at delivery – if preterm (BW <1250g) – bronchopulmonary
dysplasia.
• Neonatal complications: respiratory problems since birth, or intubated or
hospitalized for respiratory distress – congenital abnormalities or
bronchopulmonary dysplasia.
• Mother smoking during pregnancy – bronchiolitis, Asthma
• Maternal complications.
It should include:
• General Appearance –
o acute sick looking (RD)
• Vital signs including oxygen saturation
• Anthropometry measurments (weight, height…)
• Complete chest examination, and
• Digital inspection for the presence of cyanosis or clubbing.
RESPIRATORY SYSTEM EXAMINATION

• INSPECTION
o Respiratory distress: retractions, nasal flaring, accessory respiratory
muscle use (ex, scalene…)
o Tachypnea
o Wheezing on expiration
o prolonged expiration
o structural abnormalities:
▪ Increased anteroposterior (AP) diameter - chronic hyperinflation
▪ Pectus excavatum - chronic airway obstruction
• PALPATION - tracheal deviation – mediastinal mass, supratracheal
lymphadenopathy
• PERCUSSION
o Define the position of the diaphragm – if hyperinflation – Asthma
o Hyper resonance – Asthma
• AUSCULTATION
o Identify location of wheezing: if focal wheezing - a localized and mostly
structural airway abnormality and FBA
o Decreased breath sounds - nearly complete bronchiolar obstruction
o Prolonged expiratory phase – Asthma

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o Crackles in conjunction with wheezing - in asthma, pneumonia and in
those leading to bronchiectasis (eg, CF, primary ciliary dyskinesia,
immune deficiency).
o Early inspiratory crackles - asthma (due to air flowing through
secretions or slightly closed airways during inspiration)
o Late inspiratory crackles - ILD and early congestive heart failure.
NB: Thus, the presence of crackles does not exclude the diagnosis of asthma
NB: The lack of audible wheezing is not reassuring if the infant shows other signs of
respiratory distress, since complete obstruction to airflow can eliminate the
turbulence that causes wheezing.
• HEENT: Nasal examination - for signs of allergic rhinitis, sinusitis, or nasal
polyps (seen in 10-32% of cystic fibrosis pt.)
• The cardiac examination: auscultation for murmurs and evaluation for signs of
heart failure – CHD (Cyanotic heart ds)
• Skin Examination - for eczema (common in atopic patients)
INVESTIGATION
• In most cases, the probable diagnosis is established on the basis of the clinical
history and physical examination.
TO CONFIRM THE DIAGNOSIS:
1. RESPONSE TO TREATMENT
• For patients suspected of having asthma, a trial of inhaled bronchodilators with
or without glucocorticoids can be used to confirm the diagnosis prior to
initiating a more extensive work-up.
NB: A partial or negative response to bronchodilators only may not rule out asthma,
because Inflammation and airway swelling may contribute to wheezing, in addition to
bronchoconstriction, especially in infants and young children. Thus, the combination
of inhaled glucocorticoids and bronchodilators for at least two weeks (or five to seven
days of oral glucocorticoids if the patient has more severe symptoms) may result in
significant improvement in symptoms and help in making the diagnosis of asthma.
• Further work-up is indicated if the response to therapy is inadequate:
2. IMAGING STUDIES —
• A chest radiograph (AP and lateral films)
• Indications:

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o new-onset wheezing of undetermined etiology or
o chronic, persistent wheezing not responding to therapies
NB: It is not necessary to obtain a chest radiograph with every exacerbation in

children with asthma, unless there is a specific indication.
CXR IS IMPORTANT TO
• To rule out pneumonia, atelectasis, and air leak,
o if there are focal examination findings (eg, crackles or decreased breath
sounds), fever (>39ºC), severe disease, uncertainty about the diagnosis,
or tachypnea, hypoxemia, or chest pain that are present after initial
therapy has been given
• To differentiate between diffuse and focal disease:
o Diffuse - asthma, CF, primary ciliary dyskinesia, and aspiration.
o Focal - structural abnormalities or FBA.
• To reveal cardiomegaly, enlarged pulmonary vessels, pulmonary edema, or
other signs of cardiac failure.
• To detect mediastinal masses or enlarged lymph nodes and may suggest the
presence of vascular rings (eg, right aortic arch).
OTHER RADIOLOGIC STUDIES:

• CT scan - provide detailed anatomy of the mediastinum, large airways, and
lung parenchyma.
• MRI with contrast - the study of choice when a vascular ring or sling is
suspected.
• Barium swallow - done when vascular rings, swallowing dysfunction, aspiration
syndromes including GER, and some cases of tracheoesophageal fistula
suspected.
3. PULMONARY FUNCTION TESTS

• Infant PFT, if available, can help quantify airway obstruction and the response
to bronchodilators
• In older children (who are cooperative), PFT with inspiratory and expiratory
flow-volume loops is helpful in determining the presence, degree, and location
of airway obstruction, and response to bronchodilators
NB: Imaging studies should be done based on the suspected diagnosis.

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Table 64 Summary to Approach to evaluation of wheezing in children based upon suspected diagnosis
Suspected Signs and symptoms Diagnostic evaluation

diagnosis
Acute
Asthma History of recurrent wheeze, History, PFT with bronchodilators, empiric trial of
cough, at least partial bronchodilators, exercise or methacholine
response to bronchodilator challenge testing, chest radiography only if
atypical, skin (or in vitro) testing for aeroallergen
sensitization if history suggests inhalant allergen
triggers
Viral bronchiolitis Prodrome with rhinitis, occurs History, age, season, rapid antigen testing (RSV,
in infancy and early childhood, influenza), viral cultures, chest radiography
seasonal pattern
Foreign body Sudden onset of coughing and History, physical examination, chest radiography,
wheezing bronchoscopy
Chronic
Asthma As above As above
Tracheomalacia Persistent wheeze, starts early History, fluoroscopy, flexible bronchoscopy
in life, poor response to
bronchodilators, varies with
position and activity
Cystic fibrosis Chronic productive cough, Sweat chloride test, genetic testing
crackles, with or without
clubbing, failure to thrive,
recurrent respiratory
infections
Swallowing Neurologic abnormality Videofluoroscopic swallowing study (modified
dysfunction (nonuniversal), choking with barium swallow)
eating, symptoms exaggerated
by feeding
Gastroesophageal Symptoms sometimes related 24-hour esophageal pH monitoring, multichannel
reflux to eating, vomiting, refusal to intraluminal impedance monitoring
eat, failure to thrive
Vascular ring or Persistent symptoms, starts Barium swallow, MRI
sling early in infancy, may be
exaggerated by position,
homophonous wheeze
Tracheal stenosis Persistent symptoms, with or Chest radiograph, CT scan, bronchoscopy
without stridor, homophonous
wheeze
Mediastinal nodes Persistent symptoms, localized Chest radiograph, CT scan
or mass wheezing, no response to
bronchodilator, systemic
symptoms of underlying
disease

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Immunodeficiency Recurrent sinopulmonary Immunoglobulins, vaccine responses
infections, crackles, FTT,
clubbing
Primary ciliary Persistent sinusitis and otitis Ciliary biopsy, with or without genetic testing
dyskinesia media with draining ears,
recurrent respiratory
infection, wet cough with
sputum production, crackles,
clubbing, FTT
Vocal cord Inspiratory stridor, poor Exercise testing, pulmonary function tests,
dysfunction response to bronchodilators, laryngoscopy while symptomatic
absent symptoms during sleep,
teenage, exercise related
Bronchiolitis History of predisposing Chest CT scan, lung biopsy
obliterans disease, ie, viral infection or
transplantation, dyspnea,
persistent wheezing

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CHILDHOOD ASTHMA
DEFINITION
• ASTHMA is a chronic inflammatory condition of the lung airways resulting in
episodic airflow obstruction. (Which is reversible obstruction)
ETIOLOGY AND PATHOGENESIS
ASTHMA TRIGGERS
I. COMMON VIRAL RESPIRATORY TRACT INFECTION
II. AEROALLERGENS IN SENSITIZED ASTHMATIC PATIENTS
▪ Indoor Allergens
▪ Animal dander
▪ Dust mite
▪ Cockroaches
▪ Molds
▪ Seasonal Aeroallergens
▪ Pollens (trees, grasses, weeds)
▪ Seasonal molds
III. AIR POLLUTANTS
▪ Environmental tobacco smoke Figure 49 Etiology and pathogenesis of
Asthma
▪ Ozone
▪ Nitrogen dioxide VI. Cold dry air
▪ Sulfur dioxide VII. Exercise
▪ Particulate matter VIII. Crying, laughter,
▪ Wood- or coal-burning hyperventilation
smoke IX. COMORBID CONDITIONS
▪ Mycotoxins ▪ Rhinitis
▪ Endotoxin ▪ Sinusitis
▪ Dust ▪ Gastroesophageal reflux
IV. STRONG OR NOXIOUS ODORS OR X. DRUGS
FUMES ▪ Aspirin and other
▪ Perfumes, hairsprays nonsteroidal
▪ Cleaning agents antiinflammatory drugs
V. OCCUPATIONAL EXPOSURES ▪ β-Blocking agent
▪ Farm and barn exposures
▪ Formaldehydes, cedar,
paint fumes

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EPIDEMIOLOGY
▪ Childhood asthma is among the most common causes of childhood emergency
department visits, hospitalizations, and missed school days.
▪ Worldwide, childhood asthma appears to be increasing in prevalence.
▪ Asthma is more prevalent in modernized and western countries.
▪ In contrast, children living in rural areas of developing countries and farming
communities with domestic animals are less likely to experience asthma and
allergy.
▪ Asthma prevalence is correlated well with:
o Allergic rhino conjunctivitis and
o Atopic eczema prevalence
TYPES AND PATTERNS OF ASTHMA

▪ Four patterns of infant wheezing:
A. NEVER WHEEZERS (51%) – Healthy children who never wheezed
B. EARLY, TRANSIENT WHEEZERS (20%) – began wheezing before 3 years of
age and resolved by 6 years of age
▪ characterized by lower lung function at birth which improves with
growth resulting in resolution of wheezing by age 3
▪ Primarily triggered by common respiratory viral infections
C. PERSISTENT WHEEZERS (14%) – began wheezing before 3 years of age and
was still present at 6 years of age
▪ characterized by declining lung function and wheezing before and
after age 3
▪ Associated with atopy
• Clinical (e.g., atopic dermatitis in infancy, allergic rhinitis,
food allergy)
• Biologic (e.g., early inhalant allergen sensitization,
increased serum IgE, increased blood eosinophils)
D. LATE-ONSET WHEEZERS (15%) – develop wheezing between 3 and 6 years
of age
▪ Characterized by relatively stable lung function and wheezing
that does not begin until after age 3.
NB: Children in the persistent wheezing and late-onset wheezing groups are at
increased risk for persistent asthma-like symptoms into adolescence and adulthood;
ASTHMA PREDICTION
▪ Early Childhood Risk Factors for Persistent Asthma include:

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▪ Parental asthma* ▪ Allergy:
o Atopic dermatitis o Inhalant allergen
(eczema)* sensitization*
o Allergic rhinitis o Food allergen
o Food allergy sensitization
▪ Severe lower respiratory tract infection:
o Pneumonia *Indicates – Major risk factors
o Bronchiolitis requiring hospitalization
▪ Wheezing apart from colds
▪ Male gender
▪ Low birthweight
▪ Environmental tobacco smoke exposure
▪ Reduced lung function at birth
▪ Formula feeding rather than breastfeeding
▪ Asthma at age of 7-10 yr
▪ Moderate to severe asthma
ASTHMA PREDICTIVE INDEX (API)

▪ It identifies those children who will continue wheezing into older childhood.
▪ It was derived from children who had wheezed at least once during the first
three years of life.
Table 65 ASTHMA PREDICTIVE INDEX (API)
THE MAJOR CRITERIA THE MINOR CRITERIA
▪ Clinician-diagnosed eczema ▪ Clinician-diagnosed allergic
rhinitis,
▪ Parental asthma ▪ Wheezing apart from colds,
▪ Inhalant allergen sensitization ▪ ≥4% peripheral blood eosinophil
(this criterion is added on
nelson)
▪ Clinician-diagnosed eczema ▪ Food allergen sensitization
▪ A positive loose index: any parental report of wheezing at two or three years of
age and either one major criterion or two minor criteria.
o Four times more likely to have active asthma at 6, 8, 11, or 13 years of
age
▪ A positive stringent index: frequent wheezing (score of ≥3, scale: 1 to 5, from
"very rarely" to "on most days") plus the same combination of major or minor
criteria.
▪ Seven times more likely to have active asthma at 6, 8, 11, or 13 years of age.

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NB: The sensitivity of the API index is low (15 to 57 PERCENT). However, the API has a
high negative predictive value (helps identify children that have a low probability of
having later asthma when the API is negative).
Allergy in young children with recurrent cough and/or wheeze is the strongest
identifiable factor for the persistence of childhood asthma.
CLINICAL PRESENTATION:
▪ Intermittent dry coughing
▪ expiratory wheezing
▪ shortness of breath
▪ Chest congestion and tightness
▪ intermittent, nonfocal chest pain – in younger children
▪ self-imposed limitation of physical activities,
▪ general fatigue (possibly resulting from sleep disturbance)
▪ Difficulty keeping up with peers in physical activities.
Worse at night or sleep - especially during prolonged exacerbations triggered by

respiratory infections or inhalant allergens. Daytime symptoms - linked with physical
activities or play
▪ Fast breathing
▪ Hypoxia (oxygen saturation < 90%)
▪ Absence of fever
▪ Expiratory wheezing
▪ Prolonged exhalation phase
▪ Decreased breath sounds (commonly the right lower posterior lung field -
regional hypoventilation caused by airways obstruction)
▪ Rhonchi and crackles (excess mucus production and inflammatory exudate)
▪ hyperinflation of the chest
▪ In severe exacerbations (the greater extent of airways obstruction):
o inspiratory and expiratory wheezing
o increased prolongation of exhalation
o poor air entry
o suprasternal and intercostal retractions
o nasal flaring
o Accessory respiratory muscle use
o silent chest (no wheezing heard) – no air entry by complete obstruction.

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If the diagnosis is uncertain, quick resolution (within 10 min) or convincing
improvement in symptoms and signs of asthma with administration of an inhaled
short-acting β-agonist (SABA - albuterol) is supportive of the diagnosis of asthma.
INVESTIGATIONS
A. Lung function tests – can help to confirm the diagnosis of asthma and to
determine disease severity.
B. Exhaled nitric oxide – helps diagnose asthma, assess asthma control and
adherence with ICS therapy, predict response to ICS therapy, and predict future
asthma exacerbations.
C. Radiology - hyperinflation and peribronchial thickening and identify asthma
mimics and complications of asthma.
D. Allergy testing to assess sensitization to inhalant allergens
LUNG FUNCTION ABNORMALITIES IN ASTHMA:

▪ Spirometry
o Airflow limitation:
▪ Low FEV1 (relative to percentage of predicted norms)
▪ FEV1/FVC ratio <0.80
▪ Bronchodilator response assesses reversibility of airflow limitation.
▪ Reversibile – if an increase in either FEV1 >12% or predicted FEV1
>10% after inhalation SABA*
▪ Exercise challenge:
▪ Worsening in FEV1 ≥15%*
▪ Daily peak expiratory flow (PEF) or FEV1 NB: * - means Main criteria
monitoring: day-to-day and/or AM -to-PM variation consistent with asthma.
≥20%*
▪ Exhaled nitric oxide (FeNO)
o A value of >20 ppb – diagnose asthma
o FeNO can be used to predict response to ICS therapy:
▪ <20 ppb: Unlikely to respond to ICS because eosinophilic
inflammation unlikely
▪ 20-35 ppb: Intermediate, may respond to ICS
▪ >35 ppb: Likely to respond to ICS because eosinophilic
inflammation is likely
ASTHMA MASQUERADERS (COMMON DDX OF CHILDHOOD ASTHMA)

▪ Upper Respiratory Tract Conditions
o Allergic rhinitis
o Chronic rhinitis

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o Sinusitis
▪ Middle Respiratory Tract Conditions
o Laryngotracheobronchomalacia
o Laryngotracheobronchitis (e.g., pertussis)
o Vocal cord dysfunction
o Foreign body aspiration
o Chronic bronchitis from environmental tobacco smoke exposure
▪ Lower Respiratory Tract Conditions
o Viral bronchiolitis
o Gastroesophageal reflux
MANAGEMENT OF CHILDHOOD ASTHMA

(SOURCE: NELSON 21ST ED-2020 AND UPTODATE 2022)
The key components to optimal asthma management are:
1) Assessment and monitoring of disease activity;
o Assess asthma severity
o Monitor control
2) Education to enhance knowledge & skills for self-management
3) Identification and management of precipitating factors and comorbid conditions
4) Appropriate selection of medications
5) Management of acute exacerbations
The long-term goal of asthma management is optimal asthma control by reducing the
components of both.
• Impairment
o Prevent chronic symptoms
o Prevent sleep disturbance
o Infrequent SABA need
o Maintain (near) normal lung function
o Maintain normal activity
• Risk
o Prevent exacerbations
o Reduce exacerbation severity/duration
o Prevent reduced lung growth
o No (minimal) adverse effects of therapy.

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ASTHMA SEVERITY ASSESSMENT
• Assessing asthma severity will be done in patients not receiving controller
therapy depending on different age groups as follows:
Table 66 Asthma Severity Assessment (Age 0-4)
Components of Classification of Asthma severity (For children aged 0 – 4 yrs)
severity Intermittent Persistent
Mild Moderate Severe
Symptoms ≤ 2 days / wk >2 days / wk (but Daily Throughout the day
not daily)
Night time 0 1 – 2 times/ 3 – 4 times/ >1 times / week
awakening month month
SABA use for ≤ 2 days / wk >2 days / wk (but Daily Several times / day
symptom control not daily) and not
more than 1× on
any day
Interference with None Minor limitation Some limitation Extreme limitation
normal activity
Exacerbations 0 – 1 / year ≥ 2 in 6 months, or
requiring oral ≥ 4 wheezing episode lasting > 1 day PLUS risk factor for
systemic steriod persistent asthma
Recommended step for initiating therapy
Step 1 Step 2 Step 3 and Step 3 and consider

consider a short a short course of
course of systemic systemic CS
CS
Table 67 Asthma Severity Assessment (Age 5-11)
Components of Classification of Asthma severity (For children aged 5 - 11 yrs)

severity Intermittent Persistent
Mild Moderate Severe
Symptoms ≤ 2 days / wk >2 days / wk Daily Throughout the day
(but not daily)
Night time ≤ 2 days/ 3 – 4 times/ > 1 times /week 7 times /week
awakening month month (but not nightly)
SABA use for ≤ 2 days / wk >2 days / wk Daily Several times / day
symptom control (but not daily)
Interference with None Minor Some limitation Extremely limited
normal activity limitation
Lung function Normal FEV1 FEV1 ≥ 80% FEV1 = 60 - 80% FEV1 < 60%
between FEV1/FVC >80% FEV1/FVC = 75 - FEV1/FVC < 75%
80%

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exacerbations
FEV1 > 80%
FEV1/FVC
>85%
Exacerbations 0 – 1 / year ≥ 2 in 1 year
requiring oral
systemic steriod
Recommended step for initiating therapy
Step 1 Step 2 step 3 step 3 (medium, dose ICS)
(medium, dose or Step 4 and consider short
ICS) and course of OCS
consider short
course of OCS
• The level of asthma severity is based on the most severe impairment or risk
category.
• The initial treatment recommendation will vary by the level of asthma severity
and age group.
• There are 6 treatment steps correlated to the level of asthma severity. (As
described in the table below)
a. Patients with intermittent asthma are at – Step 1
b. Patients with mild persistent asthma are at – Step 2
c. Patients with moderate persistent asthma at – Step 3 or 4
d. Patients with severe persistent asthma at – Step 5 or 6
• The NIH guidelines emphasize initiating higher-level controller therapy at the
outset to establish prompt control, with measures to “step-down” therapy once
good asthma control is achieved.
NB: The stepwise approach is meant to assist, not replace, the clinical decision making
required to meet individual patient needs.

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Table 68 Stepwise approach for managing Asthma in children
Stepwise approach for managing Asthma in children
Age Intermittent Persistent asthma
asthma
Step 1 Step Step 3 Step 4 Step 5 Step 6
2
0-4 SABA PRN Low- Medium-dose ICS Medium- High-dose High-dose ICS +
yr (per need) dose dose ICS + ICS + either either LABA or
ICS either LABA or LTRA and OCS
LABA or LTRA
LTRA
5-11 SABA PRN Low- Either low-dose Medium- High-dose High-dose ICS +
yr dose ICS ± LABA, dose ICS + ICS + LABA LABA and OCS
ICS LTRA, or LABA
theophylline or
Medium-dose ICS
12 & SABA PRN Low- Low-dose ICS + Medium- High-dose High-dose ICS +
above dose LABA or dose ICS + ICS + LABA LABA and OCS
ICS Medium-dose ICS LABA
ASTHMA CONTROL ASSESSMENT

• Asthma control is dynamic and refers to the day-to-day variability of an
asthmatic patient.
• Assessing asthma control will be done in patients already receiving controller
therapy, in order to adjust therapy accordingly and is categorized in 3 levels as
follows:
ASTHMA MANAGEMENT TYPES

• Control Classification
• Clinical assessment while asthma being managed and treated
o Well controlled
o Not well controlled
o Very poorly controlled
MANAGEMENT PATTERNS
• Easy-to-control: well controlled with low levels of daily controller therapy
• Difficult-to-control: well controlled with multiple and/or high levels of
controller therapies

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• Exacerbators: despite being well controlled, continue to have severe
exacerbations
• Refractory: continue to have poorly controlled asthma despite multiple and high
levels of controller therapies.
Table 69 Assessing Asthma Control and Adjusting Therapy in Children
COMPONENTS OF CONTROL Assessing Asthma Control and Adjusting Therapy in Children
Well controlled Not well Very poorly controlled
controlled
Symptoms ≤2 days/wk but >2 days/wk or Throughout the day
not more than multiple times on
once on each day ≤2 days/wk
Night time 0-4 yr ≤1×/mo >1×/mo >1×/wk
awakening
5-11 yr ≤1×/mo ≥2×/mo ≥2×/wk
≥12 yr ≤2×/mo 1-3×/wk ≥4×/wk
SABA use for symptom control ≤2 days/wk >2 days/wk Several times per day
Interference with normal None Some limitation Extreme limitation
activity
Lung function 5-11 yr FEV1 >80% FEV1 = 60-80% FEV1 <60%
FEV1/FVC >80% FEV1/FVC = 75- FEV1/FVC <75%
80%
≥ 12 yr FEV1 >80% FEV1 = 60-80% FEV1 <60%

Exacerbations 0-4 yr 0-1/yr 2-3/yr >3/yr
requiring oral
systemic steroid ≥5 yr 0-1/yr ≥2/yr
NB: Assess impairment domain by caregiver’s recall of previous 2-4 wk. And inquiring
whether the patient’s asthma is better or worse since the last visit.
• Children whose status does not meet all the criteria of well-controlled asthma
are determined to have either not well-controlled or very poorly controlled
asthma, which is determined by the single criterion with the poorest rating.
• After assessing the asthma control, if:
• Well controlled:
o Maintain current step with regular follow-up every 1-6 month to
maintain control.
o Consider step down if well controlled for at least 3 months.
• Not well controlled:
o Step up by 1 step and reevaluate in 2-6 wk.
• Poorly controlled:
o Step up by 1-2 steps and reevaluate In 2 wk.

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o Consider short course of OCS.
• If no clear benefit in 4-6 wk, consider alternative diagnoses or adjusting

therapy.
NB: Before step-up therapy:

• Review adherence to medications, inhaler technique, and environmental
control;
• If alternative treatment option was used in a step, discontinue it and use
preferred treatment for that step.
• Referral to the specialist is recommended for treatment step 3 and more (for <4
years child) and treatment step 4 and more (for >5 years child).
• Regular follow-up visits are required:
o Twice yearly (more often if asthma not well controlled – every 2-6 wk
until good asthma control is achieved)
o Monitor lung function (spirometry) at least annually.
PRODUCTIVE CLINIC VISITS FOR ASTHMA HAS THE FOLLOWING KEY ELEMENTS AT
EACH VISITS
• Assessing Asthma control
• Specifying the goal of Asthma management
• Patient and parent education on basic facts about Asthma:
o Contrast normal vs asthmatic airway
o Pathogenesis of asthma
o Long-term-control and quick-relief medications
o Concerns about potential adverse effects of asthma pharmacotherapy.
o Teach, demonstrate, and have patient show proper technique for Inhaled
medication use (spacer use with metered-dose inhaler).
• Investigate and manage factors that contribute to asthma severity:
o Reduce environmental exposures/triggers
o Comorbid conditions: GER, rhinitis and sinusitis
▪ These conditions can mimic asthma symptoms and lead to
misclassification of asthma severity and control. Effective
management of these conditions may improve asthma symptoms
and disease severity, such that less asthma medication is needed
to achieve good asthma control.
• Regular follow up visit
THERE ARE 2 GROUPS OF ASTHMA PAHARMACOTHERAPY:

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1) Long term controller: (ICS, systemic CS-Prednisone, prednisolone, and
methylprednisolone, LABA- salmeterol, formoterol, ICS/LABA
combination- fluticasone/salmeterol, LTRA, LAMA-tiotropium, Allergen
immunotherapy.)
2) Quick reliever (“rescue” medication): (SABA, ipratropium bromide)
INHALED CORTICOSTEROID
• It is a first-line treatment for persistent asthma.
• ICS requires weeks to months of daily administration for optimal efficacy to
occur.
• It helps:
o Improves lung function and quality of life;
o Reduces: asthma symptoms, AHR, use of “rescue” medications; the need
for prednisone, urgent care visits, and hospitalizations (by approximately
50%), risk of death.
• The drugs are: Beclomethasone, Fluticasone propionate, fluticasone furoate,
budesonide, mometasone furoate, ciclesonide, and others.
NB: Inhaled medications are delivered in:

• MDI (aerosolized form)
• DPI formulation, or
• Nebulizer (suspension form)
• MDI are recommended to use a spacer device.
• Spacer device helps:
o decrease the coordination required to use MDIs, especially in young children;
o improve the delivery of inhaled drug to the lower airways; and
o Minimize the risk of drug and propellant-mediated oropharyngeal adverse
effects (dysphonia and thrush).
OPTIMAL INHALATION TECHNIQUE IS CHARACTERIZED BY

• A slow (5 sec) inhalation then a 5-10 sec breath hold. No
waiting time is required between puffs of medication.
• But for preschool age children (different technique is
used);
o Spacer and mask are used
o Each puff is administered with regular breathing for
about 30 sec or 5-10 breaths;
o A tight seal must be maintained;
o Note that this technique will not deliver as much
medication per puff as the optimal MDI technique. Figure 50 Spacer and Mask

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• MDI inhaler demonstration video:
https://www.youtube.com/watch?v=Y52QUekiG5U
ADVERSE EFFECTS OF ICS:
• Local: oral candidiasis (thrush) and dysphonia (hoarse voice)
• Systemic: growth suppression, osteoporosis…
The risk of adverse effects is related to the dose and frequency of administration.
• High doses (≥1,000 µg/day in children) and frequent
administration (4 times/day) are more likely to have both
local and systemic adverse effects.
• Nebulizer usage video:
https://www.youtube.com/watch?v=idL717ww3jE
ASTHMA EXACERBATIONS AND THEIR MANAGEMENT

• Asthma exacerbations are acute or sub-acute episodes of
progressively worsening symptoms and airflow obstruction.
• It often worsens during sleep (between midnight and 8 AM)
• Its complications include:
Figure 51 Nebulizer
o Atelectasis (common)
o Pneumomediastinum and pneumothorax (rare)
• Status asthmaticus is a severe exacerbation of asthma that does not improve
with standard therapy.
• Manifestation:
o a persistent cough, increased respiratory rate, retractions, wheezing, or
inability to speak in full sentences (particularly in the setting of an upper
respiratory infection or exposure to a known asthma trigger)
o signs and symptoms of severe exacerbation (need treatment at
emergency department)
o marked breathlessness, dyspnea, retractions, tachypnea or labored
breathing, cyanosis, use of accessory muscles, and mental status changes
(drowsiness), a silent chest with poor air exchange, inability to speak
more than short phrases, and severe airflow limitation (PEF or FEV1 value
<50%.
TREATMENT OF EXACERBATIONS:
• Assessment of severity and risk factor of asthma morbidity and mortality
• Oxygen
• Systemic medical treatment
ASSESSMENT OF EXACERBATION SEVERITY

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• Take a focused history and physical examination (nearly concurrently with
initiation of treatment)
HISTORY:
• Suspected cause of the exacerbation (eg, viral infection, environmental or food
allergen exposure)
• The time of onset of exacerbation
• Current medications
• Recent use of beta agonists (dose and frequency) and/or systemic
glucocorticoids
• Risk factors for severe, uncontrolled disease (see below)
FOCUSED EXAMINATION:
• Vital signs and pulse oximetry
• Assessment of level of consciousness, anxiety, and agitation
• Assessment of breathlessness, wheezing, air entry, accessory muscle use, and
retractions
There are several asthma severity scores designed to evaluate initial exacerbation
severity, assess response to treatment, and help determine if hospitalization is
necessary.
Table 70 Pulmonary index score (PIS)
Score Respiratory Wheezing Inspiratory/ Accessory Oxygen
rate expiratory muscle use saturation
ratio
<6 ≥6 years
years old
old
0 ≤30 ≤20 None* 2:1 None 99 to 100
1 31 to 21 to 35 End expiration 1:1 + 96 to 98
45
2 46 to 36 to 50 Entire expiration 1:2 ++ 93 to 95
60
3 >60 >50 Inspiration and 1:3 +++ <93
expiration or
minimal air entry
• The total score ranges from 0 to 15. The PIS is interpreted as follows:
o Mild exacerbation: <7
o Moderate exacerbation: 7 to 11
o Severe exacerbation: ≥12

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Table 71 Pediatric respiratory assessment measure (PRAM)
Signs 0 1 2 3
Suprasternal Absent Present
indrawing
Scalene retractions Absent Present
Wheezing Absent Expiratory Inspiratory and Audible without
only expiratory stethoscope/silent chest with
minimal air entry
Air entry Normal Decreased Widespread Absent/minimal
at bases decrease
Oxygen saturation >93% 90 to 93% <90%
on room air
Severity classification PRAM clinical score
Mild 0 to 4
Moderate 5 to 8
Severe 9 to 12
Impending respiratory 12+ following lethargy, cyanosis, decreasing respiratory
failure effort, and/or rising pCO2
Assessment of Risk factor for asthma morbidity and mortality (Fatal asthma attack)
• Previous life-threatening exacerbation
• Asthma attack despite current oral glucocorticoid use
• More than 1 hospitalization for asthma in the past year
• 3 or more emergency department visits for asthma in the past year
• More than 2 canister of SABA use per month
• Cardiovascular or chronic lung disease
• Illicit drug use or major psychosocial problems
• Food allergy
• Not taking inhaled glucocorticoids
• History of poor adherence with asthma medications or home action plan.
• Environmental allergen exposure

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HOME MANAGEMENT OF ASTHMA EXACERBATIONS ALGORITHM
Assess exacerbation severity and risk of fatal

asthma attack
Severe exacerbation and/or high risk Less severe exacerbation and low risk
• Inhaled beta agonist: • Inhaled beta agonist:
o SABA (salbutamol MDI 4 puffs or 2.5 to 5mg o SABA (salbutamol MDI 2 – 4 puffs or
solution by nebulizer) or
1.25 – 2.5 mg Nebulizer)
o Alternative (for >4 yr): ICS plus rapid onset
o Alternative (for >4 yr): ICS plus LABA
LABA (Budesonide-formoterol MDI 2 puffs)
1 – 2 puffs
• Give second beta agonist after 20 min while
immediately transporting to ED • Give up to 2 beta agonist 20 min apart
• Oral glucocorticoid (prednisone/prednisolone • Assess response 10 – 20 min after each
2mg/kg – max 60 mg) dose.
Good response Incomplete response Poor response

No wheezing or dyspnea/tachypnea Persistent wheezing and Marked wheezing and dyspnea after 2 beta
after 1 to 2 beta agonist dose dyspnea/tachypnea after 2 beta agonist doses.
OR Symptoms return within 2 hours of
AND Symptom do not return within agonist doses.
treatment
4 hours of treatment OR symptoms return within 4 hours of
• Give OCS
• Continue inhaled beta agonist treatment. • Repeat inhaled beta agonist
Q4 hrs for 24 to 48 hrs PRN • Immediately transport to ED.
• Contact physician for follow up
OCS available at home

• Give OCS: prednisone/prednisolone 2mg/kg – OCS NOT available at home
max 60 mg • Contact clinician urgently
• Continue inhaled beta agonist up to Q2 hrs • Consider third dose of beta agonist
for up to 8 hours after OCS, THEN Q4 hrs for
24 – 48 hour, and then Q4 hrs PRN
• Contact clinician
EMERGENCY DEPARTMENT (ED) MANAGEMENT OF ASTHMA EXACERBATIONS

• Severity assessment of asthma exacerbation severity in the urgent or emergency
care setting as:
o Mild – normal alertness, slight tachypnea, expiratory wheezing only, a
mildly prolonged expiratory phase (inspiratory-to-expiratory ratio of 1:1

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rather than the normal 2:1), minimal accessory muscle use, SpO2 of
>95%.
o Moderate – normal alertness, tachypnea, wheezing throughout expiration
with or without inspiratory wheezing, an inspiratory-to-expiratory ratio of
approximately 1:2, significant use of accessory muscles, and SpO2 92 to
95%
o Severe – inability to repeat a short phrase, extreme tachypnea,
inspiratory and expiratory wheezing, an inspiratory-to-expiratory ratio
exceeding 1:2, very poor aeration, significant use of accessory muscles,
and SpO2<92%.
o Impending respiratory failure - cyanosis, respiratory rate may be
inappropriately normal to low, lethargy or agitation, SpO2<90%, and
respiratory acidosis.
• We can use the Asthma severity scores too (see above).
NB: Peak flow meter is rarely used in the acute setting to assess lung function in
children during an exacerbation because it has several limitations related to effort and
technique. Peak flow measurements require maximal effort, which is difficult to
assess. Poor technique can also lead to erroneous data.
• Based on the severity, the asthma exacerbation will be treated as follows at
emergency department (see algorithm below).
ELEMENTS OF TREATMENT INCLUDE:

• Supplemental oxygen: to maintain saturation of ≥92%. All nebulized
medications should also be delivered with oxygen, generally at a flow rate of 6
to 8 L/min.
• Bronchodilators:
o Inhaled SABA:
▪ MDI (90mcg/puff): 4 to 8 puff every 20 minutes for 3 doses, then
up to every 1-hour PRN
✓ Children weighing 5 to 10 kg - 4 puffs
✓ Children weighing 10 to 20 kg - 6 puffs
✓ Children weighing >20 kg - 8 puffs
▪ Nebulizer:
✓ Intermittent (in total solution volume of 3 to 4 mL and an
oxygen flow rate of 6 to 8 L/min): 0.15 mg/kg per dose
(minimum 2.5 mg, maximum 5 mg/dose) up to every 20
minutes for up to 3 doses, then if no improvement and no
adverse effect, 0.15 to 0.3 mg/kg (maximum 10 mg) up to

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every 30 minutes as needed or switch to continuous
therapy.
✓ Continuous (if severe and in critical care setting): 0.5 mg/kg
per hour (maximum 20 mg per hour) by large-volume
nebulizer.
• 5 to 10 kg – 5 to 7.5 mg per hour
• 10 to 20 kg – 10 to 12.5 mg per hour
• >20 kg – 15 to 20 mg per hour
o Ipratropium bromide:
▪ Nebulizer (250 mcg/ml): preferred than MDI and given together
with SABA Q20 min for 3 doses.
<20 kg – 250 mcg/dose
≥20 kg – 500 mcg/dose
▪ MDI (18 mcg/puff): 4 to 8 puffs every 20 minutes as needed for up
to 3 hours. May be combined with SABA.
o IV magnesium sulfate:
▪ It has minimal adverse effects.
▪ It causes relaxation of bronchial smooth muscle.
▪ Given for age >4yrs and life-threatening exacerbation, severe
exacerbation and unresponsive moderate exacerbation.
▪ 25 to 75 mg/kg or Av. 50 mg/kg (maximum 2 grams) IV
administered over 20 minutes.
o Parenteral beta agonist:
▪ SC/IM epinephrine: 0.01 mg/kg IM or SC (max 0.4 mg/dose) Q10
min as needed until clinical improvement.
▪ IV terbutaline
• Anti-inflammatory:
o Dexamethasone (preferred) 0.3 to 0.6 mg/kg (max 12 to 16 mg/day) by
PO, IM, or IV.
o Prednisone/prednisolone: 1 to 2 mg/kg (max 60 mg/day) PO for the first
dose, and then 0.5 to 1 mg/kg BID for subsequent doses for 3- to 10-day.
o Methylprednisolone: 1 to 2 mg/kg (max 125 mg/day) IV
• NB: Timely administration of oral glucocorticoids for serious asthma
exacerbations is probably the single most effective strategy for reducing
hospitalizations for acute asthma exacerbations and relapses after ED visits.
INDICATION FOR HOSPITALIZATION

• Severe exacerbations that do not adequately improve within 1-2 hr of intensive
treatment,
• Beta-agonist therapy more often than four hours

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• Requirement for supplemental oxygen/low saturation an hour or more after
commencement of initial therapy
• Inability to self-hydrate
• High-risk features for asthma morbidity & mortality (see table)
• Inadequate access to medical care
• Poor social support system at home
INDICATION FOR ICU ADMISSION:

• Severe respiratory distress, poor response to therapy, and concern for potential
respiratory failure and arrest.
DISCHARGE
• Children with marked improvement within the first one to two hours of therapy
may be discharged to home with:
o Discharge medication
o Discharge education
o Follow up appointment: within one week of the ED visit.
NB: Timely administration of oral glucocorticoids for serious asthma exacerbations is
probably the single most effective strategy for reducing hospitalizations for acute
asthma exacerbations and relapses after ED visits.
PROGNOSIS
• Recurrent coughing and wheezing occurs in 35% of preschool-age children.
• One third of them continue to have persistent asthma into later childhood,
• and two thirds improve on their own through their teen years.
PREVENTION
• Avoidance of environmental tobacco smoke (beginning prenatally),
• prolonged breastfeeding (>4 mo),
• an active lifestyle, and
• a healthy diet
• A hygiene hypothesis purports that naturally occurring microbial exposures (in
rural areas) in early life might drive early immune development away from
allergic sensitization.

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EMERGENCY DEPARTMENT (ED) MANAGEMENT OF ASTHMA

EXACERBATIONS ALGORITHM
Assess exacerbation severity by clinical examination or PIS score
Severe
Moderate Mild
• Supplement oxygen to target of SpO2
>92% • Supplement oxygen to target of • Give Albuterol by MDI Q20-30
• Give Albuterol/ipratropium by SpO2 >92% minutes for 3 doses total.
nebulizer continuously for 1 hour or • Give Albuterol/ipratropium by • Give OCS (if no improvement after
intermittently Q20-30 mins for 3 nebulizer continuously for 1 hour first albuterol treatment or if patient
doses then continuous nebulized or intermittently Q20-30 mins for has history of severe/frequent
Albuterol only OR alternative: IM/SC 3 doses exacerbations).
epinephrine or terbutaline. • Give systemic glucocorticoids (oral
• Give IV glucocorticoids is suitable)
• Give IV magnesium sulfate
• If impending RF, consult ICU
Reassess after initial treatment
Poor response with Incomplete response with

ongoing severe S/Sx mild-moderate S/Sx
Admit to ICU and assess Admit to hospital for
alternative Dx continued treatment
Reassess after initial
treatment
Incomplete response Good response with no symptom or

Poor response • Give Albuterol by nebulizer continuously or Q30-45 minutes diminished symptom that is sustained
for additional 1 to 3 hours. for at least 60 minutes after recent
• Give IV magnesium sulfate albuterol dose. → Discharge to home
(if not already given and moderate Sx)
Reassess
Poor response Incomplete Good response

• Admit to hospital and consult ICU response
• Discharge to home with:
• While awaiting admission: Admit to hospital for o Inhaled albuterol Q4-6 hours for 3 days
o Albuterol by nebulizer continuously continued treatment o OCS for 3-5 days course
o IV magnesium sulfate (if not already o ICS if controller Rx indicated
given) or by
Prepared if given, IV Terbutaline.
Graduating Class of 2015 E.C (2022/23)
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SAMPLE HISTORY OF ASTHMA

I\D: This is _________ a 6 years old boy from Jimma town (asthma more common in urban town)
currently attending lower KG at school.
C/C: cough and wheeze of 2 days duration
HPI:
He was relatively healthy 2 days back at which time he started to experience an intermittent dry
cough which worsens at night time and sometimes early in the morning but it is not associated with
feeding (r/o: Gastro esophageal reflux). His mother also noticed a noisy breathing like a wheeze
which is not associated with runny nose, sneezing and nasal stiffness (r/o: common cold). She denies
that he has any prior wheezing episodes.
Associated with this, he also has history of difficulty of breathing and difficulty of keeping up with his
friends at school during different physical activities and playing. For these reasons, he discontinued to
attend school for 2 days.
Yesterday, his symptoms worsened during day time while playing and jumping around the house with
his brother and had a difficulty of catching his breath and continuous cough. Then his mother rushed
him to this hospital emergency department and he was given a drug which is inhaled through his
mouth. After few minutes he became well.
He has a past history of food allergy for peanut butter and a skin allergy.
He is fully vaccinated. (RF for pneumonia, some etiology of acute bronchiolitis).
He was first exclusively breastfed for 6 months and had been breastfeeding for 2 years. (RF for acute
bronchiolitis).
He lives in a total family size of 5. He has one big brother aged 8 years, one younger sister aged 3
years, and his both parents. All of them are healthy. They live in a house with 3 rooms, 2 of them have
a single window in each while the other has 2 Windows and 2 doors which is separated from the
kitchen and toilet. They have no any animal in the house. (RF for acute bronchiolitis, pneumonia).
He started to sit unsupported at age of 8 months and walk steadily unsupported at age of 1 and half
years. At age of 4, he started to run up and downstairs, to dress and undress himself without help and
to speak fully understandable sentences. (If failure to thrive- CF, immunodeficiency).
He was born by spontaneous vaginal delivery as his other siblings at gestational age of 39 weeks with a
birth weight of 2.5 kg with no neonatal and maternal complications. (Congenital abnormalities or
bronchopulmonary dysplasia)
Otherwise,
He has no history of previous asthma diagnosis and treatment
He has no history of second-hand tobacco and other smoke exposure. (Bronchiolitis, asthma)
He has no history of clear nasal discharge, sneezing (Bronchiolitis, transient asthma,
pneumonia)
He has no history of fever. (Bronchiolitis, pneumonia)
He has no history of choking (Foreign body aspiration)

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He has no history of difficulty of swallowing and any neurogenic disease. (Swallowing disorders)
He has no history of recurrent upper respiratory tract infection and poor weight gain. (Cystic
fibrosis, immunodeficiency, ciliary kinetic disorders)
He has no history of food regurgitation or vomiting (Gastroesophageal reflux)
He has no history of difficulty of making a sound and throat thightness. (Vocal cod dysfunction)
He has no history of prior surgery like lung transplantation. (Bronchiolitis obliterans)
He has no personal and family history of cardiac disease (r/o congenital heart disease),
asthma, cystic fibrosis, immunodeficiency, TB, renal disease and RVI.

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ACUTE BRONCHIOLITIS
DEFINITION
• is defined as a clinical syndrome that occurs in children <2 years of age and is
characterized by upper respiratory symptoms (eg, rhinorrhea) followed by lower
respiratory infection with inflammation, which results in wheezing and/or
crackles (rales).
ETIOLOGY
• Respiratory syncytial virus (RSV) • influenza,
- 50% of cases • Corona virus
• human metapneumovirus, • bocavirus, and
• Rhinovirus, • adenovirus.
• parainfluenza,
EPIDEMIOLOGY
• It is a leading cause of hospitalization in infants and young children.
• In tropical and semitropical climates, seasonal outbreaks of RSV usually are
associated with the rainy season.
RISK FACTORS
• Prematurity (gestational age ≤36 • crowded household,
weeks) and Low birth weight • daycare attendance,
• Age less than 12 or 24 months • being born approximately two
(more severe disease if <12 months before or after the start
weeks) of the epidemic,
• Not breastfeed • concurrent birth siblings or older
• passive smoking, siblings
• mother smoking during • high altitude (>2500 meters)
pregnancy • Male
CLINICAL COURSE
Respiratory distress ensues,
paroxysmal dry cough, dyspnea, and
irritability. Tachypnea, (which can
Exposure/contacts interfere with feeding)
with a minor Sneezing and Diminished
respiratory illness clear appetite Apnea (particularly if: very young
(within the Rhinorrhea and fever infants, Term infants at a post
previous week) conceptual age of <44 wk. and preterm
infants at post conceptual age <48 wk.)

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• Respiratory rate and oxygen saturation (is an important initial step)
• wheezing and crackles (dominant finding)
o (If no wheeze - Complete obstruction to airflow) it doesn’t R/O the Dx.
• prolonged expiration
• Increased Work of breathing - nasal flaring and retractions.
• Poorly audible breath sounds – if severe disease
DIAGNOSING BRONCHIOLITIS
• The diagnosis of acute bronchiolitis is clinical:

• A previously healthy infant presenting with a first episode of wheezing following a
period of upper respiratory symptoms.
INVESTIGATIONS
• Are not routinely recommended
o Chest radiography is not routinely indicated.
▪ Reveal if there is: associated atelectasis
o Viral testing (PCR or rapid immunofluorescence) is not routinely
recommended
MANAGEMENT
SEVERITY ASSESSMENT:
I. Severe bronchiolitis: indicated by any of the following:
• Persistently increased respiratory effort (tachypnea; nasal flaring; intercostal,
subcostal, or suprasternal retractions; accessory muscle use; grunting) as assessed
during repeated examinations separated by at least 15 minutes
• Hypoxemia (SpO2 <95 percent); SpO2 should be interpreted in the context of other
clinical signs, the state of the patient (eg, awake, asleep, coughing, etc), and
altitude
• Apnea
• Acute respiratory failure
Severe bronchiolitis requires supportive care in the inpatient setting. Supportive care
includes:
• Maintenance of adequate hydration,
• Respiratory support,
• Monitoring for disease progression

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II. Non-severe bronchiolitis: indicated by the absence of all of the above.
• Children with non-severe bronchiolitis usually can be managed in the outpatient
setting with supportive care.
• Supportive care includes:
o Maintenance of adequate hydration,
o Relief of nasal congestion/obstruction, and
o Monitoring for disease progression.
• Hospital admission is indicated if any of the following are present:
o Apnea (observed or reported)
o Persistent oxygen saturation of < 90% when breathing air
o Inadequate oral fluid intake (50–75% of usual volume)
o Severe respiratory distress – grunting, marked chest retraction or a
respiratory rate >70 breaths/minute.
o inability to breastfeed or drink, or vomiting everything
o convulsions, lethargy or unconsciousness
MANAGEMENT OF FOR BOTH NON-SEVERE AND SEVERE BRONCHIOLITIS.

• Include
o Supportive care and
o Anticipatory guidance
SUPPORTIVE MANAGEMENT
• Supplemental Oxygen: - if spo2 <90%
• Target oxygen saturations: a threshold of 90% (national guidelines in the United
States)
• Supplemental hydration
• Nutrition: Encourage the child to eat as soon as food can be taken or Nasogastric
feeding
• Frequent suctioning of nasal and oral secretions
• Antipyretic: if fever (≥ 39 ° C)
ANTICIPATORY GUIDANCE AND EDUCATION:

• Expected clinical course: Typical illness with bronchiolitis begins with upper
respiratory tract symptoms. Lower respiratory symptoms and signs develop on days 2
to 3, peak on days 3 to 5, and then gradually resolve over the course of two to three
weeks.
• Proper techniques for suctioning the nose
• The need to monitor fluid intake and output
• Avoidance of over-the-counter decongestants and cough medicines

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• Indications to return to medical care immediately: apnea, cyanosis, poor feeding, new
fever, increased respiratory rate and/or increased work of breathing (retractions,
nasal flaring, grunting), decreasing fluid intake (<75 percent of normal, no wet diaper
for 12 hours), exhaustion (eg, failure to respond to social cues, waking only with
prolonged stimulation)
• Strategies to prevent respiratory infection.
RISK FACTORS FOR SEVERE OR COMPLICATED BRONCHIOLITIS INCLUDE:

• Prematurity (gestational age ≤36 weeks)
• Low birth weight
• Age less than 12 weeks
• Chronic pulmonary disease, particularly bronchopulmonary dysplasia (also known as
chronic lung disease)
• Anatomic defects of the airways
• Hemodynamically significant congenital heart disease
• Immunodeficiency
• Neurologic disease
PROGNOSIS
• Bronchiolitis is a self-limited illness and often resolves without complications in most
previously healthy infants. Severely affected infants are at increased risk for
complications and recurrent wheezing.
• The overall mortality rate in children hospitalized bronchiolitis in developed countries
is less than 0.1%.
COMPLICATIONS
• Atelectasis (if complete obstruction)
• Pneumothorax
• Hypoxemia
• Respiratory failure
• Apnea
• Secondary bacterial infection
PREVENTION
• Hand hygiene (washing with soap or with alcohol-based rubs) to minimize transmission
of infectious agents,
• Minimizing passive exposure to cigarette smoke, and
• Avoiding contact with individuals with respiratory tract infections.

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DISCHARGE CRITERIA — Minimal clinical criteria for discharge from the hospital include:
• Respiratory rate: <60 bpm for age <6 months, <55 bpm for age 6 to 11 months, and
<45 bpm for age ≥12 months
• Caretaker knows how to clear the infant's airway using bulb suctioning
• Patient is stable while breathing ambient air: the patient remain stable for at least
12 hours prior to discharge
• Patient has adequate oral intake to prevent dehydration
• Caretakers are confident they can provide care at home
• Education of the family is complete: no smoking, proper breastfeeding

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6.5. STRIDOR AND UPPER AIRWAY OBSTRUCTION
DEFINITION
• Stridor is a harsh, musical sound during inspiration due to partial obstruction of the
lower portion of the upper airway (including the upper trachea, larynx, oropharynx
and subglottic).
• Mechanism
o During inspiration, the pressure inside the extrathoracic airway falls below
atmospheric pressure, causing airway collapse.
o In contrast, during expiration intrathoracic pressure rises on expiration and
causes airway collapse.
o Stridor is caused by the oscillation of a narrowed airway.
o It is explained by Bernoulli's Principle, which states that as the speed of a
moving fluid increases, the pressure within the fluid decreases.
•
Airflow Local area of Vacuum effect This airway Squeak
through a low pressure formed distal to walls collapse characteristic of
narrowed tube created the narrowing and vibrate stridor generated

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Table 72 DDx for Stridor
DDX Unique features

Viral croup Barking cough
Respiratory distress
Hoarse voice
If due to measles, signs of measles
Retropharyngeal Soft tissue swelling
abscess Difficulty in swallowing
Fever
Foreign body Sudden history of choking
Respiratory distress
Diphtheria Bull neck appearance due to enlarged cervical nodes
and oedema
Red throat
Grey pharyngeal membrane
Blood-stained nasal discharge
No evidence of DTP vaccination
Congenital Stridor present since birth
anomaly (laryngotracheomalacia)
Epiglottitis Soft stridor
‘Septic’ child
Little or no cough
Drooling of saliva
Inability to drink
Anaphylaxis History of allergen exposure
Wheeze
Shock
Urticaria and oedema of lips and face
Burns Swollen lips
Smoke inhalation
NB: Croup accounts for more than 90% of all cases of stridor in children. It most commonly
occurs in children 6 to 36 months of age and in preschool children, but is rare beyond age six
years.

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Table 73 Clinical Features of Croup and Epiglottitis
Clinical Features Croup Epiglottitis
Onset Over days Over hours
Preceding coryza Yes No
Cough Severe, barking Absent or slight
Able to drink Yes No
Drooling saliva No Yes
Appearance Unwell Toxic, very ill
Fever <38.5° C >38.5° C
Stridor Harsh, rasping Soft, whispering
Voice, cry Hoarse Muffled, reluctant to speak
• Diagnosis of croup is clinical, based on the presence of a barking cough and stridor,
especially during a typical community epidemic of one of the causative viruses.
CLINICAL ASSESSMENT OF A CHILD WITH A STRIDOR

• Diagnostic examinations may need to be delayed to provide appropriate initial
supportive care.
1) SECURE ABC OF LIFE

• A rapid assessment of Airway patency, breathing effort and Circulation collapse
needed to identify patients who need immediate intervention in conditions like:
o Epiglottitis
o Anaphylaxis
o Airway burns
o Foreign body aspiration
• Once the child is stable, the next step is a detailed history and physical examination
to identify the cause of the stridor.
2) HISTORY
• Characterize the stridor-
o https://www.youtube.com/watch?v=Hd7A28T0TOE hear the sound
• Age of onset:
o Neonates and infants – Congenital disorders presenting in the first few weeks of
life.
o Infants and toddlers – Croup, Foreign body aspiration and Epiglottitis
(uncommon but potentially life-threatening)
o School-aged children and adolescents – peritonsillar abscess and vocal cord
dysfunction (presenting with recurrent episodes of stridor and dyspnea)

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o All ages – Anaphylaxis and bacterial tracheitis
• Acuity of onset:
o Acute onset - within minutes or a few hours
▪ With fever – epiglottitis or bacterial tracheitis
▪ Without fever – Foreign body aspiration or anaphylaxis
o Subacute onset – over the course of a few days
▪ Laryngotracheitis (croup), Peritonsillar and retropharyngeal abscesses
o Chronic or recurrent – subglottic stenosis or exogenous compression (vascular
ring or a tumor), vocal cord dysfunction.
• Onset during:
o feeding- aspiration 2° to swallowing dysfunction, tracheoesophageal fistula,
GER
o Sleep – pharyngeal origin, Spasmodic croup
o Activity (exercise, agitated) – mild croup, vocal cord dysfunction
o Quiet/Rest - severe croup
ASSOCIATED SYMPTOMS
• Fever –
o High grade fever - serious bacterial infection (epiglottitis, peritonsillar or
retropharyngeal abscesses or bacterial tracheitis)
o Mild fever – croup
• Altered mental status (lethargy, anxiety) - an impending airway obstruction
• Drooling of saliva – epiglottis, a foreign body in the trachea, or a mass compressing
the anterior esophageal wall.
• Barking cough – croup
• Hoarseness of voice – vocal cord injury due to inflammation (croup) or paralysis
• Muffled voice – supraglottic obstruction, (such as retropharyngeal or peritonsillar
abscess or epiglottitis)
• Dysphagia - epiglottis, a foreign body in the trachea, or a mass compressing the
anterior esophageal wall.
• Choking – foreign body aspiration
• Hives – (Presence of rash, hypotension, and wheezing with acute onset of stridor) - an
allergic reaction with angioedema.
PMSHX
• Prenatal and perinatal period (infections, prematurity, complicated delivery,
necessity of intubation, and mechanical ventilation) – congenital disease
• Previous admissions secondary to respiratory diseases – chronic stridor causes
• Surgical history of the upper chest or neck - might have contributed to vocal cord
paralysis, or tracheal or subglottic stenosis

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• potential exposure to food or environmental allergens – anaphylaxis
IMMUNIZATION HISTORY
• DPT vaccination - Diphtheria
• Hib (H. influenza type b) vaccination – Epiglottitis
• Measles vaccination – croup caused by measles virus
3) PHYSICAL EXAMINATION
• General Appearance –
• Vital signs
o The height and weight –
o Failure to thrive - a chronic process
o recent weight loss - a subacute process (infection)
• HEENT
o craniofacial malformation
o swollen neck (bull neck) – Diphtheria
o grey oropharyngeal membrane (which couldn’t be scrapped) – Diphtheria
• Lymphoglandular system
o Lymphadenopathy - intrathoracic process (infection or tumor compressing the
airway)
• Respiratory –
o Inspection: both during rest and after activity
▪ Audible stridor
▪ Cyanosis, nasal flaring, and retractions.
▪ Children - sit up in a "tripod" or "sniffing" position (trunk leaning forward,
neck hyperextended, chin thrust forward) – epiglottitis (also in severe
asthma)
▪ Infants - extend their neck backwards in an effort to maximize upper
airway patency – epiglottitis Auscultation
o Stridor - heard best over the anterior neck.
▪ Inspiratory stridor – extrathoracic obstruction
▪ Expiratory stridor - intrathoracic obstruction
▪ Biphasic (inspiratory and expiratory) stridor - critical or fixed obstruction
(at any level), or obstruction between the glottis and subglottis
▪ Snoring (when asleep) or stertor (when awake) - Nasal, nasopharyngeal,
or oropharyngeal obstruction
▪ Decreased or absent air entry – severe case
• Cardiovascular findings – if complicated Diphtheria
• Skin and extremities –

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o Skin hemangiomas - Airway hemangioma possibility
o Clubbing - congenital heart disease or bronchiectasis
o Maculopapular rash – measles
4) INVESTIGATIONS
• CBC with differential
o Increased lymphocytes – viral infections (croup)
o Increased PMN cells – bacterial infections (epiglottitis)
• Viral culture – etiologic diagnosis
• Radiography
o Neck x-ray –
▪ soft tissue air-fluid levels, increased retropharyngeal space –
Retropharyngeal abscess
▪ "steeple" sign (the subglottic arch becomes edematous and shows an
inverted "V" in AP view) – croup
▪ edematous epiglottis with the thumb sign and enlarged aryepiglottic
folds in lateral view – epiglottitis
o Chest x-ray — if intrathoracic problem suspected
▪ mediastinal lymphadenopathy or masses
▪ vascular rings (a right aortic arch)
▪ foreign body aspiration (mediastinal shift, unilateral hyperinflation,
atelectasis, or actual foreign body, if radiopaque)
o CT scan of the chest and neck with contrast - diagnosis of retropharyngeal
cellulitis. also used to look for enlarged lymph nodes, tumors, aberrant
arteries, and vascular rings.
o MRI - if a vascular ring is suspected after plain radiography
• Spirometry —
o It is difficult to perform in infants and young children.
o It can be performed in children over six years of age.
o It is useful for those with chronic stridor in whom the location or nature of the
obstruction cannot be localized by the radiographic.
• Nasopharyngoscopy, laryngoscopy, and bronchoscopy - allows definitive diagnosis of
the cause of stridor.
o confirm laryngomalacia
o diagnose foreign body aspiration and remove the foreign body
o for patients with chronic or intermittent stridor
o gold standards for evaluation and diagnosis of subglottic, tracheal, and central
airway lesions

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MANAGEMENT OF CROUP
• Is based on the Westley croup score
Table 74 Westley Croup Score
Clinical feature Assigned score

Level of consciousness Normal, including sleep = 0
Disoriented = 5
Cyanosis None = 0
With agitation = 4
At rest = 5
Stridor None = 0
With agitation = 1
At rest = 2
Air entry Normal = 0
Decreased = 1
Markedly decreased = 2
Retractions None = 0
Mild = 1
Moderate = 2
Severe = 3
Discharge criteria include all of the following:
• No stridor at rest,
• Normal pulse oximetry,
• Good air exchange,
• Normal color,
• Tolerating fluids by mouth, and
• Caregivers understand instructions and are able to return for care if needed.

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Table 75 Management of Croup
Score Severity Description Management

≤2 Mild Occasional barky cough, Home treatment: Symptomatic care
no stridor at rest, mild including antipyretics, mist, and oral
or no retractions fluids
Outpatient treatment: Single dose of
oral dexamethasone 0.15 to 0.6
mg/kg (maximum 16 mg)*
3 to 7 Moderate Frequent barky cough, Single dose of oral dexamethasone
stridor at rest, and mild 0.6 mg/kg (maximum 16 mg)*
to moderate Nebulized epinephrine¶
retractions, but no or Hospitalization is generally not
little distress or needed, but may be warranted for
agitation persistent or worsening symptoms
after treatment with glucocorticoid
and nebulized epinephrine
8 to 11 Severe Frequent barky cough, Single dose of oral/IM/IV
stridor at rest, marked dexamethasone 0.6 mg/kg (maximum
retractions, significant 16 mg)*
distress and agitation Repeated doses of nebulized
epinephrine¶ may be needed
Inpatient admission is generally
required unless marked improvement
occurs after treatment with
glucocorticoid and nebulized
epinephrine
≥12 Impending Depressed level of Single dose of IM/IV dexamethasone
respiratory consciousness, stridor at 0.6 mg/kg (maximum 16 mg)
failure rest, severe retractions, Repeated doses of nebulized
poor air entry, cyanosis epinephrine¶ may be needed
or pallor Intensive care unit admission is
generally required
Consultation with anesthesiologist or
ENT surgeon may be warranted to
arrange for intubation in a controlled
setting

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MANAGEMENT OF CROUP IN OUTPATIENT AND EMERGENCY

DEPARTMENT SETTING
Diagnosis of Croup
Assess Westley Score
Mild Moderate Severe Impending RF
Supportive care (mist, Minimize Refer child to emergency

• Epinephrine with
antipyretics & fluid intake) department, minimize
discomfort/anxiety, discomfort/anxiety, allow Nebulizer
Dexamethasone 0.15-0.6
allow caregiver to hold caregiver to hold and comfort • Dexamethasone 0.15-
mg/kg (max 16 mg) PO
stat, or Prednisolone 1 and comfort child, child, administer humidified 0.6 mg/kg (max 16
air/O2 if needed
mg/kg PO stat mg) IV/IM stat
Dexamethasone 0.15-0.6 • Intubation if
mg/kg (max 16 mg) PO/IV/IM warranted
stat Dexamethasone 0.15-0.6
mg/kg (max 16 mg) PO/IV/IM
stat
Discharge home if
Epinephrine with
tolerating oral fluid, Nebulizer Admit to pediatric
Epinephrine with Nebulizer
and Provide education ICU
to caregivers with
follow-up arranged
Assess response to nebulized
within 24 hours. epinephrine
Good response; Sx Poor response; Sx

Observe for 3 – 4 hours
improvement worsens
• Antipyretics
Westley score <8?
• Encourage Oral fluid or Consider alternative Dx
• IV fluid
Yes No
Worsening of Sx (Westley
score >8)? Repeat Nebulized
Epinephrine
No Yes Admit to
pediatric ICU
Yes Discharge home, Provide education to

Recurrence of stridor No caregivers:
after 3-4 hrs.? Discharge • Anticipated course of illness
No
criteria met? • Signs of respiratory distress
Prepared by Graduating Class of 2015 E.C (2022/23) • When to seek medical assistance
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6.6. DISCUSSION OF DIFFERENTIAL DIAGNOSIS
EPIGLOTTITIS
• describes inflammation of the epiglottis.
• edema narrows the supraglottic airway and alters the shape of the epiglottis, typically
causing that structure to curl posteriorly and inferiorly into the airway.
• The epidemiology is changing rapidly because of routine vaccination against
Hemophilus influenza type B (HIB),but st
• However, HIB remains the most common pathogen associated with epiglottitis in
children.
• Other causes include other types of H influenzae (A, F, and nontypeable), H.
parainfluenzae, Streptococcus pneumoniae, Staphylococcus aureus, other
streptococci, Klebsiella, and Pseudomonas.
• Epiglottitis presents more commonly in children ages 2 to 6 years, although it can
affect children and adults of any age.
• High fever, sore throat, dyspnea, and rapidly progressing respiratory obstruction
(Dyspnea)
• Drooling and Dysphagia
• Muffled voice (Dysphonia)
• Stridor is frequently noted, but unlike croup, a cough and hoarseness are not
characteristically present.
• Children commonly sit still in the hallmark “tripod” position, leaning forward on
outstretched hands with the neck extended.
DIAGNOSIS
• Clinical suspicion- Epiglottitis should be suspected in young children,
especially those who are un- or under-immunized against Hemophilus
influenzae, type b (Hib) and who present with the characteristic clinical
features as follows:
o Tripod" position
o Anxiety
o Sore throat
o Stridor
o Drooling
Figure 52 Tripod Position
o Dysphagia
o Respiratory distress

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• The diagnosis requires visualization under controlled
circumstances of a large, cherry red, swollen epiglottis by
laryngoscopy.
• In patients with signs of total or near-total airway obstruction,
airway control necessarily precedes diagnostic evaluation.
• In a patient in whom the diagnosis is certain or probable based
on clinical grounds, laryngoscopy should be performed promptly
in a controlled environment such as an operating room or ICU.
• If epiglottitis is thought to be possible but not certain in a
patient with acute upper airway obstruction, the patient may
undergo lateral radiographs of the upper airway 1st
• Classic radiographs of a child who has epiglottitis show the
Thumb Sign. Figure 53 Thumb Sign
Lateral neck radiograph demonstrating

MANAGEMENT swollen epiglottis (Arrow).
• Until the airway is secured in young children (6 years of age or

younger),
o Avoid intravenous access,
o Unnecessary physical examination (oropharyngeal or laryngeal examination
with a tongue blade or other instruments),
o And diagnostic tests (eg, phlebotomy or epiglottic cultures) which may provoke
anxiety or crying with abrupt airway obstruction.
• Supraglottic airway use is contraindicated in patients with severe hypopharyngeal
pathology, such as epiglottitis.
• In all suspected cases of epiglottitis, the child should be transferred to the PICU or
operating room as soon as possible.
• Antibiotics
o A third-generation cephalosporin (e.g., Ceftriaxone, Cefotaxime) is the
empirical treatment of choice, usually given for 7–10 d.
o After insertion of the artificial airway, the patient should improve
immediately, and respiratory distress and cyanosis should disappear.
• Indications for rifampin prophylaxis (20 mg/kg orally once a day for 4 days; maximum
dose: 600 mg)
o For all household members include a child within the home who is younger than
4 yr of age and
o Incompletely immunized, younger than 12 mo of age and has not completed the
primary vaccination series, or immunocompromised.
BACTERIAL TRACHEITIS

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• Also called bacterial croup or membranous croup
• is a bacterial infection of the subglottic airway.
• Mean age= between 5 and 7 yr.
• There is a slight male predominance.
• Bacterial tracheitis often follows a viral respiratory infection (especially
laryngotracheitis), so it may be considered a bacterial complication of a viral disease,
rather than a primary bacteria illness.
• Etiologies
o S. aureus (most common),
o S. pneumoniae
o S. pyogenes,
o Moraxella catarrhalis
• The child has a brassy cough, apparently as part of a viral laryngotracheobronchitis.
• High fever and “toxicity” with respiratory distress can occur immediately or after a
few days of apparent improvement.
• The patient can lie flat, does not drool, and does not have the dysphagia associated
with epiglottitis.
• The predominant clinical features of bacterial tracheitis are those of airway
obstruction.
DIAGNOSIS
• The diagnosis is based on evidence of bacterial upper airway disease, which includes
o High fever,
o Purulent airway secretions, and
o An absence of the classic findings of epiglottitis.
o X-rays are not needed but can show the classic findings.
o Purulent material is noted below the cords during endotracheal intubation.
MANAGEMENT
• Narrowing of the subglottic and tracheal airway combined with a patient’s inability to
expectorate secretions cause severe airway obstruction.
• While the patient is intubated, aggressive tracheal and pulmonary toilet should be
maintained, including frequent saline lavage and suctioning through the endotracheal
tube.
• Flexible or rigid bronchoscopy may be necessary to adequately suction tenacious
secretions and remove pseudo-membranes that have been sloughed into the airway.

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RETROPHARYNGEAL ABSCESS
• Infection and abscess formation of the nodes found in the retropharyngeal space.
• The nodes involute after 5 years of age, thus, it occurs most commonly in children
between the ages of two and four years, but can occur in other age groups, including
neonates, older children and even adults.
• M>F affected.
• Etiologies: It is a polymicrobial infection.
o The predominant bacterial species are:
▪ Streptococcus pyogenes (group A streptococcus [GAS]),
▪ Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]),
and
▪ Respiratory anaerobes (including Fusobacteria, Prevotella, and
Veillonella species).
▪ Hemophilus species are found occasionally.
• Difficulty swallowing (dysphagia),
• Pain with swallowing (odynophagia), and/or drooling with decreased oral intake.
• Unwillingness to move the neck secondary to pain (torticollis), particularly
unwillingness to extend the neck
• Change in vocal quality (muffled, or with a ‘hot-potato’ quality [dysphonia]), gurgling
sound, or stertor
• Respiratory distress (stridor, tachypnea, or both); stridor develops as disease
progresses
• Neck swelling, mass, or LAP
• Chest pain (if there is mediastinal extension)
MANAGEMENT
1. Supportive care
a. maintenance of the airway,
b. adequate hydration,
c. provision of analgesia, and
d. monitoring for complications,
e. Patients with an unstable airway should be monitored in the ICU (intubation
may be necessary).
f. Immediate surgical drainage is necessary in patients with airway compromise.
2. Empiric antibiotic therapy should be initiated as soon as possible.

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FOREIGN BODY ASPIRATION

• Most victims of foreign body aspiration are older infants and toddlers.
• Males have been found to be victims up to 1.7 times more likely than females.
• The most common objects on which children choke are food items (59.5–81% of all
choking cases). Nuts, seeds, hot dogs, hard candy, gum, bones, and raw fruits and
vegetables are the most frequently aspirated food items.
• Common inorganic objects on which children choke include coins, latex balloons, pins,
jewelry, magnets, pen caps, and toys
• An infant is able to suck and swallow and is equipped with involuntary reflexes (gag,
cough, and glottis closure) that help to protect against aspiration during swallowing.
Young children are more likely to experience significant blockage by small foreign
bodies due to their smaller airway diameter
• There are typically three stages of symptoms that result from aspiration of an object
into the airway:
A. Initial event: Paroxysms of coughing, choking, gagging, and possibly airway
obstruction occurs immediately after aspiration of the foreign body. The child
is sometimes able to expel the foreign body during this stage.
B. Asymptomatic interval: The foreign body becomes lodged, reflexes fatigue,
and the immediate irritating symptoms subside. The lack of symptoms can be
particularly misleading to the provider when a child presents in this stage and
accounts for a large percentage of delayed diagnoses and overlooked foreign
bodies.
C. Complications: Obstruction, erosion, or infection develops, which again directs
attention to the presence of a foreign body. In this third stage, complications
include fever, cough, hemoptysis, pneumonia, and atelectasis.

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MANAGEMENT OF FBA
• Conscious child suspected of a foreign body partial obstruction should
be permitted to cough spontaneously until coughing is not effective (or
aphonic), respiratory distress and stridor increase, or the child
becomes unconscious.
• The airway is then opened with the head-tilt/chin-lift maneuver, and
ventilation is attempted.
• If unsuccessful, the airway is repositioned and ventilation attempted
again.
• If there is still no chest rise, attempts to remove a foreign body are
indicated.
• The most serious complication of foreign body aspiration is complete
obstruction of the airway.
• In the infant younger than 1 yr, a combination of 5 back blows and 5
chest thrusts is administered.
• The foreign body is removed if it is seen.
• If no foreign body is visualized, ventilation is again attempted.
• If this is unsuccessful, the head is repositioned and ventilation
attempted again.
• If there is no chest rise, the series of back blows and chest thrusts is
repeated.
Figure 54 Airway obstruction
FOR A CONSCIOUS CHILD >1 YR OLD management (<1 year age)
• providers should give a series of 5 abdominal thrusts (Heimlich

maneuver) with the child standing or sitting; this should occur with the
child lying down if unconscious.
CONGENITAL CAUSES
LARYNGOMALACIA
• Commonest cause of stridor in infants and children.
• Pathology: Poor laryngeal muscle tone, which collapse up on inspiration.
Altered sensorimotor integrative function – laryngeal muscles are not
triggered to keep the larynx open. Figure 55 Heimlich
maneuver
• Clinical: stridor noticed at first 2 weeks of life, worsens & peaks at 6-8
months. Later 75% resolve by 18 months and 90% by 2 years of age.
• Diagnosis: by laryngoscopy; plus complete bronchoscopy needed to look for associated
airway anomalies (Positive in 15-60%).

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• Management: watchful observation for most; surgery for the few cases which do not
resolve and develop sequelae like cyanosis.
CONGENITAL SUBGLOTTIC STENOSIS

• The 2nd commonest cause of congenital stridor in infants.
• Clinical: stridor is biphasic or primarily inspiratory.
• Recurrent croup is common.
• Symptoms often occur with / triggered by URTI.
• Diagnosis: confirmed by laryngoscopy.
• DDx: Laryngeal papilloma, hemangioma, laryngeal web,
• Management: surgery – laryngotracheal decompression or reconstruction.

