PEDIATRIC ALLERGYAND IMMUNOLOGY (JM PORTNOYAND CE CIACCIO, SECTION EDITORS)

Anaphylaxis in Children: Current Understanding and Key

Issues in Diagnosis and Treatment
Chitra Dinakar
Published online: 20 July 2012
#The Author(s) 2012. This article is published with open access at Springerlink.com
Abstract Anaphylaxis is a severe allergic reaction that is
rapid in onset and may cause death. Since it is unpredictable
and potentially fatal, prompt recognition and treatment are
vital to maximize a positive outcome. The occurrence of
anaphylaxis is increasing across all ages in the United
States, with increased risk of worse outcome in teenagers/
young adults and in those with comorbid conditions such as
asthma. Gaps in the assessment of patient-specific risk fac-
tors, identification and prevention of triggers, recognition of
signs/symptoms, and pharmacologic treatment of anaphy-
laxis have been identified at the physician and caregiver/
patient level. A PubMed literature search (January 2000
December 2011) was conducted to identify publications on
childhood anaphylaxis using the following terms: food
allergy, food allergens, food hypersensitivity, epinephrine,
epinephrine auto-injectors, anaphylactic triggers, and ana-
phylaxis. This review will critically appraise these key
issues and highlight strategies that might result in improved
management of anaphylaxis in children.
Keywords Epinephrine
.
Food allergy
.
Food
hypersensitivity
.
Pediatric
.
Children
.
Anaphylaxis
.
Diagnosis
.
Treatment
Introduction
Anaphylaxis is a potentially fatal condition that can occur
without warning [1]. Prompt diagnosis and treatment are
crucial [2, 3]. Previously, the lack of a universal defini-
tion for anaphylaxis resulted in misdiagnosis, underreport-
ing, and miscoding, impeding epidemiological research on
this condition. To address this issue, a definition was stan-
dardized in 2005 by the Joint Task Force on Practice Param-
eters, representing the American Academy of Allergy, Asthma
and Immunology (AAAAI), the American College of Allergy,
Asthma and Immunology (ACAAI), and the Joint Council of
Allergy, Asthma and Immunology (JCAAI) [4]. The Joint
Task Force defined anaphylaxis as a condition caused by an
[immunoglobulin E] IgE-mediated reaction that is often
life-threatening and almost always unanticipated. Anaphy-
lactoid reactions were defined as non-IgE-mediated reactions
with the same clinical picture as anaphylaxis. When both IgE-
mediated and non-IgE-mediated mechanisms were a possible
cause, the termanaphylactic was used to describe the reaction.
Due to the wide variability in defining anaphylaxis, inci-
dence and prevalence data should be interpreted with cau-
tion [5]. In a population-based study in Rochester,
Minnesota from 19902000, the annual age- and sex-
adjusted incidence of anaphylaxis was estimated to be 49.8
per 100,000 person-years [6]. In this study, age-specific
rates were highest for ages 09 years (75.1 per 100,000
person-years) and 1019 years (65.2 per 100,000 person-
years). In contrast, a previous study in Seattle, Washington
from 19911997 estimated the rate of anaphylaxis in chil-
dren and adolescents to be 10.5 per 100,000 person-years
[7]. The reason for this difference is likely due to differences
in the definitions of anaphylaxis used. In addition, although
both studies also reviewed samples of records with less
specific allergy codes, only the Rochester study included
these cases in the estimated incidence.
Although overdiagnosis of anaphylaxis can occur (due to
overlap of symptoms with panic attack, hyperventilation,
vasovagal episode, etc.), underdiagnosis is more common
as an episode may not be recognized due to the absence of
C. Dinakar (*)
Section of Allergy, Asthma and Immunology, Childrens Mercy
Hospital and Clinics, University of Missouri-Kansas City,
2401 Gillham Road,
Kansas City, MO 64108, USA
e-mail: cdinakar@cmh.edu
Curr Allergy Asthma Rep (2012) 12:641649
DOI 10.1007/s11882-012-0284-1
cutaneous findings or misinterpretation of nonspecific signs
(eg, confusion, nausea, dyspnea). Underreporting and mis-
coding can also lead to an underestimation of preva-
lence [5, 8]. Of the approximately 12.4 million allergy-
related emergency department visits from 19932004,
only 1 % received the diagnosis of anaphylaxis [9].
