Clinical spectrum of allergic and pseudoallergic drug reactions

Among the many types of adverse effects of drugs, allergic reactions constitute a very significant minority, with respect to both their frequency and sometimes serious consequences. To keep the term “drug allergy” meaningful, it should be limited to those adverse drug reactions that are based on immune mechanisms or that can reasonably be presumed to have this basis. Pseudoallergic drug reactions, which will also be considered in this issue, have similar clinical manifestations and some common pathogenetic mechanisms, but the initiating event does not appear to involve a reaction between the drug or a drug metabolite and specific antibodies. Clinically, drug allergy is commonly observed in nonatopic as well as atopic people. Innumerable drugs have been reported to produce these types of reactions, but in many instances drug metabolites may be the actual culprits. Clinical manifestations of drug allergy also are legion. Unfortunately, essentially none of these is unique or specific for drug allergy, but it is important for clinicians to think of this very treatable condition along with other diagnostic possibilities. It is convenient and helpful to classify allergic reactions to drugs according to Gell and Coombs' four main types of hypersensitivity processes, but in many instances more than one mechanism may be involved, just as immune responses to most antigens generally are complex. Type I reactions are generally immunoglobulin (Ig) E-mediated, and clinical manifestations include urticaria, angioedema, respiratory symptoms, and anaphylaxis. Pseudoallergic reactions of the latter type are called anaphylactoid. Type II reactions to drugs are less common but could be exemplified by hemolytic anemia after α-methyldopa administration. Type III reactions, caused by immune complexes, would be exemplified by serum sickness, various types of vasculitis, or “innocent bystander” types of hematologic reactions. Type IV reactions, which are related to cell-mediated immune responses, are exemplified by allergic contact dermatitis from ointments or allergic photodermatitis. Numerous other types of drug allergy also may fall in this category. As iatrogenic illnesses, at least some drug allergies should be preventable. The most important prophylactic measure is for physicians to routinely ask about adverse effects from previous medications before prescribing drugs.