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Drug hypersensitivity includes allergic ( AR) and nonallergic reactions ( NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions ( IR) to beta-lactams ( n = 19), NAR against aspirin ( n = 12) and other nonsteroidal anti-inflammatory drugs ( NSAIDs) ( n = 8), and IR to biologics ( n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA- DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions to aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs ( NSAIDs) constitute only a subset of all adverse reactions to these drugs, but due to their severity pose a significant burden to patients and are a challenge to the allergist. In susceptible individuals, NSAIDs induce a wide spectrum of hypersensitivity reactions with various timing, organ manifestations, and severity, involving either immunological (allergic) or nonimmunological mechanisms. Proper classification of reactions based on clinical manifestations and suspected mechanism is a prerequisite for the implementation of rational diagnostic procedures and adequate patient management. This document, prepared by a panel of experts from the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity, aims at reviewing the current knowledge in the field and proposes uniform definitions and clinically useful classification of hypersensitivity reactions to NSAIDs. The document proposes also practical algorithms for the diagnosis of specific types of NSAIDs hypersensitivity (which include drug provocations, skin testing and in vitro testing) and provides, when data are available, evidence-based recommendations for the management of hypersensitive patients, including drug avoidance and drug desensitization. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21–25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/ or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs. [ABSTRACT FROM AUTHOR]