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Anaphylaxis in infants
Author: Scott H Sicherer, MD, FAAAAI
Section Editor: Robert A Wood, MD
Deputy Editor: Elizabeth TePas, MD, MS

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2020. | This topic last updated: Sep 10, 2019.

INTRODUCTION

The prevalence of anaphylaxis in infancy, defined here as birth through two years of age, is unknown
but appears to be increasing [1-4]. In a European anaphylaxis registry with 1970 patients younger
than 18 years, 18 were under age one year (0.9 percent) [5]. In a review of children presenting with
food-induced anaphylaxis to two Boston emergency departments, 29 percent were under age two
years [6]. Anaphylaxis has been reported in infants as young as one week of age [7-9]. It can be fatal
in infancy [10-12].

This topic reviews the unique features of anaphylaxis in infants. Other aspects of anaphylaxis are
covered separately. (See "Anaphylaxis: Emergency treatment" and "Laboratory tests to support the
clinical diagnosis of anaphylaxis" and "Food-induced anaphylaxis" and "Fatal anaphylaxis" and
"Biphasic and protracted anaphylaxis".)

CLINICAL MANIFESTATIONS AND DIAGNOSIS

The diagnosis is based primarily upon a detailed history of the episode, including information about all
exposures and events in the minutes to hours preceding the sudden onset of symptoms and signs.
The clinical criteria for the diagnosis of anaphylaxis are similar in patients of all ages; however, some
aspects of diagnosis are unique in infants (table 1) [6,13-15]. These clinical criteria have been
validated for use in emergency departments and epidemiologic studies [16,17]. (See "Anaphylaxis:
Acute diagnosis", section on 'Definition and diagnosis'.)

Anaphylaxis can be difficult to recognize in infancy for a variety of reasons [6,14]:

 ● It is sometimes the first clinical manifestation of sensitization to an allergen. Caregivers might not
realize what the symptoms and signs represent if they are unaware that the infant has been
sensitized to this allergen.

● Itching, throat tightness, chest tightness, and other subjective symptoms of anaphylaxis (table 2)
cannot be described by infants.

● Many of the signs of anaphylaxis are nonspecific and are also seen in healthy infants for other
reasons (eg, regurgitation or spitting up after feeding; flushing, hoarseness/dysphonia after a
crying spell; and drowsiness after a meal or at a naptime).

● Sometimes, the onset of an anaphylactic episode in infancy is manifest only by sudden onset of
lethargy or hypotonia, abrupt cessation of activity or play, or clinging to the caregiver.

In a study of 605 children presenting to the emergency department with a food-related acute allergic
reaction, the largest proportion of children with anaphylaxis were less than two years old. Many of
these infants presented with hives and vomiting [6]. In this study and in another large study [8],
infants were less likely to have blood pressure documented during their emergency department stay
than were older children.

Tryptase measurements are less helpful in infants with anaphylaxis than in older patients. Tryptase
levels are typically within normal limits in patients of all ages with anaphylaxis triggered by food and in
those who remain normotensive. Food is by far the most common trigger of anaphylaxis in infancy.
The normal range of serum tryptase levels in a pediatric population ranging in age from six months to
18 years is comparable with the normal range reported in the adult population. The normal reference
range for baseline tryptase concentrations in early infancy differs from the normal reference range in
older infants, children, and adults. In nonatopic infants under age three months, the median baseline
tryptase concentration is 6.1±3.5 mcg/L; in atopic infants under age three months, it is 14.3±10.2
mcg/L. Levels gradually decrease during the first year of life, and, by age 9 to 10 months, median
levels are 3.9±1.8 mcg/L regardless of atopic status [18]. In patients of any age, a tryptase level
within the normal range does not rule out the clinical diagnosis of anaphylaxis [14,19-21]. (See
"Laboratory tests to support the clinical diagnosis of anaphylaxis".)

