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Idiopathic Urticaria (idiopathic + urticaria)
Kinds of Idiopathic Urticaria Selected AbstractsComparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patientsALLERGY, Issue 1 2009C. Bachert Background:, Bilastine is a novel, nonsedating H1 -antihistamine developed for symptomatic treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria. The objective of this study was to compare the efficacy and safety of bilastine 20 mg vs placebo and desloratadine 5 mg in subjects with seasonal allergic rhinitis (SAR). Methods:, This randomized, double blind, placebo-controlled, parallel-group multicentre study evaluated the effect of 2 weeks' treatment with bilastine 20 mg, desloratadine 5 mg or matched placebo once daily, in 12,70 years old symptomatic SAR patients. All subjects assessed the severity of nasal (obstruction, rhinorrhoea, itching, and sneezing) and nonnasal (ocular itching, tearing, ocular redness, itching of ears and/or palate) symptoms on a predetermined scale to provide a total symptom score (TSS), composed of nasal and nonnasal symptom scores (NSS and NNSS, respectively). The primary efficacy measure was the area under the curve (AUC) for the TSS over the entire treatment period. Results:, Bilastine 20 mg significantly reduced the AUC of TSS to a greater degree from baseline compared to placebo (98.4 with bilastine vs 118.4 with placebo; P < 0.001), but not compared to desloratadine 5 mg (100.5). Bilastine 20 mg was not different from desloratadine 5 mg but significantly more effective than placebo in improving the NSS, NNSS, and rhinitis-associated discomfort scores (P < 0.05), and rhinoconjunctivitis quality of life questionnaire total (P < 0.005) and four out of seven individual domain (P < 0.05) scores. The incidence of treatment emergent adverse events was similar for bilastine (20.6%), desloratadine (19.8%), and placebo (18.8%). Conclusion:, Bilastine 20 mg once daily was efficacious, safe and not different from desloratadine 5 mg once daily in the treatment of SAR symptoms. [source] Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin testEXPERIMENTAL DERMATOLOGY, Issue 5 2003M. Caproni Abstract:, In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-,), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22,57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-, showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system. [source] Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter studyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2006Alexander Kapp MD Background, Chronic idiopathic urticaria (CIU) is defined by the almost daily presence of urticaria for at least 6 weeks without an identifiable cause. Symptoms include short-lived wheals, itching, and erythema. CIU impedes significantly a patient's quality of life (QoL). Levocetirizine is an antihistamine from the latest generation approved for CIU. Aim, To investigate the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of CIU, as well as for the QoL and productivity. Methods, The primary criteria of evaluation were the pruritus severity scores over 1 week of treatment and over 4 weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI). Results, Baseline pruritus severity scores were comparable in the two treatment groups (2.06 ± 0.58). After 1 week, levocetirizine was superior to placebo and demonstrated a considerable efficacy (difference = 0.78, P < 0.001). This efficacy was maintained over the entire study period (4 weeks, P < 0.001). The number and size of wheals were considerably reduced compared with placebo over 1 week and over the total treatment period (P , 0.001). This was paralleled by an improvement in the QoL (DLQI: 7.3 units in the levocetirizine group and 2.4 units in the placebo group) and a higher productivity at work in the levocetirizine group (3.0 workdays lost per patient per month in the placebo group, 0.3 in the levocetirizine group). No unexpected adverse events occurred. Conclusions, Levocetirizine, 5 mg once daily, is an effective treatment for CIU, characterized not only by a rapid and sustained response, but also by an important improvement in QoL. [source] Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled studyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2001Johannes Ring MD Background Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. Methods This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12,79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. Results Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. Conclusions Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period. [source] Prospective randomized non-blinded clinical trial on the use of dapsone plus antihistamine