Adverse drug reactions with an immunological basis: from clinical practice to basic research

Allergic drug reactions with an immunological basis (ADRIB) are an important problem affecting many people. However, despite all the clinical and basic research carried out, ADRIB have not been sufficiently evaluated (1). The magnitude of the problem, in terms of the number of people affected, is not known, because there is a lack of adequate pharmacoepidemiological studies (2–4). A large number of people have been labelled as allergic to different drugs on the basis of the mere description of a temporal association between drug intake and different symptoms compatible with an allergic or pseudoallergic/idiosyncratic reaction (1, 5). These reactions are often induced by diverse drugs, such as nonsteroidal anti-inflammatory drugs (NSAID), opioids, contrast media and muscle relaxants (1, 6). This implies that very often patients diagnosed with drug allergy, pseudoallergy or falsely labelled drug allergy are not given adequate treatment, and serious consequences may arise. Furthermore, expensive or even restricted drugs are often used. ADRIB can be classified as immediate, accelerated or delayed, according to the time interval between intake of the drug and occurrence of the reaction (7, 8). Although this classification was set up by Levine on the basis of his experience with penicillin allergy (7), different studies reported in the medical literature, as well as clinical practice, show that this classification can be applied to the whole world of drug allergy (8, 9). From the clinical standpoint, immediate (IR) and nonimmediate reactions (NIR) differ in the time interval between drug intake and appearance of clinical manifestations. In IR they appear within 1 h, and often within just a few minutes, after drug intake and the main clinical manifestations are urticaria/angiedema and/or anaphylaxis (1, 8). NIR appear hours, days, or even weeks after drug intake, and elicit a spectrum of manifestations ranging from mild urticaria or exanthema to severe toxic epidermal necrolysis (8, 10). A number of organ-specific diseases can also be considered as ADRIB, and often appear within the context of a systemic reaction (10–12). The diagnostic approaches for evaluating IR and NIR are different. In IR, mostly reactions to penicillin, IgE antibodies can be revealed by skin testing and also by the in vitro assay of specific IgE antibodies (13, 14). In NIR, only intradermal or patch tests are widely accepted (15–17); the value of other methods will be discussed below. However, apart from IgE mediated reactions to betalactams (18), for both IR and NIR, the in vivo and in vitro diagnostic methods are of limited value and very often the clinical evaluation is the most important, or sometimes the only, approach for establishing whether the patient is allergic to the drug or not (1, 6). This implies that we need to rely upon a detailed clinical history, often in association with a controlled administration of the drug, to assess Allergy 2002: Volume: 57 (Suppl. 72): 41–44 Printed in UK. All rights reserved Copyright # 2002 Blackwell Munksgaard