Editorial [Hot Topic: Advances in Diagnosing Drug Hypersensitivity Reactions (Executive Editors: A. Romano and M. Ventura)]

Like the previous one published in 2006 [1], this volume addresses literature regarding the pathogenic mechanisms, diagnosis, and prevention of drug hypersensitivity reactions, in order to improve the management of a problem in constant evolution. Specifically, the present issue provides an update on the main diagnostic methods of such reactions and supplements the information of the previous volume [1], discussing some topics, such as hypersensitivity reactions to biologic agents, nonaromatic anticonvulsants, macrolide antibiotics, anticoagulants, and antineoplastic drugs, not included in the latter. Also like the previous one [1], the present volume often refers to the general guidelines for diagnosing drug hypersensitivity reactions devised by the European Network for Drug Allergy (ENDA), the European Academy of Allergology and Clinical Immunology interest group on drug hypersensitivity; it contains articles by researchers and clinicians belonging to the ENDA and to the American Academy of Allergy, Asthma and Immunology Committee on Adverse Reactions to Drugs and Biologicals. In preparing this volume, we have taken into account the needs of readers who wish to keep abreast of the latest developments regarding hypersensitivity reactions to drugs, particularly those concerning their diagnosis and prevention. In the first article, Guéant and coworkers [2] focus their attention on the genetic risk factors of hypersensitivity reactions to drugs such as β-lactams, carbamazepine, and abacavir. Most studies regard HLA haplotype association, single nucleotide polymorphisms, or polymorphisms in genes encoding drug-metabolizing enzymes. With regard to β-lactams, the genetic factors involved in IgE-mediated mechanisms appear to be connected with TNFA -308G>A, class switching to IgE by B cells (variants of IL13 and of IL4RA), and expression of IgE receptors on target cells (variant of the FcηRIβ gene). As far as delayed T-cell-mediated reactions to drugs are concerned, an association of HLA-B*1502 and HLA-B*5801 has been observed in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis connected with carbamazepine and HLA-B*5701 with abacavir hypersensitivity. HLA-B*5701 seems to be a strong predictor in whites, and the prospective HLA-B*5701 screening enables HIV patients at risk for abacavir hypersensitivity reactions to be identified, thus playing a crucial role in the effective prevention of such reactions. Carbamazepine hypersensitivity is also influenced by gene variants of cytochrome P450 enzymes on the generation of reactive metabolites, while CYP2C9*2 and CYP2C9*3 polymorphisms influence the bioactivation of sulphamethoxazole in prohapten. The pharmacogenetic studies on aspirin hypersensitivity have identified distinct types of predictors, such as HLA genotypes, a polymorphism in the promoter of the FcηRIα gene, and variants in genes of enzymes from arachidonic acid pathway. The following three articles [3-5] provide data on the main in vivo and in vitro diagnostic tests. The review by Brockow and Romano [3] addresses literature data regarding the diagnosis of drug hypersensitivity reactions by skin (prick, intradermal) and patch tests. Even though these tests are the most readily available tools for the evaluation of drug hypersensitivity reactions, their diagnostic value for many drugs have not been fully established yet. However, reliable skin test procedures for the diagnosis of drug hypersensitivity have been defined, and test concentrations have been validated for many drugs, such as β- lactams, neuromuscular blocking agents (NMBAs, or muscle relaxants), and iodinated contrast media. In many cases, skin tests can provide information about the culprit drug and the mechanism involved in certain reactions, and allow the physician to avoid hazardous provocation tests. Skin tests should be performed according to the clinical features of hypersensitivity reactions. In immediate reactions (i.e., occurring within one hour after the last drug administration), an IgE-mediated mechanism can be demonstrated by a positive skin prick and/or intradermal test after 20 minutes, whereas in non-immediate reactions (i.e., occurring more than one hour after the last drug administration), a T-cell involvement can be found by a positive patch test and/or a delayed-reading intradermal test. The predictive value of skin tests varies with the drug tested and is especially high with β-lactams (penicillins, cephalosporins, carbapenems, and monobactams), NMBAs, insulins, platins, streptokinase, and chymopapain. For this reason, these tests have also been carried out in order to identify the patients at risk, such as candidates for chemonucleolysis with chymopapain, or patients undergoing sequential therapeutic courses with platins. Moreover, skin testing with cephalosporins and carbapenems has proved to be a useful tool for finding safe alternatives in the patients with a well-demonstrated IgE-mediated hypersensitivity to penicillins.