vs. antihistamine in patients with chronic idiopathic urticariaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2008B Engin Abstract Background, Treatment of chronic idiopathic urticaria (CIU) is difficult. Objective, The purpose of this study was to evaluate the efficacy and safety of dapsone in CIU. Methods, The response to dapsone was evaluated in 65 CIU patients with a randomized, two armed study: 3-month dapsone + desloratadin and 3-month desloratadin. All were followed for up to 3 months and 3 months after; all took desloratadine 10 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score, 42 per week). Results, Sixty-five patients completed the randomized 3-month trial medication. Mean reduction in UAS from baseline at 3 months was 7 [95% confidence interval (95% CI), 6.92,7.08] for active group and 5.77 (95% CI, 5.47,6.08) for control subjects (P < 0.001). The reduction in visual analogue score (VAS) at 3 months for active group (mean, 2.58; 95% CI, 2.33,2.83) and control subjects (mean, 2.55; 95% CI, 2.38,2.73) was also significant (P < 0.001). The reduction of UAS and VAS at 3 months compared between active group and control subjects showed no significant difference. Mean reduction in UAS from the end of the study at 3 months after was 1.16 and ,4.8 for active and control subjects, respectively. These results were compared with each other, and it was statistically significant (P , 0.05). Limitations, No placebo was used. The study was not blinded. Lack of blinding may have led to bias. The follow-up period was short. Conclusion, This study shows that dapsone leads to a persistent decrease in VAS and UAS and is associated with complete remission in some patients. [source] Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled studyALLERGY, Issue 4 2010T. Zuberbier To cite this article: Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, Antépara I, Jáuregui I, Valiente R, the Bilastine International Working Group. Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study. Allergy 2010; 65: 516,528. Abstract Background:, Bilastine is a novel nonsedative H1 -receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). The aim of this study was to compare the clinical efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg and placebo in CU patients with moderate-to-severe symptoms. Methods:, Overall 525 male and female subjects aged 18,70 years were randomized to receive bilastine 20 mg, levocetirizine 5 mg or placebo, once daily for 28 days, in double-blind manner, in 46 centres across Europe and Argentina. Patients rated symptoms of pruritus, number of wheals, and maximum size of wheals (on predefined scales) as reflective (over past 12 h) symptoms twice daily, for assessment of change from baseline in the total symptoms scores (TSS) over 28 days as the primary efficacy measure. Changes in reflective and instantaneous symptoms scores, Dermatology Life Quality Index (DLQI), and CU-associated discomfort and sleep disturbance were assessed as secondary outcomes. Safety was assessed according to adverse events, laboratory tests and electrocardiograms. Results:, Bilastine reduced patients' mean reflective and instantaneous TSS from baseline to a significantly greater degree than placebo (P < 0.001); from day 2 onwards of treatment. The DLQI, general discomfort, and sleep disruption were also improved significantly in bilastine-treated patients as compared with placebo-treated patients (P < 0.001 for all parameters). Comparison with levocetirizine indicated both treatments to be equally efficacious as well as equally safe and well tolerated as compared with placebo. Conclusions:, Bilastine 20 mg is a novel effective and safe treatment option for the management of CU. [source] Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patientsALLERGY, Issue 4 2009P. C. Potter Background:, Nonsedating H1 -antihistamines are recommended for the treatment of urticaria by the recent EAACI/GA2LEN/EDF guidelines. The aim of this study was to compare the efficacy, after 4 weeks of treatment, with levocetirizine 5 mg and desloratadine 5 mg, both once daily in the morning, in symptomatic chronic idiopathic urticaria (CIU) patients. Methods:, This multi-center, randomized, double-blind study involved 886 patients (438 on levocetirizine and 448 on desloratadine). The primary objective was to compare their efficacy on the mean pruritus severity score after 1 week of treatment. Mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient's and investigator's global satisfaction with treatment, were secondary efficacy measures. Results:, Levocetirizine led to a significantly greater decrease in pruritus severity than desloratadine over the first treatment week; mean pruritus severity scores of 1.02 