Descriptive Analysis of Cross-Reactive Anaphylaxis as a Different Clinical Subtype of Nonsteroidal Anti-Inflammatory Drug (NSAID) Hypersensitivity

Int Arch Allergy Immunol. 2021;182(2):131-138. doi: 10.1159/000510335. Epub 2020 Sep 21.


Introduction: The European Network of Drug Allergy and the European Academy of Allergy and Clinical Immunology have classified hypersensitivity reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs) into 5 phenotypes according to the pathophysiology, clinical manifestations, number of drugs involved, and the presence of underlying diseases. This classification does not include anaphylaxis as part of NSAID cross-reactivity. The objective of this study was to characterize a group of patients with anaphylactic NSAID cross-reactivity.

Method: This was a retrospective, descriptive, observational study. Patients who developed anaphylaxis to one NSAID plus another acute reaction (anaphylactic or not) to at least one other NSAID of a different chemical group were included. Demographic and clinical characteristics and the diagnostic approach were studied.

Results: A total of 38 patients were included, 28 (73.7%) of whom were women. The mean age was 40 ± 17.7 years. The main organs affected in the anaphylactic reaction were the skin and the respiratory system, occurring in 35 (92.1%) and 33 (86.8%) patients, respectively. Thirty-two (84.3%) patients presented with cutaneous and respiratory involvement simultaneously. The main anti-inflammatory agent involved in anaphylactic reactions was acetylsalicylic acid in 9 (23.7%) patients, followed by dipyrone in 8 (21.1%). The most frequent allergic comorbidity was rhinitis in 20 (52%) patients. Skin tests were performed in 15 (39.5%) patients, showing positivity in 12 (80%), mainly to mites. A total of 36 of 38 patients were challenged with alternative drugs, and 35 (97.2%) tolerated meloxicam and/or etoricoxib.

Conclusion: In the present study, NSAID cross-anaphylaxis was more frequent in women, and acetylsalicylic acid and dipyrone were the main triggers. Rhinitis was the main allergic comorbidity, and there was a high incidence of atopy. The majority tolerated selective COX-2 NSAIDs.

Keywords: Anaphylaxis; Blended reaction; Cross-reactive; Hypersensitivity; Nonsteroidal anti-inflammatory drug.

MeSH terms

  • Adult
  • Anaphylaxis / diagnosis*
  • Anaphylaxis / etiology*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cross Reactions / immunology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Retrospective Studies
  • Severity of Illness Index
  • Skin Tests
  • Symptom Assessment
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal