JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

Safety of cyclooxygenase 2 inhibitors and increased leukotriene synthesis in chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory drugs

Artur Zembowicz, Lucyna Mastalerz, Malgorzata Setkowicz, Waldemar Radziszewski, Andrzej Szczeklik
Archives of Dermatology 2003, 139 (12): 1577-82
14676074

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate various forms of urticaria by a nonallergic mechanism involving inhibition of cyclooxygenases.

OBJECTIVES: To assess safety of cyclooxygenase inhibitors in patients with chronic idiopathic urticaria (CIU) and NSAID sensitivity and to evaluate a role of cysteinyl leukotriene metabolism and mast cell activation in sensitivity to NSAIDs in CIU.

DESIGN: Aspirin challenge test followed by randomized, prospective, double-blind, placebo-controlled crossover trial with cyclooxygenase 2 inhibitors.

SETTING: Tertiary referral center of a university hospital.

PATIENTS: Thirty-six patients with CIU.

INTERVENTIONS: Aspirin challenge test (up to 500 mg); randomized trial with rofecoxib (up to 37.5 mg) and celecoxib (up to 300 mg) in aspirin-sensitive patients. After completion of the trial, 7 patients received naproxen sodium (500 mg) as a positive control.

MAIN OUTCOME MEASURES: Standardized skin examination, skin biopsy with mast cell count, urinary levels of leukotriene E4 (LTE4), and serum levels of mast cell tryptase.

RESULTS: Aspirin induced skin eruption in 18 patients. Rofecoxib or celecoxib did not elicit skin eruption in any of the aspirin-sensitive patients. Patients with CIU had higher urinary excretion of LTE4 than healthy control subjects. Basal urinary levels of LTE4 and serum mast cell tryptase were increased in aspirin-sensitive compared with aspirin-tolerant patients. Severity and duration of aspirin-induced urticaria showed a positive correlation with urinary LTE4 excretion. Naproxen precipitated urticaria in 5 of 7 aspirin-sensitive patients and caused further increase in urinary LTE4.

CONCLUSIONS: Cyclooxygenase 2 inhibitors do not induce urticaria in patients with CIU sensitive to NSAIDs. Sensitivity to NSAIDs in CIU is associated with overproduction of cysteinyl leukotrienes and mast cell activation and most likely depends on inhibition of cyclooxygenase 1.

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