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Drug Hypersensitivity Reactions Involving Skin

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Book cover Adverse Drug Reactions

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 196))

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).

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Authors and Affiliations

  1. Division of Allergology, Department of Rheumatology, Clinical Immunology and Allergology, Inselspital, CH-3010, Bern, Switzerland

    Werner J. Pichler

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  1. Oliver Hausmann
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  2. Benno Schnyder
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  3. Werner J. Pichler
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Correspondence to Werner J. Pichler .

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  1. Faculty of Pharmacy, University of Toronto, Toronto, Canada, M5S 2S2

    Jack Uetrecht (Professor of Pharmacy and Medicine, Canada Research Chair in Adverse Drug Reactions) (Professor of Pharmacy and Medicine, Canada Research Chair in Adverse Drug Reactions)

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Hausmann, O., Schnyder, B., Pichler, W.J. (2010). Drug Hypersensitivity Reactions Involving Skin. In: Uetrecht, J. (eds) Adverse Drug Reactions. Handbook of Experimental Pharmacology, vol 196. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00663-0_2

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