Etiology and Pathogenesis

IgE-mediated anaphylaxis, a type I hypersensitivity reaction, is the most understood form of anaphylaxis (Figure 18-1). A person is exposed to an antigen, and upon reexposure, cross-linkage of IgE occurs followed by an immediate release of potent mediators from tissue mast cells and peripheral basophils. These mediators include histamine, leukotrienes, nitric oxide, and neutral proteases, which all lead to vasodilatation, increased vascular permeability, bronchoconstriction, and additional inflammation. At times, the reaction occurs with the first known exposure.

Figure 18-1 Type 1 (acute, anaphylactic) reactions.

Other mechanisms include direct stimulation of mast cells and basophils, as is observed with morphine and exercise- and cold-induced anaphylaxis. Blood products and radiocontrast media may lead to activation of complement and subsequent reactions. Anaphylaxis to aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) may result from the interference of the arachidonic acid pathway. Other agents may act through one or more of the above mechanisms.

The most common IgE-mediated reactions occur with food, drugs, venom, and latex. The leading cause of anaphylaxis in children is food. In the United States, the most common foods implicated in anaphylactic reactions include milk, eggs, soy, wheat, peanuts, tree nuts, and fish (although almost any food can cause a reaction). Children often develop tolerance and outgrow reactions to milk, egg, soy, and wheat; this is less likely to occur with peanuts, tree nuts, and fish. Drug allergy is another common cause of IgE-mediated anaphylaxis, with penicillin and other β-lactam antibiotics being the most commonly implicated agents. Other medications, such as aspirin and NSAIDs, may also lead to reactions. Fire ants and hymenoptera (e.g., honey bees, yellow jackets, hornets, and wasps) are common causes of anaphylaxis in both children and adults. Children with spina bifida and health care workers are at higher risk for latex allergy. Although latex allergy had been on the rise, current use of latex precautions, latex-free gloves, and health care provider awareness have stabilized the incidence of latex reactions. There is also an entity known as exercise-induced anaphylaxis. Three groups of patients present with anaphylaxis after exercising: some of whom have known specific food triggers, others in whom any food ingestion may lead to symptoms, and a third group in which there is no known food trigger. Those with a food trigger have symptoms when they exercise within 4 hours of a meal. Other causes of anaphylaxis include immunizations, radio contrast material, blood products, allergy immunotherapy, and those that remain unknown (idiopathic).

Clinical Presentation

Patients with anaphylaxis may have different clinical manifestations (Table 18-1). Anaphylaxis is often underdiagnosed or misdiagnosed because of clinicians’ failure to recognize symptoms. There has been a recent attempt to standardize the diagnostic criteria to help clinicians to better recognize anaphylaxis (Box 18-1 and Figure 18-2). Approximately 90% of children with allergic reactions have skin manifestations, which include hives, angioedema (see Chapter 20, Figures 20-1 and 20-2), pruritus, or flushing. Although the remainder may not have skin involvement, they are still having a reaction, and that reaction may be more severe than those that occur with skin findings present. Tongue and throat swelling, dysphagia, and choking are manifestations of upper airway edema. Lower respiratory tract symptoms, such as coughing and wheezing, are the next most common symptoms. Vomiting, diarrhea, and abdominal pain are often seen, especially in food-induced anaphylaxis. Cardiovascular manifestations include tachycardia, hypotension, shock, and (rarely) bradycardia. Children may also be lethargic, and some have described a “feeling of impending doom.”

Table 18-1 Signs and Symptoms of Anaphylactic Reactions