Case Presentation

PEDIATRICS UNIT 1
 Patient details:

Name : Ravin Venkatesan (B/o Roja-I)

DOB : 19.10.2017
Age/ Gender : 9 ½ months/ Male
Hospital No : H-236597
DOA : 31.05.2018
DOD : 09.08.2018
Duration of hospital stay : 2mo 10days
 Chief Complaints:
Cough and cold for 1 week
Fast breathing for 1 week
 Presenting Illness:
7 ½ months male infant, follow up case of malabsorption (? Multiple food protein allergy), OS
–ASD on anti-failure therapy had presented to the pediatric A&E with history of cough and
cold for 7 days.
History of associated fast breathing and increased efforts of breathing for 1 week.
No history of fever.
No history of recurrent aspirations.
No history of TB contacts.
No history of vomiting, loose stools, crying while passing urine, ear discharge.
No history of poor feeding, lethargy, reduced urine output.
 Treatment History:
No history of treatment for the current episode of illness.
 Past History:

Previous admission at JIPMER on postnatal day 62 (2 mo) with complaints of peri-orificial,

desquamative skin lesions and loose stools which had happened one week after the start of
cow’s milk.
He also had hypoalbuminemia (related edema), anemia; malabsorption and multiple food
protein allergy were considered and the infant was started on elemental diet.
He had also received PRBC transfusion in view of anemia.
He developed Methicillin sensitive Staphylococcus aureus and Klebsiella pneumoniae skin sepsis for
which he had received Cloxacillin and Ceftazidime for 7 days.
He had developed sepsis induced cholestasis, which subsided after antibiotic therapy.
Hypoalbuminemia and related edema had subsided after the start of elemental diet.
 Past History:
He was started on L-thyroxine in view of hypothyroidism.
During the hospital stay, he had developed respiratory distress. Hospital acquired infection was
considered and he was given a course of Meropenem and Vancomycin.
Atypical infectious etiologies due to immunodeficiency (secondary to malabsorption) were
considered and he was given a course of azithromycin and fluconazole.
Despite antibiotic therapy, respiratory distress persisted, congenital heart disease was considered and
ECHO was done which showed 2mm OS-ASD. Hence, CCF was considered and he was started on
furosemide, enalapril and digoxin.
His respiratory distress had a waxing and waning course, salbutamol nebulizations were given in
view of co-existing wheeze.
He was discharged at request on postnatal day 107 (at 3 ½ months)
 Past History:
Age Weight Status
2 mo (Day 62) 3.1 kg 1st admission at JIPMER
3 ½ mo (Day 3.3 kg Discharge at request
107)
5 mo 4.55 kg Lost to follow up. Discontinued elemental diet, anti – failure therapy
and thyroxine. Was on cow’s milk diet for 1 ½ months. Had persistent
respiratory distress. Repeat ECHO showed 3.5 mm OS – ASD. He was
started on furosemide at 2.5mg/kg/day. Advised admission but
parents deferred.
5 ½ mo 4.6 kg No respiratory distress. On furosemide at 2.5mg/kg/day.
TSH levels normal.
6 ½ mo 4.95 kg No respiratory distress.
7 ½ mo 4.9 kg 2nd admission at JIPMER in view of respiratory distress
 Family History:
2nd born out of non-consanguineous marriage.
Twin sibling healthy.
History of elder sibling death at 5 months of age; history suggestive of skin
lesions, jaundice and hematemesis (? Cholestasis).
No other significant family history.
 Antenatal History:
Uneventful antenatal period.
Twin gestation (history suggestive of dizygotic twins).
 Natal History:
Term, SGA, SVD at JIPMER;
Cried immediately after birth,
Birth weight – 2.2 kg.
 Neonatal History:
Uneventful neonatal period.
No history of NICU stay.
 Immunization History:
Immunized for age.
 Developmental History:
Gross motor developmental delay +,
Head control +, sits with support +.
Fine motor & social development is appropriate for age.
Language delay+
 Examination at admission:

General Condition: Active, alert

Pallor+
No Icterus, Cyanosis, Clubbing, Generalized lymphadenopathy, Generalized
edema
Vitals:
Temperature Pulse Rate/ Pulse Respiratory Rate SpO2 Blood Pressure CRT
Volume
Afebrile 128 per minute, 52 per minute 85 % on room air 80/ 50 mmHg 2s
Good volume to 99% on HFNC
 Anthropometry:

