Evaluation of Subjects Experiencing Allergic Reactions to Non-Steroidal Anti-Inflammatory Drugs: Clinical Characteristics and Drugs Involved.

Natalia Pérez-Sánchez,José A Cornejo-García,Gador Bogas,María J Torres,Inmaculada Doña,Almudena Testera,María Salas

doi:10.3389/fphar.2020.00503

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs), the most commonly prescribed and consumed medicines worldwide, are the main triggers of drug hypersensitivity reactions (DHRs). The underlying mechanisms of NSAID-DHRs may be related to COX-1 inhibition (cross-hypersensitivity reactions, CRs) or to immunological recognition (selective reactions, SRs), being the latter remarkably less studied. SRs include those usually appearing within the first hour after drug intake (single-NSAID-induced urticaria/angioedema or anaphylaxis, SNIUAA), and those usually occurring more than 24 h after (single-NSAID-induced delayed reactions, SNIDR). We have evaluated the largest series of patients with SRs, analyzing the number of episodes and drugs involved, the latency for reaction onset, the clinical entities, among other variables, as well as the value of available diagnostic methods. Globally, pyrazolones and arylpropionics were the most frequent culprits (39.3% and 37.3%, respectively). Pyrazolones were the most frequent triggers in SNIUAA and arylpropionics in SNIDR. Urticaria was the most common clinical entity in SNIUAA (42.4%) followed by anaphylaxis (33.3%); whereas SNIDR induced mostly fixed drug eruption (41.1%) and maculopapular exanthema (32.6%). The percentage of patients diagnosed by clinical history was higher in SNIUAA compared with SNIDR (62.7% versus 35.3%, p = 0.00015), whereas the percentage of those diagnosed by skin tests was higher in SNIDR than in SNIUAA (47.1% versus 22.8%, p = 0.00015). Drug provocation test with the culprit was performed in 67 SNIUAA (14.5%) and in 9 SNIDR (17.6%) patients. Our results may be of interest not only for allergologists but also for other clinicians dealing with these drugs, and can be useful for the correct identification of subjects experiencing DHRs to NSAIDs, and for avoiding mislabeling. Moreover, as NSAIDs are highly consumed worldwide, our results may be of interest for evaluating other populations exposed to these drugs.

Highlights

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequent triggers of drug hypersensitivity reactions (DHRs) (Doña et al, 2012; Aun et al, 2014; Blanca-Lopez et al, 2014; Jares et al, 2015)
We considered the number of episodes suffered after NSAID intake: with at least 2 episodes they were diagnosed as single-NSAIDinduced delayed reaction (SNIDR); a positive drug provocation test (DPT) with the culprit was required to confirm diagnosis when only one episode was reported
NSAIDs are the most frequent triggers of DHRs, and it appears that the number of clinical entities that they can induce is greater than initially thought (Demir et al, 2015; Cousin et al, 2016)

Summary

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequent triggers of drug hypersensitivity reactions (DHRs) (Doña et al, 2012; Aun et al, 2014; Blanca-Lopez et al, 2014; Jares et al, 2015). CRs are induced by chemically distinct (non-related) drugs and do not require previous immunological recognition; SRs require this recognition to a single/group of drug(s), with subjects tolerating other chemically non-related NSAIDs, including strong COX-1 inhibitors. The latter includes immediate reactions, which occur in most patients up to 1 h after drug intake (single-NSAIDinduced urticaria/angioedema or anaphylaxis; SNIUAA); and delayed reactions, which occur more than 24 h after drug intake (single-NSAID-induced delayed reactions; SNIDR). Regarding SNIDR, a T cell-mediated mechanism has been proposed (Kowalski et al, 2013)

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Conclusion