Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively prescribed in daily clinical practice. NSAIDs are the main cause of drug hypersensitivity reactions all over the world. The inhibition of cyclooxygenase enzymes by NSAIDs can perpetuate arachidonic acid metabolism, shunting to the 5-lipoxygenase pathway and its downstream inflammatory process. Clinical phenotypes of NSAID hypersensitivity are diverse and can be classified into cross-reactive or selective responses. Efforts have been made to understand pathogenic mechanisms, in which, genetic and epigenetic backgrounds are implicated in various processes of NSAID-induced hypersensitivity reactions. Although there were some similarities among patients, several genetic polymorphisms are distinct in those exhibiting respiratory or cutaneous symptoms. Moreover, the expression levels, as well as the methylation status of genes related to immune responses were demonstrated to be involved in NSAID-induced hypersensitivity reactions. There is still a lack of data on delayed type reactions. Further studies with a larger sample size, which integrate different genetic pathways, can help overcome current limitations of gen etic/epigenetic studies, and provide valuable information on NSAID hypersensitivity reactions.
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively administered for the treatment of pain and inflammation, while they commonly induce hypersensitivity reactions as well as unexpected adverse effects
Non-steroidal anti-inflammatory drug hypersensitivity has different clinical phenotypes and subphenotypes, and it is the consequence of complicated pathophysiological mechanisms
Its underlying mechanisms are regulated by genetic and epigenetic variants and possible interactions between them, which could be different among populations
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively administered for the treatment of pain and inflammation, while they commonly induce hypersensitivity reactions as well as unexpected adverse effects (e.g., gastrointestinal hemorrhage). The prevalence seems to rise in high-risk subjects, for instance, NSAID hypersensitivity reactions occur in 7.15% of asthmatic patients exhibited, which increases to 14.89% in those with severe asthma (Thong, 2018). Efforts have been made to investigate underlying mechanisms which can help predict NSAID hypersensitivity reactions. It is well known that NSAID consumption can alter the cyclooxygenase (COX)-1 and COX-2 pathways of arachidonic acid (AA) metabolism (Doña et al, 2020), triggering symptoms in subjects with hypersensitivity reactions. Other phenotypes, including “blended reactions,” food-dependent NSAID-induced anaphylaxis, and NSAID-induced multiple selective immediate reactions were reported (Doña et al, 2020). With advances in highthroughput sequencing technologies, many genetic studies have been conducted to elucidate genetic mechanisms of NSAID hypersensitivity phenotypes. This review aimed to summarize the current knowledge of the associations of genetic and epigenetic mechanisms in NSAID hypersensitivity
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