Prevention of nonsteroidal inflammatory drug-induced urticaria and/or angioedema

Urticaria and/or angioedema (U/AE) are the most frequent and less severe forms of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Management of NSAID-induced U/AE includes (1) the avoidance of the culprit drug and of cyclooxygenase (COX) 1 inhibitors, (2) the use of weak COX-2 inhibitors, and/or (3) desensitization to aspirin. Because these possibilities may have drawbacks, we tested the possibility of preventing NSAID-induced U/AE by the administration of antihistamines and/or a combination of antihistamines and leukotriene antagonists.

To test the preventive effect of antihistamines and/or leukotriene antagonists on the development of U/AE in patients with a history of NSAID hypersensitivity confirmed by a positive challenge result.

A single, placebo-controlled, oral challenge using the culprit NSAID was applied to 65 patients with a history of NSAID-induced U/AE. In the case of recurrence of the symptoms, another oral challenge was performed under premedication with antihistamines alone or combined antihistamines and leukotriene antagonists.

A total of 59 of 65 patients (90%) tolerated a normal dose of NSAID, confirming previous data on the poor reproducibility of nonallergic hypersensitivity reactions to NSAIDs on challenge. Of the 6 patients who experienced recurrence of the U/AE on NSAID challenge, antihistamines and combined antihistamines and leukotriene antagonists prevented the hypersensitivity reactions in 2 and 3 of them, respectively. Only 1 patient still developed a moderate NSAID-induced urticaria despite the double premedication.

Treatment with NSAIDs at normal doses is possible and well tolerated in patients who have experienced NSAID-induced U/AE, which could be prevented by the concomitant use of antihistamines and leukotriene antagonists.