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CHAPTER 7 - CARDIOLOGY
1. Evaluation of the Cardiovascular system
2. The fetal to neonatal circulatory transition
3. Congenital Heart Diseases
4. Acquired Heart Diseases

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7.1. EVALUATION OF THE CARDIOVASCULAR SYSTEM

HISTORY AND PHYSICAL EXAMINATION IN CARDIAC PATIENT
HISTORY
PERINATAL PERIOD
• A comprehensive cardiac history starts with details of the Cardiac diseases may be a
perinatal period which can be associated with cardiac conditions. manifestation of a known
Pertinent history during this period includes congenital malformation or a
o The presence of cyanosis, systemic disease that involve
o Respiratory distress, or prematurity. the heart.
o Congenital heart disease in previous pregnancy
So, we should look for the
o Maternal conditions like
possibility of other conditions
▪ Gestational diabetes, that may be associated with
▪ Teratogenic medication the cardiac disease.
▪ Systemic Lupus Erythematosus,
▪ Substance abuse
• Cardiovascular conditions can present in various
ways. Table 76 - Modified Medical Research Council
• Most common presentation include (but not limited Dyspnea Scale (MMRC)
to)
Grade Description
o Shortens of breath (Dyspnea)
0 No dyspnea except with
o Chest pain strenuous exercise
o Palpitations 1 Dyspnea when walking up an
o Syncope incline or hurrying on the
o Body swelling (Edema)Fatigue and others. level
2 Walks slower than most on
SHORTNESS OF BREATH (DYSPNEA) the level, or stops after 15
• Is subjective experience of breathing discomfort minutes of walking on the
that consists of qualitatively distinct sensations that level
vary in intensity. 3 Stops after a few minutes of
• Is not complained by young patients, so family or walking on the level
physicians report them signs like labored breathing 4 With minimal activity such as
and fast breathing. getting dressed, too dyspneic
to leave the house.
• Its cause can cardiac, respiratory system, other
systems such as neurological, musculoskeletal,
endocrine, hematologic, and psychiatric and it vary
depending on:
o Onset
o Duration
o Quality of the symptom and
o Age of the patient
CAUSES OF SHORTNESS OF BREATH
PULMONARY CAUSES

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• Pneumonia
• Pleural effusion or Empyema Clinical features of
• Tuberculosis myocarditis
• Foreign body - Chest pain
• Asthma - New-onset or worsening
heart failure
• Pneumothorax - Fever
• Pertussis - Unexplained sinus
• Croup and tachycardia
• Bronchiolitis - S3, S4, or summation
CARDIAC CAUSES gallop
- Abnormal
• Heart failure - Common causes in pediatrics are: electrocardiogram
o Congenital Heart Disease - Abnormal echocardiogram
o Rheumatic Valvular Heart Disease - Atrial or ventricular
o Severe Anemia arrhythmia
o Others causes of Heart failure are:
▪ Myocarditis,
▪ pericardial Disease,
▪ cardiomyopathy and
▪ Severe Hypertension (secondary Hypertension is common in pediatrics
like Hypertension due to nephritic syndrome).
NEUROLOGIC CAUSES
• Primary neurologic disorders, like increased intracranial pressure, neuromyopathic
weakness, may present in respiratory distress (Dyspnea), manifested by irregular
respiration, hypoventilation or hyperventilation.
o Common causes are:
▪ Meningitis,
▪ Cerebritis or encephalitis
▪ Intracranial hemorrhage
▪ Mass lesion, or toxic ingestion.
OTHER CAUSES
• Metabolic derangement that results in acidosis can produce tachypnea and possibly
dyspnea.
• Common causes of acidosis include:
o Diabetic ketoacidosis
o sepsis and
o Ingestions (such as aspirin).
CHEST PAIN
• Chest pain is a common compliant but rarely caused by cardiac origin in pediatrics
age.
• Heart conditions that may present with chest pain in children include:
o Pericarditis

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▪ Chest pain that is typically sharp, increased with inspiration, improved
by sitting up and leaning forward, worsened by lying down, and
occasionally radiates to the left shoulder.
o Myocarditis
▪ Though it’s usually painless, may occasionally cause chest pain
especially when concomitant pericarditis is present.
o Dilated cardiomyopathy
▪ may cause chest pain, syncope, decreased exercise tolerance, and heart
failure symptoms.
o Tachyarrhythmias
▪ Usually are painless, but if they persist, they
can cause angina.
Orthopnea – is shortness of
o Aortic root dissection
breath (dyspnea) that occurs
▪ abrupt onset of severe sharp (tearing) pain
when lying flat, causing the
▪ localized to the anterior chest (ascending
person to have to sleep using 2
aortic dissection) or posterior chest
(descending aortic dissection) or more pillows or sit in a
▪ It is associated with chair.
− Marfan syndrome, Paroxysmal Nocturnal
− Turner syndrome, Dyspnea (PND) – is attacks of
− Type IV Ehlers-Danlos syndrome, severe shortness of breath and
− Homocystinuria, coughing at night; usually
− Rare familial aortopathies, or awakens patient after 1 to 3
− Cystic Medial Necrosis hours of sleep. It’s not relieved
o Coronary artery abnormalities immediately after sitting
o Congenital heart disease with left ventricular outflow upright.
tract obstruction
o Heart transplant patients
o Substance abuse
o Prior Kawasaki disease.
o Variant angina
o Ruptured sinus of Valsalva aneurysm
PALPITATIONS
• an unpleasant awareness of one's own heartbeat
• can feel like a fluttering or pounding in the chest.
HEART FAILURE
• Symptoms are age dependent
o In infants – emphasis should be given on breast feeding practice
▪ Infant with heart failure will take less volume per feed and become diaphoretic
or dyspneic while feeding. After falling asleep exhausted, the baby, inadequately
fed, will awaken for the next feeding after a brief time and this cycle continues.
▪ Infants and children also present with recurrent chest infections
▪ Additional symptoms

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− Rapid breathing
− Cyanosis (may be explained by the parent as ‘turning blue around the lips)
o In older children – fatigue needs to be assessed using age-specific activities. This can be
manifested as
− exercise intolerance
− difficulty keeping up with peers during sports or
− the need for a nap after coming home from school,
− poor growth, or
− chronic abdominal complaints.
▪ In addition, history of Orthopnea and Paroxysmal Nocturnal Dyspnoea (PND) should
be assessed.
PHYSICAL EXAMINATION IN CARDIAC PATIENT

• Assessment of cardiac patient involve all systems. But emphasis should be given to
o The general appearance of the patient
o Vital signs
o Anthropometry
o HEENT
▪ To assess for anemia
▪ Any dysmorphic features
o Respiratory system
▪ To look for differentials for the complaints
▪ To assess for complications of cardiac disorders like
− Effusion
− Pulmonary edema
o Cardiovascular system (See in details later)
o Abdominal examination
▪ To assess for organomegaly,
− May suggest cause of anemia as in Hematologic malignancy
− Splenomegaly can be evidence of Infective Endocarditis.
▪ signs of fluid accumulation
o Integumentary and musculoskeletal system
▪ To look for evidences of cardiac illness like
− Splinter hemorrhage, Janeway lesions.
o Nervous system
▪ To assess for complications of cardiac illness.
GENERAL APPEARANCE
• In general appearance try to assess

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o Level of consciousness
o Syndromic features (Trisomy 21, Trisomy 18 and other malformations can cause
cardiac problems)
ANTHROPOMETRIC MEASUREMENT Table 77 - Pulse Rates at Rest
Age Normal (average)

• are important because both cardiac failure and chronic Newborn 70-190 (125)
cyanosis can result in failure to thrive. 1–11 80-160 (120)
• If length or head circumference is also affected, additional mo.
congenital malformations or metabolic disorders should be 2 yr. 80-130 (110)
suspected. 4 yr. 80-120 (100)
6 yr. 75-115 (100)
8 yr. 70-110 (90)
VITAL SIGNS 10 yr. 70-110 (90)
HEART RATE Boys Girls
12 yr. 65-105 70-110
• A normal heart rate is dependent on age. (85) (90)
• Is usually assessed from Radial artery in older children, but 14 yr. 60-100 65-105
in neonates and infants we count from the pericardium (80) (85)
(apical heart rate). 16 yr. 55-95 60-100
(75) (80)
PULSE 18 yr. 50-90 55-95
• A pulse wave is produced by ventricular contraction during (70) (75)
systole.
• Assessed using Two finger method: Palpation with tips of the
2nd and 3rd digits. (See Figure)
• The pulse should be assessed for rate, rhythm, character, volume,
the speed of upstroke, and delay.
Pulse abnormalities
Rate abnormalities
• Bradycardia and tachycardia: the normal values depend on age and
sex. (See table)
Rhythm Abnormalities Figure 56 - Two-Finger method of palpating
pulse
• Irregular Pulse – can be regularly irregular or irregularly
The thumb of the examiner should never
irregular be used to take the pulse because its own
o Irregularly Irregular Pulse strong pulse might be mistaken for the
▪ Atrial fibrillation patient's pulse.
▪ Sinus arrhythmia
▪ Atrial ectopic
▪ Ventricular ectopic
▪ Second degree AV block
o Regularly Irregular Pulse
▪ Atrial tachyarrhythmias (e.g., atrial flutter) with a fixed AV block
▪ Respiratory sinus arrhythmia
o Pulsus bigeminus: a regularly irregular rhythm in which two heartbeats occur in
rapid succession followed by a gap (the usual pattern is: high-volume pulse, low-
volume pulse, delay, repeat)

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▪ Severe left heart failure
▪ Digoxin toxicity
Korotkoff Sounds are sounds heard
• Pulse deficit: is when there is a difference between the apical
when auscultating over the
pulse rate (measured by cardiac auscultation) and the
brachial artery during
peripheral pulse rate (obtained by palpating the radial artery
sphygmomanometer.
for 1 minute). Seen in,
▪ Atrial fibrillation (usually >10 bpm) They’re caused by turbulent blood
▪ Premature ventricular contraction ( usually < 10 flow through a brachial artery that
bpm) is partially compressed by the
▪ Hypertrophic obstructive cardiomyopathy (HOCM) inflated arm cuff of a
sphygmomanometer.
Volume (amplitude) abnormalities
They are broken down into five
• Weak Pulse – can be secondary to phases, heard in sequential order
▪ pericardial tamponade, upon deflating the blood pressure
▪ left ventricular outflow obstruction (subaortic or cuff.
aortic valve stenosis), or
▪ Hypotension (hypoperfusion). Phase I: clear tapping sounds
heard for at least two consecutive
• Pulsus alternans: a pattern of a strong pulse followed by a
beats - this is the systolic blood
weak pulse
pressure.
o Sign that indicates progressive systolic heart failure.
• Pulsus paradoxus is an abnormally large decrease in stroke Phase V: the complete
volume, systolic blood pressure and pulse wave amplitude disappearance of all sounds - this
during inspiration A decrease by more than 10mmHG). Seen in is the diastolic blood pressure.
o cardiac tamponade, The second and third Korotkoff
o chronic sleep apnea, sounds have no known clinical
o croup, and significance.
o obstructive lung disease (e.g. asthma, COPD).
• Pulsus tardus et parvus – is slow-rising pulse and anacrotic
pulse, is weak (parvus), and late (tardus) relative to its expected characteristics.
o seen in aortic valve stenosis.
• Wide Pulse Pressure – is when the difference between the systolic and diastolic pressure
is wider by greater than 100mmHg.
o May suggest an aortic runoff lesion such as
▪ patent ductus arteriosus (PDA),
▪ aortic insufficiency,
▪ an arteriovenous communication,
o Or in case of increased cardiac output secondary to
▪ Anemia,
▪ anxiety, or
▪ conditions associated with increased catecholamine or thyroid hormone
secretion.
Timing Abnormalities
• Radial-Femoral Delay– Normally the femoral pulse should come immediately before the
radial pulse.
▪ In patients with coarctation of aorta, the femoral pulse may be weak
and/or may come after the radial pulse (hence radial-femoral delay).

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BLOOD PRESSURE (CHECK ANNEXE FOR BLOOD PRESSURE RANGE)
OFFICE BASED BLOOD PRESSURE MEASUREMENT
1. The patient should sit and rest before blood pressure is measured.
2. Use the correct cuff size, defined as
• The inflatable part of the blood pressure cuff should cover about 40% of the
distance around (circumference of) your upper arm.
• The cuff should cover 80% of the area from your elbow to your shoulder.
3. Ask the patient to rest the arm on a horizontal surface at the level of the heart.
4. Record the pressure in both arms and note any differences. If you’re measuring
once, use the non-dominant hand.
5. Determine the systolic and diastolic blood pressure value (e.g., auscultatory
method using Korotkoff sounds over the brachial artery).
6. Repeat measurement.
• The normal blood pressure varies significantly by age, sex, height and during different
physiologic phenomena.
o For example, exercise, excitement, coughing, crying, and struggling may raise the
systolic BP of infants and children as much as 40-50 mm Hg greater than their
usual levels.
o To diagnose Hypertension, serial measurements need to be obtained.
• Should be measured in both upper and lower extremities.
o Normally the lower extremity blood pressure is greater than the upper by app
10mm Hg.
• Auscultatory Gap
o Occurs in some patients, in which all sounds may disappear between phase II and
phase III. In auscultation alone, this gap may not be detected and can lead to
inaccurate blood pressure readings, such as underestimated systolic blood pressure
and overestimated diastolic blood pressure.
o To prevent this auscultatory error, it is important to palpate the radial artery
while the cuff pressure is increased to approximately 30 mmHg above the
disappearance of the pulse. The cuff should then be deflated at a rate of 2 to 3
mmHg/second during auscultation.
CARDIAOVASCULAR SYSTEM EXAMINATION
• CVS examination include
o Arterial Examination
▪ In addition to mentioned above we should assess all palpable pulses.
o Venous examination
▪ See below
o Precordial examination
▪ See later

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CYANOSIS (USUALLY CHECKED AT RESPIRATORY SYTEM)
• Is a bluish-purple discoloration of the tissues due to an increased concentration of
deoxygenated hemoglobin in the capillary bed, results from a variety of conditions,
many of which are life-threatening.
• Several factors can affect the detection of cyanosis
o Hemoglobin concentration (cyanosis may not be apparent
in patients with severe anemia). Heart failure Presents as
o Skin pigmentation (cyanosis can be especially difficult to
Signs of Impaired Myocardial
appreciate in infants with darkly pigmented skin)
Performance
o Physiologic factors that affect the oxygen dissociation
• Cardiomegaly
curve such as alkalosis, acidosis, cold temperature, low • Tachycardia
levels of 2,3-diphosphoglycerate, and high levels of fetal • Gallop rhythm
hemoglobin. • Arterial pulsations—cold
• Based on how cyanosis is caused, cyanosis can be classified as extremities, pallor, feeble
o CENTRAL peripheral pulses, low BP
• Pulsus paradoxus
▪ Occurs when systemic arterial concentration of
• Pulsus alternans
deoxygenated hemoglobin (Hb) in the blood • Growth failure
exceeds 5 g/dL (3.1 mmol/L) (oxygen saturation • Sweating.
≤85 percent).
Signs of Pulmonary Congestion
▪ Patients typically have cyanosis at their -
• Wheezing
− Lips • Rales
− Tongue and • Cyanosis
− Oral mucous membranes. • Dyspnea
o PERIPHERAL • Cough
▪ due to increased oxygen extraction by the Signs of Systemic Venous
tissue. Congestion
▪ results in a wide systemic arteriovenous oxygen • Hepatomegaly
difference and increased deoxygenated blood on • Neck vein distension
the venous side of the capillary beds. • Peripheral edema.
▪ Patients typically have
− cyanotic nail beds,
− decreased peripheral perfusion, and
− cold extremities
− with a pink tongue and oral mucous membranes.
• Differential Cyanosis
o manifested as blue lower extremities and pink upper extremities (usually the
right arm).
o is seen with right-to-left shunting across a ductus arteriosus in the presence of
coarctation or an interrupted aortic arch.
JUGULAR VENOUS PULSE

▪ It provides information about central venous pressure and right atrial pressure.
▪ Since the great veins are in direct communication with the right atrium, changes in
pressure and the volume of this chamber are also transmitted to the veins.

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• Usually done in cooperative older children, but have little or no significance in infants
due to
o Relatively shorter neck in infants
o Are usually not cooperative.
CARDIAC EXAMINATION HAS 3 STEPS
1. INSPECTION Precordial Examination
▪ PERICARDIAL BULGE /DEFORMITY
have 3 steps.
• Assess by laying the patient supine and
1. Inspection
looking up from the child’s feet. 2. Palpation
• Precordial bulge may suggest chronic causes 3. Auscultation
that cause cardiac enlargement. - There are rare occasions
▪ ACTIVE OR QUITE PRECORDIUM that we may use percussion
• A pericardium is said to be active if there is such as
visible cardiac activity in two or more o To estimate the cardiac
intercostal spaces or in one intercostal space size when other
with size greater than 2.5cm. modalities (like X-ray,
Echo) are not available
• A hyperdynamic (hyperactive) precordium
o To assess for
suggests a volume load such as that found with dextrocardia.
a large left-to-right shunt, although it may be But, unless you are
normal in a thin patient. specifically being asked, it’s
▪ APICAL IMPULSE better not to mention
• The relationship of the apical impulse to the percussion in Precordial
midclavicular line and the intercostal space is
examination.
also helpful in the estimation of cardiac size.
• apical impulse moves laterally and inferiorly
with enlargement of the left ventricle.
• Right-sided apical impulses signify dextrocardia, tension pneumothorax,
or left-sided thoracic space-occupying lesions.
2. PALPATION
▪ POINT OF MAXIMAL IMPULSE
o Location, character- diffuse or localized, tapping or sustained.
o Generally, the apex beat is the point of maximal impulse but right
parasternal pulsation or pulsation associated with a dilated
pulmonary artery and aortic aneurysm may be more forceful than
the left ventricular impulse.
▪ PALPABLE (ACCENTUATED) HEART SOUNDS
O Also assess for variation during inhalation and exhalation.
▪ HEAVE
O palpable pulsations of the chest wall, which originate on the heart
or the great vessels.
o Assess the presence of heave at the apex and parasternal area.
▪ THRILLS
O are the palpable equivalent of murmurs and correlate with the area
of maximal auscultatory intensity of the murmur.

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o right lower sternal border and apical systolic thrills are
characteristic of ventricular septal defect (VSD) and mitral
insufficiency, respectively.
O diastolic thrills are occasionally palpable in the presence of
atrioventricular valve stenosis.
3. AUSCULTATION
• The diaphragm of the stethoscope is placed firmly on the chest for high-pitched
sounds; a lightly placed bell is optimal for low-pitched sounds.
• Characteristics of the individual heart sounds and their variation with respirations,
then look for any abnormal heart sounds.
▪ FIRST HEART SOUND (S1)
- is best heard at the apex.
- caused by closure of the atrioventricular valves (mitral and tricuspid).
- corresponds to the QRS complex on the electrocardiogram (ECG).
- S1 is louder in
• High output state
• when there is greater excursion of valve leaflets (eg, short pr
interval, mild mitral stenosis).
- S1 is quitter in
• low output states,
• mitral regurgitation
• decreased valve excursion (long pr interval, severe mitral stenosis,
elevated ventricular end-diastolic pressure).
▪ SPLITTING OF THE FIRST HEART SOUND
- May be a normal variation
- Also occur in patients with right bundle branch block due to delayed
closure of the tricuspid valve.
▪ SECOND HEART SOUND (S2)
- Best heard at the upper left and right sternal borders.
- is caused by closure of the semilunar valves (aortic and pulmonary).
- REDUCED INTENSITY OF S2
• semilunar valve stenosis (aortic or Erb-point - 3rd left parasternal
pulmonary). intercostal space. Its where
- INCREASED INTENSITY Diastolic murmurs or aortic
• Pulmonary Artery Hypertension (esp. the regurgitation and pulmonic
Pulmonary part of S2) regurgitation and Systolic
• Systemic Hypertension (esp. the aortic part of murmurs of HOCM heard best.
S2).
▪ SPLITTING OF THE SECOND HEART SOUND
- during inspiration, the decrease in intrathoracic pressure results in
increased filling of the right side of the heart, which leads to an

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increased right ventricular ejection time and Table 79 - Grading of Murmur
thus delayed closure of the pulmonary valve; Grade Intensity
consequently, splitting of the second heart 1 Faintest sound that can be
sound increases during inspiration and detected
2 Soft murmur that is readily
decreases during expiration. detectable
- the presence of a normally split S2 is strong 3 Louder than grade 2 but not
evidence against the diagnosis of ASD. associated with a palpable
- Wide S2 splitting is noted in thrill
• ASD, 4 Easily detected murmur
associated with a palpable
• Pulmonary stenosis, thrill.
• Ebstein anomaly, 5 Very loud murmur audible
• Total Anomalous Pulmonary Venous with the stethoscope placed
Return, and lightly on the chest
6 Extremely loud murmur
• Right Bundle Branch Block. audible with the
- An accentuated pulmonic component of S2 stethoscope off the chest
with narrow splitting is a sign of pulmonary
hypertension.
- A single S2 occurs in
• pulmonary or aortic atresia or severe stenosis,
• truncus arteriosus, and,
• often, transposition of the great arteries.
- Paradoxical Splitting
• uncommon in the first decade of life.
• associated with delayed closure of the aortic valve.
• Occurs in
O left bundle branch block
O Aortic stenosis
▪ THIRD HEART SOUND (S3)
- best heard with the bell at the apex in early diastole.
- Is created during the rapid filling phase of the ventricles.
- Occurs in
• Normal children if they are in a hyperdynamic state or in an
adolescent with a relatively slow heart rate.
• heart failure with diminished cardiac output or volume overload.
- May be normal
▪ FOURTH HEART SOUND (S4)
- Always pathologic.
- Caused by the atrial contraction forces the blood to stiff ventricles.
- Corresponds to P wave on ECG
- Occurs in
• Myocardial Dysfunction or Ventricular Hypertrophy
• Semilunar Valve Stenosis,
• Hypertrophic cardiomyopathy, and
• Tachycardia-induced cardiomyopathy

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MURMURS
• Are the noises made by turbulent blood flow inside the heart.
• Characterized by their intensity, timing, location, radiation, shape, and quality of the
heart murmur.
INTENSITY
• Graded from 1 to 6. (See table)
• It is dependent on the pressure gradient across the site.
TIMING
• Characteristics of the murmur in relation to the cardiac cycle.
• Systolic Murmur
o Early systolic (e.g., small muscular VSD)
o Midsystolic or systolic ejection (e.g., aortic stenosis)
o Holosystolic or pansystolic (e.g., membranous, malalignment, and moderate or
large muscular VSDs; mitral regurgitation (MR).
• Diastolic murmurs:
o Early diastolic (eg, aortic regurgitation, ASD with right ventricular volume
overload and "relative" tricuspid stenosis)
o Late diastolic or presystolic (eg, mitral stenosis)
• Continuous murmur (eg, PDA)
• To-and-fro murmurs – when two or more murmurs occur at the same time (eg, AS with
AR)
LOCATION AND RADIATION
• Assessing where the murmur is best heard and its radiating Remember - Murmur is not a
pattern. sign of heart failure, but rather
• From Right Upper Sternal Boarder Radiating to Carotid region evidence of structural or
• left ventricular outflow obstruction (aortic stenosis [AS]) functional defect in the heart.
• From Left upper sternal border to the axilla and the back
QUALITY OF THE MURMUR
• Harsh – is characteristic of an obstructive lesion such as aortic stenosis or pulmonary
stenosis,
• Blowing – is typical of a systolic murmur of AV valve regurgitation or the diastolic
murmur of semilunar valve regurgitation.
• Rumbling – A rumbling murmur describes the low frequency diastolic murmur of
mitral stenosis.
• Vibratory or musical – A vibratory or musical murmur is characteristic of the innocent
murmur of childhood. It is typically present at the left lower sternal border.
INNOCENT MURMUR AND PATHOLOGIC MURMUR

• Innocent Murmur – are murmurs that not associated with significant hemodynamic
abnormalities.
• >30% of children may have an innocent murmur at some time in their lives.
• It is heard most frequently in children between 3 and 7 yr of age.An Innocent murmur
is characterized as a murmur with all of the following.

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o Grade ≤2 intensity
o Softer when the patient is sitting than supine
o Short systolic duration (not holosystolic; not diastolic).
o Minimal radiation – The murmur is located in a limited region of the
precordium.
o Musical or vibratory quality.
• Pathologic murmurs – any of the following
o Grade ≥3 intensity
o Holosystolic timing
o Maximum intensity at the left upper sternal border
o Harsh or blowing quality
o Abnormal second heart sound (S2) such as: wide splitting, fixed splitting,
accentuation of P2,
o Systolic click
o Diastolic murmur
o Increased intensity with upright position
o Gallop rhythm
o A friction rubs

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7.2. WORK-UPS IN CARDIAC EVALUATION

PULSE OXIMETRY (USUALLY PART OF VITAL SIGN)
• is a non-invasive method for monitoring a person's oxygen
saturation (SO2). HYPEROXIA TEST Differentiates
shunt cyanosis and pulmonary
• The sensor device is placed on a thin part of the patient's
causes of cyanosis
body, usually a fingertip or earlobe, or in the case of an
Give 100% oxygen to patient for
infant, across a foot. 10 minutes:
• It measures what percentage of hemoglobin is loaded • If PaO2 > 200 mm Hg,
(saturated). Falsely high or falsely low reading can occur congenital heart disease
when hemoglobin binds to something other than oxygen as in is ruled out
o Carbon monoxide • If PaO2 < 100 mm Hg,
possibility of congenital
o Methemoglobinemia heart disease with R to L
• Normally between 95 to 100% (at least 90%) are saturated. shunt.
• Currently, it is a routine screening test in newborn infants to
rule out cyanotic congenital heart disease.
• Comparing pulse oximetry between the right arm and a lower extremity may allow
diagnosis of a ductal-dependent lesion in which desaturated blood flows right to left
across a PDA to perfuse the lower body.
CHEST X-RAY FILM (RADIOGRAPH, ROENTGENOGRAM)
• It’s usually the first test in a child suspected to have cardiac defects.
• It can provide information about
1. CARDIAC SIZE (CARDIOTHORACIC RATIO)
▪ measurement of cardiac size is the maximal width of
the cardiac shadow in a posteroanterior (PA) chest
film taken mid-inspiration.
A B
▪ maximal chest width is obtained by drawing a z
horizontal line between the right and left inner
borders of the rib cage at the level of the top of the Figure 57 A, Parts of the heart whose
right diaphragm. outlines can be identified on a routine chest
▪ When the maximal cardiac width is more than half x-ray. B, Routine posteroanterior x-ray of
the maximal chest width (cardiothoracic ratio >50%), the normal cardiac silhouette.
the heart is usually enlarged. Ao, Aorta; LA, left atrium; LV, left ventricle; PA,
pulmonary artery; RA, right atrium; RV, right
▪ the cardiothoracic ratio should be less than 55% in ventricle; SVC, superior vena cava.
infants under 1 year of age and less than 50% in older
children and adolescents.
▪ When the maximal cardiac width is more than half the maximal chest width
(Cardiothoracic Ratio >50%), the heart is usually enlarged.
2. CARDIAC SHAPE
▪ The most common examples are the (See congenital heart diseases for more
details).
• Boot-Shaped heart: seen with Tetralogy of Fallot
• Egg-On-A-String: seen with Dextroposed transposition of the great
arteries, and

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•
the “Snowman”: seen with Supra-cardiac total anomalous pulmonary
venous return.
3. PULMONARY BLOOD FLOW (VASCULARITY)
▪ Pulmonary over-circulation is usually associated with left-to-right shunt
lesions
▪ Pulmonary under-circulation is associated with obstruction of the right
ventricular outflow tract (RVOT).
4. PULMONARY EDEMA
▪ Chest radiograph may show
• fluid in the alveolar walls (also known as, Kerley B lines)
• increased vascular shadowing in a classical batwing peri-hilum pattern
• Cephalization - upper lobe diversion of blood (increased blood flow to
the superior parts of the lung),
5. ASSOCIATED LUNG AND THORACIC ANOMALIES
▪ that may be associated with congenital syndromes (e.g., skeletal
dysplasia, extra or deficient number of ribs, abnormal vertebrae,
previous cardiac surgery).
▪ Any evidence of respiratory infection (infiltrates/consolidation).
ELECTROCARDIOGRAPHY (ECG, EKG)

• The 12-lead electrocardiogram (ECG) provides information about
o Rate,
o Rhythm,
o Depolarization and repolarization of the cardiac cells
and
o Size and wall thickness of the chambers.
P WAVE
• Represents atrial depolarization.
• In Right Atrial Enlargement
O There will be an increased amplitude of the P
Figure 58 Nomenclature of
Wave, reflected best in lead II. electrocardiogram waves and intervals.
• Left Atrial Enlargement
Note that the rate, rhythm, axis, intervals and
O There will be prolongation of the second portion of voltage have to be adjusted for the child's age.
the P wave, exhibited best in the chest leads.
PR INTERVAL (NORMALLY 120 - 200MS IN DURATION)
• Measured from the beginning of the P wave to the beginning of the QRS complex ,
increases with age.
• Shorter in
o Lown–Ganong–Levine syndrome (LGL)
o Wolff-Parkinson-White syndrome (WPW)
• Longer in
o 1ST DEGREE HEART BLOCK.
o Diseases in the atrial myocardium, the bundle of his, or the Purkinje
system.

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QRS COMPLEX
• Represents ventricular depolarization
• Greater ventricular volume or mass causes a greater magnitude of the complex.
QT INTERVAL
• is measured from the beginning of the QRS complex to the end of the T wave.
• As with R-R interval it is affected with heart rate (i.e., the faster the heart rate,
the shorter the R–R interval and QT interval).
• The corrected QT interval (corrected for rate) should be less than 0.45 second.
O QTc=QT/√𝑃𝑟𝑒𝑐𝑒𝑑𝑖𝑛𝑔 𝑅 𝑡𝑜 𝑅 𝑖𝑛𝑡𝑒𝑟𝑣𝑎𝑙
• Prolonged In
O Hypocalcemia or Severe Hypokalemia
O Prolonged QT Syndrome
O Drugs such as Quinidine and Erythromycin
T-WAVE
• Represents the repolarization of the ventricles.
• The T wave can be described by its symmetry, skewness, slope of ascending and
descending limbs, amplitude and subintervals like the Tpeak–Tend interval.
ECHOCARDIOGRAPHY (ECHO)
• is an ultrasound of the heart.
• uses standard two-dimensional, three-dimensional, and Doppler ultrasound to create
images of the heart.
• Types of Echocardiography
o Transthoracic echocardiogram
o Transesophageal echocardiogram
▪ Provides better imaging than
transthoracic
o Intracardiac echocardiography
o Intravascular ultrasound and
others.
• Gives important information regarding
(Know them well).
o Cardiac anatomy Figure 59 A two-dimensional Echocardiography
o Arterial and venous connections
o Origin of coronary arteries
o Presence and amount of shunting
o Presence and amount of valvular stenosis and regurgitation
o Atrial and ventricular sizes (including chamber size, wall thickness, and
trabeculations)
o Left ventricle (LV) and right ventricle (RV) global and regional systolic function
o Estimation of RV and Pulmonary Artery pressures
o Atrial or ventricular thrombi or vegetation on the valves
o Pericardial effusion
o Stroke volume

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▪ is the volume of blood pumped from the left ventricle per a single beat.
o Cardiac output
▪ Is the volume of blood being pumped by the heart per unit time.
▪ Calculated as: CO = HR × SV, where
• CO – Cardiac output
• HR – Heart rate
• SV – Stroke volume
o Ejection Fraction (EF)
▪ Is volumetric fraction of blood ejected from the heart with each contraction.
▪ Normal range is 55–65%
▪ Based on the EF, Heart failure can be classified as
• Heart failure with Preserved EF (HFpEF) – EF ≥ 56%.
• Heart failure with Reduced EF (HFrEF) – EF <55%
o Wall motion abnormality
o blood flowing through the heart (Doppler echocardiography)
OTHER LABORATORY TESTS

COMPLETE BLOOD COUNT (CBC)
Red Blood Cells
• Anemia may contribute and/or precipitate Heart failure
• Patients with Cyanotic heart diseases may have 2ry polycythemia because of the
chronic hypoxia
WBC
• Infections can precipitate HF
TROPONIN
• Cardiac troponin I and troponin T are sensitive biomarkers for myocyte injury.
• Are elevated in Myocarditis and myocardial Ischemia.
BRAIN NATRIURETIC PEPTIDE (BNP)

• is a hormone secreted by cardiomyocytes in the heart ventricles in response to
stretching caused by increased ventricular blood volume.
• Its net effect is reducing blood pressure, thus reducing afterload by
o Decreasing systemic vascular resistance
o Decreasing central venous pressure and
o Increasing natriuresis.
• BNP levels can help discriminate between cardiac disease and noncardiac causes of HF
symptoms.
SERUM CHEMISTRIES
• Baseline Serum electrolytes are important because
o Needed prior to initiating or during diuretics therapy
o Hypo or hyperkalemia may affect cardiac activities
o Hyponatremia may be seen in children with severe HF

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• Renal impairment may be a contributing factor for HF or exacerbates pre-existing
failure.
• Liver function studies
o may be elevated due to hepatic congestion with right-sided HF.

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7.3. THE FETAL TO NEONATAL CIRCULATORY TRANSITION
FETAL CIRCULATION
• In the fetal circulation, the right and left
ventricles exist in a parallel circuit, as
opposed to the series circuit of a newborn
or adult.
• Because the lungs do not provide gas
exchange, the pulmonary vessels are
vasoconstricted, diverting blood away
from the pulmonary circulation.
• Three cardiovascular structures unique to
the fetus are important for maintaining this
parallel circulation:
o ductus venosus,
o foramen ovale, and
o ductus arteriosus
• Approximately 50% of the umbilical venous
blood enters the hepatic circulation,
whereas the rest bypasses the liver and
joins the inferior vena cava (IVC) via the
ductus venosus, where it partially mixes
with poorly oxygenated IVC blood derived
from the lower part of the fetal body.
• This combined lower body plus umbilical Figure 60 The Fetal Circulation
venous blood flow (PO2 of 26-28 mm Hg) enters the right atrium and is preferentially
directed by a flap of tissue at the right atrium–IVC junction, the Eustachian valve, across
the foramen ovale to the left atrium.
o This is the major source of left ventricular (LV) blood flow, because pulmonary
venous return is minimal.
• LV blood is then ejected into the ascending aorta, where it supplies predominantly the
fetal upper body and brain.
• Fetal superior vena cava (SVC) blood, which is considerably less oxygenated (PO2 of 12-14
mm Hg) than IVC blood, enters the right atrium and preferentially flows across the
tricuspid valve, rather than the foramen ovale, into the right ventricle. From the right
ventricle, the blood is ejected into the pulmonary artery. Because the pulmonary arterial
circulation is vasoconstricted, only approximately 5% of right ventricular (RV) outflow
enters the lungs.

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• The major portion of this blood bypasses the lungs and flows right-to-left through the
duct arteriosus into the descending aorta to perfuse the lower part of the fetal body,
including providing flow to the placenta via the 2 umbilical arteries.
• Thus, the upper part of the fetal body (including the coronary and cerebral arteries and
those to the upper extremities) is perfuse exclusively from the left ventricle with blood
that has a slightly higher PO2 than the blood perfusing the lower part of the fetal body,
which is derived mostly from the right ventricle.
• During fetal life the right ventricle is not only pumping against systemic blood pressure,
but also performing a slight greater volume of work than the left ventricle. Thus, the RV
wall is as thick as the LV wall during fetal and immediate neonatal life, explaining the
unique features of the neonatal electrocardiogram (showing what would be called right
ventricular hypertrophy in an adult).
THE FETAL TO NEONATAL CIRCULATORY TRANSITION

• At birth, mechanical expansion of the lungs and an increase in arterial PO2 result in a
rapid decrease in pulmonary vascular resistance (PVR).
• Concomitantly, removal of the low-resistance placental circulation leads to an increase
in systemic vascular resistance (SVR). The output from the right ventricle now flows
entirely into the pulmonary circulation, and because PVR becomes lower than SVR, the
shunt through the ductus arteriosus reverses and becomes left to right.
• Removal of the placenta from the circulation also results in closure of the ductus
venosus.
• The left ventricle is now coupled to the high resistance systemic circulation, and its wall
thickness and mass begin to increase.
• In contrast, the right ventricle is now coupled to the low resistance pulmonary
circulation, and its wall thickness and mass decrease.
• The largest decline in PVR from the high fetal levels to the lower “adult” levels in the
human infant at sea level usually occurs within 2-3 days, but may be prolonged for ≥7
days after birth.
• This decrease in PVR significantly influences the timing of the clinical appearance of
many congenital heart lesions dependent on the relative levels of SVR and PVR. The left-
to-right shunt through a large ventricular septal defect (VSD) may be minimal in the 1st
week after birth, when PVR is still high.
As PVR decreases in the next 1 or 2 wks., the volume of the left-to-right shunt through the
VSD increases and eventually leads to symptoms of heart failure within the 1st or 2nd Mo of
postnatal life
o Significant differences between the neonatal circulation and that of older
infants:

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o right-to-left or left-to-right shunting may persist across the patent foramen
ovale;
o in the presence of cardiopulmonary disease, continued patency of the ductus
arteriosus may allowed left-to-right, right-to-left, or bidirectional shunting;
o the neonatal pulmonary vasculature constricts more vigorously in response to
hypoxemia, hypercapnia, and acidosis
o the wall thickness and muscle mass of the neonatal left and right ventricles are
almost equal; and
o Newborn infants at rest have relatively high oxygen consumption, which is
associated with relatively high cardiac output.
• The foramen ovale is usually functionally closed by the 3rd Mo of life, although it is
possible to pass a probe through the overlapping flaps in a large percentage of children
and in 15–25% of adults.
• Functional closure of the ductus arteriosus is usually complete by 10-15 hr of postnatal
age in a normal neonate, although the ductus may remain patent much longer in the
presence of congenital heart disease, especially when associated with cyanosis.
• In premature newborn infants, an evanescent systolic murmur with late accentuation or a
continuous murmur may be audible, and in the context of respiratory distress syndrome,
the presence of a patent ductus arteriosus should be suspected.

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7.4. CONGENITAL HEART DISEASES
OVERVIEW
• Congenital heart disease (CHD) occurs in approximately 0.8% of live births.

• The incidence is higher in still born (3–4%), Table 80 Relative frequency of major
spontaneous abortions (10–25%), and premature congenital heart lesions
infants. (Approximately 2% excluding [PDA]). Lesion % Of all lesions
Ventricular septal defect 25-30
• Congenital cardiac defects have a wide spectrum ASD(Secundum) 6-8
of severity in infants. PDA(Patent ductus 6-8
• CHD remains the leading cause of death in children arteriosus)
with congenital malformations. COA(Coarctation of aorta) 5-7
TOF(Tetralogy of Fallot) 5-7
• Most congenital defects are well tolerated in the Pulmonary valve stenosis 5-7
fetus because of the parallel nature of the fetal Aortic valve stenosis 4-7
circulation D-TGA 3-5
o One notable exception is the case of severe Hypoplastic left ventricle 1-3
Truncus arteriosus 1-2
regurgitant lesions, most frequently of the
TAPVR 1-2
tricuspid valve as in Ebstein anomalies, Tricuspid atresia 1-2
o In utero heart failure may occur → Non Single ventricle 1-2
immune hydrops fetalis. Double outlet right ventricle 1-2
• Associated non cardiac malformations noted in Others 5-10
identifiable syndromes may be seen in as many as 20-45% of patients with congenital
heart disease.
• Gender differences in the occurrence of specific cardiac lesions have been identified.
Example TGA more common in boys whereas ASD, VSD,PDA and PS are slightly common
in girls.
HISTORY
RISK FACTORS
The cause most congenital heart defect is still unknown but many cases of congenital heart
diseases are multifactorial
• Chromosomal abnormalities, in particular, trisomy 21,13 and18 and Turner syndrome.
• Maternal Infection during pregnancy
o Congenital rubella syndrome (PDA),
• Maternal history of teratogenic medications like lithium, warfarin anticonvulsants.
• Maternal alcohol consumption
o Fetal alcohol syndrome (craniofacial abnormality, IUGR, and cardiac defect--
>VSD, ASD).
• Maternal history of smoking

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• Maternal history of DM commonly associated with dTGA, VSD, and AS
• Maternal obesity
• Family history CHD, neonatal death---> Risk of recurrence is higher if first degree
relative are affected
• Prematurity and high altitude are risk factor for (PDA)
Table 81 Congenital malformation syndromes associated with CHD

SYNDROMES COMMON FEATURES
Down syndrome Endocardial cushion defect, VSD, ASD
Turner syndrome Bicuspid aortic valve, COA
Trisomy 18(EDWARD’S) VSD, ASD, PDA, COA
Trisomy 13(PATAU) VSD, ASD, PDA, COA
Marfan syndrome Aortic and mitral insufficiency, MVP
Congenital rubella syndrome PDA, Peripheral PS
Fetal alcohol syndrome ASD, VSD
VATER association VSD, TOF, ASD, and PDA
SYMPTOMS
• Symptoms vary based on,
o Type of the defect
o Size of the defect
o Whether its compensated or decompensated
o Age of the patient
o Presence or absence of complications
• Infants
o Bluish lips, skin, fingers, and toes worsen while crying
o breathlessness or fast breathing
o feeding difficulties and sweating ask frequency of feeding and time spent on
each breast
o low birth weight
• Older children
o Difficulty of walking in equal pace with peers
o Orthopnea or shortness of breath in supine position
o Delayed growth
o Dizziness
o Cough and trouble breathing
o Fainting(syncope)
o Body swelling usually start from lower extremity
o Fatigue and exercise intolerance

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o Squatting after exercise to relief shortness of breath is the feature of child
with TOF
o Low urine output due to decreased renal perfusion in a patient with (COA)
o Weakness or pain in legs after exercise(claudication) in a patient with (COA)
o History of cough and fever ( IE or Pulmonary infection as complication)
o Chest pain is unusual manifestation in pediatric patients. (see Cardiac patient
evaluation for discussion on chest pain).
• Past medical and surgical history: ask for previous history of admission with symptoms
of heart failure or any medication the patient is taking or any cardiac surgery done.
• Complications
o Cerebral thrombosis secondary to polycythemia on long standing cyanosis ask
any history of body weakness
o Brain abscess ask for fever, weakness and headache in older children.
o Infective endocarditis (fever, malaise, weight loss)
o Recurrent pulmonary infection: ask history of fever, cough and fast breathing
o Infective endarteritis (PDA)
o Reversal of shunt (Eisenmenger syndrome) => leads to cyanosis
o Recurrent heart failure (large VSD, large PDA...)
SEE PHYSICAL EXAMINATIONS ON ‘EVALUATION OF CARDIOVASCULAR SYSTEM’
CLASSIFICATION
• Congenital heart diseases can be classified in to two based on the presence or
absence of Cyanosis (See Physical examination part for more detail).
o Acyanotic congenital heart lesions and
o Cyanotic congenital heart lesions
1. ACYANOTIC CONGENITAL HEART LESIONS

• Acyanotic congenital heart lesions can be classified according to the predominant
physiologic load that they place on the heart.
A. Acyanotic Lesions Resulting in Increased Volume Load
o The most common lesions in this group are those that cause left-toright
shunting
▪ Atrial septal defect (ASD)
▪ Ventricular septal defect (VSD),
▪ AV septal defects (AV canal), and
▪ Patent ductus arteriosus (PDA)
o Common features:
▪ Degree of left to right shunt, and consequently clinical manifestations is
dependent on:

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− Size of the defect
− Pressure gradient across the defect
− Pulmonary vascular resistance
o Manifestation of increase pulmonary blood flow:
▪ Poor feeding & tachypnea.
▪ recurrent chest infections & chest wheezes.
▪ recurrent heart failure.
▪ Growth failure.
o Heart failure doesn't occur in neonates but can occur in infancy as pulmonary
vascular pressure declines
o Prolonged pulmonary blood overflow →pulmonary hypertension develops →
with time right heart pressures exceed that of the left → reversal of the shunt
(Eisenmenger syndrome) → Central Cyanosis,
o This occurs: -
▪ Early in large VSD & ECD.
▪ Late in ASD & small defects.
B. Acyanotic Lesions resulting in increased pressure load
• The pathophysiologic common denominator of these lesions is an obstruction to
normal blood flow.
• The most frequent are obstructions to ventricular outflow:
o valvular pulmonic stenosis,
o valvular aortic stenosis, and
o coarctation of the aorta
• Less common are obstruction to ventricular inflow:
o tricuspid or mitral stenosis,
o cortriatriatum and obstruction of the pulmonary veins.
• Ventricular outflow obstruction can occur: at the valve, below the valve, or above
it
2. CYANOTIC CONGENITAL HEART LESIONS

• This group of congenital heart lesions can also be further divided according to
pathophysiology: whether
a. Pulmonary blood flow is decreased (Oligemic)
o tetralogy of Fallot (TOF)
o Pulmonary atresia with an intact septum (PA)
o Tricuspid atresia(TA) and
o total anomalous pulmonary venous return with obstruction (TAPVR)
b. Pulmonary blood flow increased (Plethoric)
o transposition of the great vessels (TGA)
o single ventricle,

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o truncus arteriosus,
o total anomalous pulmonary venous return without obstruction).
• The chest radiograph is a valuable tool for initial differentiation between these 2
categories.
DISCUSSION OF SOME COMMON CHD
1. TETRALOGY OF FALLOT(TOF)
• Tetralogy of Fallot is one of the conotruncal family of
heart lesions in which the primary defect is an anterior
deviation of the infundibular septum (the muscular
septum that separates the aortic and pulmonary
outflows).
• The consequences of this deviation are the 4
components:
1. Obstruction to right ventricular (RV)outflow Figure 61 A normal heart versus the heart of a
(pulmonary stenosis), patient with TOF
2. Non-restrictive type of ventricular septal defect

(VSD),
3. Dextroposition of the aorta so that it overrides the ventricular septum, and
4. Right ventricular hypertrophy
• The degree of pulmonary outflow obstruction and whether the ductus arteriosus is
open or closed determine the degree of the patient's cyanosis and the age at first
presentation.
• Degree of pulmonary stenosis (P.S.) determine the degree of right to left shunt.
• When pulmonary stenosis is mild to moderate and balanced shunt across VSD present,
the patient may not be visibly cyanotic (Pink TOF).
• CHF is not usual manifestation of TOF
PRESENTATION
RISK FACTORS
• Viral illness during pregnancy, rubella (Germans measlēs) ask for fever, rash ..
• Alcoholism during pregnancy
• Poor maternal nutrition
• Advanced maternal age >40yrs
• Presence of Down syndrome
SYMPTOM
• Difficulty breathing on exertion in older children
• Squatting positioning after short time of activity to relief dyspnea

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• Difficulty in feeding
• Failure to gain weight
• Loss of consciousness(fainting)
• Irritability and prolonged crying
PHYSICAL FINDINGS
• Patients may be chronically sick looking
• Assess for cyanosis
• Central cyanosis:
o Usually appear later in the first year of life. Cases with mild to moderate
pulmonary stenosis may not be initially visibly cyanotic (acyanotic: pink
Fallot).in infants with severe degrees of RV outflow obstruction, neonatal
cyanosis is noted immediately.
• Growth and development may be delayed in patients with severe untreated tetralogy
of Fallot, particularly when their SaO2 is chronically <70%.
• Clubbing: related to the degree & duration of cyanosis. Cyanotic (Tet) spells: Worsening
• Older children with long-standing cyanosis who have not cyanosis, Hyperpnea (rapid,
shallow breaths), Irritability.
undergone surgery may have dusky blue skin, graysclerae with
Precipitated by rapid increase in
engorged blood vessels, and marked clubbing of the fingers and RVOT resistance as in
toes. • Pain,
• Crying
• Paroxysmal hypercyanotic (hypoxic) spells: Due to infundibular
• Feeding
spasm~ decrease of already reduced pulmonary blood flow. • Bowel movement
Calming and holding the infant in a knee-chest position may • Agitation
abort progression of an early spell. • Fever
Precordial examination
• Inspection: bulged pericordium in older children
• Palpation: parasternal heave
o systolic thrill may be felt along the left SB in the 3rd and 4th spaces.
• Auscultation: systolic murmur is usually loud and harsh, most intense at the left
sternal border.
o generally, ejection in quality at the upper sternal border:
o more holosystolic toward the lower sternal border
o S2 is single, or the pulmonic component(P2) is soft
INVESTIGATION
• CXR
o Decreased pulmonary blood flow (oligemic lung field Narrow base, concavity of
the left heart border in the area usually occupied by the pulmonary artery, and
normal overall heart size.

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o Aorta is usually big (right arch of aorta in 20%of cases)
• ECG: RVH (right axis deviation)
• Echocardiography
o Diagnostic tool
o Degree of overriding
o Degree of pulmonary stenosis
o RV wall thickness
• Cardiac catheterization: preoperative
TREATMENT
Figure 62 Boot shaped heart seen in
• Medical: Treatment of hypoxic spells TOF
o Avoid cerebral thrombosis

o In Fallot with severe cyanosis at birth → keep PDA by PGE 1 infusion.
o Prophylaxis & treatment of infective endocarditis.
• Surgical
o Palliative shunts
o Modified Blalock - Taussig operation → anastomosis between subclavian artery
& ipsilateral pulmonary artery
o Waterston operation: anastomosis between ascending aorta & right pulmonary
artery (obsolete)
o Potts operation: anastomosis between descending aorta & left pulmonary
artery (obsolete).
o Total correction: can be done between 4 months to 2 years according to
severity.
COMPLICATIONS
• Cerebral thromboses usually occurring in the cerebral veins or Dural sinuses and
occasionally in the cerebral arteries, are sequelae of extreme polycythemia and
dehydration. Thromboses occur most often in patients younger than 2 yr.
• Bacterial endocarditis may occur in the right ventricular infundibulum or on the
pulmonic, aortic, or rarely tricuspid valve.
PROGNOSIS
• After successful total correction, patients are generally asymptomatic and are able to
lead unrestricted lives.
• Asymptomatic patients nonetheless have lower-than-normal exercise capacity,
maximal heart rate, and cardiac output.
2. DEXTRO TRANSPOSITION OF GREAT ARTERIES (DTGA)

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• Common cyanotic congenital anomaly, accounts for approximately 5% of all congenital
heart disease.
• The aorta arises from the right ventricle and the
pulmonary artery from the left ventricle.
• The systemic and pulmonary circulations exist as 2
parallel circuits.
• Survival in the immediate newborn period is
provided by the foramen ovale and the ductus
arteriosus.
• Approximately 50% of patients with dTGA also have Figure 63 A normal heart versus the heart of a patient
with TGV
a ventricular septal defect (VSD), which usually
provides for better mixing.
• The clinical findings and hemodynamics vary in relation to the
presence or absence of associated defects (e.g., VSD or Reverse differential cyanosis
pulmonary stenosis). Is when there is higher post-

ductal O2 Saturation than pre-
• DTGA is more common in infants of diabetic mothers and in
ductal saturations.
males than female (3:1)
• Before the modern era of corrective or palliative surgery,
mortality was >90% in the 1st yr of life.
PRESENTATION
RISK FACTORS
• History of maternal viral infection during pregnancy
• Drinking alcohol during pregnancy
• Smoking during pregnancy
• A mother who has poorly controlled diabetes (ask for Poly-Symptoms)
SYMPTOMS
• Bluish lips, skin, fingers and toes
• Fast breathing is most often recognized within the first hours or days of life.
• The neonate will be easily fatigued with frequent interruption to breast feeding.
Physical findings, other than cyanosis, maybe remarkably nonspecific
• Visible cyanosis
• Respiratory rate > 60/min
• Failed pulse oximetry screening test (Hyperoxia test)
• Murmurs:

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o Pansystolic murmur of VSD
o Systolic ejection murmur if left ventricular outlet
obstruction is present
o Diminished femoral pulses: if there is also aortic coarctation
or arch interruption
LABORATORY FINDINGS
• CXR
o Mild cardiomegaly
o a narrow mediastinum (the classic “egg-shaped heart”)
o normal to increased pulmonary blood flow. Figure 64 Egg-Shaped heart
• ECG: usually normal
• Echocardiography: Postnatal echocardiogram is a main confirmatory test:
o Evaluate the degree of atrial mixing.
o VSD
o Valve abnormalities
o PDA
o Coronary artery anatomy
• Catheterization
o Can help assess origins/anatomy of coronary arteries prior to surgery
o Can be therapeutic: balloon atrial septostomy to increase blood mixing
TREATMENT
• Medical:
o For initial stabilization and optimization prior to surgery
o Intravenous prostaglandin infusion to keep PDA open
• Surgery: Definitive management and its performed within 1st 2 weeks of life
o Palliative operation: Rashkind balloon atrial septostomy
o Total correction: Arterial switch operation or Atrial switch operation.
PROGNOSIS
If not treated:
• 90% of patients will die within the 1st year.
• 30% of patients will die within the 1st week.
• If treated, high morbidity with continuous follow-up and decreased exercise capacity
• Higher chance of neurodevelopmental delay in infants
3. ATRIAL SEPTAL DEFECT(ASD)

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• Atrial septal defect (ASD) is a communication between the right atrium (RA) and the
left atrium (LA) secondary to a defect in the development of the atrial septum during
embryogenesis.
• Account for 10%–15% of all cases of CHD
• Girls > boys, with a girl-to-boy ratio of 2:1
• The mortality rate is low, at < 1%.
• Can occur in any portion of the atrial septum
o Ostium secundum (most common): middle
part;
o Ostium primum: lower part or
o Sinus venosus (upper part of the septum)
• The majority of cases of ASD are sporadic.
• Ostium secundum usually occurs as an isolated defect
but may be associated with a syndrome (genetic Figure 65 The anatomic locations of the different types
of ASDs
component):
o Holt-Oram syndrome: autosomal dominant, associated with upper limb
deformity and heart block
o Noonan's syndrome: autosomal dominant, associated with facial defects,
deformity of the sternum, and clotting deficiencies
o Treacher Collins syndrome: autosomal dominant, associated with craniofacial
deformities and conductive hearing loss
• Ostium primum is mainly seen in patients with Down's syndrome.
• Small defects are usually asymptomatic.
• Infants and children with smaller defects may be diagnosed incidentally:
o Due to a murmur upon physical examination
o During an echocardiogram being performed for another reason
• Larger defects present in infancy or young children with:
o Failure to thrive
o Recurrent lung infections
o Symptoms of heart failure
• Paradoxical embolism can occur with ASDs: An embolus can enter the systemic
circulation through the shunt, resulting in a stroke or acute limb ischemia.
PHYSICAL FINDINGS
• General appearance: The patient may have dyspnea or lethargy.
• Precordial bulge due to atrial enlargement
• Murmur:

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o Increased flow at the pulmonary valve → mid-systolic ejection murmur (over
the 2nd intercostal space)
o Increased flow at the tricuspid valve → soft mid-diastolic murmur (over the
lower left sternum)
o Associated mitral regurgitation → holosystolic murmur (over the apex)
• Fixed, wide split S2
• Signs of pulmonary hypertension
• Signs of Heart failure
DIAGNOSIS
• Echocardiogram confirms the diagnosis by detecting:
o Size of the defect
o Volume
o Shunt ratio
o Pulmonary arterial pressures
• Electrocardiogram (ECG) (changes are only seen in a large defect):
o Incomplete right bundle branch block
o Supraventricular tachycardia (atrial fibrillation or atrial flutter)
• Chest X-ray:
o Prominent pulmonary vasculature
o Cardiomegaly
TREATMENT
• Medical management for symptomatic ASDs:
o Nutritional support
o Manage heart failure.
o Manage pulmonary hypertension.
o Antibiotic prophylaxis until 6 months post-surgical repair
• Surgical: Transcatheter or open-heart surgical closure at 3-5 years.
PROGNOSIS
• Small to moderate-sized ASDs detected in term infants may grow smaller or close
spontaneously.
• Secundum ASDs are well tolerated during childhood, and significant symptoms do not
usually appear until the 3rd decade or later.
4. VENTRICULAR SEPTAL DEFECT (VSD)

• A ventricular septal defect (VSD) is a malformation of the interventricular septum
(IVS) resulting in an abnormal communication between the left ventricle (LV) and the
right ventricle (RV).

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• It is the most common cardiac malformation and accounts for 25% of congenital heart
disease.
CLASSIFICATION
Based on site
• Membranous (75% of cases):
o Also called perimembranous or
conoventricular
o Most common subtype
o Located at distal conal septum (just inferior
to aortic valve) in proximity to bundle of His
• Muscular (20%):
o Located along trabeculated muscular septum
o Classified as anterior, mid-muscular, apical,
or posterior
o Common in premature infants
o May be multiple
o Most likely to undergo spontaneous closure
• Inlet (5%): Figure 66 Image showing the different types of ventricular
septal defect
o Also called AV canal defect
o Located around tricuspid annulus (inlet)
o Always accompanies other endocardial cushion defects
o Will not close spontaneously
• Supracristal (5%):
o Also called outlet defect
o Located inferior to pulmonic valve at right ventricular outflow tract
o More common in Asian population
o Will not close spontaneously
BASED ON THE SIZE OF DEFECT In Nonrestrictive defects

• Restrictive VSD (<5mm) the direction of shunting
and the shunt magnitude are
• Moderate VSD (5mm-10mm) or determined by the
• Nonrestrictive VSD (>10mm) Pulmonary Vascular
Resistance (PVR)/Systemic
RISK FACTORS Vascular Resistance (SVR)
• Family history - 3x increase ratio.
• Maternal factors: Obesity, Diabetes, Alcohol use (esp. for
muscular VSD)
• Genetic syndromes: Down syndrome (Trisomy 21), Patau's syndrome (Trisomy 13),
Edwards' syndrome (Trisomy 18)

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Age of presentation is usually around 2 months, unless a larger Pathophysiology of VSD
defect is present which becomes symptomatic within weeks of In Smaller VSD - Minimal left-to-right
birth. shunting due to high resistance within
defect and thus, rarely cause Heart
The clinical findings of patients with a VSD vary according to the failure.
size of the defect and pulmonary blood flow and pressure.
In Larger VSD - Left-to-right shunt
• Small VSD: equalizes pressure between RV and
o Usually, asymptomatic LV and as fetal pulmonary vascular
resistance (PVR) decreases →
o Incidental murmur
increased pulmonary blood flow →
• Moderate/large VSD: pulmonary hypertension → RV
o Poor feeding (sweating or fatigue) hypertrophy.
o Poor weight gain - Eisenmenger’s syndrome can
o Shortness of breath occur once RV pressure is higher
o Recurrent lung infections resulting right-to-left shunting
o Infective endocarditis and cyanosis.
PHYSICAL FINDINGS
• General appearance:
o Pallor
o Failure to thrive
• Precordial exam:
o Displaced apex
o Systolic thrill
o Murmur:
▪ Small VSD:
▪ Harsh holosystolic murmur
▪ Left lower sternal border
o Large VSD:
▪ Systolic murmur with diastolic rumble
(apex)
▪ No murmur, if very large.
• Signs of Heart failure Figure 67 White arrow indicates a large VSD detected
by fetal echocardiography.
LABORATORY FINDINGS
• Echocardiography with color doppler:
o Confirmatory (can be done prenatally)

o Evaluates:
▪ Type and location
▪ Size of defect

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▪ Extent of left-to-right shunt
▪ Pulmonary arterial pressure
• Chest X-ray:
o Increased pulmonary vascularization
o Cardiomegaly
• ECG:
o Normal in smaller defects
o Moderate-to-large defects may show both LV and RV hypertrophy
o the P waves may be notched
TREATMENT
• Medical:
o Nutritional Support
o Up-to-date vaccines
o Control heart failure
o Prophylaxis against infective endocarditis (as
Indicated).
o Antibiotics for chest infections.
o Follow up with ECG & Echo to confirm
spontaneous closure.
• Surgical: Types:
o Palliative: Pulmonary artery banding (less Figure 68 Chest x-ray of patient with VSD
favored).
o Direct closure of the defect.
INDICATIONS FOR SURGERY

• Clinical symptoms and failure to thrive cannot be controlled medically.
• Infants 6 and 12 months with large defect and pulmonary HTN.
• Older than 24 months with a Qp:Qs ratio greater than 2:1.
• Patients with a supracristal VSD of any size are usually referred for surgery
because of their higher risk for developing aortic valve regurgitation.
PROGNOSIS
• A significant number (30-50%) of small defect close spontaneously, most
frequently during first 2 years of life.
• Excellent long-term survival
5. PATENT DUCTUS ARTERIOSUS (PDA)

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• The ductus arteriosus (DA) is a fetal blood vessel
The extent of the shunt in
connecting the left pulmonary artery to the aorta,
PDA depends on the size of
bypassing the pulmonary circulation. (See Fetal circulation
the ductus and on the
above) PVR/SVR ratio.
• Failure of the vessel to close and involute within 72 hours of
birth results in a condition called patent ductus arteriosus
(PDA).
• If the ductus remains patent when PVR falls, aortic blood then is shunted left
to right into the pulmonary artery.
EPIDEMIOLOFY AND RISK FACTORS

• 5%–10% of all congenital heart defects (CHDs)
• Male: female ratio is 1:2.
RISK FACTORS:
• Prematurity
• Hypoxia:
o History of perinatal asphyxia
o Birth at high altitude
• Maternal factors:
o Rubella infection
o Phenytoin use
• Genetic predisposition:
o Positive family history of PDA
o DiGeorge syndrome Figure 69 Patent Ductus Arteriosus (PDA)
o Cri-du-chat syndrome
o Noonan syndrome
o CHARGE syndrome
CLINICAL PRESENTATION Differential Diagnosis of

• Small PDA: asymptomatic machinery murmurs: e.g.:
• Large PDA - Aortopulmonary window.
o Nonspecific symptoms (e.g., failure to thrive) - Anterior venous fistula
(systemic or pulmonary).
o Bounding peripheral pulses, wide pulse pressure
- Ruptured sinus of
o Machinery murmur: loud continuous murmur heard Valsalva
best in the left infraclavicular region (2nd left
intercostal space); and loudest at S2
DIAGNOSTICS
• Echocardiography (confirmatory test)

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o Color doppler: Findings can show blood flow from the aorta into the
pulmonary artery.
• ECG All preterm infants should
o Left axis deviation due to LVH seen in large PDA be screened with echo (if
• Chest x-ray possible).
o Prominent pulmonary artery and aortic knob at the
upper left heart border
TREATMENT
• Medical therapy (pharmacological closure):
o Decrease prostaglandin synthesis:
▪ Indomethacin
▪ Ibuprofen
o Follow-up after 48 hours with echocardiography to ensure closure
o Contraindicated in:
▪ Cardiac defects where DA required to maintain perfusion for
systemic circulation
▪ Active bleeding
▪ Suspicious or diagnosed necrotizing enterocolitis
▪ Impaired renal function
• Surgical therapy:
o Indicated when medical therapy fails and/or infant > 6 kg

o Includes percutaneous closure or surgical ligation
COMPLICATIONS
• Pulmonary hypertension.
• Bronchopulmonary dysplasia.
• Congestive heart failure.
• Infective endocarditis.
• Post-surgery → paralysis of recurrent laryngeal nerve and stridor.
PROGNOSIS
• Spontaneous closure in up to 75% of infants if < 3 months of age
• Isolated PDA has an excellent prognosis (especially small defects).
6. COARCTATION OF AORTA (COA)

• Coarctation of the aorta is a narrowing of the aorta caused by the thickening of
the medial layer at a localized point, most commonly near the insertion of the
ductus arteriosus.
TYPES (SEE FIGURE)

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• Juxtaductal coarctation (adult type): 98% of all
• Preductal: The narrowing is located proximally to the ductus arteriosus.
• Postductal: The narrowing is located distally to the ductus arteriosus.
EPIDEMIOLOGY
• Accounts for approximately 6% of all congenital heart disease
• More common in boys (2:1 men:women ratio)
• Associated conditions:
o Up to 15% of girls with
coarctation of the aorta have
Turner syndrome.
o Accompanied by bicuspid aortic
valve in over 70% of cases.
o Shone complex (Mitral stenosis +
Subaortic stenosis + CoA) is
group of left side obstructive
lesions.
PATHOPHYSIOLOGY
• Narrowing of the aorta → ↑ flow
proximal to the narrowing and ↓ flow
distal to the narrowing
• Myocardial hypertrophy and increased
collateral blood flow (e.g., Intercostal
vessels, scapular vessels)
Figure 71 Schematic representation of coarctation of
• Hypoperfusion of organs and the aorta
extremities distal to the stenosis
• Differential cyanosis: cyanosis of the
lower extremities
• Brachial-femoral delay and weak
femoral pulses
• High Blood pressure (BP) in upper
extremities and Low BP in lower
extremities (>10-20mmHg except in Figure 71 Types of coarctation of the aorta
neonates)
o If distal narrowing of the left subclavian artery: ↑ BP in both arms and ↓
BP in both legs
o If origin of left subclavian artery is involved: BP in the right arm > left
arm.

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• Cold feet and lower-extremity claudication upon physical exertion
• Systolic ejection murmur over left posterior hemithorax
• Strong apical impulse displaced to the left (due to LVH)
• Headache, epistaxis, tinnitus (due to Hypertension)
DIAGNOSIS
• Echocardiogram: (IOC)
o Narrowing of the lumen
o Any additional cardiac lesions (e.g., bicuspid aortic valve)
o Doppler: increased velocity and turbulence of blood flow through the
narrowing.
• Chest X-ray:
o Neonates: cardiomegaly with pulmonary
congestion
o Older children:
▪ Figure 3 sign: formed by the
indentation at the coarctation point
along the dilated aorta
▪ Rib notching (Rosler sign): erosion of
the lower surface of the ribs due to
increased blood flow through the
Figure 72 Chest X-ray shows rib notching on
collateral intercostal arteries. the undersurface of the posterior ribs (white
• ECG: shows LV hypertrophy. arrows).
• CT and MRI can be helpful when echocardiogram
results are deficient or unclear.
• Genetic testing for women suspected of having Turner syndrome.
• For adults, CT angiography to screen for intracranial aneurysms, abdominal
aortic aneurysms, and atherosclerotic changes to the coronary arteries.
MANAGEMENT
Neonates:
• Prostaglandin E1 IV to keep the ductus arteriosus open
• Surgical management for patients dependent on PDA
Children and adults:
• Surgical treatment is indicated in the case of:
o Heart failure
o > 20 mm Hg gradient across the coarctation
o Presence of collateral blood flow

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• Therapeutic procedures include balloon angioplasty, stent placement, or patch
aortoplasty.
COMPLICATION
• Secondary hypertension
• Aortic dissection and rupture
• Berry aneurysm → cerebral hemorrhage
• Heart failure
• Infective endocarditis
PROGNOSIS
• When detected in childhood and not treated, death occurs by 20–40 years old
due to hypertensive complications such as coronary heart disease or stroke.
• If surgery performed prior to age 20, 10-year postrepair survival estimate is
90%.
6. EBSTEIN ANOMALY OF THE TRICUSPID VALVE

• is a cyanotic congenital heart disease (CHD) characterized by the downward
displacement of the septal and posterior leaflets of the
tricuspid valve (TV) into the right ventricle (RV) with
subsequent tricuspid valve regurgitation and right
heart enlargement (known as RV “Atrialization”)
• Its caused by failure of delamination (separation) of
the TV from the myocardial wall due to:
o Maternal use of lithium in early pregnancy
o Heterogeneous genetic predisposition
EPIDEMIOLOGY
• < 1% of all cases of CHD
• 1 out of every 20,000 live births Figure 73 Diagram of EA: Note the
downward displacement of the TV and
CLINICAL PRESENTATION the resulting significantly reduced
size (Atrialization) of the RV.
• Symptoms are variable because they depend on the
severity of the downward displacement of the TV,
which dictates the degree of regurgitation and dilatation of the RV.
• In utero:
o May cause hydrops fetalis
o May cause severe cardiomegaly at birth
• Infancy to adulthood:
o Failure to thrive (FTT)
o Palpitations (arrhythmia)

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o Cyanosis
o Right-sided heart failure
• Murmur → tricuspid regurgitation (holosystolic murmur audible over most of
the anterior left side of the chest)
• Paradoxical emboli → stroke
DIAGNOSIS
• Echocardiography: Doppler and transthoracic
echocardiogram findings:
o The degree of displacement of the tricuspid
leaflets (> 8 mm/m3)
o Severity of tricuspid regurgitation
o Associated cardiac lesions (ASD, PFO)
• Chest X-ray:
o cardiomegaly (Wall-to-wall heart or Box shaped
heart)
• Electrocardiogram (ECG) looking for:
o Right bundle branch block
o Wolf-Parkinson-White Syndrome (delta waves)
o A 24-hour ECG (Holter) → evaluate arrhythmias
Figure 74 “Wall-to-wall heart” in a
MANAGEMENT neonate born with an EA
• Medical therapy
o Medical management to optimize heart failure and arrhythmias is used
prior to surgical stabilization. Medical management is indicated for
neonates and symptomatic adults:
▪ Neonates: aims to reduce pulmonary vascular pressure:
▪ Keep ductus arteriosus open → prostaglandin E1
▪ Inhaled nitric oxide
▪ Child/adult:
▪ Manage heart failure and volume overload.
▪ Manage comorbidities such as arrhythmias.
• Surgical therapy
o Indicated for symptomatic infants, older children, and medically stable
adults
o Includes closure of associated defects and ablation of accessory
conduction pathways

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7.5. ACQUIRED HEART DISEASES

Common acquired heart diseases include
• Rheumatic heart disease
• Infective Endocarditis
• pericardial disease and
• myocarditis
RHEUMATIC HEART DISEASES

• Before discussing RHD, it’s better to see the preceding events developing this
complication.
• Group A streptococcus (GAS) pharyngitis is followed by Acute rheumatic fever
and finally complicated by RHD.
I. ACUTE PHARYNGITIS
• Inflammation of the pharynx, including
o erythema,
o edema,
o exudates, or
o an enanthem (ulcers, vesicles).
• Pharyngeal inflammation can be related to environmental exposures, such as
o tobacco smoke,
o air pollutants, and
o allergens; from contact with caustic substances,
o hot food, and liquids; and
Table 82 Causes of Pharyngitis

Viruses Bacteria
Adenovirus Streptococcus pyogenes (Group A streptococcus)
Coronavirus Arcanobacterium haemolyticum
Cytomegalovirus Fusobacterium necrophorum
Epstein-Barr virus Corynebacterium diphtheriae
Enteroviruses Neisseria gonorrhoeae
Herpes simplex virus (1 and 2) Group C streptococci
Human immunodeficiency virus Group G streptococci
Human metapneumovirus Francisella tularensis
Influenza viruses (A and B) Yersinia pestis
Measles virus Chlamydophila pneumoniae
Parainfluenza viruses Chlamydia trachomatis
Respiratory syncytial virus Mycoplasma pneumoniae
Rhinoviruses Mixed anaerobes (Vincent angina
o from infectious agents.

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• The pharynx and mouth can be involved in various inflammatory conditions
such as the periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA)
syndrome, Kawasaki disease, inflammatory bowel disease (IBD), Stevens-
Table 83 GAS pharyngitis and Viral Pharyngitis

Group A Streptococcal Viral
•Sudden onset of sore throat • Conjunctivitis
• Age 5-15 yr • Coryza
• Fever • Cough
• Headache • Diarrhea
• Nausea, vomiting, abdominal pain • Hoarseness
• Tonsillopharyngeal inflammation • Discrete ulcerative stomatitis
• Patchy tonsillopharyngeal exudates • Viral exanthema
• Palatal petechiae
• Anterior cervical adenitis (tender nodes)
• Winter and early spring presentation
• History of exposure to strep pharyngitis
• Scarlatiniform rash
Johnson syndrome, and systemic lupus erythematous (SLE).
• Noninfectious etiologies are typically evident from history and physical exam,
but it can be more challenging to distinguish from among numerous infectious
causes of acute pharyngitis
• The usual clinical task is to distinguish important, potentially serious, and
treatable causes of acute pharyngitis from those that are self-limited and
require no specific treatment or follow-up. Specifically, identifying patients
who have group A streptococcus pharyngitis and treating them
with antibiotics forms the core of the management paradigm.
ETIOLOGIES
• are viral and bacterial
• Epidemiologic and Clinical Features Suggestive of Group A
Streptococcal and Viral Pharyngitis
• GAS pharyngitis dx mainly clinical in our setup and mainstay

treatment should be within 9 days (golden time) of clinical
Figure 75 of Group A Streptococcal
Manifestations. Pharyngitis

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• Complications after GAS pharyngitis (expected 10-21 days after the
symptoms): joint pain, chest pain, abnormal body movement
(ARF), decreased urine output, urine color change • Non suppurative :(ARF) &
acute post streptococcal
(glomerulonephritis). glomerulonephritis).
TREATMENT o The serotypes
M1,3,5,6,18, 29 causes
• Should be within 9 days (Golden time) after start of the ARF and
symptoms o M4, 12, 25 – APSGN
(discussed in another
• Benzathine penicillin 600,000IU IM stat for children <27 kgs
chapter).
of weight; 1.2 million IU for child > 27 kg OR • Suppurative (skin lesions)-
• Amoxicillin 50 mg/Kg/day po in three divided doses for 10 Serotype M49
days
• For patients allergic to penicillin, Erythromycin 40 mg/kg/day in four divided
doses for 10 days and
• Follow up in two days.
II. ACUTE RHEUMATIC FEVER
• Is inflammatory disease involving heart, skin, joint and
Pathogenesis
brain. • Cytotoxicity theory – States
• Develops 10-21 days after GAS pharyngitis. the enzyme streptolysin O is
• Age 5-15 yrs is the greatest risky age group. directly toxic to cardiac
• 2/3 patients have history of upper respiratory tract cells, but, its unable to
explain the substantial
infection.
period (10-21 days) to
• Most patients have serologic evidence of recent GAS develop ARF from GAS
infection. pharyngitis.
• If not treated, cause permanent lesion of cardiac valves • Immune-mediated
pathogenesis- molecular
(called RHD).
mimicry resulting
• Patients developing ARF from GAS pharyngitis have special immunologic cross-reactivity
susceptibility by genetic back ground, socioeconomic between cardiac antigenic
status, and special strain of the bacteria resulted epitopes and GAS cellular
pharyngitis. and extra cellular epitopes
• Overcrowding of a family or community remains the main

risk factor for the spread of GAS infection.
• The table below gives us the detail information, and under the table we use
the moderate/high risk criteria for our Ethiopian setup (all developing
countries).

