Drug metabolism, danger signals, and drug-induced hypersensitivity

One of the most difficult challenges for the practicing allergist/immunologist today is that of evaluating and managing patients who present with histories of drug-induced reactions. Adverse drug reactions are heterogenous, and a single drug can often cause a multitude of reactions. Because the mechanisms responsible for many of these reactions are not known, they can be, and often are, difficult to classify. Moreover, for those that have features consistent with immune-mediated mechanisms, our diagnostic tools remain limited, because little is known about the relevant immunogenic determinants of most drugs. Despite these challenges, management approaches must be devised for patients who present with histories of drug-induced disease. Simply telling such a patient to avoid all drugs that have been associated with previous adverse events leaves both the patient and the referring physician frustrated. The initial part of this review focuses on exciting current research that is furthering our understanding of the mechanisms responsible for drug-induced reactions. Because it will take time to translate this new information into clinical practice, the latter part of the review focuses on ways to evaluate and manage patients who present with drug-induced reactions using the tools and the knowledge that are currently available.