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Genetic variants of the AA pathway may play an important role in NSAID-induced AU. These data may help understand the mechanism underlying this disease.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

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Background and Purpose Cross‐reactive hypersensitivity to nonsteroidal anti‐inflammatory drugs (NSAIDs) is a relatively common adverse drug event caused by two or more chemically unrelated drugs and that is attributed to inhibition of the COX activity, particularly COX‐1. Several studies investigated variations in the genes coding for COX enzymes as potential risk factors. However, these studies only interrogated a few single nucleotide variations (SNVs), leaving untested most of the gene sequence. Experimental Approach In this study, we analysed the whole sequence of the prostaglandin‐endoperoxide synthase genes, PTGS1 and PTGS2, including all exons, exon‐intron boundaries and both the 5′ and 3′ flanking regions in patients with cross‐reactive hypersensitivity to NSAIDs and healthy controls. After sequencing analysis in 100 case–control pairs, we replicated the findings in 540 case–control pairs. Also, we analysed copy number variations for both PTGS genes. Key Results The most salient finding was the presence of two PTGS1 single nucleotide variations, which are significantly more frequent in patients than in control subjects. Patients carrying these single nucleotide variations displayed a significantly and markedly lower COX‐1 activity as compared to non‐carriers for both heterozygous and homozygous patients. Conclusion and Implications Although the risk single nucleotide variations are present in a small proportion of patients, the strong association observed and the functional effect of these single nucleotide variations raise the hypothesis of genetic susceptibility to develop cross‐reactive NSAID hypersensitivity in individuals with an impairment in COX‐1 enzyme activity.