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Table 84 Modified Jones Criteria
GUIDELINE FOR DIAGNOSIS OF INITIAL OR RECURRENT ATTACK OF RHEUMATIC FEVER (MODIFIED
JONES CRITERIA, UPDATED 2015)
Major criteria Minor criteria Supporting evidence of antecedent
(manifestations) (Manifestations) Group A Streptococcal infection
• Carditis Clinical features: • Positive throat culture or rapid

• Polyarthritis - Arthralgia streptococcal antigen test
• Erythema - Fever Elevated or increasing
• Marginatum Laboratory features: Elevated streptococcal antibody titer
• Subcutaneous acute phase reactants:
nodules - Erythrocyte
• Chorea sedimentation rate
(ESR)
- C-reactive protein
(CRP)
Prolonged P-R interval
I. Initial attack: 2 major manifestations, or 1 major and 2 minor
manifestations, plus evidence of recent GAS infection.
II. Recurrent attack: 2 major, or 1 major and 2 minor, or NB: We don’t adhere to Jones
3 minor manifestations (the latter only in the criteria in the following three
Moderate/High-Risk population), plus evidence of circumstances:
recent GAS infection. 1. When Chorea is the only
major manifestation of ARF.
III. Low-Risk population is defined as acute rheumatic
2. when Indolent carditis is the
fever (ARF) incidence <2 per 100,000 school-age only manifestation of ARF
children per year, or all-age rheumatic heart disease 3. In Recurrent ARF attack.
(RHD) prevalence of <1 per 1,000 populations.
IV. Moderate/High-Risk population is defined as ARF
incidence >2 per 100,000 school-age children per year, or all-age RHD
prevalence of >1 per 1,000 populations.
V. Carditis is now defined as clinical and/or subclinical (echocardiographic
valvulitis).
VI. Arthritis (major) refers only to polyarthritis in Low-Risk populations, but
also to monoarthritis or polyarthralgia in Moderate/High-Risk populations.
VII. Minor criteria for Moderate/High-Risk populations only include
monoarthralgia (polyarthralgia for Low-Risk populations), fever of >38°C
(>38.5°C in Low-Risk populations), ESR >30 mm/hr (>60 mm/hr in Low-Risk
populations).
THE BRIEF DISCUSSIONS OF THE MAJOR CRITERIAS

1. MIGRATORY POLYARTHRITIS
• seen approximately in 75% patients with ARF and is the earliest
manifestation of ARF

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• painful, migratory joint pain exquisitely tender even with bed clothes.
• Involves large joints (knees, ankles, wrist and elbows).
• on physical Examination:
o hot, swollen, red and tender joints
o Mono articular involvement is unusual unless anti-inflammatory
drug is given (NB: so if a child with fever and arthritis is
suspected to have ARF, it’s useful to withhold salicylate and
observe for migratory progression). It Is highly responsive to
even low dose of salicylate and if not think of alternative
diagnosis.
• Become normal in 1-3 days without treatment or it can persist for several
weeks.
2. CARDITIS
• In 50-60% of patients.
• Most serious manifestation of ARF with RHD causing mortality and morbidity
• Recurrent attack increase severity of cardiac disease (the
permanent valvular lesion)
• fever, chest pain and shortness of breath (if the heart is failed).
• On physical Examination
o fever on vital sign,
o tachypnea (may not present), tachycardia, cardiac murmur
(with/without evidence of myocarditis or/and pericarditis when seen
on Echocardiography), cardiomegaly, tender hepatomegaly (the two
show HF)and edema.
▪ MR-high pitch apical holo-systolic murmur radiates to axilla
▪ AR-high pitch decrescendo diastolic murmur at LSB.
Echocardiography can show decreased ventricular
contraction, mitral/aortic regurgitation
3. SYDENHAM CHOREA
• in 10-15% of patients
• females are more affected (2:1, F:M)
• also called rheumatic chorea
• is most common form of acquired chorea in childhood.
• 20-30% unilateral
• Presents as isolated, frequently subtle, movement disorder.
• Has longer latent period than carditis and arthritis (can be months)
History:
• Emotional liability,
• poor school performance,

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• uncontrollable movements and
• facial grimacing (all exacerbated by stress and disappear with sleep)
Physical examination:
• incoordination, hypotonia
• cranial nerve is not affected.
• motor Examination should be focused and its illicit by the following 4
maneuvers (child should attempt to sit up straight unsupported on
examination table).
a) Milkmaid’s grip - child is asked to grip both of the examiner’s index
and middle finger, then hypotonic and choreic intrusion makes to
release and re-grip again and again (milking cow type feeling)
b) Touchdown - child is seated with arms and hands fully extended up
and palms facing each other
- Typical finding is pronation of one or both hands and flexion of
elbows.
c) Spooning and Pronation - child is seated with arms extended fully
forward from shoulders, hands pronated, fingers spread wide.
- Typical finding is symmetric hyperextension at
metacarpophalangeal joint( so arms and hands looks like a
spoon)
d) Darting tongue- child is asked to protrude tongue with open mouth.
- Typical finding is inability to keep the tongue in place, darting
snake like appearance
4. ERYTHEMA MARGINATUM
• Rare- 1%
• disappearing non pluritic skin lesion
• Erythematous, serpiginous, macular lesion with pale centre.
• Mainly on trunk and extremities
• Accentuated by warming the skin.
5. SUBCUTANEOUS NODULES
• Rare ≤1%
• reveals, Firm nodules approximately 0.5-1cm in diameter along extensor
surfaces of tendons near bony prominences.
• There is a correlation between presence of this nodules and significant
rheumatic heart disease.
Table 85 Differential Diagnosis of ARF
Arthritis Carditis Chorea
Juvenile idiopathic arthritis Viral myocarditis Huntington chorea

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Reactive arthritis (eg. Shigella, Viral pericarditis Wilson disease
Salmonella, Yersinia)
Serum sickness Infective endocarditis SLE
Sickle cell disease Kawasaki disease Tic disorder
Malignancy CHD Hyperactivity
SLE Mitral valve prolapses Encephalitis
Lyme disease (Borrelia Innocent murmur
burgdorferi)
Pyogenic arthritis
Poststreptococcal reactive
arthritis
TREATMENT OF ARF
• All patients should be placed on bed rest and monitored for evidence of carditis
and allow ambulation after improvement of acute inflammation. Patients with
carditis require longer bed rest.
• consists of
o Anti-inflammatory therapy
o Antibiotic therapy and
o Heart failure management
• Goals of treatment
o Symptomatic relief of Acute Manifestation (e.g. Arthritis)
o Eradication of group A streptococcus (GAS) infection
o prophylaxis against future GAS infection to prevent progression of
cardiac disease.
o provision of education for patients and caregivers.
NB: There no therapy that slows progression of valvular damage in setting of ARF.
ANTIBIOTIC THERAPY
• Once the diagnosis of acute RF has been established and regardless of the
throat culture results, the patient should receive 10 days of orally administered
penicillin or amoxicillin or a single intramuscular injection of benzathine
penicillin to ensure eradication of GAS from the upper respiratory tract. If
penicillin allergic, 10 days of erythromycin, 5 days of azithromycin, or 10 days
of clindamycin is indicated. (Dosage, similar to acute pharyngitis)
• After this initial course of antibiotic therapy, long-term antibiotic prophylaxis
for secondary prevention should be instituted.
ANTI-INFLAMMATORY THERAPY
• Anti-inflammatory agents (e.g., salicylates, corticosteroids) should be withheld
if arthralgia or atypical arthritis is the only clinical manifestation of presumed
acute RF.

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•Premature treatment with one of these agents may interfere with the
development of the characteristic migratory polyarthritis and thus obscure the
diagnosis of acute RF. Acetaminophen can be used to control pain and fever
while the patient is being observed for more definite signs of acute RF or for
evidence of another disease.
• Patients with typical migratory polyarthritis and those with carditis without
cardiomegaly or congestive heart failure should be treated with oral
salicylates.
• The usual dose of Aspirin is 50-70 mg/kg/day in 4 divided doses orally (PO) for
3-5 days, followed by 50 mg/kg/day in 4 divided doses PO for 2-3 wk and half
that dose for another 2-4 wk.
• Determination of the serum salicylate level is not necessary unless the arthritis
does not respond or signs of salicylate toxicity (tinnitus, hyperventilation)
develop. There is no evidence that NSAIDs are more effective than salicylates.
• Patients with carditis and more than minimal cardiomegaly and/or congestive
heart failure should receive corticosteroids.
• The usual dose of Prednisone is 2 mg/kg/day in 4 divided doses for 2-3 wk,
followed by half the dose for 2-3 wk. and then tapering of the dose 5 mg/24 hr.
every 2-3 days.
• When prednisone is being tapered, aspirin should be started at 50 mg/kg/day
in 4 divided doses for 6 wk. to prevent rebound of inflammation.
• Supportive therapies for patients with moderate to severe carditis include
digoxin, fluid and salt restriction, diuretics, and oxygen. The cardiac toxicity of
digoxin is enhanced with myocarditis.
• Termination of the anti-inflammatory therapy may be followed by the
• reappearance of clinical manifestations or of elevation in ESR and CRP
• (rebound). It may be prudent to increase salicylates or corticosteroids until
near-normalization of inflammatory markers is achieved
• so, follow-up of ARF is by ESR or CRP. (CRP is more sensitive and it normalizes
after acute inflammatory has resolved, but ESR can persist elevated.) CRP
twice weekly initially, then 1-2 weeks until it normalized off therapy.
• Valve surgery is indicated rarely when there is valve leaflet or chordae
tendineae is ruptured.
SYDENHAM CHOREA
• Is generally self-limiting
• psychologic & social support and rest in quit setting
• Because chorea often occurs as an isolated manifestation after the resolution
of the acute phase of the disease, anti-inflammatory agents are usually not
indicated.

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• Sedatives may be helpful early in the course of chorea; phenobarbital (16-32mg
every 6-8 hr PO) is the drug of choice. If phenobarbital is ineffective,
haloperidol (0.01-0.03 mg/kg/24 hr divided twice daily PO) or chlorpromazine
(0.5 mg/kg every 4-6 hr PO) should be initiated.
• Some patients may benefit from a few-week course of corticosteroids.
COMPLICATIONS –
• Arthritis & chorea completely resolve without sequelae.
• Infective endocarditis
• Rheumatic heart disease
• Heart failure
PROGNOSIS
• depends on clinical manifestations of initial episode, severity of the episode
and presence of recurrence
NB: Patients having previous ARF have 50% risk of recurrent attack from each
gas pharyngitis, that’s why they require long term continuous
chemoprophylaxis (2ry prophylaxis).
Risk of recurrence is high in the first 5 yrs. of initial episode & decreases
with time. Patients with pure chorea even without other manifestations of
ARF
require prophylaxis, because ~ 20% of them without prophylaxis develop RHD
• Appx, 50-70% of patients with carditis initially recover without residual heart
disease (the more severe initial cardiac involvement the greater risk of residual
heart disease).
• Patients without carditis initially are less likely to have carditis on recurrence
(but increased attack enhance risk of cardiac involvement) and risk of
permanent heart damage increase with each recurrence
PREVENTION
• Primary Prophylaxis - treating the first attack of GAS pharyngitis
in the first 9 days of the symptoms. (Mentioned above)
• Secondary Prophylaxis
o Directed at preventing acute GAS pharyngitis inpatient with substantial
risk of recurrent ARF
o Requires continuous antibiotics (see tables below)
o Should be given as soon as the DX of ARF has been made and
immediately after the full course ofantibiotic therapy has been
completed.
o Duration depends on presence of carditis or not and whether a residual
heart diseaseis developed or not. Because, carditis on initial episode is

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most likely also present on the recurrent attack and deteriorates cardiac
structures).
o Decision to discontinue depends on careful consideration of potential
risks and benefits and observation of epidemiologic factor like risks for
exposure to GAS pharyngitis.
Table 86 Chemoprophylaxis against secondary prevention of ARF
Chemoprophylaxis against secondary prevention of ARF
Drug Dose Route
Penicillin G 600,000 IU for children weighing IM

Benzathine <60Ib(27Kg) and 1.2 million IU for children
>60Ib(27kg) every 4wk
or
Penicillin V 250mg twice daily Oral
or
Sulfadiazine or 0.5g once daily for patients weighing <60Ib Oral
Sulfisoxazole 1g once daily for patients weighing >60Ib
For people who are allergic

to penicillin and
sulfonamides
Drugs
Macrolides or Azalids Variable Oral
Table 87 Recommended Duration of antibioticsCha

Recommendation
Category Duration
Rheumatic fever without carditis 5yrs or until 21 yrs of age whichever is
longer
Rheumatic fever with carditis but 10yrs or until 21 yrs of age whichever is
without residual heart disease (no longer
valvular lesion)
Rheumatic fever with carditis and 10yrs or until 21 yrs of age whichever is
residual heart disease (persistent longer, or life long
valvular lesion)
RISK FACTORS FOR RECURRENT DISEASE

• Poor adherence to secondary prophylaxis
• A greater number of Previous attacks.
• A shorter time interval since the last attack

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• Higher likelihood of ongoing exposure to streptococcal infections like children
living in crowded situations (college students, military personnel).
• Younger age
• Already established rheumatic carditis.

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RHEUMATIC HEART DISEASE (RHD)

• Is the permanent damage of valves
Diagnosis can be made
• Usually results from repeated episode of ARF
only by subclinical carditis
• Is most important sequela of ARF and is 2nd next to (SCC) which means:
arthritis. echocardiographic
• Mitral valve is the most affected and followed by aortic evidence of mitral or
aortic valvulitis in absence
valve. But isolated aortic valve is rare rather it
of auscultatory finding and
concomitantly occurs with mitral valve. not consistent with
• Right side heart manifestations are rare, it only physiologic mitral or aortic
associated with the left side valve diseaset insufficiency.
Echocardiographic finding in Rheumatic Valvulitis

Pathologic Mitral Regurgitation Pathologic Aortic Regurgitation
1. Seen in at least 2 views 1. Seen in at least 2 views
2. Jet length >= 2cm in at least 1view 2. Jet length >= 2cm in at least 1view
3. Peak velocity >3meters/sec 3. Peak velocity >3meters/sec
4. Pansystolic jet at least 1 envelope 4. Pan-systolic jet at least 1 envelope
PATTERNS OF VALVULAR DISEASES
MITRAL INSUFFICIENCY OR MITRAL REGURGITATION (MR)

• Resulted from structural changes such as, loss of valvular substances and/or
sub valvular apparatus like elongation of chordae tendinea.
• Results HF by coupling with pan-carditis during the severe carditis of ARF.
• Involve dilation of LV and enlarging LA by increased pressure in it and bring
pulmonary congestion finally.
IN MILD LESION
• History: asymptomatic
• Physical Examination: shows quite precordium,
o High pitched Holosystolic murmur (HSM) at apex radiating to axilla and
• Investigations: Echo will show the defect, but other labs may be normal.
IN SEVERE LESION
• History: palpitation, Shortness of breath and can have orthopnea & PND.
• Physical Examination:
o Palpation: PMI is shifted(cardiomegaly), apical heave (LV hypertrophy) &
apical systolic thrill
o Auscultation:
▪ Accentuated s2,
▪ prominent s3,

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▪ Apical Holosystolic Murmur radiating to axilla and short mid-
diastolic rumbling murmur (called relative mitral stenosis or
Carey-Coombs murmur) resulted from increased blood flow across
the insufficient valve. (But MS is the result of chronic lesion after
several yrs.)
• Investigations:
o ECG-
▪ Prominent, longer duration and often bifid P waves,
▪ signs of both LV & LA hypertrophy,
▪ RV hypertrophy if PHTN is developed.
o CXR- Congestion of perihilar vessels, prominent LA (More seen on Lateral
view) and LV, Signs pulmonary vein HRN.
o ECHO-
▪ enlarged LA & LV,
▪ impaired LV systolic function,
▪ chordal thickening, chordal fusion and restricted leaflet motion →
in Chronic RHD
▪ NB: Calcification is rare in children.
• Treatment:
o In mild: typical Rx of ARF plus prophylaxis against recurrence.
o In severe:
▪ Corticosteroids,
▪ Rx of HF, arrhythmia and Infective endocarditis, ACE inhibitors &
diuretics.
o Surgery is indicated for persistent HF, dyspnea on mild activities &
progressive cardiomegaly. Patients with prosthetic valve need
prophylaxis during dental procedures to prevent.
MITRAL STENOSIS (MS)

• Is chronic process (≥10 yrs.), but it may be accelerated.
• Resulted from fibrosis of mitral ring, commissural adhesion & contraction of the
leaflets
• MILD LESION: asymptomatic, normal heart size and normal finding of ECG and
CXR, only evident in ECHO
• SEVERE LESION:
o History: Exercise intolerance, dyspnea, orthopnea, PND, hemoptysis
(rupture of bronchial & perihilar vessels + pulmonary infarction).
o Physical Examination: Atrial fibrillation, RHF (hepatomegaly, ascites,
edema), moderate cardiomegaly, accentuated s1(MS)& s2(PHTN), long
low high pitched rumbling diastolic murmur with Presystolic

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accentuation at apex, HSM of TR at Left lower sternal boarder. (if
present)
o Investigation:
▪ ECG - prominent & notched p wave, varying degrees of RV
hypertrophy, AF.
▪ CXR-LA enlargement, Kerley B line (horizontal lines @ lower lung
periphery)
▪ ECHO-thickening of mitral valve, restricted mitral valve motion,
“elbow (dog leg)” appearance of anterior leaflet of mitral
valve.[is the distinguishing feature of rheumatic mitral stenosis
from congenital stenosis).
• TREATMENT – Medical + Surgical
AORTIC INSUFFICIENCY (AR)

• is acute and show poor coaptation of leaflets or leaflet prolapse.
• Can occur in isolation 1-2 yrs after initially combined with mitral
o History: palpitation, sweating and heat intolerance (because of
excessive vasodilatation), dyspnea, orthopnea, angina with heavy
exercise, nocturnal attack with sweating, tachycardia, chest pain.
o Physical Examination: Findings in children with AR is often subtle
because most have mild disease. In addition, some of the classic findings
in adults are seldom found in children, even in those with moderate to
severe AR.
o Both examination of the peripheral pulses and auscultation of the heart
are particularly important. The increased stroke volume results in abrupt
distension of the peripheral arteries and an elevation in systolic
pressure.
o Regurgitation back into the left ventricle then leads to a rapid decline
inpressure with quick collapse of the arteries, and a low diastolic
pressure that can fall below 30 mmHg in severe disease.
o Wide pulse pressure (pp) with bounding peripheral pulse(called water
hammer or Corrigan pulse) ,elevated SBP and decreased DBP, shifted PMI
(in severe), diastolic thrill.
o Murmurs: High pitched, blowing, Diastolic murmur easily audible in full
expiration & leaning forward by placing diaphragm firmly and heard best
@upper & mid-left sternal border radiating to apex and upper Rt sternal
border.
o Aortic systolic ejection murmur b/c of increased SV.

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o Apical presystolic murmur (Austin Flint murmur) resembling MS & caused
by large regurgitant aortic flow in diastole preventing the opening of MV
fully.
o Other findings are associated with a hyper-dynamic pulse: The so called
peripheral stigmata of AR: These includes:
▪ De Musset's sign - A head bob occurring with each heartbeat
▪ Traube's sign - A pistol shot pulse (systolic and diastolic sounds)
heard over the femoral arteries
▪ Duroziez's sign - A systolic and diastolic bruit heard when the
femoral artery is partially compressed
▪ Quincke's pulses - Capillary pulsations in the fingertips or lips.
▪ Mueller's sign - Systolic pulsations of the uvula
▪ Becker's sign - Visible pulsations of the retinal arteries and pupils
▪ Hill's sign - Popliteal cuff systolic pressure exceeding brachial
pressure by more than 60 mmHg.
NB: These exaggerated or bounding pulses and the above signs are not specific to
AR. They can also be seen in things that cause marked increase in stroke volume,
aortic runoff lesions, or hyperdynamic circulations (severe anemia, fever,
thyrotoxicosis, large arteriovenous fistula, PDA and severe bradycardia.)
• Investigations
o ECG-may be normal or LV hypertrophy with strain pattern and prominent
p wave.
o ECHO-dilated LV & diastolic MV flutter or oscillation caused by aortic
regurgitant flowing hitting the valve leaflet.
• Prognosis
o mild & moderate lesions are tolerated
o Unlike MR, AR doesn’t regress.
• TREATMENT: medical + surgical
TRICUSPID VALVE DISEASE

• Primary involvement is rare, but resulted from Left side HF
• Is usually TR and On Physical Examination: characterized by prominent
pulsation of Jugular vein, systolic pulsation of liver, blowing HSM at LLSB
increase with inspiration
• Concomitantly found with mitral or aortic valve disease with/out AF.
• Treatment is medical + rarely surgical.

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PULMONARY VALVE DISEASE
• Rare & PR occur 2ry to pulmonary HTN.
• Is late finding with MS.
• Murmur called Graham steel murmur is similar with AR, but lack the bounding
pulse
• Correct DX is made by two directional ECHO and Doppler studies.

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INFECTIVE ENDOCARDITIS
• Is inflammation of endocardium usually valvular part.
• Is acute or subacute or can be non-bacterial (Viral, fungal or others
• Is the complication of CHD or RHD, but can happen without any lesion.
• Main cause of mortality and morbidity despite of the advanced prophylaxis
today.
ETIOLOGIES
• viridian & staph aureus are the most common
• Streptococcus viridian - after dental procedure
• Staph aureus- common in patients with no underlying heart disease.
• Group D enterococci - after lower bowel or genitourinary manipulation.
• Pseudomonas-in IV drug users
• Fungal- after open heart surgery. (usually in infancy done for CHD)
• CONS-common in presence of indwelling central venous catheter.
PATIENT APPROACH:
• Ranges from acute/severe to non-acute manifestations (between the
extremes).
• Risk factors like-
o Prior CHD or RHD
o Preceding dental
o Urinary tract or intestinal procedure
o Intravenous drug use
o Central venous catheter
o Prosthetic heart valve.
SYMPTOMS:
• Fever (prolonged and with weight loss, in viridan & acute with sweating in
staph aureus)>> it increases afternoon
• Chills, Chest pain and abdominal pain
• Arthralgia and myalgia
• Dyspnea, malaise, weakness
• Night sweat
COMPLICATIONS
• Glomerulonephritis
• Symptoms of Anemia
• Symptoms Of Heart Failure
• Distant Infections like in CNS (Causing Stroke, seizure, headache etc)

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• Elevated TO, Tachycardia
• Embolic phenomena (Roth’s spot, petechiae, splinter hemorrhage, Osler Nodes,
CNS or ocular lesions)
• Janeway lesion (painless, small, Erythematous or hemorrhagic lesion on palms
or soles)
• New or changing murmur- is associated with HF
• Splenomegaly with petechiae (in <50%)
• Arthritis, Arrhythmia
• Clubbing
LABORATORY STUDIES
• Positive blood culture (mainly required)
• High ESR (may be low in HF or RF), Elevated CRP
• Anemia, leukocytosis, immune complexes, hypogammaglobinemia
• Cryoglobulinemia, Rheumatoid factor, hematuria, Azotemia, high creatinine
(RF by glomerulonephritis)
IMAGING
• CXR- bilateral infiltrates, nodules, pleural effusions
• ECHO- evidence of valve vegetation, prosthetic valve dysfunction or leak,
myocardial abscess, or new onset valve insufficiency.
DIAGNOSIS
Use the modified Dukes criteria:
1. Definitive IE
▪ Clinical criteria: 2 major or 1 major + 3 minors or 5 minors
▪ Pathologic criteria: microorganisms picked from culture or
histologic examination of a vegetation or pathologic lesion;
vegetation or intra cardiac abscess by histologically showing
active endocarditis
2. Possible IE – 1 major + 1 minor or only 3 minor criteria
3. Rejected diagnosis of IE
▪ Firm alternative DX explaining evidence of suspected IE or
▪ Resolution of IE syndrome with antibiotic therapy for ≤4 days, or
▪ No evidence of IE at surgery or autopsy, or on antibiotic Rx for
≤4days, or
▪ Doesn’t meet criteria for possible IE.
• Transesophageal echocardiography is required for optimal assessment of
possible prosthetic valve endocarditis or complicated endocarditis.
• Valvular disease with stenosis or regurgitation, presence of a prosthetic valve,
congenital heart disease including corrected or partially corrected conditions

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(except isolated atrial septal defect, repaired ventricular septal defect, or
closed patent ductus arteriosus), prior endocarditis, or hypertrophic
cardiomyopathy.
• Excluding single positive cultures for coagulase-negative staphylococci and
diphtheroids, which are common culture contaminants, or for organisms that
do not cause endocarditis frequently, such as gram negative bacilli.
• Prognosis- 20-25% will die despite of Rx and 50-60% has serious morbidity.
COMPLICATIONS:
• Systemic Emboli like to CNS(Major threat)
• Pulmonary Embolism in patients with VSD or TOF
• Mycotic aneurysm,
• Acquired VSD
• Heart block resulted from abscess on conduction system
• Osteomyelitis
• Arthritis
• Renal abscess
• Purulent pericarditis and
• Immune complex mediated glomerulonephritis.
Table 88 Dukes Criteria
MAJOR CRITERIA MINOR CRITERIA

1. Positive blood culture 1. Predisposition: predisposing heart
Typical microorganism for infective endocarditis conditions or injection drug use
from two separate blood cultures 2. Fever ≥38.0°C (≥100.4°F)
• Viridians streptococci, Streptococcus gallolyticus, 3. Vascular phenomena: major arterial
HACEK group organisms, Staphylococcus aureus, or emboli, septic pulmonary infarcts, mycotic
• Community-acquired enterococci in the aneurysm, intracranial hemorrhage,
absence of a primary focus, or conjunctival hemorrhages, Janeway lesions
Persistently positive blood culture, defined as 4. Immunologic phenomena:
recovery of a microorganism consistent with glomerulonephritis, Osler’s nodes, Roth’s
infective endocarditis from: spots, rheumatoid factor
▪ Blood cultures drawn >12 h apart; or 5. Microbiologic evidence: positive blood
▪ All of 3 or a majority of ≥4 separate blood culture but not meeting major criterion, as
cultures, with first and last drawn at least 1 h noted previously or serologic evidence of
apart or active infection with an organism consistent
▪ Single positive blood culture for Coxiella burnetiid with infective endocarditis
or
▪ phase I IgG antibody titer of >1:800

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2. Evidence of endocardial involvement
Positive echocardiogram
• Oscillating intracardiac mass on valve or supporting
structures or in the path of regurgitant jets or in
implanted material, in the absence of an alternative
anatomic explanation, or
• Abscess, or
• New partial dehiscence of prosthetic valve,
or
• New valvular regurgitation (increase or change in
preexisting murmur not sufficient)
TREATMENT
• Management principles are:
o Bactericidal antibiotics (Parenteral) immediately after definitive DX is
made
o Amphotericin B and 5-fluorocytosine for Fungal Endocarditis.
o Surgery
o Treating any complications like heart failure (diuretics, digitalis and ACE
inhibitors), stroke and RF immediately.
• Antibiotic therapy should be instituted immediately once a definitive diagnosis
of infectious endocarditis is made.
• When virulent organisms are responsible, small delays may result in progressive
endocardial damage and are associated with a greater likelihood of severe
complications.
• The choice of antibiotics, method of administration, and length of treatment
should be coordinated with consultants from both cardiology and infectious
diseases
• Empirical therapy after appropriate blood cultures are drawn but before the
identifiable agent is recovered may be initiated with vancomycin plus
gentamicin in patients without a prosthetic valve and when there is a high risk
of S. aureus, enterococcus, or viridans streptococci (the 3 most common
organisms).
• High serum bactericidal levels must be maintained long enough to eradicate
organisms that are growing in relatively inaccessible avascular vegetations.
• Several weeks are required for a vegetation to organize completely; therapy
must be continued through this period so that recrudescence can be avoided.

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• A total of 4-6 wk of treatment is usually recommended. Depending on the
clinical and laboratory responses, antibiotic therapy may require modification,
and some patients require more prolonged treatment.
• With highly sensitive viridians group streptococcal infections, shortened
regimens that include oral penicillin for some portion have been recommended
for certain adults, but effectiveness studies in children are lacking.
• In nonstaphylococcal disease, bacteremia usually resolves in 24-48 hr,whereas
fever resolves in 5-6 days with appropriate antibiotic therapy.
• Resolution with staphylococcal disease takes longer.
INDICATIONS OF SURGICAL TREATMENT
• Vegetation
o Persistent vegetation after systemic embolization
o Anterior mitral valve leaflet vegetation, particularly if it is highly mobile
with size >10mm*
o One or more embolic events during the 1st 2 wk of antimicrobial
therapy*
o Increase in vegetation size despite appropriate antimicrobial therapy* †
• Valvular Dysfunction
o Acute aortic or mitral insufficiency with signs of ventricular failure †
o Heart failure unresponsive to medical therapy †
o Valve perforation or rupture †
• Perivalvular Extension
o Valvular dehiscence, rupture, or fistula †
o New heart block † ‡
o Large abscess or extension of abscess despite appropriate antimicrobial
therapy
* Surgery may be required because of risk of embolization.
† Surgery may be required because of heart failure or failure of medical therapy.
‡ Echocardiography should not be the primary modality used to detect or monitor
heart block.
PREVENTION
• is by antibiotics by using d/t criteria and having good oral hygiene.
o Strategies:
▪ Oral hygiene
▪ Antimicrobial prophylaxis for highest risk for IE.

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REVISED 2007 AMERICAN HEART ASSOCIATION SUGGEST THE FOLLOWING AS

HIGHEST RISK, INCLUDES PATIENTS WITH:
• Prosthetic Valve (Like mechanical, bioprosthetic and homograft)
• Prosthetic materials used for cardiac valve repair (anoplasty rings and chords)
• A prior history of IE
• Unrepaired cyanotic CHD
• Repaired CHD with residual shunts or valvular regurgitation at the site or
adjacent to the site of the prosthetic patch or prosthetic device
• Repaired CHD defects with catheter-based intervention involving an occlusion
device or stent during six months after the procedure
• Valve regurgitation due to structurally abnormal valve in a transplanted heart

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CHAPTER 8 - HEMATOLOGY
1. Anemia
2. Hemostasis and Bleeding Disorders

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8.1. ANEMIA
DEFINITION
• Anemia is defined as an Hb level below the normal range. The normal range
varies with age and sex. (See table below)
Table. Normal Mean and Lower Limits of Normal for Hemoglobin, Hematocrit, and
Mean Corpuscular Volume
• 51% of under 5yr children in developing country are anemic (different degrees)
(WHO)
• There are many methods of classification of anemia but the popular ones are
1. MORPHOLOGIC CLASSIFICATION
• Based on the MCV value and microscopic appearance
Table 89 Morphologic classification of anemia
Normocytic Anemia Microcytic Anemia Macrocytic Anemia

Aplastic anemia Iron deficiency Normal newborn
Leukemia Thalassemia Vitamin B12 or olate
Drug induced Lead toxicity deficiency
Hemophagocytic Anemia of chronic Down syndrome
syndromes disease Hypothyroidism
Acute infection Copper deficiency (occasionally)
Transient- Sideroblastic Drugs (zidovudine,
erythroblastopenia anemia chemotherapy)
Anemia of chronic disease Chronic liver disease
(Early Stage)
Renal disease
Hypothyroidism
Drug induced

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2. PHYSIOLOGIC CLASSIFICATION
• There are 2 major categories:
A. INCREASED DESTRUCTION OF RBCS AND BLOOD LOSS
• Hemolytic anemia
o Cellular-
▪ Membrane defects - Hereditary spherocytosis
▪ Enzyme defects - G6PD deficiency, pyruvate kinase def.
▪ Hemoglobinopathies - Sickle cell anemia, thalassemia
o Extra cellular –
▪ Autoimmune hemolytic anemia
▪ Hemolytic Dx of the new born
▪ Drug induced
▪ Fragment hemolysis – DIC, hemolytic uremic syndrome, TTP,
prosthetic heart valve
▪ Hypersplenism
▪ Plasma factors -liver Dx, abetalipoproteinemia
▪ Infections, toxins &venoms
• Blood loss
o Occult Bleeding - Blood in the feces that is not visibly apparent i.e.
Hidden. They can be seen in different causes of Upper GI or Lower GI
bleeding.
o Overt Bleeding - as in leech infestation and bleeding disorders
B. DECREASED PRODUCTION
• Mainly caused by nutritional deficiency, infections and chronic illnesses IDA,
Folate & VB12 def.
• Anemia of chronic illness
• Physiologic anemia of infancy
• Aplastic /hypo plastic anemia-secondary to infections ex. parvovirus B19
• Drugs, radiation, immune mediated
• Congenital hypo plastic anemia (diamond-Blackfan anemia)
8.1.1 APPROACH TO A PATIENT WITH ANEMIA
HISTORY AND PHYSICAL EXAMINATION

GENERAL APPROACH
• Usually careful history and physical examination (Hx and P/E) suggest the type
of Anemia the patient have. Clinical findings generally do not become apparent
until the hemoglobin level falls to
<7-8 g/dL.

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HISTORY
The symptoms may vary on the degree of the Anemia and the etiologic agents.
• Symptoms attributable to anemia – Common symptoms of anemia include lethargy,
tachycardia, and pallor. Infants may present with irritability and poor oral intake.
However, because of the body's compensatory abilities, patients with chronic anemia
may have few or no symptoms compared with those with acute anemia at comparable
hemoglobin (HGB) levels.
• Symptoms of hemolysis – Changes in urine color, scleral icterus, or jaundice may
indicate the presence of a hemolytic disorder. Hemolytic episodes that occur only in
male family members may indicate the presence of a sex-linked disorder, such as
glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Bleeding symptoms – Specific questions related to bleeding from the gastrointestinal
tract, including changes in stool color, identification of blood in stools, and history of
bowel symptoms, should be reviewed. It is also important to determine whether there
is a personal or family history of inflammatory bowel disease, celiac disease, intestinal
polyps, colorectal cancer, hereditary hemorrhagic telangiectasia, von Willebrand
disease, platelet disorders, or hemophilia.
• Severe or recurrent epistaxis also may result in anemia from blood loss and iron
deficiency.
• In adolescent girls, menstrual history should be obtained, including duration and
amount of bleeding. Severe epistaxis and/or heavy menstrual bleeding should raise
suspicion for an underlying bleeding disorder.
• Pica – The presence of pica, the intense craving for nonfood items, should be assessed
given its strong association with iron deficiency. In young children, pica may manifest
as craving dirt, rocks, and paper. In adolescents, craving for ice, or pagophagia, may
be more common.
• Past medical history – The past medical history should focus on characterizing past
episodes of anemia and identifying underlying medical conditions:
• Birth history – The birth and neonatal history should include gestational age, duration
of birth hospitalization, and history of jaundice and/or anemia in the newborn period.
Results of newborn screening (which typically includes screening for sickle cell
disease) should be reviewed.
• Previous History of anemia – Previous complete blood counts (CBCs) should be
reviewed, and, if prior anemic episodes occurred, they should be characterized
(including duration, etiology, therapy, and resolution). Prior episodes of anemia
suggest an inherited disorder, whereas anemia in a patient with previously
documented normal CBC suggests an acquired etiology. Patients with certain
hemoglobinopathies (such as HGB E or the various thalassemias) may have a history of
treatment on multiple occasions for an erroneous diagnosis of iron deficiency anemia.
• Underlying medical conditions – Past medical history and review of symptoms should
be obtained to elucidate chronic underlying infectious or inflammatory conditions that
may result in anemia. Travel to/from areas of endemic infection (eg, malaria,
hepatitis, tuberculosis) should be noted (the Centers for Disease Control and

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Prevention provides updated information on malaria and tuberculosis). Recent
illnesses should be reviewed to investigate for possible infectious etiologies of anemia.
• Drug and toxin exposure – Current and past medications (including homeopathic or
herbal supplements) should be reviewed with particular attention to oxidant drugs
that can cause hemolysis, particularly in patients with underlying G6PD deficiency (eg,
drugs such as fluoroquinolones, dapsone, nitrofurantoin, and sulfonylureas; foods such
as fava beans; and others. Possible environmental toxin exposure should be explored,
including lead exposure and nitrates in well water.
• Family history – Family history of anemia should be reviewed in depth. Family
members with jaundice, gallstones, or splenomegaly should be identified. Asking if
family members have undergone cholecystectomy or splenectomy may aid in the
identification of additional individuals with inherited hemolytic anemias.
• Dietary history – The dietary history is focused on assessing iron intake and, to a
lesser degree, folate and vitamin B12 content.
• For infants and toddlers, the type of diet, type of formula (if iron fortified), and age
of infant at the time of discontinuation of formula or breast milk should be
documented. In addition, the amount and type of milk the patient is drinking should
be determined.
o Infants and children who are exclusively fed goat's milk can develop anemia
due to folate deficiency.
o Exclusively breastfed infants who do not receive sufficient iron
supplementation may be anemic at the time of the initial screening at age 9 to
12 months, whereas infants receiving iron-fortified formula until age 12
months are unlikely to be anemic at this time, though they may be at risk for
iron deficiency during the second year of life after transitioning to cow's milk.
Pica (particularly pagophagia, the eating of ice) may suggest lead poisoning
and/or iron deficiency.
• In older children and adolescents, it is important to ask about special dietary
practices (eg, vegetarian or vegan diet), junk food intake, and picky eating habits.
Additional details of dietary screening for iron deficiency are provided separately.
• Developmental history – Parents should be asked questions to determine if the child
has reached age-appropriate developmental milestones. Developmental delay can be
associated with iron deficiency, lead toxicity, vitamin B12/folic acid deficiency, and
Fanconi anemia.
• If the onset on the anemia is at birth, we should suspect hemolytic Anemia of the
newborn. so, we need to assess
o Ask maternal & Neonate’s blood group.
o Ask the Gestational Age
o Presence of Jaundice.
• Anemia at 2-3 months of age - usually physiologic anemia
• Peak age for folate def. 4-7 months.
• Peak age for IDA 9-12 months. Screening for iron deficiency anemia is recommended
in all children at 9 to 12 months of age.

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• Iron deficiency rare in the absence of blood loss before 6 months in term or before
doubling birth weight in preterm infants.
• Neonatal anemia with
o reticulocytotic suggests hemolysis or blood loss
o reticulocytopenia, it suggests bone marrow failure or suppression (as in
Congenital infection with parvovirus B19 and Congenital red cell aplasia or
Diamond–Blackfan anemia)
• Sickle cell anemia and β-thalassemia appear as fetal hemoglobin disappears (4–8
months of age)
• Common causes of Pathologic anemia in newborns include:
o blood loss,
o immune hemolytic disease (ie, Rh or ABO incompatibility),
o congenital infection,
o twin-twin transfusion, and
o congenital hemolytic anemia (eg, hereditary spherocytosis, glucose-6-
phosphate dehydrogenase [G6PD] deficiency)
• In Anemia of Prematurity, the anemia will be due to
o Inadequate Erythropoietin production.
o Reduced red cell lifespan.
o Frequent blood sampling whilst in hospital.
o Iron and folic acid deficiency (LBW infants are at risk of IDA & folate def. early
• Some inherited causes of anemia are X-linked (eg, G6PD deficiency and X-linked
sideroblastic anemia) and occur most commonly in males.
• In post-menarchal girls, excessive menstrual bleeding is an important cause of anemia.
• Drug Intake
• Physiologic Vs Pathologic Anemia
o At birth, normal full-term infants have higher hemoglobin (Hb) levels and larger
red blood cells (RBCs) than do older children and adults. However, within the
1st wk. of life, a progressive decline in Hb level begins and then persists for 6-8
wk. The resulting anemia is known as the Physiologic Anemia of Infancy.
• Pathologic anemia in newborns and young infants is distinguished from physiologic
anemia by any of the following:
o Anemia (HGB <13.5 g/dL) within the first month of life
o Anemia with lower HGB level than is typically seen with physiologic anemia (ie,
<9g/dL)
o Signs of hemolysis (eg, jaundice, scleral icterus, or dark urine) or symptoms of
anemia (eg, irritability or poor feeding)
o G6PD -susceptible agents
o Immune-mediated hemolysis (e.g., penicillin)
o Bone marrow suppression
o Phenytoin: increases folate requirements
o Symptoms of MALABSORPTION SYNDROMES (Like, Diarrhea, weight loss,
flatulence, abdominal bloating, abdominal cramps, and pain)

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o Malabsorption of vitamins B12 and E and iron
o Inflammatory bowel disease predisposes to Anemia Of Chronic Disease or Blood
Loss
o Milk protein allergy-induced blood loss
o Intestinal resection and vitamin B12 deficiency
• BLOOD LOSS or History of bleeding disorder.
o Hx of blood loss (occult or Overt)
o GI - Hookworm infection, severe dysentery, IBD, PUD diverticular diseases,
hemorrhoids
o GU - Hematuria, schistosomiasis
o History of BAREFOOT walking (hookworm infestation rate is 25%in children
under 5yr of age)
• Symptoms of CHRONIC ILLNESSES AND INFECTIONS.
o Giardia causes iron malabsorption
o Intestinal bacterial overgrowth (blind loop) is a risk for developing vitamin B12
deficiency
o Fish tapeworm is also a risk factor for vitamin B12 deficiency
o Epstein–Barr virus, cytomegalovirus cause bone marrow suppression
o Mycoplasma and hemolysis
o Parvovirus is strongly associated with bone marrow suppression
o Chronic infection like TB and RVI
o Endocarditis
o Malarial attacks
o Hepatitis and aplastic anemia
• GROWTH AND DEVELOPMENT (Assessing developmental Milestones)
• Hx of JAUNDICE and Gallbladder disease,
Symptoms
Early symptoms
• Malaise
• Fatigability
• Anorexia
• Poor concentration
• Pallor (When Hg <7-8 g/dL.)
• Palpitation
• Shortness of breath on Exertion
Eventual symptoms
• Mental and physical retardation
• Symptoms of congestive heart failure:
o General body swelling,

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o Inability to carry out the usual childhood activities like playing and
keeping up with their peers.
• General appearance
o Acutely sick looking with anemia and fever - infectious causes
like malaria, sepsis,
o Other diseases like Leukemia, neuroblastoma usually
present with infection.
o Chronically Sick Looking as in anemia of chronic Illness(Disease)
• Vital signs
o Increased RR, PR & hypotension – case could be acute blood loss or
severe infection
o In chronic cases, Bounding pulse, Wide pulse pressure - because of High
output state.
• Anthropometric assessment
o presence of Acute or Chronic nutritional Deficiency.
o In Neonates
▪ Measure Head Circumference to assess Subgalial hemorrhage,
Cephalhematoma
• HEENT
o Frontal bossing (Due to peripheral hematopoiesis) – can be due to
Thalassemia major, severe iron deficiency.
o Eye –
▪ Pale Conjunctiva (Indicative of anemia)
▪ Icterus – indicate hemolysis, severe malaria or some liver
disease
o Tongue & buccal mucosa Pallor (Indicate anemia)
o Angular stomatitis in Iron Deficiency Anemia
o Glossitis - VitaminB12 deficiency and IDA
o papillary atrophy in tongue – IDA
• LGS
o Thyroid Examination
o LN enlargement - TB, Leukemia, HIV, IMN, lymphoma
o Parotid enlargement- HIV
• CHEST
o In Anemia due to Acute blood loss, the patients may be in Respiratory
Distress.
o Basal crepitation (In care of heart failure)
• CVS

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o Signs of heart failure
▪ Ex Gallop Rhythm, Cardiac Enlargement
▪ Flow Murmur (Functional Murmur) can be heard. Flow Murmur is a
heart murmur that is primarily due to physiologic conditions
outside the heart, as opposed to structural defects in the heart
itself.
• ABDOMEN
o Organomegaly - Hepatosplenomegaly (HSM) in infants suggest- congenital
infections (usually associated with jaundice, anemia &
thrombocytopenia)
▪ Causes - toxoplasmosis, syphilis, CMV, Rubella & parvovirus B19
o Splenomegaly -common in malaria infants & children
o Malignancies, TB, HIV, lymphoma, Epstein–Barr virus, portal
hypertension,
• Integumentary system:
o Skin Petechiae, purpura & bruising
▪ Suggest cause of BM failure, autoimmune hemolysis with
autoimmune thrombocytopenia, hemolytic uremic syndrome or
any cause of bleeding Disorder.
▪ Palmar pallor
o Hair
▪ Silky or easily pluck able hair- HIV, Malnutrition
o Nails
▪ Koilonychia (Spoon nails) - Seen In IDA
• MSS:
o Fracture- Chronic hemolysis, malignancy etc
o bone tenderness- leukemia also ass. With joint swelling
NS
• Peripheral neuropathy - Seen in Vit B12 deficiency
Figure 76 Koilonychia (Spoon nails)
LABORATORY STUDIES
The initial laboratory evaluation of the Anemic child generally consists of
• CBC with differential,
• Peripheral morphology,
• Stool exam,
• Blood film and
• Reticulocyte count.
1. Complete Blood Count — The CBC provides information about the RBCs and
other cell lines (ie, white blood cells [WBCs] and platelets). All three cell lines
should be evaluated for abnormalities.

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a. Hemoglobin and hematocrit
b. Red blood cell indices — The RBC indices are an integral part of the
evaluation of the anemic child. These include:
- Mean corpuscular volume (MCV) is measured directly by
automated blood cell counters and represents the mean value
(in femtoliters [fL]) of the volume of individual RBCs in the
blood sample.
- Normal values for MCV vary based upon age (infants have
increased MCV compared with older children). In preterm
infants, MCV values increase with decreasing gestational age.
- MCV is the most useful RBC parameter when evaluating a
patient with anemia and is used to classify the anemia as
Microcytic, Normocytic and Macrocytic.
ii. Red cell distribution width (RDW) –
- is a quantitative measure of the variability of RBC sizes in
the sample (Anisocytosis).
- Normal values vary little with age and are generally
between 12 and 14 percent.
iii. Mean Corpuscular Hemoglobin Concentration (MCHC)
- is a calculated index (MCHC = HGB/HCT), yielding a value of
grams of HGB per 100 mL of RBC.
- MCHC values vary depending upon the age (infants have
higher values than older children) and sex (males have
slightly higher values than females) of the child. MCHC also
increases with decreasing gestational age.
iv. Anemia can also be classified on the basis of MCHC as
Hypochromic, Normochromic and Hyperchromic
2. Blood Smear — A review of the peripheral smear is an essential part of any
anemia evaluation. Even if the patient's RBC indices are normal, review of the
blood smear may reveal abnormal cell that can help identify the cause of
anemia. The following features should be noted:
a. RBC size – A normal RBC should have the same diameter as the nucleus
of a small lymphocyte. This comparison will help the investigator
identify the patient with microcytosis or macrocytosis.
b. Central pallor – Increased central pallor indicates hypochromic cells,
which most often are seen in iron deficiency and thalassemia. On the
other hand, spherocytes and reticulocytes do not display central pallor
because they are not biconcave discs.

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c. Fragmented cells – Although the patient's overall RBC indices may be
normal, review of the blood smear may reveal the presence of small
numbers of fragmented cells, indicating a Microangiopathic process.
d. Other features – Other anemias may be characterized by typical
morphologic abnormalities, which may go undetected without inspection
of the peripheral smear; these include:
- Sickle cells, as seen in sickle cell disease
- Elliptocytes, as seen in congenital Elliptocytosis
- Stomatocytes, as seen in hereditary or acquired stomatocytosis
- Pencil poikilocytes, which can be seen in iron deficiency anemia
or thalassemia
- Target cells, as seen in the various hemoglobinopathies,
including thalassemia, as well as in liver disease and post
splenectomy
- Bite cells and Heinz bodies are seen in hemolytic anemia due to
oxidant sensitivity, such as G6PD deficiency
- Hyper segmented neutrophils suggest vitamin B12 or folate
deficiency.
- The presence of early WBC forms (eg, blasts) along with anemia
should raise the suspicion of leukemia or lymphoma.
3. Reticulocyte count —
• Identified by the presence of residual RNA.
• The reticulocyte is reported as a percentage of the RBC population.
• After the first few months of life, the normal reticulocyte percentage is the
same as that of the adult, approximately 1.5 percent.
• The simplest approach is to calculate the absolute reticulocyte count (ARC)
as follows:
- Absolute Reticulocyte Count (ARC) = Percent Reticulocytes x
RBC count/L
• The ARC is an indication of bone marrow erythropoietic activity and is used
to classify the bone marrow response to anemia with a high ARC reflects an
increased erythropoietic response to hemolysis or blood loss.
• Anemia with a low or normal ARC reflects deficient production of RBCs (ie,
a reduced marrow response to the anemia).

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Diagnostic approach by laboratory test abnormalities the history, physical
examination, and initial laboratory tests are used to narrow the diagnostic
possibilities and guide further testing.
- Abnormalities in other cell lines —
the first step in narrowing the
diagnostic possibilities is determining
whether the patient has an isolated
anemia or if other cell lines (i.e.,
white blood cells [WBCs] and platelets
[PLT]) are also abnormal
- Pancytopenia - Causes of
pancytopenia in children include
leukemia, infection, myelosuppressive
medications, aplastic anemia, and
hypersplenism etc.
- Anemia with thrombocytopenia -
Causes of anemia associated with low
PLT count include hemolytic uremic
syndrome (HUS), thrombotic
thrombocytopenic purpura (TTP), and Evans syndrome.
- Anemia with thrombocytosis - Iron deficiency anemia is commonly associated
with thrombocytosis but can also be associated with thrombocytopenia. Other
causes of anemia associated with elevated PLT count include post-splenectomy
anemia and infection or inflammation.
- Anemia with leukocytosis - Causes of anemia associated with elevated WBC
count include leukemia and infection.
PROGNOSIS
• Varies with the type of anemia and age of the patient
• Death may result because of cardiac failure.
GENERAL MANAGEMENT OF ANEMIA

• Vitamins and minerals supplements (Iron tablets, folate and vitamin b12)
changing child's diet medication and/or discontinuing causative medications
• Treatment of the underlying disorder (like malaria and hook-worm)
• Surgery to remove the spleen (if related to certain hemolytic anemias)
• Blood transfusions, if necessary (to replace significant loss)
• Blood transfusions in those without symptoms is not recommended until the
hemoglobin is below 6 to 8 g/dl.

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• antibiotics (as appropriate if infection is the cause) stem cell transplant (for
bone marrow failure, such as aplastic anemia, Fanconi anemia or Diamond-
Blackfan anemia)
• Erythropoiesis-stimulating agents
• Hyperbaric oxygen

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8.2. HEMOSTASIS AND BLEEDING DISORDERS
HEMOSTASIS
• Hemostasis is the process of blood clotting in areas of blood vessel injury.
• Over time, the clot is lysed by the fibrinolytic system, and normal blood flow is
restored.
• Hemostasis has 2 major components:
o Primary Hemostasis: which contains
▪ Blood Vessels
▪ Platelets
o Secondary Hemostasis:
▪ Coagulation proteins,
▪ Anticoagulant proteins, and
▪ Fibrinolytic system.
THE HEMOSTATIC PROCESS

Mechanism of action of common
PRIMARY HEMOSTASIS Anti-platelet drugs
• Processes involved in the formation of a platelet plug (white • Aspirin - Irreversible COX-1
inhibition resulting in
thrombus) following endothelial injury. inhibition of release of
• Vascular injury results in release of endothelin which causes Thromboxane A2 (TXA2)
vasoconstriction and platelet accumulation and the location of • Clopidogrel - ADP receptor
inhibitor
injury. • Abciximab - Glycoprotein
• Platelets undergo 3 main changes IIb/IIIa inhibitor.
1. Adhesion
▪ platelets bind to vWF via platelet GpIb receptor at
the endothelial injury site.
2. Activation
▪ After binding to vWF, platelets change their shape and release mediators
that lead to activation of more platelets (positive
feedback). A white thrombus is transient,
▪ These are mediated through unstable, and easily dislodged. It
stabilizes through the process of
- Adenosine diphosphate (ADP), secondary hemostasis.
- Thromboxane A2 (TXA2),
- Platelet-activating factor (PAF) and Calcium.
3. Aggregation
▪ formation of a white thrombus composed of platelets and fibrinogen
▪ Mediated by GpIIb/IIIa-receptor and fibrinogen

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SECONDARY HEMOSTASIS
• Processes that lead to stabilization of the platelet plug
(white thrombus) by creating a fibrin network.
• It is achieved through two coagulation pathways that
merge into a common pathway.
I. Extrinsic pathway of coagulation: triggered by
endothelial injury
II. Intrinsic pathway of coagulation: triggered by
tissue factor (exposed collagen, kallikrein, and
kininogen (HMWK) activate factor XII).
III. Common Pathway Figure 77 Coagulation cascade
INHIBITION OF HEMOSTASIS
• In order to prevent hypercoagulability as well as excessive bleeding, activation of
the coagulation cascade and the processes that inhibit it occur
Diseases that affect the
simultaneously in the circulatory system (procoagulant- inhibitors of the coagulation
anticoagulant balance). cascade may lead to
hypercoagulability.
• These include
o Tissue factor pathway inhibitor: inhibits tissue factor
o Protein C and protein S: which inhibits factors Va and VIIIa.
o Antithrombin: Degrades thrombin and factors IXa and Xa
o Drug-induced: anticoagulant treatment.
8.2.1. DISORDERS OF PRIMARY HEMOSTASIS

TYPICAL FEARURES OF DISORDERS OF PRIMARY HEMOSTASIS
• Immediate onset of bleeding after trauma or surgery
• Bleeding of mucous membranes, e.g:
o Epistaxis
o Bleeding gums
o Gastrointestinal bleeding
o Menorrhagia
• Cutaneous and subcutaneous bleeding, e.g:
o Petechiae
o Purpura
o Superficial ecchymoses
o Easy bruising
Figure 78 Petechiae and Purpura
CAUSES OF DISORDERS OF PRIMARY HEMOSTASIS

• Platelet Disorders: can be due to

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o Platelet deficiency (Thrombocytopenia): decreased platelet number.
o Platelet dysfunction (thrombocytopathy): disorders that lead to dysfunctional
adhesion or aggregation of platelets.
• Disorders affecting the vessel wall
o Thrombotic microangiopathy (e.g., HUS and TTP)
THROMBOCYTOPENIA (NORMAL PLATELET COUNT 150-450×10 9 /L)

• Thrombocytopenia refers to a reduction in platelet count to <150×109/L.
• Causes of thrombocytopenia include
1. Increased destruction
▪ Immune mediated
- Acute and chronic ITP
- Thrombocytopenia associated with HIV
- Neonatal immune thrombocytopenia
- Drug-induced immune thrombocytopenia (including heparin-induced
thrombocytopenia)
- Posttransplant thrombocytopenia
▪ Nonimmune thrombocytopenia
- Thrombocytopenia of infection
- Thrombotic microangiopathic disorders (i.e. HUS, TTP, HELLP Syndrome)
- Drug induced (quinine, etc.)
2. Decreased production
▪ Hereditary disorders
▪ Acquired disorders
- Aplastic anemia
- Myelodysplastic syndrome
- Marrow infiltrative process—neoplasia
- Nutritional deficiency states (iron, folate, vitamin B12, anorexia
nervosa)
3. Sequestration
▪ Hypersplenism
▪ Hypothermia
▪ Burns

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IDIOPATHIC (AUTOIMMUNE) THROMBOCYTOPENIC PURPURA

• It’s the most common cause of acute onset of thrombocytopenia
Differential Diagnosis for ITP
in an otherwise well child. • Evans syndrome
• Hemolytic-Uremic Syndrome
EPIDEMIOLOGY (HUS)
• Peak age 1-4 yr. • Thrombotic
Thrombocytopenic Purpura
• More often in late winter and spring after the peak season of (TTP)
viral respiratory illness. • Disseminated Intravascular
Coagulation (DIC)
CLINICAL MANIFESTATIONS • Heparin-Induced
Thrombocytopenia (HIT)
• a sudden onset of generalized petechiae and purpura.
• SLE
• bleeding from the gums and mucous membranes. • HIV infection
• a history of a preceding viral infection 1-4 wks before the onset • Hematologic Malignancy
of thrombocytopenia (in 50 to 65% of the patients). • autoimmune
lymphoproliferative
UK CLASSIFICATION OF ITP (BASED ON SYMPTOMS, NOT ON syndrome
LEVEL OF THROMBOCYTOPENIA) • Thrombocytopenia–Absent
Radius (TAR) syndrome.
I. No symptoms.
II. Mild symptoms: bruising and petechiae, occasional minor
epistaxis, very little interference with daily living.
III. Moderate symptoms: more severe skin and mucosal lesions, more troublesome
epistaxis and menorrhagia.
IV. Severe symptoms: bleeding episodes—menorrhagia, epistaxis, melena—
requiring transfusion or hospitalization, symptoms interfering seriously with the
quality of life.
LABORATORY FINDINGS
Mechanism of
• CBC thrombocytopenia in ITP
o Severe thrombocytopenia (platelet count <20 × 109/L) is Antibodies against αIIb-β3 and
common. GPIb bind to platelet surface,
circulating antibody-coated
o Anemia: if there is profuse bleeding platelets are recognized by the
o White Blood Cell (WBC) count and differential count should Fc receptor on splenic
be normal. macrophages, ingested, and
destroyed.
• Peripheral Morphology
o Normal or increased numbers of megakaryocytes.
o Megakaryocytes may appear to be immature and reflect increased platelet
turnover.
o Otherwise, normal.
• Direct Antiglobulin Test (Coombs): to rule out Evans syndrome (autoimmune
hemolytic anemia and thrombocytopenia).
• HIV testing

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• ANA: if there are features of SLE
• Indications for Bone Marrow Aspiration/Biopsy The presence of abnormal
o Abnormal WBC count or differential findings such as
o unexplained anemia, hepatosplenomegaly, bone or
o history and physical examination findings suggestive of a joint pain, remarkable
lymphadenopathy other
bone marrow failure syndrome or malignancy.
cytopenias, or congenital
anomalies suggests other
TREATMENT diagnoses.
• Initial approaches to the management of ITP include the
following:
1. No therapy/Observation
▪ Recommended by the American Society of Hematology guidelines for
children with only mild bleeding symptoms such as bruising or petechiae.
2. Treatment with either IVIG
▪ IVIG 0.8-1.0 g/kg - induces a rapid rise in platelet count There are no data showing
(usually >20 × 109 /L) in 95% of patients within 48 hr. that treatment affects either
3. Corticosteroid therapy: effective in 70–80% of patients short- or long-term clinical
outcome of ITP. Instead, they
▪ Prednisone at 1-4 mg/kg/24 - induce a more rapid rise in
Improve the recovery of
platelet count than in untreated patients with ITP. thrombocytopenia.
▪ Continued for short term, usually till platelet count is
>20×109/L.
4. Splenectomy: curative in 80% of patients
▪ is reserved for
IVIG appears to induce a response
A. the older child (≥4 yr) with severe ITP that has lasted by downregulating Fc-mediated
>1 yr (chronic ITP) and whose symptoms are not easily phagocytosis of antibody coated
controlled with therapy and platelets.
B. when life-threatening hemorrhage (ICH) complicates

acute ITP, if the platelet count cannot be corrected rapidly with
transfusion of platelets and administration of IVIG and corticosteroids.
5. Rituximab
▪ As an alternative to Splenectomy to treat Chronic ITP.
▪ Induces partial or complete remission on 30–40% of children.
6. Thrombopoietin receptor agonists
OUTCOME
• In 70–80% of children who present with Acute ITP, spontaneous resolution occurs
within 6 mo.
• The outcome/prognosis may be related more to age; ITP in younger children is
more likely to resolve, whereas development of chronic ITP in adolescents
approaches 50%.

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• Severe bleeding is rare (<3%) and ICH occurs in fewer than 1% of patient.
CHRONIC AUTOIMMUNE THROMBOCYTOPENIC PURPURA

• When an Acute ITP persists for more than 12 months. Occurs in approximately 20%
of the patients.
• At that time, a careful reevaluation for associated disorders should be performed,
especially for
▪ autoimmune disease (e.g., SLE),
▪ chronic infectious disorders (e.g., HIV), and
▪ nonimmune causes of chronic thrombocytopenia
▪ H. pylori infection
• Therapy should be aimed at
▪ Controlling symptoms
▪ Preventing serious bleeding.
• Splenectomy is successful in inducing complete remission in 64–88% of children
with chronic ITP.
• Romiplostim and Eltrombopag can be used to induce thrombopoiesis.
VON WILLEBRAND DISEASE (VWD)

• Von Willebrand disease (VWD) is the most common inherited bleeding disorder.
• VWD is caused by a defect in or deficiency of von Willebrand factor (VWF).
• Von Willebrand factor (VWF) – is a plasma protein that’s synthesized and stored in
endothelial cells (in Weibel-Palade bodies) and platelets (in α-granules)
o It changes conformation and provides the glue to which the platelet VWF
receptor, the glycoprotein Ib complex, binds, tethering platelets to sites of
injury.
o VWF also serves as a carrier protein for factor VIII (FVIII), protecting FVIII
from degradation in plasma.
Table Types of vWF Deficiency

Types Inheritance Mechanism
Type 1 (60–80%) AD inheritance Mild to moderate deficiency of vWF
and factor VIII
Type 2 AD inheritance Dysfunctional vWF
Type 3 AR inheritance Complete absence of vWF and
factor VIII
PRESENTATION
• Often asymptomatic
• Positive family history
• Symptomatic individuals may develop the following symptoms:

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o Mucocutaneous bleeding
o Ecchymoses, easy bruising
o Epistaxis
o Bleeding of gingiva and gums
o Petechiae
• Prolonged bleeding from minor injuries
• Bleeding after surgical procedures or tooth extraction
• GI bleeding (can be caused by angiodysplasia)
• Menorrhagia (affects up to 92% of women with vWD)
• Postpartum hemorrhage
LABORATORY DIAGNOSIS
• ↑ Bleeding time
• Normal or ↑ aPTT (may be prolonged as a result of factor VIII deficiency)
• Normal PT and platelet count
• ↓ Factor VIII
• ↓ vWF antigen levels
• Ristocetin cofactor assay: failure of platelet aggregation or a ristocetin cofactor
level < 30 IU/dL
TREATMENT
• Desmopressin (DDAVP): stimulates vWF release from endothelial cells.
o Not effective for type 3
• Concentrates containing vWF and factor VIII: indicated for severe bleeding, as
prophylaxis for surgical procedures and if DDAVP treatment is ineffective
• Oral contraceptives for menorrhagia.

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8.2.2. DISORDERS OF SECONDARY HEMOSTASIS

COMMON FEATURES OF DISORDERS OF SECONDARY HEMOSTASIS
• Onset: delayed (minutes to hours after trauma)
• Deep tissue bleeding, e.g.:
o Hemarthrosis (esp. in hemophilia)
o Hematomas
• Large, palpable ecchymoses
LABORATORY TESTS (KNOW IT DEPTH!)

PROTHROMBIN TIME
• The production of Fibrin via the extrinsic pathway and the final common pathway
(common to both extrinsic and intrinsic cascades) requires tissue thromboplastin
(tissue factor), factor VII (extrinsic pathway), and factors X, V, prothrombin
(factor II), and fibrinogen.
• The functioning of these pathways is measured by the plasma prothrombin time.
• The test bypasses the intrinsic pathway and uses thromboplastins to substitute for
platelets.
• Within this combined pathway, factors VII, X, and prothrombin are vitamin-K
dependent and are altered by warfarin.
o For this reason, the PT is used as a measure of the anticoagulant activity of
warfarin and other vitamin K antagonists.
INTERNATIONAL NORMALIZED RATIO (INR)
• INR is derived from Prothrombin Time (PT) which is calculated as a ratio of the
patient’s PT to a control PT standardized for the potency of the thromboplastin
reagent.
• It’s calculated by as (Patient PT/Control PT).
• For Normal patients who are not on anticoagulation, the INR is usually 1.0
regardless of the ISI or the particular performing laboratory.
ACTIVATED PARTIAL THROMBOPLASTIN TIME
• The activated partial thromboplastin time (aPTT) measures the intrinsic and
common pathways of coagulation.
• It is called partial since platelet substitutes are used which are only partial
thromboplastins; they are incapable of activating the extrinsic pathway, which
requires complete tissue thromboplastin (Tissue Factor).
• The aPTT is sensitive to inhibitors such as heparin and to deficiencies of all
coagulation factors except factors VII and XIII.
• It is less sensitive than the PT to deficiencies of the common pathway (factors X
and V, prothrombin, and fibrinogen).

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• High levels of a single factor (eg, factor VIII) can shorten the aPTT.
HEREDITARY CLOTTING FACTOR DEFICIENCIES

FACTOR VIII OR FACTOR IX DEFICIENCY (HEMOPHILIA A OR B)
• Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX
deficiency) are the most common and serious congenital Hemophilia usually affects
males, as it is primarily an X-
coagulation factor deficiencies.
linked recessive disease.
• The clinical findings in hemophilia A and hemophilia B are
virtually identical.
• Reduced levels of the contact factors (factor XII, high- Severity Of Hemophilia is
molecular-weight kininogen, and prekallikrein) are assessed by % activity of the
associated with significant prolongation of activated partial specific clotting factor.
thromboplastin time (aPTT; also referred to as PTT), but are (Normal is 100% which is
not associated with hemorrhage. equivalent to 100 IU/dL of factor
VIII or factor IX in 100ml of
plasma.)
- Mild Hemophilia (>5%) of the
• Since both factor VIII or factor IX doesn’t cross the specific clotting factor are
placenta, bleeding symptoms may be present from birth available,
or may occur in the fetus. - Moderate Hemophilia (1-5%)
• 2% of neonates with hemophilia sustain intracranial of the specific clotting factor
hemorrhages, and 30% of male infants with hemophilia available
bleed with circumcision. - Severe Hemophilia (<1%) of
• 90% will have evidence of increased bleeding by 1 yr of the specific clotting factor is
available
age.
• The hallmark of hemophilic bleeding is hemarthrosis
(bleeding into joint space), the earliest most often being
in the ankle.
• Oral mucosa bleeding, epistaxis, excessive bleeding following small procedures
(e.g., dentist procedures) can also be present.
• Patients with mild hemophilia who have factor VIII or factor IX levels >5 IU/dL
usually do not have spontaneous hemorrhages and may not be diagnosed till
older age.
LABORATORY FINDINGS AND DIAGNOSIS

• Screening
o Prothrombin time: normal
o Activated partial thromboplastin time (aPTT): usually prolonged
• If aPTT prolonged → Mixing Study should be done (Confirmatory)
Mixing Study

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First, measure the aPTT of the patient's blood. Then, mix the patient's plasma with
external plasma that is known to contain sufficient clotting factors and measure
the resulting aPTT. If the patient suffers from hemophilia, the aPTT will be
corrected in the sample with the external plasma.
• If Mixing Study is positive, then quantitative assessment of factor
activity levels will give us the quantitative finding. Hemophilia occurs in ≈ 1:
• If correction does not occur on mixing, an inhibitor may be 5,000 males, with 85% having
present, which are antibodies against the active clotting site. factor VIII deficiency and 10–
15% having factor IX
For these patients quantitative Bethesda assay for inhibitors
deficiency.
should be performed to measure the antibody titer.
TREATMENT
• Substitution of clotting factors
o Mild or moderate hemophilia: when needed (e.g., trauma or Life-threatening hemorrhages
surgery) require replacement therapy to
o Severe hemophilia: prophylactic (additional substitution may achieve a level equal to that of
normal plasma (100 IU/dL, or
be needed in, e.g., trauma)
100%).
• Desmopressin: for mild Hemophilia A
o Triggers the release of vWF from endothelial cells, which
leads to an increase in factor VIII plasma concentration.
• Antifibrinolytic therapy (e.g., ε-Aminocaproic acid, tranexamic acid)
o Inhibits the break-down of clots to reduce the risk of bleeding.
• Emicizumab: a humanized monoclonal bispecific antibody that reduces the risk of
bleeding events
o Used for treatment of hemophilia A
o Mechanism of action: bridges activated factor IX and factor X by binding to
both factors (thereby replacing the deficient factor VIII) → activation of factor
X → restored clotting cascade.

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CHAPTER 9 - ONCOLOGY
1. Hematologic malignancies
2. Solid tumors
3. Oncologic emergencies

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9.1. HEMATOLOGIC MALIGNANCIES
9.1.1. THE LEUKEMIA`S

• The leukemia`s group of malignant disease in which genetic abnormalities in a
hematopoietic cell gives rise to an unregulated clonal proliferation of cells.
• Is the most common malignant neoplasm in childhood
o 31 per of all malignancies in children 15
• Annual incidence 4.5 per 10 children.
• ALL accounts for 77%, AML =11%, CML =2-3%, juvenile myelo monocytic
leukemia =1-2
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
• Peak incidence at, 2-3 years of age
• Occurs more in boys than girls
• More common in children with chromosomal abnormalities; like down synd.
Bloom syn. Ataxia telangiectasia and Fanconi anemia
ETIOLOGY
• Most are unknown; although several genetic and environmental factors are
associated
• Mostly caused by post conception somatic mutation in lymphoid cells.
o Exposure to medical diagnostic radiation in utero and in childhood
o Drugs, Alkylating agents, Benzene exposure
o Association between B-cell ALL and EBV infection; in developing
countries
CELLULAR CLASSIFICATION
• Depends on characterizing the malignant cells in the marrow to determine the
morphology as measured by cell membrane markers, cytogenetic and molecular
features
• Morphology- adequate for establishing diagnosis; other studies for disease
classification
WHO CLASSIFICATION LEUKEMIA
• B-lymphoblastic leukemia
• precursor B-ALL/-85
• T -lymphoblastic leukemia
• mature b-cell
• Burkitt leukemia; one of the most rapidly growing human cancer
▪ chromosomal abnormalities used to sub classify all into prognostic group.
• Initial presentation usually Nonspecific and brief
o Anorexia, fatigue, malaise, irritability and LGIF
o Bone joint pain or asp in lower extremities bone pain is severe and can
wake the pt. at night.

