Allergic reactions in man

The general features of allergic drug reactions in man have recently been reviewed by Parker (85). By definition allergic drug reactions are produced by specific immunologic processes. Allergic drug reactions must be distinguished from adverse reactions due to overdosage, normal pharmacologic action, toxic metabolite formation, idiosyncrasy, nonspecific release of pharmacologic effector molecules, or drug interactions. The clinical manifestations of drug allergy are quite protean. In addition to classical manifestations of allergy such as serum sickness, anaphylaxis, contact dermatitis or urticaria, drug allergy may produce hemolytic anemia, thrombocytopenia, granulocytopenia, hepatitis, nephritis, pneumonitis, vasculitis, or neuritis where a single organ or cell type is affected. While many drugs produce reactions with suggestive of allergy, definitive experimental evidence either for or against mechanism is usually not available. Some of these reactions may involve allergic mediators released or produced nonimmunologically through pharmacologic, osmotic, or toxic effects on cells involved in immune inflammation (mast cells, basophils, phagocytes, and lymphocytes) or through nonspecific activation of effector molecules in extracellular fluid such as the complement proteins. Drugs may also induce the formation of autoantibodies through mechanisms that are largely obscure, but may in some instances involve the direct participation of the drug as a hapten and in other instances occur indirectly through a pharmacologic or toxic action on the cells responsible for immune homeostasis.