Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification

Allergol Immunopathol (Madr). 2023 Sep 1;51(5):84-92. doi: 10.15586/aei.v51i5.946. eCollection 2023.

Abstract

Background: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting.

Methods: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines.

Results: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs.

Conclusions: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Keywords: Adverse Drug Reactions; Classification; Hypersensitivity; NSAIDs; Phenotyping.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Angioedema* / epidemiology
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Drug Hypersensitivity* / diagnosis
  • Drug Hypersensitivity* / epidemiology
  • Humans
  • Retrospective Studies
  • Single-Blind Method
  • Urticaria* / epidemiology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal