Different Patterns of Response in Hypersensitivity Reactions to Arylpropionic Acid Derivatives

J Allergy Clin Immunol Pract. 2023 Dec;11(12):3715-3723. doi: 10.1016/j.jaip.2023.08.014. Epub 2023 Aug 14.

Abstract

Background: Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce.

Objective: To characterize in detail patients reporting DHRs to APs.

Methods: We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches.

Results: Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P = .005 and P = .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P = .0002 and P = .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required.

Conclusions: Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs.

Keywords: Anaphylaxis; Angioedema; Drug hypersensitivity; Drug provocation test; Ibuprofen; Nonsteroidal anti-inflammatory drugs (NSAIDs); Urticaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioedema* / diagnosis
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Drug Hypersensitivity* / diagnosis
  • Humans
  • Ibuprofen / adverse effects
  • Ketoprofen* / adverse effects
  • Naproxen / adverse effects

Substances

  • Ibuprofen
  • dexketoprofen trometamol
  • Ketoprofen
  • Naproxen
  • Anti-Inflammatory Agents, Non-Steroidal