CASE REPORT

An 11-month-old, 10 kg, breastfed boy with eczema and a history of intermittent cough and wheeze
suddenly developed a raised, red rash on his face, trunk, and extremities while being fed a snack
consisting of a pudding made with egg, milk, and rice. His lips and cheeks became swollen, and his
eyes swelled shut. He vomited twice. Initially, he was irritable. Later, he became sleepy.
He was taken immediately to the nearest emergency department. On arrival, he was noted to have
generalized hives, periorbital swelling, tachypnea, and wheezing. His oxygen saturation was 92
percent in room air. He was treated with supplemental oxygen by facemask and an intramuscular
injection of epinephrine 0.1 mg of a 1 mg/mL (1:1000) solution. The epinephrine injection was
repeated 15 minutes later. He was then transferred to a children's hospital. On arrival there, three
hours after his symptoms began, he was lethargic and had a fading, raised, red rash superimposed
on scaly red areas on his face, trunk, and extremities.

The clinical diagnoses were (1) anaphylaxis and (2) eczema/atopic dermatitis.

Serum immunoglobulin E (IgE) levels were highly positive (10 kUA/L) to egg white but absent or
undetectable to cow's milk and rice. Six weeks later, skin prick tests were positive to egg white but
negative to cow's milk and rice. No other food allergens were tested.

Long-term risk reduction measures were implemented. His parents were given verbal and written
instructions about how to avoid feeding him egg in any form. These instructions included a list of
foods that commonly contain egg (eg, ice cream, pudding) and how to check the ingredient labels on
processed foods and packaged foods for words that might indicate egg (eg, albumin, ovalbumin,
lecithin; Food Allergy Research and Education [FARE]) [21].

A personalized written anaphylaxis emergency action plan was developed for him [22,23]. An
autoinjector containing 0.1 mg epinephrine was prescribed because it was available and appropriate
for this 10 kg infant. A discussion was also undertaken about using the 0.15 mg autoinjector if the 0.1
mg dose is not available because it is an acceptable alternative even though it exceeds 0.01 mg/kg,
the recommended pediatric epinephrine dose for intramuscular injection. His parents were instructed
on when and how to use an epinephrine autoinjector and referred to the relevant website for a review
of these instructions. A cloth Medic-Alert bracelet stating "anaphylaxis to egg" was recommended
because he attended a childcare center three days a week. (See "Management of food allergy:
Avoidance" and "Long-term management of patients with anaphylaxis".)

TRIGGERS

Food is the most common trigger of anaphylaxis in infants [7-9,21,24-28]; however, most of the other
triggers of anaphylaxis in older age groups (eg, medications, natural rubber latex, insect stings and
bites) have also been reported to trigger anaphylaxis in this age group [29-36]. Vaccines to prevent
infectious disease rarely trigger anaphylaxis in patients of any age, including infants [35]. Infants with
nonimmune triggers such as cold air or cold water exposure, those with multiple anaphylaxis triggers
from different classes of agents (eg, food, medication), and those without an identifiable anaphylaxis
trigger (idiopathic anaphylaxis) should have a careful skin examination for cutaneous mastocytosis
lesions and measurement of a baseline tryptase level [36,37]. (See "Anaphylaxis: Emergency
treatment" and "Food-induced anaphylaxis" and "Idiopathic anaphylaxis" and "Mastocytosis
(cutaneous and systemic): Epidemiology, pathogenesis, and clinical manifestations" and
"Mastocytosis (cutaneous and systemic): Evaluation and diagnosis in adults" and "Mast cell
disorders: An overview".)

Foods — Egg, cow's milk, and peanut are common anaphylaxis triggers in infants, and both
accidental and intentional exposures to known allergens are common in this age group. As an
example, in a prospective, observational study, advice and written instructions were provided to
families of 512 infants with milk or egg allergy aged 3 to 15 months at study entry [38]. Despite this
education, allergic reactions occurred in 53 percent of the infants. Reactions were associated not only
with misreading food labels or food cross-contamination but were also due to intentional exposure of
infants to foods that should not have been given to them and infants being fed by persons other than
their parents.

However, any food can trigger anaphylaxis in infants [7,9,21,24-28]. This includes foods often
presumed to be harmless (eg, goat's milk, sheep's milk, hypoallergenic formula, probiotics
contaminated with cow's milk), foods infrequently given to infants (eg, sesame), and foods eaten by
indigenous peoples (eg, seal meat and whale meat eaten by indigenous people in circumpolar
regions).

