eMedicine Specialties > Emergency Medicine > Pediatric

Pediatrics, Anaphylaxis

Author: Jeffrey F Linzer Sr, MD, MICP, FAAP, FACEP, Associate Professor of Pediatrics and Emergency Medicine, Emory University School of Medicine; Associate Medical Director for Business Affairs and Compliance and EMS/Pre-Hospital Care Coordinator, Department of Pediatrics, Division of Pediatric Emergency Medicine, Emory University School of Medicine; Emergency Pediatric Group, Children's Healthcare of Atlanta at Egleston; Co-Medical Director and Consulting Staff, Children's Sedation Service, Children's Healthcare of Atlanta at Egleston
Contributor Information and Disclosures

Updated: Oct 5, 2009

Introduction

Background

Anaphylaxis is an acute, potentially life-threatening syndrome, with multisystemic manifestations resulting from the rapid release of inflammatory mediators.

The term anaphylaxis, derived from Greek for "contrary to protection," was coined by Charles R. Richet and Paul Portier in 1902 after their experiments showed a small, nonlethal dose of toxin caused rapid death in sensitized dogs. While the clinical presentation and management are the same, some authors use the term anaphylaxis for immunoglobulin E (IgE)–mediated reactions and anaphylactoid for non–IgE-mediated reactions. The term anaphylaxis syndrome is best used to describe the clinical event.

In children, foods can be a very significant trigger for IgE-mediated anaphylaxis. Milk, eggs, wheat, and soy (MEWS) as a group are the most common food allergens; however, peanuts and fish are among the most potent. Children can develop anaphylaxis from the fumes of cooking fish or residual peanut in a candy bar.

Other common triggers include preservatives (in food and drugs), medications (antibiotics), insect venom (bee sting), and bioactive substances (eg, blood, blood products). Environmental allergens such as pollens, molds, and dust mites are a less common and infrequent cause of anaphylaxis.

Non-IgE triggers include infection, opiates, radiocontrast dye, and exercise.

Pathophysiology

Both IgE and non-IgE activation of mast cells and basophils ignites a cascade that results in the release and production of several inflammatory and vasoactive substances. These bioactive materials include histamine, tryptase, heparin, prostaglandins (PGD₂, PGF₂), leukotrienes (LTC₄, LTD₄, and LTE₄), cytokines (TNF‑α), and platelet-activating factor (PAF). In anaphylaxis, these substances most commonly involve the skin, respiratory, cardiovascular, and gastrointestinal systems. As a result, urticaria, angioedema, bronchospasm, bronchorrhea, laryngospasm, increased vascular permeability and decreased vascular tone, and bloody diarrhea can develop.
 
The most common cause of mediator release is due to an IgE-mediated reaction. A previously sensitized B lymphocyte produces IgE against a specific antigen. The IgE resides on the mast cells and basophils. When the specific antigen, or one similar to it, binds to the high affinity FcεRI-α receptor of the immunoglobulin, mast cell and basophil degranulation occurs.
 
Non-IgE mediator release can be triggered by several different mechanisms including stimulation of the complement cascade to produce C3a, C4a, and C5a anaphylatoxin, neuropeptide and cytokine activity, and direct contact (kallikrein-kinin system) stimulation by certain agents (eg, opiates, radiocontrast media).
 
Many of the clinical presentations seen in anaphylaxis are due to activation of multiple histamine receptors,¹ For example, acute bronchospasm (wheezing, dyspnea) is a result of the interaction between H₁ and H₂ receptor activity; bronchial smooth muscle constriction and increased mucus viscosity from H₁ receptor activity and H₂ activity causes increased mucus production. The combination of H₁ and H₂ receptor stimulation results in increased vascular permeability, flushing, hypotension, tachycardia, and headache. H₁ and H₃ activity results in cutaneous itch and nasal congestion.
 
However, histamine is not the only agent that causes the symptoms in anaphylaxis.² Prostaglandin, leukotrienes, and PAF all contribute to the bronchoconstriction, vascular changes, and changes in vascular capacitance (increased vascular permeability and vasodilatation). A recent study showed an inverse correlation between PAF acetylhydrolase activity and the severity of anaphylaxis.³ Compared to a placebo group, those patients with anaphylaxis due to peanuts were more likely to have a fatal outcome with low PAF acetylhydrolase activity.

Frequency

United States

Frequency estimates are difficult to determine. Part of the reason may be due to the methodology used by researchers (differing criteria and populations), part likely is due to underreporting, and part is likely due to lack of consistent diagnoses.

