Residency · Residency · Pediatrics

Anaphylaxis in Children

Introduction

Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction that occurs rapidly after exposure to a triggering allergen. In children, the incidence of anaphylaxis has been rising, with food allergens being the most common trigger, unlike adults where medications and insect stings predominate. Prompt recognition and immediate administration of intramuscular epinephrine is the cornerstone of management. Delays in epinephrine administration are the most consistent factor associated with fatal anaphylaxis.

Pathophysiology

Anaphylaxis is predominantly an IgE-mediated (Type I) hypersensitivity reaction. The allergen cross-links IgE molecules on the surface of mast cells and basophils, triggering degranulation and the release of histamine, tryptase, prostaglandins, leukotrienes, and platelet-activating factor. These mediators cause vasodilation, increased vascular permeability, bronchospasm, and mucus hypersecretion. Non-IgE-mediated (anaphylactoid) reactions can occur through direct mast cell activation (for example, from radiocontrast media or exercise) and are clinically indistinguishable from IgE-mediated anaphylaxis. Cardiovascular collapse results from profound vasodilation and intravascular volume loss through capillary leak.

Common Triggers in Children

Food Allergens (Most Common in Pediatrics)

Peanuts and tree nuts are the most common cause of fatal food-related anaphylaxis. Cow's milk and egg are especially common in younger children. Shellfish, fish, wheat, soy, and sesame are also important triggers. Reactions can occur with trace exposures, and co-factors such as exercise, NSAIDs, and alcohol in adolescents can lower the threshold for a reaction.

Other Triggers

Insect stings from Hymenoptera (bees, wasps, hornets, fire ants) are an important cause. Medications including antibiotics (penicillins, cephalosporins), NSAIDs, anesthetic agents, and biologics can trigger anaphylaxis. Latex allergy is especially relevant in children with spina bifida or those with repeated surgical exposures. Exercise-induced anaphylaxis may be food-dependent, occurring when exercise follows ingestion of a specific food. Idiopathic anaphylaxis occurs when no identifiable trigger is found despite thorough evaluation.

<image>Infographic showing the most common triggers of pediatric anaphylaxis organized by age group, with food allergens (peanut, tree nut, milk, egg) predominating in young children, and insect stings and medications becoming more common in adolescents, with icons representing each allergen category</image>

Clinical Presentation and Diagnostic Criteria

Diagnostic Criteria (NIAID/FAAN)

Anaphylaxis is highly likely when any one of three criteria is met. Criterion 1 requires acute onset (minutes to hours) of skin or mucosal involvement (urticaria, flushing, angioedema) plus either respiratory compromise or hypotension/end-organ dysfunction. Criterion 2 requires two or more of the following after exposure to a likely allergen: skin or mucosal involvement, respiratory compromise, hypotension, or persistent GI symptoms. Criterion 3 requires hypotension after exposure to a known allergen for that patient.

Organ System Involvement

Skin and mucosal involvement (urticaria, flushing, pruritus, angioedema) is present in 80-90% of cases but may be absent in up to 20%. Respiratory symptoms (stridor, wheezing, dyspnea, hoarseness, throat tightness, rhinorrhea) occur in approximately 70%. Cardiovascular involvement (tachycardia, hypotension, dizziness, syncope, cardiac arrest) occurs in 45%. Gastrointestinal symptoms (nausea, vomiting, abdominal cramping, diarrhea) occur in 45%. Neurologic manifestations include anxiety, confusion, and a sense of impending doom.

Biphasic Reactions

Biphasic reactions are recurrences of symptoms 4-72 hours after initial resolution without re-exposure. They occur in approximately 5-20% of anaphylaxis episodes and are more common with delayed epinephrine administration and severe initial presentations. This justifies an observation period of 4-6 hours, extended up to 24 hours for severe reactions.

Management

Immediate Treatment

The trigger should be removed if still present (stop IV medication, remove stinger). Epinephrine IM (1:1,000 concentration, 0.01 mg/kg, maximum 0.3 mg in children and 0.5 mg in adolescents/adults) is injected into the anterolateral thigh as the first and most important intervention. The patient is positioned supine with legs elevated if tolerated, or in a sitting position if respiratory distress predominates. Help should be called and preparation for cardiopulmonary resuscitation initiated. Epinephrine is repeated every 5-15 minutes if symptoms persist, with most patients responding within 1-2 doses.