Several studies have shown that anaphylaxis is often
miscoded or misclassified, with 21 %57 % of food
allergy or anaphylaxis cases coded with less specific
allergy or anaphylaxis codes (eg, unspecified allergy)
[68]. As the percentage of cases identified from review
of nonspecific diagnoses was similar in the Rochester
study (25 %), and the Seattle study (21 %), the fre-
quency of miscoding appears to be similar in both
adults and children.
Anaphylaxis Triggers
Across all age groups, the most common triggers for ana-
phylaxis are ingested foods (33 %), insect stings (19 %), and
medications (14 %) [6]. Less common triggers include cats,
latex, cleaning agents, environmental allergens, and exer-
cise. For about a quarter of cases, the trigger is unknown. In
children, food-induced anaphylaxis is the most common
trigger and accounts for 37 %85 % of cases, whereas insect
bites/stings account for 5 %13 % and medications account
for 5 %12 % [1012]. Despite differences between studies,
food allergy is clearly the most common cause of anaphy-
laxis in children.
In children, the most common food allergens are milk
products (19 %29 %), peanuts (9 %36 %), tree nuts
(9 %19 %), eggs (5 %22 %), shellfish (4 %17 %),
and fruits and vegetables (9 %) [10, 13, 14, 15];
regional differences most likely account for the differences
between studies. In the United States, shellfish is the most
common food allergen in persons aged 5 years, whereas
eggs, fruits, peanuts, and tree nuts are more common in those
aged <5 years [8]. The most common medication allergens are
antibiotics (67 %) [10, 12].
Data suggest that the prevalence of food allergy is
increasing. An analysis of multiple United States national
surveys showed that food allergy in school-aged children
increased from 3.3 % in 1997 to 3.9 % in 2007 [16]. In a
recent United States survey of 38,480 children, the prevalence
of food allergy was 8 %, with 38.7 % of those having a history
of severe reactions [14].
Information regarding the prevalence of fatal allergic
reactions is limited. In an Australian study, the causes of
anaphylaxis fatalities were drugs or probably drugs (58 %),
insect bites/stings (18 %), undetermined (13 %), food (6 %),
and other (5 %) [17]. Although most admissions for food-
induced anaphylaxis occurred in children less than 5 years
of age, all food-induced anaphylaxis fatalities were in
patients between 8 and 35 years of age. Similarly, although
insect sting-induced admissions peaked between 5 and
9 years of age, most insect sting-induced anaphylaxis deaths
occurred between 35 and 84 years of age. Based on extrap-
olation of data from a United States-based population study,
it is estimated that there are about 150 deaths annually due
to food-induced allergic reactions [18]. In this study, fatal-
ities occurred in patients aged 2 to 33 years, with 9 % in
children less than 7 years of age and 53 % in teenagers.
In addition to these IgE-mediated triggers of anaphylaxis,
other causes of anaphylaxis that should be considered in-
clude: galactose alpha-1,3-galactose, a carbohydrate
contained in red meat that was recently described to cause
anaphylaxis [19]; non-IgE-triggered mechanisms, such as
through the complement and coagulation pathways initiated
by oversulfated chondroitin components in heparin [20];
reactions in patients with mastocytosis and mast cell disor-
ders; and idiopathic anaphylaxis [21].
