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Anaphylaxis, urticaria, and angioedema frequently share a common pathophysiology in that these conditions most commonly result from immunoglobulin E (IgE)-mediated mast cell activation, resulting in the release of histamine, leukotrienes, and other mast cell mediators. Urticaria and angioedema are isolated to mucocutaneous symptoms, whereas anaphylaxis is an acute systemic reaction that may rapidly lead to cardiopulmonary collapse.



Anaphylaxis is an acute, life-threatening, systemic syndrome mediated by sudden release of histamine, leukotrienes, and other mast cell– and basophil-derived mediators. It most often is caused by IgE-mediated hypersensitivity reactions to exposures to allergens. The estimated overall lifetime prevalence of anaphylaxis from all causes is 0.5% to 2%, and 0.7% to 2% of anaphylactic reactions are fatal. Rapid recognition, diagnosis, and therapy of anaphylaxis are imperative to prevent morbidity and mortality.

Although anaphylaxis can occur at any age, adolescents and young adults are most at risk for experiencing serious anaphylaxis. Preexisting asthma is a primary risk factor for fatal anaphylaxis, and delay in administering epinephrine therapy has been strongly associated with anaphylaxis-caused mortality. Additional risk factors for poor outcomes with anaphylaxis include concomitant therapy with β-adrenergic or α-adrenergic antagonists, which blunts the effectiveness of epinephrine treatment, and angiotensin-converting enzyme inhibitors, which interfere with physiologic compensatory mechanisms, thereby leading to severe or protracted anaphylaxis.

Risk factors for anaphylaxis include exposure to parenteral antigens (ie, intravenous [IV] medications) and repeated, interrupted exposure to antigens (ie, medication or food ingestion). The most common causes of anaphylaxis include foods, medications, stinging insects, latex, and blood products. Of these causes, foods and medications account for the majority of serious anaphylactic reactions resulting in emergency room visits or causing anaphylaxis mortality. Among foods, peanuts, tree nuts, cow’s milk, egg, and seafood (crustaceans, mollusks, fish) most commonly cause anaphylaxis. Rarely, the temporal combination of ingestion of food and exercise may trigger anaphylaxis. This food-dependent, exercise-induced anaphylaxis is best evaluated by an allergy specialist. The most commonly implicated causative medications are β-lactam antibiotics (penicillins and cephalosporins), other antibiotics, radiocontrast agents (through direct mast-cell stimulation), and neuromuscular blocking agents. Other uncommon causes of anaphylaxis include physical factors such as exposure to cold, heat, or ultraviolet light. Finally, idiopathic anaphylaxis occurs when no inciting allergen can be identified through the clinical history or by diagnostic testing.

In the pediatric population, anaphylactic reactions to vaccines are a concern. True IgE-mediated anaphylaxis reaction to immunizations is rare and more commonly involves activation of IgE in response to vaccine components rather than the immunizing antigen itself. Gelatin, added to vaccines as a stabilizing agent, has been implicated in anaphylactic reactions to measles, mumps, and rubella (MMR), varicella, influenza, and Japanese encephalitis vaccines. Children with a history of allergy to egg should be seen by an allergy specialist prior to receiving influenza and yellow fever vaccines, as egg protein used in these ...

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