Adverse reactions to drugs: relationship to immunopathic disease

Immunopathic disease resulting from drug treatment occurs when drugs interact with lymphoid cells and induce an immunological reaction. Drugs, being foreign to the body, are immunogenic, either as such or as haptens bound to carrier proteins. The immune response is usually innocuous or unnoticed but occasionally becomes pathogenic. The impact is especially obvious when the immunopathic response affects blood, skin, liver or kidney. Immunopathic responses and effector mechanisms of injury, whether to drugs or other antigens, are considered in terms of four types: Type I--anaphylactic and mediated by immunoglobulin (Ig) E antibody, and exemplified by immediate penicillin reactions; Type II--cytolytic and complement-associated, mediated by IgG antibody, and exemplified by haemolytic reactions; Type III--vasculonecrotic (Arthus reaction), mediated by immune complexes, and exemplified by serum sickness-like reaction; Type IV--delayed hypersensitivity involving T lymphocytes but no antibody, and exemplified by contact dermatitis. In addition, certain drugs induce true autoimmune reactions exemplified by reactions to procaine amide (lupus erythematosus) and alpha methyldopa (positive Coombs test result). Drug reactions must be interpreted in terms of modern immunology, with involvement of both the B and T lymphocyte systems. Inherited predisposition exists, probably dependent both on immune response genes and on the rate of enzymatic handling of drugs. Diagnosis depends on a carefully taken history of drug administration, recognition of clinical manifestations, and results of tests now available in departments of clinical immunology.