Delayed hypersensitivity mechanisms directed by drug-specific T cells are probably the most important mechanisms in the etiology of the most common drug eruptions—morbilliform exanthems—and also of rare and severe forms such as hypersensitivity syndrome, acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drugspecific T cells have been detected in these types of drug eruptions. Contrary to what has been believed for years, the antigen is more often the native drug itself than its metabolites. It remains to better understand why the stimulation of T cells by medications leads to reactions that are clinically so diverse | Chapter 056. Cutaneous Drug Reactions Part 3 DELAYED HYPERSENSITIVITY Delayed hypersensitivity mechanisms directed by drug-specific T cells are probably the most important mechanisms in the etiology of the most common drug eruptions morbilliform exanthems and also of rare and severe forms such as hypersensitivity syndrome acute generalized exanthematous pustulosis AGEP Stevens-Johnson syndrome SJS and toxic epidermal necrolysis TEN . Drugspecific T cells have been detected in these types of drug eruptions. Contrary to what has been believed for years the antigen is more often the native drug itself than its metabolites. It remains to better understand why the stimulation of T cells by medications leads to reactions that are clinically so diverse. Some answers were provided by the study of effector cells obtained at the site of skin lesions. Drug-specific cytotoxic T cells have been detected in the skin lesions of fixed drug eruptions and of TEN. In TEN blisters that result from accumulation of interstitial fluid under the necrotic epidermis contain T lymphocytes that are able to kill autologous lymphocytes and keratinocytes in a drug-specific HLA-restricted and perforin granzyme-mediated pathway. Drug-specific clones producing CXCL8 a neutrophil-attracting chemokine were obtained from skin tests of patients with AGEP a neutrophil-mediated drug reaction. One may therefore assume that the final pattern of drug eruptions results both from the nature of effectors cytotoxic T cells in blistering reactions chemokines in reactions mediated by neutrophils or eosinophils and from the intensity of stimulation and response. GENETIC FACTORS AND CUTANEOUS DRUG REACTIONS Specific genetically determined defects in the ability of an individual to detoxify toxic reactive drug metabolites predispose such individuals to the development of drug toxicity. It has also been suspected that a slow acetylator phenotype increases the risk of rash from sulfonamides. However in two large .
