Drug Allergy: Definitions and Phenotypes

Drug hypersensitivity reactions (DHRs) are objectively reproducible symptoms or manifestations caused by exposure to a drug at a dose tolerated by normal persons. The term drug allergy is used to describe immunologically mediated DHRs. Pretest assessment of a given DHR is needed to determine the best test procedure and management. Clinically, DHRs should be phenotyped according to (1) chronology, (2) clinical manifestation, and the (3) involved drug. The different phenotype classifications relate to each other. Immediate DHRs occurring within 6 hours after drug intake nearly always manifest clinically with urticaria, angioedema, or manifestations of anaphylaxis and are most often elicited by nonsteroidal antiinflammatory drugs, β-lactams, radiocontrast media, or muscle relaxants. Nonimmediate DHRs after more than 6 hours mostly are different forms of exanthems (such as the common maculopapular exanthema or drug rash with eosinophilia and systemic symptoms), and typical elicitors strongly depend on the form of the exanthem. Phenotyping and pooling all available data allows the best prediction for the probability of a DHR, the culprit drug, and the mechanism of the DHR involved. In this review, phenotyping of DHRs by chronology, clinical manifestations, and typical elicitors, as well as the associations between the phenotypes, are explained.