Infants may be sensitized to foods through a variety of routes including in utero, through breast milk,
through direct ingestion of the food, or by skin contact, especially inflamed skin (ie, atopic dermatitis)
[7-9,21,24-28,39,40]. Skin contact with food, including skin care products containing foods, or
inhalation of aerosolized food particles can potentially sensitize an infant (ie, lead to production of
food-specific IgE) but rarely trigger anaphylaxis [14,21]. (See "Pathogenesis of food allergy".)

Caregivers may be unaware of the initial exposure to the food. Therefore, anaphylaxis after food
ingestion is possible even when a caregiver reports that the infant had never been previously fed the
culprit food.

Other triggers — Less common triggers include the following:

● Medications, typically antibiotics (especially beta-lactam antibiotics) and nonsteroidal

antiinflammatory drugs (NSAIDs), such as ibuprofen; however, any medication, excipient, or
contaminant may be implicated [29-31]

● Natural rubber latex (eg, bottle nipples, pacifiers, toys) [32]

● Insect stings or bites [33,34]

 ● Vaccines to protect against infectious diseases (rare trigger; approximate rate of occurrence: less
than one per million injections) [35]

● Airborne environmental allergens (rare triggers; eg, cat, horse, and hamster or other rodent
dander [epithelium])

● Nonimmune triggers (eg, cold water or cold air exposure)

AT-RISK INFANTS

Clinical risk factors and comorbid diseases that increase the risk of severe anaphylaxis are in the
process of being defined more clearly in infants (see "Fatal anaphylaxis"). The following are likely to
be important [14]:

● Recurrent wheezing/asthma
● Eczema/atopic dermatitis
● Mastocytosis (especially if there is extensive skin involvement or bullous lesions and an elevated
baseline tryptase level for age) [37]

Comorbidities in caregivers (eg, depression, cognitive dysfunction, or use of sedatives, ethanol, or

recreational drugs) may play a role in failure to recognize symptoms and signs of anaphylaxis in
infants [19,22].

DIFFERENTIAL DIAGNOSIS

In infancy, as at any age, anaphylaxis is characterized by the sudden onset of symptoms and signs
that typically involve two or more body organ systems (table 1) [13-15]. (See "Acute events in infancy
including brief resolved unexplained event (BRUE)".)

Other causes of acute skin symptoms — Acute urticaria in infancy is commonly caused by an
acute viral infection or by a food, medication, or other allergen trigger. It is rare for hereditary
angioedema to present in infancy. (See "Mastocytosis (cutaneous and systemic): Epidemiology,
pathogenesis, and clinical manifestations" and "New-onset urticaria" and "An overview of
angioedema: Pathogenesis and causes".)

Other causes of acute respiratory distress — Sudden onset of respiratory distress in infants may
be caused by the following [14]:

● Congenital upper or lower respiratory tract obstruction (eg, laryngeal web, tracheal or laryngeal
malacia, vascular ring) (see "Congenital anomalies of the intrathoracic airways and
 tracheoesophageal fistula")

● Acquired upper or lower respiratory tract obstruction (eg, foreign body aspiration, croup, asthma,
bronchiolitis)

The various causes of acute respiratory distress in infants and children are reviewed in detail
separately. (See "Acute respiratory distress in children: Emergency evaluation and initial stabilization"
and "Emergency evaluation of acute upper airway obstruction in children" and "Assessment of stridor
in children".)

Other causes of acute gastrointestinal symptoms — Sudden onset of gastrointestinal symptoms

and signs in infants may be caused by the following [14]:

● Congenital gastrointestinal tract obstruction (eg, pyloric stenosis, malrotation)

● Acquired gastrointestinal tract obstruction (eg, intussusception)
● Gastroenteritis (viral or bacterial)
● Food protein-induced enterocolitis syndrome (FPIES)

These causes are discussed in detail separately. (See "Food protein-induced enterocolitis syndrome
(FPIES)" and "Approach to the infant or child with nausea and vomiting" and "Acute viral
gastroenteritis in children in resource-rich countries: Clinical features and diagnosis" and "Approach
to diarrhea in children in resource-rich countries".)

