leukotriene-e4 and Urticaria

Pseudoallergens and leukotrienes (LTs) may have a role in chronic urticaria (CU). The aim of our study is to evaluate the response to the low pseudoallergen diet therapy in patients with CU and the change in LT levels in diet responsive and non-responsive patients. 34 patients with CU were put on diet for 4 weeks. All patients kept a daily score sheet of pruritus and whealing symptoms. The urticarial activity score (UAS) of each patient was calculated with the sum of pruritus and wheal score. The sum score of the first 7 consecutive days (UAS7-first week) and last 7 days (UAS7-fourth week) were used to compare the clinical outcome of the diet. A reduction of ≥50% in UAS7-fourth week compared to UAS7-first week was considered as "response". Urinary LTE4 (uLTE4) level of each patient was measured at baseline and after the 4 week of diet therapy. 14 of the patients (41.2%) were responsive to diet therapy. Baseline uLTE4 levels were similar between responsive and non-responsive patients (P = 0.540). Second uLTE4 levels (after the 4 week of diet therapy) were significantly lower in responsives than in non-responsive patients (P < 0.001). Second uLTE4 levels of responsives were significantly lower than the baseline values (P = 0.019), whereas this was not significant for non-responsives (P = 0.070). There was a significant correlation between the change in uLTE4 levels and the change in mean urticarial activity scores (r = 0.554, P = 0.001) in the whole study population. In conclusion, low pseudoallergen diet helps to reduce the urticarial activity in CU. The change in urticarial activity correlates with the change in LT levels.

Topics: Adult; Aged; Allergens; Chronic Disease; Diet; Female; Food Hypersensitivity; Humans; Leukotriene E4; Male; Middle Aged; Pruritus; Treatment Outcome; Urticaria; Young Adult

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 not cyclooxygenase-2.. To assess whether patients with CIU and aspirin sensitivity share common eicosanoid alterations with patients who have aspirin-sensitive asthma.. Seventy-four patients with CIU and a history of sensitivity to aspirin and NSAIDs underwent placebo-controlled oral aspirin challenge tests. Concentrations of urinary leukotriene E4 (uLTE4) were measured by ELISA and plasma stable prostaglandin D2 metabolite, 9alpha,11beta prostaglandin F(2) 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.. In 30 of 74 patients, the aspirin challenge was positive, resulting in urticaria/angioedema. In these 30 patients, baseline uLTE4 levels were higher than 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 9alpha,11beta prostaglandin F(2) levels rose significantly in both aspirin responders and nonresponders, although in the latter group the increase occurred later than in the former. In patients who reacted to aspirin, frequency of (-444)C allele of LTC4S was significantly higher than in patients who did not react.. CIU with aspirin sensitivity is characterized by the eicosanoid alterations, which are similar to those present in aspirin-induced asthma.

Topics: Adult; Alleles; Aspirin; Asthma; Dinoprost; Drug Hypersensitivity; Eicosanoids; Female; Genotype; Glutathione Transferase; Humans; Leukotriene E4; Male; Middle Aged; Polymorphism, Single Nucleotide; Single-Blind Method; Urticaria

Nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate various forms of urticaria by a nonallergic mechanism involving inhibition of cyclooxygenases.. 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.. Aspirin challenge test followed by randomized, prospective, double-blind, placebo-controlled crossover trial with cyclooxygenase 2 inhibitors.. Tertiary referral center of a university hospital.. Thirty-six patients with CIU.. 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.. Standardized skin examination, skin biopsy with mast cell count, urinary levels of leukotriene E4 (LTE4), and serum levels of mast cell tryptase.. 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.. 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.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biopsy; Celecoxib; Computer Graphics; Cross-Over Studies; Cyclooxygenase Inhibitors; Cysteine; Double-Blind Method; Drug Eruptions; Female; Humans; Lactones; Leukotriene E4; Leukotrienes; Male; Middle Aged; Multivariate Analysis; Naproxen; Prospective Studies; Pyrazoles; Serine Endopeptidases; Skin; Sulfonamides; Sulfones; Treatment Outcome; Tryptases; Urticaria

Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients.