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o as disease progresses symptoms of marrow failure appear; -
▪ Pallor fatigue, exercise intolerance bruising, oral mucosal
bleeding or epistaxis fever or from the disease or infection
• Organ infiltration can cause
▪ LAP, hepatosplenomegaly, testicular enlargement or CNS involvement or
cranial neuropathies, headache, seizure
▪ Respiratory distress from anemia or mediastinal node compression.
ON PHYSICAL EXAMINATION
• Findings of pallor, listlessness, purpuric and petechial rash, mucous membrane
hemorrhage.
• LAP, splenomegaly or less often hepatomegaly
• Exquisite bone joint tenderness joint swelling and effusion
• Rarely; Sign of increased ICP; papilledema, retinal hemorrhage and CNS palsies
• Large anterior Mediastinal mass or most frequently in adolescent boys with T-
ALL
• B-ALL- most common immune phenotype with onset @ 1-10 year of age
• leukocyte presentation (median) 33,000/ul
▪ Thrombocytopenia in 75%
▪ Hepatosplenomegaly in 30-40%
▪ T - ALL have higher leukocyte count
▪ CNS involvement a, presentation in 5 % of patients (10-15 % blasts in CSF)
Fever in a patient with acute leukemia must always be treated as a sign of infection
until proven otherwise!
DIAGNOSIS
• Strongly suggested by peripheral morphology:
o Sign of marrow failure i.e., Pancytopenia with few reticulocytes…
• Anemia and thrombocytopenia in most patients.
• When peripheral blood result suggests possibility of leukemia → Do marrow
aspiration and Biopsy.
• ALL is diagnosed by bone marrow evaluation that shows >25% of marrow cells as
homogenous population of lymphoblast.
• Diagnosis of leukemia is made readily in patients with typical sign and
symptoms of anemia, thrombocytopenia, elevated WBC with blasts present on
smear
• Elevated LDH is also a clue
• When there is only pancytopenia
▪ Aplastic anemia
▪ Myelofibrosis
▪ Familial hemophagocytic lymphohistiocytosis
• High index of suspicion to differentiate ALL from infectious mononucleosis.in
patients with acute onset of fever and LAP
• JIA in patients w-fever, bone pain but often no tenderness and joint swelling

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• also, must be differentiated from AML other BM infiltrating malignancies
TREATMENT
• Early and aggressive chemotherapy improves the prognosis, e.g., 80–90% of
patients with ALL achieve complete remission with chemotherapy.
• Risk directed therapy → The standard of current ALL treatment
• Accounts for
▪ Age at diagnosis
▪ Initial WBC count
▪ Immunophenotypic and cytogenetic characteristics of blasts
▪ Rapidity of early treatment response
▪ Assessment of MRD at the end of induction therapy
• Age 1-10years and leukocyte count <50,000/ul ---- Standard Risk
• Age <1year and older than 10 and WBC count (initial)> 50,000 ----> High Risk
• T-ALL
• Slow response to treatment Adversely affect out come
• chromosomal abnormalities
o Hypodiploidy
o Philadelphia chromosome
o MLL gene arrangement
• Standard treatment involves chemotherapy for 2-3years and most achieve
remission at the end of induction phase
1) INITIAL TREATMENT - REMISSION INDUCTION
• To eradicate the leukemic cells from the bone marrow
• Treatment given for 4 weeks
• consists of
o Vincristine weekly + corticosteroid/dexamethasone or prednisone +
o Single dose of long-acting pegylated asparaginase + daunomycin weekly
(for patients at higher risk)
• 98 %of patients are in remission which is defined as
o <5% blasts in the marrow and
o neutrophils and platelet count returns to near- normal levels
• Intrathecal chemo at the start and once during induction
2) SECOND PHASES – CONSOLIDATION
• Intensive CNS therapy in combination with continued intensive systemic
treatment
• To prevent later CNS relapse
• Intrathecal chemo LP
• Brain irradiation for patients with higher risk of CNS relapse;
o CSF lymphoblast at Diagnosis and
o Increased CSF leukocytes or physical signs of CNS leukemia (cranial nerve
palsy)
3) INTENSIFICATION PHASE
▪ Includes phases of aggressive treatment (delayed intensification) + relative
toxic phases (interim maintenance)

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▪ to eradicate residual disease
o 14-28 week of therapy
▪ Multiagent chemo
o Cytarabine, methotrexate, asparaginase and vincristine
4) MAINTENANCE PHASE
▪ Lasts for 2-3 years
▪ Patients are given;
o Daily mercaptopurine
o weekly methotrexate PO
o Intermittent doses of vincristine and corticosteroid
▪ Patients with poor prognostic features (induction failure or extreme
hypodiploidy) may undergo bone marrow transplantation at first remission
▪ Adolescent and young adults have inferior prognosis relative to children <15years
old, thus require more intensive therapy
▪ They have better outcomes when treated with pediatric rather than protocols
TREATMENT OF RELAPSE
▪ Time from diagnosis + site of relapsed ds (important prognostic indicators)
✓ Relapse commonly occurs in the marrow
o 15-20% of patients with ALL and carries the most serious complications if
it occurs during/shortly after completion of therapy
o Intensive chemo with agents not previously used
o Allogeneic stem cell transplantation
✓ CNS relapses
▪ Decrease to <5
▪ Diagnosis confirmed by demonstrating the presence of leukemic cells in
the CSF
▪ Treatment includes intrathecal medications and cranial or craniospinal
irradiation
▪ Systemic chemo also used
✓ Testicular relapse/ in <2% of boys
▪ Usually after completion of treatment
▪ Painless swelling of both1/both testis
▪ Diagnosis - Biopsy of affected the tests
▪ Systemic chemotherapy + local irradiation
SUPPORTIVE CARE
▪ Patients with high WBC are prone to Tumor Lysis Syndrome (See oncologic
emergencies) – Which can result in
o Acute Kidney Injury caused with high levels of uric acid serum
prevented or treated with allopurinol or urate oxidate
▪ Marked increase in uric acid excretion can result in
• the precipitation of uric acid in the renal tubules and
renal vasoconstriction,
• impaired autoregulation,
• decreased renal flow,
• oxidation, and inflammation,

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▪ resulting in Acute Kidney Injury.
▪ Chemotherapy produces myelosuppression which can reduce
o Erythrocyte (RBCs) sometimes requiring transfusion.
▪ Aggressive empirical antibiotics treatment for Sepsis in Neutropenic fever
(See oncologic emergencies).
▪ Prophylaxis for Pneumocystis jirovecii during chemo and for months after
completion of treatment
PROGNOSIS
• Overall 5years survival is approximately 90%
ACUTE MYELOID LEUKEMIA (AML)
• Accounts for 11% of the cases of childhood leukemia in the United States; it is
diagnosed in approximately 370 children annually.
• The relative frequency of AML increases in adolescence, representing 36% of
cases of leukemia in 15-19 years old
• Several chromosomal abnormalities associated with AML have been identified
• Risk factors include;
o Ionizing radiation,
o Chemotherapeutic agents (e.g., alkylating agents, epipodophyllotoxin),
o Organic solvents,
o Paroxysmal nocturnal hemoglobinuria, and
o Certain syndromes: Down syndrome, Fanconi anemia, Bloom syndrome,
Kostmann syndrome, Shwachman-Diamond syndrome, Diamond-Blackfan
syndrome, Li-Fraumeni syndrome, and neurofibromatosis type 1.
CELLULAR CLASSIFICATION
• The characteristic feature of AML is that >20% of bone marrow cells on bone
marrow aspiration is diagnostic
• WHO has proposed a new classification system that incorporates morphology,
chromosome abnormalities, and specific gene mutations
▪ Acute myeloid leukemia with recurrent genetic abnormalities
▪ AML with myelodysplasia-related changes
▪ Therapy-related myeloid neoplasms
▪ Acute myeloid leukemia, not otherwise specified
▪ Myeloid sarcoma
▪ Myeloid proliferations related to Down syndrome
• Symptoms and signs of AML is a result of replacement of bone marrow by
malignant cells and caused by secondary bone marrow failure.
• Can present with any or all of the findings associated with marrow failure in
ALL
• In addition, patients with AML present with signs and symptoms that are
uncommon in ALL, including
• Subcutaneous nodules or “blueberry muffin” lesions (especially in
infants),

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• Infiltration of the gingiva (especially in monocytic subtypes),
• Signs and laboratory findings of disseminated intravascular coagulation
(especially indicative of APL), and
• Discrete masses, known as chloromas or granulocytic sarcomas. These
masses can occur in the absence of apparent bone marrow involvement
and typically are associated with a t (8;21) translocation.
• Chloromas also may be seen in the orbit and epidural space.
DIAGNOSIS
•Analysis of bone marrow aspiration and biopsy specimens reveals hyper
cellular marrow consisting of a monotonous pattern of cells with blast
population >20%.
• Flow cytometry and Special stains assist in identifying myeloperoxidase-
containing cells/AUER RODS, confirming AML.
TREATMENT AND PROGNOSIS
• Aggressive multiagent chemotherapy is successful in
inducing remission in approximately 85–90% of patients.
• Survival rate of 60–70%
• Induction chemotherapy regimens
o Anthracycline in combination with high-dose
Cytarabine
• Up to 5% of patients die of either
o Infection or Figure 79 Acute myeloid leukemia
o Bleeding before a remission can be achieved. (AML)
• Post remission therapy is chosen based on a combination Acute myeloid leukemia (AML): bone-
of cytogenetic and molecular markers of the leukemia as marrow findings of Auer rods (pink,
well as the response to induction chemotherapy (MRD needle-like structures in the cytoplasm)
in a myeloblast
assessment).
• Patients with unfavorable prognostic features (e.g.,
monosomies 7 and 5, 5q−, and 11q23 abnormalities) who have inferior
outcome with chemotherapy might benefit from stem cell transplant in first
remission.
• Increased supportive care in AML (because the intensive therapy they receive
produces prolonged bone marrow suppression with a very high incidence of
serious infections, especially viridians streptococcal sepsis and fungal
infection).
o These patients may require prolonged hospitalization, filgrastim
(granulocyte colony-stimulating factor), and prophylactic
antimicrobials.

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9.1.2. LYMPHOMA
• Third most common cancer among U.S. children (≤14 years old), with an annual
incidence of 15 cases per 1 million children.
• The most common cancer in adolescents, accounting for >25% of newly diagnosed
cancers in those 15-19 years old.
• The 2 broad categories of lymphoma;
o Hodgkin lymphoma and
o non-Hodgkin lymphoma
HODGKIN LYMPHOMA
• Malignant process involving the lymphoreticular system that accounts for 6% of
childhood cancers.
• Accounts for approximately 5% of cancers in children ≤14 years old; it accounts
for approximately 15% of cancers in adolescents (15-19 years), making HL the
most common malignancy in this age-group
• There is a bimodal age distribution, with peaks at 1
o 5-35 years of age and
o again after 50 years
• Male predominance among young children but lessens with age.
• Infectious agents may be involved, such as HHV 6, CMV, and (EBV)
PATHOGENESIS
• The Reed-Sternberg (RS) cell, a pathognomonic
feature of HL, is a large cell (15-45 µm in
diameter) with multiple or multilobulated nuclei
• Revised World Health Organization Classification
of Lymphoid Neoplasms for HL
o Nodular lymphocyte predominance
o Classical Hodgkin lymphoma
▪ Lymphocyte rich
▪ Mixed cellularity
▪ Nodular sclerosis
▪ Lymphocyte depletion
Figure 80 Pathognomonic histologic finding for Hodgkin
CLINICAL MANIFESTATIONS lymphoma: The Reed-Sternberg cell 'owl-eyes'
• Typical presentation with painless, nontender,

firm, rubbery, cervical or supraclavicular lymphadenopathy and usually some
degree of mediastinal involvement.
• Hepatosplenomegaly may be encountered.
• Depending on the extent and location of nodal and extra nodal disease,
patients may present with
o Symptoms and signs of airway obstruction (dyspnea, hypoxia, cough),
pleural or pericardial effusion,
o Hepatocellular dysfunction, or
o Bone marrow infiltration (anemia, neutropenia, or thrombocytopenia).

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• Systemic symptoms, classified as B symptoms (that are considered important
in staging) are unexplained fever >38°C (100.4°F), weight loss >10% total body
weight over 6 mo., and drenching night sweats.
DIAGNOSIS
• Any patient with persistent, unexplained lymphadenopathy unassociated with
an obvious underlying inflammatory or infectious
process should undergo Chest Radiography to
identify the presence of a large mediastinal
mass before undergoing lymph node biopsy
• Formal excisional biopsy is preferred over
needle biopsy to ensure that adequate tissue is
obtained, both for
o Light microscopy and
o for appropriate Immunohistochemical and
molecular studies.
• Next, Extent of disease (Stage) should be
determined to allow selection of appropriate
Figure 81 Hodgkin lymphoma. CXR showing mediastinal
therapy lymphadenopathy.
• Evaluation includes history, physical
examination, and imaging studies,
• Laboratory studies should include
• Complete Blood Cell Count (CBC) to identify abnormalities that might suggest
marrow involvement;
• Erythrocyte Sedimentation Rate (ESR); and measurement of serum ferritin,
which is of some prognostic significance and, if abnormal at diagnosis, serves as
a baseline to evaluate the effects of treatment
• A Chest Radiograph is particularly important for measuring the size of the
mediastinal mass in relation to the maximal diameter of the thorax
o Determines bulk disease which is prognostically significant.
• Chest CT defines the extent of a mediastinal mass if present and identifies
hilar nodes and pulmonary parenchymal involvement,
• Bone Marrow Aspiration and Biopsy should be performed to rule out advanced
disease.
• Bone scans are performed in patients with bone pain and/or elevation of
Alkaline Phosphatase (ALP).
• PET scans are essential as a prognostic tool in HL, enabling therapy to be
reduced in those predicted to have a good outcome and identifying those at
risk of relapse.

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THE STAGING CLASSIFICATION CURRENTLY USED FOR HL IS,
LUGANO CLASSIFICATION FOR HODGKIN LYMPHOMA
Table 90 Lugano Classification for Hodgkin Lymphoma
STAGE INVOLVEMENT EXTRANODAL STATUS
I One node or group of Single extra nodal lesions
adjacent nodes without nodal involvement
II Two or more nodal groups Stage I or II by nodal
on the same side of the extent with limited
diaphragm contiguous extranidal
involvement
II bulky II with bulk disease Not applicable
III Nodes on both sides of the Not applicable
diaphragm; nodes above
the diaphragm with spleen
involvement
IV Additional noncontiguous Not applicable
extra lymphatic
involvement
•
The absence or presence of
o fever >38°C (100.4°F) for 3 consecutive days,
o drenching night sweats, or
o unexplained loss of >10% of body weight in the 6-mo. preceding
admission are to be denoted in all cases by the suffix letter A or B,
respectively
TREATMENT
• Treatment of HL in pediatric patients is risk adapted and involves the use of
combined chemotherapy with or without low-dose involved-field radiation
therapy based on response.
• Treatment is determined largely by
o Disease stage,
o Presence or absence of B symptoms, and
o The presence of bulky nodal disease.
• Complete response rate of 70–80% and cure rate of 40–50% in patients with
advanced-stage disease.
• The combination chemotherapy regimens in current use are based on
o COPP (cyclophosphamide, vincristine [Oncovin], procarbazine, and
prednisone) or
o ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and
dacarbazine), with the addition of prednisone, cyclophosphamide, and
etoposide (ABVE-PC and BEACOPP) or

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o BAVD (brentuximab vedotin, doxorubicin [Adriamycin], vincristine,
dacarbazine) in various combinations for intermediate- and high-risk
groups.
• Risk-adapted protocols are based on both staging criteria and rapidity of
response to initial chemotherapy. The aim is to reduce total drug doses and
treatment duration and to eliminate radiation therapy, if possible.
RELAPSE
• Most relapses occur within the 1st 3 years after diagnosis, but relapses as late
as 10 years have been reported.
• Patients who achieve an initial chemo-sensitive response but relapse or
progress before 12 mo. from diagnosis are candidates for myeloablative
chemotherapy and autologous stem cell transplantation, with or without
radiation therapy
PROGNOSIS
• With the use of current therapeutic regimens, patients with favorable
prognostic factors and early-stage disease have an event-free survival (EFS) of
85–90% and an overall survival (OS) at 5 years of >95%.
• Patients with advanced-stage disease have slightly lower EFS (80–85%) and OS
(90%), respectively, although OS has approached 100% with dose-intense
chemotherapy.
• Prognosis after relapse depends on the time from completion of treatment to
recurrence, site of relapse (nodal vs extra nodal), and presence of B symptoms
at relapse.
• Patients whose disease relapses >12 months after chemotherapy alone or
combined-modality therapy have the best prognosis, and their relapses usually
respond to additional standard therapy, resulting in a long-term survival of 60–
70%
NON-HODGKIN LYMPHOMA
• Accounts for approximately 60% of lymphomas in children.
• 2nd most common malignancy between ages 15 and 35 years.
• In contrast to adult NHL, which is predominantly indolent, pediatric NHL is
usually high grade.
• Most children and adolescents with NHL present with de novo disease,
• A small number of patients have NHL secondary to specific etiologies, including
o inherited or acquired immunodeficiencies (e.g., severe combined
immunodeficiency syndrome, Wiskott-Aldrich syndrome),
o virus-associated malignancy (e.g., HIV, EBV),
o and as part of genetic syndromes (e.g., ataxia telangiectasia, Bloom
syndrome)

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PATHOGENESIS
• Three most prevalent subtypes of childhood and adolescent NHL with different
treatment approaches are
o Lymphoblastic Lymphoma (LBL),
o Mature B-cell Lymphoma, and
o Anaplastic Large Cell Lymphoma (ALCL).
▪ LBL arises from precursor T lymphocytes and less often from precursor B
lymphocytes, with biology and treatment approaches similar to Acute
Lymphoblastic Leukemia.
▪ Mature B-cell Lymphomas comprise 2 main pathologies,
o Burkitt lymphoma (BL) and
o Diffuse Large B-cell Lymphoma (DLBCL).
▪ DLBCL is further divided into several subtypes: the Germinal Center B-cell–Like,
which carries a favorable prognosis and accounts for the vast majority of
pediatric cases of DLBCL, and the subtypes with poorer prognosis,
▪ Most cases of ALCL are of mature T-cell origin, with a smaller percentage of
null-cell and B-cell origin
• Depends primarily on pathologic subtype and sites of involvement.
• The current revised staging system used for NHL is the International Pediatric
Non-Hodgkin Lymphoma Staging System (IPNHLSS)
• Approximately 70% of patients with NHL present with advanced disease (stage
III or IV), including extra nodal disease with bone marrow and central nervous
system (CNS) involvement. B symptoms of fever, weight loss, and night sweats
can be seen, particularly in ALCL, but unlike HL, are not prognostic.
Table 91 The International Pediatric Non-Hodgkin Lymphoma Staging System (IPNHLSS)

Stage I
A single tumor with the exclusion of the mediastinum and abdomen. (N: nodal; EN: extra nodal;
bone (B) or skin (S): EN-B, EN-S) S
Stage II
A single extra nodal tumor with regional node involvement. Two or more nodal areas on the same
side of the diaphragm. A primary gastrointestinal tract tumor (usually in the ileocecal area), with or
without involvement of associated mesenteric nodes, that is completely resectable. (If malignant
ascites or extension of the tumor to adjacent organs, it should be regarded as stage III.)
Stage III
Two or more extra nodal tumor(s) (including bone or skin: EN-B, EN-S) above and/or below the
diaphragm. Two or more nodal areas above and below the diaphragm. Any intrathoracic tumor
(mediastinal, hilar, pulmonary, pleural, or thymic). Intraabdominal and retroperitoneal disease,

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including liver, spleen, kidney, and/or ovary localizations, regardless of degree of resection. (Except
a primary gastrointestinal tract tumor [usually in the ileocecal region], with or without involvement
of associated mesenteric nodes, that is completely resectable.) Any paraspinal or epidural tumor,
whether or not other sites are involved. Single bone lesion with concomitant involvement of extra
nodal and/or nonregional nodal sites.
Stage IV
Any of the above findings with initial involvement of the central nervous system (stage IV CNS), bone
marrow (stage IV BM), or both (stage IV combined) based on conventional methods. For each stage,
type of examination and degree of BM and CNS involvement should be specified, using the
abbreviations to identify involvement.
• The primary site of tumor involvement and the pattern of metastasis vary by
pathologic subtype.
o LBL typically manifests as a symptomatic mediastinal mass and also has
a predilection for spreading to the bone marrow, CNS, and testes in
males.
o BL commonly manifests as
▪ Diffuse leukemia presentation or massive abdominal (sporadic
type) or
▪ Head and Neck (endemic type)
tumor and can metastasize to the
bone marrow or CNS.
o DLBCL usually manifests as either an
abdominal or a mediastinal primary tumor
and, rarely, disseminates to the bone
marrow or CNS.
o ALCL manifests either as a primary
cutaneous manifestation (10%) or as
systemic disease (90%) with dissemination
to liver, spleen, lung, or mediastinum. Figure 82 Burkitt lymphoma (Endemic type)
Bone marrow or CNS disease is rare in ALCL.
• Site-specific manifestations of NHL include
o Painless, rapid lymph node enlargement;
o Cough or dyspnea with thoracic involvement;
o Superior mediastinal syndrome (see oncologic emergencies);
o Ascites, increased abdominal girth or intestinal obstruction with an
abdominal mass;
o Nasal congestion, earache, hearing loss, or tonsil enlargement with
Waldeyer ring involvement; and
o Localized bone pain
• Can present as a life-threatening oncologic emergency.

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o Superior Mediastinal Syndrome can occur as a consequence of a large
mediastinal mass causing obstruction of blood flow or respiratory
airways.
o Spinal cord tumors can cause cord compression and acute paraplegias
requiring emergent radiation therapy.
o Tumor lysis syndrome (TLS) can occur from rapid cell turnover, which is
especially common in BL. TLS can result in severe metabolic
abnormalities, including hyperuricemia, hyperphosphatemia,
hyperkalemia, and hypocalcemia. This can rapidly lead to renal
insufficiency /failure, as well as cardiac abnormalities, if not
aggressively treated.
LABORATORY FINDINGS
• CBC; measurements of electrolytes, lactate dehydrogenase, uric acid, calcium,
phosphorus, blood urea nitrogen, creatinine, bilirubin, alanine
aminotransferase, and aspartate aminotransferase;
• Bone marrow aspiration and biopsy;
• Lumbar puncture with cerebrospinal fluid cytology, cell count, and protein;
chest radiographs; and abdominal ultrasound for initial diagnosis.
• Staging relies on more detailed anatomic imaging, with CT for neck, chest,
abdomen and pelvic imaging and MRI the preferred modality for suspected CNS
disease of brain and spine
TREATMENT
• Primary modality of treatment for childhood and adolescent NHL is multiagent
systemic chemotherapy and/or immunotherapy with intrathecal chemotherapy
• Surgery is used mainly for diagnosis.
• Radiation therapy is used only in special circumstances, such as CNS
involvement in LBL or the presence of acute superior mediastinal syndrome or
paraplegias.

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9.2. SOLID TUMORS IN CHILDREN
9.2.1. CENTRAL NERVOUS SYSTEM TUMORS

• Central nervous system (CNS) tumors include both nonmalignant and malignant
tumors of the brain and spinal cord.
• Primary central nervous system (CNS) tumors are a heterogeneous group of
diseases that collectively are the most common malignancy in childhood and
adolescence. The overall mortality among this group approaches 30%.
• Primary malignant CNS tumors are the second most common childhood
malignancies after hematologic malignancies and are the most common
pediatric solid organ tumor
• Patients with CNS tumors have the highest morbidity—primarily neurologic—of
all children with malignancies.
o Outcomes have improved over time with innovations in neurosurgery,
radiation therapy, chemotherapy, and immune therapy. The treatment
approach for these tumors is multimodal.
INCIDENCE
• In the United States the average annual incidence of primary nonmalignant and
malignant CNS tumors for children and adolescents ≤19 years of age was 6.21
cases per 100,000 population
o 58 percent of cases were malignant
o 42 percent were nonmalignant.
• In the United States, CNS tumors are the most common solid tumors in children
and a leading cause of cancer death in children 0 through 14 years.
• Malignant CNS tumors account for approximately 15 to 20 percent of all
childhood malignancies.
o Age – The incidence of childhood CNS tumors varies with age
o Sex – The rate is higher in males compared with females
o Race and ethnicity – The incidence of CNS tumors per 100,000
population in CBTRUS is greatest in White and Asian/Pacific Islander
children.
DISTRIBUTION BY TUMOR TYPE

• Glioma account for approximately one-half of all CNS tumors in children and
adolescents.

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• Medulloblastoma – It accounts for approximately 6 to 7 percent of all pediatric
CNS tumors (malignant and nonmalignant) [2]. It occurs primarily in the
cerebellum
• Embryonal tumors –Embryonal tumors are highly malignant brain tumors
associated with a very poor prognosis
• Tumors of the sellar region – Tumors of the sellar region include pituitary
tumors and craniopharyngiomas. Together, they account for approximately 15
percent of all pediatric CNS tumors
• Glioneuronal and neuronal tumors –They account for approximately 7 percent
of all pediatric CNS tumors
• Tumors of cranial and paraspinal nerves –. They account for approximately 5
percent of all pediatric CNS tumors
• Germ cell tumors –. They account for approximately 3 to 4 percent of all
pediatric CNS tumors. Approximately two-thirds of these tumors occur in the
pineal and suprasellar areas, and the remaining occur in the supratentorial
region.
• Meningiomas –They account for approximately 2 to 3 percent of all pediatric
CNS tumors
• Lymphomas <1 percent of all pediatric CNS tumors).
• Unclassified tumors – Unclassified tumors include hemangiomas and other
unspecified neoplasms.
RISK FACTOR
• Most are unknown
• two established risk factors for CNS tumor include:
1. Exposure to ionizing radiation − Cranial irradiation results in an
increased risk of developing meningiomas, gliomas, and nerve sheath
tumors. In particular, high-dose cranial irradiation in patients with acute
lymphoblastic leukemia is associated with a 6- and 10-fold increase in
the risk of glioma and meningioma, respectively
2. Genetic predisposition 8 percent with CNS tumors
▪ Genetic syndromes that confer an increased risk of developing
tumors of the nervous system include
• Neurofibromatosis (NF)
• Tuberous sclerosis
• Von Hippel-Lindau disease
• Basal cell nevus syndrome,
• Li-Fraumeni
• Turcot syndrome

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• Prognosis – Survival time after diagnosis with primary brain or other CNS tumor
varies considerably, depending on the age of the child and the tumor type.
• CNS tumors can produce symptoms and signs by
o Local invasion;
o Compression of adjacent structures; and
o Increased intracranial pressure (ICP) by either a mass effect, which
compresses normal CNS structures, or by causing obstruction of
cerebrospinal fluid flow, resulting in Hydrocephalus.
• The clinical manifestations of childhood CNS tumors may be subtle and/or
nonspecific and vary with the child's age and tumor location.
AGE OF THE PATIENT

• In infant, macrocephaly is the most common presenting symptom because of
o the unfused cranial sutures can accommodate rising ICP without acutely
compromising the neurologic status;
• In infants and young children may be unable to articulate certain symptoms
(e.g., headaches) and therefore are more likely to present with irritability.
• Nausea and vomiting are common presenting symptoms at any age.
• In older children and adolescents, other common findings include
o Headache,
o Abnormal gait,
o Poor coordination,
o Papilledema, and
o Seizures.
TUMOR LOCATION
• Common symptoms based upon the tumor location include the following
o Posterior fossa tumors – Nausea, vomiting, headache, and abnormal gait
and coordination.
o Brainstem tumors – Abnormal gait and coordination and cranial nerve
palsies.
o Spinal cord tumors – Back pain and/or weakness and abnormal gait.
o Supratentorial and central tumors – Symptoms are generally
nonspecific, and, therefore, these tumors tend to have longer delayed in
their diagnosis from the onset of the first symptoms. The most common
presenting symptoms are headache and seizures.
COMMON PRESENTING SIGNS AND SYMPTOMS

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• Headache
o is the most common manifestation of CNS tumors, occurring in
approximately one-third of affected children.
o generally due to increased ICP.
o classically described as an early morning headache that is often relieved
by vomiting.
o However, many children do not present with these classic symptoms.
o Headaches may be either focal or diffuse.
o DDx migraine, tension headaches
▪ the presence of other CNS manifestations with the headache can
differentiate headaches associated with increased ICP from other
causes
• Nausea and vomiting
o Common symptoms at any age.
o Posterior fossa tumors are particularly likely to cause nausea and
vomiting.
• Ataxia and gait abnormalities
o Ataxia and difficulty with coordination = Posterior fossa lesions.
o Clumsiness, worsening handwriting, changes in speech, or difficulty in
motor skills such as running or hopping = Initial cerebellar dysfunction
o Abnormal gait= Spinal cord tumors.
• Seizures
o Seizures may be a clinical finding, particularly in patients with low-grade
supratentorial lesions
• Cranial nerve palsies —
o Cranial neuropathies, such as diplopia (double vision), nystagmus,
inability to adduct the eye during attempted lateral gaze, facial palsy,
drooling, and difficulties with swallowing, suggest underlying brainstem
pathology
o Younger children may not be able to complain of diplopia. Instead, they
may squint, cover one eye with their hand, or tilt their head to one side.
• Impaired vision
o Vision impairment may be due to cranial neuropathy (eg, diplopia) from
a brainstem lesion,
o increased ICP leading to papilledema, or
o a lesion along the optic pathway that courses from the occipital pole of
the cerebral cortex through the optic chiasm to the retina
• Torticollis (head tilt)
o is often underestimated as a first symptom of CNS tumors.
o can occur with posterior fossa tumors and cervical spinal cord tumors .

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o Sudden-onset nontraumatic torticollis should therefore raise a suspicion
of spinal cord tumor or posterior fossa tumor, particularly in the
presence of any other focal signs in a young child.
o Tumors that arise from the floor of the fourth ventricle are often
associated with torticollis and ataxia
• Papilledema
o refers to bilateral optic disc swelling that is due to ICP.
o It occurs when ICP is transmitted to the optic nerve sheath.
o It is a physical finding in approximately 10 to 15 percent of children with
CNS tumors and is more frequent in patients with posterior fossa lesions
• Macrocephaly
o is the most common presenting symptom in infants.
o Infants may also present with bulging fontanelle and/or splayed sutures.
o It can also be seen in older children with brain tumors, but it is less
common in this age group compared with infants.
• Developmental delay and behavioral changes
o Infants and young children may present with irritability and failure to
achieve developmental milestones.
o Changes in behavior or personality and declining school performance are
subtle signs of increased ICP in older children.
• Endocrinopathies (growth impairment, diabetes insipidus, precocious puberty,
and obesity)
o may be present at the time of diagnosis in children with
chiasmatic/hypothalamic lesions such as craniopharyngioma
• Diencephalic syndrome
o is a rare consequence of hypothalamic tumors and is characterized by
failure to thrive with severe emaciation but normal linear growth,
increased appetite, and hyperactivity
• Neurocutaneous syndromes
o Children with neurocutaneous syndromes (eg, tuberous sclerosis [TS],
neurofibromatosis type 1 [NF1]) are at increased risk of developing brain
tumors
• Congenital central nervous system tumors Congenital CNS tumors are rare,
representing less than 2 percent of all childhood brain tumors.
• Spinal tumors
o Peripheral or back pain, focal weakness, gait abnormalities, and spinal
deformity are the most common presenting symptoms of a spinal cord
tumor.
DIAGNOSIS

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NEUROIMAGING
• Indications
o Persistent headache (defined as a continuous or recurrent headache
lasting for >4 weeks) with any of the following features:
▪ Wakes a child from sleep
▪ Occurs upon waking
▪ Occurs in a child <4 years of age
▪ Associated with disorientation or confusion
o Persistent vomiting upon waking
o Visual findings, including any of the following:
▪ Papilledema
▪ Optic atrophy
▪ New-onset nystagmus
▪ Reduced acuity not due to refractive error
▪ Visual field reduction
▪ Proptosis
▪ New-onset paralytic (noncomitant) squint
o Motor findings, including any of the following:
▪ Regression in motor skills
▪ Focal motor weakness
▪ Abnormal gait and/or coordination
▪ Bell's palsy with no improvement over four weeks
▪ Swallowing difficulties without an identifiable local cause
• Choice of modality
o CT SCAN— MRI provides superior imaging compared with CT for brain
tumors; however, CT is often the first imaging study performed because
it is more widely available, has a shorter required study time, and
usually does not require sedation.
▪ CT is the preferred initial study in an emergent situation with a
medically unstable child in whom elevated intracranial pressure
(ICP) is suspected. However, it is important to note that a normal
CT study does not completely exclude the possibility of a brain
lesion.
o MRI – is the modality of choice with a child suspected to have a primary
spinal tumor. MRI of the spine is also performed in staging brain tumors
that have a predilection for leptomeningeal spread.
o Positron emission tomography scans (PET) - are not routinely used at
all centers as part of standard work-up for brain tumors, but they can
provide useful information to supplement those from MRI scans.

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▪ PET scans utilize a positron-emitting radionuclide isotope coupled
with a sugar (eg, fluorodeoxyglucose) to differentiate malignant
lesions with a high metabolic rate from more benign lesions and
surrounding tissue with a lower metabolic rate.
▪ PET scan is useful in determining the areas of maximum glucose
utilization within the tumor, which can guide the neurosurgeon to
biopsy the location within the tumor with the most aggressive
behavior. It is also used to differentiate recurrent tumor from
changes due to radiotherapy.
HISTOLOGY
• This diagnostic step is to obtain tissue to establish the histologic diagnosis and,
whenever possible, reduce the tumor burden for most CNS tumors. The long-
term prognosis of some types of tumors, such as medulloblastoma and
ependymoma, is dependent on the degree of surgical resection. Postsurgical
therapy, which may include radiation and/or chemotherapy, is dependent upon
the histologic diagnosis.
SPECIFIC CNS TUMORS

ASTROCYTOMA
• Astrocytomas are a heterogeneous group of tumors that account for
approximately 40% of pediatric CNS malignancies. These tumors occur
throughout the CNS
o Low-grade astrocytomas (LGAs) , the predominant group of
astrocytomas in childhood, are characterized by an indolent clinical
course.
o Pilocytic astrocytoma (PA) is the most common astrocytoma in children,
accounting for approximately 20% of all brain tumors
o Diffuse astrocytoma (DA) The 2nd most common astrocytoma which
consists of a group of tumors characterized by a pattern of diffuse
infiltration of tumor cells amidst normal neural tissue. DA accounts for
15% of brain tumors, with the fibrillary type the most common in
children.
o Pilomyxoid astrocytoma
o Malignant astrocytomas are less common in children and adolescents
than in adults, accounting for 7–10% of all childhood brain tumors.
EMBRYONAL TUMORS OR PRIMITIVE NEUROECTODERMAL TUMORS (PNETS)

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• These are the most common group of malignant CNS tumors of childhood,
accounting for approximately 20% of pediatric CNS tumors. They have the
potential to metastasize to the neuraxis and beyond.
• The group includes
o Medulloblastoma,
o Supratentorial PNET,
o Ependymoblastoma,
o Medulloepithelioblastoma, and
o Atypical teratoid/rhabdoid tumor,
• Medulloblastoma accounts for 90% of embryonal CNS tumors and is a cerebellar
tumor occurring predominantly in males and at a median age of 5-7 yr.
CRANIOPHARYNGIOMA
• Craniopharyngioma is a common tumor of childhood, accounting for 7–10% of all
childhood tumors.
GERM CELL TUMORS
•Germ cell tumors of the CNS are a heterogeneous group and primarily tumors of
childhood, arising predominantly in midline structures of the pineal and
suprasellar regions.
• They account for 3–5% of pediatric brain tumors.
• The peak incidence of germ cell tumors occurs in children 10-12 yr old. Overall,
there is a male preponderance, although there is a female preponderance for
suprasellar tumors.
TUMORS OF THE BRAINSTEM
• Tumors of the brainstem are a heterogeneous group and account for 10–15% of
childhood primary CNS tumors.
• Outcome depends on tumor location, imaging characteristics, and the patient's
clinical status. Patients with these tumors may present with motor weakness,
cranial nerve dysfunction, cerebellar dysfunction, and signs of increased ICP.
METASTATIC TUMORS
• Metastatic spread of other childhood malignancies to the brain is uncommon.
Childhood ALL and NHL can spread to the leptomeninges, causing symptoms of
communicating hydrocephalus.
MANAGEMENT
• An open surgical procedure is the preferred approach for most childhood brain
tumors to obtain tissue for a histologic diagnosis and bulk removal where
possible. Tumors deeply located in the brain are not amenable to open surgical
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• Patients with clinical and/or neuroimaging evidence of elevated intracranial
pressure (ICP) require urgent neurosurgical intervention (eg, tumor resection
and/or placement of a shunt to relieve hydrocephalus). In addition, for most
children undergoing surgery for tumor resection, we suggest perioperative
glucocorticoid therapy to reduce peritumoral edema.
• Patients with brain tumors commonly experience seizures, which may require
antiseizure medication. The choice of agent is based on drug interactions,
safety profile, and clinician and patient preference. We suggest not using
prophylactic anticonvulsants in patients without a history of seizures (Grade
2C). However, some neurosurgeons may reasonably choose to provide seizure
prophylaxis in the perioperative setting if the patient is deemed to be at high
risk of postoperative seizures based on the location of the tumor and/or extent
of resection.
• Children with certain brain tumors (eg, lesions located in the hypothalamus or
pituitary gland) may present with endocrine abnormalities, including growth
failure, hypothyroidism, and diabetes insipidus (DI). Management focuses on
treating the specific endocrine abnormalities and may require hormonal
replacement therapy
• The use of radiation therapy is dependent on the histologic diagnosis of the
tumor. Although radiation therapy is an effective adjunct, it is associated with
both acute and long-term complications. In particular, infants and young
children with developing nervous systems are at increased risk for long-term
neurodevelopmental impairment. Long-term complications are generally
irreversible and include radiation necrosis, white matter injury, vasculopathy,
and secondary malignancies
• The use of chemotherapy is dependent on the underlying tissue histology. It is
routinely used in combination with surgery and radiation therapy for older
children to treat embryonal tumors (eg, medulloblastoma
• For children with life-threatening tumors, pediatric palliative care is an
important component of management.
• Rarely, brain parenchymal metastases occur from lymphoma, neuroblastoma,
rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and clear cell sarcoma of
the kidney.
• Medulloblastoma is the childhood brain tumor that most often metastasizes
extraneurally.

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9.2.2. NEUROBLASTOMA
• Neuroblastomas are embryonal cancers
of the peripheral sympathetic nervous
system with heterogeneous clinical
presentation and course, ranging from
tumors that undergo spontaneous
regression to very aggressive tumors
unresponsive to intensive multimodal
therapy.
EPIDEMIOLOGY
• Neuroblastoma is the most common

extracranial solid tumor in children
and the most commonly diagnosed malignancy in infants. It accounts for 8–10%
of childhood malignancies and one third of cancers in infants.
• Neuroblastoma accounts for >15% of the mortality from cancer in children. The
median age of children at diagnosis of neuroblastoma is 22 month , and 90% of
cases are diagnosed by 5 yr of age. The incidence is slightly higher in boys and
in Caucasian population
• Clinical diversity correlates closely with numerous clinical and biological
factors (including patient age, tumor stage and histology, and genetic and
chromosomal abnormalities). For example, most infants with disseminated
disease have a favorable outcome following treatment with chemotherapy
and/or surgery, although the majority of children older than one year of age
with advanced-stage disease die from progressive disease despite intensive
multimodality therapy.
• Neuroblastoma has been associated with central hypoventilation,
Hirschsprung disease, and neurofibromatosis type 1 (neurocristopathy
syndrome), and as a familial disorder associated with mutations in the
anaplastic lymphoma kinase (ALK) gene.
• Neuroblastomas can arise anywhere throughout the sympathetic nervous
system.
• Most common sites
1) Adrenal gland (40 percent)
2) Abdominal (25 percent)
3) Thoracic (15 percent)
4) Cervical (5 percent)

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5) Pelvic sympathetic ganglia (5 percent)
• Neuroblastoma metastasizes to lymph nodes, bone marrow, cortical bone,
dura, orbits, liver, and skin, and less frequently to pulmonary and intracranial.
PRESENTING SYMPTOMS
• The presenting symptoms reflect the location of the primary tumor and the
extent of metastatic disease, if present.
• Patients with localized disease can be asymptomatic, whereas children with
advanced disease appear ill at presentation, usually with systemic symptoms.
Signs and symptoms of neuroblastoma may include
• Abdominal mass (retroperitoneal
or hepatic)
• Abdominal pain or constipation
• Proptosis
• Periorbital ecchymoses ("raccoon
eyes," from periorbital ecchymosis
caused by orbital metastases)
Horner syndrome (miosis, ptosis,
anhidrosis
• Localized back pain, weakness
(from spinal cord compression)
• Scoliosis, bladder dysfunction
• Palpable nontender subcutaneous nodules Opsoclonus myoclonus syndrome
• unexplained secretory diarrhea (from paraneoplastic production of vasoactive
intestinal polypeptide [VIP])
• Systemic symptoms (fever, weight loss)
• Bone pain
• Anemia
• Heterochromia iridis (different colors of the iris or Additional clinical evidence
for neuroblastoma (eg, adrenal mass on ultrasonography, elevated urine
catecholamines)
• Abdominal tumors — Approximately two-thirds of primary neuroblastomas
arise in the abdomen; among these, approximately two-thirds are from the
adrenal glands . Abdominal tumors can present with abdominal pain or fullness,
abdominal mass, hypertension, or rarely intestinal obstruction.
• When the primary tumor arises from the organs of Zuckerkandl (a pair of
embryonic organs that persist until shortly after birth and are located near
the aortic bifurcation), the child may have symptoms related to compression
of the bowel or bladder (eg, constipation, reduced bladder capacity, enuresis)

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. Large abdominal tumors also can compress venous or lymphatic drainage,
leading to scrotal and lower extremity edema. A sudden and dramatic
increase in tumor size with abdominal distention and discomfort can result
from spontaneous hemorrhage into the tumor .
• An abdominal mass may be detected in an asymptomatic child by the primary
care clinician during a routine examination. The mass is typically, but not
always, non-tender, fixed, and firm.
• Catecholamine secretion
• Degradation of norepinephrine, epinephrine, and dopamine lead to the final
end products VMA and HVA. Elevated levels of VMA and HVA can be detected
in the serum and urine of approximately 70 to 90 percent of patients with
neuroblastoma
• Paraneoplastic syndromes
• Metastatic disease — Neuroblastoma metastasizes by both lymphatic and
hematogenous routes. Regional lymph node involvement is found in 35 percent
of children who have apparently localized disease
• Hematogenous spread extends most often to bone, bone marrow, skin,
and liver. Metastatic involvement of the liver is common in infants and
can cause respiratory compromise . Neuroblastomas also may spread to
lung and brain parenchyma, but this usually occurs as a manifestation of
relapsing or end-stage disease .
• Metastatic spread to the bones and bone marrow can cause pain
(especially with ambulation), blood count abnormalities, and fever . In
young children, who cannot complain of pain, bone pain may manifest as
a limp or unexplained irritability. Tumor infiltration of the periorbital
bones, typically unilateral, can cause the characteristic periorbital
ecchymosis ("raccoon eyes"), ptosis, and proptosis
• Metastatic spread to the skin manifests as papules or subcutaneous nodules
that can be distributed over the entire body. These lesions are present in
approximately one-third of children with congenital neuroblastoma and are
typically described as firm, bluish-red, and non-tender. The lesions have a
distinctive response to rubbing, characterized by central blanching with a
surrounding halo of erythema that persists for 30 to 60 minutes.
• Prenatal diagnosis — Obstetrical sonography has been used with increasing
frequency over the past three decades. As the ease and accuracy of third-
trimester imaging has improved, and the indications for these studies have
broadened, the incidence of prenatal diagnosis of neuroblastoma has risen
steadily.

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Table 92 Presentation of Neuroblastoma
Location Presentation
Abdomen Fullness, discomfort
Fixed, hard abdominal mass
Sudden enlargement (hemorrhage)
Thoracic Coincidentally in CXR
Respiratory symptoms, pain
Superior Vena Cava Syndrome
Horner syndrome
Cervical Cervical mass
infection
Horner syndrome
Paraspinal Radicular pain
(Extension into Paraplegia
neural foramina) Bladder/Bowel dysfunction
DIAGNOSTIC AND STAGING EVALUATION
• Diagnostic evaluation — All patients with suspected neuroblastoma should

undergo a complete history and physical examination. Most patients will
undergo laboratory evaluations including
1) routine blood counts,
2) serum chemistries, and tests of liver and kidney function
3) Evaluation of urine or serum catecholamine metabolite levels,
vanillylmandelic acid (VMA), and Homovanillic acid (HVA) ,
since levels are elevated in greater than 70 to 80 percent of
patients with neuroblastoma.
• Biopsy — The diagnosis of neuroblastoma is definitively confirmed on histology
using biopsy
o In most patients, diagnostic tissue is usually obtained by incisional
or image-guided core needle biopsy of the primary tumor . A bone
marrow biopsy/aspirate may be used to diagnose patients
suspected to have metastatic disease involving the bone marrow.
• Urine catecholamines — Neuroblastoma tumor cells take up and metabolize
catecholamines, and the resulting degradation products can be detected in
serum and urine. Urinary HVA and VMA levels are useful for both diagnosis and
for monitoring disease activity over time.
• Diagnostic criteria — Minimum criteria for establishing a diagnosis of
neuroblastoma have been agreed upon by an international consensus panel . A
definitive diagnosis of neuroblastoma requires one of the following:
1) An unequivocal histologic diagnosis from tumor tissue by light
microscopy, with or without immunohistochemistry, electron

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microscopy, or increased urine (or serum) catecholamines or their
metabolites
2) Evidence of metastases to bone marrow on an aspirate or biopsy
with concomitant elevation of urinary or serum catecholamines or
their metabolites
• Staging studies
• The following studies are necessary for optimal staging:
1) Ultrasonography
2) CT or MRI –
▪ CT or MRI of the primary tumor may reveal a heterogeneous mass,
possibly containing calcifications . When the mass is adjacent to
the spine, an MRI is particularly helpful for evaluation of spinal
canal invasion .
▪ Additionally, a head CT or MRI should be pursued for patients
presenting with proptosis, periorbital ecchymosis, or as clinically
indicated by symptoms.
3) I123-MIBG scan versus FDG-PET – Patients with a confirmed
diagnosis of neuroblastoma should be evaluated for bony
metastatic disease. For such patients, I123 MIBG is preferred to
FDG positron emission topography (FDG-PET) scan or technetium
scan for evaluation of the bone, given its higher sensitivity and
specificity for detection of metastatic disease
Table 93 International Neuroblastoma Risk Group (INRG) Staging System (INSS)

Tumor Description
Stage
L1 Localized tumor not involving vital structures, as defined by the list
of IDRFs, and confined to one body compartment
L2 Local-regional tumor with presence of one or more IDRFs
M Distant metastatic disease (except stage MS tumor)
MS Metastatic disease in children younger than 18 months, with
metastases confined to skin, liver, and/or bone marrow
TREATMENT
1) Treatment for children with low-risk neuroblastoma typically includes

Surgery
− Surgery for stages L1 and L2 and observation for asymptomatic stage MS,
with cure rates generally >90% without further therapy. Treatment

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with chemotherapy or radiation for the rare child with local recurrence
can still be curative.
− NB Stage MS neuroblastomas have a very favorable prognosis, and many
regress spontaneously without therapy. Chemotherapy or resection of
the primary tumor does not improve survival rates, but for infants with
massive liver involvement and respiratory compromise, chemotherapy or
radiation is used to alleviate symptoms. For children with stage MS
neuroblastoma who require treatment for symptoms, the survival rate is
81%.
2) Treatment of intermediate-risk neuroblastoma includes surgery,
chemotherapy, and in some cases, radiation therapy.
− The chemotherapy usually includes moderate doses of cisplatin or
carboplatin, cyclophosphamide, etoposide, and doxorubicin given over
several months. Radiation therapy is used for tumors with incomplete
response to chemotherapy. Children with intermediate-risk
neuroblastoma, including children with L2 disease and infants with M
disease (both with favorable characteristics), have an excellent
prognosis and >90% survival with this moderate treatment
3) Children with high-risk neuroblastoma historically have had poor long-term
survival rates between 25% and 35% with treatment that consisted of
intensive chemotherapy, high-dose chemotherapy with autologous stem cell
rescue, surgery, radiation, and 13-cis -retinoic acid (isotretinoin,
Accutane).
− Induction chemotherapy for children with high-risk neuroblastoma
includes combinations of cyclophosphamide, topotecan, doxorubicin,
vincristine, cisplatin, and etoposide. After completion of induction
chemotherapy, resection of the residual primary tumor is followed by
high-dose chemotherapy with autologous stem cell rescue and focal
radiation therapy to tumor sites. Cases of high-risk neuroblastoma are
associated with frequent relapses, and children with recurrent
neuroblastoma have a <50% response rate to alternative chemotherapy
regimens.
9.2.3. WILMS TUMOR

• Wilms tumor, also known as nephroblastoma, is the most common primary
malignant renal tumor of childhood. It is the second most common malignant
abdominal tumor in childhood after neuroblastoma. The most common sites of
metastases are the lungs, regional lymph nodes, and liver.
EPIDEMOLOGY

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• 5% - 6% of childhood cancers
• 5-10% of patients have bilateral tumors
• Median age at presentation:
• Unilateral tumors: 44 months
• Bilateral tumors: 31 months
• Males and females are equally affected
ETIOLOGY
• Wilms tumor is an embryonal malignancy of the kidney.

• Most cases are sporadic,
• 1-2% of patients have a familial predisposition
o inherited in an autosomal dominant manner with variable penetrance
o earlier age at diagnosis
o increased frequency of bilateral disease.
• Median age: 3 years

• Presentation
o Asymptomatic, abdominal swelling > 50%
o Abdominal pain 40%
o Gross painless hematuria (18%)
o Constitutional symptoms such as fever, anorexia, and weight loss are
other findings at diagnosis
PHYSICAL EXAM
• Hypertension is present in about 25% of patients at presentation and has been
attributed to increased renin activity.
• Smooth, firm, ballotable mass, rarely crosses midline
• Congenital abnormalities
• Occasionally, rapid abdominal enlargement and anemia occur because of
bleeding into the renal parenchyma or pelvis.
• Wilms tumor thrombus extends into the Inferior Vena Cava (IVC) in 4– 10% of
patients and rarely into the right atrium; dislodgment of the intravascular
tumor may produce a fatal pulmonary embolism.
• Patients might also have microcytic anemia from iron deficiency or anemia of
chronic disease, polycythemia, elevated platelet count, and acquired
deficiency of von Willebrand factor or factor VII deficiency.

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Table 94 Differentials of Malignant of Abdominal Mass
TUMOR PATIENT CLINICAL SIGNS LABORATORY FINDINGS
AGE
Wilms tumor Preschool Unilateral flank mass, Hematuria, polycythemia,
aniridia, hemihypertrophy thrombocytosis, elevated partial
thromboplastin time
Neuroblastoma Preschool Gastrointestinal/genitourinary Increased urinary
obstruction, raccoon eyes, vanillylmandelic acid,
myoclonus- opsoclonus, homovanillic acid, or ferritin;
diarrhea, skin nodules stippled calcification in the mass
Non-Hodgkin >1 yr Intussusception in >2 yr old Increased lactate
lymphoma dehydrogenase; blood cytopenia
caused by bone marrow
involvement
Rhabdomyosarcoma All Gastrointestinal/genitourinary Hypercalcemia; blood cytopenia
obstruction, abdominal pain, caused by bone marrow
vaginal bleeding, involvement
paratesticular mass
Germ cell Preschool, Females: Abdominal pain, Increased B-human chorionic
tumor/teratoma teenage vaginal bleeding Males: gonadotropin, increased a-
Testicular mass, new-onset fetoprotein
hydrocele, sacrococcygeal
mass/dimple
Hepatoblastoma Birth-3 yr Right upper quadrant mass, Increased a-fetoprotein
jaundice Early puberty in
males
Hepatocellular School Right upper quadrant mass, Increased a-fetoprotein
carcinoma age, jaundice, hepatitis B,
teenage cirrhosis
DIAGNOSIS
• An abdominal mass in a child should be considered malignant until diagnostic
imaging, laboratory finding, and/or pathology can define its true nature
o Imaging studies
o abdominal flat plate radiography
o abdominal ultrasonography (US),
o CT, and/or MRI

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Table 95 Children's Oncology Group (COG) Staging of Wilms Tumor
Stage Criteria
Stage I Confined to kidney Complete excision with renal capsule intact and negative resection
margins Lymph nodes negative for Wilms tumor spread
Stage II Regional extension beyond kidney capsule, but confined to flank May include: Tumor
penetration through capsule but confined to Gerota's fascia Infiltration into renal vein
Complete excision with negative resection margins Lymph nodes negative for Wilms tumor
spread
Stage III Residual tumor, but confined to abdomen May include: Regional lymph node involvement
Peritoneal contamination: Biopsy Pre- or intraoperative tumor rupture Tumor growth
through peritoneal surface Positive resection margins
Stage IV Distant metastases: Lung, liver, bone, brain
Stage V Involvement of bilateral kidneys at diagnosis
Adapted from Davidoff (2012)
MANAGEMENT
• There are 2 management protocol which differ in their initial treatment
approach
o Children's Oncology Group (COG) protocols
o The International Society of Pediatric Oncology (SIOP) protocols
• COG advocates surgery prior to initiating treatment whereas SIOP recommends
preoperative chemotherapy.
o Early surgery provides accurate diagnosis and staging and can facilitate
risk-adapted therapy.
o Preoperative chemotherapy can make surgery easier and reduces the risk
of intraoperative tumor rupture and hemorrhage.
THE SURGERY
1. Radical nephrectomy, with meticulous dissection to avoid rupture of the
tumor capsule, and lymph node sampling despite the absence of abnormal
nodes on preoperative imaging studies or intraoperative assessment.
2. Partialnephrectomy is performed in patients with bilateral disease or those with
unilateral Wilms tumor and predisposing syndrome such as the Denys-Drash and
WAGR syndromes, to minimize the risk of future renal failure.

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Table 96 Neuroblastoma and Wilms tumor comparison
Parameter Neuroblastoma Wilms tumor
Age Younger age group: < 2 years of Slightly older age group: peak 3 - 4
age commonly years of age
Presentation Painful abdominal mass Painless abdominal mass
Calcification Calcification very common: 80-90% Calcification uncommon: 10%
Tumor Solid mass lesion, rarely cystic Often cystic components at US
composition components on US
Tumor Poorly marginated mass that may Well circumscribed mass - claw sign
margin extend up into chest Adrenal NBL demonstrating it arises from the
displaces the kidney kidney
Vessel Encases vascular structures but Displaces adjacent structures -
involvement does not invade them - elevates invades the vasculature with
the aorta away from the vertebral extension into renal vein/IVC
column
Metastatic Bone/bone marrow (common) Lung (common)
sites Liver Liver
Lung/pleura Local lymph nodes
Neuroblastoma Wilms Tumor

Associated with opsoclonus-myoclonus Associated with WAGR syndrome and Beckwith-
syndrome Wiedemann syndrome
May CROSS the midline Usually does NOT cross the midline
Usually fixed and immobile May be DISPLACED
Constitutional symptoms ARE common Constitutional symptoms NOT common
9.2.4. RETINOBLASTOMA
• Retinoblastoma is an embryonal malignancy of the retina and the most common
intraocular tumor in children.
• Retinoblastoma is the most common primary intraocular
malignancy of childhood and accounts for 10 to 15
percent of cancers that occur within the first year of
life. Untreated retinoblastoma is a deadly disease;
however, with advances in treatment, overall survival Figure 83 Abnormal red-eye reflex in a child
with Retinoblastoma (Leukocoria)
in the contemporary era is >95 percent.
TERMINOLOGY
• Retinoblastoma occurs in heritable and nonheritable forms
o Non-hereditary, unilateral or unifocal or nonfamilial, sporadic or somatic
o 75% of patients
o Mutation of both alleles in a somatic cell
o Median time to diagnosis: 29-30 months

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o Usually diagnosed at older ages
• Hereditary, bilateral, multifocal, familial, germline
o 25% of patients
o Germline mutation of RB1
o 25% cases: Inherited from a carrier parent
o 75% cases: “de novo” mutation early in embryogenesis
o Median time to diagnosis: 14-16 months
o usually diagnosed at younger ages.
EPIDEMIOLOGY
• 250-350 new cases of retinoblastoma are diagnosed each year in the United
States
• The cumulative lifetime incidence of retinoblastoma is approximately 1 in
20,000 live births, and retinoblastoma accounts for 4% of all pediatric
malignancies.
• The median age at diagnosis is approximately 2 yr, and >90% of cases are
diagnosed in children <5 yr old. Overall, 66–75% of children with retinoblastoma
have unilateral tumors, with the remainder having bilateral retinoblastoma.
• Bilateral involvement is more common in younger children, particularly in those
diagnosed before age 1 yr , and is always heritable.
• Risk of retinoblastoma may be increased in children conceived by in vitro
fertilization.
• The genetic abnormality associated with heritable retinoblastoma also is
associated with an increased risk of developing second malignancies, including
osteogenic sarcoma, soft tissue sarcomas (particularly leiomyosarcoma), and
malignant melanoma.
• The differential diagnosis of retinoblastoma includes other causes of
leukocoria, including
o persistent hyperplastic primary vitreous
o Coats disease,
o vitreous hemorrhage
o cataract,
o endophthalmitis from Toxocara canis ,
o choroidal coloboma,
o retinopathy of prematurity
• familial exudative vitreoretinopathy.
NATURAL HISTORY

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• Untreated, retinoblastoma is a deadly disease. The tumors grow to fill the eye
and destroy the globe. Metastatic spread is typically diagnosed within the first
12 months of clinical presentation of retinoblastoma
• However, the prognosis for eye salvage is far lower and depends on the stage
of disease at diagnosis. Spontaneous regression may occur in a small number of
cases but is a rare occurrence.
• The most common routes of metastatic spread are direct infiltration via the
optic nerve to the central nervous system (CNS) or spread via the choroid into
the sclera and into the orbit.
• Additional routes of spread include dispersion of the tumor cells through the
subarachnoid space to the contralateral optic nerve or through the
cerebrospinal fluid to the CNS; hematogenous dissemination to the lung, bone,
liver, or brain; and lymphatic dissemination if the tumor spreads anteriorly into
the conjunctivae, eyelids, or extraocular tissue
• The most common cause of death for patients with heritable retinoblastoma is
a secondary malignancy and not the initial primary retinoblastoma.
PATHOGENSIS
• Histologically, retinoblastoma appears as a small, round, blue cell tumor
with rosette formation (Flexner-Wintersteiner rosettes)
• In general, the classic presentation of early retinoblastoma is a solitary or
multifocal, well-circumscribed, translucent intraretinal mass. As the
disease advances, the tumor becomes more pink in color, with dilated
feeding blood vessels and may exhibit one of three main growth patterns
1. Endophytic tumors arise from the inner surface of the retina and grow into the
vitreous and can also grow as tumors suspended within the vitreous itself,
known as vitreous seeding
2. Exophytic tumors grow from the outer retinal layer and can cause retinal
detachment
3. Diffuse infiltrating tumors grow intraretinally and remain flat; these are less
common and can cause iris neovascularization.
• Intraocular
o Leukocoria 65-75%
o Strabismus 10-15%
o Nystagmus 5-10%
• Advanced Intraocular Figure 84 Leukocoria
o Buphthalmos Greek: “leukos” (white) and “kore” (pupil)
o Glaucoma

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o Periorbital cellulitis
• Extraocular
o Proptosis + LN
o Metastases
• the mean age at diagnosis was 20 months.
• Retinoblastoma classically presents with leukocoria, a white pupillary reflex ,
which often is first noticed when a red reflex is not present at a routine
newborn or well-child examination or in a flash photograph of the child.
• Strabismus often is an initial presenting complaint.
• Decreased vision, orbital inflammation, hyphemia, and pupil irregularity can
occur with advancing disease.
• Pain can occur if secondary glaucoma is present.
• Only approximately 10% of retinoblastoma cases are detected by routine
ophthalmologic screening in the context of a positive family history.
DIAGNOSIS
• The evaluation in children with suspected retinoblastoma is carried out by or in
consultation with an ocular oncologist and typically includes:
• Complete physical examination
• Ophthalmologic examination under anesthesia (EUA)
• Ocular ultrasonography
• Optical coherence tomography (OCT)
• Magnetic resonance imaging (MRI) of the brain and orbits
• Metastatic disease is rarely present at the time of diagnosis, and formal staging
studies are not routinely performed. However, if there is clear evidence of
tumor outside of the eye, a full metastatic evaluation should be pursued,
including:
o Bone marrow aspiration and biopsy
o Lumbar puncture
o Radionuclide bone scan
• The diagnosis of retinoblastoma can usually be made based on the dilated
indirect ophthalmoscopic examination and imaging studies. The characteristic
finding is a chalky, off-white retinal mass with a soft, friable consistency.
• Pathology is not necessary to confirm the diagnosis, and biopsy is
contraindicated because of the risk of extraocular tumor seeding.
MANAGEMENT
• Treatment of retinoblastoma is aimed at achieving the following goals
o Eradication of the disease to prevent mortality

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o Salvage of the globe, if done without risk to the child's life
o Preservation of vision to the greatest extent possible
o Prevention of late sequelae, particularly subsequent neoplasms
o First-line therapeutic options include systemic chemotherapy,
ophthalmic artery chemosurgery (OAC), cryotherapy, laser
photocoagulation, or enucleation. The choice of initial treatment is
based on the tumor size, location, and laterality; presence or absence of
vitreous or subretinal seeds; patient age; and visual prognosis.
• Most unilateral disease presents with a solitary, large tumor.
• Enucleation is performed if useful vision cannot be salvaged and for
unresponsive or recurrent tumors
• With bilateral disease, chemo reduction in combination with focal therapy
(laser photocoagulation or cryotherapy)
• If feasible, small tumors can be treated with focal therapy with careful follow-
up for recurrence or new tumor growth.
• Larger tumors often respond to multiagent chemotherapy, including
carboplatin, vincristine, and etoposide given intravenously. The delivery of
chemotherapy via the ophthalmic artery is becoming more common, as is
delivery of intravitreal chemotherapy. If these approaches fail, external beam
irradiation should be considered, although this approach may result in
significant orbital deformity and increased incidence of second malignancies in
patients with germline RB1 mutations.
• Brachytherapy, or episcleral plaque radiotherapy, is an alternative with less
morbidity.
PROGNOSIS
• Although the survival rate of children with retinoblastoma in the United States
and developed countries is extremely high, retinoblastoma progresses to
metastatic disease and death in >50% of children worldwide.
SCREENING
• Children with a positive family history of retinoblastoma should undergo a
dilated eye examination under general anesthesia early in life and at regular
interval until genetic testing is performed and results are available.
• Infants with a negative genetic test require no further screening; infants with a
positive genetic test require regular screening ophthalmologic examinations
until age 5 yr.
9.2.5. BONE TUMOR

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• The annual incidence of malignant bone tumors in the United States is
approximately 7 cases per 1 million white children younger than 14 yr, with a
slightly lower incidence in black children.
• Osteosarcoma is the most common primary malignant bone tumor in children
and adolescents, followed by Ewing sarcoma in children <10 yr old, Ewing
sarcoma is more common than osteosarcoma. Both tumor types are most likely
to occur in the 2nd decade of life.
Table 97 Comparison between Osteosarcoma and Ewing family of tumors
FEATURE OSTEOSARCOMA EWING FAMILY OF TUMORS
Age 2nd decade 2nd decade
Race All races Primarily whites
Sex (M:F) 1.5:1 1.5 1
Predisposition Retinoblastoma, Li-Fraumeni None known
syndrome, Paget disease, radiotherapy
Site Metaphysis of long bones Diaphysis of long bones, flat bones
Presentation Local pain and swelling; often history Local pain and swelling; fever
of injury
Radiographic Sclerotic destruction (less often lytic); Primarily lytic, multilaminar periosteal
findings sunburst pattern reaction ("onion-skinning")
Differential Ewing sarcoma, osteomyelitis Osteomyelitis, eosinophilic granuloma,
diagnosis lymphoma, neuroblastoma,
rhabdomyosarcoma
Metastasis Lungs, bones Lungs, bones
Treatment Chemotherapy Chemotherapy
Ablative surgery of primary tumor Radiotherapy and/or surgery of primary
tumor
Outcome Without metastases, 70% cured; with Without metastases, 65-75% cured; with
metastases at diagnosis, <20% survival metastases at diagnosis, 20-30% survival
OSTEOSARCOMA
EPIDEMOLOGY
• The annual incidence of osteosarcoma in the United States is 5.6 cases per 1
million children <15 yr old.
• The highest risk period for development of osteosarcoma is during the
adolescent growth spurt, suggesting an ssociation between rapid bone growth
and malignant transformation.
• Patients with osteosarcoma are taller than their peers of similar age.
PATHOGENESIS

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• Although the cause of osteosarcoma is unknown, certain genetic or acquired
conditions predispose patients to development of
osteosarcoma.
• Patients with hereditary retinoblastoma, Li-Fraumeni
syndrome, Rothmund-Thomson syndrome and others
have an increased risk for Osteosarcoma
• Pain, limp, and swelling are the most common
presenting manifestations of osteosarcoma. Because
these tumors occur most often in active adolescents,
initial complaints may be attributed to a sports injury
or sprain; and bone or joint pain not responding to
conservative therapy within a reasonable time should
be investigated thoroughly.
• Additional clinical findings may include limitation of
motion, joint effusion, tenderness, and warmth.
Results of routine laboratory tests, such as a complete
Figure 85 Typical locations of malignant bone tumors
blood cell count and chemistry panel, are usually
normal, although alkaline phosphatase or lactate dehydrogenase values may be
elevated.
DIAGNOSIS
• Bone tumor should be suspected in a patient who presents with deep

bone pain, often causing nighttime awakening, and has a palpable
mass with radiographs that demonstrate a lesion.
• The lesion may be mixed lytic and blastic in appearance, but new
bone formation is usually visible. The classic radiographic appearance
of osteosarcoma is the sunburst pattern.
• Before biopsy, MRI of the primary lesion and the entire bone should
be performed to evaluate the tumor for its proximity to nerves and
bloodvessels, soft tissue and joint extension, and skip lesions.
• The metastatic workup includes CT of the chest and radionuclide
bone scanning or positron emission tomography (PET) scan to
evaluate for lung and bone or soft tissue metastases, respectively
Figure 86 Radiograph of
The differential diagnosis of a lytic bone lesion includes histiocytosis, osteosarcoma of the femur
Ewing sarcoma, lymphoma, and bone cyst. with typical 'sunburst'
appearance of bone
formation
TREATMENT

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• With chemotherapy and surgery, 5 yr disease-free survival of patients with
nonmetastatic extremity osteosarcoma is 65–75%.
• Complete surgical resection of the tumor is important for cure. The current
approach is to treat patients with preoperative chemotherapy in an attempt to
facilitate limb salvage operations and to treat micrometastatic disease
immediately. Up to 80% of patients are able to undergo limb salvage operations
after initial chemotherapy. It is important to resume chemotherapy as soon as
possible after surgery.
• Lung metastases present at diagnosis should be resected by thoracotomies at
some time during treatment. One of the most important prognostic factors in
osteosarcoma is the histologic response to chemotherapy; a poor histologic
response is ≥10% viable tumor.
• MAP (methotrexate, doxorubicin, cisplatin) is the standard chemotherapy
regimen for osteosarcoma.
PROGNOSIS
• Surgical resection alone is curative only for patients with low-grade parosteal
osteosarcoma. Conventional osteosarcoma requires multiagent chemotherapy.
Up to 75% of patients with nonmetastatic extremity osteosarcoma are cured
with current multiagent treatment protocols Patients with bone metastases
and those with widespread lung metastases have an extremely poor prognosis
EWING SARCOMA
EPIDEMIOLOGY
• The incidence of Ewing sarcoma in the United States is

2.1 cases per 1 million children.
• It is rare among black children. Ewing sarcoma, an
undifferentiated sarcoma of bone, also may arise from
soft tissue.
• Treatment protocols for these tumors are the same
whether the tumors arise in bone or soft tissue.
Anatomic sites of primary tumors arising in bone are
distributed evenly between the extremities and the
central axis (pelvis, spine, and chest wall).
• Primary tumors arising in the chest wall are often
referred to as Askin tumors.

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• Symptoms of Ewing sarcoma are similar to those of osteosarcoma. Pain,
swelling, limitation of motion, and tenderness over the involved bone or soft
tissue are common presenting symptoms.
• Patients with huge chest wall primary tumors may present with respiratory
distress.
• Patients with paraspinal or vertebral primary tumors may present with
symptoms of cord compression.
• Ewing sarcoma often is associated with systemic manifestations, such as fever
and weight loss, and may be accompanied by elevated inflammatory markers;
patients may have undergone treatment for a presumptive diagnosis of
osteomyelitis or a fever of unknown origin
DIAGNOSIS
• The diagnosis of Ewing sarcoma should be suspected in a patient who presents

with pain and swelling, with or without systemic symptoms,
and with a radiographic appearance of a primarily lytic bone
lesion with periosteal reaction, the characteristic onion-
skinning.
• A large, associated soft tissue mass often is visualized on
MRI or CT.
• The differential diagnosis includes
a. osteosarcoma,
b. osteomyelitis,
c. Langerhans cell histiocytosis,
d. primary lymphoma of bone,
e. metastatic neuroblastoma,
Figure 87 A Tibial x-ray showing
f. rhabdomyosarcoma in the case of a pure soft the Inion skinning.
tissue lesion.
TREATMENT
• Multiagent chemotherapy is important because it can shrink the tumor rapidly

and is usually given before local control is attempted.
• Standard chemotherapy for nonmetastatic Ewing sarcoma Includes vincristine,
doxorubicin, cyclophosphamide, etoposide, and ifosfamide.
• Chemotherapy usually causes dramatic shrinkage of the soft tissue mass and
rapid, significant pain relief
• Ewing sarcoma is considered a radiosensitive tumor, and local control may be
achieved with irradiation or surgery

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• Radiation therapy is associated with a risk of radiation-induced second
malignancies, especially osteosarcoma, as well as failure of bone growth in
skeletally immature patients.
• It is important to provide the patient with crutches if the tumor is in a weight-
bearing bone, to avoid a pathologic fracture before definitive local control
PROGNOSIS
• Patients with small, nonmetastatic, distally located extremity tumors have the
best prognosis, with a cure rate of up to 75%. Patients with pelvic tumors have,
until recently, had a much worse outcome.
• Patients with metastatic disease at diagnosis, especially bone or bone marrow
metastases, have a poor prognosis, wit <30% surviving long term

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9.3. ONCOLOGIC EMERGENCIES

• Defined as the occurrence of a clinically life-threatening situation, which is
triggered either directly or indirectly by the cancer itself or its treatment
• Emergencies in patients with cancer may be classified into three groups:
o Pressure or obstruction caused by a space-occupying lesion
o Metabolic or hormonal problems (paraneoplastic syndromes)
o Treatment-related complications
Table 98 Common oncologic emergencies
Category Type
Metabolic Hypercalcemia, Hyponatremia, Hypoglycemia. Tumor Lysis
Emergencies Syndrome, Syndrome of Inappropriate Secretion of Antidiuretic
Hormone (SIADH)
Cardiovascular Pleural and Pericardial Effusions, Cardiac Tamponade, Superior
Emergencies Vena Cava Syndrome
Gastrointestinal Typhlitis, Perirectal Abscess, Pancreatitis, Gastrointestinal
Emergencies hemorrhage
Genitourinary Oliguria or Anuria, Hemorrhagic cystitis,
Emergencies Hypertension
Infectious Neutropenic fever, Sepsis
Emergencies
Neurologic Spinal cord compression,
Emergencies Increased Intracranial Pressure Seizures
• Emergencies can occur at any time during a child's course of care for cancer
o As initial manifestation of cancer
o As the diagnosis is being made
o As a consequence of therapy
o At the time of tumor/ cancer progression or recurrence
• We must be able to recognize life-threatening emergencies and treat them
quickly
SUPERIOR VENACAVA SYNDROME

• Superior vena cava syndrome (SVCS) is the clinical manifestation of superior
vena cava (SVC) obstruction, with severe reduction in venous return from the
head, neck, and upper extremities. Malignant tumors, such as lung cancer,
lymphoma, and metastatic tumors, are responsible for the majority of SVCS
cases In young adults, malignant lymphoma is a leading cause of SVCS.
Hodgkin's lymphoma involves the mediastinum more commonly than other
lymphomas but rarely causes SVCS.

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• When SVCS is noted in a young man with a
mediastinal mass, the differential diagnosis
is lymphoma vs primary mediastinal germ
cell tumor. Metastatic cancers to the
mediastinum, such as testicular and breast
carcinomas, account for a small proportion
of cases.
• Patients with SVCS usually present with
neck and facial swelling (especially
around the eyes), dyspnea, and cough.
Other symptoms include hoarseness, tongue
Figure 88 Superior vena cava syndrome (SVCS)
swelling, headaches, nasal congestion,
epistaxis, hemoptysis, dysphagia, pain, dizziness, syncope, and lethargy.
Bending forward or lying down may aggravate the symptoms.
• The characteristic physical findings are dilated neck veins; an increased
number of collateral veins covering the anterior chest wall; cyanosis; and
edema of the face, arms, and chest. More severe cases include proptosis,
glossal and laryngeal edema, and obtundation. The clinical picture is milder if
the obstruction is located above the azygos vein. Symptoms are usually
progressive, but in some cases they may improve as collateral circulation
develops.
• Signs and symptoms of cerebral and/or laryngeal edema, though rare, are
associated with a poorer prognosis and require urgent evaluation.
DIAGNOSIS
• The diagnosis of SVCS is a clinical one. The most significant chest radiographic
finding is widening of the superior mediastinum, most commonly on the
right side. Pleural effusion occurs in only 25% of patients, often on the right
side. The majority of these effusions are exudative and occasionally chylous.
However, a normal chest radiograph is still compatible with the diagnosis if
other characteristic findings are present. CT provides the most reliable view of
the mediastinal anatomy.
TREATMENT
• The one potentially life-threatening complication of a superior mediastinal

mass is tracheal obstruction. Upper airway obstruction demands emergent
therapy.

