Use of ketoprofen oral challenges to detect cross-reactors among patients with a history of aspirin-induced urticaria

Background: In patients with a history of urticaria induced by a single nonsteroidal anti-inflammatory drug (NSAID), advising elimination of all drugs that inhibit cyclooxygenase 1 (COX-1) can lead to unnecessary avoidance of useful NSAIDs. Objective: To classify patients with a history of aspirin-induced urticaria as cross-reactors or single-drug reactors by oral challenges with another strong COX-1 inhibitor, namely, ketoprofen. Methods: Forty otherwise healthy patients with a history of acute urticaria after the ingestion of aspirin underwent single-blind, placebo-controlled oral challenges with ketoprofen. In patients who did not tolerate ketoprofen, tolerance tests with drugs exerting either COX-1 inhibition at high doses (acetaminophen and nimesulide) or no COX-1 inhibition at therapeutic doses (rofecoxib and tramadol) were performed. Results: In 24 patients (60%), ketoprofen induced urticaria that was controlled by an intravenous antihistamine; 18 (75%) of the 24 patients reacted after the first provocative dose. On subsequent challenges, 3 (38%) of 8 ketoprofen reactors did not tolerate nimesulide, whereas acetaminophen tramadol and rofecoxib were tolerated by 18 of 18, 14 of 14, and 16 of 16 ketoprofen reactors, respectively. Three ketoprofen reactors reported the onset of spontaneous recurrent urticaria 1 to 3 years after the challenge tests. Conclusion: In patients with a history of urticaria induced by a single NSAID, oral challenges with alternative COX-I inhibitors are helpful in detecting whether they are true single-NSAID reactors; weak COX-1 inhibitors should be challenged subsequently only in those who show multiple-NSAID intolerance.