Other causes of acute central nervous system symptoms and signs — Sudden onset of central
nervous system (CNS) symptoms may be due to the following [14] (see "Evaluation of stupor and
coma in children"):

● Seizure (see "Seizures and epilepsy in children: Classification, etiology, and clinical features")
● Head trauma (see "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and
children")
● Infections such as meningitis (see "Bacterial meningitis in children older than one month: Clinical
features and diagnosis")
● Stroke (see "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk
factors")

Other causes of syncope — These include life-threatening conditions such as arrhythmias and
structural heart disease and more benign conditions such as breath-holding spells [14]. (See "Causes
of syncope in children and adolescents" and "Nonepileptic paroxysmal disorders in infancy", section
on 'Breath-holding spells'.)
Other causes of shock — These include hypovolemic shock, cardiogenic shock, other forms of
distributive shock (eg, neurogenic shock), and septic shock (the latter involves hypovolemic,
cardiogenic, and other elements) [14]. Feeding of a causal food in FPIES may lead to the
development of shock associated with profuse vomiting and diarrhea [21]. (See "Initial evaluation of
shock in children" and "Food protein-induced enterocolitis syndrome (FPIES)".)

Other entities — A number of other conditions, some of which are age unique, may be difficult to
differentiate from anaphylaxis in infants. These include the following [14,41]:

● Congenital or metabolic disorders (see "Inborn errors of metabolism: Epidemiology,

pathogenesis, and clinical features")

● Drug overdose or poisoning from a chemical, toxic plant, or food

● Munchausen syndrome by proxy (see "Medical child abuse (Munchausen syndrome by proxy)")

● Apparent life-threatening event/sudden infant death syndrome (see "Sudden infant death
syndrome: Risk factors and risk reduction strategies")

● Hypotonic/hyporesponsive episode

● Apnea and unresponsiveness in an former premature infant (born at or before 32 weeks

gestation)

MANAGEMENT OF ACUTE ANAPHYLAXIS

Initial management begins with rapid assessment (airway, breathing, circulation, responsiveness,
skin, and body mass [weight]) and prompt injection of epinephrine (adrenaline) [14,42,43]. (See
"Anaphylaxis: Emergency treatment", section on 'Immediate management'.)

Epinephrine should be given by intramuscular injection in the mid-outer thigh in a dose of 0.01 mg/kg,
drawn up from a 1 mg/mL solution; for example, the correct dose for a 10 kg infant is 0.1 mg (0.1
mL). The time of the injection should be recorded. The dose can be repeated in 5 to 15 minutes, if
needed; most infants respond to one or two doses. Failure to inject epinephrine promptly in
anaphylaxis may lead to hypoxic/ischemic encephalopathy or to death. Intramuscular epinephrine
injection may be associated with mild transient pharmacologic effects such as pallor, tremor, or
tachycardia.

Serious adverse effects such as ventricular arrhythmias and pulmonary edema can occur after
epinephrine overdose, particularly when administered through the intravenous route. Examples
include administration of an intravenous bolus dose or an overly rapid intravenous infusion or a
dosing error due to an intravenous infusion of the 1 mg/mL solution that is appropriate for
intramuscular administration instead of the dilute solutions that are appropriate for intravenous
administration (0.1 mg/mL or 0.01 mg/mL).

An epinephrine overdose can be difficult to recognize in infants. As an example, cough and

respiratory distress commonly occur after a large epinephrine overdose that causes pulmonary
edema, yet these symptoms are also common symptoms of anaphylaxis itself [14,42].

For these reasons, we recommend that intravenous epinephrine should be administered to infants
with anaphylaxis only by clinicians who are trained and experienced in titrating doses of epinephrine
against blood pressure and cardiac rate and function as assessed by continuous electronic
monitoring of heart rate, blood pressure, respiratory rate, and oxygenation. (See "Anaphylaxis:
Emergency treatment", section on 'Epinephrine'.)

Infants with anaphylaxis should be treated with supplemental oxygen and intravenous fluids as
needed. H1-antihistamines, beta-2 adrenergic agonists, and glucocorticoids are adjunctive
pharmacologic treatment in addition to epinephrine and should not replace epinephrine as the initial
treatment. These are discussed in detail separately. (See "Anaphylaxis: Emergency treatment",
section on 'Adjunctive agents'.)