Diagnosis and Management
Recommendations for the management of anaphylaxis are
predominantly based on expert opinion and consensus. The
AAAAI/ACAAI/JCAAI practice parameter and the World
Allergy Organization guidelines provide an evidence-based
approach to diagnosis and management of anaphylaxis [3,
21]. In addition, guidelines published by the National
Institute of Allergy and Infectious Diseases (NIAID) for
the diagnosis and management of food allergy [2] provide
a paradigm for the acute management of food-induced ana-
phylaxis, which is similar to treatment of anaphylaxis as a
result of other causes. A version of this guideline that
focuses on the pediatric population is also available [22].
Guidelines for both adults and children stress rapid diag-
nosis as being key to optimal management [2, 3, 21,
22]. Anaphylaxis affects multiple organs, including the skin,
respiratory tract, gastrointestinal tract, cardiovascular sys-
tem, and central nervous system [23]. Signs and symptoms
of anaphylaxis for adults and children are summarized in
Table 1 [3, 11]. Although cutaneous symptoms predomi-
nate in adults, the primary presenting symptoms in children
are respiratory in nature (e.g., wheezing, shortness of breath)
[11]. In addition, cardiovascular symptoms tend to be less
common in children (17 %) than in adults (30 %35 %) [3,
11]. This could be due to increasing age and comorbid
disease in adults; however, it could also be due to differ-
ences in the prevalence of triggers between adults and
children. Food related causes, which tend to cause respira-
tory tract involvement, are more common in children where-
as medication and venom causes, which tend to cause
cardiovascular reactions, are more common in adults [10].
642 Curr Allergy Asthma Rep (2012) 12:641649
Typically, exposure to the triggering allergen is followed
by the rapid development of symptoms over minutes to
several hours. In both adults and children, the time course
of the reaction may be uniphasic (occurring immediately
after exposure and resolving with or without treatment in
minutes to hours), biphasic (recurring after the apparent
resolution of initial symptoms, usually about 8 h after the
first reaction), or protracted (persisting for hours or days
following the initial reaction) [2, 22]. Early recognition of
signs and symptoms, timing of the reaction, and existence of
comorbid conditions and concomitant factors can aid in
diagnosis [2].
The development of diagnostic criteria represents an
important advancement in anaphylaxis management, and
it is estimated that these criteria enable health care
providers to identify about 95 % of cases [1]. Never-
theless, accurate diagnosis in children presents chal-
lenges. This is partially due to the inability of children
to accurately describe their symptoms [24], and the lack
of cutaneous symptoms in about 18 % of cases [10].
Parents and caregivers of children with food allergies are
often unable to recognize and manage anaphylaxis. In stud-
ies evaluating parents, only 48 % of parents could identify
more than one symptom that would require use of epineph-
rine [25], and only 43.5 % reported receiving education
regarding their childs food allergy and management of
his/her reactions [26]. Venues where children are supervised
or receive care, such as schools and child care centers, also
need to be prepared to recognize and manage anaphylaxis.
In a study of anaphylactic events in 48 Massachusetts public
school districts, of 114 subjects who received epinephrine in
the school setting (46 % were of elementary age), school
personnel were unaware that the individual had a life-
threatening allergy in 24 % of cases [27].
Physicians may also be unable to correctly diagnose
food-induced anaphylaxis because of inadequate knowledge
of food allergies. In a case-based survey of 419 pediatricians
without specialized allergy training, only 56 % of respond-
ents could appropriately recognize and treat food-induced
anaphylaxis [28]. An analysis of referrals to a pediatric
allergy clinic found that only 34.5 % of food allergy cases
were accurately diagnosed [26]. These observations under-
score a need to educate physicians and families on recogni-
tion of anaphylaxis and improve competence in recognizing
this potentially fatal condition.
Treatment
First-Line Treatment
Evidence-based guidelines recommend the prompt adminis-
tration of epinephrine as first-line treatment for an anaphy-
lactic episode [2, 3, 21]. Timely administration of
epinephrine can be life-saving and help delay the progres-
sion of a life-threatening reaction so that medical attention
can be provided [29]. Table 2 outlines the basic steps for
management of anaphylaxis [21].
