Chapter e104: Drug Allergy

Christopher M. Bland; Bruce M. Jones

KEY CONCEPTS

Drug allergy accounts for 6% to 10% of adverse reactions to medications. Most of these immune events are mediated by IgE or activated T cells.
Two theories—the prohapten/hapten concept and the p-i concept—have been proposed to explain how drugs stimulate the immune response.
Anaphylaxis is an acute, life-threatening allergic reaction involving multiple organ systems that generally begins within 1 hour but almost always within 2 hours after exposure to the inciting allergen. Anaphylaxis requires prompt treatment to restore respiratory and cardiovascular functions. Epinephrine is the drug of first choice and should be administered to counteract bronchoconstriction and peripheral vasodilation. IV fluids should be administered aggressively to restore intravascular volume.
Factors that influence the likelihood of drug allergy are the chemical composition of the drug, whether the drug contains proteins of nonhuman origin, the route of drug administration, and the sensitivity of the individual as determined by genetics or environmental factors. For some drugs, the presence of specific human leukocyte antigen alleles is a risk factor for allergic-mediated skin reactions.
Ideally, cephalosporins should be avoided in patients with a history of an immediate penicillin allergy, but the risk of an allergic response to a cephalosporin, even in a person with a positive penicillin skin test result, is low. Similarities in the R1 side chain of the agents should be considered when assessing the risk of cross-reactivity.
Fewer than 1% of patients receiving nonionic radiocontrast agents experience some type of adverse reaction. Of the variety of reactions reported, about 90% are nonimmediate and mostly urticarial, with severe immediate reactions occurring as infrequently as 0.02%.
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can produce two general types of reactions, urticaria/angioedema and rhinosinusitis/asthma, in susceptible patients. Most patients with aspirin sensitivity who require aspirin for prevention of cardiovascular disease can safely undergo and complete a graded challenge or desensitization.
Cross-reactivity between sulfonamide antibiotics and nonantibiotics is low. The low cross-reactive rate may be explained by differences in the chemical structures and reactive metabolites of the sulfonamide antibiotics and nonantibiotics.
The basic principles of management of allergic reactions to drugs or biologic agents include (a) discontinuation of the medication or offending agent when possible; (b) treatment of the adverse clinical signs and symptoms; and (c) substitution, if necessary, of another agent.
The reference standard for evaluating the risk of an immediate hypersensitivity to penicillin is the penicillin skin test. Skin testing can demonstrate the presence of penicillin-specific immunoglobulin E, if present, and predict immediate reactions. Skin testing is not indicated for non-IgE-mediated reactions.
When an allergenic drug is considered medically necessary and no therapeutic alternative or reliable skin testing method exists, two options are available to the clinician: induction of drug tolerance (previously known as desensitization) and graded dose challenge or rechallenge.