Adjunctive Therapies

IV fluid resuscitation with 20 mL/kg normal saline boluses is administered for hypotension, and 40-60 mL/kg may be required due to massive capillary leak. Albuterol nebulization addresses persistent bronchospasm. H1 antihistamines (diphenhydramine 1-2 mg/kg, maximum 50 mg) provide relief from urticaria and pruritus but do not treat or prevent anaphylaxis. H2 antihistamines (ranitidine or famotidine) may provide additional benefit when combined with H1 blockers. Corticosteroids (methylprednisolone 1-2 mg/kg) may help prevent biphasic reactions, though evidence is limited. Glucagon is used for patients on beta-blockers with refractory hypotension (1-5 mg IV in adolescents).

Refractory Anaphylaxis

For patients unresponsive to IM epinephrine and fluids, an epinephrine IV infusion at 0.1-1 mcg/kg/min is initiated. Vasopressors (norepinephrine) are used for persistent cardiovascular collapse. Methylene blue may be considered for refractory vasoplegia (experimental). Advanced airway management should be pursued early for impending airway obstruction, as edema can progress rapidly.

<image>Step-by-step emergency management algorithm for pediatric anaphylaxis showing the sequence from recognition through epinephrine administration (with proper injection site and dosing), IV access, fluid resuscitation, adjunctive medications, and decision points for escalation to epinephrine infusion and advanced airway management</image>

Disposition and Follow-Up

Observation Period

A minimum of 4-6 hours of observation is required after the last dose of epinephrine. Extended observation of 12-24 hours is appropriate for severe reactions, biphasic reaction risk factors, or delayed initial presentation.

Discharge Planning

An epinephrine auto-injector should be prescribed (EpiPen Jr 0.15 mg for 10-25 kg; EpiPen 0.3 mg for greater than 25 kg), with two devices prescribed. A written anaphylaxis action plan should be provided along with education on allergen avoidance, reading food labels, and cross-contamination risks. Medical alert identification (bracelet or necklace) is recommended. Referral to a pediatric allergist/immunologist should occur within 4-6 weeks for confirmatory testing and long-term management.

Long-Term Management

Skin prick testing and specific IgE measurements confirm the triggering allergen. Oral food challenges (the gold standard) are performed under medical supervision for equivocal results. Allergen immunotherapy options include venom immunotherapy (highly effective for insect sting anaphylaxis) and oral immunotherapy (OIT) for peanut allergy (FDA-approved Palforzia for ages 4-17). For school and daycare, a 504 plan or individualized healthcare plan should be established, with staff trained on epinephrine auto-injector use.

<image>Educational illustration showing the correct technique for epinephrine auto-injector use in a child, including proper grip, injection site on the outer mid-thigh, through clothing if needed, and the recommended 10-second hold time, with common errors highlighted</image>

Clinical Pearls

Epinephrine is the only first-line treatment for anaphylaxis, and antihistamines and steroids are adjuncts, not substitutes. Epinephrine should not be delayed for any reason, as delayed administration is the primary modifiable risk factor for fatal anaphylaxis. Absence of skin findings does not rule out anaphylaxis, since up to 20% of cases lack urticaria or flushing. Food is the most common trigger in children, whereas medications and insect stings predominate in adults. Two epinephrine auto-injectors should always be prescribed along with a written action plan at discharge. Biphasic reactions justify an observation period, and families should be educated to return immediately if symptoms recur.

References

1. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report — NIAID/FAAN. Journal of Allergy and Clinical Immunology. 2006;117(2):391-397.
2. Simons FER, Ebisawa M, Sanchez-Borges M, et al. 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines. World Allergy Organization Journal. 2015;8(1):32.
3. Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis — a 2020 practice parameter update, systematic review, and GRADE analysis. Journal of Allergy and Clinical Immunology. 2020;145(4):1082-1123.
4. PALISADE Group of Clinical Investigators. AR101 Oral Immunotherapy for Peanut Allergy. New England Journal of Medicine. 2018;379(21):1991-2001.

Read this lecture as Markdown