Allergic reactions to drugs: involvement of T cells

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Abstract
Drug side effects are common. They are usually classified as type A reactions if they are related to the pharmacological activity of the drug, and type B reactions if unrelated to the pharmacological activity. Immune mediated side effects are type B reactions and account for about one seventh of all drug related side effects.1Their frequency is, however, highly dependent on the type of drug. Some drugs are notorious for their allergic side effects—for example, some antibiotics and antiepileptics—while other drugs are seldom related to allergies. The diagnosis of drug allergy is difficult for various reasons. Firstly, the clinical manifestations of drug allergies are very heterogeneous. Drug allergic reactions imitate diseases, causing symptoms similar to infectious, autoimmune, or superantigen triggered diseases. If no skin symptoms are present, drug induced allergic reactions such as hepatitis or interstitial lung diseases are likely to be underdiagnosed. Moreover, viral infections such as HIV or EBV might be crucial cofactors to elicit symptoms.2 3 Secondly, there are no reliable tests generally available to diagnose drug allergy and to pinpoint the relevant drug. The large number of different drugs able to elicit side effects limits the possibility of having standardised tests prepared for each compound, even if one neglects metabolites. Skin test systems have been systematically developed for penicillin hypersensitivity only, but they are tailored to detect IgE mediated allergies and are not standardised to detect other types of drug induced immunological side effects. Moreover, the presence of minor or more general cross reactivity limits the relevance of these tests.4 Finally, the pathophysiology of most drug related side effects is unknown. Only a small proportion of drug allergies is IgE mediated. How sensitisation to the drug occurs, to what extent T cells are involved, and how the different pathologies are related to the …