Anaphylaxis in infants

INTRODUCTION — 

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".)

EPIDEMIOLOGY — 

The prevalence of anaphylaxis in infancy, defined here as birth through one year of age, is unknown but appears to be increasing [1-4]. In US infants and toddlers, the rate of emergency department (ED) visits for anaphylaxis more than doubled from 2006 to 2015, although hospitalization rates did not [5,6]. In a European anaphylaxis registry with 1970 patients younger than 18 years, 18 were under the age of one year (0.9 percent) [7]. In a review of children presenting with food-induced anaphylaxis to two Boston EDs, 29 percent were under the age of two years [8]. From 3 to 22 percent of ED anaphylaxis patients are infants [9-12]. Data from Australia suggest that the implementation of guidelines recommending early allergen introduction in infants, while associated with attenuated rates of food anaphylaxis in general, may have led to increases in ED visits for allergic reactions and an increase in food anaphylaxis admission rates in infants [13,14]. Anaphylaxis has been reported in infants as young as one week of age [9,10,15]. It can be fatal in infancy [16-18].

CLINICAL MANIFESTATIONS AND DIAGNOSIS

Clinical diagnostic criteria — 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 (signs and symptoms) for the diagnosis of anaphylaxis are similar in patients of all ages; however, some aspects of diagnosis are unique in infants (table 1) [3,4,8,9,19-21]. The 2023 US practice parameter update on anaphylaxis [21] suggests using the National Institute of Allergy and Infectious Diseases (NIAID)/Food Allergy & Anaphylaxis Network (FAAN) diagnostic criteria (table 2) [19] or the World Allergy Organization (WAO) criteria [22] because, although clinical criteria have been validated for older age groups [23,24], there are no validated infant criteria. (See "Anaphylaxis: Acute diagnosis", section on 'Definition'.)

Hurdles to diagnosis in infants — Anaphylaxis can be difficult to recognize in infancy for a variety of reasons [3,4,8,20,25]:

●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 cannot be described by infants. The accepted diagnostic criteria (table 2) include terms and features not assessed easily in infants (eg, dyspnea, reduced peak flow, crampy abdominal pain).

●Many of the signs of anaphylaxis are nonspecific and are also seen in infants for other reasons (eg, regurgitation or spitting up after feeding; flushing, hoarseness/dysphonia after a crying spell; rashes from a viral infection; clinging from hunger or boredom; inconsolable crying from hunger or a dirty diaper; 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.

●Infants may demonstrate allergic symptoms that are less common in older age groups, including skin mottling, ear pulling/scratching, tongue thrusting, pulling or licking (ie, from oral pruritus), or putting fingers in ears during an allergic reaction.

●Infants are less likely to have blood pressure (BP) documented during their ED stay than older children [8,9]. In addition, there may be a lack of knowledge of age-appropriate systolic BP in a general ED without pediatric clinicians.

●Other characteristics related to poor perfusion may be noted including skin mottling or cyanosis, tachycardia, lethargy, poor head control, and limpness.

Typical presenting features — Infants more often present with skin symptoms and less often with respiratory symptoms than older children [21], and parents/caregivers may report subtle behavioral changes as described above (see 'Hurdles to diagnosis in infants' above). In a study of 605 children presenting to the ED with a food-related acute allergic reaction, the largest proportion of children with anaphylaxis were less than two years old, and many of these infants presented with hives and vomiting [8]. In clinical studies of infant anaphylaxis, mucocutaneous (79 to 99 percent), gastrointestinal (26 to 89 percent), and respiratory (7 to 83 percent) symptoms were more common than cardiovascular (0 to 8 percent) symptoms [11,12,20,26-28], although one anaphylaxis registry study from France reported 21 percent with cardiovascular symptoms [29].

For infants and toddlers, patient age does not correlate with reaction severity, and anaphylaxis is unlikely to be the initial reaction to a medication or food on the first exposure in infants [21].

Tryptase level — While an elevated tryptase level at the time of a reaction supports the diagnosis of anaphylaxis, a tryptase level within the normal range does not rule out the clinical diagnosis of anaphylaxis [3,30,31]. In addition, 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. 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 [32]. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)

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 [33,34]. (See "Idiopathic anaphylaxis" and "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis" and "Mast cell disorders: An overview" and "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis".)

TRIGGERS — 

Food is the most common trigger of anaphylaxis in infants [9-12,15,26,28,29,31,35,36], but 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 [33,37-42]. Vaccines to prevent infectious disease rarely trigger anaphylaxis in patients of any age, including infants [42]. Nonimmune triggers (eg, cold air or water) are also rare. (See "Anaphylaxis: Confirming the diagnosis and determining the cause(s)" and "Food-induced anaphylaxis" and "Idiopathic anaphylaxis".)