The optimal observation period following successful treatment of an anaphylaxis episode in an infant
is unknown; however, a minimum observation period of two hours, and preferably a period of eight
hours, is suggested. Biphasic anaphylaxis, defined as symptoms occurring without any further
exposure to the trigger, from 1 to 72 hours after resolution of initial anaphylaxis symptoms appears to
be uncommon in infants [8,44]. (See "Anaphylaxis: Emergency treatment", section on 'Observation
and admission'.)

LONG-TERM MANAGEMENT

The care upon resolution of an anaphylaxis episode is covered in detail separately. (See
"Anaphylaxis: Emergency treatment", section on 'Follow-up care' and "Long-term management of
patients with anaphylaxis".)

Trigger identification and avoidance in order to prevent recurrence of anaphylaxis are important
aspects of long-term risk reduction.

Trigger identification and avoidance — In infants, anaphylaxis is usually IgE mediated and is
usually triggered by food. For this reason, food allergy will be used as the principal example in this
section. Allergen sensitization can be determined by skin prick testing or by measurement of allergen-
specific IgE in serum [19]. An individualized approach to testing is recommended, focusing upon the
substances to which the infant was exposed in the minutes to hours immediately preceding the
anaphylactic episode. In breastfed infants, the dietary intake of the mother should also be taken into
consideration. (See "Diagnostic evaluation of food allergy".)

Foods — Positive skin prick tests to food or elevated specific IgE levels to food indicate
sensitization but are not diagnostic of anaphylaxis or any other allergic disease. Foods that the
infant eats and tolerates without developing anaphylaxis symptoms do not need to be tested,
because sensitization to foods is common in healthy infants in the general population. Panels
of skin tests to foods and measurement of specific IgE levels to panels of foods are unnecessary and
potentially misleading. Intradermal tests to foods are contraindicated [21,45,46]. (See "Overview of in
vitro allergy tests" and "Overview of skin testing for allergic disease" and "Diagnostic evaluation of
food allergy", section on 'Accuracy'.)

Positive skin test results typically appear smaller in infants than in older children and adults. The food
allergen-specific serum IgE levels that have a 95 percent predictive value for a positive failed food
challenge are lower in infants than in older children and adults; however, infant norms are only
available for a few foods such as egg and cow's milk [21]. (See "Diagnostic evaluation of food
allergy".)

In carefully selected infants, a medically supervised, graded food challenge test conducted in an
appropriately equipped health care setting staffed by trained and experienced health care
professionals is sometimes needed to determine the risk of anaphylaxis recurrence. A challenge may
be helpful if the clinical diagnosis of anaphylaxis is questionable or if there is little or no evidence of
sensitization to the food implicated in triggering the episode. A challenge can trigger anaphylaxis
and is therefore strictly contraindicated in an infant who has a convincing clinical history of
anaphylaxis and is sensitized to the suspect food as evidenced by a positive skin prick test or
an elevated specific IgE level [19,21,46-48]. (See "Oral food challenges for diagnosis and
management of food allergies".)

Prevention of future episodes of anaphylaxis requires vigilant allergen avoidance. This can be
stressful for caregivers, especially if the implicated allergen is a food such as egg, cow's milk, or
peanut that is ubiquitous in the diet and is commonly found in prepackaged or processed foods.
Caregivers should be given written information about how to avoid exposing the infant to his or her
confirmed food trigger of anaphylaxis [21,22,46,49]. (See "Management of food allergy: Avoidance"
and "Patient education: Food allergy treatment and avoidance (Beyond the Basics)".)

Several treatment strategies with the goal of curing or providing long-term remission from food allergy
are under investigation. These approaches are either allergen specific or aimed at modulating the
overall allergic response. These investigational therapies are discussed in greater detail separately.
(See "Investigational therapies for food allergy: Immunotherapy and nonspecific therapies".)

Insect stings — Anaphylaxis to Hymenoptera stings or insect bites is rare in infancy. Strict
avoidance of exposure to the stinging or biting insect is the key to prevention of recurrent episodes.
However, if the anaphylactic reaction occurred to a Hymenoptera sting, and sensitization to stinging
insect venom has been confirmed, allergen-specific subcutaneous immunotherapy is indicated [42].
(See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action".)

