Safety of Cyclooxygenase 2 Inhibitors and Increased Leukotriene Synthesis in Chronic Idiopathic Urticaria With Sensitivity to Nonsteroidal Anti-inflammatory Drugs

Abstract

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 E 4 (LTE 4 ), and serum levels of mast cell tryptase.

Differential Contribution of the CysLTR1 Gene in Patients with Aspirin Hypersensitivity

“…Although recent data suggest that abnormal arachidonate metabolism is a common finding in both AIA and aspirininduced urticaria [9][10][11], there have been very few studies to suggest a genetic predisposition to aspirin-induced urticaria for patients with aspirin hypersensitivity. In the present study, we speculated that the CysLTR1 and LTC4S genes might be useful for differentiating the two major phenotypes of aspirin hypersensitivity.…”

“…However, in contrast to AIA, the association of the cutaneous reaction with aspirin hypersensitivity has not been investigated. Up to 40% of patients with chronic urticaria exhibit increased wheal size and swelling after intake of aspirin [6,9], and it has been suggested that increased levels of CysLTs resulting from alterations in arachidonate metabolism may exacerbate latephase allergic reactions in AICU patients, as in AIA patients [9][10][11]. However, the pharmacologic effects of CysLT receptor antagonists on AICU patients have not been investigated.…”

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

“…In support, there is also the evidence that elevated levels of LTE 4 have been found in the urine of patients with AD (Adamek-Guzik et al, 2002;Øymar and Aksnes, 2005). Chronic urticaria (CU) may manifest as an idiopathic reaction or as a reaction to a known cause, such as cold, pressure, food additives, or NSAIDs; however, this does not occur with selective COX-2 inhibitors (Zembowicz et al, 2003). Of interest, the prevalence of aspirin sensitivity among patients with CU is estimated to be between 20 and 30% (Grattan, 2003), and recently the LTC 4 S Ϫ444AϾC polymorphism has been suggested to be a risk factor for aspirin-induced urticaria (Sá nchezBorges et al, 2009).…”

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA# and GA2LEN/HANNA*

“…Although measurements of sufidoleucotrienes from leucocytes and basophile activation tests have been proposed, there is no in vitro test approved for routine diagnosis of cutaneous type of NSAID hypersensitivity (49,55).…”