Anthropometric Measured Z score Interpretation

Parameter
Weight 4.9 kg Conventional Z Failure to thrive
Length 64 cm scores can’t be
applied as the infant
Head Circumference 40 cm
was born SGA
 Examination at admission:
Respiratory System: Intercostal and subcostal retractions, bilateral air entry
equal, bilateral wheeze and crepitations.
Cardiovascular System: S1, S2 – Normal; No murmurs heard.
Per Abdomen: Soft, No organomegaly.
Nervous System: No abnormalities detected.
 Investigations:
Date 31.5.18 8.6.18 (Week 2) 27.6.18 (Week 4) 1.7.18 (Week 5)
Hemoglobin 11.3 10.7 10.8 11.0
Total Leucocyte 17480 18220 15970 23930
Count
Differential Count N39L46M12 N59L30M11 N50L37M12 N56L30M14
Platelet Count 556000 415000 288000 478000
Peripheral Smear - - Microcytic -
hypochromic RBCs
Date 9.7.18 (Week 6) 15.7.18 (Week 7) 25.7.18 (Week 8)

Hemoglobin 11.9 9.0 9.3

Total Leucocyte Count 13900 8230 16940

Differential Count N30L64M5E1 N21E3L65M11 N26E4L59M11

Platelet Count 338000 140000 450000

Peripheral Smear Microcytic hypochromic RBCs - -

Date 31.5.18 (W1) 27.6.18 (W4) 1.7.18 (W5) 8.7.18 (W6) 15.7.18 (W7) 25.7.18 (W8)
Urea/Creatinine 59/ 0.56 35/ 0.41 30/ 0.42 30/ 0.51 15/ 0.42 19/ 0.42
Sodium/ 132/ 4.8/ 96.8 129/ 4.24/ 132/ 5.05/ 98 132.4/ 5.19/ 133.8/ 4.64/ 133.1/ 4.87/
Potassium/ 101.2 102.4 102.4 97.1
Chloride

Calcium/ 9.1/ 1.8 9.0/ - 8.8/ 3.3 9.6/ 2.3 8.8/ 2.4 2.5/ 2.1
Magnesium

Inorganic 7.3/ 4.1 5.6/ - 5.4/ 2.9 7.0/ - -/ - -/ -

Phosphorus/ Uric
Acid
Date 16.6.18 (W3) 27.6.18 (W4) 1.7.18 (W5) 25.7.18 (W8)

T. Bil. / D. Bil. 0.43/ 0.23 0.30/ 0.18 -/ - -/ -

AST / ALT 69/ 115 38/ 96 -/ - 31/ 52

ALP /GGT 158/ 14 150/ 8 -/ - 173/ 15

T. Protein/ Albumin 7.0/ 4.6 6.5/ 3.9 5.7/ 3.7 7.5/ 4.1

PT-INR (3.7.18) – 15.8s/ 1.19

 Week 1
O2 by HFNC
CRP at admission - Negative
3% saline and salbutamol nebulizations
Course of Oseltamivir
Community acquired pneumonia - amoxicillin/ clavulanic acid - 6 days
Influenza A and B – Negative
Blood C/S - sterile
Changed to O2 by nasal prongs
F-100 diet (tube feeds)
 Week 2
Persistent respiratory distress
Lansoprazole - gastroesophageal reflux
Persistent wheeze - 5 day course of oral prednisolone
 Week 3
Persistent respiratory distress
Atypical pneumonia - 5 day course of azithromycin given.
HRCT Thorax – Multiple tree in bud centrilobular opacities distributed in
bilateral lung fields – possibility of infective bronchiolitis.
TB Work –up Negative
 Week 4
Respiratory distress and oxygen dependency persisted.
Course of oral fluconazole in view of suspected fungal pneumonia
Planned for bronchoscopic evaluation.
 Week 5
Oxygen dependency and persistent respiratory distress

Leucocyte counts - neutrophilic leukocytosis, CRP was positive;

