Drug hypersensitivity reactions in skin: understanding mechanisms and the development of diagnostic and predictive...

Cutaneous manifestations of drug hypersensitivity can be serious and potentially life threatening and may prevent effective drug therapy. T cells play an important role in the pathology of drug hypersensitivity reactions. Classical studies suggest that T-cell activation requires drug bioactivation, covalent binding to protein and antigen processing to stimulate an immune response. Recent studies have shown that drugs can also be presented to T cells in the absence of antigen processing and drug metabolism. In this article, sulfamethoxazole is used as a paradigm to describe the chemical mechanisms involved in the initiation and maintenance of an aberrant drug antigen specific T-cell response. Presentation of the same drug to different individuals can cause a variety of skin diseases. Such reactions have been classified according to the phenotype and functionality of the T-cell response. This review summarises the different forms of cutaneous hypersensitivity reactions and describes how T-cell clones generated from hypersensitive patients have been used to study the cellular mechanisms of anticonvulsant hypersensitivity. Potential uses of in vitro cell culture assays for patient diagnosis and drug evaluation are also discussed.