Foods — Egg, 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 [43]. 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 [10-12,15,26,28,29,31,35,36,44,45]. This includes foods often presumed to be harmless (eg, goat's milk, sheep's milk, hypoallergenic formula), foods infrequently given to infants (eg, sesame), and foods less commonly eaten outside of certain cultures.

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) [9,10,15,31,35,36,44-48]. 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 immunoglobulin E [IgE]) but rarely trigger anaphylaxis [3,31]. (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 [37,38,49]

●Natural rubber latex (eg, bottle nipples, pacifiers, toys) [39]

●Insect stings or bites, including fire ants [40,41,50]

●Vaccines to protect against infectious diseases (rare trigger; approximate rate of occurrence: less than one per million injections) [42]

●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 [3,4]:

●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) [34]

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 [51,52].

DIFFERENTIAL DIAGNOSIS BY PRIMARY MANIFESTATION — 

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 2) [3,4,19].

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 "New-onset urticaria (hives)" and "An overview of angioedema: Pathogenesis and causes" and "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis".)

Acute respiratory distress — Sudden onset of respiratory distress in infants may be caused by the following [3,4]:

●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)

Skin manifestations, mucosal swelling, and/or a history of exposure to a typical trigger can help differentiate anaphylaxis from other causes of respiratory distress. In addition, patients with asthma can also have anaphylaxis, and wheezing can be a presenting symptom of anaphylaxis. 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".)

Acute gastrointestinal symptoms — Sudden onset of gastrointestinal symptoms and signs in infants may be caused by the following [3,4]:

●Gastrointestinal tract obstruction (eg, pyloric stenosis, malrotation, intussusception) (see "Infantile hypertrophic pyloric stenosis" and "Intestinal malrotation in children" and "Intussusception in children")

●Gastroenteritis (viral or bacterial) (see "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis" and "Diagnostic approach to diarrhea in children in resource-abundant settings" and "Approach to the infant or child with nausea and vomiting")

●Food protein-induced enterocolitis syndrome (FPIES) (see "Food protein-induced enterocolitis syndrome (FPIES)")

These causes are discussed in detail separately.

Acute central nervous system symptoms and signs — Sudden onset of central nervous system (CNS) symptoms may be due to the following [3,4] (see "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")

Syncope — These include life-threatening conditions such as arrhythmias and structural heart disease and more benign conditions such as breath-holding spells [3,4]. (See "Causes of syncope in children and adolescents" and "Breath-holding spells".)

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) [3,4]. Feeding of a causal food in FPIES may lead to the development of shock associated with profuse vomiting and diarrhea [31]. (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 [3,4,20,53]:

●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" and "Acute events in infancy including brief resolved unexplained event (BRUE)")

●Hypotonic/hyporesponsive episode

●Apnea and unresponsiveness in a former premature infant (born at or before 32 weeks gestation)

MANAGEMENT OF ACUTE ANAPHYLAXIS

Rapid overview — Initial management begins with rapid assessment (airway, breathing, circulation, responsiveness, skin, and body mass [weight]) and prompt injection of epinephrine (adrenaline) [3,4,54,55]. A rapid overview of emergency management of anaphylaxis in infants and children is shown in the table (table 3). (See "Anaphylaxis: Emergency treatment", section on 'Immediate management'.)

Intramuscular epinephrine — 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.

Intravenous epinephrine and risk of overdose — 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 [3,54].

For these reasons, 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'.)

Supplemental therapies — 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. They are discussed in detail separately. (See "Anaphylaxis: Emergency treatment", section on 'Adjunctive agents'.)

Observation period — 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 [9,56] and under 3 percent among several studies [26,28,29]. (See "Anaphylaxis: Emergency treatment", section on 'Observation and admission'.)

LONG-TERM MANAGEMENT

Overview — Trigger identification and avoidance in order to prevent recurrence of anaphylaxis are important aspects of long-term risk reduction. Caregivers should also receive education on treatment of reactions with autoinjectable epinephrine. These aspects of management are reviewed briefly here and covered in detail separately. (See "Long-term management of patients with anaphylaxis" and "Anaphylaxis: Emergency treatment", section on 'Follow-up care'.)

