Safety of cyclooxygenase 2 inhibitors and increased leukotriene synthesis in chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory drugs.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate various forms of urticaria by a nonallergic mechanism involving inhibition of cyclooxygenases.


OBJECTIVE
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.


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


METHODS
Tertiary referral center of a university hospital.


METHODS
Thirty-six patients with CIU.


METHODS
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.


METHODS
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.
Zembowicz
Artur
A
Department of Pathology, Harvard Medical School and Massachusetts General Hospital, Boston, USA.
Mastalerz
Lucyna
L
Setkowicz
Malgorzata
M
Radziszewski
Waldemar
W
Szczeklik
Andrzej
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D001706:Biopsy; D000068579:Celecoxib; D003196:Computer Graphics; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D003545:Cysteine / Q000652:urine; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D017999:Leukotriene E4 / Q000652:urine; D015289:Leukotrienes / Q000652:urine; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009288:Naproxen / Q000009:adverse effects; D011446:Prospective Studies; D011720:Pyrazoles; D012697:Serine Endopeptidases / Q000097:blood; D012867:Skin / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use*; D013450:Sulfones; D016896:Treatment Outcome; D053802:Tryptases; D014581:Urticaria / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D015289:Leukotrienes; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C112381:cysteinyl-leukotriene; C116926:rofecoxib; D009288:Naproxen; D017999:Leukotriene E4; D012697:Serine Endopeptidases; D053802:Tryptases; D000068579:Celecoxib; D003545:Cysteine; D001241:Aspirin