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• Diuretics with a low-salt diet, head elevation, and oxygen may produce
temporary symptomatic relief. Glucocorticoids may be useful at shrinking
lymphoma masses; they are of no benefit in patients with lung cancer.
• Radiation therapy is the primary treatment for SVCS caused by non-small cell
lung cancer and other metastatic solid tumors. Chemotherapy is effective when
the underlying cancer is small cell carcinoma of the lung, lymphoma, or germ
cell tumor. SVCS recurs in 10–30% of patients; it may be palliated with the use
of intravascular self-expanding stents
TUMOR LYSIS SYNDROME

• Caused by massive tumor cell lysis with the release of large amounts of
potassium, phosphate, and nucleic acids into the systemic circulation.
• The classic triad of TLS includes hyperuricemia, hyperphosphatemia, and
hyperkalemia.
• If not successfully treated, TLS can result in
cardiac arrhythmias, renal failure,
seizures, coma, DIC, and death
• Elevated uric acid comes from the
breakdown of the released nucleic acids.
• Lymphoblasts are especially rich in
phosphate (4x the content of normal
lymphocytes)
• In TLS, uric acid, phosphate, potassium and
Figure 89 Mechanism of TLS
nucleic acids are released in the circulation
in large quantities from death of tumor cells.
• TLS can occur before therapy in patients with a large tumor burden
o Burkitt lymphoma,
o Lymphoblastic lymphoma,
o High–white blood cell count
leukemia
• But TLS usually occurs during or
shortly (1–5 days) after
chemotherapy; with
administration of these drugs:
o Glucocorticoids,
o Hormonal agents (such as
letrozole and tamoxifen,)
And
Figure 90 Mechanism of TLS (2)

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o Monoclonal antibodies such as rituximab and gemtuzumab.
• When the solubility product factor (Ca X P) reaches 60, calcium phosphate
precipitates in the microvasculature, causing a secondary hypocalcemia.
• Precipitation of uric acid crystals and calcium phosphate within the renal
tubules and microvasculature leads to AKI.
DIAGNOSIS
• Laboratory TLS - ≥ 2 of the listed metabolic abnormalities within 3 days before
Hyperkalemia 6.0 Hyperuricemia Hyperphosphatemia Hypocalcemia 7.0

mEq/L >8.0 mg/dL 4.5 mg/dL mg/dL
Or 25% increase Or 25% increase Or 25% increase Or 25% decrease

from baseline from baseline from baseline from baseline
or 7 days after initiation of treatment. (See below)
• Clinical TLS - Presence of laboratory tumor lysis syndrome PLUS:
o Acute kidney injury: Cr increased 0.3 mg/dL above baseline, oliguria (<
0.5 mL/kg/h) for 6 hr, or Cr ≥1.5 ULN
o Seizures, neuromuscular irritability
o Cardiac arrhythmia or sudden death.
PATIENT STRATIFICATION BY RISK FOR TLS FOR VARIOUS TYPES OF CANCER

Table 99 Patient Stratification By Risk for TLS For Various Types Of Cancer
Type of cancer Risk
High Intermediate Low
NHL Burkitt, DLBCL Indolent NHL
lymphoblastic
ALL WBC > WBC 50,000- WBC<50,000/mm³
100,000/mm3 100,000/mm3
AML WBC > WBC 10,000- WBC<10,000/mm3
50,000/mm³ 50,000/mm3
Other hematologic Rapid proliferation Remainder of
malignancies (including with expected rapid patients
CML) and solid tumors response to therapy
NHL, non-Hodgkin's lymphoma; DLBCL, diffuse large B-cell lymphoma; ALL, acute lymphoblastic
leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia.
INVESTIGATION
• Initial studies include:-
o CBC
o Serum Electrolytes
o Uric acid, RFT

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• ECG (if the serum K>6.0 mEq/L)
• Imaging (as indicated)
PREVENTION AND MANAGEMENT OF TLS

1. FLUIDS AND HYDRATION
• Promote excretion of uric acid and phosphorus; increase GFR & renal blood
flow
• Hydration at a rate of >2L /m2/day should start 24hr before chemotherapy
• Urine output goal of 3 ml/kg/h (>100ml/m2/hr) should be maintained
• Diuretics may be needed to maintain this urine output
• Strict measurement of intake and output should be carried out every 2-4hr
2. ALLOPURINOL
• A xanthine analog which blocks conversion of xanthine and hypoxanthine to
uric acid; works as a competitive inhibitor of xanthine oxidase
• Does not remove preformed uric acid
3. RASBURICASE
• Indicated for patients at high risk of TLS
• May require reinitiation of allopurinol several days after Rasburicase
4. HYPERKALEMIA
• Moderate (≥6.0 mmol/L)
o Avoid IV and oral potassium

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o Hydration
o ECG and cardiorespiratory monitor
o Kayexalate (1 g/kg orally with 25% sorbitol every 6 hours)
• Severe (>7.0 mmol/L and/or symptomatic)
o Albuterol nebulization treatment
o Insulin (0.1 units/kg) with concurrent 25% dextrose (2 mL/kg)
o Calcium gluconate (100 to 200 mg/kg)
o Dialysis
5. HYPERPHOSPHATEMIA AND HYPOCALCEMIA
• Hyperphosphatemia:
o Moderate (≥5.0 mg/dL)—
• Low phosphate diet
• hydration
• aluminum hydroxide 50-150 mg/kg/24 hours in divided doses
every 4-6 hours
o Severe (with symptomatic hypocalcemia)
• Dialysis
• Hypocalcemia:
o Asymptomatic—no therapy
o Symptomatic
• Treatment of hyperphosphatemia- reduce ca-p binding
• calcium gluconate 0.5-1.0 ml/kg of 10% calcium gluconate
HYPERLEUKOCYTOSIS
• Hyperleukocytosis is defined as a total white cell count > 100,000/mm3
• Leukostasis is a medical emergency most commonly seen in patients with AML
or CML in blast crisis
o Characterized by an extremely elevated blast cell count and symptoms
of decreased tissue perfusion
o Pathologic diagnosis in which white cell plugs are seen in the
microvasculature
EPIDEMIOLOGY
➢ The incidence of hyperleukocytosis and leukostasis vary by leukemia type
➢ Hyperleukocytosis is more common in infant ALL, AML, T-cell ALL with a
mediastinal mass, and hypodiploid ALL.
o 9-13% of children with ALL
o 5-22% of children with AML
o It occurs in an even higher percentage of patients with CML.
PATHOGENSIS

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• The presence of a high number of blasts in the microcirculation leads to
sludging
o Which interferes with oxygenation of local tissue, ultimately leading to
tissue ischemia
o Worsening leukostasis, thrombosis, and leading to secondary
hemorrhage.
o Thrombi in the circulation lead to vascular damage and parenchymal
ischemia manifested as pulmonary or cerebrovascular hemorrhage and
edema
• Myeloblasts are larger, less deformable, and more adherent to vasculature
than lymphoblasts.
o Due to these intrinsic properties, leukostasis and thrombosis are far
more prevalent in AML than in ALL.
o At presentation, patients with AML are more likely to have intracranial
hemorrhage or thrombosis or pulmonary hemorrhage and leukostasis
o Whereas ALL is more likely to lead to metabolic disturbance from TLS
CLINICAL FEATURE
• Most are asymptomatic
• CNS: Blurred vision, Confusion, Somnolence, Delirium, Papilledema, Stupor,
Coma
• Pulmonary: tachypnea, dyspnea, hypoxia
• GUS: Oliguria, Anuria, rarely priapism
• Vascular: DIC, retinal hemorrhage, Myocardial infarction, Renal vein thrombosis
Investigations: CBC, serum electrolytes, RFT, uric acid, LDH, coagulation profiles,
CxR
Management
• IV hydration
• Allopurinol or urate oxidase should be started
• Platelet transfusion to prevent cerebral hemorrhage ( if platelet < 20,000)
o Platelets do not add substantially to blood viscosity
o In contrast, packed red cells increase viscosity
• Coagulation abnormalities should be corrected
• Exchange transfusion and/or leukapheresis can rapidly lower the WBC and may
improve coagulopathy but is contraindicated in APL.

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NEUTROPENIC FEVER
• A single oral temperature >38.30C (101.0F) or an oral temperature >38.0C
(100.40F) sustained for 1hr or that occurs twice within a 24hr period and
• An ANC <500 or ANC < 1000 expected to decrease to < 500 over the subsequent
48 hr
RISK CATEGORY
LOW RISK
• Anticipated brief (<7days duration) neutropenic periods,
• few or no co morbidities,
• good supportive care at home
• Diagnosis: ALL, NHL, solid tumors in remission
• Nontoxic appearance
• No focal infection, mucositis, diarrhea
HIGH RISK
• Anticipated prolonged neutropenia (>7days)
• Profound neutropenia
• Significant medical co-morbid conditions
• AML, high-risk ALL in consolidation or delayed intensification
• High-dose cytarabine
• Evidence of infection: Pneumonia, cellulitis, abdominal pain
• Known colonization with MRSA
• Prior history of bacteremia/sepsis
• Mucositis following chemotherapy
INVESTIGATION
• Complete blood count
• Serum chemistries
• Urinalysis and urine culture
• Blood cultures from all lumens of indwelling catheters and from a peripheral
vein
• Other studies only as clinically indicated (CXR, abdominal ultrasound, LP).

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• Broad spectrum Antibiotics with

anti-pseudomonal coverage is
recommended for uncomplicated
episodes of fever in neutropenic
patients
o Cefepime,
o Ceftazidime,
o Meropenem,
o Piperacillin-tazobactam
• Abdominal pain, bloody rectum,
add Metronidazole
• Low risk patients
o Oral therapy - Ciprofloxacin and amoxicillin-clavulanic acid
• MRSA suspicion or in the following situation add Vancomycin
o Patients with AML receiving high-dose cytarabine
o Presentation with hypotension or evidence of shock
o Mucositis
o Prior history of alpha-hemolytic Streptococcus infection.
o Skin breakdown or catheter site infection.
o Colonization with resistant organisms treated only with vancomycin.
o Vegetation on echocardiogram
o Severe pneumonia
• Modifications of initial therapy
o Change in clinical status or vital signs
o Isolation of a blood-borne organism
o Documented clinical or microbiologic infection
o Development of signs or symptoms of a localized infection
o Persistent fever for more than four days
• Antifungal
o persistent fever (ie, ≥4 days) and neutropenia despite empiric
antibacterial therapy
o AML
o relapsed acute leukemia,
o high-risk ALL
o prolonged neutropenia (>10 days),
o highly myelosuppressive chemotherapy,
o high-dose glucocorticoids ≥14 days
o allogeneic hematopoietic cell transplant recipients

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• Fluconazole, If high suspicion of aspergillosis- Caspofungin OR Liposomal
amphotericin
DURATION OF THERAPY
• The duration of empiric antibiotic therapy depends upon the clinical
circumstances of the individual patient.
o negative blood cultures for at least 48 hours,
o resolution of fever for at least 24 hours, and
o resolution of neutropenia [ANC] >500 cells/microL)
TYPHILITIS / NEUTROPENIC ENTEROCOLITIS

• Typhlitis is a necrotizing colitis localized to the cecum
• Usually occurs subsequent to mucosal injury caused by cytotoxic
chemotherapeutic agents
• Bacterial or fungal invasion of cecal mucosa may progress from inflammation to
full-thickness infarction and perforation
• Neutropenic enterocolitis/typhlitis; occurs most commonly in children with
hematologic malignancies who are neutropenic and have breakdown of gut
mucosal integrity as a result of cytotoxic chemotherapy.
• Typhlitis is a life-threatening oncologic emergency occurring in the presence of
neutropenia often in the induction phase of chemotherapy for leukemia.
PATHOGENESIS
• The pathogenesis of typhlitis is incompletely understood. It probably involves a
combination of factors, including:
o mucosal injury,
o profound neutropenia, and
o impaired host defense to invasion by microorganisms
ETIOLOGY
• The responsible pathogens include
o Gram-negative bacteria, such as Pseudomonas species, E coli, and
Clostridium species are the most common
o Staphylococcus, Streptococcus, and Enterococcus species have been
identified
o fungal

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CLINICAL FEATURE
• Present with triad of neutropenia, fever and abdominal pain
• Physical examination findings include
o Bowel distention
o Absence of bowel sounds
o Tenderness on palpation maximal in the right lower quadrant
o Palpable mass in the right lower quadrant
ON HISTORY
• Watery diarrhea (often containing sloughed mucosa)
• RLQ abdominal pain,
• Bleeding may occur
DIAGNOSIS
• CBC
• Plain abdominal X-ray: pneumatosis intestinalis, free air in the peritoneum or
bowel wall thickening
• Abdominal U/S: reveal thickening of the bowel wall in the region of the cecum
• Abdominal CT scan
o Definitive imaging study
o Demonstrate diffuse thickening of the cecal wall
MANAGEMENT
MEDICAL MANAGEMENT
• Discontinue any enteral feeding and keep NPO
o IV fluid and electrolyte replacement
o NG tube decompression
o Broad spectrum antibiotics and antifungal
o Transfusion of Platelets and Packed RBC
o Vasopressors as needed
SURGICAL MANAGEMENT
• Indications
o Persistent GI bleeding despite resolution of neutropenia and
thrombocytopenia
o Evidence of free air in the abdomen on abdominal radiograph
o Uncontrolled sepsis from bowel infarction resulting in clinical
deterioration requiring fluid and pressor support

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o Development of symptoms of an intraabdominal process that would
normally require an operation
NEUROLOGIC EMERGENCIES
• Neurologic emergencies in children with cancer can be
o A direct effect of the malignancy
o Increased intracranial pressure from a CNS tumor
o Indirectly from abnormalities of metabolism, hemostasis, or organ
system dysfunction
• Seizures: CNS tumors, intrathecal chemotherapy, metabolic derangements.
• Raised ICP: CNS tumors, shunt obstruction, pseudotumor cerebri, infection,
CVA.
• CVA: Asparaginase, hyperleukocytosis, coagulopathy/hemorrhage, radiation-
induced vasculopathy.
SPINAL CORD COMPRESSION

ETIOLOGY AND PATHOGENESIS
•Acute compression of the spinal cord occurs in 3-5% of children with cancer,
often at diagnosis.
• Causes: Sarcomas, neuroblastoma, germ cell tumors, lymphoma, and dropped
metastases from primary CNS tumors
PATHOPHYSIOLOGY
• Direct extension of the tumor
• Metastatic spread to the vertebrae with secondary cord compression
• Spread to the epidural space via infiltration of the vertebral foramina
• Subarachnoid spread down the spinal cord from primary CNS tumor (such as
medulloblastoma
CLINICAL FEATURE
• Any child with cancer and back pain should be presumed to have spinal cord
involvement until further workup indicates otherwise
o Back pain with localized tenderness occurs in 80% of patients
o Bowel or bladder function abnormalities if spinal compression is not
diagnosed early
o Loss of strength and sensory deficits with a sensory level may also occur.
IMPORTANT NEUROLOGIC EXAMINATION

• A rectal examination assesses sphincter tone

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• Localized tenderness to vertebral percussion occurs in many patients
• Most patients have objective loss of motor strength in the extremities at the
time of diagnosis
• Based on clinical findings, the level of spinal cord involvement can usually be
determined
• The absence of weakness or sensory abnormalities does not exclude spinal cord
compression
INVESTIGATIOINS
• Spinal radiographs
• MRI
• CT myelography
MANAGEMENT
• It is crucial to initiate treatment immediately
o In the presence of neurologic abnormalities, start Dexamethasone
loading dose of 1-2mg/kg, followed by MRI investigation
o With back pain and the absence of neurologic symptoms, start
dexamethasone 0.25-1 mg/kg/dose every 6 hr and perform MRI within 24
hr
o If an epidural mass is compressing the spinal cord, the cord must be
decompressed immediately
• Specific chemotherapy
• Radiotherapy

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CHAPTER 10 - NEPHROLOGY
1. Introduction
2. Renal Failure
o Acute Kidney Injury
3. Glomerular Diseases
o Anatomy of Glomerulus
o Glomerular Diseases
4. Acute nephritic syndrome
5. Nephrotic syndrome

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10.1. INTRODUCTION
PHYSIOLOGY OF THE KIDNEY

• The kidney is one of the most highly differentiated organs in the body. At the
conclusion of embryologic development, nearly 30 different cell types form a
multitude of filtering capillaries and segmented nephrons enveloped by a
dynamic interstitium. This cellular diversity modulates a variety of complex
physiologic processes.
• Endocrine functions, the regulation of blood pressure and intraglomerular
hemodynamics, solute and water transport, acid base balance, and removal of
drug metabolites are all accomplished by intricate mechanisms of renal
response. This breadth of physiology hinges on the clever ingenuity of nephron
architecture that evolved as complex organisms came out of water to live on
land.
• The kidneys’ ability to perform many of its functions Renal clearance =
depends on the fundamental functions of filtration, Filtration – reabsorption + secretion
reabsorption and secretion, whose sum is called renal
clearance.
FUNCTIONS OF KIDNEY
1. Regulation of:
a. Body fluid osmolarity and volume
b. Electrolyte balance
c. Acid-base balance
d. Blood pressure
2. Excretion of
a. metabolic products
b. foreign substances (drugs and other chemicals etc.)
c. excess substances (water, etc)
3. Secretion of
a. erythropoietin
b. 1,25-dihydroxy vitamin D3 (vitamin D activation)
c. Renin
d. Prostaglandin
4. Involved in metabolism
GROSS ANATOMY OF THE KIDNEY

• Kidneys are paired brownish structures

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• Are bean-shaped
• are located retroperitoneally in the abdominal cavity
• Vertically extend from T12-L3
• Positionally, the right kidney is slightly lower than the left
MICROANATOMY OF THE KIDNEYS

• The kidney has 2 layers:
o The outer layer of the kidney is the cortex containing
the major (upper) portion of the nephrons.
o middle layer is the medulla.
• The medulla is composed of the triangular shaped pyramids
and the renal columns.
• The pyramids contain the collecting tubules and loops of
Henle, the lower portion of the nephrons.
• The renal columns are regions between the pyramids in which
blood vessels run to and from the cortex.
• The papilla of each pyramid projects into a funnel-shaped
area known as the calyx.
Figure 91 Gross anatomy of kidney
• The calyces (plural of calyx) collect the urine released from
the papillae and allow it to drain into a large area known as
the renal pelvis and then into the ureter.
THE NEPHRON
• Nephrons are functional and structural units of the kidney i.e. individually and
collectively they perform the functions of the kidney.
• Each kidney is made up of about 1 million.
• Formation of nephron completed at 34-36 wk of gestational
age. New nephrons cannot be formed after birth, but
functional maturation with tubular growth and elongation
continues during the 1st decade of life.
• Each nephron has two major components:
o A glomerulus
o A long tube
• Glomerulus → Proximal tubule (cortex) →loop of Henle
(medulla) →distal tubule (cortex) → cortical collecting Figure 92 Microanatomy of The Kidneys
tubule → medullary collecting tubule→ collecting duct.
10.2. RENAL FAILURE

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ACUTE KIDNEY INJURY

• Acute kidney injury (AKI) has been traditionally defined as an abrupt loss of
kidney function leading to a rapid decline in the glomerular filtration rate
(GFR), accumulation of waste products such as blood urea nitrogen (BUN) and
creatinine, and dysregulation of extracellular volume and electrolyte
homeostasis.
• AKI is currently defined by
o arise from baseline of Scr at least 0.3 mg/dL within 48 h or
o at least 50% (≥1.5 times) higher than baseline within 1 week, or
o a reduction in urine output to <0.5 mL/kg per h for longer than 6h.
• The incidence of AKI varies from 2–5% of all hospitalizations to > 25% in
critically ill infants and children.
• AKI can be
o Oliguric- UOP<1ml/kg/hr for infants and <0.5 ml/kg/hr. for children (in
adults ≤400 ml) (most common type)
o Non-oliguric- UOP>1ml/kg/hr for infants and >0.5 ml/kg/hr for children)
(in adults >400 ml)
o Usual causes are drugs like aminoglycosides, interstitial nephritis, acute
tubular necrosis.
• N.B. Polyuria- UOP greater than 3ml/kg/hr. some patients with a urinary
concentrating defect will present with polyureic AKI, particularly those with
acute tubular necrosis and with nephrotoxic AKI.
• A classification system proposed by the Kidney Disease Improving Global
Outcomes (KDIGO) AKI Consensus Conference takes both serum creatinine and
urine output criteria into account to define and stage AKI.
Table 100 KDIGO Staging of Acute Kidney Injury
STAGE SERUM CREATININE URINE OUTPUT
1 1.5-1.9 times <0.5 ml/kg/hr. for 6-12hr
baseline, or ≥0.3 mg/dl
increase
2 2-2.9 times baseline <0.5 ml/kg/hr. for≥ 12
hrs.
3 3 times baseline or sCr ≥4mg/dl <0.3 ml /kg/hr. for ≥24hr,
or initiation of replacement OR Anuria for ≥12 hr.
therapy or eGFR <35ml/min per
1.73 m2

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Table 101 Pediatric-Modified Rifle (Prifle) Criteria
CRITERIA ESTIMATED CCl URINE OUTPUT
Risk eCCl decrease by 25% <0.5 mL/kg/hr for 8 hr
Injury eCCl decrease by 50% <0.5 mL/kg/hr for 16 hr
Failure eCCl decrease by 75% or <0.3 mL/kg/hr for 24 hr or anuric
eCCl for 12 hr
<35 ml/min/1.73 m2
Loss Persistent failure >4 wk
End-stage End-stage renal disease
(persistent failure
>3 mo)
CAUSES OF AKI
• Conventionally classified into three categories: prerenal, intrinsic renal, and
postrenal.
Table 102 Causes Of Aki
Prerenal causes Intrinsic renal Postrenal
Dehydration Glomerulonephritis Posterior urethral
Gastroenteritis Postinfectious/poststreptococcal valves
Hemorrhage Lupus erythematosus Ureteropelvic
Burns Henoch-Schönlein purpura junction obstruction
Sepsis Membranoproliferative Ureterovesicular
Capillary leak Anti–glomerular basement junction obstruction
Hypoalbuminemia membrane Ureterocele
Cirrhosis Hemolytic-uremic syndrome Tumors
Abdominal compartment Acute tubular necrosis Urolithiasis
syndrome Cortical necrosis Urethral strictures
Cardiac failure Renal vein thrombosis Hemorrhagic cystitis
Anaphylaxis Rhabdomyolysis Neurogenic bladder
Acute interstitial nephritis Anticholinergic drugs
Tumor infiltration
Toxin and drugs
Tumor lysis syndrome
Vasculitis

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PRERENAL AKI, ALSO CALLED PRERENAL AZOTEMIA,
• is the most common form of AKI in children.
• is characterized by a diminished effective circulating arterial volume, which
leads to inadequate renal perfusion and a decreased GFR. Evidence of
structural kidney damage is absent.
• Common causes of prerenal AKI include dehydration, sepsis, hemorrhage,
severe hypoalbuminemia, and cardiac failure.
• If the underlying cause of the renal hypoperfusion is reversed promptly, renal
function returns to normal.
• If hypoperfusion is sustained, intrinsic renal parenchymal damage can develop.
INTRINSIC RENAL AKI

• includes a variety of disorders characterized by renal parenchymal damage,
including
o sustained hypoperfusion and ischemia.
o Ischemic/hypoxic injury and
o nephrotoxic insults are the most common causes of intrinsic AKI in the
United States and are more common with an underlying comorbid
condition;
▪ Most are associated with cardiac, oncologic, urologic, renal, and
genetic disorders or prematurity.
POSTRENAL AKI
• includes a variety of disorders characterized by obstruction of
o the urinary tract.
o In neonates and infants, congenital conditions, such as posterior urethral
valves and bilateral ureteropelvic junction obstruction, account for the
majority of cases of AKI.
o Other conditions, such as urolithiasis, tumor (intraabdominal lesion or
within the urinary tract), hemorrhagic cystitis, and neurogenic bladder,
can cause AKI in older children and adolescents.
• In a patient with two functioning kidneys, obstruction must be bilateral to
result in AKI.
• Relief of the obstruction usually results in recovery of renal function, except in
patients with associated renal dysplasia or prolonged urinary tract obstruction.
• The clinical context, careful history taking, and physical examination often
narrow the differential diagnosis for the cause of AKI.
Prerenal azotemia

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o suspected in the setting of vomiting, diarrhea, glycosuria causing
polyuria, and several medications including diuretics, NSAIDs, ACE
inhibitors, and ARBs.
o Physical signs of orthostatic hypotension, tachycardia, reduced jugular
venous pressure, decreased skin turgor, and dry mucous membranes are
often present in prerenal azotemia.
o Congestive heart failure, liver disease, and nephrotic syndrome can be
associated with reductions in renal blood flow and/or alterations in
intrarenal hemodynamics leading to reduced GFR.
Postrenal azotemia
o A history of nephrolithiasis, posterior urethral valve or pelvic or
paraaortic malignancy, neuroblastoma would suggest the possibility of
postrenal AKI.
o Whether or not symptoms are present early during obstruction of the
urinary tract depends on the location of obstruction.
o Colicky flank pain radiating to the groin suggests acute ureteric
obstruction.
o Definitive diagnosis of obstruction requires radiologic investigations.
Intrinsic azotemia
o Usually depends on the underlying causes.
LABORATORY FINDINGS
• CBC
o anemia (usually dilutional or hemolytic, as in SLE, renal vein thrombosis,
HUS);
o leukopenia (SLE, sepsis);
o thrombocytopenia (SLE, renal vein thrombosis, sepsis, HUS)
• Serum electrolyte
o hyponatremia (dilutional);
o hyperkalemia (decreased renal secretion of K),
o hyperphosphatemia (decreased renal secretion of phosphate)
• Metabolic acidosis;
o hypocalcemia (hyperphosphatemia),
o Renal function test
• Elevated serum concentrations of BUN & Cr (Diagnostic)
o Also used in case of differentiation of the cause as prerenal or intrinsic
renal

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o The low tubular flow rate and increased renal medullary recycling of
urea seen in prerenal azotemia may cause a disproportionate elevation
of the BUN compared to creatinine (BUN:Scr ≥20:1)
• Other causes of disproportionate BUN elevation are
o Upper gastrointestinal bleeding,
o hyperalimentation,
o increased tissue catabolism, and
o glucocorticoid use.
• Renal failure indices
o FeNa
▪ The FeNa is the fraction of the filtered sodium load that is not
reabsorbed by the tubules,
▪ is a measure of both the kidney’s ability to reabsorb sodium as
well as endogenously and exogenously administered factors that
affect tubular reabsorption.
▪ Prerenal azotemia, the FeNa may be <1%, (suggesting avid
tubular sodium reabsorption)
▪ Intrinsic renal: the FeNa is frequently >1% (because of tubular
injury and resultant impaired ability to reabsorb sodium).
o Urine osmolality (not specific)
▪ >500 mOsm/kg in prerenal azotemia, consistent with an intact
medullary concentration gradient and elevated serum vasopressin
levels causing water reabsorption by passive diffusion from the
collecting duct into a concentrated medullary interstitium,
resulting in concentrated urine.
▪ <350 mOsm/kg due to loss of concentrating ability is common in
most forms of AKI that affect the tubules and interstitium.
• Others
o Serum C3 level
▪ Serum antibodies (poststreptococcal glomerulonephritis), anti-
nuclear (SLE), neutrophil cytoplasmic (Wegener granulomatosis,
microscopic polyarteritis), or glomerular basement membrane
(Goodpasture disease) antigens.
o U/A: -
▪ hematuria, proteinuria, and RBC or granular urinary casts suggests
intrinsic ARF, in particular glomerular disease.
▪ WBC & WBC casts, with low-grade hematuria and proteinuria,
suggests tubulointerstitial disease.
▪ Urinary eosinophils may be present in children with drug-induced
tubulointerstitial nephritis.

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• Renal biopsy is done when the causes is not identified.
Table 103 Urine analysis findings of common conditions
HYPOV ATN* AIN* GLOMERULONEPH OBSTRUCTI
OLEMIA RITIS ON
Sediment Bland Broad, White blood Red blood cells, Bland or

brownis cells, red blood cell bloody
h eosinophils, casts
granular cellular
casts casts
Protein None or None or Minimal but Increased, Low
low low may be >100 mg/dL
increased
with NSAIDs
Urine <20 >30 >30 <20 <20 (acute)

sodium,
mEq/L* >40 (few
days)
Urine >400 <350 <350 >400 <350
osmolality,
mOsm/kg
Fractional <1 >1 Varies <1 <1 (acute)
excretion of
sodium %[†] >1 (few
days)
* ATN – Acute Tubular Necrosis, AIN – Acute interstitial Nephritis
COMMON COMPLICATIONS OF ACUTE KIDNEY INJURY

Table 104 Complications of AKI
METABOLIC CARDIOPULMONARY GI NEUROLOGIC HEMATOLOG
Hyperkalemia Pulmonary edema Nausea Neuromuscular Bleeding
Metabolic acidosis Arrhythmias Vomiting irritability Anemia
Hyponatremia Pericarditis Malnutrition Asterixis
Hypocalcemia Pericardial effusion Hemorrhage Seizures
Hyperphosphatemia Hypertension Mental status
Hypermagnesemia Myocardial infarction changes
Hyperuricemia Pulmonary embolism

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TREATMENT OF AKI
• In infants and children with Urinary Tract Obstruction, such as in a newborn
with suspected Posterior Ureteral Valves,
o A bladder catheter should be placed immediately to ensure adequate
drainage of the urinary tract.
• If there is no evidence of volume overload or cardiac failure, the intravascular
volume should be expanded by
o Intravenous administration of Isotonic Saline, 20 mL/kg over 30 min.
o In the absence of blood loss or hypoproteinemia, colloid-containing
solutions are not required for volume expansion.
• After volume resuscitation, Hypovolemic patients generally void within 2 hr;
o failure to do so suggests intrinsic or postrenal AKI.
• Diuretic therapy should be considered only after the adequacy of the
circulating blood volume has been established.
o Furosemide (2-4 mg/kg) may be administered as a single intravenous dose.
o Bumetanide (0.1 mg/kg) may be given as an alternative to furosemide
• If adequate urine output is not achieved escalation of furosemide is indicated
until adequate urine output is established.
• Mannitol may be effective in the prevention of pigment (myoglobin,
hemoglobin)-induced renal failure.
HYPERKALEMIA
• In AKI, rapid development of hyperkalemia (serum potassium level > 6mEq/L)
can lead to cardiac arrhythmia, cardiac arrest, and death.
• The earliest electrocardiographic change seen in patients with developing
hyperkalemia is the appearance of peaked T waves. This may be
o widening of the QRS intervals,
o ST segment depression,
o ventricular arrhythmias, and cardiac arrest.
• So, the principal management of this hyperkalemia is
o Decreasing the intake,
o Decreasing the absorption,
o Increasing the excretion and shifting of potassium into the cell.
• Exogenous sources of potassium (dietary, intravenous fluids, total parenteral
nutrition) should be eliminated.
• Sodium polystyrene sulfonate resin (Kayexalate), 1 g/kg, should be given orally
or by retention enema.
▪ This resin exchanges sodium for potassium and can take several hours
to take effect.

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▪ A single dose of 1 g/kg can be expected to lower the serum
potassium level by about 1 mEq/L.
▪ Resin therapy may be repeated every 2 hr, the frequency being
limited primarily by the risk of sodium overload.
o In severe case (when there is associated ECG change ) when serum
potassium is >7meq/l.
▪ Calcium gluconate 10% solution, 100 mg/kg/dose max 3000mg/dose.
▪ NB: Calcium gluconate counteracts the potassium- induced increase
in myocardial irritability but does not lower the serum potassium
level.
▪ Regular insulin, 0.1 units/kg, with glucose 50% solution, 1 mL/kg,
over 1hr.(shifts k to the cell)
▪ Sodium bicarbonate, 1-2 mEq/kg intravenously, over 5-10 min. (shifts
k to the cell)
• Mild metabolic acidosis is common in AKI because of the retention of hydrogen
ions, phosphate, and sulfate, but it rarely requires treatment.
o If acidosis is severe (arterial pH < 7.15; serum bicarbonate < 8 mEq/L) or
contributes to significant hyperkalemia, treatment is indicated.
o The acidosis should be corrected partially by the intravenous route,
generally by giving enough bicarbonate to raise the arterial pH to 7.20
(which approximates a serum bicarbonate level of 12 mEq/L).
o The remainder of the correction may be accomplished by oral
administration of sodium bicarbonate after normalization of the serum
calcium and phosphorus levels.
o Correction of metabolic acidosis with intravenous bicarbonate can
precipitate tetany in patients with renal failure because rapid correction of
acidosis reduces the ionized calcium concentration.
HYPOCALCEMIA
• Is primarily treated by lowering the serum phosphorus level.
• Calcium should not be given intravenously, except in cases of tetany, to avoid
deposition of calcium salts into tissues.
• Patients should be instructed to follow a low-phosphorus diet, and phosphate
binders should be orally administered to bind any ingested phosphate and
increase the GI phosphate excretion.
• Common agents include Sevelamer (Renagel), Calcium carbonate (Tums
tablets or Titralac suspension), and Calcium acetate (PhosLo).
• Aluminum-based binders, commonly employed in the past, should be avoided
because of the risk of aluminum toxicity.

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HYPONATREMIA
• Is most commonly a dilutional disturbance that must be corrected by fluid
restriction rather than sodium chloride administration.
• Administration of hypertonic (3%) saline should be limited to patients with
o symptomatic hyponatremia (seizures, lethargy) or
o those with a serum sodium level < 120 mEq/L.
BLEEDING
• AKI patients are predisposed to GI bleeding because of
o uremic platelet dysfunction,
o increased stress, and
o heparin exposure if treated with hemodialysis or continuous renal
replacement therapy.
• Oral or Intravenous H2 blockers such as Ranitidine are commonly administered
to prevent this complication.
N.B: Ranitidine is preferred over Cimetidine because Cimetidine affects the Scr which
makes difficult for follow up in a patient with renal disease
NEUROLOGIC SYMPTOMS
• Neurologic symptoms in AKI can include headache, seizures, lethargy, and
confusion (encephalopathy).
• Potential etiologic factors include
o hypertensive encephalopathy,
o hyponatremia,
o hypocalcemia,
o cerebral hemorrhage,
o cerebral vasculitis, and
o the uremic state.
• Benzodiazepines are the most effective agents in acutely controlling seizures,
and subsequent therapy should be directed toward the precipitating cause.
ANEMIA
• The anemia of AKI is generally mild (hemoglobin 9-10 g/dL) and primarily
results from volume expansion (hemodilution).
• Children with HUS, SLE, active bleeding, or prolonged AKI can require
transfusion of packed red blood cells if their hemoglobin level falls below 7
g/dL.
• In hypervolemic patients, blood transfusion carries the risk of further volume
expansion, which can precipitate hypertension, heart failure, and pulmonary
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o Slow (4-6 hr) transfusion with packed red blood cells (10 mL/kg)
diminishes the risk of hypervolemia.
NUTRITION
• In most cases, sodium, potassium, and phosphorus should be restricted.
• Protein intake should be moderately restricted while maximizing the caloric
intake to minimize the accumulation of nitrogenous wastes.
• In critically ill patients with AKI, parenteral hyperalimentation with essential
amino acids should be considered.
DIALYSIS
• Indications for dialysis in AKI include the following:
o Anuria/oliguria(but not for all patients)
o Volume overload with evidence of hypertension and/or pulmonary
edema
o Refractory to diuretic therapy
o Persistent hyperkalemia
o Severe metabolic acidosis unresponsive to medical management
o Uremia (encephalopathy, pericarditis, neuropathy)
o Calcium: phosphorus imbalance, with hypocalcemia tetany that cannot
be controlled by other measures.
PROGNOSIS
• The mortality rate in children with AKI is variable and depends entirely on the
nature of the underlying disease process rather than on the renal failure itself
o Eg. PSGN – MR is less than 1%
o AKI with MOF MR is greater than 90%
• The prognosis for recovery of renal function depends on the disorder that
precipitated AKI.
• Recovery of renal function is likely after AKI resulting from prerenal causes
ATN, acute interstitial nephritis, or tumor lysis syndrome
• Recovery of renal function is unusual when AKI results from most types of
rapidly progressive glomerulonephritis, bilateral renal vein thrombosis, or
bilateral cortical necrosis.

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10.3. GLOMERULAR DISEASES

ANATOMY OF THE GLOMERULUS
• The kidneys lie in the retroperitoneal space slightly above the level of the
umbilicus.
• They range in length and weight, respectively, from approximately 6cm and
24g in a full-term newborn to ≥ 12 cm and 150 g in an adult.
• The kidney has an
o Outer layer,
o The cortex, which contains the
glomeruli, proximal and distal
convoluted tubules, and collecting
ducts, and
o an Inner layer, the medulla, that
contains the straight portions of the
tubules, the loops of Henle, the vasa
recta, and the terminal collecting
ducts.
• Each kidney contains approximately 1
million nephrons (each consisting of a
glomerulus and associated tubules). There is
a large distribution of normal nephron Figure 93 Nephrons
numbers in humans, ranging from 200,000 to
1.8 million nephrons per kidney.
• In humans, the formation of nephrons is complete at 34-36 wk of gestation, but
functional maturation with tubular growth and elongation continues during the
1st decade of life.
• Because new nephrons cannot be formed after birth, any disease that results in
progressive loss of nephrons can lead to renal insufficiency.
• The glomerular network of specialized capillaries serves as the filtering
mechanism of the kidney. The glomerular capillaries are lined by endothelial
cells and have very thin cytoplasm that contains many holes (fenestrations).
• The glomerular basement membrane (GBM) forms a continuous layer between
the endothelial and mesangial cells on one side and the epithelial cells on the
other.
• The membrane has three layers: a central electron- dense lamina densa; the
lamina rara interna, which lies between the lamina densa and the endothelial
cells; and the lamina rara externa, which lies between the lamina densa and
the epithelial cells.

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• The visceral epithelial cells cover the capillary and project cytoplasmic foot
processes, which attach to the lamina rara externa. Between the foot
processes are spaces or filtration slits. The mesangium (mesangial cells and
matrix) lies between the glomerular capillaries on the endothelial cell side of
the GBM and forms the medial part of the capillary
wall.
• The mesangium may serve as a supporting, stalk-like
structure for the glomerular capillaries and probably
has a role in the regulation of glomerular blood flow,
filtration, and the removal of macromolecules (such as
immune complexes) from the glomerulus.
• The Bowman's capsule, which surrounds the
glomerulus, is composed of a basement membrane,
which is continuous with the basement membranes of
Figure 94 Glomerulus
the glomerular capillaries and the proximal tubules,
and the parietal epithelial cells, which are adjacent to
the visceral epithelium.
GLOMERULAR DISEASES
• Patients with glomerular disease usually have some hematuria with varying
degrees of proteinuria.
• The diagnosis of glomerular injury can be delayed because patients will not
manifest gross hematuria, and only rarely with the exception of
o IgA nephropathy and
o sickle cell disease is gross hematuria present.
• Sustained proteinuria >1–2 g/24 h is also commonly associated with glomerular
disease.
• Patients often will not know they have proteinuria unless
they become edematous or notice foaming urine on
voiding.
• The so called nonsustained proteinuria, generally <1 g/24
h, and is sometimes called functional or transient
proteinuria.
o caused by Fever, exercise, obesity, sleep apnea,
emotional stress, and congestive heart failure can
explain transient proteinuria.
Figure 95 Glomerulus under microscope
• Proteinuria only seen with upright posture is called
Orthostatic proteinuria and has a benign prognosis.

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CLINICAL SYNDROMES
• Various forms of glomerular injury can also be parsed into several distinct
syndromes on clinical grounds.
• Commonly these syndromes are classified in to six category
1. Acute nephritic syndrome
2. Nephrotic syndrome
3. Pulmonary renal syndrome
4. Basement membrane syndrome
5. Glomerular vascular syndrome
6. Infectious disease- associated syndrome
Table 105 Differentiating features of glomerular syndromes

GLOMERULAR SYNDROMES PROTEINURIA HEMATURIA VASCULAR INJURY
ACUTE NEPHRITIC SYNDROME
• PSGN +/++ ++/+++ -
• Subacute bacterial endocarditis +/++ ++ -
• Lupus nephritis +/++ ++/+++ +
• IGA nephropathy +/++ +++ -
• HSP +/++ ++/+++ ++++
• Membranoproliferative ++ ++/+++ ++++
glomerulonephritis + +/++ -
• Mesangioproliferative
glomerulonephritis
Pulmonary renal syndromes
• Goodpasture’s syndrome ++ ++/+++ -
• Cryoglobulinemia +/++ ++/+++ ++++
NEPHROTIC SYNDROME
• Minimal change disease ++++ - -
• Focal segmental +++/++++ + -
glomerulosclerosis ++++ + -
• Membranous nephropathy
BASEMENT MEMBRANE SYNDROME
• Anti-GBM disease ++ ++/+++ -
• Alport’s syndrome ++ ++ -
• Thin basement membrane disease + ++ -
GLOMERULAR VASCULAR SYNDROMES
• Sickle cell disease +/++ +++ +++
• Thrombotic microangiopathies ++ ++ +++

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• Antiphospholipid syndrome ++ ++ +++
INFECTIOUS DISEASE ASS SYNDROMES
• PSGN +/++ ++/+++ -
• Subacute bacterial endocarditis +/++ ++ -
• HIV +++ +/++ -
• Hepatitis B and C +++ +/++ -
• Syphilis +++ + -
• Leprosy +++ + -
• Malaria +++ +/++ -
+++ +/++ -
• Schistosomiasis
• We are going to discuss common cases that we face in our ward.

Table 106 Nephrotic Vs Nephritic Syndrome
Feature NEPHHTOTIC NEPHRITIC SYNDROME
SYNDROME
Proteinuria >3.5g/d 1-2g/d
Hyperlipidemia and Present Absent
lipiduria with faulty casts
Hypertension volume of Not a feature An important feature
urine passed in 24hr Normal Oligouria
Hematuria Not common A common and integral
component of syndrome
AKI Uncommon Common
Relapse Common Uncommon
Course Chronic 70-80% cases recover completely
progressive while others pass on to RPGN
disorder
10.4. ACUTE NEPHRITIC SYNDROME

• Refers to a set of renal disease in which an immunologic mechanism triggers
inflammation and proliferation of glomerular tissue that can result in damage
to the basement membrane, mesangium, or capillary endothelium.
ACUTE NEPHRITIC SYNDROME IS CHARACTERIZ ED BY

o Hematuria
o Oliguria
o fluid retention manifested by –edema and hypertension
o ARF, manifested by sudden decrease in the GFR
• We are going to discuss commonest type of acute nephritic syndromes.

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POSTSTREPTOCOCAL GLOMERULONEPHRITIS
• The most common cause of GN in children.
• Group A β-hemolytic streptococcal infections are common in children and can
lead to the postinfectious complication of Acute Glomerulonephritis (GN).
• Acute Poststreptococcal Glomerulonephritis (APSGN) is a classic example of the
acute nephritic syndrome characterized by:
o The sudden onset of gross hematuria,
o Edema,
o Hypertension, and
o Renal dysfunction.
• It is one of the most common glomerular causes of gross hematuria in children.
• APSGN follows infection of the throat or skin by certain nephritogenic strains of
group A β-hemolytic streptococci.
• 97% of cases occur in less developed countries. The overall incidence has
decreased in industrialized nations, presumably as a result of
o improved hygienic conditions and
o the near eradication of streptococcal pyoderma
• Poststreptococcal GN commonly follows
o Streptococcal pharyngitis during cold-weather months (serotypes M1,
M4, M25, and some strains of M12).
o Streptococcal skin infections or pyoderma during warm-weather months
(serotype M49).
• Probable mechanisms of immunologic injury are by Molecular mimicry whereby
circulating antibodies elicited by streptococcal antigens react with normal
glomerular antigens, in situ immune complex formation of antistreptococcal
antibodies with glomerular deposited antigen, and complement activation by
directly deposited streptococcal antigens.
• Poststreptococcal GN is most common in children ages 5-12 yrs.
• The typical patient develops an acute nephritic syndrome 1-2 wk. after an
antecedent streptococcal pharyngitis or 3-6 wk. after a streptococcal
pyoderma.
• The history of a specific infection may be absent, because symptoms may have
been mild or have resolved without patients receiving specific treatment or
seeking the care of a medical provider.

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• The severity of kidney involvement varies from asymptomatic microscopic
hematuria with normal renal function to gross hematuria with Acute renal
failure.
• Depending on the severity of renal involvement, patients can develop various
degrees of edema, hypertension, and oliguria.
• Patients are at risk for developing encephalopathy and/or heart failure
secondary to hypertension or hypervolemia.
• Hypertensive encephalopathy must be considered in patients with
o Blurred vision,
o Severe headaches,
o Altered mental status, or
o New seizures.
• The effects of acute hypertension depend on
o the severity of hypertension and
o the absolute change in comparison with the patient's baseline blood
pressure and the rate at which it has risen.
• Respiratory distress, orthopnea, and cough may be symptoms of pulmonary
edema and heart failure.
• Peripheral edema typically results from salt and water retention and is
common.
• Nephrotic syndrome develops in a minority (<5%) of childhood cases.
• Atypical presentations of APSGN include
o Those with subclinical disease and
o Those with severe symptoms but an absence of initial urinary
abnormalities
• In individuals who present with a purpuric rash, it is difficult to distinguish
APSGN from Henoch-Schönlein purpura without a renal biopsy.
Natural history of the disease

• The acute phase generally resolves within 6-8 wk.
• Urinary protein excretion and hypertension usually normalize by 4-6 wk after
onset,
• Persistent microscopic hematuria can persist for 1-2 yr after the initial
presentation.
INVESTIGATIONS
• U/A
o Hematuria
o Red blood cell cast

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o Proteinuria in nephritic range
o Polymorphonuclear leukocytes
• CBC
o Anemia (usually hemodilution and low-grade hemolysis)
o Serum C3
o C3 level is significantly reduced in > 90% of patients in the acute phase,
and returns to normal 6-8 wk. after the onset.
o C4 is most often normal in APSGN
• Confirmation of the diagnosis requires clear evidence of a prior streptococcal
infection.
o A positive throat culture report might support the diagnosis or might
represent the carrier state.
o A rising antibody titer to streptococcal antigen(s) confirms a recent
streptococcal infection.
▪ The anti-streptolysin O titer is commonly elevated after a
pharyngeal infection.
▪ The best single antibody titer to document cutaneous
streptococcal infection is the anti-deoxyribonuclease B level.
• Magnetic resonance imaging of the brain is indicated in patients with severe
neurologic symptoms and can demonstrate posterior reversible encephalopathy
syndrome in the parietooccipital areas on T2-weighted images.
• CXR - indicated in those with
o signs of heart failure or
o Respiratory distress, or
o Physical exam findings of a heart gallop, decreased breath sounds, rales,
or
o hypoxemia.
• Renal biopsy – Indicated
o Nephrotic syndrome,
o Absence of evidence of streptococcal infection,
o normal complement levels
o when hematuria and proteinuria, diminished renal function, and/or a
low C3 level persist more than 2 mo after onset.
COMPLICATIONS
• Acute complications result from hypertension and acute renal dysfunction.
• Hypertension is seen in 60% of patients and is associated with hypertensive
encephalopathy in 10% of cases.
• Heart failure, pulmonary edema

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• Electrolyte abnormality
o Hyperkalemia, Hyperphosphatemia, Hypocalcemia, Acidosis,
• Seizures, and
• Uremia.
TREATMENT
• Generally, the management is supportive.
• 10-day course of systemic antibiotic therapy with Penicillin.
o NB: It is only to limit the spread of the nephritogenic organisms,
antibiotic therapy does not affect the natural history of APSGN.
• If there is hypertension, treat hypertension (see on management of
hypertension on chapter) common drugs are frusemide, calcium channel
blocker, vasodilators, ACE inhibitors.
• Diuretics-frusemide
• Salt restriction and fluid restriction
PROGNOSIS
• Complete recovery occurs in > 95% of children with APSGN.
• Recurrences are extremely rare.
• Mortality in the acute stage can be avoided by appropriate management of
acute renal failure, cardiac failure, and hypertension.
• Infrequently, the acute phase is severe and leads to glomerulosclerosis and
chronic renal disease in < 2% of affected children.
HENOCH–SCHONLEIN PURPURA (HSP)

• Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood.
• Characterized by leukocytoclastic vasculitis and immunoglobulin A deposition
in the small vessels in the:
o Skin,
o Joints,
o Gastrointestinal tract, and
o Kidney
EPIDEMIOLOGY
• Occurs more common in white and Asian populations.
• The incidence of HSP is estimated at 14-20 per 100,000 children per year
• Affects males more than females, with a 1.2-1.8:1 male/female ratio.

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• Approximately 90% of HSP cases occur in children, usually between ages 3 and
10 yr.
• HSP is distinctly less common in adults, who often have severe and chronic
complications.
• HSP is more common in the winter and spring and is unusual in summer months.
PATHOGENESES
• Many cases of HSP follow a documented upper respiratory infection.
• The exact pathogenesis of HSP remains unknown. Given the seasonality of HSP
and the frequency of preceding upper respiratory infections, infectious triggers
such as group A β-hemolytic streptococcus, Staphylococcus aureus,
mycoplasma, and adenovirus have been suspected.
• The common finding of deposition of IgA, specifically IgA1, suggests that HSP is
a disease mediated by IgA and IgA immune complexes.
• The classic tetrad of HSP nephritis includes a palpable purpura, arthritis or
arthralgia, abdominal pain, and evidence for renal disease.
• The hallmark of HSP is its rash
o Palpable purpura starting as pink macules or wheals and developing into
petechiae, raised purpura, or larger ecchymoses.
o The skin lesions are usually symmetric
and occur in gravity-dependent areas
(Lower Extremities), extensor aspect
of the upper extremities or on pressure
points (Buttocks).
o The skin lesions often evolve in groups,
typically lasting 3-10 days, and may
recur up to 4 mos. after initial
presentation.
• Subcutaneous edema localized to the dorsa of
hands and feet, periorbital area, lips, scrotum, Figure 96 Henoch-Schönlein purpura
or scalp is also common. Maculopapular, reddish, non-blanching, palpable skin
lesions (purpura) are seen on both the distal right arm
• Musculoskeletal involvement, including and leg. On the lower leg, the lesions are partially
arthritis and arthralgias, is common, occurring confluent and present with scaling and erosion.
in up to 75% of children with HSP.
o The arthritis tends to be selflimited and oligoarticular, with a
predilection for large joints such as the knees and ankles, and does not
lead to deformities.

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o Swelling, tenderness without erythema is common presentation.
o The arthritis usually resolves within 2 wk.
• Gastrointestinal (GI) manifestations occur in up to 80% of children with HSP
o include abdominal pain, vomiting, diarrhea, paralytic ileus, and melena.
o Intussusception, mesenteric ischemia, and intestinal perforation are rare
but serious complications.
RENAL INVOLVEMENT
• Occurs in approximately 50% of HSP cases,
o More commonly in older children
o Age > 8 yr confers a 3-fold greater risk for renal involvement).
• Most patients (80%) initially display only mild renal involvement,
o principally isolated microscopic hematuria without significant
proteinuria.
• About 20% of patients can present with a more severe renal involvement,
o including a combined acute nephritic and nephrotic picture (hematuria,
o hypertension,
o renal insufficiency,
o significant proteinuria, and nephrotic syndrome).
• Most patients who develop nephritis
o have urinary abnormalities by 1 mo, and The platelet count in IgAV is
o nearly all have abnormalities by 3-6 mo after the normal or elevated, as opposed
onset of HSP. to other causes of purpura.
• Therefore, a urinalysis should be performed weekly in
patients with HSP during the period of active clinical disease.
o Thereafter, once a month for up to 6 mo.
o If all urinalyses are normal during this follow-up interval, nephritis is
unlikely to develop.
• Indications for a kidney biopsy in children with HSP nephritis include
o significant proteinuria (urine protein > 1 g/day or urine
protein/creatinine ratio > 1.0)
o significant hypertension, or
o elevated serum creatinine.
PROGNOSIS AND TREATMENT

• The prognosis of HSP nephritis for most patients is excellent.
• Spontaneous and complete resolution of the nephritis typically occurs in the
majority of patients with mild initial manifestations (isolated hematuria with
insignificant proteinuria).

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• However, such patients uncommonly can progress to severe renal involvement,
including development of Chronic Renal Failure.
• Patients with Acute Nephritic or Nephrotic Syndrome at presentation have a
guarded renal prognosis, particularly if they are found to have
o concomitant necrosis or
o substantial crescentic changes on renal biopsy.
• Untreated, the risk of developing chronic kidney disease, including end-stage
renal disease, is 2–5% in all patients with HSP,
o but almost 50% in those with the most severe early renal clinical and
histologic features.
• No convincing randomized clinical studies or evidence-based guidelines exist
for treatment of HSP nephritis. In particular, no studies have demonstrated any
efficacy of short courses (weeks) of oral corticosteroids administered promptly
after the onset of HSP in either preventing the development of nephritis or
decreasing the severity of subsequent renal involvement.
• Mild HSP nephritis does not require treatment, because it usually resolves
spontaneously.
• The efficacy of treatment for moderate or severe HSP nephritis, which is far
more likely to progress to chronic kidney disease, is more difficult to assess.
• Several uncontrolled studies have reported a significant benefit from aggressive
immunosuppression (high-dose and extended courses of corticosteroids with
azathioprine, mycophenolate mofetil, or cyclophosphamide) in patients with
poor prognostic features on renal biopsy; such patients are at high risk of
progressing to chronic kidney disease based on historical controls.
• Aggressive therapy with careful monitoring may be reasonable in those with the
most severe HSP nephritis (>50% crescents on biopsy).
• One common approach in children with severe clinical renal involvement
(nephrotic range proteinuria, elevated serum creatinine, hypertension) is the
use of oral prednisone (1 mg/kg per day for 3 mo.), along with angiotensin-
converting enzyme inhibitors, followed by azathioprine or mycophenolate
mofetil if severe clinical involvement persists.
• For children with severe histologic manifestations (>50% glomerular crescents),
treatment with intravenous methylprednisolone pulses for 3 days, followed by a
combination of oral prednisone (for 3 mo.) and azathioprine or mycophenolate
mofetil (extended course) may be considered.
• For children with the most severe histology (>75% glomerular crescents) and
progressive renal failure, intravenous steroids plus plasmapheresis may be
considered.

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• If progression to end-stage renal disease occurs, renal transplantation is the
treatment of choice.
HEMOLYTIC-UREMIC SYNDROME
• It is the most common form of Thrombotic Microangiopathy (TMA) in children
resulting in acute kidney injury.
HUS is characterized by the triad:

a. Microangiopathic hemolytic anemia,
b. Thrombocytopenia, and
c. Renal insufficiency
• HUS has clinical features in common with thrombotic thrombocytopenic
purpura (TTP)
NB: in TTP characterized by PENTAD
a. macroangiopathic hemolytic anemia,
b. thrombocytopenia,
c. renal insufficiency,
d. fever and
e. CNS manifestation.
• Based on the etiologic causes it is classified as
o Genetic,
o Infection-induced, and
o drug-induced,
• HUS associated with systemic diseases characterized by microvascular injury.
• The most common form of HUS is caused by infection induced and it is by Shiga
Toxin–Producing Escherichia Coli (STEC),
o which causes prodromal acute enteritis and is commonly termed STEC-
HUS or diarrhea-associated HUS.
• STEC-HUS accounts for about 90% of all HUS cases in childhood.
• Disease commonly is transmitted by undercooked meat or unpasteurized (raw)
milk and apple cider.

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Table 107 Different forms of HUS
DIARRHEA- HUS SECONDARY ATYPICAL HUS DUE DRUG SYSTEMIC DISEASE

ASSOCIATED TO SYSTEMIC TO COMPLEMENT INDUCED ASSOCIATED
HUS INFECTIONS DYSREGULATION
• STEC • Neuraminidase • Factor H deficiency •Cyclosporine • Systemic lupus

(Escherichia (Streptococcus (mutations, • Tacrolimus erythematosus
coli O157:H7) pneumoniae) autoantibodies) •Mithramycin • Coexisting nephropathies
• STEC (E.coli • Human • Factor I deficiency • Quinine • Malignant hypertension
0121 and immunodeficiency (mutations) • Cocaine • Malignancies
0104:H4) virus • Factor B (gain-of- • Anti • Cobalamin C defect
• Non-STEC • Influenza function mutations) vascular • Diacylglycerol kinase
(Shigella • Human herpes • Membrane cofactor endothelial epsilon mutation
dysenteriae virus 6 (MCP) deficiency growth factor
type 1) • Parvovirus B19 (mutations) therapy
• Malaria • C3 deficiency
(mutations,
autoantibodies)
• Thrombomodulin
deficiency (mutations)
• Anti–complement
factor H antibody
• A rare but distinct entity of infection-triggered HUS is related to

Neuraminidase-producing S. pneumoniae.
• HUS, typically severe, develops during acute infection with this organism,
typically manifesting as pneumonia with empyema.
• A thrombotic microangiopathy, similar to HUS or TTP, also can occur in
patients with untreated HIV infection and influenza infection.
• Genetic forms of HUS (atypical, nondiarrheal) compose the second major
category of the disease. Inherited deficiencies of either von Willebrand factor–
cleaving protease (ADAMTS13) or complement factor H, I, or B can cause HUS.
• A major feature characteristic of genetic forms of HUS is the absence of a
preceding diarrheal prodrome.
• HUS (diarrhea form) is most common in preschool and school-age children, but
it can occur in adolescents and adults.
• In HUS caused by toxigenic E. coli, the onset of HUS occurs 5-7 days after the
onset of gastroenteritis with fever, vomiting, abdominal pain, and diarrhea.
The diarrhea is often bloody, but not necessarily so.

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• The prodromal intestinal symptoms may be severe and require hospitalization,
but they can also be relatively mild and considered trivial.
• Following the prodromal illness, the sudden onset of pallor, weakness, and
lethargy heralds the onset of HUS, and it reflects the development of
microangiopathic hemolytic anemia.
• Oliguria can be present in early stages but may be masked by ongoing
diarrhea, because the prodromal enteritis often overlaps the onset of HUS,
particularly with ingestion of large doses of toxin. Thus, patients with HUS can
present with either significant dehydration or volume overload, depending on
whether the enteritis or renal insufficiency from HUS predominates, and the
amount of fluid that has been administered.
• Patients with pneumococci-associated HUS usually are quite ill with
pneumonia, empyema, and bacteremia when they develop HUS.
• The onset can be insidious in patients with the genetic forms of HUS, with HUS
triggered by a variety of illnesses, including mild, nonspecific gastroenteritis or
respiratory tract infections.
• The majority of patients with HUS have some Central Nervous System (CNS)
involvement.
o Most have mild manifestations, with significant irritability, lethargy, or
nonspecific encephalopathic features.
o Severe CNS involvement occurs in ≤ 20% of cases.
o Seizures and significant encephalopathy are the most common
manifestations in those with severe CNS involvement, resulting from
focal ischemia secondary to microvascular CNS thrombosis.
o Small infarctions in the basal ganglion and cerebral cortex have also
been reported, but large strokes and intracranial hemorrhage are rare.
o Hypertension may produce an encephalopathy and seizures.
• Intestinal complications can be protean and include severe inflammatory
colitis, ischemic enteritis, bowel perforation, intussusception, and pancreatitis.
• Patients can develop petechiae, but significant or severe bleeding is rare
despite very low platelet counts.
DIAGNOSIS
• The diagnosis is made by the combination of microangiopathic hemolytic
anemia with schistocytes, thrombocytopenia, and some degree of kidney
involvement.
• The anemia can be mild at presentation, but it rapidly progresses.
• Thrombocytopenia is an invariable finding in the acute phase, with platelet
counts usually 20,000-100,000/mm3.

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• Partial thromboplastin and prothrombin times are usually normal. The Coombs
test is negative, with the exception of pneumococci-induced HUS, where the
Coombs test is usually positive.
• Leukocytosis is often present and significant.
• Urinalysis typically shows microscopic hematuria and low-grade proteinuria.
• The renal insufficiency can vary from mild elevations in serum blood urea
nitrogen and creatinine to acute, anuric kidney failure.
• The etiology of HUS is often clear with the presence of a diarrheal prodrome or
pneumococcal infection.
• The presence or absence of toxigenic organisms on stool culture has little role
in making the diagnosis of diarrhea-associated STECHUS.
• Only a minority of patients infected with those organisms develops HUS, and
the organisms that cause HUS may be rapidly cleared. Therefore, the stool
culture is often negative in patients who have diarrhea-associated HUS.
• If no history of diarrheal prodrome or pneumococcal infection is obtained, then
evaluation for genetic forms of HUS should be considered, because those
patients are at risk for recurrence, have a severe prognosis, and can benefit
from a different therapy.
PROGNOSIS AND TREATMENT

• With early recognition and intensive supportive care, the mortality rate for
diarrhea-associated HUS is < 5% in most major medical centers. Up to half of
patients may require dialysis support during the acute phase of the disease.
• During recovery
o Platelet counts usually recovery occurs first,
o Renal recovery occurs after platelet recovery usually about 5 days later,
and
o Finally, by resolution of anemia.
• Most recover renal function completely, but of surviving patients, 5% remain
dependent on dialysis, and up to 30% are left with some degree of chronic renal
insufficiency.
• The prognosis for HUS not associated with diarrhea is more severe.
Pneumococci associated HUS causes increased patient morbidity (>80% require
dialysis), with the mortality rate reported as 20%.
• The familial, genetic forms of HUS can be insidiously progressive or relapsing
diseases and have a poor prognosis. Identification of specific factor deficiencies
in some of these genetic forms provides an opportunity for directed therapy to
improve the outcome.

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• The primary approach that has substantially improved an acute outcome in HUS
is early recognition of the disease, monitoring for potential complications, and
meticulous supportive care.
SUPPORTIVE CARE
• Careful management of fluid and electrolytes, including
o prompt correction of a volume deficit,
o control of hypertension, and
o early institution of dialysis if
▪ the patient becomes significantly Oliguric or anuric,
▪ particularly with hyperkalemia. (see indications of Dialysis under
AKI)
• Early intravenous volume expansion before the onset of oliguria or anuria may
be nephroprotective in diarrhea-associated HUS.
• Red cell transfusions are usually required because hemolysis can be brisk and
recurrent until the active phase of the disease has resolved.
• In pneumococci-associated HUS, it is critical that any administered red cells be
washed before transfusion to remove residual plasma, because endogenous
IgM directed against the revealed T antigen can play a role in accelerating the
pathogenesis of the disease.
• Platelets should generally not be administered, regardless of the platelet
count, to patients with HUS because they are rapidly consumed by the active
coagulation and theoretically can worsen the clinical course.
• Despite low platelet counts, serious bleeding is very rare in patients with HUS.
• There is no evidence that any therapy directed at arresting the disease process
of the most common, diarrhea-associated STEC-HUS provides benefit, and some
can cause harm. Attempts have been made using anticoagulants, antiplatelet
agents, fibrinolytic therapy, plasma therapy, immune globulin, and antibiotics.
Anticoagulation, antiplatelet, and fibrinolytic therapies are specifically
contraindicated because they increase the risk of serious hemorrhage.
• Antibiotic therapy to clear enteric toxigenic organisms (STEC) can result in
increased toxin release,
o potentially exacerbating the disease, and therefore is not
recommended. However, prompt treatment of causative pneumococcal
infection is important.
• Plasma therapy can be of substantial benefit to patients with identified deficits
of ADAMTS13 or factor H. It may also be considered in patients with other
genetic forms of HUS, such as the undefined familial (recessive or dominant)
form or sporadic but recurrent HUS.

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• Most patients with Diarrhea-Associated HUS recover completely, with little
risk of long-term sequelae.
• Patients with Hypertension,
o Any level of renal insufficiency, or residual urinary abnormalities
persisting a year after an episode of diarrhea-positive HUS (particularly
significant proteinuria) require careful follow-up.
• Patients who have recovered completely with no residual urinary abnormalities
after 1 yr are unlikely to manifest long term sequelae.
• Because of some reports of late sequelae in such patients, annual examinations
with a primary physician are still warranted.
10.5. NEPHROTIC SYNDROME

• Nephrotic syndrome is the clinical manifestation of glomerular diseases
associated with heavy (nephrotic-range).
• Proteinuria (Nephrotic-range proteinuria is defined as
o Proteinuria > 3.5 g/24 hrs. or Urine dipstick interpretation
o urine protein: creatinine ratio > 2 or • Negative <10mg/dl
o Proteinuria >40mg/kg/day or • Trace between 10 and
29mg/dL
o Proteinuria >1000mg/m2/day Or
• 1+ between 30 and 100
o Proteinuria >40mg/m2/hr. or
mg/dL
o dipstick protein ≥3+
• 2+ between 100 and
• Characterized by: 300mg/dL
o Hypoalbuminemia (≤2.5 g/dL), • 3+ between 300 and
o Heavy (nephrotic-range) proteinuria 1000 mg/dL
o Edema, and • 4+ >1000 mg/dL
o Hyperlipidemia (cholesterol > 200 mg/dL)
• Nephrotic syndrome affects 1-3 per 100,000 children < 16
yr of age.
• Without treatment, nephrotic syndrome in children is associated with a high
risk of death, most commonly from infections.
• Fortunately, 80% of children with nephrotic syndrome respond to
corticosteroid therapy.
• Causes of nephritic syndrome can be Primary (idiopathic) or Secondary
causes.

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Table 108 Causes of Nephrotic syndrome
IDIOPATHIC SECONDARY CAUSES OF NEPHROTIC SYNDROME

NEPHROTIC SYNDROME
- Minimal change Infections Drugs Immunologic or Associated With

disease Allergic Disorders Malignant Disease
- Focal segmental Endocarditis Captopril Vasculitis Lymphoma
glomerulosclerosis Hepatitis B, C Penicillamine syndromes Pheochromocytoma
- Membranous HIV-1 Gold Castleman disease Leukemia
nephropathy Infectious Nonsteroidal Kimura disease Thymoma
-Glomerulonephritis mononucleosis anti- Bee sting Solid tumors
associated with Cytomegalovirus inflammatory Snake venom
nephrotic syndrome– Malaria drugs Food allergens
membranoproliferative Syphilis Pamidronate, Serum sickness
glomerulonephritis, (congenital and bisphosphonates Poison ivy, poison
secondary) Interferon oak
- Crescentic Toxoplasmosis Mercury
glomerulonephritis, Tuberculosis Heroin
- Immunoglobulin A Schistosomiasis Lithium
nephropathy Filariasis Rifampicin
Sulfasalazine
CLINICAL CONSEQUENCES OF NEPHROTIC SYNDROME

EDEMA:
• Edema is the most common presenting symptom of children with nephritic
syndrome.
• Underfill hypothesis and the overfill hypothesis, that have been proposed as
mechanisms causing nephrotic edema.
• The underfill hypothesis is based on nephrotic-range proteinuria that leads to
a fall in the plasma protein level with a corresponding decrease in intravascular
oncotic pressure. This leads to leakage of plasma water into the interstitium,
generating edema. As a result of reduced intravascular volume, there is
increased secretion of vasopressin and atrial natriuretic factor, which, along
with aldosterone, results in increased sodium and water retention by the
tubules. Sodium and water retention therefore occur as a consequence of
intravascular volume depletion.
• The overfill hypothesis postulates that nephrotic syndrome is associated with
primary sodium retention, with subsequent volume expansion and leakage of
excess fluid into the interstitium. There is accumulating evidence that the

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epithelial sodium channel in the distal tubule may play a key role in sodium
reabsorption in nephrotic syndrome.
HYPERLIPIDEMIA
• The alterations in the lipid profile in children with nephrotic syndrome,
including
o an increase in Cholesterol,
o Increase in Triglycerides,
o Increase in Low-Density Lipoproteins (LDL), and
o Very-Low-Density Lipoproteins (VLDL).
o The high-density lipoprotein level remains unchanged or is low.
• Hyperlipidemia is thought to be the result of increased synthesis as well as
decreased catabolism of lipids.
INCREASED SUSCEPTIBILITY TO INFECTIONS

• Children with nephrotic syndrome are especially susceptible to infections such
as cellulitis, spontaneous bacterial peritonitis, and bacteremia.
• This occurs as a result of
o Hypoglobulinemia (mainly) as a result of the urinary losses of
immunoglobulin IgG.
o Defects in the complement cascade from urinary loss of complement
factors (predominantly C3 and C5), as well as alternative pathway
factors B and D, lead to impaired opsonization of microorganisms.
• Children with nephrotic syndrome are at significantly increased risk for
infection with encapsulated bacteria and, in particular, pneumococcal
disease.
• Spontaneous Bacterial Peritonitis (SBP) presents with
o fever,
o abdominal pain, and
o peritoneal signs.
• Pneumococcus is the most frequent cause of peritonitis, but also Gram-
negative bacteria also are associated with a significant number of cases.
• Peritoneal leukocyte counts >250 cells/µL are highly suggestive of
Spontaneous Bacterial Peritonitis.
HYPERCOAGULABILITY
• Nephrotic syndrome is a hypercoagulable state resulting from multiple factors:
o vascular stasis from hemoconcentration and intravascular volume
depletion,
o increased platelet number and aggregability, and

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o changes in coagulation factor levels.
o There is an increase in hepatic production of fibrinogen along with
urinary losses of antithrombotic factors such as antithrombin III and
protein S.
• Deep Venous Thrombosis may occur in any venous bed, including the cerebral
venous sinus, renal vein, and pulmonary veins.
• The clinical risk is low in children (2–5%) compared with adults but has the
potential for serious consequences.
IDIOPATHIC NEPHROTIC SYNDROME

• Approximately 90% of children with nephrotic syndrome have Idiopathic
Nephrotic Syndrome.
• Idiopathic nephrotic syndrome is associated with primary glomerular disease
without an identifiable causative disease or drug.
• Idiopathic nephrotic syndrome includes multiple histologic types:
o Minimal change disease,
o Mesangial proliferation,
o Focal segmental glomerulosclerosis,
o Membranous nephropathy, and
o Membranoproliferative glomerulonephritis.
• Minimal Change Nephrotic Syndrome (MCNS)
o 85% of total cases of nephrotic syndrome in children,
o the glomeruli appear normal or show a minimal increase in mesangial
cells and matrix.
o Findings on immunofluorescence microscopy are typically negative, and
electron microscopy simply reveals effacement of the epithelial cell foot
processes.
o More than 95% of children with Minimal Change Disease respond to
• Mesangial proliferation
o is characterized by a diffuse increase in mesangial cells and matrix on
light microscopy.
o Immunofluorescence microscopy might reveal trace to 1+ mesangial IgM
and/or IgA staining.
o Electron microscopy reveals increased numbers of mesangial cells and
matrix as well as effacement of the epithelial cell foot processes.
o Approximately 50% of patients with this histologic lesion respond to
• In Focal Segmental Glomerulosclerosis (FSGS),

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o glomeruli show lesions that are both focal (present only in a proportion
of glomeruli) and segmental (localized to ≥ 1 intraglomerular tufts).
o The lesions consist of mesangial cell proliferation and segmental scarring
on light microscopy. Immunofluorescence microscopy is positive for IgM
and C3 staining in the areas of segmental sclerosis.
o Electron microscopy demonstrates segmental Scarring of the Glomerular
tuft with obliteration of the glomerular capillary lumen.
o Only 20% of patients with FSGS respond to prednisone.
o The disease is often progressive, ultimately involving all glomeruli with
end-stage renal disease in most patients.
• The Idiopathic Nephrotic Syndrome is more common in males than in females
(2: 1) and most commonly appears between the ages of 2 and 6 yr.
• MCNS is present in 85–90% of patients < 6 yr of age.
• In contrast, only 20–30% of adolescents who present for the first time with
nephritic syndrome have MCNS.
• The more common cause of idiopathic nephritic syndrome in this older age-
group is FSGS. FSGS is the most common cause of end-stage renal disease in
adolescents.
• The initial episode of idiopathic nephrotic syndrome, as well as subsequent
relapses, may follow minor infections and, uncommonly, reactions to insect
bites, beestings, or poison ivy.
• Children usually present with mild edema, which is initially noted around the
eyes and in the lower extremities.
• Anorexia, irritability, abdominal pain, and diarrhea are common.
• Important features of Minimal Change Idiopathic Nephrotic Syndrome are the
absence of hypertension and gross hematuria.
DIAGNOSIS
• The diagnosis of nephrotic syndrome is confirmed by urinalysis with the first
morning urine protein: creatinine ratio and serum electrolytes, blood urea
nitrogen, creatinine, albumin, and cholesterol levels; an evaluation to rule out
secondary forms of nephrotic syndrome (children ≥ 10 yr) by the complement
C3 level, antinuclear antibody, double-stranded DNA; hepatitis B and C and HIV
and kidney biopsy (for children ≥ 12 yr, who are less likely to have MCNS).
• The urinalysis reveals 3+ or 4+ proteinuria, and microscopic hematuria is
present in 20% of children.
• A spot urine protein: creatinine ratio should be > 2.0.