Hospital acquired infection - Cefaperazone+Sulbactam/ Amikacin.
Blood Culture for fungus - Sterile
.
 Week 6
Blood culture - Staphylococcus aureus and hence antibiotic was changed to Cloxacillin.
Improved respiratory distress.
 Week 7
Completed 14 days of Cloxacillin.
Repeat blood culture - sterile.
Respiratory distress gradually reduced
Off oxygen
Oral feeds
Planned for repeat TB work up.
 Week 8
Empirical ATT
Bronchoscopy
Broncho-alveolar lavage:
M/E – few RBCs, 580 WBCs (95% neutrophils, 5% mononuclear cells); sheets
of neutrophils, few bronchial epithelial cells, alveolar macrophages.
AFB – Negative, Gene Xpert for MTB – Negative
Fungal C/S – Sterile
 Week 9
C/S – Pseudomonas aeruginosa S/Amikacin, Cefoperazone+Sulbactam, Ceftazidime,
Ciprofloxacin, Piperacillin+Tazobactam
Sweat Chloride (iontophoresis) – 27.7.18 132mmol/l (6.9g/m2/min)
Stool for fat globules – Negative
 Week 10
14 day course of ceftazidime and sulbactam
Sweat Chloride (iontophoresis) – 07.08.2018 – 133 mmol/l (9.0 g/m2/min)
 Final Diagnosis
? Cystic Fibrosis
Persistent Pneumonia (Pseudomonas aeruginosa)
? Pulmonary Tuberculosis
Hospital Acquired Blood Stream Infection (Staphylococcus aureus)
Failure to thrive
Nutritional (Iron Deficiency) Anemia
 Cystic Fibrosis

Most common autosomal recessive disorder in Caucasians

Affects 1 in 2500

Estimated incidence in Asians 1:10,000 to 1:12,000

36
 Gene Locus
Chromosome 7; Locus 7q31.2
The CFTR gene:
250, 000 bp long
27 exons
Protein has 1,480 amino acids with a molecular mass of 168, 138 Da
37
CFTR Function
Cilia Function in CF

•Altered microenvironment
•Low HCO3− & acidic Ph
•Alters mucus rheology
•Poor mucociliary clearance
 Classes of CFTR Mutations

I II III IV V
Defective Defective Defective Defective Reduced
Production Processing Regulation Conductance Amounts

40
1,000 mutations in CFTR known
Worldwide most common mutation is ΔF508(66%)
Deletion of Phenyalanine at position 508.
In Indian Scenario, ΔF508 accounts for 19-44%
Carrier frequency of ΔF508 Indian population is 1 in 238
 Respiratory
Recurrent LRTI
Extensive
Sinusitis Colonisation
Bronchiolitis
Nasal Polyps

Pulmonary Parenchymal
Fibrosis Pneumothorax
(Bromnheictasis)
 Common Organisms
Which are the organisms commonly involved in colonization ??
 Gastrointestinal System

Meconium Ileus
Pancreatic Insufficiency
Rectal Prolapse Adenocarcinoma

Failure To thrive
Malabsorption
DIOS
 Other Systems

Inspissated Bile Hyperoxaliuria

Hepatic
steatosis Hypocitraturia
Renal
Cirrhosis Calculi

Males :Infertile- No
Fractures Endocrine wolfian structures
Clubbing Diabetes Female: Subfertile-
•Malnutrition Arthropathy Fertility malnutrition
•Immune Complexes Tenacious Cervical
Secretions.
 Nutritional

Impaired
calorie
Malabsorpt Intake
ion
Micronut
rient &
EfA
Deficien
cy

Increased colonisation
Failure to thrive with Pseudomonas
 Indian Presentation

Molecular Basis of Cystic Fibrosis Disease: An Indian Perspective :R. Prasad • H. Sharma • G. Kaur
 Diagnosis
Presence of typical clinical features OR
A history of CF in a sibling OR
A positive newborn screening test

Plus lab evidence of CFTR dysfunction

Two elevated sweat chloride obtained on separate days OR
Two CF mutations OR
Abnormal nasal potential difference
Sweat Chloride
 Sweat Test

False positive False negative

Eczema (atopic dermatitis) Malnutrition
Ectodermal dysplasia
Edema
Congenital adrenal hyperplasia
Adrenal insufficiency Insufficient sweat quantity
Nephrogenic diabetes insipidus Hyponatremia
Prostaglandin E infusions
 Other Investigations
Respiratory tract culture for CF-associated pathogens,
Throat Swab
Sputum Culture
Bronchoalveolar lavage
Pulmonary function testing
Early-Obstructive pattern
Late-Restrictive
 Pancreatic tests

Measurement of fecal elastase,

Duodenal fluid after stimulation with secretin and cholecystokinin.