In a review of the literature by Neugut et al, the overall occurrence of anaphylaxis in the United States ranges from 1.24-16.8%.⁴ However, a working group on anaphylaxis from the American College of Allergy, Asthma, and Immunology estimated the lifetime prevalence at 0.5-2%.⁵

International

Prevalence is similar to that in the United States.⁵

Mortality/Morbidity

Risk of death due to respiratory and cardiovascular complications is significant. Mortality rate estimates vary from 100 to more than 500 cases per year in the United States. The estimated death rate is 0.002%.⁴

Race

While asthma is more prevalent and has a higher mortality rate in African American children, race does not appear to affect the frequency of having anaphylaxis.⁸

Sex

Anaphylaxis appears to be more common in boys until the age of 15 years when the balance changes and female preponderance continues through adulthood.^5,9

Age

While Bohlke and colleagues estimated the rate of anaphylaxis in children at 10.5 per 100,000 person-years,¹⁰ the Rochester Epidemiology Project showed a rate of 75.1 per 100,000 person-years in children aged 9 years and 65.2 per 100,000 person-years in children in the 10- to 19-year-old group.⁷

Clinical

History

Anaphylaxis is a range of signs and symptoms from hives with wheezing to cardiovascular collapse and death.¹¹ It can occur with or without shock. More than 80% of the patients will present with cutaneous symptoms (eg, hives, pruritus, facial swelling). Generally, at least 2 organ systems (skin, respiratory, cardiovascular, gastrointestinal systems) are involved; however, anaphylaxis can present with a low systolic blood pressure for age or decrease in systolic blood pressure by more than 30% after known allergen exposure alone.¹²

The Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium proposed a diagnostic criteria that would identify at least 95% of the patients with anaphylaxis.¹² The primary clinical diagnostic criteria includes the acute onset of skin and/or mucosal symptoms along with either respiratory compromise (eg, bronchospasm, stridor, shortness of breath) and/or reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia, syncope, incontinence).

• Usually, cutaneous symptoms present first.
• Often, a history of exposure to a known trigger is given, (eg, bee sting, peanut ingestion, antibiotic administration). At times, the inciting agent may be unknown or unclear.
• Symptoms may develop slowly and insidiously over several hours or may rapidly progress over several minutes. Parenteral agents generally have a faster onset of symptoms than ingested ones.
• Children may not be able to express the initial symptoms of anaphylaxis. They may initially have apparent discomfort or a generalized irritability. Additionally, the child may not be able to identify the triggering agent (eg, food) even when known to the parent or caretaker.
• Between 5% and 20% of patients may experience a recurrence of anaphylaxis 8-12 hours after the initial presentation.¹³ Prolonged symptoms can last up to 32 hours despite treatment.¹¹

Physical

Initial symptoms may include an awareness that "something isn't right"; a tingling sensation in the mouth; itchy, watery nose and eyes; and/or the feeling of being warm and flushed.

• Cutaneous (skin)
  • Urticaria (hives, welts, "whelps")
  • Pruritus (itching)
  • Angioedema (swelling) of the face, extremities, or both
• Ear, nose, mouth
  • Nasal congestion
  • Sneezing
  • Rhinorrhea (runny nose)
  • Metallic taste
  • Laryngeal edema (throat tightness)
• Respiratory
  • Cough
  • Wheezing
  • Hoarseness
  • Chest pain (respiratory symptom in children)
  • Shortness of breath
  • Stridor ("crowing" inspiratory sound)
• Gastrointestinal
  • Nausea/vomiting
  • Abdominal cramps
  • Diarrhea (at times bloody)
• Cardiovascular
  • Tachycardia (rapid heart rate)
  • Arrhythmias (irregular heart beat)
  • Decreased peripheral perfusion
  • Hypotension (low blood pressure - usually a late finding in children)
• Central nervous system
  • Dizziness
  • Syncope (fainting)
  • Altered mental status
  • Coma

Causes

Foods are the most common trigger of anaphylaxis in children, with peanuts being the primary cause.¹⁴

The following is only meant to be illustrative of the more common triggers but should not be considered an exhaustive listing. These triggering agents may cause an IgE- or non–IgE-mediated anaphylaxis.

• Foods (most common cause in children) - Milk, eggs, wheat, soy, fish, shell fish, legumes (peanuts), tree nuts
• Medicinals - Antibiotics (penicillins, cephalosporins), local anesthetics (lidocaine), analgesics (aspirin, nonsteroidal anti-inflammatory drugs [ibuprofen], opiates [codeine, morphine]), dextran, radiocontrast media
• Biologicals - Venoms (bee sting, ant or snake bite), blood and blood products, vaccines, allergen extracts
• Preservatives and additives - Metabisulfite, monosodium glutamate
• Other -Latex, unknown/idiopathic

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