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• The serum creatinine value is usually normal, but it may be abnormally
elevated if there is diminished renal perfusion from contraction of the
intravascular volume.
• The serum albumin level is < 2.5 g/dL, and serum cholesterol and triglyceride
levels are elevated. Serum complement levels are normal.
• A renal biopsy is not routinely performed if the patient fits the standard
clinical picture of MCNS.
TREATMENT
• Children with their first episode of nephrotic syndrome and mild to moderate
edema may be managed as outpatients.
• Tuberculosis must be ruled out prior to starting immunosuppressive therapy
with corticosteroids by placing a purified protein derivative or obtaining an
interferon release assay, and confirming a negative result.
• Children with onset of uncomplicated nephrotic syndrome between 1 and 8 yr
of age are likely to have steroid-responsive MCNS, and steroid therapy may be
initiated without a diagnostic renal biopsy.
• Children with features that make MCNS less likely (gross hematuria,
hypertension, renal insufficiency, hypocomplementemia, or age < 1 yr or > 12
yr) should be considered for renal biopsy before treatment.
USE OF CORTICOSTEROIDS TO TREAT MINIMAL CHANGE NEPHROTIC SYNDROME

• Corticosteroids are the mainstay of therapy for MCNS.
• In children with presumed MCNS,
o Prednisone or prednisolone should be administered as a single daily dose
of 60 mg/m2 /day or 2 mg/kg/day to 60 mg daily (max) for 4-6 wk
o Followed by alternate-day prednisone (starting at 40 mg/m2 qid or
1.5 mg/kg qid) for a period ranging from 8 wk to 5 mo, with tapering
of the dose.
• 80–90% of children respond to steroid therapy.
• Definitions regarding the response to steroid therapy are as follows:
o Response is defined as the attainment of remission
o Remission consists of a urine protein: creatinine ratio of < 0.2 or < 1+
protein on urine dipstick testing for 3 consecutive days within the initial
4 wk of corticosteroid therapy. .
o Relapse is an increase in the first morning urine protein: creatinine ratio
>2 or a reading of 3+ and higher for 3 consecutive days on Albustix
testing.

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o Frequently relapsing is two or more relapses within 6 mo after the
initial therapy or four relapses in a 12-mo period.
o Steroid dependent is a relapse during steroid tapering or a relapse
within 2 wk of the discontinuation of therapy.
o Steroid resistance is the inability to induce remission within 4 wk of
daily steroid therapy.
MANAGING THE CLINICAL SEQUELAE OF NEPHROTIC SYNDROME

• EDEMA
o Children with severe symptomatic edema,
▪ including large pleural effusions,
▪ ascites, or
▪ severe genital edema, should be hospitalized.
o In addition to sodium restriction (<1,500 mg daily), water/fluid
restriction may be necessary if the child is hyponatremic.
o A swollen scrotum may be elevated with pillows to enhance fluid
removal by gravity.
o Diuresis may be augmented by the administration of loop diuretics
(furosemide), orally or intravenously, although extreme caution should
be exercised only if the patient has gross edema, ascites or genital
edema, severe pleural effusion with breathing difficulty.
o Aggressive diuresis can lead to intravascular volume depletion and an
increased risk for acute renal failure and intravascular thrombosis.
o When a patient has severe generalized edema with evidence of
intravascular volume depletion (e.g., hemoconcentration, hypotension,
tachycardia), intravenous administration of 25% albumin (0.5-1.0 g
albumin/kg) as a slow infusion followed by furosemide (1-2 mg/kg/dose
intravenously) is sometimes necessary.
• DYSLIPIDEMIA.
o Dyslipidemia should be managed with a low-fat diet.
o Dietary fat intake should be limited to <30% of calories with a saturated
fat intake of <10% calories.
o Dietary cholesterol intake should be <300 mg/day.
o There are insufficient data to recommend the use of 3-hydroxy-3-
methylgluataryl coenzyme A (HMG-CoA) reductase inhibitors routinely
in children with dyslipidemia.
• INFECTIONS.
o Families of children with nephrotic syndrome should be counseled
regarding the signs and symptoms of infections such as cellulitis,
peritonitis, and bacteremia.

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o In the case of spontaneous bacterial peritonitis, peritoneal fluid should
be collected if there is sufficient fluid to perform a paracentesis and
sent for cell count, Gram stain, and culture.
o The antibiotic provided must be of broad enough coverage to include
Pneumococcus and Gram-negative bacteria. A third-generation
cephalosporin is a common choice of intravenous antibiotic.
• THROMBOEMBOLISM.
o Children who present with the clinical signs of thromboembolism should
be evaluated by appropriate imaging studies to confirm the presence of
a clot.
o Anticoagulation therapy in children with thrombotic events appears to
be effective—heparin, low-molecular-weight heparin, and warfarin are
therapeutic options.
RELAPSE OF NEPHROTIC SYNDROME

• Relapse of nephrotic syndrome is defined as a urine Protein:Creatinine ratio of
> 2 or ≥ 3+ protein on urine dipstick testing for 3 consecutive days.
• Relapses are common, especially in younger children, and are often triggered
by upper respiratory or gastrointestinal infections.
• Relapses are usually treated similar to the initial episode, except that daily
prednisone courses are shortened. Daily high-dose prednisone is given until the
child has achieved remission, and the regimen is then switched to alternate-
day therapy. The duration of alternate-day therapy varies depending on the
frequency of relapses of the individual child.
• Children are classified as infrequent relapsers or frequent relapsers, and as
being steroid dependent, based on the number of relapses in a 12-mo period or
their inability to remain in remission following discontinuation of steroid
therapy.
STEROID RESISTANCE
• Steroid resistance is defined as the failure to achieve remission after 8 wk of
• Children with steroid-resistant nephrotic syndrome require further evaluation,
including a diagnostic kidney biopsy, evaluation of kidney function, and
quantitation of urine protein excretion (in addition to urine dipstick testing).
• Steroid-resistant nephrotic syndrome is usually caused by FSGS (80%), MCNS, or
membranoproliferative glomerulonephritis.
IMPLICATIONS OF STEROID-RESISTANT NEPHROTIC SYNDROME

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• Steroid-resistant nephrotic syndrome, and specifically FSGS, is associated with
a 50% risk for end-stage kidney disease within 5 yr of diagnosis if patients do
not achieve a partial or complete remission.
• Persistent nephrotic syndrome is associated with a poor patient-reported
quality of life, hypertension, serious infections, and thromboembolic events.
ALTERNATIVE THERAPIES TO CORTICOSTEROIDS IN THE TREATMENT OF

NEPHROTIC SYNDROME
• Steroid-dependent patients, frequent relapsers, steroid-resistant patients and
patients with severe steroid toxicity(cushingoidappearance,
hypertension,cataracts, and/orgrowth failure)are candidates for alternative
therapies.
• Cyclophosphamide prolongs the duration of remission and reduces the number
of relapses in children with frequently relapsing and steroid-dependent
nephrotic syndrome.
• The potential side effects of the drug (neutropenia, disseminated varicella,
hemorrhagic cystitis, alopecia, sterility, increased risk of future malignancy)
should be carefully reviewed with the family before initiating treatment.
• Cyclophosphamide (2 mg/kg) is given as a single oral dose for a total duration
of 8-12 wk. Alternate-day prednisone therapy is often continued during
cyclophosphamide administration.
• During cyclophosphamide therapy, the white blood cell count must be
monitored weekly and the drug should be withheld if the count falls below
5,000/mm3. The cumulative threshold dose above which oligospermia or
azoospermia occurs in boys is > 250 mg/kg.
• Calcineurin inhibitors (cyclosporine or tacrolimus) are recommended as initial
therapy for children with steroid-resistant nephrotic syndrome.
• Children must be monitored for side effects, including hypertension,
nephrotoxicity, hirsutism, and gingival hyperplasia. Mycophenolate can
maintain remission in children with steroid-dependent or frequently relapsing
nephrotic syndrome.
IMMUNIZATIONS IN CHILDREN WITH NEPHROTIC SYNDROME.

• To reduce the risk of serious infections in children with nephrotic syndrome,
give the full pneumococcal vaccination (with the 13-valent conjugant vaccine
and 23-valent polysaccharide vaccine) and influenza vaccination annually to
the child and their household contacts;
• defer vaccination with live vaccines until the prednisone dose is below either 1
mg/kg daily or 2 mg/kg on alternate days.

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• Live virus vaccines are contraindicated in children receiving corticosteroid-
sparing agents such as cyclophosphamide or cyclosporine.
PROGNOSIS
• Most children with steroid-responsive nephrotic syndrome have repeated
relapses, which generally decrease in frequency as the child grows older.
• Those who are likely to follow an infrequently relapsing course.,
o Children who respond rapidly to steroids those who have no relapses
during the first 6 mo after diagnosis.
• Children with steroid-resistant nephrotic syndrome, most often caused by
FSGS, generally have a much poorer prognosis.
• These children develop progressive renal insufficiency, ultimately leading to
end-stage renal disease requiring dialysis or kidney transplantation.
• Recurrent nephrotic syndrome develops in 30–50% of transplant recipients with
FSGS.

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CHAPTER 11 - DIABETES MELLITUS

11.1. INTRODUCTION
Diabetes mellitus (DM) is a common, chronic, metabolic disease characterized by
hyperglycemia as a cardinal biochemical feature. DM is not a single entity but rather a
heterogeneous group of disorders in which there are distinct genetic patterns as well as
other etiologic and pathophysiologic mechanisms that lead to impairment of glucose
tolerance through deficient insulin production or action.
The American Diabetes Association has proposed a diabetes classification system that
includes 4 categories:
1. Type 1 diabetes,
2. Type 2 diabetes,
3. Other specific types, and
4. Gestational diabetes.
11.2. TYPE 1 DIABETES MELLITUS

• Is an autoimmune disorder that causes Pancreatic B-cells Table 109 Actions of Insulin in our
body
destruction.
• The destruction leads to insulin deficiency that result in Liver
Increase Glucose
uptake, lipogenesis
hyperglycemia and disrupt energy storage and metabolism. and Glycogen
• In T1DM there is dependence on exogenous insulin to prevent formation.
the development of ketoacidosis, a life-threatening Inhibit Ketogenesis
and glycogenolysis.
complication of T1DM.
Increase glucose
Muscle
EPIDEMIOLOGY AND RISK FACTORS uptake, glucose
oxidation, glycogen
• T1DM accounts for approximately 10% of all cases of diabetes and protein
synthesis
in all ages. Increase glucose
• F:M ratio is equal, except in some population there is a slight Adipose uptake, lipid
tissue
male predominance. synthesis and
Triglyceride uptake
• Peaks of presentation occur in 2 age groups:
o At 5-7 yr. of age and at the time of puberty.
▪ The 1st peak may correspond to the time of
increased exposure to infectious agents coincident with the
beginning of school;
▪ The 2nd peak may correspond to the pubertal growth spurt
induced by gonadal steroids and the increased pubertal growth
hormone secretion (which antagonizes insulin).
GENETIC FACTORS
• Family history & Genetic Predisposition increase the risk
o Concordance in identical twin ranges between 40 and 60%.
o Polymorphism of HLA complex account for 40–50% of the genetic risk

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• The risk of developing type 1 DM is
o 3–4% if the parent has type 1 DM and
o 5–15% in a sibling (depending on which HLA haplotypes are shared).
ENVIRONMENTAL FACTORS
• Viral Infections
o Congenital Rubella Syndrome
▪ Prenatal infection with rubella is associated with β-cell autoimmunity
in up to 70%, with development of T1DM in up to 40% of infected
children.
o Enteroviruses
o Mumps Virus
• Gastrointestinal microbes
• Diet
o Cow milk increase the risk of T1DM. (ask on dietary history).
o Vit D, Vit E, Vit C, Zink deficiencies have also been linked with increased
risk.
• Psychologic stress
o There is an increased prevalence of stressful psychologic situations among
children who subsequently developed T1DM.
PATHOGENESIS AND NATURAL HISTORY OF TYPE 1 DIABETES MELLITUS
• Host develops autoimmunity against the host’s own β-cells. (Islet autoantibodies)
• This continues till progressive destruction of β-cells reaches a critical mass of β-
cells is lost and insulin deficiency develops.
• Insulin deficiency will leads to the onset of clinical signs and symptoms of T1DM.
• Thus, the natural history of T1DM involves some or all of the following stages, with 2
distinct identifiable stages prior to onset of symptoms:
1. Presence of 2 or more islet autoantibodies with normoglycemia and
presymptomatic; can last years to decades
2. β-cell autoimmunity with dysglycemia and presymptomatic; Shorter
3. Onset of symptomatic disease; usually quite brief, weeks, rarely months
4. Transient remission, usually within weeks of onset, may last 6-12 mo.
5. Established disease, lifelong
6. Development of complications, quite variable
PATHOPHYSIOLOGY
T1DM is a progressive low-insulin catabolic state in which feeding does not reverse,
but rather exaggerates, these catabolic processes.
• With moderate Insulinopenia → glucose utilization by muscle and fat decreases
and postprandial hyperglycemia appears
• At even lower insulin levels, the liver produces excessive glucose via
glycogenolysis and gluconeogenesis, and fasting hyperglycemia begins.
• Hyperglycemia produces an osmotic diuresis (glycosuria) when the renal
threshold is exceeded (i.e., 180 mg/dL).

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• The resulting loss of calories and electrolytes, as well as the Effects of counter regulatory
worsening dehydration, produces a physiologic stress with hormones on Glucose
hypersecretion of stress hormones. regulation.
• These hormones, (Epinephrine, glucagon, cortisol, and 1. Impairing insulin Secretion
growth hormone) in turn, contribute to the metabolic → Epinephrine
decompensation. 2. Antagonizing its action →
epinephrine, cortisol,
CLINICAL MANIFESTATIONS growth hormone
3. Promoting glycogenolysis,
Features of diabetes do not become evident until a threshold gluconeogenesis, lipolysis,
(around 70-80%) loss of insulin secretion and beta cell mass occurs. and ketogenesis → glucagon,
The presentation of the patients can be epinephrine, growth
hormone, and cortisol.
CLASSICAL SYMPTOMS (HYPERGLYCEMIA WITHOUT ACIDOSIS) 4. Decreasing glucose
- Polyuria: Patients present with Re-emergence of utilization and glucose
bedwetting, nocturia, and a need to leave classes in school clearance → epinephrine,
to use the bathroom are complaints that suggest polyuria. growth hormone, cortisol.
- Polydipsia (exceeding 2L/m2/24hr)
- Polyphagia
- Weight loss
- Fatigue, weakness
DIABETIC KETOACIDOSIS (See Later)
SILENT PRESENTATION Daily loss of Water and
- Diagnosis before onset of clinical symptoms which typically glucose can reach as high as
occurs in children with family history of T1DM due to close 5L and 250g, respectively,
monitoring. representing 1,000 calories,
or 50%, of the average daily
DIAGNOSIS OF DIABETES caloric intake.
The diagnosis of diabetes is straight forward. We diagnose diabetes

using either of the 4 lab results.
• Random Blood Sugar (RBS) - A random blood sugar test checks blood glucose at
a random time of day.
o If greater or equal to 200mg/dl with Symptoms of diabetes include
polyuria, polydipsia, and unexplained weight loss with glucosuria and
ketonuria.
• Fasting Blood Sugar (FBS) - Is a test that determine how much glucose is in the
blood after overnight (8 Hours) of fasting. Fasting doesn’t
include water intake. *To make the diagnosis of DM,
o If greater or equal to 126mg/dl or * the FBS, RBS and OGTT need
• HgA1c - evaluates the average amount of glucose in the to be repeated on different
blood over the last 2 to 3 months. day.
o If greater or equal to 6.5 or *
• 2-hour Glucose Tolerance Test (OGTT) - (often used to
diagnose Gestational DM)

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o If greater or equal to 200mg/dl. *
Once hyperglycemia is confirmed, we need to determine if DKA is present. (See
below)
11.3. COMPLICATIONS OF DIABETES

The complications of diabetes can be classified as Acute complications or Chronic
complications.
ACUTE COMPLICATIONS OF DIABETES

1. HYPOGLYCEMIA
Clinical manifestations of Hypoglycemia can be classified into two
Whipple’s triads of
• Neurogenic symptoms due to activation of autonomic
hypoglycemia
nervous system
- Sweating 1.Symptoms consistent
- shakiness, trembling with hypoglycemia.
- tachycardia 2.A low plasma glucose,
- anxiety, nervousness and
- weakness 3.Relief of symptoms
after the plasma
- hunger
glucose level is raised.
- nausea, vomiting
• Neuroglycopenic symptoms due to decreased cerebral
glucose use
- visual disturbances
- lethargy, lassitude
- restlessness, irritability
- difficulty with speech and thinking,
- inability to concentrate
- mental confusion
- somnolence, stupor, prolonged sleep
- loss of consciousness, coma
- hypothermia
- twitching, convulsions.
2. HYPEROSMOLAR HYPERGLYCEMIC STATE
• More common in T2DM patients.
3. DIABETES KETOACIDOSIS (KNOW IN DEPTH)
• Diabetes ketoacidosis (DKA): is one of the acute complications
of Diabetes mellitus due to insulin deficiency or ineffectiveness. DKA is the first
• Severe Insulinopenia (or lack of effective insulin action) results manifestation of T1DM in
in a physiologic cascade of events in 3 general pathways 20-40% of the patients.
1. Hyperglycemia

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o Causes Osmotic Diuresis with loss of water and electrolytes
2. Increased catabolic processes
o Result in cellular losses of sodium, potassium, and phosphate.
3. Increased release of free fatty acids from peripheral fat stores makes
ketone body formation favorable.
o The hormonal interplay of insulin deficiency and excess counter regulatory
hormones shunts the free fatty acids into ketone body formation.
o Accumulation of these keto acids results in metabolic acidosis which is
called Diabetic Ketoacidosis (DKA).
PRESENTATION OF DKA
• Symptoms include
o Poly symptoms
o Weight loss
o Abdominal Pain
o Nausea and Vomiting
o Confusion, Loss of consciousness
• Signs Include
o Tachycardia, Tachypnea
o Hypotension and Shock
o Kussmaul Breathing
- Deep, Rapid, non-labored breathing
o Signs of Dehydration
- Assessed by the peripheral signs of Dehydration
o Altered Mental status.
PRECIPITATING FACTORS
1. Omission or reduction of insulin dose.
2. Previously unknown diabetic (new diagnosis)
3. Infection (pneumonia /UTI/gastroenteritis/sepsis)
4. Stress, psychosocial, trauma
5. Pregnancy
DIAGNOSIS OF DKA
The diagnosis of DKA is made by the presence of Triads of DKA
o Hyperglycemia • Hyperglycemia (>200mg/dl)
- Random blood sugar >200mg/dl • Ketosis
o Acidosis • High anion gap metabolic acidosis
- Venous PH < 7.3 and or (PH or Bicarb)
- Bicarbonate < 15 mmol/L.

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o Ketosis
- Ketonuria or Ketonemia DDx for DKA
• Starvation ketosis
ADDITIONAL INVESTIGATIONS INCLUDE • Alcoholic ketoacidosis
(AKA)
• Complete Blood Count
• Other causes of High anion
o May show us evidences of infections i.e., gap acidosis
leucocytosis o Lactic acidosis
• Serum Electrolyte o Toxins (salicylate,
o Hyponatremia - due to efflux of fluid to Methanol, Ethylene
glycol, …)
intravascular space in the presence of o Renal Failure
hyperglycemia. An increased or even normal serum
sodium concentration in the presence of
hyperglycemia indicates a rather profound degree
of free water loss.
▪ Serum sodium should increase by 1.6 for every 100mg/dl
increase from baseline (100mg/dl is taken as
baseline). Corrected Na+ Concentration
▪ Declining sodium while on treatment may • [Na+] + (1.6 mEq/L of Na
indicate excessive free water accumulation for every 100mg/dL serum
and increased risk of cerebral edema. glucose that is above
o Hyperkalaemia - because of an extracellular shift 100mg/dl).
of potassium caused by insulin deficiency, • E.g.- If the patient’s
hypertonicity, and acidosis. Patients with low serum Na+ is 133 mEq/L
normal or low serum potassium concentration on and his RBS is 643mg/dl,
admission have severe total-body potassium The corrected Na+
deficiency and require careful cardiac monitoring concentration will be,
and more vigorous potassium replacement because =133+ (1.6 x (5))
= 141 mEq/L (which is
insulin treatment lowers potassium further and can
in normal range)
provoke cardiac dysrhythmia.
o Hyperphosphatemia- due to shifts of intracellular
phosphate to the extracellular space.
o High anion gap (Indicating Acidosis)
▪ The anion gap is a measurement of the difference-or gap-
between the negatively charged and positively charged
electrolytes.
▪ Anion gap = (Na+) - [(Cl- + HCO3- (mEq/l)]
▪ (Normal Range is between 3-11 mEq/L)
• EKG – Assess for signs of Hyper/hypokalemia.
• Renal Function Test – May show elevated Creatinine and ↑BUN to Cr ratio.
This is due to pre-renal cause of Acute kidney injury due to the
dehydration.

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CLASSIFICATION OF DKA
Table 110 Classification of DKA
Normal Mild Moderate Severe

CO2 (mEq/L, 20-28 16-20 10-15 <10
venous)
pH (venous) 7.35-7.45 7.25-7.35 7.15-7.25 <7.15
Clinical No change Oriented, alert Kussmaul Kussmaul or
but fatigued respirations; depressed
oriented respirations;
but sleepy; sleepy to depressed
arousable sensorium to coma
o Patients can be classified depending on the range of symptoms and
degree of acidosis.
o We commonly use the clinical staging to Grade DKA in our setup.
o Severe hypernatremia (corrected Na >150 mEq/L) would also be
classified as Severe Diabetic Ketoacidosis.
11.4. TREATMENT OF DIABETES

• Excellent diabetes control involves many goals:
o To maintain blood glucose and HbA1c levels as close to normal without
causing hypoglycemia,
o To eliminate polyuria and nocturia,
o To prevent ketoacidosis,
o To permit normal growth and development and
o Avoid development of diabetes related complications—all while
minimizing the impact on lifestyle.
TREATMENT OF DKA
• Treatment of DKA must address both the initiating event in this cascade
(Insulinopenia) and the subsequent physiologic disruptions (i.e., acidosis,
dehydration and electrolyte imbalances).
• Principles of management of DKA: include as follows
1. Fluid Replacement
2. Potassium replacement therapy
3. Insulin therapy
4. Monitoring
5. Treatment of the precipitating factor
6. Prevention and treating of Complication (e.g. Cerebral edema)
1. FLUID REPLACEMENT
• In the first hour an initial intravenous bolus of 10-20 mL/kg of glucose-free
isotonic sodium salt solution such as Ringer lactate or 0.9% sodium chloride is
given over 1 hr. Further fluid boluses should be given only for hemodynamically
unstable patients.
• After the initial fluid resuscitation, the 48-hour fluid is calculated as below

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85𝑚𝑙
(𝑤ℎ𝑖𝑐ℎ 𝑖𝑠 𝑡ℎ𝑒 𝑑𝑒𝑓𝑖𝑐𝑖𝑡) + (𝑀𝑎𝑖𝑛𝑡𝑎𝑖𝑛𝑎𝑛𝑐𝑒 𝑓𝑙𝑢𝑖𝑑) − (𝑏𝑜𝑙𝑢𝑠 𝑔𝑖𝑣𝑒𝑛 𝑖𝑛 𝑡ℎ𝑒 𝑓𝑖𝑟𝑠𝑡 ℎ𝑜𝑢𝑟)
𝑘𝑔
24 − 48 ℎ𝑟
o If the patient presented with Shock, the bolus shouldn’t be subtracted
from deficit fluid.
• Initial fluid is normal saline and we change fluid to 5% DW NS if blood glucose
drops below 250mg/dl.
2. POTASSIUM (K+) REPLACEMENT THERAPY
• If the patient is Hypokalemic, start potassium replacement with initial volume
expansion and before starting insulin therapy.
• Give after the child received the first bolus and after adequate urine output.
o Give 40meq/L potassium if serum K+ is between 3-4.
o If serum K+ is > 5 Withhold potassium in the fluid.
3. INSULIN THERAPY
• Insulin should be given after 1-2 hrs of fluid resuscitation.
• Insulin rates of 0.05 U/kg/hr to 0.1 U/kg/hr are typically suggested
• In circumstances where continuous IV administration is not possible,
o Insulin 0.5 IU/kg,
▪ Half IV and half IM (for the 1st dose), then
▪ subcutaneously Q6hr.
• If the random blood glucose drops, adjust the decline by changing the fluid
from Normal saline (NS) to 5% dextrose (D5W) or 10% dextrose rather than
decreasing the dose of insulin.
o However, if there is a rapid decline in glucose Resolution of Acidosis
levels (>100 mg/hr), you can reduce SC insulin by Acidosis is said to be resolved
50% every 6 hours to keep blood glucose about (200 using the biochemical markers
mg/dl) until resolution of DKA. - HCO3 (total Co2) > 15meq/l,
- PH > 7.30,
4. MONITORING - Serum Sodium between 135–
145meq/l,
• During the treatment of DKA, we need to follow In the absence of this markers
i. The Vital Signs – (BP, PR, RR and Respiratory Negative Urine Ketone can be
pattern, and Temperature), used.
ii. Fluid input and output - (IV fluid, Urine, Emesis),

iii. Neurologic status - (GCS, Mental Status, Orientation),
iv. PH and Bicarbonate level,
v. Serum electrolytes Q6hr if possible,
vi. Urine ketone Q2hr,
vii. RBS Q1hr.
5. TREATMENT OF PRECIPITATING FACTORS
• Infections (Most common) The most common infections being
o Pneumonia (History of Caught, Fever and Fast breathing) and
o Urinary tract infections (History of fever, Urgency, Frequency, Burning
sensation during urination)
• Stress

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•Trauma
•Drug Discontinuation or Inadequate therapy (common in adolescent age due
to physiologic changes)
• Myocardial Infarction (Rare in pediatrics age group) and
• Cerebrovascular accident (also Rare in pediatrics age group)
6. PREVENTION AND TREATING OF COMPLICATION
Complication of treatment of DKA include
• Hypoglycemia
o Prevented by administering D5W (5% glucose when blood glucose level
drops below 250mg/dl).
• Hypokalemia
o Prevent by supplementing potassium during the fluid therapy (see
above).
• Cerebral Edema
o Usually develops several hours after the institution of fluid therapy
o Manifestations include headache, alteration in level of consciousness,
bradycardia, emesis, and unequal or fixed, dilated pupils
o Treatment:
▪ Restriction to ½ Maintenance fluid
▪ Elevate the head 300
▪ Administer Mannitol 1g/kg IV
▪ Administer Hypertonic saline
INSULIN THERAPY IN TYPE 1 DIABETES
• Insulin therapy is initiated at the time of diagnosis for all patients with T1DM.
• The starting dose may range from 0.4 to 1.2 units/kg/day and is calculated
based on a number of factors including age, pubertal stage, and presence or
absence of DKA.
o Prepubertal children presenting without DKA can be started on a dose of
0.4-0.5 units/kg/day.
o Overweight pubertal adolescents presenting with DKA may need up to 1-
1.2 units/kg/day.
• The precise optimal insulin dose can only be determined empirically, after
beginning with the above-mentioned starting doses, with frequent self-
monitored blood glucose levels and insulin adjustment.
DIABETES EDUCATION (IMPORTANT)
• One part of treatment is providing education to the patient and the patient’s
family
• In the acute phase, the parents need to be educated about
o Regular self-monitoring of Blood glucose and urine ketone if possible.

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o Preparing and injecting the correct insulin dose
subcutaneously on proper time and location (See figure
97).
o Early identification of Symptoms of hypoglycemia and
to have a simple sugar nearby in case he/she
experienced these symptoms.
o Having a basic meal plan
▪ The caloric mixture should comprise
approximately 55% carbohydrate, 30% fat, and Figure 97 Injection sites for insulin
15% protein, but must be individualized to meet
specific patient needs.
▪ Patients are advised to avoid simple sugars. Instead to use
complex carbohydrates which should encompasses 70% of their
total carbohydrate intake.
MONITORING
• Blood glucose should be monitored at home both before and after meal
o Current recommended blood glucose targets are 90-130 mg/dL before
meals and 90-150 mg/dL before bedtime; however glycemic goals must
be individualized to the patient based on age, hypoglycemia risk, and
other factors
• Glycosylated Hemoglobin (HbA1c) - evaluates the average amount of glucose
in the blood over the last 2 to 3 months
o It is currently recommended that HbA1c measurements be obtained 3-4
times/yr to obtain a profile of long-term glycemic control. The lower the
HbA1c level, the more likely it is that microvascular complications such
as retinopathy and nephropathy will be less severe, delayed in
appearance, or even avoided altogether.
o The HbA1c target for all children with diabetes is <7.5%; for those over
18 yr it is ≤7.0%.
Table 111 Screening for complication in T1DM
WHEN TO FREQUENCY PREFERRED POTENTIAL
COMMENCE METHOD INTERVENTION
SCREENING OF SCREENING
Retinopathy After 5 yr duration in 1-2 yearly Fundal photography Improved
prepubertal children, glycemic
after 2 yr in pubertal control, laser
children therapy
Nephropathy After 5 yr duration in Annually Spot urine sample Improved

prepubertal children, for albumin: glycemic
after 2 yr in pubertal creatinine control, blood
children ratio pressure
control,
ACE inhibitors
Neuropathy Unclear in children; Unclear Physical Improved
adults at diagnosis in examination glycemic
control

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T2DM and 5 yr after
diagnosis in T1DM
Macrovascular After age 2 yr Unclear Lipids Statins for
Disease hyperlipidemia
Blood pressure
control
Thyroid At diagnosis Every 2-3 yr or Lipids Thyroxine
Disease more
frequently based
on symptoms or
the presence of
antithyroid
antibodies
Celiac Dieses At diagnosis Every 2-3 yr Tissue Gluten-free diet
transglutaminase,
endomysial antibody
11.5. TYPE 2 DIABETES MELITUS

(See Medstar Internal Medicine 2nd edition for more details)
• Type 2 diabetes mellitus is a metabolic disorder Table 112 Differentiating type 1 and type 2
diabetes.
characterized by peripheral insulin resistance and a T1DM T2DM
failure of beta cells to compensate, leading to Age Usually in Age >30
hyperglycemia. <30
Onset of Sudden Gradual
EPIDEMIOLOGY symptoms
Body Habitus Thin or Often
• More common in adult age group, but Its prevalence is Normal obese
Endogenous Low or May be
increasing in pediatrics age group Most being diagnosed insulin absent elevated
in adolescence and incidence increases with increasing Ketoacidosis Common Rare
age. Concordance 50% 90%
in Identical
RISK FACTORS twins
Family 5 to 10% 75 to 90%
• Family history of diabetes (i.e., parent or sibling with History
Treatment
Requires Don’t
type 2 diabetes) insulin need
• Overweight or obese (BMI ≥25 kg/m2) from the insulin
• Physical inactivity outset initially
• Race/ethnicity (e.g., African American, Latino, Native

American, Asian American, Pacific Islander)
• Previously identified with impaired fasting glucose (IFG), IGT, or HA1c of 5.7-
6.4%

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• History of Gestational DM
If the diagnosis between type 1
• Hypertension (blood pressure ≥140/90 mmHg)
and type 2 diabetes mellitus is
• HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a
not clear, helpful labs include:
triglyceride level >250 mg/dL (2.82 mmol/L)
• Fasting Insulin or
• Polycystic ovary syndrome or acanthosis nigricans • C Peptide
• History of cardiovascular disease Both usually high or normal in
type 2 diabetes mellitus, low
PRESENTATION in type 1 diabetes mellitus.
• Childhood type 2 DM can present in the following ways: • Also, autoantibodies for
type 1 diabetes mellitus
ASYMPTOMATIC may help to distinguish
• Identified based on screening (for type 2 DM or urinalysis between type 1 and type 2
as part of a regular physical exam) DM.
SYMPTOMATIC
• Due to hyperglycemia symptoms (Polyuria, Polydipsia, and Nocturia) or
• After the occurrence of complications
• Patients may have peripheral signs of insulin resistance like Acanthosis
nigricans (See figure 98).
DIABETIC KETOACIDOSIS (SEE ABOVE)

• 10% of T2DM present with DKA
HYPEROSMOLAR HYPERGLYCEMIC STATE

• characterized by hypertonicity, extreme hyperglycemia (>
600 mg/dl), and severe dehydration. The profound
hyperglycemia results in continued osmotic diuresis and
intravascular depletion. Figure 98 Acanthosis nigricans in Type 2
• Less common than DKA in pediatrics age group DM
CRITERIA TESTING FOR TYPE 2 DIABETES IN CHILDREN

• Overweight (body mass index >85th percentile for age and sex, weight for
height >85th percentile, or weight >120% of ideal for height)
Plus Any 2 of the following risk factors:
▪ Family history of type 2 diabetes in 1st- or 2nd-degree relative
▪ Race/ethnicity (Native American, African-American, Hispanic,
Asian/Pacific Islander)
▪ Signs of insulin resistance or conditions associated with insulin resistance
(acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary
syndrome)
• Age of initiation: age 10 yr or at onset of puberty if puberty occurs at a
younger age
• Frequency: every 2 yr
• Test: fasting plasma glucose is preferred.

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11.6. OTHER CAUSES OF POLY SYMPTOMS
1. CENTRAL DIABETES INSIPIDUS (NEUROGENIC)

• Polyuria and polydipsia and resulting from vasopressin (ADH) deficiency
• Causes can be from
o Idiopathic (appr 10%)
o genetic mutations in the vasopressin gene
o brain tumors,
o head injury/trauma,
o congenital malformations of the hypothalamus or pituitary
o infectious diseases affecting vasopressin neurons or fiber tracts
o granulomatous diseases and
o autoimmunity.
• It may also be inherited as Autosomal Dominant. (usually present in the first
• Drugs like ethanol, phenytoin, opiate antagonists, halothane, and α-adrenergic
agents can inhibit the rerelease of ADH temporarly.
• Usually, the urine volume is very high (> 8–10 L/day).
• Polydipsia is usually a feature and is very troublesome
2. NEPHROGENIC DIABETES INSIPIDUS
• Nephrogenic diabetes insipidus occurs due to nonresponse of kidneys to ADH
which may be Congenital or Acquired
PRESENTATION
CONGENITAL (GENETIC)
• Usually affects males (X – Linked), though women can transfer the gene to their
child.
• The polyuria and polydipsia associated with genetic NDI usually occur within
the 1st several weeks of life, but may only become apparent after weaning or
with longer periods of night-time sleep.
• Many infants initially present with fever, vomiting, and dehydration.
• Failure to thrive may be secondary to the ingestion of large amounts of water,
resulting in caloric malnutrition.
• Longstanding ingestion and excretion of large volumes of water can lead to
nonobstructive hydronephrosis, hydroureter, and megabladder.
ACQUIRED
• Acquired NDI can result from hypercalcemia or hypokalemia and is associated
with lithium, demeclocycline, foscarnet, clozapine, amphotericin, methicillin,
and rifampin.
• Impaired renal concentrating ability can also be seen with ureteral obstruction,
chronic renal failure, polycystic kidney disease, medullary cystic disease,
Sjögren syndrome, and sickle cell disease.

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• Decreased protein or sodium intake or excessive water intake, as in primary
polydipsia, can lead to diminished tonicity of the renal medullary interstitium
and NDI.
• They will usually complain of extreme thirst, Frequent need to get up to
urinate during the night and preference to cold water.
COMPLICATIONS
• Dehydration which manifests as
o Dry mouth
o Sunken Eyeball
o Changes in skin elasticity
o Thirst
o Fatigue
• Electrolyte Imbalance which can manifest as
o Weakness
o Nausea
o Vomiting
o Loss of appetite
o Muscle cramps
o Confusion
OTHER TYPES OF DIABETES INSIPIDUS
Gestational diabetes insipidus.
• Gestational diabetes insipidus is rare. It occurs only during pregnancy when an
enzyme made by the placenta destroys ADH in the mother.
Primary Polydipsia (A.K.A Dipsogenic Diabetes Insipidus)
• this condition can cause production of large amounts of diluted urine. The
underlying cause is drinking an excessive amount of fluids. Primary polydipsia
can be caused by damage to the thirst-regulating mechanism in the
hypothalamus.
• The condition has also been linked to mental illness, such as schizophrenia.
INVESTIGATIONS
1. OSMOLALITY
• The diagnosis of DI is established if the serum osmolality is >300 mOsm/kg, and
the urine osmolality is <300 mOsm/kg.
• DI is unlikely if the serum osmolality is <270 mOsm/ kg or the urine osmolality
is >600 mOsm/kg.
2. WATER DEPRIVATION TEST
• This test measures changes in body weight, urine output, and urine
composition when fluids are withheld. Also measuring blood levels of ADH
during this test is necessary.
• Decreased ADH to serum osmolality ratio indicates CDI and increased ratio
means it is NDI.

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3. MAGNETIC RESONANCE IMAGING (MRI).
• An MRI can look for abnormalities in or near the pituitary gland. This test is
non-invasive. It uses a powerful magnetic field and radio waves to construct
detailed pictures of brain tissues.
4. GENETIC SCREENING.
• If others in your family have had problems with excess urination, your doctor
may suggest genetic screening.
TREATMENT
FLUID THERAPY
• Fluid replacement orally
• Neonates and young infants require large amount of fluid (~3 L/m2/24 hr)
INITIAL THERAPY
• Low sodium and low protein diet to reduce the amount of solute
• Thiazide Diuretics if not responding to diet modification
• Use Amiloride to for Lithium induced diabetic insipidus.
o If patient is taking Lithium for other condition (i.e. Bipolar disorder),
monitor serum Lithium level.
• If still symptomatic, add NSAID (ex. Indomethacin)
CENTRAL DIABETES INCIPIDUS
There are three main options for the treatment of polyuria in patients with central DI:
• Desmopressin, which is an ADH analogue and is the preferred drug in almost all
patients.
• Other drugs, such as chlorpropamide, carbamazepine, thiazide diuretics, and
nonsteroidal anti-inflammatory drugs.
• A low-solute (mostly low-sodium, low-protein) diet to lower amount of solute.
NEPHROGENIC DIABETES INSIPIDUS
• Urine Output can be lowered with Salt Restriction and Low-protein diet.
o Diuretics, (esp, Thiazide diuretics) and
o Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).
• In infants, early recognition is of immediate clinical significance because
treatment can avert the physical and mental retardation that results from
repeated episodes of dehydration and hypernatremia.
• In Hereditary nephrogenic DI (esp in infants and young children)
o Offer water every two hours, to avoiding severe dehydration and
hypernatremia.

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CHAPTER 12 - NEUROLOGY
1. Common neurologic complaints
a. Approach to Body Weakness
b. Approach to abnormal body movement
c. Altered mental status
2. Physical examination of neurologic patient
3. Discussion of selected cases
a. Acute Bacterial Meningitis Beyond the Neonatal Period
b. Brain Abscess
c. Poliomyelitis
d. Guillain-Barre syndrome (GBS)
e. Transverse myelitis
f. Myasthenia Gravis
g. Cerebral palsy
h. Rabies
i. Infants Botulism
j. Foodborne botulism
k. Infant botulism

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12.1. APPROACH TO BODY WEAKNESS

• Weakness is a reduction in the power that can be exerted by one or more
muscles.
• It is due to disorders of UMNs or LMNs
• UMNs originate in the cerebral motor cortex
• LMNs and muscle units includes anterior horn cells, their motor roots,
peripheral motor nerves, neuromuscular junctions, and muscles
• Maintenance of normal strength, tone, and coordination requires integrated
communication of cerebral cortex, basal ganglia, cerebellum, spinal cord,
brainstem, thalamus
• These motor system dysfunction leads to weakness, paralysis ataxia, abnormal
movements, and loss of full control of bodily movements
• The mode of onset, distribution, and accompaniments of weakness help suggest
its cause Table 113 Clinical Distinction Between Upper
• The distribution of weakness depends Motor Neuron and Lower Motor Neuron
on the location of the lesion e.g. A Sign UMNL LMNL
tumor in the left parietal region may Tone Increased (spastic) Decreased
produce a right hemiparesis Reflexes Increased Decreased
• UMNs Weakness occurs in extensors Babinski
Present Absent
and abductors of the upper limb, sign
Atrophy None Severe
flexors of the lower limb
Fasciculation None Common
• Dysfunction of UMNs causes loss of
voluntary control, but not total loss of movement because motor nuclei of the
basal ganglia, thalamus, and brainstem have tracts that produce simple or
complex stereotyped patterns of movement
• UMNL is presented with hypertonia, decreased deep tendon reflexes,
spasticity, hyperreflexia and abnormal involuntary postures
• LMNs Weakness does not have any selectivity and depends on level involvement
at anterior horn cells, nerve root, limb plexus, and peripheral nerve
• Destruction of LMNs, the final common pathway, result in hypotonia and total
absence of movement
• Myopathic Weakness is most marked in proximal muscles.

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DIFFERENTIAL DIAGNOSIS BODY WEAKNESS

Table 114 Differential Diagnosis Body Weakness
ANATOMICAL REGIONS CORRESPONDING DISORDERS
CNS – Brain Brain tumor
Trauma (accidental, non-accidental)
Infections:
• Meningitis
• Encephalitis
• Abscess
• TORCH*
Ischemia (arterial or venous)
Hemorrhage
Demyelinating disease
Metabolic disease
CNS – Spinal Cord Transverse myelitis

Tumor
Abscess
Trauma
Infarction
Anterior Horn cells Poliomyelitis
Peripheral Nerve Guillain-Barre syndrome

Tick paralysis
Bell palsy
Neuromuscular Junction Myasthenia gravis

Botulism
Muscle Muscular dystrophy

Dermatomyositis
Polymyositis
*TORCH: [Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella,

Cytomegalovirus, and Herpes)
DDX OF UPPER MOTOR NEURON WEAKNESS IN CHILDREN

• Tumors: Neuroblastoma, lymphoma, sarcoma
• Traumatic brain injury
• Infections: Meningitis
• Stroke

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• Spinal cord trauma or mass
• Metabolic diseases
• Demyelinating syndromes
• Neurodegenerative diseases
DDX OF UPPER MOTOR NEURON WEAKNESS IN NEONATES

• TORCH infections
• Developmental brain anomalies
• Hemorrhage
• Stroke
• Hypoxia
• Genetic syndromes
• Metabolic/electrolyte disturbances
• Toxic exposure
SOME OF SELECTED DDX OF BODY WEAKNESS FOR DISCUSSION (SEE LATER)
1. Poliomyelitis
2. Cerebral palsy
3. Transverse myelitis
4. Myasthenia gravis
5. Infant botulism
6. Rabies
7. Guillan-barren Syndrome

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12.2. APPROACH TO ABNORMAL BODY MOVEMENT
HISTORY
• Characterization of the abnormal body movement
o Duration
o Mode of onset and its progression
o Frequency
o Time of occurrence
o State of consciousness
o Generalized or focal onset
▪ If it is focal from which part, does it start from face or extremity.
o Aura: -sensory experiences reported by the patient not observed
externally.
▪ It could be visual, olfactory, auditory, déjà vu, tingling, chest
tightness, epigastric pain, fear.
o Child behavior before the event like cyanosis, urine on cloth.
o Vocalization
o Posture of the patient
o Automatism: automatic semipurposefull movements.
▪ Example: -chewing, salivation, dilation of pupils, flushing, lip
smacking, picking at clothes.
o Postictal state
▪ Sleep, headache, hemi paresis, aphasia.
• Determinig the type of abnormal body movement
• Identifying the underlying entity
o History of personality change or symptoms of increased intracranial
pressure can suggest an intracranial tumor.
o Similarly, a history of cognitive regression can suggest a degenerative or
metabolic disease.
o Certain medications such as stimulants or antihistamines, can precipitate
seizures.
o Any evidence of active CNS infection.
o Any history of trauma.
• Risk factor for the underlying cause
• Previous similar attack
• Family history
• Immunization history
• Detailed prenatal history (asphyxia, jaundice, meningitis)
• Detailed developmental history

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o developmental delay can suggest etiologic congenital or perinatal brain
dysfunction.
TYPES OF ABNORMAL BODY MOVEMENT (DDX)

• Seizure
• Sydenham chorea
• Spasm
• Tremor
• Paroxysmal vertigo
• Syncope Seizure mimicking events
• Psychogenic seizures
SEIZURE
• is a transient occurrence of signs and/or symptoms resulting from abnormal
excessive or synchronous neuronal activity in the brain.
o Simple seizure: -no alteration in consciousness.
o Complex seizure: -no alteration in consciousness.
EPILEPSY
• is present when two or more unprovoked seizures occur in a time frame of
longer than 24 hours.
EPIDEMIOLOGY
• 4-10% of children experience at least 1 seizure (febrile or afebrile) in the 1st 16
yr of life
• life time incidence of epilepsy is 3%.
• Annual prevalence is 0.5-1.0%.
EPILEPSY SYNDROME
• is a disorder that manifest as one or more of specific seizure type:
• Epileptic Encephalopathy is an epilepsy syndrome in which there is a severe
EEG abnormality which is thought to result in cognitive and other impairments
in the patient.
• Idiopathic epilepsy is epilepsy syndrome that is genetic or presumed genetic;
there is no underlying disorder affecting development or other neurologic
function
o e.g. petit mal epilepsy
• Symptomatic epilepsy refers to an epilepsy syndrome caused by an underlying
brain disorder that may or may not be genetic
o e.g. epilepsy secondary to tuberous sclerosis or to an old stroke.

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• Unknown epilepsy - designating that the underlying cause of the epilepsy is as
yet unknown.
MECHANISM
1. Decreased excitability in inhibitory GABAergic interneurons, leading to
increased excitability and epilepsy.
2. Activation of metabotropic and ionotropic glutamate receptors, as well as the
tropomyosin-related kinase B receptor.
CAUSES OF SEIZURE
1. Idiopathic
2. CNS infections
o Meningitis
o Encephalitis
o Brain abscess
o Syphilis(tertiary)
3. Metabolic
o Electrolyte imbalance (calcium, sodium, magnesium, phosphorus)
o Hypoglycemia
4. Structural
o Head trauma
o Brain tumor
o Stroke
5. Others
o Sepsis
o Drug abuse
o Ingestion of toxins (accidental and non-accidental)
CLASSIFICATIONS OF SEIZURE
• Seizure can be classified as
o Focal: initial activation of a system of nervous limited to one part of
hemisphere.
o Generalized: first clinical and EEG changes indicate synchronous
involvement of all both hemisphere.
TYPES OF FOCAL AND GENERALIZED SEIZURES:

• Tonic: increased tone or rigidity.
• Atonic: flaccidity or lack of movement during convulsion.
• Clonic: rhythmic fast muscle contraction and slightly longer relaxation.
• Myoclonic: shock like contraction of a muscle < 50msec often repetitive.
• Absence seizure: - are generalized seizures consisting of staring,
unresponsiveness, and eye flutter lasting usually for few seconds.

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Febrile seizure
• a seizure that occurs at 38oc or higher, that are not the result of CNS infection or
any metabolic imbalance, and in the absence of prior afebrile seizures. (Occurs
b/n 6-60 months).
o Simple FS: - primary generalized, usually tonic-clonic, lasting for a
maximum of 15 min, and not recurrent with in 24hrs.
o Complex FS: - is focal, more prolonged (>15 min), and/or reoccurs within 24
hr.
o Febrile status epilepticus: - lasting longer than 30 min.
• Risk factor for febrile seizure
o Febrile seizures often occur in otitis media, roseola and human herpesvirus
(HHV) 6 infection, shigella, or similar infections.
o In patients with febrile status, HHV-6B (more frequently) and HHV-7
infections were found to account for one-third of the cases.

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12.3. APPROACH TO PATIENT WITH ALTERED MENTAL STATUS
STATE OF ALTERED CONSCIOUSNESS

QUANTITATIVE DESCRIPTION
COMA
• Is a state of unarousable and unresponsiveness
• Is the most profound degree to which arousability and consciousness are
impaired
o Arousal- determined in the brainstem’s ascending reticular activating
system (ARAS). Depends on intact communication between ARAS and its
targets in the hypothalamus, thalamus and cerebral cortex.
o Awareness- is generated in the cortex
▪ Is an alteration in consciousness in which a person appears to be
asleep, cannot be aroused and shows no awareness of the
environment
▪ Is a transient (patients recover, die or evolve in to a more
permanent state ) and acute life threatening emergency
STUPOR
• Spontaneous unarousability
• Interruptible only by vigorous, direct external stimulation
OBTUNDATION (HYPERSOMNIA, PATHOLOGIC DROWSINESS)

• an increase above the patient’s normal sleep/wake ratio accompanied during
wakefulness by reduced attention and interest in the environment
• Responsive to pain and other stimuli
DELIRIUM
• Clouding of consciousness
• An acute or sub-acute reduction in attention, awareness, orientation and
perception
o Can be
▪ Hyperactive delirium-patients show both hyperactivity and
diminished sleep
▪ Hypoactive delirium-patients have little interaction with their
environment and appear somnolent
o Usually fluctuating and accompanied by abnormal sleep/wake patterns
and psychomotor disturbance
SYNCOPE
• Brief loss of consciousness
• Caused by global decline in cognitive function
DEMENTIA

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• a sustained or permanent multidimensional or global decline in cognitive
function
PERSISTENT VEGETATIVE STATE (PVS)

• Sustained, complete loss of cognition
• Such patients often have reflexive vocalization, facial expressions and
movements that can be misinterpreted by hopeful observers
• Required features of PVS are
o No evidence of awareness
o No evidence of sustained, reproducible, purposeful or voluntary
behavioral response to stimuli
o Sleep/wake cycle manifested by presence of intermittent spontaneous
eye opening
o Sufficiently preserved hypothalamic and brainstem autonomic function
to permit survival with medical and nursing care
o Bowel and bladder incontinence
o Some degree of preserved cranial nerve and spinal reflexes
MINIMALLY CONSCIOUS STATE

• Patients with severe alteration in consciousness with some degree of preserved
awareness. They can occasionally demonstrate purposeful movements like
o Following simple commands,
o Making gestural or verbal response to questions,
o Making intelligible verbalizations,
o Smiling or crying in response to evocative sounds or images
o Reaching accurately toward the location of an object or
o Fixating on and pursuing visual stimuli
LOCKED-IN STATE
• Preservation of intellectual activity accompanied by severe or total incapacity
to express voluntary response
• Due to damage or dysfunction of descending motor pathways in the brain or
peripheral motor nerve
• Most of the patients can use vertical eye movement
BRAIN DEATH
• Criteria include
o Coma,
o Apnea and
o Absent brain stem reflex
• Diagnosis implies no chance of recovery
QUALITATIVE DESCRIPTION
1. PEDIATRIC GLASGOW COMA SCALE
• is an objective measure of the improvement or worsening of the patient’s level
of consciousness over time

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• helps in
o Interventions such as the need for endotracheal intubation
o used as a prognostic indicator in both traumatic and non-traumatic
coma
• Score of 15 indicates full function, whereas a score of 3 indicates no function.
• Disadvantages
o does not assess brainstem function and
o fails to discriminate between low scores and intubated patients
• It has three components
o Eye opening
▪ Evaluate the arousability and alertness of the patient.
▪ Spontaneous eye opening indicates intact arousal mechanisms but
does not imply awareness
o Verbal response
▪ Requires a high degree of integration within the CNS.
▪ Oriented responses indicate awareness of person, place, and
time.
o Motor functioning,
▪ Reflects mentation and integrity of the major CNS pathways
▪ the best motor response from any limb is taken as the score
▪ Spinal cord lesions resulting in paralysis or significant orthopedic
injuries to the extremities prevent evaluation of the motor
portion of the GCS
Table 115 Pediatric Glasgow coma scale
Activity Best response Score
Eye opening Spontaneous 4
To speech 3
To pain 2
None 1
Verbal response Oriented 5
Words 4
Vocal sounds 3
Cries 2
None 1
Motor Obeys command 5
Localizes pain 4
Flexion to pain 3
Extension to pain 2
None 1
Normal total score based on age
Birth-6mo 9

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7mo-12mo 11
1-2yr 12
2-5yr 13
>5yr 14
2. THE FULL OUTLINE OF UNRESPONSIVENESS (FOUR)

• Evaluates eye response, motor response, brain stem reflexes (focuses on
pupillary and corneal reflex) and respiratory assessment (include the
intubated patient along with the respiratory effort) on a 4 point scale.
• Have a similar predictive value with GCS.
Table 116 FOUR

Activity Best response Score
Eye response Eyelid open and comply with verbal response 4
Eyelid open but not tracking 3
Eyelid closed but open to loud noise 2
Eyelid closed but open to noxious stimuli 1
Eyelid remain closed 0
Motor response Thumbs up, fist or peace sign 4
Localize to pain 3
Flexion to pain 2
Extension to pain 1
No response 0
Brainstem reflex Pupillary and corneal reflex present 4
One pupil wide and fixed 3
Pupil or corneal reflex absent 2
Pupil and corneal reflex absent 1
Absent pupil, corneal and cough reflex 0
Respirations Normal breathing pattern 4
Cheyne-stoke respiration 3
Irregular breathing 2
Intubated but breathing above the vent 1
Breathing at a vent rate or apnea 0
3. REED CLASSIFICATION
• Used to measure the level of consciousness in specific disease states such as-
o Poisoning or intoxication
o Hepatic failure
• Cardiovascular system is included because toxic ingestion may depress
myocardial activity and cause vasodilation
• Grade 0,1 and 2 have good prognosis.
Table 117 REED classification
REED classification
Grade 0 Asleep

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Can be aroused
Will answer questions
Grade 1 Comatose
Withdraw from painful stimuli
Intact reflex
Grade 2 Comatose
Does not withdraw from painful stimuli
No respiratory, circulatory depression
Intact reflex
Grade 3 Comatose
Reflex absent
No respiratory, circulatory depression
Grade 4 Comatose
Reflex absent
Respiratory or circulatory problem
4. AVPU (ALERT, VOICE, PAIN, UNRESPONSIVENESS)

• Is a system used by first responders and emergency medical professionals
• Advantage – unlike GCS , it is not developmentally dependent ( a child does not
have to understand spoken language or follow commands)
o ALERT= can answer questions
o VOICE= respond to verbal commands
o PAIN= responds to pain
o UNRESPONSIVENESS
CAUSES OF COMA
• coma is caused by one of these three etiologies
1. structural brain disease
2. diffuse brain injury
3. psychogenic cause
• Traumatic and non-traumatic causes of coma have roughly equal annual
incidence of approximately 30 per 100,000 children each.
• etiologic classification of altered mental status
1. infectious
▪ viral- aseptic meningitis
▪ Bacterial- meningitis, brain abscess, empyema…
▪ Fungal
▪ Protozoal
2. metabolic or systemic
▪ hypoglycemia
▪ DKA
▪ Inborn error of metabolism
▪ Encephalopathy
3. toxic
4. traumatic

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5. anatomic
▪ tumor
▪ hydrocephalous
▪ hematoma
6. hypoxic ischemic
▪ neonatal hypoxia
▪ near drowning
▪ CO poisoning
7. epileptic
8. vascular
9. psychologic
COMMON CAUSES OF ALTERED MENTAL STATUS BY AGE

1. Neonate
▪ hypoglycemia, birth asphyxia, congenital anomalies of CNS infection with
shock, cardiogenic shock, congenital infection, bacterial meningitis
2. Infants
▪ Meningitis, trauma, systemic infection with shock, ingestion, inborn error
of metabolism, hypoglycemia, hyponatremia
3. Child
▪ Meningitis, trauma, ingestion, reye syndrome, systemic infection with
shock
4. Adolescent
▪ Meningitis, intentional ingestion, trauma, seizure, DKA,
MANAGEMENT APPROACH
• Coma is an acute life-threatening emergency, requiring prompt intervention
for preservation of life. The assessment and management of coma are
performed jointly.
• Approach can be divided into 4 parts
1. Stabilization
2. Rapid clinical assessment
3. Reversal of immediately treatable toxic or metabolic cause
4. Determination of level of CNS function and cause of the coma
1. STABILIZATION
▪ Initial stabilization includes assessment of patients ABC-
o Airway patency
▪ may involve positioning, suctioning or intubating
o Breathing
▪ Oxygen support if indicated
▪ Respiratory pattern,
o Circulation- includes evaluation of
▪ Vital sign
▪ Presence and volume of peripheral pulses and
▪ Adequacy of end organ perfusion(best evaluated in the skin,
kidney and brain)

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▪ Obtunded, stupors and comatose patients usually requires intubation (unless
mental status is improving or can be readily reversed) to-
o Secure airway
o Treat hypoventilation
o Protect the airway if gag reflex is not present
o To facilitate hyperventilation in a child with suspected intracranial
pressure.
2. RAPID CLINICAL ASSESSMENT
▪ Focused history and physical examination with targeted neurologic evaluation
▪ Focused history includes
o recent history preceding the altered mental status
o medical history and family history such as seizure, DM
o trauma history
o recent fever or signs of systemic infection
o dietary history in infants
▪ hypoglycemia (fasting or emesis)
▪ hyponatremia (ingestion of free water)
▪ exposure to toxins or drugs especially when there is unexplained
symptoms
▪ vaccination history
▪ endemic malaria
PHYSICAL EXAMINATION (SEE THE NEXT SECTION FOR FURTHER DETAILS)

• General physical examination- should focus on
• General appearance
− qualitative description of state of consciousness
− posturing
• Vital signs-
o Hyperthermia- suggests infection, inflammatory disorders,
environmental or exertional heat stroke, status epilepticus,
anticholinergic poisoning ……
o Hypothermia –can occurwith drug intoxication, environmental exposure
or hypothyroidism
o Tachycardia – fever, pain, hypovolemia, status epilepticus…
o bradycardia- hypoxemia, hypothermia, increased ICP, aspart of cushing
triad
o hypotension- hypovolemic,septic or cardiogenic shock, intoxication or
adrenal insufficiency
o hypertension –increased ICP,
• HEENT
o Signs of head trauma
o Bulging fontanel – sign of increased ICP
▪ In the absence of febrile illness trauma should be suspected in
infant with bulging fontanel
▪ Fundoscopic examination

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− Retinal hemorrhage can be seen in children with abusive head
trauma, associated with shaken baby syndrome
− Papilledema – suggests increased ICP of several hours
duration.
• Respiratory examination
• Cardiovascular examination
• Integumentary system
o Bruising –suggests traumatic injury
o Petechial and purpuric rashes- may suggest meningococcal infection
o Jaundice- may suggest hepatic encephalopathy
o Special attention should be given to identify any physical exam that may
suggest a specific toxidrome
• Neurologic assessment – should focus on
o Identifying lateralizing or focal finding
o Recognizing brainstem dysfunction
o Defining severity of illness
• lateralizing or focal finding- can be determined
o By examining the pupil for asymmetry in size or reactivity
o By examining the motor system( the face or extremities) for asymmetry
• Brainstem dysfunction- is evaluated
o By observing the respiratory pattern
o Assessing corneal reflexes
o Testing oculocephalic (doll’s eye) or oculovestibular (cold caloric )
reflex
• Respiratory pattern - Significant brainstem dysfunction is rarely associated
with a normal breathing pattern
o Cheyne-stoke respiration
o Periods of hyperpnoea alternate with short apneic phases
o Observed in the presence of
▪ Bilateral hemispheric dysfunction
▪ Diencephalic dysfunction
▪ May also preced transtentorial herniation
o Central neurogenic hyperventilation
▪ Tachypnea and hyperpnoea
▪ Occur when there is midbrain dysfunction, toxic metabolic
encephalopathy
o Apneustic breathing
▪ Prolonged pause at the end of full inspiration
▪ Damage to middle to lower pontine region
o Ataxic or irregular breathing
▪ Medullary lesion
o Agonal respiration
▪ Slow regular breathing
▪ Medullary lesion
o Kussmaul breathing

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▪ Rapid and deep breathing
▪ DKA patients
3. REVERSAL OF IMMEDIATELY TREATABLE TOXIC OR METABOLIC CAUSES

• If the etiology of altered consciousness is not known yet, emphasis should shift
a systemic review of reversible cause
1. Hypoglycemia
2. Narcotic intoxication
3. Benzodiazepine ingestion
1. Hypoglycemia
• is a medical emergency
• A blood glucose level should be obtained as soon as possible in an
altered child
• All unresponsive children should receive dextrose unless a diagnosis
other than hypoglycemia is apparent.
• The dextrose bolus should be followed by a continuous infusion of
glucose and electrolytes to prevent rebound hypoglycemia. If
• The child’s mental status improves
• There is laboratory confirmation of hypoglycemia
2. Narcotic intoxication
• Naloxone is administered to children who have marked depression of
consciousness without an obvious cause, particularly if
A. hypoventilation is observed and
B. opioid ingestion is suspected
3. Benzodiazepine ingestion
• Flumazenil, a specific competitive antagonist of benzodiazepines,
should only be given if benzodiazepine ingestion is suspected as
administration of flumazenil to a patient who has ingested multiple
agents may precipitate seizures.
4. LEVEL OF CNS INFECTION AND CAUSES OF COMA
• The coma can be initially considered stable if
a) Focal neurologic findings are not present,
b) There is no evidence of significant brainstem dysfunction,
c) Intracranial pressure is not raised,
d) There is no evidence of head trauma or CNS infection, and
e) The child does not have a rapidly reversible toxic or metabolic cause
• If coma is stable detailed physical examination and expanded laboratory
evaluation can be undertaken to determine the level of CNS function and the
cause of the coma.
• The origin of coma (hemispheric vs brainstem) and its cause (metabolic vs
structural) can be elucidated by evaluation of
a) Pupillary size and reactivity,
b) Eye movements,
c) Motor responses, and

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d) Respiratory pattern.
A. PUPILLARY SIZE AND REACTIVITY

• Is determined by the balance between sympathetic and parasympathetic
stimulation, which result in pupillary dilation and constriction.
o Normal finding
▪ Pupillary light reflex involves adjustment in pupil size with
changes in light levels
▪ Direct response- constriction of the pupil in the eye to which the
light is directed
▪ Consensual response- constriction of the pupil in the eye
opposite to the eye which the light is directed
o Abnormal findings
▪ Generally preserved in metabolic encephalopathy (the only
exception is drug effect), whereas their absence strongly suggests
a structural lesion.
▪ Unilaterally dilated and fixed pupil
• Is a sign of uncal herniation with entrapment of the
oculomotor nerve (cranial nerve)
▪ Small, reactive pupils.
• diencephalic dysfunction
• metabolic cause
▪ Ipsilateral miosis associated with Horner syndrome (miosis,
ptosis, and anhidrosis).
• Hypothalamic damage
▪ Midsized, fixed pupils
• Injury to nuclei located in the midbrain disrupts both
sympathetic and
parasympathetic
pathways
• Damage to the midbrain
tectal regions
(accommodation may be
intact, so that pupillary
size fluctuates
spontaneously)
▪ Symmetrically small pupils
(pin point pupil)
• Pontine lesions
principally hemorrhage
▪ Fixed, dilated pupils
• Central herniation
EYE MOVEMENT
• Helpful in differentiating hemispheric from brainstem causes of coma.

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• Frontal regions of the cerebral hemispheres are responsible for

• voluntary eye movements
• The quick phase of nystagmus, and
• Control over brainstem reflexes that determine eye movements.
• Eye movement
• Roving eye movement
o Bilateral hemispheric depression if brainstem function is
intact
• Tonic lateral deviation of the eyes
o Seizure emanating from the contralateral hemisphere
o Ipsilateral hemispheric injury with unopposed stimulation
from the undamaged hemisphere
o contralateral pontine lesion
• Degree of eye deviation is usually more dramatic with hemispheric damage
than with brainstem damage
B. REFLEX EYE MOVEMENTS

• If the patient’s eyes are not moving, then reflex eye movements are tested
by the oculocephalic and oculovestibular responses
• Positive reflexes indicate the absence of cortical input on an intact
brainstem
• The oculocephalic (doll’s eye) reflex-
• Is tested in both horizontal and vertical plane.
• Is elicited
o By rotating the child’s head from side to side and observing the
eye movements. If brainstem function is intact, the eyes do not
turn with the head but moves in the opposite direction, thus
appearing to maintain visual fixation.
o By rapidly flexing and extending the neck. A positive response
is upward gaze when the neck is flexed and downward
deviation when the head is extended
• Contraindicated if cervical spine injury is suspected.
• The oculovestibular (caloric) reflex is tested
• Otoscopy should first confirm that the external ear canals are
patent and the tympanic membranes are intact.
• With the head at 30 degrees elevations from horizontal, irrigation
of the external ear canal with ice-cold water (10 to 30 ml) induces
slow deviation of the eyes toward the irrigated side. Five minutes
should intervene before the other side is tested.
• Failure of the eyes to move conjugately as expected suggests a
lesion of one or more cranial nerves or their nuclei within the
brainstem.
• Low brainstem lesions
• oculocephalic and oculovestibular reflexes are absent

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• Damage to the medial longitudinal fasciculus
• Ipsilateral eye fails to adduct on irrigation of the contralateral ear
canal
• Corneal reflex
• The normal effector response involves both upward deviation of the eye
(oculomotor nerve) and closure of the eyelid (facial nerve)
• Tests the sensory function of trigerminal nerve and the motor function of
the facial nerve.
• The patient’s cornea is lightly touched with a fine wisp of cotton or a drop
of sterile water. An intact reflex produces a bilateral (direct and
consensual) eye blink
• Absence of a blink in response to a loud noise or bright light implies
o Dysfunction of the pontine reticular formation secondary to
either metabolic or structural causes.
• Unilateral absence of a blink
o Implies a facial nerve lesion.
C. MOTOR RESPONSES
• includes observation of
o Body position,
o Spontaneous movements, and
o Response to noxious stimuli
• Intact brain stem function
o Normal body position
o Spontaneous non posturing movements
• Hemiparesis or hemiplegia implies
o structural lesion in the
▪ contralateral hemisphere
▪ Subcortical region or
▪ Ipsilateral spinal cord injury.
• hypertonia or hyperreflexia suggests
o Previous corticospinal tract disease or Figure 99 Decorticate
Posturing
o An acute brainstem injury at the midbrain-pontine level.
o Severe metabolic derangements, such as hepatic coma,
hypoglycemia, anoxia, and uremia.
• Hypotonia implies
o bilateral hemispheric dysfunction or
o a medullary or spinal cord lesion
• flaccid response to noxious stimulation
o is associated with Pontomedullary or spinal cord damage

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• In patients with severe depression of brain function, motor function can be
assessed only after the application of a noxious stimulus, such as
a sternal rub or increasing subungual pressure to the fingernails
or toenails.
• Decorticate posturing
o Produces adduction and flexion at the elbow s, wrists and
fingers with leg extension and rotation.
o Implies hemispheric dysfunction with an intact brainstem
• Decerebrate posturing
o Extension and internal rotation of the arms and legs.
o Implies brain stem involvement from a compressive or
destructive process.
• Opisthotonos with clenched teeth
o is a severe form of decerebration
o usually suggests brainstem compression or
o Severe structural injury to the midbrain-pontine region. Figure 100 Decerebrate position
o It can also occur in association with severe metabolic
diseases, such as hepatic coma, anoxia,

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12.4. PHYSICAL EXAMINATION OF NEUROLOGIC PATIENT

• Major components of neurologic examination are
1. Mental State
2. HEENT
3. Cranial nerve assessment
4. Motor examination
5. Sensory examination
6. Reflexes
7. Coordination
8. Station and gait
1. MENTAL STATUS
• Can be assessed in terms of both
o The level of arousal and
o The interaction with the environment
• The level of alertness of a neonate depends on many factors, including
o The time of the last feeding,
o Room temperature, and
o Gestational age,
• An older child’s mental state can be assessed by
o Watching the child play.
o Having the child tell a story,
o Draw a picture, or
o Complete a puzzle
2. HEENT
• Includes-
1) Correct measurement of the Head Circumference (HC).
▪ Should be performed at every visit for patients younger than 3 yr
▪ The HC of an average term infant measures 34-35 cm at birth, 44
cm at 6 mo, and 47 cm at 1 yr of age. (see Growth and
Development for further details).
▪ Smaller measurement (below 5th percentile) is called
microcepahly which can be due to
• Intrauterine infection or
• Drug exposure or
• Perinatal or postnatal injury
2) Larger head measurement greater than 90th percentile is macrocephaly
which can be due to
▪ Most commonly familial
▪ Neurocutaneous disorder e.g., neurofibromatosis
▪ Chromosomal defect (e.g., Klinefelter syndrome), or
▪ Storage disorder.
▪ Hydrocephalus
▪ Chronic subdural hemorrhages.

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3) Assessment of the head shape
▪ A variety of abnormal head shapes can be seen when cranial
sutures fuse prematurely, as in the various forms of inherited
craniosynostosis
4) Assessment of the fontanels
▪ An infant has two fontanels at birth:
a. A diamond-shaped anterior fontanel at the junction of the
frontal and parietal bones that is open at birth, it varies
greatly in size, but it usually measures approximately 2 × 2
cm. The average time of closure is 18 mo, but the fontanel
can close normally as early as 9 mo. A very small or absent
anterior fontanel at birth might indicate craniosynostosis or
microcephaly,
b. A triangular posterior fontanel at the junction of the
parietal and occipital bones. If it is open at birth, it should
close over the ensuing 6-8 wk; its persistence suggests
underlying hydrocephalus or congenital hypothyroidism.
5) Observation of any marked venous distension that could be due to
increased ICP and thrombosis of the superior sagittal sinus.
6) Presence of Dysmorphic facial features
7) Presence cutaneous abnormalities, such as cutis aplasia or abnormal
hair whorls, can suggest an underlying brain malformation or genetic
disorder.
8) Presence of Cranial bruits may be noted over the anterior fontanel,
temporal region, or orbits.
▪ it may be associated with severe anemia, increased ICP, or
arteriovenous malformations of the middle cerebral artery or vein
of Galen
3. CRANIAL NERVE ASSESSMENT

I. Olfactory Nerve (Cranial Nerve I)
✓ Anosmia, or loss of smell, can be due to
▪ Transient abnormality -most common cause
• In association with an upper respiratory tract infection
or allergies.
▪ Permanent causes of anosmia include
• head trauma with damage to the ethmoid bone or
• Shearing of the olfactory nerve fibers as they cross the
cribriform plate,
• Tumors of the frontal lobe,
• Intranasal drug use, and
• Exposure to toxins (acrylates, methacrylates, cadmium).
▪ Rarely, anosmia is Congenital, in which case it can occur as an
isolated deficit or as part of Kallmann syndrome, a familial
disorder characterized by hypogonadotropic hypogonadism and
congenital anosmia.

