Drug Hypersensitivity

The in vitro diagnosis of allergic reactions to drugs is of particular interest to clinicians, as neither the clinical history nor the in vivo tests are fully conclusive. In addition, these tests may often be associated with risk, as occurs with the drug provocation test. Various different in vitro tests are available for the evaluation of drug hypersensitivity depending on the immunological mechanism involved, either IgE mediated or T cell mediated. For IgE-mediated reactions, the determination of serum-specific IgE, antigen-specific histamine release and sulphidoleukotriene production after in vitro stimulation of effector cells, as well as analysis of the activation markers of these cells (the basophil activation test), provide greater diagnostic precision. Serum-specific IgE assays are still the most common in vitro method for evaluating immediate reactions. However, either there is no great commercial availability of fixed drugs for this study, with the exception of antibiotics (penicillin G and V, ampicillin, amoxicillin and cefaclor), a few muscle relaxants and certain substances, like insulins and ACTH. The most validated immunoassay, ImmunoCAP (Phadia, Uppsala, Sweden), has been widely used to evaluate immediate reactions to beta-lactams, mainly penicillins, with a specificity approaching 90% and a sensitivity of up to 50% (Blanca et al., 2001; Sanz et al., 2002a) The in vitro study of the cell response in non-immediate reactions mainly assesses the T-cell response. A cellular response involving drug-related T-cell activity may be assessed in vitro by means of both the lymphocyte transformation test (LTT) (Pichler & Tilch, 2004) and the flow cytometric lymphocyte activation test, based on upregulation of the activation marker CD69 (Beeler et al., 2008). The combination of these tests with an assay of the production of drug-specific cytokines (e.g., IFN-g, IL-2, IL-5, IL-8 and IL-12) can increase the sensitivity and specificity to 48% and 82%, respectively (Romano et al., 2011; Rozieres et al., 2009a).