NSAID hypersensitivity

Ibuprofen etc are a common cause of reactions, but mostly non immune mediated, via COX -1 inhibition. Previously called pseudo-allergy or intolerance, best called hypersensitivity, then subdivided into allergic or non-allergic. Often occurs in patients with underlying problem eg asthma, chronic urticaria, rhinosinusitis – exacerbates underlying condition. Hypersensitivity can be to a single drug, or cross-reactive, ie to unrelated drugs from different families (salicylates ie aspirin, propionic derivatives eg ibuprofen, acetic acid derivatives eg diclofenac, etc). Cross reactivity suggests a non-immune mechanism. Without history to support single drug (or family) hypersensitivity, you would have to advise the patient to avoid all NSAIDs.


  • Skin testing with culprit drug is appropriate if you have an acute urticarial or angioedema reaction in a single drug/family.
  • Oral challenge is appropriate to confirm all types of hypersensitivity, esp in equivocal histories. At the same time, challenge with aspirin to check cross-reactivity, and with next best alternative NSAID. Start 1/10 dose, increase every 2 hours.
  • For nasal/bronchial symptoms, inhaled lysine aspirin is safer and faster, but only 77-90% sensitive cf 90% for oral. Intranasal is equivalent if inhaled/oral not possible.
  • If patient is on long term steroids, or else has been well controlled for a long time, sensitivity seems less!
  • Consider proceeding to challenge with COX2 (coxib) if challenge positive.

Aspirin desensitization works for NSAID exacerbated respiratory disease, and NSAID induced (cross reactive) skin disease, controversial for chronic urticaria and no data for single drug skin disease or anaphylaxis. But needs maintenance dosing so only really useful for chronic conditions eg needing antiplatelet therapy.

Allergy 2013:68;1219