title: Drug hypersensitivity reactions involving skin.
abstract: Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd).
authors.affiliation: Division of Allergology, Department of Rheumatology, Clinical Immunology and Allergology, Inselspital, CH-3010 Bern, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hausmann
authors.forename: Benno
authors.initials: B
authors.lastname: Schnyder
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: D000818:Animals; D003875:Drug Eruptions / Q000276:immunology* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D006241:Haptens / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology; D012008:Recurrence; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
chemical_list: D006241:Haptens; D011948:Receptors, Antigen, T-Cell