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• smell can be tested reliably as early as the 32nd wk of gestation by
presenting a stimulus and observing for an alerting response or
withdrawal, or both
II. Optic Nerve (Cranial Nerve II)
• Include Assessment of
▪ The optic disc
▪ Retina and
▪ Vision
PUPILLARY REFLEX
• Is determined by the balance between sympathetic and parasympathetic
stimulation, which result in pupillary dilation and constriction respectively
• The neural pathway has one afferent limb and two efferent limbs
o The afferent limb (sympathetic fibers) has nerve fibers running with the
optic nerve (CNII)
o Each efferent limb (parasympathetic fibers) has nerve fibers running
along the oculomotor nerve (CN III).
• Normal finding
o Pupillary light reflex involves adjustment in pupil size with changes in
light levels
o Direct response- constriction of the pupil in the eye to which the light is
directed
o Consensual response- constriction of the pupil in the eye opposite to
the eye which the light is directed
• Abnormal findings
o Generally preserved in metabolic encephalopathy (the only exception is
drug effect), whereas their absence strongly suggests a structural lesion.
o Unilaterally dilated and fixed pupil
▪ Is a sign of uncal herniation with entrapment of the oculomotor
nerve (cranial nerve)
o Small, reactive pupils.
▪ diencephalic dysfunction
▪ metabolic cause e.g. hepatic encephalopathy
o Ipsilateral miosis associated with Horner syndrome (miosis, ptosis, and
anhidrosis).
▪ Hypothalamic damage
o Midsized, fixed pupils
▪ Injury to nuclei located in the midbrain disrupts both sympathetic
and parasympathetic pathways
▪ Damage to the midbrain tectal regions (accommodation may be
intact, so that pupillary size fluctuates spontaneously)
o Symmetrically small pupils (pin point pupil)
▪ Pontine lesions principally hemorrhage, atropine overdose, lead
poisoning
o Fixed, dilated pupils

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▪ Central herniation
III. Oculomotor (Cranial Nerve III), Trochlear (Cranial Nerve IV), and Abducens
(Cranial Nerve VI) Nerves
• The globe is moved by six extraocular muscles, which are innervated
by the oculomotor, trochlear, and abducens nerves
• The oculomotor nerve innervates
▪ The superior recti
▪ Inferior recti
▪ Medial recti,
▪ Inferior oblique and
▪ Levator palpebrae superioris muscles.
• Complete paralysis of the oculomotor nerve causes
▪ Ptosis,
▪ Dilation of the pupil,
▪ Displacement of the eye outward and downward,
▪ Impairment of adduction and elevation.
IV. The trochlear nerve
• Supplies the superior oblique muscle, which depresses and intorts the
globe during activities such as reading and walking downstairs.
• Patients with an isolated paralysis of the trochlear nerve often have a
compensatory head tilt away from the affected side, which helps to
alleviate their diplopia.
V. The abducens nerve
• Innervates the lateral rectus
muscle;
• Paralysis causes medial
deviation of the eye with an
inability to abduct beyond the
midline.
• Patients with increased ICP may
have diplopia (double vision)
and exhibit incomplete
abduction of the eyes on lateral
gaze as a result of partial
palsies of nerve VI. This false-
localizing sign occurs because
CN VI has a long intracranial
course, making it particularly
susceptible to being stretched.
• These muscles and nerves can
be assessed by having the
patient follow an interesting
toy or the examiner’s finger in
the six cardinal directions of
gaze.

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▪ The physician observes
o The range and nature of the eye movements (conjugate vs
deconjugate, smooth vs choppy or saccadic)
o Presence and direction of any abnormal eye movements.
• Premature infants older than 25 wk of gestational age and comatose
patients can be evaluated for CN III, IV and VI using
▪ Reflex eye movement, the oculocephalic
o Positive reflexes indicate the absence of cortical input on
an intact brainstem
• The oculocephalic (doll’s eye) reflex-
▪ Is tested in both horizontal and vertical plane.
▪ Is elicited
o By rotating the child’s head from side to side and
observing the eye movements. If brainstem function is
intact, the eyes do not turn with the head but moves in
the opposite direction, thus appearing to maintain visual
fixation.
o By rapidly flexing and extending the neck. A positive
response is upward gaze when the neck is flexed and
downward deviation when the head is extended
▪ Contraindicated if cervical spine injury is suspected.
▪ Low brainstem lesions
o oculocephalic and oculovestibular reflexes are absent
▪ Damage to the medial longitudinal fasciculus
o Ipsilateral eye fails to adduct on irrigation of the
contralateral ear canal.
VI. Trigeminal Nerve (Cranial Nerve V) and Facial Nerve (Cranial Nerve VII)
• The three divisions of the trigeminal nerve—ophthalmic, maxillary,
and mandibular—convey information about
▪ Facial protopathic (pain, temperature) and
▪ Epicritic (vibration, proprioception) sensation
• The facial nerve is a predominantly motor nerve
▪ A facial nerve palsy may be
o Congenital;
o Idiopathic (Bell palsy); or
o Secondary to
• Trauma,
• Demyelination (Guillain-Barré syndrome),
• Infection (Lyme disease, herpes simplex virus, HIV),
• Granulomatous disease,
• Neoplasm, or
• Meningeal inflammation or infiltration.

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• Corneal reflex
▪ Tests the sensory function of trigerminal nerve and the motor
function of the facial nerve.
▪ The normal effector response involves both upward deviation of
the eye (oculomotor nerve) and closure of the eyelid (facial
nerve)
▪ The patient’s cornea is lightly touched with a fine wisp of cotton
or a drop of sterile water. An intact reflex produces a bilateral
(direct and consensual) eye blink
▪ Absence of a blink in response to a loud noise or bright light
implies
o Dysfunction of the pontine reticular formation secondary
to either metabolic or structural causes.
▪ Unilateral absence of a blink
o Implies a facial nerve lesion.
VII. Vestibulocochlear Nerve (Cranial Nerve VIII)
• The vestibulocochlear nerve has two components within a single trunk:
▪ The vestibular nerve, which is involved with equilibrium,
coordination, and orientation
o Dysfunction results in vertigo, the sensation of
environmental motion. this can be tested with the fukuda
stepping test and oculovestibular test
▪ The cochlear nerve, which sub serves hearing.
• The oculovestibular (caloric) reflex
▪ Otoscopy should first confirm that the external ear canals are
patent and the tympanic membranes are intact.
▪ With the head at 30 degrees elevations from horizontal, irrigation
of the external ear canal with ice-cold water (30 to 50ml) induces
slow deviation of the eyes toward the irrigated side. A much
smaller quantity of ice water (2 mL) is used in awake, alert
patients to avoid inducing nausea. Five minutes should intervene
before the other side is tested.
▪ Failure of the eyes to move conjugately as expected suggests a
lesion of one or more cranial nerves or their nuclei within the
brainstem.
VIII. Glossopharyngeal Nerve (Cranial Nerve IX)
• The nerve is tested by stimulating one side of the lateral oropharynx or
soft palate with a tongue blade and observing for symmetric elevation
of the palate (gag reflex).
4. MOTOR EXAMINATION
• The motor examination includes assessment of
1. Muscle bulk,
2. Tone, and

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3. Strength, as well as
4. Observation for involuntary movements.
1. BULK
• Decreased muscle bulk (atrophy) may be secondary to
o Disuse or
o Diseases of the lower motor neuron, nerve root, peripheral nerve, or
muscle.
2. TONE
• Abnormalities of tone include
o Spasticity,
o Rigidity, and
o Hypotonia.
• Intact brain stem function
o Normal body position
o Spontaneous non posturing movements
• Hemiparesis or hemiplegia implies
o structural lesion in the
▪ contralateral hemisphere
▪ Subcortical region or
▪ Ipsilateral spinal cord injury.
• hypertonia or hyperreflexia suggests
▪ Previous corticospinal tract disease or
▪ An acute brainstem injury at the midbrain-pontine level.
▪ Severe metabolic derangements, such as hepatic coma,
hypoglycemia, anoxia, and uremia.
• Hypotonia implies
▪ bilateral hemispheric dysfunction or
▪ a medullary or spinal cord lesion
• Flaccid response to noxious stimulation
▪ is associated with Pontomedullary or spinal cord damage

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12.5. SPECIAL DIAGNOSTIC PROCEDURES
LUMBAR PUNCTURE AND CEREBROSPINAL FLUID EXAMINATION

• Examination of the CSF and measurement of the pressure it creates in the
subarachnoid space are essential in
▪ Confirming the diagnosis of
• Meningitis,
• Encephalitis (autoimmune, infectious), and
• Idiopathic intracranial hypertension (previously referred to as
pseudotumor cerebri)
• Helpful in assessing
• Subarachnoid hemorrhage;
• Demyelinating, degenerative, and collagen vascular diseases
and
• Intracranial neoplasms.
• Steps to do the procedure
▪ Having an experienced assistant who can position, restrain, and comfort
the patient is critical to the success of the procedure.
▪ The patient should be situated in a lateral decubitus or seated position
with the neck and legs flexed to enlarge the intervertebral spaces. Sick
neonates should be maintained in a seated position to prevent problems
with ventilation and perfusion
▪ Identify the appropriate interspace
by drawing an imaginary line from
the iliac crest downward
perpendicular to the vertebral
column. In adults, lumbar
punctures are usually performed in
the L3-L4 or L4-L5 interspaces.
▪ The skin and underlying tissues are
anesthetized by injecting a local
anesthetic
▪ E.g., 1% lidocaine at the time
of the procedure or
▪ By applying a eutecticmixture
of lidocaine and prilocaine
(EMLA) to the skin 30 min
before the procedure. (not
routinely done at JMC)
▪ A 22-gauge, 1.5- to 3.0-inch, sharp,
beveled spinal needle with a properly
fitting stylet is introduced in the midsagittal plane and directed slightly
cephalad.
• Contraindications to performing a lumbar puncture include

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▪ Suspected mass lesion of the brain, especially in the posterior fossa or
above the tentorium and causing shift of the midline;
▪ Suspected mass lesion of the spinal cord;
▪ Symptoms and Signs of impending cerebral NB- If optic disc edema or focal
herniation in a child with probable findings suggest a mass lesion; a
meningitis; rapid CT scan of the head should be
▪ Critical illness (on rare occasions); obtained before proceeding with
▪ Skin infection at the site of the lumbar lumbar puncture to prevent uncal or
puncture; and cerebellar herniation as the CSF is
▪ Thrombocytopenia with a platelet count of <
removed
20 × 109/L.
CSF PARAMETERS
CSF Normal value Abnormal value indicates
parameters
Neonates Infants and
children
Opening 11.5-28 cm H2O
pressure
PMNs 1-2/mm3 None Elevated values indicate
• bacterial meningitis,
• The early phase of aseptic meningitis
WBCs 15/mm3 5/mm3 CSF lymphocytosis can be seen in
• A septic, tuberculous, or fungal meningitis;
• Demyelinating diseases;
• Brain or spinal cord tumor;
• Immunologic disorders, including collagen vascular diseases; and
• Chemical irritation (following myelogram, intrathecal methotrexate).
RBCs None Presence indicates
• A traumatic tap or
• A subarachnoid hemorrhage
CSF protein 120 mg/dL 10-40 Elevated in
mg/dL ▪ Infectious, immunologic, vascular, and degenerative diseases;
▪ Blockage of CSF flow; as well as tumors of the brain (primary CNS
tumors, systemic tumors metastatic to the CNS, infiltrative acute
lymphoblastic leukemia) and spinal cord.
▪ With a traumatic tap, the CSF protein is increased by approximately 1
mg/dL for every 1,000 red blood cells/mm3.
CSF glucose 60% of the blood glucose Hypoglycorrhachia is found in association with
▪ Diffuse meningeal disease, particularly bacterial and tubercular
meningitis.
▪ Widespread neoplastic involvement of the meninges,
▪ Subarachnoid hemorrhage,
▪ Disorders involving the glucose transporter protein type 1 (e.g., GLUT1
deficiency),
▪ Fungal meningitis, and, occasionally, aseptic meningitis
▪ Normal CSF contains no red blood cells. Bloody sample can be either

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▪ A traumatic tap
▪ Pathologic process like
▪ Subarachnoid hemorrhage
▪ Hyperbilirubinemia,
▪ Carotenemia, and
▪ Markedly elevated CSF protein.
▪ To differentiate between the two
▪ Bloody CSF should be centrifuged immediately. A clear
supernatant is consistent with a bloody tap,
▪ Whereas Xanthochromia (yellow color that results from the
degradation of hemoglobin) suggests a subarachnoid hemorrhage.
Xanthochromia may be absent in bleeds < 12 hr old
▪ Elevation of CSF immunoglobulin G, which normally represents approximately
10% of the total protein, is observed
▪ In subacute sclerosing panencephalitis,
▪ Postinfectious encephalomyelitis, and
▪ In some cases of multiple sclerosis
▪ A Gram stain of the CSF is essential if there is a suspicion for bacterial
meningitis;
▪ Acid-fast stain can be used to assess for tuberculous and
▪ India ink preparation can be used to assess for fungal meningitis.
▪ CSF is then plated on different culture media depending on the suspected
pathogen.
▪ Traumatic LP
▪ Blood can make an impact on the cell count and protein measurements.
▪ “Corrected" WBC count – for those which are not grossly
bloody, subtract 1 WBC for every 1000 RBC. (UpToDate).
▪ “Corrected” CSF Protein - subtracting 1 mg/dL for every 1000
RBCs/microL.
NEURO RADIOLOGIC PROCEDURES

1. Skull x-rays- can demonstrate
▪ Fractures,
▪ Bony defects,
▪ Intracranial calcifications, or
▪ Indirect evidence of increased ICP.
▪ Acutely increased ICP causes separation of the sutures,
▪ Whereas chronically increased ICP is associated with
▪ erosion of the posterior clinoid processes,
▪ Enlargement of the sella turcica, and
▪ Increased convolutional markings.
2. Cranial ultrasonography- is
▪ Imaging method of choice for detecting
▪ Intracranial hemorrhage,
▪ Periventricular leukomalacia, and

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▪ Hydrocephalus in infants with patent anterior fontanels.
▪ Less sensitive than either cranial CT scanning or MRI for detecting hypoxic–
ischemic injury
▪ In general, ultrasound is not a useful technique in older children
3. Cranial CT
▪ Is a valuable diagnostic tool in the evaluation of many neurologic
emergencies, as well as some non-emergent conditions.
▪ In the emergency setting,
▪ A non-contrast CT scan can demonstrate
▪ Skull fractures,
▪ Pneumocephalus,
▪ Intracranial hemorrhages,
▪ Hydrocephalus, and
▪ Impending herniation.
▪ CT imaging can be used to demonstrate
▪ Intracranial calcifications or,
▪ With the addition of 3-dimensional reformatting, to evaluate
patients with craniofacial abnormalities or craniosynostosis.
▪ CT is less useful for diagnosing acute infarcts in children, because
radiographic changes might not be apparent for up to 24 hr.
▪ MR is generally preferred because it provides a more detailed view of the
anatomy without exposure the patient to ionizing radiation
4. Cranial CT angiography
▪ useful tool for visualizing vascular structures
▪ Is accomplished by administering a tight bolus of iodinated contrast
through a large-bore intravenous catheter and then acquiring CT images as
the contrast passes through the arteries.
5. Brain MRI
▪ Pre-requisite
▪ It is highly susceptible to patient motion artifact so many children
younger than age 8 yr require sedation.
▪ It is recommended that infants be kept (NPO) for 4 hr or longer
and older children for 6 hr or longer before deep sedation
▪ MRI can be used to evaluate for
▪ Congenital or acquired brain lesions,
▪ Migrational defects,
▪ Dysmyelination or demyelination,
▪ Posttraumatic gliosis, neoplasms, cerebral edema, and acute stroke
▪ MR angiography is the procedure of choice for infants and young children
due to the lack of ionizing radiation and contrast
6. Functional MRI
7. Proton MR spectroscopy (MRS)
8. Catheter angiography
▪ The gold standard for diagnosing vascular disorders of the CNS, such as
▪ Arteriovenous malformations,
▪ Aneurysms

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▪ Arterial occlusions, and
▪ Vasculitis.
9. Positron emission tomography (PET)
▪ provides unique information on brain metabolism and perfusion by
measuring blood flow, oxygen uptake, and/or glucose consumption.

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12.6. CNS INFECTIONS
12.6.1. ACUTE BACTERIAL MENINGITIS BEYOND THE NEONATAL

PERIOD
ETIOLOGY AND EPIDEMIOLOGY

• Historically, the most common causes of bacterial meningitis in children older
than 1 mo of age are Hemophilus influenza type b, Streptococcus pneumoniae,
and Neisseria meningitidis.
• The incidence of meningitis caused by all three organisms has been
significantly reduced in countries that have introduced universal immunization
against these pathogens. S. pneumoniae is now the most common cause of
bacterial meningitis in the United States, while H. influenza associated disease
is exceptionally rare.
Table 118 etiologic agents based on some risk factors
Age Causative agent
0-4 weeks S. agalactiae, E. coli, L. monocytogenes, K.
Pneumoniae, Enterococcus spp., Salmonella spp.
4-12 weeks S. agalactiae, E. coli, L. monocytogenes, H. influenzae,
S. pneumoniae, N. meningitides
3 months – 18 years H. influenzae, N. meningitides, S. Pneumonia
Immunocompromised S. pneumoniae, N. meningitidis, L. monocytogenes,
state aerobic Gram-negative bacilli (including P. aeruginosa)
Head trauma; post- S. aureus, S. epidermidis, aerobic Gram-negative bacilli
neurosurgery (including P. aeruginosa)
CSF shunt S. epidermidis, S. aureus, aerobic Gram-negative bacilli
(including P. aeruginosa), Propionibacterium acnes
• Meningococci (19.4%) and pneumococci (12.9%) were the major disease-causing
organisms in Ethiopia
• Ethiopia has the second-largest population (≈94 million in 2013) among the
meningitis belt countries of sub-Saharan Africa. The largest meningitis
epidemics occurred in 1981 and 1989, resulting in ≈45,000 and ≈50,000 cases,
respectively.
RISK FACTORS;
• The major one is the lack of preexisting immunity to specific pathogens and
serotypes, reflected by the higher incidence of meningitis in young infants.
• Additional risk factors include:
o History of close contact, crowding/poor living conditions
(household, daycare centers, college dormitories, military barracks) - N.
meningitidis or H. influenzae type

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o History of head injury, otitis media (ear ache, discharge),
mastoid tenderness, sinusitis, pneumonia, CSF otorrhea
or rhinorrhea, the presence of a cochlear implant, and
immunosuppression – S. pneumoniae
• Poverty/low income
• Male sex
• Age:
o <5 yrs. aged children; first peak
o 15-24; second peak - meningococcal infection.
• Geographic location and travel history: Epidemics in ‘African meningitis belt’
in a cyclical pattern in 8-15 yrs. 80-85% outbreaks occur there.
NB: Northern and western parts of Ethiopia are parts of this belt)
• Previous medical treatment and existing conditions
o Defects of the complement system (C5-C8)
o recurrent meningococcal infection
o Splenic dysfunction (in sickle cell anemia) or asplenia - pneumococcal, H.
influenza type b, and meningococcal sepsis and meningitis
o T-lymphocyte defects (congenital or acquired by chemotherapy,
AIDS, or malignancy)- Listeria monocytogenes.
• The risk of pneumococcal meningitis is increased in the following conditions
o Congenital or acquired CSF leak in:
▪ lumbar dual sinus,
▪ cranial or midline facial defects (cribriform plate),
▪ fistulas of the middle ear or inner ear
▪ basilar or other skull fracture (head trauma)
▪ Lumbosacral dermal sinus and myelomeningocele - staphylococcal,
anaerobic, and Gram-negative enteric bacterial meningitis
▪ CSF shunt infections -Pseudomonas aeruginosa, Staphylococcus
spp., Propionibacterium spp.
• Most often, meningitis is preceded by several days of fever accompanied by URT or
GI symptoms, followed by nonspecific signs of CNS infection, such as increasing
lethargy and irritability
• Less commonly it can have sudden onset with rapidly progressive manifestation of
shock, purpura and DIC decreased levels of consciousness often leading to coma
and death in 24 hrs
• The signs and symptoms can be
o nonspecific/associated with systemic infection including;
▪ fever, anorexia and poor feeding, headache, upper respiratory
symptoms, myalgias, arthralgias, tachycardia, hypotension, and
various cutaneous signs.
▪ The rash of meningococcemia is typified by an initial petechial rash
that evolves into ecchymotic and purpuric lesions.

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o Specific to CNS inflammation;
• Meningeal irritation is manifested as
• nuchal rigidity,
• back pain,
• Kernig sign (flexion of the hip 90 degrees with subsequent pain with
extension of the leg), and
• Brudzinski sign (involuntary flexion of the knees and hips after
passive flexion of the neck while supine).
➢ In children, particularly in those younger than 12-18 mo, the Kernig and
Brudzinski signs are not consistently present.
➢ Although it was previously thought that these signs have low sensitivity,
newer studies have shown the sensitivity and specificity to be 53% and
85% respectively for Kernig’s and of Brudzinski’s to be 66% and 74%
respectively.
Figure 101 Positive clinical examination findings for meningitis
• Increased ICP is suggested by

o Headache, emesis,
o bulging fontanel or diastasis (widening) of the sutures,
o oculomotor (anisocoria, ptosis) or abducens nerve paralysis,
o hypertension with bradycardia, apnea or hyperventilation (Cushing’s
triad)
o decorticate or decerebrate posturing,
o stupor, coma, or signs of herniation.
Normal CSF pressure in children at the lumbar puncture is 9 to 21mmHg. Measured
ICP >28mmHg for longer than five minutes with sign and symptoms is generally
regarded as threshold for treatment.

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• Papilledema is suggestive of a more chronic process/complicated meningitis, such
as the presence of an intracranial abscess, subdural empyema, or occlusion of a
Dural venous sinus.
• Focal neurologic signs (10-20%) usually are a result of vascular occlusion.
• Cranial neuropathies of the ocular, oculomotor, abducens, facial mm and
auditory nerves may also be the result of focal inflammation.
• Seizures- focal or generalized
o Occur in 20–30%
o related to cerebritis, infarction, or electrolyte disturbances
• Alteration in mental status (eg, lethargy, confusion, irritability) may be the
consequence of increased ICP, cerebritis, or hypotension;
• Photophobia
• tac he cérébrale (which is elicited by stroking the skin with a blunt object and
observing a raised red streak within 30-60 sec)
DIAGNOSIS
• Lumbar puncture (LP)is the most important step in the diagnosis of meningitis.
• CSF obtained from children with bacterial meningitis can be negative on Gram
stain and culture as early as 2-4 hr after administration of
antibiotics, especially in situations of N. meningitidis and sensitive S.
pneumoniae meningitis.
• Antibiotic pretreatment is associated with higher CSF glucose and lower
protein.
• However, pleocytosis with a predominance of neutrophils will usually persist
for several days after the administration of appropriate parenteral antibiotics.
• Therefore, despite negative cultures, the presumptive diagnosis of bacterial
meningitis can be made on the basis of an abnormal CSF cell count, protein,
and glucose.
Table 119 CSF findings in meningitis
CONDITON PRESSURE LEUKOCYTES PROTEIN GLUCOSE COMMENTS
(cmH2 O) (mm3 ) (mg/dl) (mg/dl)
Normal <28 <5, ≥75% 20-45 >50 (or
Lymphocytes 75% serum
In neonates: <20 glucose)
Acute Usually 100-10,000 or Usually Decreased, Organisms
bacterial elevated more; 100-500 usually <40 usually
meningitis usually 300- (or <50% of seen on
2,000; serum Gram stain
PMNs glucose) and isolated
predominate by
culture
See the Lumbar Puncture Under Neurologic evaluation above for details

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• The characteristic presentation of meningitis is a triad of fever, neck stiffness,
and abnormal mental status. Many other conditions can present with similar
manifestations but have normal CSF findings
o Febrile illness – Children with other infectious conditions can present
with a constellation of symptoms that mimic meningitis. Common
conditions among children with normal CSF findings included:
▪ Pneumonia
▪ Otitis media
▪ Pharyngitis/tonsillitis
▪ Upper respiratory infection with cervical adenopathy
▪ Viral infection/herpangina (predominantly in children <5 years)
▪ Gastroenteritis
o Nuchal rigidity – While nuchal rigidity is highly suggestive of meningitis,
it can occur in other conditions, such as retropharyngeal abscess,
cervical spine injury or infection
o Depressed mental status – Important causes of altered depressed mental
status in children include head trauma, seizure, metabolic and toxic or
drug ingestions.
• The term Aseptic meningitis has been used to describe inflammation of
meninges not caused by pyogenic bacteria. Although it is most commonly
caused by certain viruses, it has a number of other etiologies, both infectious
and noninfectious.
• Although classic CSF profiles associated with bacterial versus viral infection
tend to be distinct, these cases can overlap in the number of CSF leukocytes
and glucose and protein levels. Quite often, children are empirically treated
with antibiotics for > 48 hr to await CSF culture and PCR data to delineate
between these two groups of pathogens.
TREATMENT
• Essential to improving clinical outcomes in patients with bacterial meningitis is
prompt recognition, diagnostic testing, and initiation of appropriate
antimicrobial therapy.
• Some patients with meningitis will develop multiple organ system failure,
shock, and acute respiratory distress syndrome, requiring further management
in an intensive care unit.
INITIAL (EMPIRICAL) ANTIBIOTIC THERAPY:

• Vancomycin (60 mg/kg/day given every 6-8 hr; some experts would start as
high as 80 mg/kg/day; goal trough 15-20 µg/mL) plus ceftriaxone (50
mg/kg/dose given every 12 hr).
o In JUMC, the patient is started on ceftriaxone while waiting for culture
and sensitivity result.

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• Patients allergic to penicillin or cephalosporin antibiotics can be treated with
Meropenem (40 mg/kg/dose every 8 hr); fluoroquinolones or
chloramphenicol.
o Alternatively, allergic patients can be desensitized to the antibiotic.
• L. monocytogenes infection is suspected, as in
o young infants or
o those with aT-lymphocyte deficiency,
o Ampicillin (300 mg/kg/day, divided every 6 hr). Intravenous
trimethoprim-sulfamethoxazole is an alternative treatment.
• If a patient is immunocompromised and Gram-negative bacterial meningitis is
suspected, initial therapy might include cefepime or meropenem.
DURATION OF ANTIBIOTICS:
• Is dependent on the etiologic agents
o Uncomplicated S. pneumoniae meningitis – for 10-14 days with
▪ 3rd-generation cephalosporin or
▪ intravenous penicillin (300,000-400,000 units/kg/day, divided
every 4-6 hr).
▪ If resistant; vancomycin should be used.
o N. meningitidis meningitis, - for 5-7 days with
▪ IV penicillin (300,000 units/kg/day), or
▪ ceftriaxone.
o Uncomplicated H. influenzae type b meningitis - for 7-10 days with
▪ ampicillin for β-lactamase–negative strains, or
▪ 3rd-generation cephalosporin for β-lactamase–positive isolates.
• Patients who receive antibiotics prior to LP and do not have an identifiable
pathogen, but do have evidence of bacterial meningitis based on their CSF
profile, should receive therapy with ceftriaxone or cefotaxime (300mg/kg/24
hr., every 6hr) for 7-10 days.
• Escherichia coli or P. aeruginosa may require therapy with a 3rd- or 4th-
generation cephalosporin (Ceftriaxone for E. coli, ceftazidime for P.
aeruginosa) or carbapenem for 3 wk or at least 2 wk after CSF sterilization,
which may occur after 2-10 days of treatment.
• Repeat examination of CSF is indicated in some neonates, in all patients with
meningitis from Gram-negative bacilli, and in patients with infection caused by
a β-lactam–resistant S. pneumoniae.
• If focal signs are present or the child does not respond to
treatment, a Para meningeal focus may be present, and a CT or MRI scan
should be performed.
CORTICOSTEROIDS
• Decreases the inflammation that occurs by rapid killing of bacteria in CSF and
concomitant toxic cell products release, which decreases the additional
neurologic injury.

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• IV dexamethasone, 0.15 mg/kg/dose given every 6 hr for 2 days, in the
treatment of H. influenzae type b meningitis in children older than 6 wk of
age.
• Corticosteroids appear to have maximum benefit if given 1-2 hr before
antibiotics are initiated. They also may be effective if given concurrently with
or soon after the first dose of antibiotics.
COMPLICATIONS
• Acute CNS Complications
o Seizures
o CN palsies
o Increased ICP
o Stroke
o Cerebral or cerebellar herniation
o Hydrocephalus (especially neonates and infants)
• Acute systemic complications
o Prolonged fever (>10) days
o Thrombocytosis
o Anemia
o Infectious pericarditis or arthritis
o DIC
o Central Diabetes Insipidus
o SIADH (30-50% of patients); Hyponatremia-cerebral edema and seizures
• Chronic Neurologic complications
o Sensorineural hearing loss- 30% in pneumococcal, 5-20% in H. influenza,
10% in N. meningitides.
o Visual impairment
o Delay in acquisition of language and behavioral problems
o Recurrent seizures
o Mental retardation
o Symmetric peripheral Gangrene from coagulation cascade that is
initiated by endotoxemia and severe hypotension.
PROGNOSIS
• Mortality rates have reduced to <10%. The highest MRs are seen in
pneumococcal meningitis.
• Poor prognosis
o Age <6 months
o High concentration of bacteria and bacterial products in CSF
o Absent pleocytosis in patients with severe overwhelming sepsis
associated with meningitis.
o Seizure occurring >4days into therapy
o Coma or focal neurologic signs on presentation.
PREVENTION

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• Vaccination and antibiotic prophylaxis to close contacts
• N. meningitides – Close contacts should be treated with rifampin 10
mg/kg/dose every 12 hr (maximum dose of 600 mg) for 2 days as soon as
possible after identification of a case of suspected meningococcal meningitis or
sepsis
o Alternatively; ceftriaxone 125 mg intramuscularly once for children
under age 15 yr, or 250 mg intramuscularly once for persons older than
15 yr, or ciprofloxacin 500 mg orally once.
o Quadrivalent conjugate meningococcal vaccine (types A, C, Y, and W-
135; Menactra and Menveo)
• H. influenza – rifampin prophylaxis is 20 mg/kg/day (maximum dose of 600 mg)
given once each day for 4 days.
o All children should be immunized with H. influenzae type b conjugate
vaccine beginning at 2 mo of age.
• S. Pneumoniae - no antibiotic prophylaxis to contacts.
o Routine administration of PCV13 conjugate vaccine against S.
pneumoniae is recommended for children younger than 5 yr of age and
other at-risk children.
12.6.2. BRAIN ABSCESS

• Brain abscess is a focal infectious collection within the brain parenchyma,
which can arise as a complication of another infection or through trauma or
surgery.
PATHOPHYSIOLOGY
• Cerebral abscesses, unlike in adults, occur in both hemispheres in children.
• Nearly 80% of abscesses occur in the frontal, parietal, and temporal lobes,
• While abscesses in the occipital lobe, cerebellum, and brainstem account for
the remainder of cases. In 18% of cases, multiple brain abscesses are present,
and in nearly 20% of cases, no predisposing risk factor can be identified.
• Development of brain abscess is most often associated with an underlying
etiology, including:
DIRECT SPREAD —
• Most brain abscesses occur via direct spread.
• From a contiguous site – The direct spread of organisms from a contiguous site
(25 to 50 percent of cases) usually causes a single brain abscess. Primary
infections that can directly spread to the cerebral cortex include
• Subacute and chronic otitis media and mastoiditis (spread to the inferior
temporal lobe and cerebellum)
• Frontal or ethmoid sinuses (spread to the frontal lobes)
• Dental infection (usually spreads to the frontal lobes)
• From a foreign body – can occasionally result from facial trauma.
• From a surgical procedure – Development of brain abscess after neurosurgery
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HEMATOGENOUS SPREAD —
• Brain abscesses associated with bacteremia (20 to 35 percent of cases) usually
result in multiple abscesses that are most commonly located in the distribution
of the middle cerebral artery.
• Abscesses usually form at the grey-white matter junction where micro
infarction damages the blood-brain barrier.
• Conditions such as
o Chronic pulmonary, skin, pelvic infections, and intra-abdominal
infections esophageal dilation and endoscopic sclerosis of esophageal
varices.
o Infective endocarditis (brain abscess complicates 2 to 4 percent of
cases).
o Cyanotic congenital heart diseases (most common in children).
o Intrapulmonary right-to-left shunting in patients with pulmonary
arteriovenous malformations
Tissue damage seen in brain abscess is primarily caused by the host's acute
inflammatory response to the invading pathogen.
• The clinical findings depend in part upon the duration of disease.
o The early lesion that occurs in the first one to two weeks is poorly
demarcated and is associated with localized edema. This early stage
(commonly called cerebritis), there is evidence of acute inflammation
but no tissue necrosis.
o However, after two to three weeks, necrosis and liquefaction occur, and
the lesion becomes surrounded by a fibrotic capsule.
ETIOLOGY
• The predominant organisms that cause brain abscesses are
o Streptococci - (S. anginosus, S. constellatus and S. intermedius)
o Followed by staph aureus (11%).
o The other bacteria isolated include;
▪ Gram-negative aerobic organisms (Hemophilus spp., Escherichia
coli, Klebsiella pneumoniae, Proteus spp., and other
Enterobacteriaceae) and anaerobes.
• In neonates with meningitis, abscess formation is a complication in 13% of
cases, with Citrobacter koseri, Cronobacter sakazakii, Serratia marcescens, and
Proteus mirabilis
• Atypical bacteria (Nocardia, Mycobacterium, and Listeria spp., and fungi
(Aspergillus, Candida, Cryptococcus) are more common in children with
impaired host defenses.
• Up to 27% of cases are polymicrobial. Abscesses associated with mucosal
infections (sinusitis or dental infections) frequently are polymicrobial and
include anaerobic organisms.

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• Often the early stages of cerebritis and abscess formation are asymptomatic or
associated with nonspecific symptoms, including low-grade fever, headache,
and lethargy.
• The headache is usually localized to the site of the abscess and not relieved by
analgesics.
• As the inflammatory process proceeds, vomiting, severe headache, seizures,
papilledema, focal neurologic signs (hemiparesis), and coma may develop.
• A cerebellar abscess is characterized by nystagmus, ipsilateral ataxia and
dysmetria, vomiting, and headache.
• If the abscess ruptures into the ventricular cavity(signified by sudden worsening
of the headache accompanied by new onset meningismus), overwhelming shock
and death occur in 27–85% of cases.
DIAGNOSIS
• The key to diagnosis of brain abscesses is prompt imaging of the CNS.
• Brain MRI with contrast is the diagnostic test of choice because it can aid in
differentiating abscesses from cysts and necrotic tumors .
• Cranial CT can provide a more rapid result, but cannot provide the fine tissue
detail offered by MRI. Both MRI and CT scans with contrast can demonstrate a
ring-enhancing abscess cavity.
• The Peripheral WBC count can be normal but is elevated in 60% of cases.
• Blood cultures are positive in only 28% of cases and CSF cultures in only 24%.
• Molecular diagnostics with PCR are being evaluated to establish a bacterial
etiology in aspirates from brain abscesses.
• Lumbar puncture is not routinely recommended in cases of brain abscesses,
because the procedure could cause brain herniation from elevated intracranial
pressure. When tested, the cerebrospinal fluid (CSF) is normal in 16% of cases,
71% of cases exhibit CSF pleocytosis, and 58% will have an elevated CSF protein
level.
• An electroencephalogram (EEG) may identify corresponding focal slowing.
Figure 102 MRI of a brain abscess showing the classic "ring-enhanced" lesion
MANAGEMENT

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• The Management of brain abscess includes prompt diagnosis, empiric therapy,
and surgical management.
ANTIMICROBIAL THERAPY
• A brain abscess can be treated with antibiotics without surgery if
o the abscess is <2.5 cm in diameter,
o the illness is of short duration (<2 wk),
o there are no signs of increased intracranial pressure, and
o the child is neurologically intact.
• Empiric antibiotic regimens:
o *3rd generation cephalosporin +Metronidazole + vancomycin
o Or Cefepime/Meropenem + Metronidazole + vancomycin (G-ve
suspected) Or Penicillin G/ Ampicillin + Gentamicin (L. monocytogenes
suspected, esp. in neonates)
o Addition of Amphotericin B in case of immunocompromised patient and
fungi suspected.
• The duration of parenteral antibiotic therapy depends on the organism and
response to treatment but is most typically 4-6 wk.
• Glucocorticoids can reduce edema, but doesn't change outcome.
SURGICAL MANAGEMENT
• In most settings, needle aspiration or surgical excision should be performed to
identify the causative pathogen prior to the initiation of antibiotic therapy and
to reduce the size of the collection. It is important that the aspirate be
cultured for aerobes and anaerobes, fungi, and Mycobacterium tuberculosis.
• However, under certain circumstances, drainage of a presumed bacterial brain
abscess may be delayed or not required. These include:
o When a brain abscess occurs in the setting of bacteremia, in which case
antibiotic therapy is based upon the results of blood culture.
o Early cerebritis without evidence of cerebral necrosis.
o Abscesses located in vital regions of the brain or those inaccessible to
aspiration.
o Lesions <2.5 cm and a Glasgow coma score of >12. However, aspiration
may still need to be performed on these smaller lesions to identify the
etiologic agent
• Aspiration — Needle aspiration is generally preferable to surgical excision since
the neurologic sequelae are reduced. This is particularly important when
speech areas and regions of the sensory or motor cortex are involved and in
patients who are comatose.
o However, it may be accompanied by the need for more prolonged
antibiotic therapy and a more prolonged postoperative neurologic
recovery time compared with open surgical excision.
• If the abscess fails to change in size or expands in diameter, it should be re-
aspirated.

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• An elevated C-reactive protein on admission may predict the need for repeated
aspiration.
• Surgical excision — Surgical excision is a more radical approach that generally
results in greater neurologic deficits and is now infrequently performed.
However, excision may be the initial treatment of choice in the following
circumstances:
o Traumatic brain abscesses (to remove bone chips and foreign material)
o Encapsulated fungal brain abscesses
o Multiloculated abscesses
• In addition, the following are indications for excision after initial aspiration and
drainage
o No clinical improvement within one week
o Depressed sensorium
o Signs of increased intracranial pressure
o Progressive increase in the diameter of the abscess
o Associated infectious processes, such as mastoiditis, sinusitis, or a
periorbital abscess, may require surgical drainage.
PROGNOSIS
• Mortality rate with prompt management ranges from 5-10%.
• Factors associated with high mortality rates at the time of admission include
delayed administration of antimicrobials, age < 1 yr, multiple abscesses, and
coma.
• Long-term sequelae occur in about one third of the survivors and include
hemiparesis, seizures, hydrocephalus, cranial nerve abnormalities, and
behavioral and learning difficulties.

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12.7. DIFFERENTIAL DIAGNOSIS FOR BODY WEAKNESS

POLIOMYELITIS
• Causative agent
o Poliovirus is an RNA virus in the family Picornaviridae, genus enterovirus
o There are three antigenically distinct types, and infection with one does
not protect against the others
o Type I virus is generally more virulent than types II and III
o Type I has been the most frequent cause of endemic and epidemic
paralytic disease and type II is the least paralytogenic strain
EPIDEMIOLOGY
• The most devastating result of poliovirus infection is paralysis, although 90–95%
of infections are inapparent
• Despite the absence of symptoms, clinically inapparent infections induce
protective immunity
• Clinically apparent but nonparalytic illness occurs in approximately 5% of all
infections
• Before a vaccine was available, infection with poliovirus was common
worldwide, with seasonal peaks and epidemics in the summer and fall in
temperate area.
• Humans are the only known reservoir for the polioviruses
• Transmission route
o Spread is from individual to individual by the faecal-oral route
• Incubation time(IP): 6–20 days
• IP can be shorter or more prolonged in certain cases
• Occur in sporadic, endemic, or epidemic form
• Infants under the age of one year are rarely attacked
• In a country where hygiene is poor, most sufferers are between the ages of two
and four years
• After the age of five years, most individuals are immune, and after 25 years the
disease is rare
• In general, paralysis is more likely to develop in male children and female
adults
• Mortality and the degree of disability are greater after the age of puberty
• Pregnancy is associated with an increased risk for paralytic disease
RISK FACTORS
• Lack of universal vaccination

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• Poor sanitation
• Overcrowding
• History of IM injections (provocation paralysis) – bulbar poliomyelitis
• Increased physical activity, exercise, and fatigue in early phase of illness a
higher risk for paralytic disease
• Surgery e.g., tonsillectomy
• Puberty
• Pregnancy
PATHOPHYSIOLOGY
• In the acute stage, the spinal cord is congested, soft and edematous, and
minute hemorrhages may be visible in the grey matter
• One of the striking features of the pathology of this disease is the selectivity of
distribution of the lesions and the almost consistent sparing of other parts of
the CNS
• In the spinal cord, the most severe grey matter lesions are in the anterior
columns
• The degree of damage varies from one level to another but is often most
intense at the cervical or lumbar enlargements of the cord
• The inflammatory reaction can also involve the intermediate and posterior
horns, but not to the extent of the involvement of the anterior horns
• Within the brainstem, cellular infiltration can be seen in many of the cranial
nerve motor nuclei, but is most apparent in the region of the vestibular nuclei
and the reticular formation
• Unlike most other types of viral encephalitis, the cerebral cortex is
characteristically spared
• The earliest visible changes in the spinal cord in the acute stage consist of
infiltration with lymphocytes and polymorphonuclear leucocytes in the anterior
horns
• Congestion of vessels and petechial hemorrhages may also be observed when
the inflammatory reaction is intense
• The spinal meninges commonly exhibit inflammatory cell infiltration of variable
degree, while the cerebral meninges may be entirely spared
• With the passage of time beyond the acute insult, the cellular infiltration
becomes less dense, but neurons that are irreversibly damaged undergo
necrosis and neuronophagia
• This is followed by atrophy of the anterior roots due to loss of myelinated
nerve fibers and denervation atrophy of the muscles involved

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• In the chronic stages, severely damaged anterior horns contain few or no viable
neuronal elements, and may assume a cavitied or cystic appearance to gross
observations
• An acute infectious disease, is also characterized by preferential involvement
of the motor neurons of the spinal cord and brain which results in an
asymmetric flaccid paralysis of the voluntary muscles
• The virus multiplies in the pharynx and ileum, probably in lymphoid tissue of
the tonsils and Peyer's patches
• The virus then spreads to cervical and mesenteric lymph nodes and can be
detected in the blood shortly thereafter
• Infection of the nervous system by way of viraemia is likely
• Transmission of poliovirus along the peripheral nerve fiber pathway is a
possibility under certain circumstances
• The virus replicates in the gastrointestinal tract (oropharynx and small
intestine) following oral ingestion → enters the bloodstream → potential
invasion of the grey matter of the spinal cord (particularly the lower motor
neurons of the anterior horn) → myelitis
CLINICAL FEATURES
ABORTIVE POLIOMYELITIS
• Abortive poliomyelitis (minor illness) is a non-specific illness lasting for hours to
a few days, characterized by fever, headache, malaise, sore throat, anorexia,
nausea, vomiting, and abdominal pain
• There are no signs of CNS involvement and the CSF is normal
• However, the protein of the CSF may be found to be elevated two or three
weeks later, indicating that inflammatory changes may have occurred sub-
clinically.
• This phase is followed by temporary improvement with remission of fever for
48hours, or may merge into the second phase, 'major illness', in which
headache is more severe and is associated with pain in the back and limbs,
sometimes with muscle tenderness
• The symptoms closely resemble those of other forms of viral Meningitis
• It is in approximately 5% of patients, a nonspecific influenza-like syndrome
occurs 1-2 wk after infections
• The illness is short lived, lasting up to 2-3 days
• The physical examination may be normal or may reveal nonspecific pharyngitis,
abdominal or muscular tenderness, and weakness
• Recovery is complete, and no neurologic signs or sequelae develop
NON-PARALYTIC POLIOMYELITIS

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• In nonparalytic cases, the patient recovers after exhibiting, in mild or more
severe form, either or both of the phases of the preparalytic stage
• The spinal fluid usually contains an increase in cells and protein
• In approximately 1% of patients infected with wild-type poliovirus, signs of
abortive poliomyelitis are present, as are more intense headache, nausea, and
vomiting, as well as soreness and stiffness of the posterior muscles of the neck,
trunk, and limbs
• Fleeting paralysis of the bladder and constipation are frequent
• Approximately two thirds of these children have a short symptom-free
interlude between the 1st phase (minor illness) and the 2nd phase (CNS disease
or major illness)
• Nuchal rigidity and spinal rigidity are the basis for the diagnosis of nonparalytic
poliomyelitis during the 2nd phase
• Physical examination reveals nuchal-spinal signs and changes in superficial and
deep reflexes
• Gentle forward flexion of the occiput and neck elicits nuchal rigidity
• The examiner can demonstrate head drop by placing the hands under the
patient's shoulders and raising the patient's trunk
• Although normally the head follows the plane of the trunk, in poliomyelitis it
often falls backward limply, but this response is not attributable to true paresis
of the neck flexors
• In struggling infants, it may be difficult to distinguish voluntary resistance from
clinically important true nuchal rigidity
• The examiner may place the infant's shoulders flush with the edge of the table,
support the weight of the occiput in the hand, and then flex the head
anteriorly
• True nuchal rigidity persists during this maneuver. When open, the anterior
fontanel may be tense or bulging
• In the early stages the reflexes are normally active and remain so unless
paralysis supervenes
• Changes in reflexes, either increased or decreased, may precede weakness by
12-24 hr
• The superficial reflexes, the cremasteric and abdominal reflexes, and the
reflexes of the spinal and gluteal muscles are usually the first to diminish
• The spinal and gluteal reflexes may disappear before the abdominal and
cremasteric reflexes
• Changes in the deep tendon reflexes generally occur 8-24 hr after the
superficial reflexes are depressed and indicate impending paresis of the
extremities

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• Tendon reflexes are absent with paralysis.
• Sensory defects do not occur in poliomyelitis
PARALYTIC POLIOMYELITIS
• Paralytic poliomyelitis develops in approximately 0.1% of persons infected with
poliovirus, causing 3 clinically recognizable syndromes that represent a
continuum of infection differentiated only by the portions of the CNS most
severely affected
• These are
o Spinal paralytic poliomyelitis
o Bulbar poliomyelitis
o Polio encephalitis.
SPINAL PARALYTIC POLIOMYELITIS

• Occur as the 2nd phase of a biphasic illness, the 1st phase of which corresponds
to abortive poliomyelitis
• The patient then appears to recover and feels better for 2-5 days, after which
severe headache and fever occur with exacerbation of the previous systemic
symptoms
• Severe muscle pain is present, and sensory and motor phenomena
(e.g.,paresthesia, hyperesthesia, fasciculations, and spasms) may develop
• On physical examination the distribution of paralysis is characteristically spotty
• Single muscles, multiple muscles, or groups of muscles may be involved in any
pattern
• Within 1-2 days, asymmetric flaccid paralysis or paresis occurs
• Involvement of 1 leg is most common, followed by involvement of 1 arm
• The proximal areas of the extremities tend to be involved to a greater extent
than the distal areas
• To detect mild muscular weakness, it is often necessary to apply gentle
resistance in opposition to the muscle group being tested
• Examination at this point may reveal nuchal stiffness or rigidity, muscle
tenderness, initially hyperactive deep tendon reflexes followed by absence or
diminution of reflexes, and flaccid paralysis
• In the spinal form, there is weakness of some of the muscles of the neck,
abdomen, trunk, diaphragm, thorax, extremities.
• Sensation is intact; sensory disturbances, if present, suggest a disease other
than poliomyelitis
• The paralytic phase of poliomyelitis is extremely variable; some patients
progress during observation from paresis to paralysis, whereas others recover,
either slowly or rapidly

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• The extent of paresis or paralysis is directly related tothe extent of neuronal
involvement; paralysis occurs if >50% of the neurons supplying the muscles are
destroyed
• The extent of involvement is usually obvious within 2-3 days; only rarely does
progression occur beyond this interval
• Bowel and bladder dysfunction ranging from transient incontinence to paralysis
with constipation and urinary retention often accompany paralysis of the lower
limbs
• The onset and course of paralysis are variable in developing countries
• The biphasic course is rare; typically the disease manifests in a single phase in
which prodromal symptoms and paralysis occur in a continuous fashion
• In developing countries, where a history of intramuscular injections precedes
paralytic poliomyelitis in approximately 50–60% of patients, patients may
present initially with fever and paralysis (provocation paralysis)
• The degree and duration of muscle pain are also variable, ranging from a few
days usually to a week
• Occasionally, spasm and increased muscle tone with a transient increase in
deep tendon reflexes occur in some patients, whereas in most patients, flaccid
paralysis occurs abruptly
• Once the temperature returns to normal, progression of paralytic
manifestations stops.
PRESENTATION (SIGN AND SYMPTOMS)

• Fever, malaise, headache, nausea
• Severe back, neck, and muscle pain _ first evidence of parenchymal
neurological involvement
• Asymmetric flaccid paralysis worsens over hours to days
o Paralysis is usually more severe in proximal muscles
o Ascending paralysis with diaphragmatic involvement → respiratory
failure
• Diminished deep tendon reflexes
• Muscle atrophy
• Hypotonia
• Fasciculations
• Recurrence of the febrile illness with meningeal signs
• Weakness or paralysis develops quickly, and, once begun, it achieves its
maximal severity within 48 hours in most cases

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• The most life-threatening aspect of bulbar polio results from inflammation of
certain nuclear groups of the medullary reticular formation, the so-called vaso-
motor
BULBAR POLIOMYELITIS
• Occur as a clinical entity without apparent involvement of the spinal cord
• Infection is a continuum, and designation of the disease as bulbar implies only
dominance of the clinical manifestations by dysfunctions of the cranial nerves
and medullary centers.
• The clinical findings seen with bulbar poliomyelitis with respiratory difficulty
POLIO-ENCEPHALITIS
• Is a rare form of the disease in which higher centers of the brain are severely
involve
• Seizures, coma, and spastic paralysis with increased reflexes may be observed
• Irritability, disorientation, drowsiness, and coarse tremors are often present
with peripheral or cranial nerve paralysis that coexists
• Hypoxia and hypercapnia caused by inadequate ventilation due to respiratory
insufficiency may produce disorientation without true encephalitis
PARALYTIC POLIOMYELITIS WITH VENTILATORY INSUFFICIENCY

• Results from several components acting together to produce ventilatory
insufficiency resulting in hypoxia and hypercapnia
• Because respiratory insufficiency may develop rapidly, close continued clinical
evaluation is essential
• The cervical and thoracic spinal cord segments are chiefly affected
• Bulbospinal poliomyelitis with respiratory insufficiency affects the respiratory
muscles and results in coexisting bulbar paralysis
• The clinical findings associated with involvement of the respiratory muscles
include
o anxious expression
o inability to speak without frequent pauses, resulting in short, jerky,
breathless sentences
o increased respiratory rate
o movement of the ala nasi and of the accessory muscles of respiration
o inability to cough or sniff with full depth;
DIAGNOSIS

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• The World Health Organization (WHO) recommends that the laboratory
diagnosis of poliomyelitis be confirmed by isolation and identification of
poliovirus in the stool, with specific identification of wild-type and vaccine-
type strains
• In suspected cases of acute flaccid paralysis, 2 stool specimens should be
collected 24-48 hr. apart as soon as possible after the diagnosis of poliomyelitis
is suspected
• Poliovirus concentrations are high in the stool in the 1st wk after the onset of
paralysis, which is the optimal time for collection of stool specimen
• Polioviruses may be isolated from 80–90% of specimens from acutely ill
patients, whereas <20% of specimens from such patients may yield virus within
3-4 wk after onset of paralysis
• Because most children with spinal or bulbospinal poliomyelitis have
constipation, rectal straws may be used to obtain specimens; ideally a
minimum of 8-10 g of stool should be collected
• The CSF is often normal during the minor illness and typically contains a
pleocytosis with 20-300 cells/µL with CNS involvement
• The cells in the CSF may be polymorphonuclear early during the course of the
disease but shift to mononuclear cells soon afterward
• By the 2nd wk of major illness, the CSF cell count falls to near-normal values
• In contrast, the CSF protein content is normal or only slightly elevated at the
outset of CNS disease but usually rises to 50-100 mg/dL by the 2nd wk of illness
• In polioencephalitis, the CSF may remain normal or show minor changes
• Serologic testing demonstrates seroconversion or a 4-fold or greater increase in
antibody titers from the acute phase of illness to 3-6 wk late
• The blood picture is usually normal, although a mild leucopenia may be found
in the early stage of the illness
• The best diagnostic test is PCR amplification of poliovirus RNA from CSF
• Poliovirus RNA can also be isolated from stool or oropharynx (throat swab).
• CSF also will show:
o High protein levels
o Pleocytosis with either neutrophils (early infection) or lymphocytes (late
infection
o Poliovirus may be detected by cell culture followed by identifcation
using plaque reduction neutralization tests or PCR.
• During the first 3–10 days of the illness, poliovirus can also be detected from
oropharyngeal specimens
• Poliovirus is rarely detected in the blood or cerebrospinal fluid

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COMPLICATIONS
• Acute gastric dilation
• single or multiple superficial intestinal erosions; perforation is rare
• In the later stages, because of immobilization, hypertension may occur along
with hypercalcemia from skeletal decalcification, nephrocalcinosis, and
vascular lesion
• Cardiac irregularities
• Acute pulmonary edema
TREATMENT
• There is no specific antiviral treatment for poliomyelitis
• The management is supportive and aimed at limiting progression of disease,
preventing ensuing skeletal deformities, and preparing the child and family for
the prolonged treatment required and for permanent disability if this seems
likely
• Ranging from pain and fever relief to intubation and mechanical ventilation for
patients with respiratory insufficiency
• All intramuscular injections and surgical procedures are contraindicated during
the acute phase of the illness, especially in the 1st wk of illness, because they
might result in progression of disease.
ABORTIVE POLIOMYELITIS
• Supportive treatment with analgesics, sedatives, an attractive diet, and bed
rest until the child's temperature is normal for several days is usually
sufficient.
• Avoidance of exertion for the ensuing 2 wk is desirable, and careful neurologic
and musculoskeletal examinations should be performed 2 mo later to detect
any minor involvement.
NONPARALYTIC POLIOMYELITIS
• Treatment for the nonparalytic form is similar to that for the abortive form; in
particular, relief is indicated for the discomfort of muscle tightness and spasm
of the neck, trunk, and extremities.
• Analgesics are more effective when they are combined with the application of
hot packs for 15 30 min every 2-4 hr.
• Hot tub baths are sometimes useful.
• A firm bed is desirable and can be improvised at home by placing table leaves
or a sheet of plywood beneath the mattress.
• A footboard or splint should be used to keep the feet at a right angle to the
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• Because muscular discomfort and spasm may continue for some wk, even in the
nonparalytic form, hot packs and gentle physical therapy may be necessary.
PARALYTIC POLIOMYELITIS
• Hospitalization with complete physical rest in a calm atmosphere for the 1st 2-
3 wk
• Suitable body alignment is necessary for comfort and to avoid excessive
skeletal deformity
• A neutral position with the feet at right angles to the legs, the knees slightly
flexed, and the hips and spine straight is achieved by use of boards, sandbags,
and, occasionally, light splint shells
• The position should be changed every 3-6 hr
• Moist hot packs may relieve muscle pain and spasm
• Opiates and sedatives are permissible only if no impairment of ventilation is
present or impending
• Constipation is common, and fecal impaction should be prevented
• When bladder paralysis occurs, a parasympathetic stimulant such as
bethanechol may induce voiding in 15-30 min
• If bethanechol fails, manual compression of the bladder and the psychologic
effect of running water should be tried
• If catheterization must be performed, care must be taken to prevent urinary
tract infections
• An appealing diet and a relatively high fluid intake should be started at once
unless the patient is vomiting
• The management of pure bulbar poliomyelitis consists of maintaining the
airway and avoiding all risk of inhalation of saliva, food, and vomitus
• Gravity drainage of accumulated secretions is favored by using the head-low
(foot of bed elevated 20-25 degrees) prone position with the face to 1 side
• Aspirators with rigid or semirigid tips are preferred for direct oral and
pharyngeal aspiration, and soft, flexible catheters may be used for
nasopharyngeal aspiration
• Fluid and electrolyte equilibrium is best maintained by intravenous infusion
because tube or oral feeding in the 1st few days may incite vomiting
• In addition to close observation for respiratory insufficiency, the blood pressure
should be measured at least twice daily because hypertension is not
uncommon and occasionally leads to hypertensive encephalopathy
• Patients with pure bulbar poliomyelitis may require tracheostomy because of
vocal cord paralysis or constriction of th hypopharynx
• Impaired ventilation must be recognized early; mounting anxiety, restlessness,
and fatigue are early indications for preemptive intervention.

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PREVENTION
• Vaccination is the only effective method of preventing poliomyelitis
• Immunization
o inactivated poliovirus vaccine (IPV)
o 4 doses of IPV, at 2, 4, and 6–18 months; booster dose at 4–6 years
o Breastfeeding is not a contraindication to administration of polio vaccine
to an infant or mother
• Since physical activity in the preparalytic stage increases the risk of severe
paralysis during the acute illness, bed rest is indicated
• Relief of muscle pain can be accomplished by periodic application of hot moist
packs
• Active and passive movements are indicated as soon as the pain has
disappeared.
• Respiratory failure is treated with respiratory assistance
• All residents and long-term visitor (i.e., >4 weeks) of all ages receive a dose of
bOPV or IPV between 4 wk and 12mo before traveling
• Avoid tonsillectomy and intramuscular injections
• Decreased physical activity, exercise, and fatigue during the early phase of
illness.
PROGNOSIS
• The outcome of inapparent, abortive poliomyelitis and aseptic meningitis
syndromes is uniformly good, with death being exceedingly rare and with no
long-term sequelae
• The outcome of paralytic disease is determined primarily by degree and
severity of CNS involvement
• In severe bulbar poliomyelitis, the mortality rate may be as high as 60%,
whereas in less-severe bulbar involvement and/or spinal poliomyelitis, the
mortality rate varies from 5% to 10%
• Maximum paralysis usually occurs 2-3 days after the onset of the paralytic
phase of the illness, with stabilization followed by gradual return of muscle
function
• The recovery phase lasts usually about 6 mo, beyond which persisting paralysis
is permanent
• The return of strength and reflexes is slow and may continue to improve for as
long as 18 mo after the acute disease
• Mortality and the degree of disability are greater after the age of puberty
• Pregnancy is associated with an increased risk for paralytic disease

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• After an interval of 30-40 yr, as many as 30–40% of persons who survived
paralytic poliomyelitis in childhood may experience muscle pain and
exacerbation of existing weakness or development of new weakness or paralysis
• This entity, referred to as postpolio syndrome
• Respiratory failure is responsible for most of the deaths
• Recovery from paralysis usually begins within 1st days or one week
• The rate of recovery is most rapid during the first three months
• Muscles that remain completely paralysed after an interval of three months
usually do not show return of function
• Weakened muscles continue to improve for a period up to one year
• In 1988 the World Health Assembly resolved to eradicate poliomyelitis globally
by 2000, and remarkable progress had been made toward reaching this targe
• To achieve this goal, the WHO used 4 basic strategies: routine immunization,
National Immunization Days, acute flaccid paralysis surveillance, and mop-up
immunization
• This strategy has resulted in a >99% decline in poliomyelitis cases
• Atrophy of the limb, failure of growth, and deformity are common and are
especially evident in the growing child
GUILLAIN-BARRE SYNDROME (GBS)

• Guillain-Barre syndrome (GBS) is an autoimmune disorder that is thought to be
a post infectious polyneuropathy, involving mainly motor but also sensory and
sometimes autonomic nerves
o Autoimmune antibody attacks the peripheral nerve roots
o About ⅔ of GBS patients experience symptoms of an upper respiratory or
gastrointestinal tract infection 1–4 weeks prior to onset of GBS
o The causal connection between pathogens and GBS is still undetermined
o Typically, an attack on the myelin sheath
• Associated pathogens
o Campylobacter jejuni: campylobacter enteritis(diarrhea) is the most
common disease associated with GBS
o Viral respiratory illness
o Cytomegalovirus: most common virus associated with GBS
o HIV
o Mycoplasma pneumoniae
• Vaccination (esp. influenza vaccine)
EPIDEMIOLOGY
• Risk of occurrence is similar throughout the world, in all climates, and among
all races

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• Individuals older than 40 years have a steadily increasing risk, peaking at age
70–80 years, compared with younger individuals
• Children are at lower risk than adults, with incidence ranging from 0.5–1.5
cases per 100,000 children
• One should keep GBS in the differential diagnosis when a floppy baby has no
other evidence of hypotonia
• In the post-polio era, Guillain-Barré syndrome (GBS) is the most common cause
of acute flaccid paralysis in healthy infants and children
• GBS occurs world-wide with an annual incidence of 0.34 to 1.34 cases per
100,000 persons aged 18 years or less
• While all age groups are affected, the incidence is lower in children than in
adults
• The incidence increases by approximately 20 percent with every 10-year
increase in age beyond the first decade of life
• GBS occurs rarely in children younger than two years of age, but can occur
even in infants
• Affects peoples of all ages, commonly from 3-12 years old
• Males are affected approximately 1.5 times more often than females in all age
groups
RISK FACTORS
• Consumption of undercooked poultry
• Unpasteurized milk
• Contaminated water
• Administration of vaccines against rabies, influenza, and conjugated
meningococcal vaccine (serogroup C)
• Infectious precursors of GBS include mononucleosis, Lyme disease,
cytomegalovirus
ETIOLOGY
• Guillain-Barré syndrome is an autoimmune-mediated disease with
environmental triggers (eg, pathogenic or stressful exposures)
• Several infections (eg, Epstein-Barr virus, cytomegalovirus, hepatitis, varicella,
Mycoplasma pneumoniae, C jejuni)
• Immunizations have also been known to precede or to be associated with the
illness
• Occasionally, surgery has been noted to be a precipitating factor
PATHOPHYSIOLOGY

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• Postinfectious autoimmune reaction that generates cross-reactive antibodies
(molecular mimicry)
• Infection triggers humoral response → formation of autoantibodies against
gangliosides (e.g. GM1) or other unknown antigens of peripheral Schwann cells
→ immune-mediated segmental demyelination → axonal degeneration of
motor and sensory fibers in peripheral and cranial nerves (CN III–XII). The end
result is an acute polyneuropathy. This immune response can be directed
towards the myelin or the axon of periphera nerve.
• Approximately two-thirds of patients give a history of an antecedent
respiratory tract or gastrointestinal infection
• Campylobacter infection is the most commonly identified precipitant of GBS
and can be demonstrated in as many as 30 percent of cases
• A small percentage of patients develop GBS after another triggering event such
as immunization, surgery, trauma, or bone-marrow transplantation
SUBTYPES
• GBS peripheral nerve damage can be classified histopathologically into 2 main
types: demyelinating forms and axonal-degenerating form.
• In the demyelinating form, segmental demyelination of peripheral nerves is
thought to be immune mediated and both humoral and cell-mediated immune
mechanisms have been implicated
• GBS with axonal degeneration may occur without demyelination or
inflammation
• In 1995, GBS was subdivided into 4 distinct forms based on histopathological
and neurophysiological basis:
• Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor
axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy
(AMSAN), and Miller-Fisher syndrome (MFS)
• The acute motor axonal neuropathy (AMAN) subtype of GBS is a purely motor
disorder that is more prevalent amongst pediatric age groups
• One third of patients with AMAN may actually be hyperreflexic
• Hyperreflexia is significantly associated with the presence of anti-GM1
antibodies
CLINICAL FEATURES
INITIAL SYMPTOMS
• Onset of symptoms is within 2–4 weeks of an illness or immunization
• Back and limb pain

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• Onset of weakness is preceded by approx. 10 days non-specific GIT, respiratory
tract and systemic infections
• The maximal severity of weakness is reached by 4 wk after onset
• Paresthesias affecting distal extremities
ADVANCED SYMPTOMS
• Ascending paralysis
o Bilateral flaccid paralysis
o Spreads from the lower to the upper limbs in a “stocking glove”
distribution
o Weakness is symmetric
• Landry paralysis: involvement of the respiratory muscles → respiratory failure
• Muscle reflexes
o Reduced or absent
o Commonly beginning in the lower limbs
• Paresthesia
o Peripheral, symmetric
o Usually affecting hands and feet A cranial nerve variant of
• Neuropathic pain: develops in about ⅔ of affected Guillain-Barré syndrome
individuals called the Miller Fisher
• Autonomic dysfunction is dangerous variant manifests with triad
ataxia, partial
o Cardiovascular
ophthalmoplegia, and
o Arrhythmia areflexia. Weakness
o Blood pressure dysregulation: ↑ or ↓ commonly begins in cranial
o Voiding dysfunction nerve
o Intestinal dysfunction
• Cranial nerve involvement
o Facial diplegia due to frequent bilateral facial nerve involvement
• Gastroparesis
• Vocal cord paralysis: dyspnea or a hoarse voice
• Bulbar palsy: dysphonia, dysphagia , and lost Bulbar reflexes
• Respiratory muscles
DIAGNOSTICS
CEREBROSPINAL FLUID: ALBUMINOCYTOLOGIC DISSOCIATION

• ↑ Protein levels and normal white blood cell count in cerebrospinal fluid
• Typically, the LP findings are suggestive of demyelination (i.e increased
protein >45 mg/dL within 3 weeks of onset) without evidence of active
infection (lack of CSF pleocytosis)

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• The CSF findings may be normal within the first 48 hours of symptoms, and
occasionally the protein may not rise for a week
• Usually by 10 days of symptoms, elevated CSF protein findings will be most
prominent
• Most patients have fewer than 10 leukocytes per milliliter, but occasionally a
mild elevation (i.e 10-50 cells/mL) is seen
• Greater than 50 mononuclear cells/mL of CSF makes the diagnosis of GBS
doubtful
ELECTRONEUROGRAPHY
• ↓ Nerve conduction velocity (NCV) due to demyelination
SERUM ANTI-GANGLIOSIDE ANTIBODIES

• In adults with GBS, serum ganglioside antibodies directed against GM1, GM1b,
GD1a, and GalNAc-GDIa have been associated with Campylobacter jejuni
infection, acute motor axonal neuropathy, a more severe course, and more
residual neurologic deficits
MRI
• Enhancement of nerve roots
• Nerve conduction studies
TREATMENT
• Supportive:
o Hospitalization and
o Cardiac monitoring
o Respiratory support,
o Nasogastric feeding,
o care of bladder (catheterization & neostigmine, physiotherapy
• Specific: IVIG is effective, slows progression, speeds recovery
▪ IVIG: 0.4gm/kg/day for 5 days.
o Alternatives: Plasmapharesis is equally effective as IVIG.
o Combined IVIG and interferon is effective in some patients
o Steroids are not effective
o Exchange Transfusion
PROGNOSIS
• Spontaneous recovery begins within 2-3 wk but can take 12 months
• Therapy with IVIG hastens recovery but does not alter the long-term outcome
• As many as 60% become nonambulant during their illness, but most eventually
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• 95 % make full recovery
• The tendon reflexes are usually the last function to recover
• Improvement usually follows a gradient opposite the direction of involvement,
with bulbar function recovering first and lower extremity weakness resolving
last
• Bulbar and respiratory muscle involvement can lead to death if the syndrome is
not recognized and treated
• Fatigue is the most common long-term residuum of GBS
• Relapses occur in about 4% of children with GBS and are generally responsive to
immunomodulatory treatment.
TRANSVERSE MYELITIS
• Transverse myelitis, an acute postinfectious demyelinating disorder of the
spinal cord
• Inflammation of spinal cord leads to lose of myelin coating from damage to
nerve fibers so that result in decreased electrical conductivity in the CNS
• Trauma and tumors (neuroblastoma, lymphoma, sarcoma) compressing the
spinal cord necessitate immediate neurosurgical management to preserve vital
function
RISK FACTORS
• Bacterial Infections -mycoplasma pneumonia, Lyme disease
• Viral Infections - Herpes simplex, Herpes zoster, Cytomegalovirus, Epstein-Barr
virus, HIV/AIDS
• Vaccinations rarely e.g. against hepatitis B, measles-mumps-rubella,
diphtheria-tetanus- pertussis
• Multiple sclerosis
• Vascular etiology
CLINICAL FEATURES
• Weakness and numbness of the limbs
• Symptoms of an epidural abscess include fever, spinal pain, and neurological
deficits
• Deficits in sensation and motor skills
• Dysfunctional sphincter activities
• Impaired function of the bladder and bowel
• Progresses rapidly over hours to days
• Acute symmetric paralysis of the lower limb
• Autonomic signs of hypothermia in the affected limbs are common

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INVESTIGATIONS
• CSF is usually normal
• MRI- Lesions of the spinal cord
• CT scan
• Lumbar puncture after imaging
TREATMENT
• Treatment options also vary according to the underlying caus
• Treated with high-dose steroids
• In some cases, plasmapheresis
MYASTHENIA GRAVIS
• Myasthenia gravis is an autoimmune disease
• Most commonly, antibodies block the acetylcholine receptors (AChR) at the
neuromuscular junction, decreasing the number of effective receptors, which
results in rapid fatigability of striated muscle
• The three childhood varieties are juvenile myasthenia gravis in late infancy
and childhood, transient neonatal myasthenia, and congenital myasthenia.
EPIDEMIOLOGY
• The age of onset for immune-mediated MG ranges anywhere from 11 mo to 17
yr of age
• In the prepubertal age-groups, the female: male ratio is about 1.5: 1
• In the post pubertal age-groups, the female: male ratio is about 1:1
RISK FACTORS
• Intercurrent infection
• Surgery
• Organophosphate chemicals
• Emotional stress
• Familial history
• Hypothyroidism, usually Hashimoto thyroiditis
• Antibiotics: aminoglycosides
JUVENILE MYASTHENIA
• Variable ptosis
• Diplopia
• Ophthalmoplegia
• Facial weakness

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• Dysphagia
• Poor head control and extremity weakness
• Rapid fatigue of muscles distinguishes myasthenia from other neuromuscular
disorders, with progressive worsening over the day
TRANSIENT NEONATAL MYASTHENIA GRAVIS

• Develops in the first hours to days after birth in neonates born to mothers with
myasthenia gravis
• Almost all infants born from mothers with myasthenia have maternal anti-AChR
antibodies, but only 10-20% will develop signs
• Signs include ptosis, ophthalmoplegia, weak facial movements, poor feeding,
hypotonia, respiratory difficulty, and variable extremity weakness
• Neonates with transient myasthenia gravis require cholinesterase inhibitors and
supportive care for a few days to weeks until the weakness remits
CONGENITAL MYASTHENIA GRAVIS

• The congenital myasthenic syndromes (CMS) are due to gene mutations in the
components of the neuromuscular junction
• They typically present in infancy with hypotonia, ophthalmoparesis, facial
diplegia and extremity weakness
• Respiratory function and feeding may be compromised
DIAGNOSTIC STUDIES
• Autoimmune myasthenia is most commonly diagnosed through the combination
of clinical symptoms and antibody testing
• The majority of individuals have antibodies to the AChR
• Nerve conduction studies classically reveal an electrodecrement with 3-Hz
repetitive stimulation
• Nerve biopsy
COMPLICATIONS
• Risk of aspiration
TREATMENT
• Administration of a cholinesterase inhibitor (edrophonium chloride) can result
in transient improvement in strength, particularly of ptosis, and thus can
additionally be use for diagnostic verification
CEREBRAL PALSY
• Most common motor disability in children

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• is a heterogenous group of disorders affecting the muscle tone and the
development of movement and posture.
• CP results from a non-progressive damage to the brain in utero or during
infantile development up to the age of 3 years.
•
ETIOLOGY
Idiopathic (most cases)
RISK FACTORS
• Preterm birth and low birth weight (most important risk factors)
• TORCH infection
• Perinatal asphyxia
• Intracranial hemorrhage
CLASSIFICATION
• Spastic cerebral palsy: spastic paresis of one or more limbs (75% of cases)
• Non-spastic cerebral palsy:
o Dyskinetic: abnormal involuntary movements (choreoathetoid, dystonic
o Ataxic: intention tremor, lack of balance and coordination
SUBTYPES
SPASTIC HEMIPLEGIA
• Hand preference occur at early age
• Walking is delayed, gait is circumdactive
SPASTIC DIPLEGIA
• Crawling is commando like rather than four limbed crawling
• When suspended from axilla the lower limbs take scissoring posture
SPASTIC QUADRIPLEGIA
• The most severe type
• High incidence of associations e.g. (mental retardation, seizures,.....)
Spastic monoplegia
Spastic paraplegia
Ataxic cerebral palsy
CLINICAL FEATURES
• All types
o Patients do not reach certain milestones
o Intellectual disability
o Joint contractures

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• Spastic type:
o ↑ Muscle tone in one or more limbs
o ↑ DTRs
o Persistence of primitive reflexes
o Scissor gait
• Non-spastic type:
o Dysarthria and dysphagia
TREATMENT
NONPHARMACOLOGICAL MANAGEMENT
• Physiotherapy
• Occupational therapy
• Speech therapy
• Psychosocial support
• Care of feeding & defecation
• Assist walking: Walkers, standing frames, motorized wheel chair
• Treat epilepsy
• Rehabilitation according to the degree of mental retardation
PHARMACOLOGICAL MANAGEMENT
• Antispasmodics; baclofen
• Anticholinergics for rigidity and sialorrhea
RABIES
EPIDEMIOLOGY
• Rabies is present on all continents except Antarctica
• Rabies predominantly afflicts underaged, poor, and geographically isolated
populations
• True animal reservoirs that maintain the presence of rabies virus in the
population are limited to terrestrial carnivores and bats.
• Worldwide, transmission from dog’s accounts for > 90% of human cases
ETIOLOGY
PATHOGEN
• Rhabdoviridae
• Rhabdoviruses are rod or bullet shaped
• Genus: Lyssavirus
• ssRNA
TRANSMISSION

