Response to a selective COX-2 inhibitor in patients with urticaria/angioedema induced by nonsteroidal anti-inflammatory drugs

Allergy. 2011 Nov;66(11):1428-33. doi: 10.1111/j.1398-9995.2011.02684.x. Epub 2011 Aug 11.


Background: In subjects with hypersensitivity reactions with cross-intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs), tolerance to selective COX-2 inhibitors has not been evaluated in large series of well-phenotyped cases.

Methods: We evaluated 252 patients with urticaria and/or angioedema caused by hypersensitivity owing to cross-intolerance to NSAIDs. In addition to the clinical history, diagnosis was confirmed by provocation to an alternative NSAID. Two groups were considered: (A) patients with cross-intolerance to NSAIDs and intolerance to paracetamol and (B) patients with cross-intolerance to NSAIDs and good tolerance to paracetamol. Etoricoxib was administered to Group A patients and to a representative sample of Group B patients. In the event of a positive response, serum tryptase levels were determined and skin biopsy was performed in five patients in each group.

Results: Ibuprofen was the most commonly implicated drug, followed by acetylsalicylic acid (ASA). Urticaria was the most common manifestation, followed by angioedema. Most of the patients developed symptoms within 1 h. Twenty-five percent in Group A (n = 47) and 6% in Group B (n = 50) were intolerant to etoricoxib. Skin biopsy showed mast cell activation with the release of tryptase to the extracellular space but without the increase in serum tryptase levels.

Conclusion: Selective COX-2 inhibitors may be unsafe in subjects with urticaria and/or angioedema caused by hypersensitivity reactions to NSAIDs with cross-intolerance if they are intolerant to paracetamol. A quarter of patients who were intolerant to this drug were also intolerant to etoricoxib. In subjects with hypersensitivity to NSAIDs and intolerance to paracetamol, selective COX-2 inhibitors should be administered as a controlled, incremental dose provocation test to assess tolerance.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / adverse effects
  • Adolescent
  • Adult
  • Angioedema / chemically induced*
  • Angioedema / complications
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Aspirin / adverse effects
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects*
  • Drug Hypersensitivity / diagnosis
  • Drug Hypersensitivity / etiology*
  • Etoricoxib
  • Humans
  • Hypersensitivity, Immediate / diagnosis
  • Hypersensitivity, Immediate / etiology
  • Ibuprofen / adverse effects
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Single-Blind Method
  • Sulfones / administration & dosage
  • Sulfones / adverse effects*
  • Urticaria / chemically induced*
  • Urticaria / complications
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Pyridines
  • Sulfones
  • Acetaminophen
  • Aspirin
  • Ibuprofen
  • Etoricoxib