In children, the recommended dose of epinephrine is
0.01 mg/kg of a 1:1000 (1 mg/mL) solution via intramus-
cular injection into the mid-anterolateral thigh [3]. Auto-
injector dosing for epinephrine is 0.15 mg for children who
Table 1 Signs and symptoms of
anaphylaxis
Symptoms All ages [3] Children [11]
Clinical features Frequency Clinical features Frequency
Respiratory Dyspnea, wheeze 45 %50 % Difficulty/noisy breathing 83 %
Upper airway
angioedema
50 %60 % Wheeze 59 %
Rhinitis 15 %20 % Cough 33 %
Swelling tongue 13 %
Swelling/tightness in throat 11 %
Difficulty talking/hoarse voice 13 %
Cutaneous Urticaria,
angioedema
85 %90 % Urticaria 72 %
Flushing 45 %55 % Angioedema 55 %
Pruritus without rash 2 %5 % Pruritus 11 %
Gastrointestinal Nausea, vomiting,
diarrhea, cramping
pain
25 %30 % Vomiting, diarrhea,
abdominal cramps
29 %
Cardiovascular Dizziness, syncope,
hypotension
30 %35 % Hypotension, pale and floppy,
impaired/loss of consciousness,
collapse
17 %
Curr Allergy Asthma Rep (2012) 12:641649 643
weigh 1025 kg and 0.3 mg for those who weigh >25 kg
[22]. Repeated dosing of epinephrine is recommended for
suboptimal response or symptom progression [2, 3].
Intravenous infusion of epinephrine or intravenous bolus
should be considered if shock has developed or cardiac
arrest is imminent [22].
According to a consensus statement from the AAAAI
regarding the management of anaphylaxis in patients with
a previous anaphylactic reaction in the child care setting,
epinephrine should be given at the start of any reaction
occurring subsequent to contact with a known or suspected
allergen [30]. Calling for medical help and concurrent elim-
ination of additional allergen exposure is also recommended
[2]. Although it is generally recommended to place the
patient in a recumbent position with lower extremities ele-
vated, individuals who are experiencing respiratory distress,
which is common in children, and/or vomiting should instead
be placed in a comfortable position with lower extremities
elevated [21]. If possible, supplemental oxygen and fluid
resuscitation should be provided [31].
Epinephrine has alpha- and beta-adrenergic properties
through which it increases blood pressure, prevents and
relieves hypotension and shock, decreases upper airway
obstruction (e.g., in the larynx), decreases urticaria and
angioedema, and decreases wheezing [21]. Patients may
experience self-limiting effects after epinephrine administra-
tion, such as pallor, tremor, anxiety, palpitations, dizziness,
and headache [21]. In both adults and children, significant
adverse effects, such as ventricular arrhythmias, hyperten-
sive crisis and pulmonary edema, can occur after an
overdose of epinephrine by any route of administration,
although typically they are reported after intravenous dosing
(e.g., rapid infusion, bolus administration, dosing error due
to administration of concentrated solution appropriate for
intramuscular injection). Misunderstanding about the cor-
rect dose and route of epinephrine administration in hospital
and emergency department settings can lead to serious car-
diovascular complications from overdose [32]. In infants
especially, it is important to use caution when calculating
and drawing up an epinephrine dose, to stay vigilant for
changes in vital signs, and to ensure use of age-appropriate
blood pressure norms [21].
Epinephrine Auto-Injectors
Epinephrine auto-injectors (EAIs) are the cornerstone of
treatment in the first-aid management of anaphylaxis in the
community setting. For allergic reactions occurring in the
community setting, it is recommended to administer the
patients EAI without delay [31]. A second dose can be
administered after 510 min based on patient status.
EAIs are often prescribed because of their ease of use and
ability to rapidly produce peak epinephrine concentrations
following intramuscular injection [33, 34]. Children at risk
for anaphylaxis may need to carry 2 doses of epinephrine for
several reasons: the first dose may not be administered
effectively; symptoms may persist despite a successful first
injection; or the patient may experience biphasic anaphylax-
is. In a study of children with multiple food allergies, 19 %
of food-induced anaphylactic reactions required 2 doses of
Table 2 Basic management of anaphylaxis
1. Have a written emergency protocol for the recognition and treatment of anaphylaxis and rehearse it regularly.
2. Remove exposure to the trigger if possible (eg, discontinue an intravenous diagnostic or therapeutic agent that seems to be triggering symptoms).
3. Assess the patients circulation, airway, breathing, mental status, skin, and body weight (mass).
Promptly and simultaneously, perform steps 46
4. Call for help: resuscitation team (hospital) or emergency medical services (community) if available.
5. Inject epinephrine (adrenaline) intramuscularly in the mid-anterolateral aspect of the thigh (0.01 mg/kg of a 1:1000 (1 mg/mL) solution),
maximum of 0.3 mg for children (0.5 mg for adults); record the time of the dose and repeat it in 515 min, if needed. Most patients respond to 1
or 2 doses.
6. Place the patient in a position of comfort and elevate the lower extremities. (Note: in adults, fatality can occur within seconds if the patient stands
or sits suddenly. It is not known if this also applies to children.)
7. When indicated, give high-flow supplemental oxygen (68 L/min) by face mask or oropharyngeal airway.
8. Establish intravenous access using needles or catheters with wide-bore cannulae (1416 gauge). When indicated, give 12 L of 0.9 % (isotonic)
saline rapidly (e.g., 10 mL/kg in the first 510 min to a child).
9. When indicated at any time, perform cardiopulmonary resuscitation with continuous chest compressions.
a
In addition,
10. At frequent, regular intervals monitor patients blood pressure, cardiac rate and function, respiratory status, and oxygenation (monitor
continuously, if possible).
a
Resuscitation guidelines recommend initiating cardiopulmonary resuscitation with chest compressions only (hands-only), before giving rescue
breaths. In children, the rate should be at least 100 compressions/min at a depth of 5 cm (4 cm in infants)
(Adapted from Simons et al. [21])
644 Curr Allergy Asthma Rep (2012) 12:641649
epinephrine and 6 % of reactions required 3 doses [35].
Existing EAIs, EpiPen (Dey Pharma, L.P., Basking Ridge,
NJ), TwinJect (Shionogi Inc, Florham Park, NJ), Adrena-
click (Shionogi Inc.), Anapen (Lincoln Medical Ltd, Salis-
bury, Wiltshire, UK), and Jext (ALK Abell Ltd, Reading,
Berkshire, UK) are available in 2 pre-set doses of epineph-
rine (0.15 and 0.3 mg). It is important to note that at the time
this review was written, Twinject was no longer manufac-
tured in the United States and Adrenaclick was not marketed
anymore.
While EAIs have significantly improved emergency care
of anaphylactic reactions, there are several limitations with
the devices currently available. One of the primary limita-
tions is their symmetrical, pen-like appearance, which can
result in accidental needle sticks [35]. From 19942007,
prior to the redesign of the EpiPen, a total of 15,190 cases
of unintentional injections from EAIs were reported with the
number of reports increasing significantly (P<0.001) annu-
ally across all age groups [24]. In addition to adverse effects
such as local ischemia of the digit [36], accidental finger
injections may also result in partial or complete loss of the
epinephrine dose for the person having an anaphylactic
episode, known as the lost dose hazard. The symptoms
and signs of local ischemia reported include pain or numb-
ness, pallor, cyanosis, hypothermia, absence of sensation or
hyperesthesia, and weak or absent pulse, as well as skin
peeling, sensory loss, neuropraxia, and protracted ischemia
reperfusion pain. It is to be noted that none developed tissue
necrosis and that overall epinephrine is associated with a
good safety profile and most adverse events related to unin-
tentional injection of epinephrine resolve without additional
complications within 224 h with or without treatment [36].