Medications — The most common approach to management of infants who have medication-
induced anaphylaxis is to avoid giving the implicated agent and substitute a non-cross-reacting
medication, preferably from a different therapeutic class. Clinician-supervised desensitization to the
medication that triggered the anaphylaxis is indicated if an effective and safe substitute
pharmacologic agent is not available [42].

Vaccines — Anaphylaxis to a vaccine for prevention of an infectious disease is rare. When it

occurs, it is usually due to a vaccine constituent, such as gelatin, egg, latex, or yeast, rather than to
the microbial agent in the vaccine. Specific protocols for evaluation and management of patients with
a history of anaphylaxis to a vaccine are available [35,42,50]. (See "Allergic reactions to vaccines".)

Other — For infants with anaphylaxis to natural rubber latex, airborne environmental allergens, or
nonimmune triggers, caregivers should be given written instructions about how to avoid exposing the
infant to the trigger [32,42].

Preparedness to treat a recurrence of anaphylaxis — Caregivers should be instructed in how to

treat anaphylaxis in the event of recurrence after unintentional exposure to the triggering allergen
[22,42,51].

Epinephrine for first-aid treatment of anaphylaxis in the community — Caregivers of infants who
are at risk for anaphylaxis should be equipped with an epinephrine autoinjector [22,42,43,51,52]. A
personalized written anaphylaxis emergency action plan for the infant should be developed with the
caregiver's input [22,23,51]. (See "Anaphylaxis: Emergency treatment", section on 'Anaphylaxis
emergency action plan' and "Patient education: Use of an epinephrine autoinjector (Beyond the
Basics)".)

The lowest dose of epinephrine available in an autoinjector is 0.1 mg; however, it is only available
from one manufacturer. This dose is appropriate for infants weighing between 7.5 to 15 kg, according
to manufacturer instructions. The 0.15 mg autoinjector is also an option for infants weighing 10 to 15
kg (and can be used for infants with weights as low as 7.5 kg if the 0.1 mg autoinjector is not
available) [53]. There are no ideal options for infants weighing <7.5 kg. One option is to draw up an
exact dose from an ampule. However, caregivers without medical training find it difficult to draw up an
infant dose from an ampule of epinephrine rapidly and accurately; therefore, this alternative is not
recommended [54]. Additionally, other alternatives such as an unsealed prefilled syringe are not
recommended [55]. Another option is prescribing the 0.1 mg autoinjector for infants weighing less
than but close to 7.5 kg, although this is not ideal either [53,56]. (See "Prescribing epinephrine for
anaphylaxis self-treatment".)

We summarize the dosing options as follows:

● For infants weighing <7.5 kg (16.5 lb), ideal dosing requires an ampule and syringe or a prefilled
syringe. The 0.1 mg autoinjector is an option for infants near the upper end of this weight range if
an autoinjector is felt to have important benefits over other delivery devices.

● For infants/children weighing 7.5 to 10 kg (22 lb), the autoinjector options include a 0.1 mg
autoinjector (ideal) or a 0.15 mg autoinjector (option if the 0.1 mg autoinjector is not accessible).

• For a 7.5 kg child, the 0.1 mg autoinjector delivers 133 percent of the ideal dose, and the
0.15 mg autoinjector delivers 200 percent of the ideal dose.

• For a 10 kg child, the 0.1 mg autoinjector delivers the ideal dose, and the 0.15 mg
autoinjector delivers 150 percent of the ideal dose.

● For infants/children weighing >10 kg to 15 kg, either the 0.1 mg (matches manufacturer labeling,
but only one product available) or 0.15 mg autoinjector is appropriate.

• For a 12.5 kg child, the 0.1 mg dose delivers 80 percent of the ideal dose, while the 0.15 mg
autoinjector delivers 120 percent of the ideal dose.

● For infants/children weighing >15 to 25 kg, the 0.15 mg autoinjector is appropriate.

Infants with anaphylaxis occurring in community settings are less likely than patients in older age
groups to receive an epinephrine injection [57]. Caregivers need instruction and regular coaching in
how to use an epinephrine autoinjector correctly and safely in an infant [58].

