Marilyn T. Haupt and Bala K. Grandhi

Chapter Outline

1. Acute onset of a reaction (minutes to hours) with involvement of the skin, mucosal tissue, or both and at least one of the following: (a) respiratory compromise (b) or reduced blood pressure or symptoms of end-organ dysfunction;

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient—involvement of the skin/mucosal tissue, respiratory compromise, reduced blood pressure or associated symptoms, and persistent gastrointestinal symptoms; or

3. Reduced blood pressure after exposure to a known allergen (adapted from Sampson and colleagues¹).

History and Incidence

Allergic emergencies have been described in humans since ancient times.9–11 At the turn of the twentieth century, a more detailed description of these events was reported by two French physiologists, Portier and Richet.¹² They coined the term anaphylaxis, which originates from the French word anaphylactique, which means “reverse protection.” It was believed that these reactions were in contrast to the attenuated or tachyphylactic reactions that commonly protect subjects from reintroduced antigens such as viruses. More recent research defining the role of IgE; the interactions between IgE, antigen, mast cells, basophils, and eosinophils; and the biochemical mediators from these cells has clarified the events leading to clinical anaphylaxis.^2,13–15

The true incidence of the various types of anaphylactic reactions is difficult to determine because these reactions are often spontaneous and unpredictable and are clinically similar to other acute reactions. Lifetime prevalence of anaphylaxis due to all triggers is estimated to be 0.05% to 2%.¹⁶ Estimates of the incidence of the most commonly reported episodes are possible, however. In the United States, penicillin alone probably accounts for several hundred fatalities each year.^17–19 Anaphylaxis to the cephalosporins also is commonly reported.²⁰ It has been estimated that among patients with an allergic reaction to a penicillin, there is a 3% to 7% rate of allergic reaction to a cephalosporin. Reports of anaphylactic reactions to the newer β-lactam antibiotics are accumulating.²¹

Insects, especially those of the Hymenoptera order, which includes bees, wasps, hornets, and fire ants, account for numerous immediate hypersensitivity reactions. About 3% of adults and 1% of children are affected and the anaphylaxis can be fatal at the first sting. About 50 people experience fatal reactions to insect stings every year in the United States, and about half of them do not have a prior sting exposure.22–24 Fire ants are aggressive insects from South America that now reside in the southern United States. In some areas, they have been known to sting 58% of the residents yearly and account for serious allergic reactions.²⁵

Snake bites account for probably a dozen or so anaphylactic deaths per year in the United States. Snake bites may be associated with typical anaphylactic symptoms and other problems related to the enzymes, proteins, and peptides in venom. Local tissue necrosis, coagulation problems, hemolysis, and neurologic transmission defects have been described. In the United States, most anaphylactic reactions to snake bites are caused by pit vipers. These snakes include rattlesnakes, water moccasins, and copperheads.26,27

Food-induced anaphylaxis is probably the most common cause of anaphylaxis and accounts for 30% of fatalities. Peanuts (legumes) and typical nuts from trees account for 90% of fatal cases. Additional common food antigens include fish, soybeans, egg whites, and shellfish.²⁸ Biphasic reactions are much more common in food-induced anaphylaxis than in other types of anaphylaxis and have been reported in 25% of fatal cases.^29–31

Iodinated contrast agents account for approximately 125 deaths per year³² and lead to clinical symptoms similar to anaphylaxis. Life-threatening reactions are extremely rare, with an incidence of 0.1%.^33,34 With the advent of low osmolar iodinated contrast agents, the risk of anaphylaxis to contrast agents has decreased drastically.³⁵

Latex, used in surgical gloves, balloons, condoms, rubber bands, and many other products, may produce anaphylaxis.36,37 The use of universal precautions as a result of the acquired immunodeficiency syndrome epidemic has increased the number of reactions to latex in health care workers. Children with spina bifida and genitourinary tract abnormalities are especially susceptible to latex-induced anaphylaxis because of frequent exposure to latex-containing bladder catheters and other products.

Anaphylactic reactions during anesthesia have been described and typically are associated with hypotension and cardiopulmonary arrest. One review suggests that most cases of intraoperative anaphylaxis are from muscle relaxants (e.g., suxamethonium, tubocurarine, pancuronium).³⁸ Latex, protamine, and blood products also may cause intraoperative anaphylaxis.

Anaphylaxis and other types of IgE-mediated allergic reactions tend to occur in susceptible, genetically predisposed individuals. The reason for the genetic inheritance of sensitivity to the antigens that produce anaphylaxis continues to be speculative. A popular theory is that type I reactions, when confined to an area of parasitic invasion (e.g., intestinal tract), facilitate the killing and removal of parasites and confer a survival advantage to individuals capable of mounting a type I response. Various clinical and laboratory observations support this view.39–41 The sites of IgE synthesis in laboratory subjects correspond to the sites of entry of many parasites. These sites include the lymphoid tissue of the respiratory tract, the gastrointestinal tract, and the skin. Eosinophils, cells that migrate to the site of antigen introduction in anaphylaxis, elaborate mediators that are toxic to the outer parasitic covering.

When type I reactions to antigen are no longer restricted to local areas because of genetically determined or acquired factors, the release of mediators becomes generalized. Problems typical of a systemic response include increased microvascular permeability, loss of intravascular volume, abnormal vascular reactivity (especially vasodilation), and impaired pulmonary gas exchange. Local IgE-mediated reactions become decompensatory when systemic involvement ensues.

Pathogenesis and Pathophysiology