Topics: Analysis of Variance; Chronic Disease; Histamine; Humans; Leukotriene E4; Skin; SRS-A; Urticaria

Topics: Abdominal Pain; Adult; Anaphylaxis; Angioedema; Anti-Asthmatic Agents; Biomarkers; Cromolyn Sodium; Diarrhea; Dinoprost; Female; Histamine Antagonists; Humans; Leukotriene E4; Male; Mast Cells; Mastocytosis; Middle Aged; Omalizumab; Prostaglandin D2; Treatment Outcome; Tryptases; Urticaria

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.. We performed a long-term observation on clinical course, aspirin sensitivity, and urinary eicosanoids in patients with aspirin-induced urticaria.. 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.. 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.. 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).

Topics: Adult; Aspirin; Cyclooxygenase Inhibitors; Dinoprost; Drug Eruptions; Female; Follow-Up Studies; Humans; Leukotriene E4; Male; Middle Aged; Urticaria

After in vitro allergen-specific stimulation, basophils become activated and release sulfidoleukotrienes LTC4, LTD4 and LTE4. This can be detected by means of the CAST assay. We assessed the positivity criteria and the reliability of antigen-specific sulfidoleukotriene production (CAST) in the in vitro diagnosis of betalactam (BL) allergic patients.. We studied a sample of 67 patients (age 48.94 +/- 15.76 years) who had presented with anaphylaxis or urticaria-angioedema within the first 60 minutes after administration of Amoxicillin (54/67), Penicillin G (7/67), Cefuroxime (5/67) or Cefazoline (1/67). All of them had a positive skin test to at least one of the antigenic determinants of Penicillin. As control group 30 adults with negative skin tests who tolerated BL were included. All of them underwent skin tests, oral provocation tests, specific IgE (CAP-FEIA, Pharmacia) and CAST.. Positivity criteria were established by means of ROC curves: a sLT release induced by Betalactams of at least 100 pg/ml and greater than or equal to 3 times the basal value. The overall sensitivity of CAST is 47.7% and specificity 83.3%. Sensitivity of specific IgE is 37.8% and specificity 83.3%.. We have established validated positivity criteria for the CAST technique in patients allergic to Betalactams. This technique is a useful in vitro diagnostic method in patients with IgE-mediated allergy to Betalactam antibiotics.

Topics: Amoxicillin; Anaphylaxis; Angioedema; Anti-Bacterial Agents; Cefazolin; Cefuroxime; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Lactams; Leukotriene C4; Leukotriene D4; Leukotriene E4; Leukotrienes; Male; Middle Aged; Penicillin G; Skin Tests; Urticaria

The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU).. Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine.. For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients.. Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

Topics: Administration, Oral; Adult; Aspirin; Biomarkers; Bronchoconstrictor Agents; Chronic Disease; Controlled Clinical Trials as Topic; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Hypersensitivity; Female; Food Additives; Humans; Italy; Leukotriene E4; Male; Methylhistamines; Middle Aged; Sodium Benzoate; Sodium Glutamate; Sulfites; Tartrazine; Time Factors; Urticaria

Cold urticaria is a rare condition characterized by abnormal wealing following exposure to cold. It has been suggested that lipid-derived mediators may be involved in the pathogenesis of this condition. We have investigated whether the inflammatory reaction in cold urticaria is associated with the release of cysteinyl-leukotrienes. Leukotriene E4 (LTE4; a stable metabolic product of LTC4 and LTD4) and histamine were measured in the blood draining the site of a cold-challenge in five patients with clinical histories of cold urticaria. Three of the patients showed a typical clinical response to the challenge, and this was associated with an increase in the concentration of LTE4 and histamine. No increase in LTE4 or histamine levels were observed following cold challenge in the non-responding individuals.

Topics: Adolescent; Adult; Chromatography, High Pressure Liquid; Cold Temperature; Female; Histamine; Humans; Leukotriene E4; Male; SRS-A; Time Factors; Urticaria

Intradermal injections of 1-50 pmol leukotriene B4, C4, D4 and E4, (LTB4, LTC4, LTD4 and LTE4) were performed in healthy subjects and patients with recurrent urticaria. A wheal and erythema were seen 15 minutes after injection and were most marked after LTC4 and LTD4. LTE4 also produced a wheal whereas the reaction to LTB4 did not significantly differ from the saline control. When mixed with histamine no potentiation of the wheals was noted and no significant difference in reaction was observed between the healthy controls and those with urticaria.

Topics: Drug Hypersensitivity; Erythema; Histamine; Humans; Intradermal Tests; Leukotriene B4; Leukotriene E4; Male; Skin; SRS-A; Urticaria