Dataset Information

T cell-mediated hypersensitivity reactions to drugs.

ABSTRACT: The immunological mechanisms driving delayed hypersensitivity reactions (HSRs) to drugs mediated by drug-reactive T lymphocytes are exemplified by several key examples and their human leukocyte antigen (HLA) associations: abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02, allo-purinol and HLA-B*58:01, and both amoxicillin-clavulanate and nevirapine with multiple class I and II alleles. For HLA-restricted drug HSRs, specific class I and/or II HLA alleles are necessary but not sufficient for tissue specificity and the clinical syndrome. Several models have been proposed to explain the immunopathogenesis of severe T cell-mediated drug HSRs, and our increased understanding of the risk factors and mechanisms involved in the development of these reactions will further the development of sensitive and specific strategies for preclinical screening that will lead to safer and more cost-effective drug design.

SUBMITTER: Pavlos R

PROVIDER: S-EPMC4295772 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

T cell-mediated hypersensitivity reactions to drugs.

Pavlos Rebecca R Mallal Simon S Ostrov David D Buus Soren S Metushi Imir I Peters Bjoern B Phillips Elizabeth E

Annual review of medicine 20141027

The immunological mechanisms driving delayed hypersensitivity reactions (HSRs) to drugs mediated by drug-reactive T lymphocytes are exemplified by several key examples and their human leukocyte antigen (HLA) associations: abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02, allo-purinol and HLA-B*58:01, and both amoxicillin-clavulanate and nevirapine with multiple class I and II alleles. For HLA-restricted drug HSRs, specific class I and/or II HLA alleles are necessary but not sufficient for ...[more]

PMID: 25386935

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Project description:The incidence of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) has risen over last years, representing an important health problem. HSRs to ICMs are classified into immediate reactions (IRs) and non-immediate reactions (NIRs) according to if they occur within 1 h or longer after ICM administration. The diagnosis of HSRs to ICM is complex as skin test (ST) sensitivity ranges widely, and drug provocation test (DPT) protocols are heterogeneous. In this manuscript, we describe the clinical characteristics of a series of patients confirmed as HSR to ICM and the diagnosis procedure carried out, looking into those cases confirmed as HSRs to multiple ICMs. For this purpose, we prospectively evaluated patients suggestive of HSRs to ICMs and classified them as IRs or NIRs. STs were carried out using a wide panel of ICMs, and in those with a negative ST, a single-blind placebo controlled DPT was performed with the culprit. If ST or DPT were positive, then tolerance was assessed with an alternative negative ST ICM. We included 101 cases (12 IRs and 89 NIRs) confirmed as allergic. Among them, 36 (35.64%) cases were allergic to more than one ICM (8 IRs and 28 NIRs). The most common ICM involved were iomeprol and iodixanol. Although not statistically significant, the percentage of patients reporting anaphylaxis was higher in patients allergic to multiple ICMs compared with patients allergic to a single ICM (50 vs. 25%). Likewise, the percentage of positive results in STs was higher in patients allergic to multiple ICMs compared with those allergic to a single ICM (for IR 62.5 vs. 25%, p > 0.05; and for NIR, 85.71 vs. 24.59%, p < 0.000). In cases allergic to more than one ICM, DPT with negative-ST ICM was positive in more than 60% (24/36) of cases. Therefore, allergy to multiple ICMs is common, associated to severe reactions in IRs, and confirmed frequently by positive STs. The allergological work-up should include DPT not only to establish the diagnosis but also to identify safe alternative ICM, even if ICM is structurally unrelated and ST is negative. More studies are needed to clarify mechanisms underlying cross-reactivity among ICMs.

Dataset Information

T cell-mediated hypersensitivity reactions to drugs.

Publications

T cell-mediated hypersensitivity reactions to drugs.

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