Increased ingested fat in a 72-hour stool collection

Stool for Fat globules

Management of Cystic Fibrosis

54
 Respiratory Nutritional

Physiotherapy Feeding
Antibiotics Micronutrient supplementation
Mucolytics Pancreatic enzyme therapy
Antiinflammatory agents
Complications
 Physiotherapy
• Postural drainage
• Percussion and vibration techniques
• Huffing and directed coughing.
• Devices
• Positive expiratory mask therapy
• High pressure positive expiratory masks
• Oscillating device -flutter/cornet
• Greater sputum expectoration
• Improved lung function results.
 Hypertonic Saline
Concentration of 5% to 7%
Improves mucociliary clearance
Small improvement in lung function up to 4 weeks of treatment
No improvement in lung function in the long term.
Reduce the frequency of pulmonary exacerbations
Improvement in quality of life in adults.
Used with bronchodilator, its safe and inexpensive
Nebulised hypertonic saline for cystic fibrosis (Cochrane Review) Wark P, McDonald VM
 Mucolytics
Human recombinant • Improves pulmonary function
DNase (2.5 mg)- single • Decreases number of pulmonary exacerbations
aerosol/day

N-acetylcysteine(5-10% • Airway clearance

solution) • Augment airway levels of glutathione

• Draw water into the airway

Hypertonic saline • Rehydrate mucus & periciliary fluid layer
• Improved mucociliary clearance
 Antibiotics
• Organisms to target
• S. aureus
• Non -typeable Haemophilus inflenzae
• P. aeruginosa
• B. cepacia
 Antibiotics

Oral Intravenous Aerosolized

• Duration 2 weeks. • Duration 2 weeks • Tobramycin

• Azithromycin (3 times • Pseudomonas-Require 2 • Aztreonam
/wk) improves lung drugs. • Pseudomonas density in
function in chronic P. sputum Hospitalizations
aeruginosa infection Pulmonary function
≥10%
 Other medications

• Ibuprofen (50-100 μg/mL) for 4 yr, slows disease progression,

particularly in younger patients with mild lung disease.

• Steroids –benefit risk ratio low

*Cystic Fibrosis Pulmonary Guidelines Chronic Medications for Maintenance of Lung Health
 Complications

• Atelectasis

• Hemoptysis

• Pneumothorax

• ABPA (5-10%)

• Respiratory Failure
 Nutritional
• Dietary goals
Energy intake- 120-150% of RDA
Protein -150-200% of RDA for age
Fat intake - 40% of total energy requirements
• Supplementation
Fat soluble Vitamin A- 5,000-10,000 IU Vitamin D -400-800 IU Vitamin E- 5-10 IU/kg/d
Vitamin K is not needed with enzyme therapy.
Water soluble vitamins -2RDA
Iron, Zinc
 Pancreatic Enzyme
Infants- Per 120 mL give 1/4 to 1/3 of a capsule.
Children and adults- Initial dose of 1-2 capsules / meal and ½ to 1 capsule with fat
containing snacks
Dose can be increased gradually
Clinical symptoms
Stools morphology
Weight & growth
Not to exceed 10,000u/kg/day
 Instructions
• Traine to swallow the capsule
• Microsphere should not be sprinkled or mixed with whole meal but given from
a spoon in one swallow
• Beginning or early in the meal
• ½ dose at beginning and ½ in middle of meal.
• Stools are persistently greasy despite a recent increase in dose ,use antacid .
• Treatment makes an acidic duodenum more alkaline, therefore encouraging
maximum enzyme activity
 Ivacaftor (Kalydeco)

• Potentiator of CFTR mutation, G551D (5%),a class III CFTR mutation.

• Improvement in
• FEV1 by an average of 10.6%,
• Decreased frequency of pulmonary exacerbations by 55%,
• Decreased sweat chloride by an average of 48 mEq/L,
• Increased weight gain by an average of 2.7 kg.
• Approved for CFTR-G551D patients ≥6 yr old, as a 150 mg, twice per day, oral therapy.
 Psychological & Genetic Management

• Counselling and emotional support

• Cystic Fibrosis Foundation

67
 Prognosis

Survival has improved

• Result of improved nutritional status, physiotherapy and antibiotic treatment.
• Median cumulative survival of 37-40 yr.

68
Thank You!