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J Allergy Clin Immunol. 1996 Sep;98(3):678-85.

Intolerance to nonsteroidal antiinflammatory drugs: results of controlled drug challenges in 98 patients.

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  • 1Sección de Alergia, Hospital Universitario, Nuestra Señora del Pino, Las Palmas de Gran Canaria, Spain.



Controlled oral challenge is the only definitive way to detect the different clinical manifestations of intolerance to nonsteroidal antiinflammatory drugs (NSAIDs).


This study was carried out to describe the clinical manifestations of drug challenges in a population with histories of intolerance to NSAIDs.


Two-hundred forty subjects were included in a single-blind, placebo-controlled drug challenge protocol.


Eighty patients exhibited a positive response to drug challenge: 52 had isolated periorbital angioedema, 13 had cutaneous rashes, eight had bronchial asthma (7 with associated periorbital angioedema), three had nasoocular reactions, and four had systemic anaphylaxis. In another 18 patients who were referred for treatment because of a reaction suggesting systemic anaphylaxis, the implicated drug was not given, but tolerance to other NSAIDs was found. The mean age of patients with isolated periorbital angioedema was significantly lower (p < 0.001) than that of the other groups of NSAID reactors. A significant increase (p < 0.001) in atopy was found among patients with isolated periorbital angioedema (100%) in comparison with other patients with NSAID intolerance (45.6%). NSAID cross-reactivity was a common finding, but cross-reactivity was not found in two cases of periorbital angioedema, one case of urticaria, one case of bronchial asthma, and 18 cases of systemic anaphylaxis.


In atopic subjects, isolated periorbital angioedema constitutes the most frequent manifestation of NSAID intolerance. Such patients are younger than other NSAID reactors and commonly have intolerance to several NSAIDs.

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