Clinical course and urinary eicosanoids in patients with aspirin-induced urticaria followed up for 4 years.

BACKGROUND: Little is known about the course of aspirin-induced urticaria. A special regulatory role of cysteinyl leukotrienes and prostaglandin D(2) (PGD(2)) has been postulated. OBJECTIVE: We performed a long-term observation on clinical course, aspirin sensitivity, and urinary eicosanoids in patients with aspirin-induced urticaria. METHODS: For 4 years, we followed up 22 patients with chronic idiopathic urticaria and aspirin hypersensitivity who restrained from the use of aspirin and other COX-1 inhibitors. Aspirin challenges were performed in 2002 (all results were positive) and repeated in 2006. Levels of urinary leukotriene E(4) (LTE(4)) and the main PGD(2) metabolite, 9 alpha 11 beta PGF(2), were measured at the same time points. RESULTS: During the follow-up period, the severity of urticaria has decreased. In 14 of 22 patients, the results of aspirin challenge remained positive. In 2002, these 14 patients responded to aspirin with a significant increase in urinary LTE(4) and 9 alpha 11 beta PGF(2) levels. When studied 4 years later, they showed a similar response of 9 alpha 11 beta PGF(2) (P = .047) and a tendency toward an increase in LTE(4) level (P = .057). There was a correlation between the urinary LTE(4) concentration after aspirin challenge and the intensity of skin eruptions. The dose of aspirin had no effect on the magnitude of response of both LTE(4) and the PGD(2) metabolite. In the remaining 8 patients, negative aspirin challenge results were not associated with changes in the urinary eicosanoids studied. CONCLUSIONS: Aspirin hypersensitivity manifesting as urticaria/angioedema remains present after 4 years in about two thirds of patients. Aspirin-precipitated skin reactions associate with increased excretion of LTE(4) and PGD(2).

Mechanism of chronic urticaria exacerbation by aspirin.

In some patients with chronic idiopathic urticaria (CIU), aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase 1 (COX-1) precipitate wheals and swelling. There is no in vitro diagnostic, and diagnosis can be established only by provocation challenges with aspirin or other NSAIDs. Skin reactions triggered by aspirin are associated with the inhibition of cyclooxygenase, specifically COX-1, but not COX-2, and are characterized by overproduction of cysteinyl leukotrienes (cys-LTs). Aspirin and other NSAIDs should be avoided, but highly specific COX-2 inhibitors, known as coxibs, are well tolerated and can probably be safely used. Evidence has been accumulated that these reactions are due to the interference of aspirin-like drugs with arachidonic-acid metabolism. In this article, we discuss the mechanism of these reactions, and the characteristic course of aspirin-induced urticaria and its management.

Histological spectrum of cutaneous reactions to aspirin in chronic idiopathic urticaria.

BACKGROUND: During a clinical trial, we obtained 16 biopsies of skin eruptions induced by aspirin in patients with chronic idiopathic urticaria (CIU). In this setting, aspirin triggers skin eruptions through a well-established non-immunological mechanism involving the inhibition of cyclooxygenase type I. This presented the rare opportunity to evaluate histological features of a series of skin eruptions induced by a drug acting through a defined mechanism in a controlled experimental setting. OBJECTIVE: Histological analysis of 16 biopsies of skin eruptions induced by oral aspirin challenge in patients with CIU. DESIGN: Microscopic analysis of tissue sections. PATIENTS: 16 patients with CIU. RESULTS: Aspirin (up to 500 mg) induced a restricted range of histological responses with a classic pattern of urticarial tissue reaction occurring in the majority of (12 of 16) cases. Two biopsies showed an interstitial fibrohistiocytic (granuloma annulare-like) reaction pattern. One case showed only a sparse perivascular lymphocytic infiltrate, and paucicellular dermal mucinosis was observed in one case. CONCLUSIONS: Polymorphism of histological patterns induced by aspirin suggests that in addition to the drug-specific mechanisms triggering drug eruptions, individual factors also play a role in determining the ultimate histological phenotype of a drug response.

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. 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.

[Topical corticosteroids in dermatology--advantages and side effects]. / Kortykosteroidy w miejscowej terapii chorób skóry--korzysci i efekty uboczne.

In the article, the authors have presented the crucial stages of scientific research concerning topical steroids which contribute to reduce undesirable side effects and to improve the therapeutic index. Attention has been paid to the variety of factors which influence the absorption of steroids by the skin (kinds of drugs, their forms, types of dressing, regions of the skin, time of application). The mechanism of antiinflammatory, antipruritic and antiproliferation actions of steroids, conditioning their topical therapeutic effect, has been given. A four- and seven-graded classification, which takes into consideration the force of action of the topical steroids and is helpful in the daily medical practice, has been mentioned. There have been also listed most common systemic complications and especially the effects of chronic topical application of steroids on the skin.

[Familial Darier disease and mental retardation in mother and her two sons]. / Rodzinna choroba Dariera i uposledzenie umyslowe u matki i jej dwóch synów.

Darier disease (DD) is an uncommon genetic skin disorder, which begins in adolescence or early adult life. This disease is observed more often among men and where the disease course is more severe. Many dermatologists observe in patients with DD neuropsychiatric disorders: psychosis, depression and rare mental retardation. We present familial DD in a mother and her two sons. Men demonstrated a typical onset and course of the disease. The onset of the disease in the 52nd year of age and the skin lesions (more characteristic for the Lyell disease) which occurred suddenly in women, were atypical. Besides skin lesions, mental retardation with a various degree of intensity was observed in all three patients.

[Cutaneous changes occurring after taking non-steroidal anti-inflammatory drugs--five-years' retrospective studies]. / Zmiany skórne po niesterydowych lekach przeciwzapalnych--piecioletnie badanie retrospektywne.

In the last years we can observe an increase incidence of dermatoses after drug administration, which later require specialistic help and hospitalization. It especially concerns with nonsteroidal, anti-inflammatory drugs (considering their widespread application, possibility of purchasing them without prescription and large media advertising. The authors of this article wanted to present the significance of this problem analysing a group of patients at the Department of Dermatology in Cracow in the years 1997-2001. Attention was paid to a variety of cutaneous changes after they had been treated with nonsteroidal anti-inflammatory drugs (NSAID). The dermatoses which are not commonly considered as drug related, have also been presented. In general, medical documentation of 193 patients being suspected of having symptoms of drug related character of cutaneous changes were presented. The given drug was recognized as being the cause of disease development based on the method recommended by the French Surveillance Network. In 31 patients a connection of the cutaneous changes with NSAID administration was proved. In the analysed group of patients, women dominated (61.3%), the mean age of the examined patients was 42 years. The increase in occurrence frequency of dermatoses after taking NSAID was observed in regard to all the hospitalized patients (from 0.48% in the year 1997 to 0.99% in the year 2001). From among the drugs responsible for causing cutaneous changes which required hospitalization, aspirin took the first place, pyralgin the second, and paracetamol the third one. Urticaria prevailed in cutaneous changes after having taken NSAID. More rarely other cutaneous changes, like erythema multiforme or drug induced exanthema, took place. The fact that various drugs often cause similar cutaneous changes and even the same drug can provoke different morphological reactions makes the diagnostic process of the described dermatoses extremely difficult.