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Hypersensitivity to aspirin: Common eicosanoid alterations in urticaria and asthma
Lucyna Mastalerz, MD, PhD, Malgorzta Setkowicz, MD, Marek Sanak, MD, PhD, and Andrew Szczeklik, MD, PhD* Krakow, Poland

METHODS Subjects
The study population consisted of 74 patients with CIU in apparent remission, that is, without any skin symptoms for at least 4 weeks preceding the study (Table I). Diagnosisof CIU required presence of urticaria and/or angioedema every day or almost every day for more than 6 weeks over the last 0.5 to 6 years. All patients gave the history of skin reactions after the ingestion of aspirin or other NSAIDs but had no history of asthma, nasal polyps, or anaphylaxis. Two weeks before beginning of the study, any local steroids or antihistamines and leukotriene receptorantagonists were stopped. Patients were asked to avoid over-the-counter medications and food with artificial flavoring or preservatives. A group of healthy control subjects for comparison of basal urinary LTE4 and plasma 9a,11bPGF2 levels consisted of 52 healthy subjects (Table I). They were healthy and had no history of CIU, asthma, or atopic diseases. The patients gave informed consent, and the studywas approved by the University Ethics Committee.

Key words: Urticaria, eicosanoids, aspirin, NSAIDs, asthma

Shortly after its introduction into therapy, aspirin was implicated as the cause of an anaphylactic reaction. The first case report of acute angioedema/urticaria was published in 1902.1 Soon it was realized that aspirin might also precipitate violent acute bronchospasm. Over the years,it became evident that aspirin-induced asthma (AIA), as it started to be called, is a distinct clinical
From the Departments of Medicine and Dermatology, Jagiellonian University School of Medicin, Kracow, Poland. Received for publication July 25, 2003; revised December 19, 2003; accepted for publication December 22, 2003. Reprint requests: Andrzej Szczeklik, MD, PhD, Jagiellonian University,School of Medicine, Department of Medicine, ul. Skawinska 8, 31 e 066 ´ Krakow, Poland. 0091-6749/$30.00 Ó 2004 American Academy of Allergy, Asthma and Immunology doi:10.1016/j.jaci.2003.12.323

Study design
After a 2-week run-in period, the patients underwent aspirin testing. The single-blind, placebo-controlled oral challenge test with aspirin was carried out on 2 consecutive days. On day 1, 3capsules of 771

Food and drug reactions and anaphylaxis

Background: Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can precipitate adverse reactions in two apparently different clinical conditions: bronchial asthma and chronic idiopathic urticaria (CIU). Recent evidence indicates that the reactions are triggered by the drugs that inhibit cyclooxygenase-1 but notcyclooxygenase-2. Objective: To assess whether patients with CIU and aspirin sensitivity share common eicosanoid alterations with patients who have aspirin-sensitive asthma. Methods: Seventy-four patients with CIU and a history of sensitivity to aspirin and NSAIDs underwent placebocontrolled oral aspirin challenge tests. Concentrations of urinary leukotriene E4 (uLTE4) were measured by ELISA and plasma stableprostaglandin D2 metabolite, 9a,11b prostaglandin F2 by GC/MS. All measurements were carried out at baseline and after aspirin dosing. Patients were genotyped for the leukotriene C4 synthase (LTC4S) promoter single nucleotide polymorphism. Results: In 30 of 74 patients, the aspirin challenge was positive, resulting in urticaria/angioedema. In these 30 patients, baseline uLTE4 levels were higherthan in nonresponders and the healthy control subjects and increased further (significantly) after the onset of clinical reaction. No such increase occurred in subjects with negative aspirin challenge. Baseline uLTE4 levels correlated with severity of skin reactions. Plasma 9a,11b prostaglandin F2 levels rose significantly in both aspirin responders and nonresponders, although in the latter group the...