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• Most common animal reservoir worldwide: dogs
• Most common animal reservoirs in the US: bats, raccoons, skunks, and foxes
• Spread through saliva of rabid animal after bite injury
• Via aerosols (e.g., bat caves); rare
PATHOPHYSIOLOGY
• Rabies virus binds the ACh receptor of peripheral nerves in the bite wound →
migrates retrogradely along the axonal microtubules (using motor protein
dynein) → enters the CNS → infects the brain
CLINICAL FEATURES
• General
o Incubation period: 4–12 weeks average
o Prodromal symptoms
▪ fever, malaise
• Encephalitic rabies (most common type)
• Hydrophobia: Rabies patients experience involuntary, painful pharyngeal
muscle spasms when trying to drink; later on in the disease, the sight of water
alone may provoke nausea or vomiting.
• CNS symptoms
o Anxiety, agitation, and combativeness alternating with calm periods
o Confusion, Photophobia, Seizures
o hypersalivation, hyperhidrosis
o Coma and death within days to weeks of the development of
neurological symptoms
• Paralytic rabies (< 20% of cases)
o Flaccid paralysis
o Paraplegia
o Respiratory failure and death
• The pathognomonic feature of rabies is hydrophobia due to pharyngeal muscle
spasm. This may present along with agitation, strange behavior, mental status
changes, and possibly foaming at the mouth.
DIAGNOSTICS
• In the case of a bite injury from a suspicious animal
• Postmortem diagnosis
• Postmortem brain tissue autopsy
o Negri bodies (eosinophilic cytoplasmic inclusion bodies typically found in
the cerebellum and hippocampus)
TREATMENT
RABIES RISK ASSESSMENT

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• Administer PEP
• Bite by a known wild reservoir for rabies (e.g., bats, raccoons, skunks, foxes),
if the animal is not available for testing or if the test comes back positive
• Observe/test animal and possibly administer PEP
• Attack by an unvaccinated domestic carnivore without symptoms of rabies
(e.g., dog) → observe animal for a 10-day period
RABIES POST-EXPOSURE PROPHYLAXIS
• Cleaning and debridement, as with all bite wounds
• Nonimmunized patient: postexposure prophylaxis (passive-active immunization)
• Rabies immunoglobulin is given into the site of the wound by injection (passive
immunization)
• PLUS inactivated rabies vaccine is given IM; (active immunization)
SYMPTOMATIC ENCEPHALITIC OR PARALYTIC RABIES
• Palliative treatment (pain management and sedation)
PREVENTION
VACCINATION (PREEXPOSURE PROPHYLAXIS)
• Vaccine: inactivated (killed) vaccine
o Indications
▪ People with frequent occupational contact with potentially rabid
animals
▪ Travelers to regions in which rabies is widespread
INFANTS BOTULISM
PATHOGEN
• Clostridium botulinum
o Gram-positive rod
o Spore-forming
o Obligate anaerobe
o Produces heat-labile neurotoxin
PATHOPHYSIOLOGY
• Botulinum toxin: protease that cleaves SNARE proteins and prevents fusion of
transmitter-containing vesicles with the presynaptic membrane → inhibition of
acetylcholine release from the presynaptic axon terminals
CLINICAL FEATURES
• Neurological symptoms
o Descending paralysis
o Peripheral flaccid muscle paralysis that descends caudally

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o Pupils: accommodation paralysis, mydriasis, diplopia
o Pharynx: dysarthria, dysphagia
o Floppy baby syndrome in infants
• Gastrointestinal symptoms
o Gastrointestinal discomfort, nausea, and vomiting, later followed by
constipation
o 4 D's of botulism: Dysarthria, Diplopia, Dysphagia, and Dyspnea.
TREATMENT
• Therapeutic/cosmetic botulinum toxin use
o Local injection of botulinum toxin A (Botox) can be used to treat various
conditions, including:
▪ Muscle spasms
▪ Focal dystonia
▪ Hyperhidrosis
• Also used to reduce facial wrinkles
FOODBORNE BOTULISM
ETIOLOGY
• Ingestion of preformed botulinum toxin via contaminated foods
• The anaerobic spores survive in poorly pasteurized canned foods (e.g.,
vegetables with soil contact, meat, home-fermented tofu)
o Germination of the spores produces dangerous toxins (botulinum toxins =
enterotoxins A-F) and gas → bulging cans
• Specific treatment
o Horse-derived heptavalent botulism antitoxin
INFANT BOTULISM
• Etiology: ingestion of spores
o Spores may be present in honey, juice, and contaminated soil.
o Germination of the spores in intestinal tract → synthesis of botulinum
toxin
• Clinical features: Infants may present with infantile hypotonia
o Ptosis
o Floppy movements
o General weakness
o Poor feeding (weak sucking)
• Differential diagnosis: floppy infant syndrome

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Table 120 Differential diagnosis of floppy infant syndrome
Differential diagnosis of floppy infant syndrome

Condition Etiology Clinical features Management
Infant botulism Spores of Clostridium Constipation (can be a Supportive care
botulinum (found in soil presenting sign) IV human botulism immune
or contaminated honey) Descending palsy globulin
(usually starts with
ptosis)
Hypotonia
Poor feeding, weak
sucking
Respiratory
compromise
Neonatal Transfer of Hypotonia Monitoring in neonatal ICU
myasthenia acetylcholine receptor Poor sucking Respiratory support
gravis antibodies from a Respiratory distress Acetylcholinesterase
mother with myasthenia inhibitors
gravis In severe cases:
plasmapheresis, IV IgG
Spinal muscular Defect in the SMN1 • Symmetrical LMN • Supportive care
atrophy type 1 gene on chromosome 5q palsy (more • Nusinersen
causing abnormal SMN prominent in lower • Risdiplam
complex formation with extremities) • Onasemnogene
subsequent death of • Atrophy and abeparvovec
anterior motor neurons fasciculations
throughout the body
(typically prominent
in the tongue)
• Weak cry and cough
Myotonic CTG trinucleotide • Hypotonia, • Supportive care
dystrophy type 1 repeat expansion in the especially affecting
DMPK gene the face
Autosomal dominant • Associated with
(almost exclusively cataracts,
maternal inheritance arrhythmias, and
pattern) intellectual
disability
• For adult
presentation
Trisomy 21 • Meiotic • Characteristic facies • Supportive care
nondisjunction (hypertelorism, • Management of
resulting in trisomy epicanthal folds, gastrointestinal and
21 broad and flat nasal cardiovascular
anomalies

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• Translocation bridge, small
trisomy 21 mouth)
• Mitotic • Hypotonia
nondisjunction • Congenital heart
resulting in trisomy defects
21 • Duodenal atresia
• Delayed intellectual
and motor
development
DIFFERENTIAL DIAGNOSES
• Guillain-Barré syndrome
• Myasthenia gravis
• Lambert-Eaton syndrome
• Tick paralysis ptosis, and thus can additionally be used for

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CHAPTER 13 - GENTETIC DISORDERS

AND DYSMORPHIC FEATURES
1. Chromosomal disorders
a. Down Syndrome
b. Edward Syndrome
c. Turner syndrome
2. Neural Tube defects
3. Hydrocephalus
4. Cleft Lip and palate

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13.1. CHROMOSOMAL DISORDERS

DYSMORPHIC FEATURE
• A dysmorphic feature is a difference of body structure.
o It can be an isolated finding in an otherwise normal individual, or it can
be related to a congenital disorder, genetic syndrome, or birth defect.
o One of the key challenges in identifying and describing dysmorphic
features is the use and understanding of specific terms between
different individuals.
o Clinical geneticists and pediatricians are usually those most closely
involved with the identification and description of dysmorphic features,
as most are apparent during childhood.
o Dysmorphic features are invariably present from birth, although some
are not immediately apparent upon visual inspection.
• Common Chromosomal Disorders associated with Dysmorphic Features
o Down Syndrome
o Edward Syndrome
o Turner Syndrome
DOWN SYNDROME
• Trisomy 21 is the most common and best-known chromosomal disorder in
humans and the most common cause of intellectual disability.
EPIDEMIOLOGY AND RISK FACTOR
• Incidence;(1:733) prevalence are increasing b/c of increase in life span in the
last decade.
• Age-related demographics; occurrence is strongly dependent on maternal age.
o 15-29 years-1case in 1500 live births
o 30-34 years-1 case in 800 live births
o >45 years-1 case in 50 live births
• Sex-related demographics; M>F (1.15:1)
NB:50% of female patients with trisomy 21 are fertile and these females have up to
50% chance of having a live child who also has trisomy 21. On the other hand, men
with down syndrome are usually infertile, except for those with mosaicism.
• Race-related demographics; found in all race (African American patients live
shorter life spans white patients)
TYPES OF DOWN SYNDROME

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• Down syndrome is caused by the following 3 cytogenic variants;
1. Three full copies of chromosome 21 (trisomy 21)
o Prevalence; 95 %
o Origin; maternal non disjunction, with meiosis I in 97% and the rest are
paternal
2. Chromosomal translocation that results in 3 copies of the critical region for
down syndrome
o Prevalence ;4%
o NB; Carries high recurrence rate relative to other form which is 100% for
translocation 21;21, other t (15;21) have a 5-7% recurrence.
o The majority of translocations in Down syndrome are fusions at the
centromere between chromosomes 13, 14, 15, 21, and 22 known as
Robertsonian translocations.
o The translocations can be de novo or inherited.
o It is not possible to distinguish the phenotypes of persons with full
trisomy 21 and those with a translocation.
3. Mosaicism (with some cells having 46 chromosomes)
o Prevalence;1%
o Patients who are mosaic tend to have a milder phenotype.
HISTORY
• When recording the history from the parents of a child with Down syndrome,
the clinician should include the following;
o Parental concern about
▪ hearing, vision, developmental delay, respiratory infections,
and other problems.
o Vomiting
▪ secondary to GI tract blockage by duodenal web or atresia
o Absence of stools secondary to Hirschsprung disease
o Diaphoresis while feeding, arrhythmia, fainting episodes, palpitations,
or chest pain secondary to heart lesion
o Symptoms of sleep apnea,
▪ including snoring, restlessness during sleep, difficulty awaking,
daytime somnolence, behavioral changes, and school problems
(because of Macroglossia)
o Symptoms Of Atlantoaxial Instability – may cause vague neck pain,
occipital headache, or occasionally intermittent (and potentially fatal)
cervical spinal cord compression.
▪ Easy fatigability,

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▪ limited neck mobility ▪ hyperreflexia,
or head tilt, ▪ clonus,
▪ torticollis, ▪ extensor-plantar reflex,
▪ difficulty walking, ▪ loss of upper-body strength,
▪ change in gait ▪ abnormal neurologic reflexes,
pattern, ▪ change in bowel and bladder
▪ loss of motor skills, function,
▪ incoordination, ▪ Increased muscle tone in the
▪ clumsiness, legs, and changes in sensation
▪ sensory deficits, in the hands and feet
▪ spasticity,
o Delay in cognitive abilities, motor development, language development
(specifically expressive skills), and social competence
• Assess Feeding history to ensure adequate caloric intake
• Prenatal diagnosis of Down syndrome
• Maternal and paternal age (RF)
• Family history of similar illness b/c of recurrence
• In rare cases, the symptoms progress to paraplegia, hemiplegia, quadriplegia.
DYSMORPHIC FEATURES
• Up slanting palpebral fissures,
• epicanthic folds, and
• brachycephaly are nearly universal features of DS.
• The other dysmorphic features of DS are each Figure 103 Brushfield spots are visible between the
inner and outer circles of the iris.
present in (47 to 82 %) of cases.
• These features predominantly affect the head and neck and
the extremities.
HEAD AND NECK;

• Brushfield spots
• Up slanting palpebral fissures
• Epicanthic folds
• Flat facial profile/flat nasal bridge
• Folded or dysplastic ears
• Low-set small ears
• Brachycephaly
• Open mouth
Figure 104 Facial features of Down
• Protruding tongue syndrome

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• Furrowed tongue
• Short neck
• Excessive skin at nape of the neck
• Narrow palate
• Abnormal teeth
EXTREMITIES
Figure 105 Sandal gap
• Short broad hands
• Incurved fifth finger with hypoplastic mid phalanx
• Transverse palmar crease
• Space between the first and second toes (Sandal Gap)
• Hyper flexibility of joints
CARDIOVASULAR SYSTEM
• Endocardial Cushing defect
• Ventricular septal defect
Figure 106 Single transverse
• Atrial septal defect palmar crease
• Patent ductus arteriosus
• Aberrant subclavian artery
• Pulmonary hypertension
SKIN
• Cutis marmorata
NEONATAL FEATURES
• Ten of the characteristic dysmorphic features are common in Figure 107 Cutis marmorata
newborns with DS and are usually recognized soon after birth.
• These 10 criteria are called HILL’S CRITERIA used to diagnosis down syndrome
in the absence of prenatal diagnosis.
• In the presence of 8 criteria we can diagnosis a full-blown down syndrome
o Flat facial profile o Transverse palmar
o Slanted palpebral fissures (Simian) crease
o small, dysplastic ears o Excessive skin at nape of
o Hypotonia the neck
o Poor Moro reflex o Hyperflexibility of joints
o Dysplasia of mid-phalanx o Dysplasia of pelvis
of fifth finger
COMPLICATIONS

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• Complications of Down syndrome involve almost every organ system of the
body
HEENT
• Congenital or acquired hearing loss
• Serous otitis media
• Refractive errors (myopia)
• Congenital or acquired cataracts
• Nystagmus
• Strabismus
• Glaucoma
• Blocked tear duct
• Sinusitis and nasopharyngitis may occur secondary to narrow nasal passages and
sinuses.
CARDIOPULMONARY
• Cardiovascular complications are important in Down syndrome.
o Acquired mitral, tricuspid, or aortic valve regurgitation
o Endocarditis
o pulmonary arterial hypertension
o mitral valve prolapses
o Obstructive sleep apnea
▪ econdary to enlarged tonsils or to other causes of upper airway
obstruction.
GASTROINTESTINAL
• Celiac disease
• Gastroesophageal reflux
• Infants with oral-motor difficulties may present with choking and gagging on
feedings,
• Dysphagia may affect children as well as adults.
• Chronic constipation.
• Delayed tooth eruption
MUSCULOSKELETAL
• Atlantoaxial instability defined as increased mobility of the cervical spine at
the level of the first and second vertebrae, can lead to subluxation of the
cervical spine

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• Hip dysplasia
• Slipped capital femoral epiphyses
• Avascular hip necrosis
• Recurrent joint dislocations (shoulder, knee, elbow, thumb)
ENDOCRINE
• Congenital or acquired hypothyroidism
• Diabetes mellitus
• Infertility
• Obesity
• Hyperthyroidism
HEMATOLOGIC
• Transient myeloproliferative syndrome
• Acute lymphocytic leukemia
• Acute myelogenous leukemia
CUTANEOUS
• Hyperkeratosis
• Seborrhea
• Xerosis
• Perigenital folliculitis
NEUROPSYCHIATRIC
• Developmental delay
• Seizures
• Autism spectrum disorders
• Behavioral disorders (disruptive)
• Depression
• Alzheimer disease (Alzheimer disease are present in almost all individuals with
Down syndrome by age 40 years)
• Abuse - Individuals with Down syndrome are at high risk for physical and sexual
abuse

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Figure 108 Summary of features and complications of Down Syndrome

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INVESTIGATIONS
• The diagnosis of Down syndrome is most commonly made by prenatal
screening followed by definitive diagnostic testing.
• When prenatal diagnosis has not been made, down syndrome is usually
apparent from the clinical examination of the newborn.
• Diagnosis should be confirmed through chromosomal analysis.
• Since Down syndrome is associated with multisystem involvement, additional
diagnostic studies are performed as appropriate.
PRENATAL SCREENING AND DIAGNOSIS

• Prenatal screening using a combination of maternal serum biomarkers and
ultrasonography can detect up to 95% of pregnancies affected by Down
syndrome. The false positive rate is 5%.
• Recently updated guidelines from the American College of Obstetricians and
Gynaecologists (ACOG) state the following:
o All women should be offered screening for aneuploidy before 20 weeks'
gestation
o All pregnant women, regardless of their age, should have the option of
diagnostic testing.
FIRST-TRIMESTER SCREENING
• For pregnant women, for whom an early diagnosis is important, a first-
trimester "combined test" performed at 11-14 weeks involving
o sonographic testing for NT together with
o testing for PAPP-A and hCG
• provides a detection rate of 82-87% for Down syndrome.
SECOND-TRIMESTER SCREENING
• Tests used for second-trimester screening include the triple and quadruple
screens.
• The triple screen calculate the risk of Down syndrome by measuring
▪ serum hCG,
▪ AFP and
▪ unconjugated estriol
o Can detect up to 69% of Down syndrome pregnancies.
• Currently, the quadruple test, usually performed at 15-18 weeks' gestation,
o is the most common screening test performed in the second trimester.
o This screen measures inhibin A in addition to the biochemical markers
measured in the triple screen

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o Provides an 81% detection rate for Down syndrome.
o In addition, the quadruple test serves as a screening test for open
neural tube defects (since it involves measurement of AFP) and can also
detect trisomy 18.
INTEGRATED SCREENING
• With integrated screening, the pregnant woman undergoes a first-trimester
screening (involving NT testing, PAPP-A, hCG) followed by the quadruple
screen in the second trimester.
• This combined screening approach increases the detection rate of Down
syndrome to 95%, with a false positive rate of only 5%.
ULTRASONOGRAPHY
• Prenatal ultrasonography may reveal the following in a fetus with Down
syndrome:
o In the second trimester
▪ absent or hypoplastic nasal bone,
▪ thickened nuchal fold,
▪ echogenic bowel,
▪ shortened long bones, and
▪ pyelectasis
POSTNATAL WORKUP
Commonly performed studies in individuals with Down syndrome include the
following.
• Cytogenetic studies
o The clinical diagnosis of trisomy 21 should be confirmed with cytogenetic
studies.
o Karyotyping is essential to determine the risk of recurrence. In
translocation Down syndrome, karyotyping of the parents and other
relatives is required for proper genetic counselling.
• Interphase fluorescence in situ hybridization
o Fluorescence in situ hybridization (FISH) may be used for rapid
diagnosis of trisomy 21.
▪ It can be successful in both prenatal diagnosis and diagnosis in the
neonatal period.
• Measurement of immunoglobulin G
o Measurement of immunoglobulin (Ig) G levels focuses on identifying
deficiencies of subclasses 2 and 4.
• Radiography and Ultrasonography

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o Current evidence does not support performing routine screening
radiographs for assessment of potential
atlantoaxial instability in asymptomatic
children.
o Cervical radiography with lateral flexion
and extension views) is required to
measure the atlantodens distance and to
rule out atlantoaxial instability at the age
of 3 years.
• MRI is also recommended regularly for Figure 109 Atlantodens Instability
evaluation.
• Echocardiography should be performed on all infants suspected of having
trisomy 21 to identify congenital heart disease, regardless of findings on
physical examination.
INVASIVE DIAGNOSTIC TESTS

• Amniocentesis, routinely performed at 14-16 weeks’ gestation, remains the
criterion standard of invasive diagnostic tests.
o Testing for chromosomal disorders is 99.5% accurate.
• Chorionic villus sampling (CVS) is performed at 10-13 weeks’ gestation
o The accuracy of CVS (96-98%) is less than that of midtrimester
amniocentesis, because of confined placental mosaicism and maternal-
cell contamination.
• Percutaneous umbilical blood sampling (PUBS) is approximately 95%
successful in obtaining a blood sample for cytogenetic testing.
OTHER LAB STUDIES

• A complete blood count (CBC) with differential and bone marrow examination
to rule out leukaemia is indicated.
• Thyroid-stimulating hormone (TSH) and thyroxine (T4) levels should be
obtained at birth, at 6 and 12 months, and annually thereafter, to rule out
hypothyroidism.
PRINCIPLE OF TREATMENT
• Management of down syndrome requires an organized approach to ongoing
evaluation and monitoring for associated abnormalities and prevention of
common disorder.

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EDWARD SYNDROME (TRISOMY 18)

• Among live born children, trisomy 18 is the second most common autosomal
trisomy after trisomy 21.
• The disorder is characterized by;
o severe psychomotor and growth retardation,
o microcephaly,
o microphthalmia,
o malformed ears,
o micrognathia or retrognathia,
o microstomia,
o distinctively clenched fingers, and other congenital malformations.
• Trisomy 18 severely affects all organ systems.
• In translocations that result in partial trisomy or in cases of mosaic trisomy 18,
clinical expression is less severe, and survival is usually longer.

• Prevalence:1;6000-8000 live births
MORTALITY/MORBIDITY
Approximately 95% of conceptuses with trisomy 18 die as embryos or fetuses;
5-10% of affected children survive beyond the first year of life.
• Race - Trisomy 18 has no racial predilection.
• Sex - Approximately 80% of trisomy 18 cases occur in females.
• Age - Trisomy 18 is detectable during the prenatal and new-born periods.
RISK FACTORS
• The incidence rate increases with advanced maternal age.
• In approximately 90% of cases, the extra chromosome is maternal in origin,
with meiosis II errors occurring twice as frequently as meiosis I errors.
• This is in contrast to other human trisomies, which exhibit a higher frequency
of nondisjunction in maternal meiosis I.
TYPE OF TRISOMY 18
• Full trisomy 18 is responsible for 95% of Edwards syndrome cases.
• Mosaicism and
• translocations cause few cases.
NB; An extra chromosome 18 is responsible for the phenotype
COMMON PHYSICAL FINDING

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• Small and premature appearance
• Tight palpebral fissures
• Narrow nose and hypoplastic nasal alae
• Narrow bifrontal diameter
• Prominent occiput
• Micrognathia
• Cleft lip or palate
• Microcephaly
• Congenital heart disease (e.g., VSD, PDA, ASD) Figure 110 Infant with trisomy 18 and overlapping
fingers
• Short sternum, small nipples
• Limited hip abduction
• Clinodactyly and overlapping fingers; index
over 3rd, 5th over 4th;
closed fist
• Rocker-bottom feet and Hypoplastic nails
• Severe developmental delays and prenatal and
postnatal growth restriction
Figure 111 Rocker-Bottom Feet
• Premature birth, polyhydramnios
• Inguinal or abdominal hernias Figure 112 Male infant
• NB; Only 5% live >1 year with Trisomy 18 at age 4
days.
Note the Prominent

WORKUP
occiput, Micrognathia,
Low-set ears, short
• First trimester non-invasive screening based on sternum, Narrow Pelvis,
maternal age, serum markers, and sonographic “soft Prominent calcaneus, and
flexion abnormalities of
markers” have demonstrated a high sensitivity for the finger.
the diagnosis of trisomy 18.
• Low levels of human chorionic gonadotrophin
(hCG) and low unconjugated estriol (uE3) in
maternal serum during mid trimester are useful
predictors for an increased risk for trisomy 18.
PRENATAL DIAGNOSIS
• Amniocentesis
• Chorionic villus sampling (CVS)
• Percutaneous umbilical blood sampling (PUBS)
POSTNATAL DIAGNOSIS
• Hematological studies in patients with trisomy 18 during the first week of life
o Thrombocytopenia

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o Neutropenia:
o Abnormal erythrocyte values
▪ anemia was detected in 40%, and
▪ polycythemia was detected in 17%.
• Conventional Cytogenetic and Fluorescence In Situ Hybridization (fish)
studies
o FISH for rapid diagnosis (most laboratories, ≤24 hours) is more sensitive
for mosaicism in the neonatal period (if unknown prenatally), followed
by karyotyping, which is necessary even if FISH confirms the diagnosis
for the rare translocation;
o karyotyping is also necessary if the diagnosis is made prenatally to
confirm the type of trisomy 18.
PRINCIPLE OF TREATMENT
• Management of Edward syndrome requires an organized approach to ongoing
common disorder.
TURNER SYNDROME (45, X)

• Turner syndrome is a condition characterized by complete or partial monosomy
of the X chromosome and defined by a combination of phenotypic features.
• Half of the patients with Turner syndrome have a 45, X chromosome
complement.
• The other half exhibits mosaicism and varied structural abnormalities of the X
or Y chromosome.

• Prevalence; 1 in 5,000 female live births
• Sex; occur only in female
• Race; no racial or ethnic predilections are known.
NB; Maternal age is not a predisposing factor for children with 45, X.
• In 75% of patients, the lost sex chromosome is of paternal origin whether an X
or a Y).
• It has been estimated that 95-99% of 45, X conceptions are miscarried

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COMMON FINDING ASSOICIATED WITH TURNER SYNDROME

• Clinical findings in the newborns can include
o small size for gestational age
o webbing of the neck,
o protruding ears
o lymphedema of the hands and feet
• Older children and adults have short stature and exhibit variable dysmorphic
features.
o Congenital heart defects (40%)
and structural renal anomalies
(60%) are common.
o The most common heart defects
are
▪ coarctation of the aorta,
▪ bicuspid aortic valves,
▪ aortic stenosis, and
▪ mitral valve prolapse.
o The gonads are generally streaks
of fibrous tissue (gonadal
dysgenesis).
o There is primary amenorrhea
and lack of secondary sex
characters.
o These children should receive
regular endocrinologic testing.
o Most patients tend to be of
normal intelligence, but
intellectual disability is seen in
up to 6% of affected children. Figure 113 Features of Turner syndrome
o They are also at increased risk for

behavioral problems and deficiencies in spatial and motor perception.
o Patients with 45,X/46,XY mosaicism, can have Turner syndrome,
although this form of mosaicism can also be associated with male pseudo
hermaphroditism, male or female genitalia in association with mixed
gonadal dysgenesis, or a normal male phenotype.
o This variant is estimated to represent approximately 6% of patients with
mosaic Turner syndrome.

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SIGNS ASSOCIATED WITH TURNER SYNDROME
• Short stature • Gonadal dysgenesis (infertility,
• Congenital lymphedema primary amenorrhea)
Horseshoe kidneys • Gonadoblastoma (increased risk
• Patella dislocation if Y chromosome material is
• Increased carrying angle of present)
elbow (cubitus valgus) • Learning disabilities (nonverbal
• Madelung deformity perceptual motor and
(chondrodysplasia of distal radial visuospatial skills) (in 70%)
epiphysis) • Developmental delay (in 10%)
• Congenital hip dislocation • Social awkwardness
• Scoliosis • Hypothyroidism (acquired in 15-
• Widespread nipples 30%)
• Shield chest • Type 2 diabetes mellitus (insulin
• Redundant nuchal skin (in utero resistance)
cystic hygroma) • Strabismus
• Low posterior hairline • Cataracts
• Coarctation of aorta • Red-green color blindness (as in
• Bicuspid aortic valve males)
• Cardiac conduction • Recurrent otitis media
abnormalities • Sensorineural hearing loss
• Hypo plastic left-heart syndrome • Inflammatory bowel disease
and other left-heart • Celiac disease (increased
abnormalities incidence)
Figure 115 PUFFINESS OF THE HAND AND FEET
Figure 115 Redundant Nuchal skin

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DIAGNOSIS
• Turner syndrome is occasionally diagnosed incidentally during prenatal testing.
• More commonly, it is suspected based upon characteristic clinical features.
• The diagnosis is confirmed by karyotype analysis.
• Prompt diagnosis is important to permit management of comorbidities,
including effective treatment of short stature.
• Indications for testing — A karyotype analysis for Turner syndrome should be
performed in any female with characteristic features, which vary by age group.
• Prenatal
o Cases of Turner syndrome are sometimes discovered incidentally during
chorionic-villus sampling or amniocentesis that was performed for
unrelated reasons, such as advanced maternal age.
• Newborn period
o Turner syndrome may be apparent at birth, presenting with congenital
lymphedema of the hands and feet, webbed neck, nail dysplasia, narrow
and high-arched palate, and short fourth metacarpal.
• Infants and children
o In infants and children, Turner syndrome should be suspected in any
female with unexplained growth failure, defined as a growth velocity
less than the 10th percentile for age or stature that is substantially less
than predicted from parental heights
• Adolescence –
o Turner syndrome should be suspected in adolescent girls who fail to start
or complete breast development, or those with secondary amenorrhea,
especially if short stature and/or other features suspicious of Turner
syndrome are present.
• Diagnostic test
o Standard karyotype analysis
▪ The karyotype analysis is sufficient to establish the diagnosis in
most cases. However, in certain cases, the karyotype should be
repeated to confirm the initial result:
▪ If the initial karyotype is normal in a patient with a strong clinical
suspicion of Turner syndrome, a second karyotype should be
performed using a different tissue such as the skin (fibroblasts),
bladder epithelial cells in a urine sample, or buccal mucosa cells.
o Real-time PCR
o High-throughput pyrosequencing
o Whole-exome sequencing
• ADDITIONAL TESTING

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o Y chromosome mosaicism
• Once the diagnosis of Turner syndrome is established by karyotype analysis,
management includes evaluation and monitoring for associated abnormalities,
including
o cardiac pathology,
o thyroid disease,
o hearing and eye abnormalities,
o and learning disabilities.
• Age four years and older –
o Serum thyrotropin (thyroid-stimulating hormone [TSH]), to screen for
chronic autoimmune thyroiditis, and
o tissue transglutaminase (tTG) with total immunoglobulin A (IgA), to
screen for celiac disease.
• Age 10 years and older – because of the risks of diabetes mellitus, fatty liver
disease, and kidney dysfunction.
o Fasting blood glucose, glycated hemoglobin (A1C),
o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
o Serum creatinine, and urinalysis.
Key screening steps at diagnosis are:

• Renal ultrasonography.
• Comprehensive cardiovascular evaluation by a cardiology specialist, consisting
of echocardiography in infants and children and magnetic resonance imaging
(MRI) in older girls and women.
PRINCIPLE OF MANAGEMENT
• Management of turner syndrome requires an organized approach to ongoing
common disorder.

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13.2. NEURAL TUBE DEFECTS

• Neural tube defects (NTDs) result from failure of the neural tube to close
spontaneously between the 3rd and 4th wk of in utero development.
• Account for the largest proportion of congenital anomalies of the CNS.
• Although the precise cause of NTDs remains unknown, evidence suggests that
many factors
o hyperthermia,
o drugs (valproic acid),
o malnutrition,
o low red cell folate levels,
o chemicals,
o maternal obesity or diabetes, and
o genetic determinants (mutations in folate-responsive or folate-
dependent enzyme pathways) can adversely affect normal development
of the CNS from the time of conception
THE MAJOR NTDS INCLUDE

• Spina bifida occulta,
• Meningocele,
• Myelomeningocele, encephalocele,
• anencephaly,
• Caudal regression syndrome, dermal
sinus, tethered cord, syringomyelia,
diastematomyelia, and lipoma involving
the conus medullaris and/or filum
terminale and the rare condition in Figure 116 Neural tube defects
encephaly.
• NB; Prenatal screening of
maternal serum for AFP in
the 16th-18th wk of gestation
is an effective method for
identifying pregnancies at
risk for fetuses with NTDs in
utero.
• We will discuss from this
major NTDs the more
common case in our setup; Figure 117 Types of NTDs

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1. SPINA BIFIDA OCCULTA (OCCULT SPINAL DYSRAPHISM)

• Def; Spina bifida occulta is a common anomaly consisting of a midline defect of
the vertebral bodies without protrusion of the spinal cord or meninges.
• This simple defect does not have an associated spinal cord malformation.
o Occult Spinal Dysraphism defined by clinically more significant forms of
closed spinal cord malformations like; a hemangioma, discoloration of
the skin, pit, lump, dermal sinus, or hairy patch.
DIAGNOSIS
• Spine x¬-ray shows a defect in closure of the posterior vertebral arches and
laminae, typically involving L5 and S1; there is no abnormality of the meninges,
spinal cord, or nerve roots.
• A spine x-ray occult spinal dysraphism might show bone defects or may be
normal.
• All cases of occult spinal dysraphism are best investigated with MRI.
2. MENINGOCELE
• Definition- Meningocele is formed when the meninges herniate through a
defect in the posterior vertebral arches or the anterior sacrum.
• Most meningoceles are well covered with skin and pose no immediate threat to
the patient.
• Careful neurologic examination is mandatory.
• Orthopedic and urologic examination should also be considered.
• In asymptomatic children with normal neurologic findings and full-thickness
skin covering the meningocele, surgery may be delayed or sometimes not
performed.
• Patients with leaking cerebrospinal fluid (CSF) or a thin skin covering should
undergo immediate surgical treatment to prevent meningitis.
• An anterior meningocele projects into the pelvis through a defect in the
sacrum. Symptoms of constipation and bladder dysfunction develop owing to
the increasing size of the lesion.
DIAGNOSIS;
• Spine x-ray to determine neural tissue involvement.
• MRI to determine neural tissue involvement
• U/S to determine neural tissue involvement
• Cystometrogram to identify children with neurogenic bladder who are at risk
for renal deterioration.

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• cranial CT scan or an MRI of the head is recommended for children with a
meningocele because of the association with hydrocephalus in some cases
3. MYELOMENINGOCELE
• the most severe form of dysraphism, a so-called aperta or open form, involving
the vertebral column and spinal cord.
• Incidence; 1 in 4,000 live births.
• NB; the risk of recurrence after one affected child is 3–4% and increases to 10%
with two prior affected children.
o Folate is intricately involved in the prevention and etiology of NTDs
o Maternal periconceptional use of folic acid supplementation reduces the
incidence of NTDs in pregnancies at risk by at least 50%.
o To be effective, folic acid supplementation should be initiated before
conception and continued until at least the 12th wk of gestation, when
neurulation is complete.
• The lumbosacral region accounts for at least 75% of the cases.
• Many organs and structures, including the skeleton, skin, and gastrointestinal
and genitourinary tracts, in addition to the peripheral nervous system and the
CNS affected.
• The extent and degree of the neurologic deficit depend on the location of the
myelomeningocele and the associated lesions.
• A lesion in the low sacral region causes bowel and bladder incontinence
associated with anesthesia in the perineal area (no motor defect).
• A lesion in the midlumbar or high lumbothoracic region typically have a flaccid
paralysis of the lower extremities, an absence of deep tendon reflexes, a lack
of response to touch and pain, and a high incidence of lower-extremity
deformities (clubfeet, ankle and/or knee contractures, and subluxation of the
hips).
• A lesion above the midlumbar region tends to produce lower motor neuron
signs because of abnormalities and disruption of the conus medullaris and
above spinal cord structures.
• Infants with myelomeningocele typically have an increased neurologic deficit as
the myelomeningocele extends higher into the thoracic region.
NB; Hydrocephalus in association with a type II Chiari malformation develops in at

least 80% of patients with myelomeningocele.

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• The possibility of hydrocephalus developing after the neonatal period should
always be considered, no matter what the spinal level.
• Chiari malformations, types I-IV, refer to a spectrum of congenital hindbrain
abnormalities affecting the structural relationships between the cerebellum,
brainstem, the upper cervical cord, and the bony cranial base.
• Classification is based on the morphology of the malformations.
o Chiari I: >5mm descent of the caudal tip of cerebellar tonsils past the
foramen magnum.
o Chiari II: brainstem, fourth ventricle, and >5 mm descent of the caudal
tip of cerebellar tonsils past the foramen magnum with spina bifida.
o Chiari III: herniation of the cerebellum with or without the brainstem
through a posterior encephalocele.
o Chiari IV: Cerebellar hypoplasia or aplasia with normal posterior fossa
and no hindbrain herniation.
TREATMENT
• Require a multidisciplinary team approach, including surgeons, other
physicians, and therapists, with one individual (often a pediatrician) acting as
the advocate and coordinator of the treatment program.
• Surgery is often done within a day or so of birth but can be delayed for several
days (except when there is a CSF leak) to allow the parents time to begin to
adjust to the shock and to prepare for the multiple procedures and inevitable
problems that lie ahead.
• Clubfeet can require taping or casting.
• Careful evaluation and reassessment of the genitourinary system is an
important component of management.
NB; Renal dysfunction is one of the most important determinants of mortality.

• Periodic urine cultures and assessment of renal function, including serum
electrolytes and creatinine as well as renal scans, vesiculourethrograms,
renal ultrasonograms, and cystometrograms, are obtained586 according to
the risk status and progress of the patient and the results of the physical
examination
• This approach to urinary tract management has greatly reduced the need
for urologic diversionary procedures and has decreased the morbidity and
mortality associated with progressive renal disease in these patients.
• Functional ambulation is the wish of each child and parent and may be
possible, depending on the level of the lesion and on intact function of the
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• Almost every child with a sacral or lumbosacral lesion obtains functional
ambulation; approximately half the children with higher defects ambulate
with the use of braces, other orthotic devices, and canes.
PREVENTION
• All women of childbearing age who can become pregnant take 0.4 mg of folic
acid daily.
• If, however, a pregnancy is planned in high-risk women (previously affected
child), supplementation should be started with 4 mg of folic acid daily,
beginning 1 mo before the time of the planned conception.
• Certain drugs, including drugs that antagonize folic acid, such as trimethoprim
and the anticonvulsants carbamazepine, phenytoin, phenobarbital, and
primidone, increase the risk of myelomeningocele
• Some epilepsy clinicians recommend that all female patients of childbearing
potential who take anticonvulsant medications also receive folic acid
supplements
o is associated with a markedly reduced risk of NTDs.
PROGNOSIS
• For a child who is born with a myelomeningocele and who is treated
aggressively, the mortality rate is 10–15%, and most deaths occur before age 4
yr, although life-threatening complications occur at all ages.
• Learning problems and seizure disorders are more common than in the general
population.
4. ENCEPHALOCELE
• Two major forms of dysraphism affect the skull, resulting in protrusion of tissue
through a bony midline defect, called cranium bifidum.
o A cranial meningocele consists of a CSF-filled meningeal sac only, and
o A cranial encephalocele contains the sac plus cerebral cortex,
cerebellum, or portions of the brainstem.

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13.3. HYDROCEPHALUS
• Hydrocephalus is not a specific disease.
• It represents a diverse group of conditions that result
from;
o Impaired circulation
o Absorption of CSF or,
o In rare circumstances, from increased
production of CSF by a choroid plexus papilloma.
PHYSIOLOGY OF CSF
Figure 118
• The CSF is formed primarily in the ventricular system
Hydrocephalus
by the choroid plexus, which is situated in the lateral,
third, and fourth ventricles.
• Most CSF is produced in the lateral ventricles (75%)
• In a normal child, approximately 20 mL/hr of CSF is produced.
• The total volume of CSF approximates 50 mL in an infant and 150 mL in an
adult.
• Most of the CSF is extraventricular.
CIRCULATION OF CSF
o CSF is formed by active secretion → by choroids plexus in the
lateral ventricles → pass via foramen of Monro to the 3rd
Ventricle → then via aqueduct of Sylvius to the 4th ventricle
→ then via foramena of Luscka & Magendi to the
subarachnoid space.
Figure 119 Circulation of CSF

TYPES OF HYDROCEPHALUS
1. Obstructive or non-
communicating hydrocephalus
− Results from obstruction
within the ventricular
system
2. Non-obstructive or
communicating hydrocephalus
− Results from obliteration
of the subarachnoid
cisterns or malfunction of
the arachnoid villi.

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CAUSES OF OBSTRUCTIVE HYDROCEPHALUS
I. Obstruction of aqueduct of sylvius:
− Congenital atresia; may be sex linked recessive, may be associated with
spina bifida occulta
− Obstruction from outside by; brain tumors, malformation of vein of
Galen.
− Obstruction from inside; Post hemorrhagic (especially in premature).Post
meningitis (TB, pneumocci, mumps)
II. Congenital atresia of:
− Foramen of Monro.
− Foramina of Luscka & Magendi: cystic dilatation of 4th ventricle usually
with agenesis of cerebellar vermis (Dandy Walker malformation).
III. Arnold Chiari malformation: Congenital downward displacement of
cerebellum, pons & medulla.
IV. Congenital infection especially toxoplasmosis
V. Brain tumors
CAUSES OF NON-OBSTRUCTIVE HYDROCEPHALUS

I. Defective CSF production
− Subarachidonic space adhesion(post hemorrhagic, post meningitis)
− Leukemic infiltration
− Dural sinus thrombosis
II. Excessive CSF production (rarely)
− Choroid plexus papilloma
− Choroid plexus congestion (as in case of meningitis)
Table 121 Grading of Hydrocephalus
• The clinical presentation of hydrocephalus
is variable and depends on many factors,
including the age at onset, the nature of
the lesion causing obstruction, and the
duration and rate of increase of the
intracranial pressure.
IN INFANTS
I. HEAD SIGNS ARE MARKED AS CRANIAL SUTURES ARE STILL OPENED.

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• Large head with progressive increase in size (increasing head circumference on
serial measurement).
• Fontanels are widely opened & bulging
• Sutures are widely separated
• Dilated scalp vein
• Eyes deviated downwards ~ sunset appearance
• Skull percussion-cracked pot sound (Macewen sign).
• Craniotabes in all bones
• Back of the skull; Prominent occiput in (Dandy Walker), Foreshortened occiput
in(Arnold Chiari)
II. NEUROLOGIC SINGS:

• Mild, as rapid increase in skull size protect against marked increase intra
cranial tension.
o Mild vomiting
o Squint
o Delayed motor milestones
o Pyramidal tract lesion signs are common especially in lower limbs.
o In advanced cases mental retardation & optic atrophy may occur.
III. GENERAL EXAMINATION: -

• Back of spine for tuft of hair, lipoma or angioma in spina bifida.
• Meningomyelocele in Arnold Chiari malformation.
• Cerebellar ataxia in Dandy walker malformation.
• Fundus examination for chorioretinitis in toxoplasmosis.
IN OLDER CHILD
• Marked neurologic manifestations as the sutures are not easily separated with
subsequent marked increase intracranial tension
o Bursting headache (severe in the morning)
o Blurring of vision
o Projectile vomiting (unrelated to meals, not preceded by nausea)
o Bradycardia & hypertension (Cushing response)
DIAGNOSIS
1. CLINICAL PICTURE AS MENTIONED ABOVE

• The occipitofrontal head circumference is recorded and compared with
previous measurements.

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• The size and configuration of the anterior fontanel are noted.
• The back is inspected for abnormal midline skin lesions, including tufts of hair,
lipoma, or angioma that might suggest spinal dysraphism.
• A cranial bruit is audible in association with many cases of vein of Galen
arteriovenous malformation.
• Transillumination of the skull is positive with massive dilation of the ventricular
system or in the Dandy-Walker syndrome.
• Inspection of the eyegrounds (for chorioretinitis) suggests an intrauterine
infection, such as toxoplasmosis, as a cause of the hydrocephalus
2. SKULL X RAY
• Before closure of sutures - Wide fontanels, wide separation of sutures. -
Craniofacial disproportion with large cranium
• After closure of sutures- increase intra cranial tension (beaten silver
appearance, wide sell)
3. TRANS FONTANEL CRANIAL ULTRASOUND
4. CT & MRI
• Diagnostic; can detect ventricular dilatation.
• Detect degree of cortical atrophy.
• May detect the cause.
TREATMENT
• Therapy for hydrocephalus depends on the cause.
1. Medical: Decrease CSF production by;
− Carbonic anhydrase inhibitors; acetazolamide (Diamox tablets)
− Furosemide (LASIX)
− Draw backs: - Transient effect, Electrolyte & pH disturbances.
2. Surgical
− Choroid plexectomy or diathermy for choroid papilloma
− Extra cranial shunt operation
TYPES OF EXTRA CRANIAL SHUNT OPERATION

− ventriculoperitoneal (most common procedure)
− Ventriculoarterial (right)
− Ventriculopleual
o The major complications of shunting are;

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Occlusion (characterized by headache, papilledema,
▪
emesis, mental status changes)
▪ Bacterial infection (fever, headache, meningismus),
usually caused by Staphylococcus epidermidis.
− NB: With meticulous preparation, the shunt infection rate can be
reduced to < 5%.
PROGNOSIS
• The prognosis depends on the cause of the dilated ventricles and not on the
size of the cortical mantle at the time of operative intervention.
• Long term complication are;
o mean intelligence quotient is reduced
o Vision problems are common, including strabismus, visuospatial
abnormalities, visual field defects, and optic atrophy with decreased
acuity secondary to increased ICP.
o Accelerated pubertal development in patients with shunted
hydrocephalus or myelomeningocele is relatively common, possibly
because of increased gonadotropin secretion in response to increased
ICP.
14.4. CLEFT LIP AND PALATE

• Clefts of the lip and palate are distinct entities
which are closely related embryologically,
functionally, and genetically.
INCIDENCE AND EPIDEMIOLOGY

• Cleft lip; 1:750 white birth
• Cleft palate; 1:2500 white birth
• Clefts of the lip are more common in males
• Ethnic factors also affect the incidence of cleft
lip and palate; the incidence is highest among
Asians (~1 in 500) and Native Americans (~1 in
300) and lowest among blacks (~1 in 2,500).
CAUSES OF CLEFT LIP AND PALATE

Figure 120 Cleft Palate and lip
• Maternal drug exposure,
• Syndrome-malformation complex, or
• Genetic factors

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• Cleft lip can vary from a small notch in the vermilion border to a complete
separation involving skin, muscle, mucosa, tooth, and bone.
• Clefts of the lip may be unilateral (more often on the left side) or bilateral and
can involve the alveolar ridge.
• Isolated cleft palate occurs in the midline and might involve only the uvula or
can extend into or through the soft and hard palates to the incisive foramen.
• When associated with cleft lip, the defect can involve the midline of the soft
palate and extend into the hard palate on one or both sides, exposing one or
both of the nasal cavities as a unilateral or bilateral cleft palate
TREATMENT
• The immediate problem in an infant born with a cleft lip or palate is feeding.
• Surgical closure of a cleft lip is usually performed by 3 mo of age, when the
infant has shown satisfactory weight gain and is free of any oral, respiratory, or
systemic infection.
• Modification of the Millard rotation–advancement technique is the most
commonly used technique.
• The initial repair may be revised at 4 or 5 yr of age.

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CHAPTER 15 - DERMATOLOGY
1. Introduction
2. Discussion of selected cases
a. Scabies
b. Tinea Capitis
c. Psoriasis
d. Impetigo
e. Tungiasis

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15.1. INTRODUCTION
PRIMARY SKIN LESIONS

1. Macules – alteration in skin color which cannot be felt andthat is <1 cmin
diameter.
2. Patches- macules which is>1 cm in diameter
3. Papules - palpable solid elevated lesion<1 cm in diameter
4. Plaque - papules>1 cm in diameter
5. Nodules - palpable lesion>1cm with a round surface
6. Tumors - larger nodule that is suspected to be neoplastic in origin
7. Vesicles - raised fluid filled lesion <1cm in diameter
8. Bullae - raised fluid filled lesion >1 cm in diameter
9. Pustules - a small elevation of skin containing purulent material(pus)
10. Wheals - flat topped, palpable lesion of variable size, duration and
configuration that represent dermal collection of edema fluid
11. Cysts- circumscribed thick-walled lesions which are covered by a normal
epidermis and contain fluid or semisolid material
• Primary lesions may change to secondary lesions or secondary lesions may develop
overtime where no primary lesion excited.
SECONDARY SKIN LESIONS

1. Scales -dry or greasy laminated mass or compressed layer of keratin that
represent thickened stratum corneum
2. Purpura -bleeding into the skin that has red-purple color(flat/palpable)
3. Petechiae -small purpura<2-3mm
4. Erosion -focal loss of epidermis and they heal without scarring
5. Ulcer -extend to dermis and tend to heal with scarring
6. Excoriations -ulcerated lesion inflicted by scratching
7. Fissures -caused by splitting or cracking
8. Crust -matted, retained accumulation of blood, pus or serum usually mixed
with epithelial debris on the surface of weeping lesion
9. Scar -end stage lesion that can be thin, depressed and atrophic, raised and
hypertrophic or flat and pliable
10. Lichenification -visible and palpable epidermal thickening with accentuated
skin markings-caused by chronic irritation (rubbing, scratching) or inflammation

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Figure 121 Skin lesions

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15.2. DISCUSSION OF SELECTED CASES
1. SCABIES
• Causative agent-female mite called sarcoptesscabieivarhominus
• Transmitted by
o physical contact with an affected individualI.e is affected by the extent and
duration of contact
o Rarely by fomites b/c the isolated mite dies within 2-3 days
• Intensive pruritus particularly at night
• Red papules (1-2mm) -----first sign
• Thread like burrow------classic lesion
• i.e. may not be seen in infants (bullae and
pustules are common)
• Common site
o Covered areas like:
▪ interdigital space
▪ wrist flexors
▪ belt line
▪ anterior axillary folds, umbilicus
groin in males &areola in females
i.e. face, palms and soles are spared

o In infants, scalp, neck and face are
often affected
o other clue-poor response to topical
antibiotic &transient response to
topical steroids
ATYPICAL SCABIES
• The following are clinical manifestations of
special forms:
a) Scabies in infant and very young Figure 122 Scabies
children often manifests itself as
vesicles, papules, and pustules in body areas that are not classically
involved in the adult type such as the hands, feet, and body folds.
▪ Lesions are also found on the head, palms, and soles,
and behind the ears.

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b) Crusted scabies (Norwegian scabies) is a psoriasiform dermatosis of the
hands and feet, with nail hyperkeratosis and an erythematous scaly
eruption on the face, neck, scalp, and trunk.
▪ Predisposing conditions for crusted scabies includes
immunocompromised patients such as patients with HIV, organ-
transplant recipients, and patients treated with steroids.
▪ It is also common among mentally retarded or incapacitated
persons and people with human T-lymphotropic virus.
▪ The number of mites in that form of infestation is extremely
large, and they are readily seen under the microscope. Skin
samples from patients with crusted scabies can contain up to 4700
mites per gram of skin.
c) Nodular scabies is characterized by few violaceous, firm pruritic nodules
on covered body parts, especially on the male genitalia, groin, and
axillae. It may represent a hypersensitivity reaction to mite antigens.
The nodules can persist for weeks to months after treatment.
d) Scabies in the elderly manifests itself differently because their reaction
to the mite is aberrant compared with younger patients. Although
pruritus can be severe, the inflammatory reaction may not be as
noticeable. Bedridden patients usually show involvement of the back.
e) Bullous scabies can be seen in adults older than 65 years.
There is no linkage to an underlying condition or disease. It can mimic
bullous pemphigoid clinically, pathologically, and immunopathologically.
COMPLICATIONS (IF LEFT UNTREATED)

• secondary infection
• eczematous dermatitis
• impetigo
• folliculitis
• cellulitis
• Glomerulonephritis
• Latent period of 1 month follows initial infestation.
DIAGNOSIS
• Definitive diagnosis requires microscopic identification of the mite and/or its
eggs or fecal pellets on specimens collected by skin scraping, biopsy or other
means.
• The yield from skin scrapings is highly dependent on the experience of the
operator and the severity of the infestation.

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TREATMENT
1) 5% permethrin cream - currently considered drug of choice.
a. The usual adult dose is 30 grams.
b. For adults and children, the cream should be massaged into the skin
from below the chin to the soles of the feet. Scabies rarely infests the
scalp of adults, although the hairline, neck, temple, and forehead may
be infested infants and geriatric patients. Infants should be treated on
the scalp, temple and forehead.
c. The patient should be instructed to remove the medication by
thoroughly bathing 8 to 14 hours after application. Repeat after one
week.
2) Sulfer ppt (6%-10%)-Apply for three nights and repeat after one week
3) 25%Benzoyl benzoate lotion-Apply for three nights and repeat after one week
4) 10% crotamiton cream or lotion
a. Massage thoroughly into skin once a day for two to five days. Remove by
bathing 48 hours after last application.
5) Additional therapies; lindane,oralivermectin(for immune compromised)
6) Clothing, bed lines&towels should be washed with hot water
7) Entire family should be treated
N.B. Pruritus (hypersensitivity to mite antigens may persist for a number of days to
weeks
• Nodules may take several months to resolve
• Transmission is unlikely more than 24 hours after treatment
TREATMENT FAILURES
Treatment failures can result from:
• Inadequate application of scabicide;
• Infected, crusted, or keratotic lesions with insufficient penetration of
scabicide;
• Reinfestation from untreated contacts;
• Resistance of mites to scabicide.
2. TINEACAPITIS
• Is dermatophytic infection of the scalp most often caused by Trichophyton
tonsurans, occasionally by Microsporidium.

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EPIDIMOLOGY
If the patient is above age of 14 with the same compliant, We should consider
Seborric Dermatitis.)
• Common in black children age 4-14 yr.

CLINICAL MANIFESTATION-
• varies with the infecting organism
ENDOTHRIX INFECTION
• Caused by T. tonsurans
• An infection within the hair shaft characterized by
“black-dot ringworm”
• Initially many small circular patches of alopecia in
which hairs are broken off close to hair follicle diffuse
scaring with minimal hair loss; resemble seborrheic
dermatitis, psoriasis, atopic dermatitis
• Kerions (elevated boggy granulomatous mass caused by
sever inflammation) which are often studded with
pustules
Figure 123 Picture of T. Capitis
• fever, pain, lymphadenopathy & permanent scarring
&alopecia chronic alopecia
ECTOTHRIX INFECTION
• Caused by some other types of Trichophyton infections
• Spores are are distributed in sheath like fashion around the hair shaft
• M.audoini
o Initially a small papule at the base of hair follicle, spreads peripherally,
forming an erythematous &scaly circular plaque (ring worm)
o Numerous patches of alopecia
o Severe pruritus
FAVUS
• Chronic form of tinea capitis which is rare
• Caused by T. schoenleinii
• Starts as yellowish red papule at the opening of hair follicles, the papules
expand and coalesce to form cup shaped yellowish, crusted papule that
fluoresce dull green under wood lump
METHOD OF TRANSMISSION

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• Mostly by contact with infected hair, combs, hats &seats
• may also be air born with in the immediate environment (school mate &house
hold members) zoophilic; cats and dogs → M. canis
• Seborrheic dermatitis
• Psoriasis
• Alopecia areata
• Dystrophic hair disorders
DIAGNOSIS
• Wood lamp
• Microscopic examination with KOH preparation
• Culture
TREATMENT
• Topical treatment is not effective
• Systemic treatment is mandatory
• Griseofulvin for children;
o 20 -25mg/kg/day
o Average of 6-8 weeks of treatment
• Terbinafine(Lamisil):3 to 6mg/kg /d for 2 to 4 weeks.
• Fluconazole: 6mg/kg/day once daily for 6weeks
• Itraconazole: 5mg/kg/day,once daily or divided into two doses, for 2 to 4
weeks.
• Adjuvant therapies→ vigorous shampooing with 2.5% selenium sulfate, zinc,
pyrithione or ketoconazole for patient and potential carrier

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3. PSORIASIS
• Psoriasis is a chronic and recurrent inflammatory disorder which is
characterized by epidermal cell proliferation(rapid cell turn over).
• It results from a polygenic predisposition combined with immune dysfunction.
EPIDMOLOGY
• Psoriasis is a very common skin disease which affects 2% of the world
population.
• It has two peaks in age of onset in which the first peak is at 20-30 years and the
second peak is at 50-60 years of age.
• Males and females are affected with equal proportion ( 1:1).
PATHOGENESIS
• Psoriasis has some genetic background and 35% to 90% of patients reported
family history of psoriasis.
• The exact cause of psoriasis is unknown.
• There is an interactions b/n environment and genetic factors which are
important for disease causation.
• Historically it was believed to be a disease of keratinocyte but now regarded as
T-cell driven disease which means psoriasis is an autoimmune disease, but no
true auto antigen has been identified.
• The main pathogenesis of psoriasis includes activation of T- lymphocytes
against unknown antigen that results in increased cytokine release and then
increased accumulation and activation of lymphocytes andantigen-presenting
cells (APCs), neutrophils which finally results in increased proliferation of
keratinocytes.
• Accelerated epidermal cell proliferation results from recruitment of a large
proportion of resting cells into the proliferative cycle.
• The pathogenesis of psoriasis involves immune mediated inflammation and
epidermal cell proliferation.
• There are Triggering Factors for the occurance of psoriasis
o Trauma [Koebner phenomenon]
o Infections [streptococcal, HIV]
o Endocrine factors [Hypocalcemia]
o Psychogenic stress
o Drugs[Lithium, IFNs, b-Blockers, Antimalarials]
o Obesity, Alcohol consumption and Smoking

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CLINICAL FEATURES
• The Classic lesion of psoriasis is a well-demarcated, raised, erythematous
plaque with a silvery white scale on the overlying surface.
• The skin lesions of psoriasis often tends to be in symmetrical distribution.
• Auspitz sign
o If you remove the scale of psoriatic skin lesion it has pin point bleeding
which is called “Auspitz sign”
o “Auspitz sign” is a pathognomic sign of psoriasis.
CLINICAL PATTERNS OF PSORIASIS
1. PSORIASIS VULGARIS (CHRONIC PLAQUE PSORIASIS)

• It is the most common form of psoriasis which accounts 90% of cases.
• It mainly distributes on the extensor aspects of the extremities(elbows and
knees), Scalp, lower back, buttocks, and genital area.
2. GUTATTATE PSORIASIS
• It is common in children and young adults.
• It often follows acute streptococcal sore throat infections[Pharyngitis].
• The size of the lesion is 2 mm to 1 cm in diameter and it is characterized by
round or oval slightly scaly plaque.
• It usually scattered in wide areas particularly on the trunk and proximal
extremities.
• It can also occur as acute eruption on chronic plaque psoriasis. Guttate
psoriasis→ Chronic plaque psoriasis
3. SMALL PLAQUE PSORIASIS

• It is characterized by well demarcated erythematous scaly plaques and the skin
lesion size is usually 1 to 2 cm.
4. INVERSE (FLEXURAL) PSORIASIS
• It is usually localized to the major skin folds such as the axillae, genito-crural
region, inframammary and neck region.
• The lesions are moist and scaling.The scaling is minimal or absent.
5. ERYTHRODERMIC PSORIASIS
• It represents the generalized form of the disease (more than 90 % of the body
surface area affected).
• Erythema is the most prominent feature and the scaling is instead of being
localized thick, adherent and white it is superficial and diffuse.
• It is also called exfoliative dermatitis.

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• It has mortality if not treated and the Complications of erythrodermic psoriasis
are
o Hypothermia
o High-output cardiac failure
o Impaired hepatic and renal function
• Clinical features of erythrodermic psoriasis as compared to other types of
exfoliative dermatitis are
o previous chronic plaques in classic locations
o characteristic nail changes
o facial sparing
6. PUSTULAR PSORIASIS
• It is characterized by sterile small pusutles with the size of 2 to 3 mm in
diameter.
• Pustular psoriasis tends to be generalized or localized.
Generalized form of pustular psoriasis is called von Zumbusch type.
6.1. Generalized Pustular Psoriasis
• Is an unusual manifestation of psoriasis
• Presents with erythema and sterile pustules
• There are various triggering factors of generalized psoriasis such as
Pregnancy, rapid tapering or withdrawal of systemic corticosteroids,
hypocalcemia, infections or the application of irritants.
o Palmo plantar psoriasis
o Acrodermatitis continua of Hallopeau
o In case of Acrodermatitis continua of Hallopeau there are pustules
within the nail bed, and partial shedding of the nail plate.
• The other type of localized pustular psoriasis is pustulosis palmaris et
plantaris which presents as multiple sterile pustules on the palms and soles
Nail Psoriasis
• Nail changes are frequent in psoriasis and it occurs in 40% of patients.
• Fingernails are more affected than toe nails.
• Nail pitting is the commonest manifestation.
• Oil spotting is nearly specific for psoriasis.
• There is increased incidence of psoriatic arthritis occurrence in patients who
have nail changes.
PSORIATIC ARTHRITIS

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• It is an inflammaton of the small or big joints associated with cutaneous
psoriasis.
• Psoriatic arthritis is a sero negative for rheumatoid factor.
• 40% of patients with cutaneous disease are affected by psoriatic arthritis.
• Psoriatic arthritis has strong genetic component.
• There are five patterns of psoriatic arthritis and it includes the following:
a. Asymmetric Oligoarthritis
b. Symmetric polyarthritis with rheumatoid like
c. Spondylo arthritis
d. Distal inter phalangeal joint arthritis
e. Mutilating arthritis
DIAGNOSIS
• The diagnosis of psoriasis is mainly clinical.
• Biopsy is indicated when the diagnosis is doubtful .
• Imaging studies in case of psoriatic arthritis.
PROGNOSIS AND CLINICAL COURSE

GUTTATE PSORIASIS
• It is a self-limited disease and it lasts from 6-12weeks without treatment.
• 1/3 of cases later develop the chronic plaque type of psoriasis.
CHRONIC PLAQUE PSORIASIS
• In most cases it is a life long disease.
• Spontaneous remission can occur in 50% of cases.
ERYTHRODERMIC AND GENERALIZED PUSTULAR PSORIASIS
• In such cases the disease tends to be severe and persistent.
MANAGEMENT OF PSORIASIS
• Explain the patient that psoriasis remains to be chronic and recurrent but it
can be controlled with treatment.
• Patients should be aware of the psoriasis triggers & avoid them.
• Different treatment options are available to reduce or temporarily eliminate
the symptoms of psoriasis.
TREATMENT MODALITIES
• Topical Preparations
• Photo(chemo) therapy
• Systemic treatments
• Severity of psoriasis can be classified as :

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o Mild < 10% BSA
o Moderate > 10% BSA
o Severe > 30% BSA
• In case of mild to moderate psoriasis topical treatment is indicated.
• In case of moderate to severe psoriasis systemic therapy is indicated.
• Exceptions are
o Painful palmoplantar involvement with limited activities.
o Psoriatic arthritis
o Impact on quality of life
Table 122 Topical Treatment Of Psoriasis
Medication Uses in Psoriasis Side effects
Topical steroids Plaque-type psoriasis Skin atrophy, hypopigmentation,
striae
Calcipotriene Use in combination with topical Skin irritation, photosensitivity
(vitamin D steroids for added benefit (but no contraindication with
derivative) UVB phototherapy)
Tazarotene Plaque-type psoriasis, best when Skin irritation, photosensitivity
(Toicla retinoid) used with topical corticosteroids
Salicylic or Plaque-type psoriasis to reduce Systemic absorption can occur if
Lactic acid scaling and soften plaques applied to >20% BSA. Decreases
(Keratolytic efficacy of UVB phototherapy
agents)
Coal tar Plaque-type psoriasis Skin irritation, odor, staining
of clothes
PHOTOTHERAPY
• For psoriasis resistant to topical therapy and covering > 10% of body surface
area.
• It has Immunomodulatory and anti-inflammatory effects.
• Three main types of phototherapy:
o Broadband UVB
o Narrowband UVB
o PUVA (administration of psoralen before UVA exposure)
o PUVA
o Re-PUVA
SYSTEMIC THERAPY

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• Reserved for patient with wide spread involvement and severe cases.
Methotrexate, retinoids, cyclosporine, hydroxyurea or biologic therapy may be
used.
4. IMPETIGO
• Impetigo is a contagious that affects the most superficial layer of the skin
(stratum cornium) infection of the skin.
• It can either present primarily on normal intact skin or secondary on diseased
skin.
• S.aureus and, to a lesser degree, Streptococcus pyogenes are the major causes
of impetigo.
• Impetigo is highly contagious, superficial skin infection that primarily affects
children.
• It has Worldwide occurrence, spreading rapidly via direct person to-person
contact.
• Biting insects and small non-biting flies can contribute to the spread of the
streptococcal infection.
• Bacteria skin Infections are common in tropical and subtropical regions.
• Impetigo occurs in all age groups
o Preschool and young school-age children are most often affected.
o Adults can acquire impetigo through close contact with infected
children.
• There are two clinical patterns of bacterial skin infections which are Non-
bullous impetigo and Bullous impetigo.
NON-BULLOUS IMPETIGO
• It accounts for more than 70 % of impetigo.
• It occurs in children of all ages as well as in adults.
• It is caused by group A beta streptococcus and in some geographical areas it is
caused by S. aureus or by both organisms.
• Clinical presentations of non-bullous impetigo
o Infection occurs at minor sites of trauma.
o Trauma exposes cutaneous proteins which allow the bacteria to adhere,
invade and establish infection. Lesions commonly arise on the skin of the
face (especially around the nares) or extremities after trauma.
o Nasal carriers of S. aureus can present with a very localized type of
impetigo confined to the anterior nares and the adjacent lip area.
o The initial lesion is a transient vesicle or pustule on an erythematous
base that quickly evolves into a honey-colored crusted plaque.

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o The crusts are thicker and ‘dirtier’ in case of streptococcus compared to
staphylococcal skin infection.
o Constitutional symptoms are absent but in severe cases there may be
fever and other constitutional symptoms.
o Regional lymphadenopathy can occur in up to 90% with prolonged and
untreated infection.
o If Lesions usually occur on exposed part of the body such the face,scalp,
arms or legs.
o Untreated, the lesions may slowly enlarge and involve new sites over
several weeks and in others, the lesions extend deeper to form an ulcer
which is called Ecthyma
BULLOUS IMPETIGO
• It is less common than non-bullous impetigo.
• It is caused by S. aureus and usually it is sporadic.
• Bullous impetigo often occurs in children less than 3 years old.
• It is due to cutaneous responses to toxin producing S. aureus organisms which
produce exfoliative toxins types A and B.
o Exfoliative toxin A acts as a serine protease and cleave desmoglein 1 to
form blister .
o Bullous impetigo is considered as localized form of SSSS (Staphylococcal
scalded skin syndrome)
• Clinical presentation of bullous impetigo
o Bullous impetigo occurs more commonly in the newborn and in older
infants.
o It affects the face, trunk, buttocks, perineum or extremities.
o It is characterized by the rapid progression of vesicles into flaccid
blisters.
o Regional lymphadenitis is rare.
o In immunodeficient states, exfoliative toxin may disseminate
hematogenously and cause SSSS.
o The localization of the epidermal splitting in bullous impetigo probably
related to local production of the toxin whereas in SSSS the toxin is
disseminated haematogenously.
• Treatment
o In localized and mild infection, a topical antibiotic such as fuicidic acid
cream or gentian violet 0.5% apply BID.
o If the infection is widespread or severe, or is accompanied by
lymphadenopathy systemic treatment is mandatory.

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5. TUNGIASIS
•
Tungiasis is a skin infection caused by a burrowing flea called tunga
penetrans/chigao flea/jigga.
• he skin is infested by the adult through a bite on the surface.then it burrows
through the skin to the epidermis to be fed from the blood vessels in the upper
dermis.
EPIDEMOLOGY
• It is more common in Caribbean region, Africa, india, Pakistan and latin
America.
• It’s very common in our setup.
• People who walk on bare foot in dry soil, sandy beaches, stables and farm are
at higher risk.
• Most common site is feet.
• Tungiasis by itself only caused morbidity, though secondary infection may lead
to mortality
• The clinical presentation depend on the stage of the disease
I.
Stage 1 - Stage of Penetration (Asymptomatic)
II.
Stage 2 (1-2 days) - Complete Penetration of the body except the Anus part
and the flea begins to feed on the host’s blood.
o Erythema, boring pain and the curious sensation of pleasant itching
occur.
III. Stage 3 - maximum hypertrophy is achieved and the flea’s midsection swells to
the size of a pea
o Due to the expanding flea, the outer layer of the skin is stretched thin,
resulting in the appearance of a white halo around the black dot (rear
end of the flea) at the center of the lesion
o Egg release is common
− pain can be severe, especially at night or, if the nodule is on the
foot, while walking.
− Eggs will also begin to be released and a watery secretion can
be observed.
IV. Stage 4-the flea loses its signs of vitality and appears near death
o As a result, the lesion shrinks in size, turns brown, and appears wrinkled
o the lesion is seen as brown or black.
• Extremely itchy, erythematous skin in the parts of feet

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•After this stage they may develop papules/nodules which has apunctum(sharp
point or tip with a black dot )
• The lesion can range from 4-10 mm
• Some may develop ulceration afterwards
• Multiple lesions on the feet can lead to difficulty in walking
COMPLICATION
• Predispose to PSGN
• Secondary bacterial infection
o Tetanus
o Gangrene
INVESTIGATION
• Parasitological diagnosis
o Extraction of the gravid flea and/ or the eggs in the lesion is bothe
diagnostic and therapeutic.
• Dermoscopy
o Typical lesion with central irregular brown discoloration with middle
plugged opening or a gray-blue discoloration can be identified.
• Cercarial dermatitis
• Insect bites
• Sea bather’s eruption
MANAGEMENT
• General
o Tetanus toxoid vaccine
▪ As prophylaxis
▪ For patients whose TT vaccination is unknown or not up to date
• Specific
o Observation
▪ Most resolve by themselves within 2 weeks
▪ The flea sloughs off naturally as the skin sheds
▪ physical removal of the flea
▪ Topical ivermectin
▪ Cryotheraphy
▪ Antibiotic
• Topical---if secondary infection is suspected Systemic ----if
superinfection is severe

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REFERENCES
Elsevier (2015) Nelson Essentials of Pediatrics. 7th Edition, Marcdante & Kliegman,
Harrison's Principles of Internal Medicine, 21e Loscalzo J, Fauci A, Kasper D, Hauser
S, Longo D, Jameson J. Loscalzo J, & Fauci A, & Kasper D, & Hauser S, & Longo D, &
Jameson J(Eds.),Eds. Joseph Loscalzo, et a

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ANNEXES

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NEW WHO GROWTH STANDARDS

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MID UPPER ARM CIRCUMFERANCE

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GROWTH CURVE FOR PATIENTS WITH DOWN SYNDROME

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The end.

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CLINICAL GUIDE

Your feedback and suggestions are welcome Email address:

In addition to the organizational changes, we

Finally, we have also revised and expanded the

Dr. Nahom Asnake

Dr. Meghfira Abrar Dr Dereje Gondol

Dr. Betelhem Birhanu

Dr. Benti Shentema

Dr. Dinaol Dinagde Dr Meron Biable

Dr. Minase Getachew Dr Kirubel Misganaw

Dr. Mulat Alemu

Dr. Natnael Alemu Dr. Elsabeth Sisay

Dr Hermela Zewge Dr Nardos Befekadu

Dr. Fasika Solomon Dr Fikraddis Cheru

Dr. Kinfegabriel Wagaye Dr Martha Fisseha

Prepared by Graduating class of 2015 E.C (2022/23)

TORCH: CONGENITAL AND PERINATAL INFECTIONS ........................................ 144

Prepared by Graduating class of 2015 E.C (2022/23)

VON WILLEBRAND DISEASE (VWD) .................................................... 380

Prepared by Graduating class of 2015 E.C (2022/23)

POLIOMYELITIS .......................................................................... 539

Prepared by Graduating class of 2015 E.C (2022/23)

Prepared by Graduating Class of 2015 E.C (2022/23)

1.1. PEDIATRICS HISTORY TAKING

COMPONENTS OF PEDIATRICS HISTORY

HISTORY OF PRESENT ILLNESS

Prepared by Graduating Class of 2015 E.C (2022/23)

DEVELOPMENTAL HISTORY (SEE GROWTH AND DEVELOPMENT)

Prepared by Graduating Class of 2015 E.C (2022/23)

PAST MEDICAL & SURGICAL HISTORY

• Childhood illnesses like measles, chicken pox, mumps

PERSONAL, FAMILY & SOCIAL HISTORY

SYSTOLIC BLOOD PRESSURE CALCULATION

Prepared by Graduating Class of 2015 E.C (2022/23)

PHYSICAL EXAMINATIONS RELATED TO EACH SYSTEM ARE MENTIONED IN THEIR

Prepared by Graduating Class of 2015 E.C (2022/23)

DETERMINANTS OF THE IMMUNE RESPONSE

Prepared by Graduating Class of 2015 E.C (2022/23)

Type of antigen Vaccine example

Prepared by Graduating Class of 2015 E.C (2022/23)

3. OUTREACH (MOBILE SCHEDULE FOR REMOTE AREAS)

Prepared by Graduating Class of 2015 E.C (2022/23)

SIDE EFFECTS OF VACCINES

Prepared by Graduating Class of 2015 E.C (2022/23)

Prepared by Graduating Class of 2015 E.C (2022/23)

THE CONTRAINDICATIONS FOR SPECIFIC VACCINES INCLUDE:

Prepared by Graduating Class of 2015 E.C (2022/23)

1.3. GROWTH AND DEVELOPEMENT

STAGES OF GROWTH AND DEVELOPMENT

Prepared by Graduating Class of 2015 E.C (2022/23)

7 – 12 years (𝒂𝒈𝒆 (𝒚𝒓) ∗ 𝟕) − 𝟓

Prepared by Graduating Class of 2015 E.C (2022/23)

CHRONOLOGY OF HUMAN DENTITION OF PRIMARY (DECIDUOUS) AND SECONDARY

Prepared by Graduating Class of 2015 E.C (2022/23)

Prepared by Graduating Class of 2015 E.C (2022/23)

Needed for school age children

Figure 1 Factors affecting Child's Development

• There are four fields of developmental skills:

Prepared by Graduating Class of 2015 E.C (2022/23)

CAUSES OF ABNORMAL DEVELOPMENT