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Anaphylaxis, urticaria, and angioedema frequently share a common pathophysiology in that these conditions most commonly result from 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 systemic type I (IgE-mediated) hypersensitivity reaction mediated by histamine, leukotrienes, and other mast cell–derived mediators.1 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 serious anaphylaxis. Preexisting asthma is a primary risk factor for fatal anaphylaxis, and delay in epinephrine therapy has been strongly associated with anaphylaxis mortality. Additional risk factors for poor outcomes with the occurrence of anaphylaxis include concomitant therapy with β-adrenergic or α-adrenergic antagonists, which blunts the effects 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 parenteral antigen exposure (ie, IV medications) and repeated, interrupted antigen exposure (ie, medication or food ingestion). The most common causes of anaphylaxis include (1) medications, (2) foods, (3) stinging insects, (4) latex, and (5) blood products. Of these causes, medications and foods account for the majority of serious anaphylactic reactions resulting in emergency room visits or causing anaphylaxis mortality. 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. Among foods, peanuts, tree nuts, cow’s milk, egg, and seafood (crustaceans, mollusks, fish) most commonly cause anaphylaxis.2 Rarely, the temporal combination of food ingestion and exercise may trigger anaphylaxis.3 This food-dependent, exercise-induced anaphylaxis is best evaluated by an allergy specialist. Other uncommon causes of anaphylaxis include physical factors such as cold, heat, or ultraviolet light exposure. Finally, idiopathic anaphylaxis occurs when no inciting allergen can be identified by considering the patient’s history or by diagnostic testing.

In the pediatric population, anaphylactic reactions to vaccines are a concern. True IgE-mediated anaphylaxis to immunizations is rare and more commonly involves IgE 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 vaccines has been implicated in anaphylactic reactions to these immunizations. IgE-mediated reactions to the specific vaccine antigen is exceedingly rare, but has been reported for diphtheria and tetanus.


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