Studies indicate that only 25 %55 % of patients carry their
EAI with them at all times, as recommended [29, 37]. This
may be due, at least in part, to the bulky size and shape of
currently available EAIs. It is important to note that the
second-dose feature available in some types of EAIs (i.e.,
TwinJect; Shionogi Inc) requires handling an exposed, used
needle [38]. In the school setting, such injectors should be
disposed of after the first dose has been used to reduce the risk
of needle-stick injury. Therefore, a separate unit should be
used if a second dose is required [38]. The pre-set, fixed dose
ranges (0.15 and 0.3 mg) of currently available auto-injectors
can be a limitation in the pediatric setting as the 0.15-mg dose
may be too strong for infants and toddlers weighing <15 kg,
and the 0.3-mg dose may be subtherapeutic for children
weighing >30 kg, particularly those who are overweight or
obese [39]. However, data to indicate what dose is correct,
inadequate, or adequate in children are currently lacking and
further studies are needed.
Current EAIs have a needle length of 1.27 cm for the
0.15 mg dose EAI and 1.58 cm for the 0.3 mg dose EAI,
which may be too short to penetrate the subcutaneous tissue
to achieve intramuscular injection in children who are over-
weight or obese [40]. Therefore, with currently available
EAIs, it is important to recognize that children who are
overweight or obese may be inadvertently receiving a subcu-
taneous injection, which will result in delayed epinephrine
absorption and a lower plasma concentration of epinephrine
[33]. To address this problem, additional research on needle
length is necessary. The United States Food and Drug Admin-
istration has issued guidance to the medical device industry
regarding the incorporation of human-factor engineering prin-
ciples into improving the design and safety of medical
devices [41]. Much of this guidance involves identifying and
preventing user-related hazards. As this guidance becomes
operational, it is hoped that further research will be undertaken
to address the discussed unmet needs.
In order for EAIs to be effective, they must be used
correctly and in a timely manner. However, there is a lack
of patient/caregiver education and ongoing skill-retention
regarding symptomrecognition and proper epinephrine admin-
istration in several settings [25, 42]. In a survey that assessed
patient/parent knowledge and usage of EAIs, 86 % of families
indicated they kept the epinephrine device with them at all
times, yet only 71 % of participants had their device with them
at their office visit, and only 32 % of participants could
correctly demonstrate how to use the EAI [29]. Furthermore,
10 % of participants possessed devices that were expired,
leaving just 55 % of families with unexpired epinephrine on
hand at the time of the survey [29]. School-aged children (aged
5 years) were less likely than younger children to have their
EAI with them when eating lunch (25 % vs 42 %) or a snack
(28 % vs 37 %) [37]. In a recent study of 14,677 patients who
filled an initial prescription for an EAI only 46 % ever refilled
the prescription (63 %for children), and only 11 % refilled it at
all the expected refill times [43]. It has been shown that
parental empowerment and training on the use of an EAI
significantly (P0.05) correlates with greater parental comfort
with administration [44], and EAI-training improves the odds
of having an EAI readily available [37]. In a quality-
improvement project at the Childrens Mercy Hospital (Kansas
City, MO) in which data from 277 patients at-risk for anaphy-
laxis was collected, less than half (44 %) of the patients had
their EAI devices with them. The most common reason cited
(47%56%) for not having the EAI device during their visit
was not realizing they had to carry it at all times (other reasons
included forgot, expired, lost, etc.). At the initial visit, only
about 3 out of 5 caregivers were able to correctly perform all
the steps to use the device. Our study reveals that a systematic
and periodic process of screening, education, and re-education
on carriage, and knowledge of use of this device is needed.
This process is nowroutine and mandatory in our clinics for all
patients at risk for anaphylaxis.
