Immediate-type allergy to drugs and related compounds: evaluation and management

Adverse drug reactions (ADR) constitute a major health issue in outpatient and inpatient clinical settings. An allergic drug reaction is an immunologically mediated adverse drug reaction that exhibits specificity and recurrence on re-exposure to the offending and/or cross-reactive compound(s). Diagnosis of drug allergy is difficult, as a broad spectrum of different drugs can elicit various immune-mediated diseases with distinct (sometimes unclear) pathomechanism, the exact structure (epitope) that causes the reaction is frequently unknown, the presence of an in vitro or in vivo test results might not be predictive of a clinical situation, and the gold standard or reference test for diagnosis, the drug challenge, is a complicated and sometimes dangerous endeavour. Nevertheless, during the past few years serious attempts have been made to standardise and validate in vitro and in vivo techniques for the diagnosis of drug allergy. New techniques, e.g. flow-assisted analysis of in vitro basophil activation, are replacing older ones like histamine release for immediate-type hypersensitivity reactions. However, additional comprehensive studies are required to further validate the technique and allow its entrance in mainstream diagnostic use, particularly for non-IgE-mediated hypersensitivity. This review attempts to summarize the major causes of immediate hypersensitivity reactions to drugs and related compounds. Special attention is paid to the diagnostic and therapeutic management of this common iatrogenic complication.