Editorial [Hot Topic: An Update on the Diagnosis of Allergic and Non-Allergic Drug Hypersensitivity (Executive Editors: M.T. Ventura and A. Romano) ]

This volume is dedicated to hypersensitivity reactions to drugs, which are increasing, partly because of indiscriminate consumption of the latter. In fact, in industrialized countries drug abuse represents one of the greatest problems of public health. The revised nomenclature for allergies [1], which is based on the mechanisms that initiate and mediate hypersensitivity reactions, classifies such reactions to drugs as either allergic or non-allergic. The former are mediated by immunologic mechanisms, either antibodies or cells; all other reactions should be referred to as nonallergic drug hypersensitivity. In addition, allergic reactions to drugs are classified as IgE-mediated or non-IgEmediated; some of the latter are cell-mediated. In IgE-mediated reactions, the drug or drug metabolite reacts with IgE bound to the surface of mast cells and leads to the activation, degranulation, and release of mast-cell vasoactive mediators like histamine and tryptase. In cell-mediated allergic reactions, CD4+ and CD8+ T cells recognize drugs through their αβ receptors. Drug-specific T cells generate inflammatory reactions, mainly cutaneous, through the release of various cytokines (e.g., interleukin-5, interferon) and chemokines (e.g., interleukin-8). Non-allergic immediate hypersensitivity reactions to drugs (i.e., occurring less than one hour after drug administration) are frequent, and their symptoms are similar to those observed in IgE-mediated allergic reactions. Non-allergic reactions may involve different pathogenic mechanisms, such as the capability of iodinated contrast media (ICM) of releasing mediators through a non-immunologic mechanism and the inhibitory effect on cyclooxygenase-1 of nonsteroidal anti-inflammatory drugs (NSAIDs). This volume contains articles by researchers and clinicians belonging to the European Network for Drug Allergy (the European Academy of Allergology and Clinical Immunology's interest group on drug hypersensitivity). In preparing this issue, we have tried to meet the needs of readers who wish to learn about the latest developments regarding this subject, particularly those concerning pathogenic mechanisms and diagnostic aspects. In the first article, Guglielmi and coworkers [2] focus their attention on the risk factors of hypersensitivity reactions to drugs, which are related to the latter and the treatment regimens, as well as to the host. As far as genetic factors are concerned, most studies regard HLA haplotype association or polymorphisms in genes encoding drugmetabolising enzymes. There are also studies concerning single nucleotide polymorphisms, which may be involved in multifactorial and multigenic diseases, and aimed at enabling patients at risk for hypersensitivity reactions to be identified. The following three articles [3-5] provide data on hypersensitivity reactions to antibacterial drugs such as quinolones and β-lactams. The review by Schmid and coworkers [3] analyzes the different pathogenic mechanisms involved in hypersensitivity reactions to quinolones, with special attention to T cell-mediated ones. The authors also provide data on IgE-mediated reactions, such as anaphylactic shock, urticaria and angioedema, and highlight the usefulness of the sepharose radioimmunoassay of serum-specific IgE against quinolones in the diagnosis of such reactions. They also stress that cross-reactivity among quinolones at both the IgE- and T-cell level is clinically well documented. Therefore, patients with hypersensitivity reactions to any quinolone should not be re-exposed to any antimicrobial agents of that class. The paper by Antunez and coworkers [4] focuses its attention on diagnostic tests for IgE-mediated hypersensitivity reactions to β-lactams, mainly penicillins. Diagnostic work-ups for such reactions include skin tests, serum-specific IgE assays, flow cytometric basophil activation tests and, in case of negative responses to these in vivo and in vitro tests, controlled administrations of suspect antibiotics. The authors emphasize the importance of the side-chain antigenic determinants of the various β-lactams and thus the need to use in diagnosis the suspect β-lactams themselves. In fact, hypersensitivity reactions to β-lactams may not be detected by tests performed only with penicillin determinants in cases where side-chain determinants play an important role in sensitization. The article by Guéant et al. [5] demonstrates the usefulness of skin testing with responsible cephalosporins, the sepharose radioimmunoassay of serum-specific IgE against cephalosporins, and challenges in diagnosing immediate reactions to these β-lactams....