Preparedness for appropriately treating anaphylactic reac-
tions is suboptimal in child care centers. In a survey of 42
Curr Allergy Asthma Rep (2012) 12:641649 645
child care centers tending children aged 6 months to 6 years
in the suburbs of Chicago, only 24 % of center directors
initially stated that they would administer EpiPen for a
severe allergic reaction and only 55 % had trained staff for
this emergency [13]. An assessment of the long-term effec-
tiveness of an allergy seminar identified a need for recurring
anaphylaxis education among child care providers [42].
Although 77 % of child care center directors could demon-
strate EAI technique at 4 weeks post-training, knowledge
decreased to 48 % at 6 months, and 31 % at 1 year.
Gaps in anaphylaxis management extend to clinicians as
well, including incomplete understanding of how and when
to use EAIs, and inadequate provision of, or arrangement for
patient education. An assessment of 29 attending pediatri-
cians found that only 24 % provided families with written
indications for use of the EAI, only 21 % could correctly
demonstrate technique, and 14 % of pediatricians familiar
with EpiPen/EpiPen Jr incorrectly thought the device should
be refrigerated [29]. In a separate survey of food-allergic
individuals or caregivers (n01887), only 58.7 % of respond-
ents reported receiving training from the prescriber on the
use of auto-injectors [45]. Further, 86.6 % of participants did
not recall receiving oral counseling during dispensation of
EAI at the pharmacy [45]. These findings highlight the need
for all health care professionals to become comfortable with
EAI usage and to educate patients and their families appro-
priately. Health care professionals should also remind
patients that EAIs expire 1 year after dispensing [2], and
need to be stored at room temperature [38].
Physicians can help strengthen parental education by
appropriate referral to an allergist for children with anaphy-
laxis [3]. Just 1 visit to an allergy clinic has been reported
to improve parental knowledge of allergen avoidance, man-
agement of allergic reactions, and use of an EAI [26].
Physicians should also develop emergency action plans
(e.g., http://www.foodallergy.org/files/FAAP.pdf) for chil-
dren with food allergies [3]. An e-mail survey of 1885
individuals who had survived anaphylaxis or had been respon-
sible for someone who had survived anaphylaxis, reported
that 62 %64 % of participants did not have a plan of action
readily available [46]. Food-allergy emergency action plans
are essential in the school setting also. A recent survey of
elementary and middle school nurses from 43 schools in
South Carolina found food-allergy emergency action plans
in place in only 44 % of schools [47]. As an added consider-
ation, Bansal et al. reported that most child care centers (98 %;
n041) do not have medications on hand to treat an allergic
reaction unless provided by the caregiver [13]. Thus, in addi-
tion to establishing a standard anaphylaxis-management pro-
tocol, state/federal policy must permit schools to have a
supply of epinephrine on hand for general use [27, 38].
In summary, in the community, prompt administration of
epinephrine via an EAI is crucial. Ongoing education is
required to ensure patients and child care providers always
have an unexpired EAI with them, know how to correctly
use their EAI, and know what to do in case of a severe
allergic reaction. In addition, health care professionals need
to become comfortable with EAI usage and provide appro-
priate education for patients/caregivers.
Second-Line Treatment
Second-line treatment options in the outpatient setting in-
clude
2
-agonists, antihistamines, and glucocorticoids.
These agents may be administered in a hospital-based set-
ting, along with vasopressors, glucagon, and activated char-
coal [2, 3, 48]. Although commonly used, data
supporting the role or effectiveness of second-line treatment
options in the management of anaphylaxis are limited [49,
50]. Hence, these second-line treatments should be consid-
ered only as adjunct therapy to epinephrine.
Preventive Measures
Preventive measures may reduce the risk of anaphylaxis in
susceptible individuals. Anaphylaxis education should begin
prior to discharge from the health care facility and include a
prescription for an EAI, education on technique, recommen-
dation of a medical identification bracelet or wallet card, and
referral to an allergy/immunology specialist for assessment of
triggers. Anaphylaxis triggers should be identified by taking a
detailed history, and be confirmed when possible by using
allergen skin tests or serum allergen specific IgE levels [21].