H1-antihistamines — H1-antihistamines relieve urticaria but do not relieve upper or lower airway
obstruction, hypotension, or shock. They are not lifesaving and therefore should not be substituted for
epinephrine in the initial treatment of anaphylaxis [42,43,59,60]. In addition, first (old)-generation H1-
antihistamines often cause clinically relevant sedation and associated lack of responsiveness that can
hamper the recognition of progression of an anaphylaxis episode [42,43,59-62]. In overdose, they can
also lead to respiratory arrest and death in infants. The use of H1-antihistamines as adjunctive
treatment for anaphylaxis is discussed separately. (See "Anaphylaxis: Emergency treatment", section
on 'H1 antihistamines'.)
 Glucocorticoids — Glucocorticoids are given to prevent biphasic or protracted reactions;
however, there is little evidence to support this practice. Fortunately, these types of reactions are
uncommon in anaphylaxis in infants [8]. The use of glucocorticoids as adjunctive treatment for
anaphylaxis is discussed separately. (See "Anaphylaxis: Emergency treatment", section on
'Glucocorticoids'.)

Management of comorbidities — Comorbidities in the infant (eg, recurrent wheezing/asthma,

mastocytosis) or in the caregiver (eg, depression, substance abuse) should be managed
appropriately [14,22]. (See "Treatment of recurrent virus-induced wheezing in young children" and
"Asthma in children younger than 12 years: Management of persistent asthma with controller
therapies" and "Advanced systemic mastocytosis: Management and prognosis" and "Treatment and
prognosis of cutaneous mastocytosis".)

Medical identification — Infants with a history of anaphylaxis who are in the care of someone other
than their parents or other primary caregiver(s) should wear medical identification to help prevent
accidental exposures [38]. In young infants, this may be in the form of a T-shirt or Velcro patch (for
clothing) with a specific allergy alert message (eg, "I am allergic to egg"). Medical identification
bracelets made of fabric are available for older infants [14]. (See "Long-term management of patients
with anaphylaxis".)

Anaphylaxis education — Being responsible for the recognition and management of an episode of
anaphylaxis, particularly the possibility of having to inject epinephrine, provokes high anxiety levels in
caregivers of infants with a history of anaphylaxis [14,22,38,49,63]. Individualized teaching/coaching
sessions help to diminish this anxiety and should be repeated at regular intervals. (See "Long-term
management of patients with anaphylaxis".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Anaphylaxis".)

SUMMARY

● Anaphylaxis is likely under-recognized in infancy because many episodes are "first" episodes,
infants cannot describe their symptoms, and many of their signs are either nonspecific or are
commonly seen for other reasons in healthy infants. Diagnosis therefore depends upon a high
index of suspicion and meticulous history of antecedent exposures and events, chronologic
 development of symptoms, and careful physical examination. (See 'Clinical manifestations and
diagnosis' above.)

● Food is the most common trigger of anaphylaxis in infants. (See 'Triggers' above.)

● The differential diagnosis of anaphylaxis in infants includes congenital and acquired causes of
acute urticaria/angioedema, acute respiratory distress, acute gastrointestinal symptoms, and
shock. Some conditions in the differential diagnosis, such as food protein-induced enterocolitis
and apparent life-threatening events, are age unique. (See 'Differential diagnosis' above.)

● Medical management is extrapolated from the treatment of anaphylaxis in older children and
adults. The initial medication of choice is epinephrine injected intramuscularly in the mid-outer
thigh. (See 'Management of acute anaphylaxis' above and "Anaphylaxis: Emergency treatment".)

● Long-term risk reduction measures include confirmation of anaphylaxis triggers suggested by the
history, instruction of caregivers in how to identify triggers and avoid exposing the infant to them,
and preparedness for treatment of future anaphylactic episodes. (See "Long-term management
of patients with anaphylaxis" and "Prescribing epinephrine for anaphylaxis self-treatment".)

ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge F Estelle R Simons, MD, FRCPC and Hugh
A Sampson, MD, who contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 5750 Version 22.0

GRAPHICS

Diagnostic criteria for anaphylaxis

Anaphylaxis is highly likely when any ONE of the following three criteria is fulfilled:
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or
both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)

AND AT LEAST ONE OF THE FOLLOWING:

A. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, hypoxemia)

B. Reduced BP* or associated symptoms of end-organ dysfunction (eg, hypotonia, collapse, syncope,
incontinence)

2. TWO OR MORE OF THE FOLLOWING that occur rapidly after exposure to a LIKELY allergen for that
patient (minutes to several hours):

A. Involvement of the skin mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula)

B. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, hypoxemia)

C. Reduced BP* or associated symptoms (eg, hypotonia, collapse, syncope, incontinence)

D. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

3. Reduced BP* after exposure to a KNOWN allergen for that patient (minutes to several hours):

A. Infants and children - Low systolic BP (age-specific)* or greater than 30% decrease in systolic BP

B. Adults - Systolic BP of less than 90 mmHg or greater than 30% decrease from that person's baseline

BP: blood pressure.

* Low systolic blood pressure for children is defined as:
Less than 70 mmHg from 1 month to 1 year
Less than (70 mmHg + [2 x age]) from 1 to 10 years
Less than 90 mmHg from 11 to 17 years

Adapted with permission from: Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and
management of anaphylaxis: summary report-Second National Institute of Allergy and Infectious Disease/Food Allergy and
Anaphylaxis Network symposium. J Allergy Clin Immunol 2006; 117:391. Copyright © 2006 The American Academy of
Allergy, Asthma, and Immunology.

Graphic 72225 Version 16.0

Symptoms and signs of anaphylaxis in infants*

Anaphylaxis signs that are Anaphylaxis signs in

Anaphylaxis symptoms that
potentially difficult to infants: Obvious but may be
infants cannot describe
interpret in infants and why nonspecific

General

Feeling of warmth, weakness, Nonspecific behavioral changes, such

anxiety, apprehension, impending as persistent crying, fussing,
doom irritability, fright

Skin/mucus membranes

Itching of lips, tongue, palate, Flushing (may also occur with fever, Rapid onset of hives (potentially
uvula, ears, throat, nose, eyes, and hyperthermia, or crying spells) difficult to discern in infants with
so forth; mouth-tingling or metallic acute atopic dermatitis; scratching
taste and excoriations, as such, will be
absent in young infants); angioedema
(face, tongue, oropharynx)

Respiratory

Nasal congestion, throat tightness; Hoarseness, dysphonia (common after Rapid onset of coughing, choking,
chest tightness; shortness of a crying spell); drooling, increased stridor, wheezing, dyspnea, apnea,
breath secretions (common in infants) cyanosis

Gastrointestinal

Dysphagia, nausea, abdominal Spitting up/regurgitation (common Sudden, profuse vomiting

pain/cramping after feeds), loose stools (normal in
infants, especially if breastfed);
colicky abdominal pain

Cardiovascular

Feeling faint, presyncope, Hypotension; measured with an Weak pulse, arrhythmia,

dizziness, confusion, blurred vision, appropriate size blood pressure cuff, diaphoresis/sweating, pallor,
difficulty in hearing, palpitations low systolic blood pressure for infants collapse/unconsciousness
is defined as less than 70 mmHg from
age 1 month to 1 year and less than
(70 mmHg + [2 x age in years]) in
the first and second years of life;
tachycardia, defined as greater than
120 to 130 beats per minute from the
third month to second year of life
inclusive; loss of bowel and bladder
control (ubiquitous in infants)

Central nervous system

Headache Drowsiness, somnolence (common in Rapid onset of unresponsiveness,

infants after feeds) lethargy, or hypotonia; seizures

* More than one body system involved.

From: Simons FER. Anaphylaxis in infants: Can recognition and management be improved? J Allergy Clin Immunol 2007;
120:537. Table used with the permission of Elsevier Inc. All rights reserved.

Graphic 64957 Version 7.0

Contributor Disclosures
Scott H Sicherer, MD, FAAAAI Grant/Research/Clinical Trial Support: HAL Allergy [Food allergy]; Food Allergy
Research and Education [Food allergy]; NIAID [Food allergy clinical trials]. Other Financial Interest: Johns
Hopkins University Press [Royalties]. Robert A Wood, MD Grant/Research/Clinical Trial Support: NIAID; DBV
Technologies; Aimmune; Astellas; HAL-Allergy; Sanofi; Regeneron [Food allergy]. Elizabeth TePas, MD,
MS Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
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