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 [31,57,58]. 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 IgE-mediated 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 [31,57,58]. (See "Overview of in vitro allergy tests" and "Overview of skin testing for IgE-mediated allergic disease" and "Diagnostic evaluation of IgE-mediated 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 milk [31]. (See "Diagnostic evaluation of IgE-mediated 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 [31,51,58-60]. (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, 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 their confirmed food trigger of anaphylaxis [31,52,58,61]. (See "Management of food allergy: Avoidance" and "Patient education: Food allergen 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 "Food allergy management: Allergen-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 [54]. (See "Hymenoptera venom immunotherapy: Indications, efficacy, 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 [54].

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 [42,54,62]. (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 [39,54].

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 [4,52,54].

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 [4,52,54,55,63]. A personalized written anaphylaxis emergency action plan for the infant should be developed with the caregiver's input [4,52,64] and may be associated with an increase in appropriate use of epinephrine [65]. (See "Anaphylaxis: Emergency treatment", section on 'Anaphylaxis emergency action plan' and "Patient education: Using 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) [66]. 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 [67]. Additionally, other alternatives such as an unsealed prefilled syringe are not recommended [68]. 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 [66,69]. (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 [70]. Caregivers need instruction and regular coaching in how to use an epinephrine autoinjector correctly and safely in an infant [71].

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 [4,54,55,72,73]. 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 [54,55,72-75]. In overdose, they can also lead to respiratory arrest and death in infants. However, antihistamines, particularly cetirizine, are used as an adjunctive therapy for anaphylaxis once epinephrine is administered. The use of H1 antihistamines as adjunctive treatment for anaphylaxis is discussed separately. (See "Anaphylaxis: Emergency treatment", section on 'H1 antihistamines'.)

Glucocorticoids — One rationale for giving glucocorticoids in the setting of anaphylaxis is to prevent biphasic or protracted reactions; however, there is little evidence to support this practice. In addition, these types of reactions are uncommon in anaphylaxis in infants [4,9]. Thus, glucocorticoids are typically reserved for patients with severe symptoms who require hospitalization or those with known asthma and persistent respiratory symptoms. The use of glucocorticoids as adjunctive treatment for anaphylaxis is discussed in detail 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 use) should be managed appropriately and are discussed separately [3,52]. (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 "Cutaneous mastocytosis: Treatment, monitoring, and prognosis".)

Infants may be under treatment with a beta blocker for dermatologic or cardiac treatment, and this medication could theoretically interfere with the actions of epinephrine administered for anaphylaxis, reducing its effect or resulting in enhanced alpha-adrenergic effects. In general, parents/caregivers should be counseled about the risks [21], but epinephrine should not be withheld when needed in anaphylaxis. Considerations include evaluation of relative risks, prescribing the beta blocker at the lower recommended range, optimizing allergen avoidance strategies, advising parents/caregivers to contact emergency medical services if anaphylaxis occurs, and having medical staff consider if glucagon is needed for refractory anaphylaxis or adding inhaled medications (beta-agonists and/or ipratropium) for significant bronchospasm [76].

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 [43]. 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 [3]. (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 [3,43,52,61,77]. Individualized teaching/coaching sessions help to diminish this anxiety and should be repeated at regular intervals. (See "Long-term management of patients with anaphylaxis".)

CASE EXAMPLE — 

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 hen's egg, cow's 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 (ED). 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 anaphylaxis and eczema/atopic dermatitis.

Serum IgE levels were highly positive (10 kU_A/L) to egg white but absent or undetectable to milk and rice. Six weeks later, skin prick tests were positive to egg white but negative to 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]) [31].

A personalized written anaphylaxis emergency action plan was developed for him [64]. 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 medical identification 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".)

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 AND RECOMMENDATIONS

●Clinical manifestations and diagnosis – 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 (table 1). Diagnosis (table 2) 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.)

●Triggers – Food is the most common trigger of anaphylaxis in infants, although other triggers (eg, medications, natural rubber latex, insect stings and bites) are reported in infants. (See 'Triggers' above.)

●Risk factors and comorbid disease – Clinical risk factors and comorbid diseases that increase the risk of severe anaphylaxis include asthma/recurrent wheezing, eczema/atopic dermatitis, and mastocytosis. 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. (See 'At-risk infants' above.)

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

●Management of acute anaphylaxis – Medical management is extrapolated from the treatment of anaphylaxis in older children and adults. A rapid overview of emergency management of anaphylaxis in infants and children is shown in the table (table 3). The initial medication of choice is epinephrine injected intramuscularly in the mid-outer thigh. (See 'Management of acute anaphylaxis' above and "Anaphylaxis: Emergency treatment", section on 'Epinephrine'.)

●Long-term management approaches – 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 acknowledge F Estelle R Simons, MD, FRCPC and Hugh A Sampson, MD, who contributed to earlier versions of this topic review.