Avoidance of suspected triggers or co-triggers is key to the
management of anaphylaxis; however, this approach is often
unsuccessful due to inadequate patient education and under-
standing of allergen avoidance, and a lack of awareness of
triggers, particularly during a first episode [51, 52]. Physicians
should provide families of allergic children with detailed
information regarding relevant triggers and how to avoid
them. In addition, the Food Allergy and Anaphylaxis Network
website contains information on food allergen avoidance,
among other issues, and may be a useful resource for families
and physicians (http://www.foodallergy.org).
In addition to avoidance, the guidelines recommend
patients should receive a prescription for an EAI and referral
to an allergy/immunology specialist [3]. However, retro-
spective studies report low compliance with these guidelines
in both adults and children, although concordance with
recommended care was somewhat better among patients
who were admitted to the hospital (59 % prescribed EAI;
35 % referred to allergist) [53]. In children considered to
have food-induced anaphylaxis, 51 %63 % received an
EAI prescription and 24 %33 % were referred for follow-
up [14, 15]. Among those admitted to hospital, 94 % were
646 Curr Allergy Asthma Rep (2012) 12:641649
prescribed an EAI and 69 % were referred to an allergist
[15]. These data indicate that many patients are not receiv-
ing basic tools to prevent or manage subsequent anaphylaxis
events.
Several other preventive measures are available for allergen
triggers, such as immunotherapy for insect bites/sting reac-
tions, avoidance of the drug or therapeutic substitution with a
noncross-reacting medication, and desensitization protocols
for drug allergy. Patients with frequent episodes of idiopathic
anaphylaxis may benefit from prophylactic treatment with a
systemic glucocorticoid and an H1-antihistamine [3] or pro-
phylactic omalizumab injections [21].
Experimental approaches to prevent food-allergy reac-
tions include immunotherapy [54, 55], anti-IgE therapy
[56], and possibly early introduction of solids and allergenic
food contrary to past infant-feeding guidelines [57]. Preclin-
ical data hint at the potential efficacy of Chinese herbal
medicine [58] and probiotic supplementation [59] in food
allergy prevention. However, studies are needed to investi-
gate the effectiveness and safety of the above approaches for
preventing anaphylaxis in children with food allergy.
Conclusions
Numerous gaps in the diagnosis and management of ana-
phylaxis in children exist at both the physician and caregiv-
er/patient level. The key to successful management involves
recognition of populations at risk (e.g., children with food
allergies) and rapid diagnosis with early initiation of effec-
tive evidence-based therapy. Ongoing education is required
to improve the ability of physicians and families to recog-
nize anaphylaxis in children. Epinephrine is the recommen-
ded first-line treatment for anaphylaxis in both inpatient and
outpatient settings, and should be administered promptly
upon recognition of signs and symptoms. Although
second-line treatments are available, they should be consid-
ered only as adjunct therapy to epinephrine. Ongoing edu-
cation is required to ensure patients and child care providers
understand the importance of always having an unexpired
EAI with them, knowing how to correctly use their EAI, and
knowing what to do in case of a severe allergic reaction.
Epinephrine auto-injectors allow for the prompt admin-
istration of epinephrine in the community setting and must
be prescribed to all patients at risk. Advances in the design
of these devices to improve safety and convenience of
carriage and use, may further aid in successful management
of children with anaphylaxis.
Acknowledgments The author received editorial/writing support in
the preparation of this manuscript provided by Marinella Calle, PhD, of
Excerpta Medica, funded by Sanofi US. The author did not receive
honoraria related to the preparation of this manuscript.
Disclosure No potential conflicts of interest relevant to this article
were reported.
Open Access This article is distributed under the terms of the Crea-
tive Commons Attribution License which permits any use, distribution,
and reproduction in any medium, provided the original author(s) and
the source are credited.
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