Drug Hypersensitivity Reactions

Abstract

Adverse reactions caused by drugs can be divided into two main groups, type A and type B reactions. Type A reactions represent nearly 80 %–85 % of these side effects and are caused by predictable pharmacological actions of the drug, while type B reactions develop on the basis of individual predisposition (idiosyncratic reactions, immune-mediated and nonimmune-mediated hypersensitivity reactions) and account for 15 %–20 % of adverse effects. The skin is the organ most commonly, but not exclusively, affected in drug hypersensitivity reactions both in the immune-mediated (allergic) and in the nonimmune-mediated (pseudoallergic) forms; these reactions are observed in 2 %–3 % of hospitalised patients. Immune-mediated drug hypersensitivity reactions comprise a heterogeneous group of diseases which can be classified according to Gell and Coombs (antibody-mediated drug hypersensitivity reactions: type I, IgE; type II and III, IgG; and type IV, T cell mediated). After better understanding of T-cell functions and discovery of subgroups, the late type IV reaction has been further subdivided in the revised form of Gell and Coombs classification (type IVa, T helper 1; type IVb, T helper 2; type IVc, T cytotoxic mediated and type IVd). Nonimmune-mediated hypersensitivity reactions are the so-called pseudoallergic reactions, which usually imitate IgE-mediated reactions with wheal and oedema formation, but sometimes anaphylaxis can also develop. These pseudoallergic reactions tend to arise less rapidly than true IgE-mediated allergies, they require higher doses of the drugs and neither IgE nor T-cell reactions can be demonstrated later. Non-specific histamine release, arachidonic acid pathway activation, bradykinin pathway alteration and complement activation can be detected in the background. Nonsteroidal anti-inflammatory drugs (NSAIDs), plasma expanders and radiocontrast media are the most common causes of pseudoallergic reactions.