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

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.

Food‐dependent NSAID‐induced hypersensitivity (FDNIH) reactions: Unraveling the clinical features and risk factors

“…That could explain why pyrazolone derivatives are much more prevalent in the control group than in the FDNIH, since this group is the most frequently involved in single NSAID hypersensitivity reactions in Spain. 43,44 The multivariate analysis has helped to identify some risk factors for FDNIH. With 4 variables, LTP or gliadin sensitization, anaphylactic reaction, and the NSAID involved in the reaction different from a pyrazolone, we correctly classified 95.3% of cases, with a sensitivity of 92% and specificity of 96%.…”

“…These differences can be explained, at least in part, by differences in the demographic (children vs adults) and clinical conditions of the studied populations. That could explain why pyrazolone derivatives are much more prevalent in the control group than in the FDNIH, since this group is the most frequently involved in single NSAID hypersensitivity reactions in Spain 43,44 …”

Immunological Mechanisms in Cutaneous Adverse Drug Reactions

“…While these symptoms can range from being confined to the skin to accompanying systemic symptoms, especially in severe ADRs, exanthematous ADR is the most common form of cutaneous ADR ( Babu and Belgi, 2002 ). Typically, the skin lesions develop at least 1 h after the initial drug administration ( Christiansen et al ., 2000 ; Rozieres et al ., 2009 ; Torres et al ., 2009 ; Rodilla et al ., 2010 ; Phillips et al ., 2019 ; Pérez-Sánchez et al ., 2020 ).…”

Hypersensitivity reactions to arylpropionic acid derivatives: different drugs inducing different response patterns

“…CR patients were sub-classified into: i) NERD, if patients with underlying rhinitis and/or asthma with or without nasal polyposis reported respiratory symptoms (rhinitis, asthma and/or glottis edema) after NSAID intake; ii) NECD, if patients with underlying CSU experienced exacerbation of skin symptoms (urticaria and/or angioedema, AE) after NSAID intake; iii) NIUA, if patients without underlying CSU had urticaria and/or angioedema after NSAID intake; iv) blended reactions, if patients had a combination of skin (urticaria and/or angioedema) and respiratory symptoms (rhinitis, asthma and/or glottis edema) after NSAID intake. SR patients were sub-classified into: v) SNIUAA, if patients experienced urticaria, angioedema, or anaphylaxis within one hour up to 24 hours after NSAID intake; vi) SNIDR, in patients experienced cutaneous manifestations with or without systemic involvement more than 24 hours after NSAID intake [18].…”

“…In addition to ASA, DPT to the culprit AP was performed in subjects who tolerated ASA if they reported less than 2 episodes induced by APs [10,18]. If they reacted, they were classified into SRs, whereas if they tolerated the culprit APs, they were confirmed as non-allergic ( Figure 1) [10].…”