and 1.18 for levocetirizine and desloratadine, respectively (P < 0.001). The result was similar for the entire 4-week treatment period (P = 0.004). In addition, levocetirizine decreased pruritus duration and the mean CIU composite scores to a significantly greater extent than desloratadine during the first week (P = 0.002 and 0.005, respectively) and over the entire study (P = 0.009 and P < 0.05, respectively). Similarly, levocetirizine increased the patients' global satisfaction after one and 4 weeks (P = 0.012 and 0.021, respectively), compared with desloratadine. Safety and tolerability were similar in both groups. Conclusions:, Levocetirizine 5 mg was significantly more efficacious than desloratadine 5 mg in the treatment of CIU symptoms. [source] How to prescribe antihistamines for chronic idiopathic urticaria: desloratadine daily vs PRN and quality of lifeALLERGY, Issue 4 2009J.-J. Grob Background:, Chronic idiopathic urticaria (CIU) impairs quality of life (QoL). Currently, no consensus exists regarding how second-generation H1 -antihistamines (proven to control CIU symptoms) should be taken long-term: as daily treatment or only when symptoms return (PRN). We sought to determine which regimen improves or better maintains QoL in CIU: desloratadine (DL) daily or PRN. Methods:, Subjects with CIU initially responding to DL 5 mg/day for 4 weeks were randomized for an additional 8 weeks, to DL 5 mg/day (arm 1: ,continuous', n = 46) or to DL only on days when urticarial wheals were present (arm 2: "PRN", n = 60). To ensure blinding, treatment was presented in both arms as a combination of daily treatment (arm 1: DL; arm 2: placebo), plus a "rescue" tablet (arm 1: placebo; arm 2: DL) to be taken only in case of symptoms. The main outcome measure was QoL assessed by the VQ-Dermato, a validated French QoL instrument, and the Dermatology Life Quality Index (DLQI). Results:, At 4 and 8 weeks after randomization, subjects taking continuous DL showed statistically significant improvements in VQ-Dermato Global Index score (P = 0.001 and P = 0.016, respectively) and dimension scores for daily living activity, mood state, and social functioning vs subjects taking DL PRN. Improvement in DLQI score at Week 4 was also significantly greater with continuous DL (P = 0.001). Conclusion:, Continuous daily therapy with DL 5 mg is a better regimen than PRN treatment to maintain or improve QoL in subjects with CIU. [source] Ebastine in allergic rhinitis and chronic idiopathic urticariaALLERGY, Issue 2008J. Sastre Histamine is a key mediator in the development of allergy symptoms, and oral H1 -antihistamines are among the most widely used treatments for symptomatic relief in conditions such as allergic rhinitis and chronic urticaria. Ebastine is a second-generation antihistamine which has been shown to be an effective treatment for both seasonal and perennial allergic rhinitis. In controlled clinical trials in adult and adolescent patients with allergic rhinitis, ebastine 10 mg once-daily improved symptoms to a significantly greater extent than placebo and to a similar extent as loratadine 10 mg and cetirizine 10 mg (both once-daily), while ebastine 20 mg proved to be more effective than these two comparator antihistamines. In addition, ebastine was significantly more effective than placebo at relieving the symptoms of chronic idiopathic urticaria. Ebastine provides efficacy throughout the 24-h dosing interval with once-daily administration and clinical benefit is seen from the first day of treatment. Small studies have found beneficial effects for ebastine in patients with other disorders, including cold urticaria, dermographic urticaria, atopic asthma, mosquito bites and (in combination with pseudoephedrine) the common cold. In addition to the regular ebastine tablet, a fast-dissolving tablet (FDT) formulation, which disintegrates in the mouth without the aid of a drink, is also available. It has been shown to be bioequivalent to the regular tablet, and to be significantly more effective than desloratadine at reducing histamine-induced cutaneous wheals. A number of patient surveys demonstrated that the majority of individuals who tried the fast-dissolving formulation reported it to be convenient for use, fast-acting and preferred it to their previous antihistamine medication. Perhaps most importantly, a large proportion of patients indicated that they would prefer to use this new formulation in the future. Ebastine has a rapid onset of action and it can be administered once-daily, with or without food. Dose modifications are not needed in elderly patients, or in those with renal or mild to moderate hepatic impairment. Ebastine is generally well-tolerated, and clinical studies showed that at usual therapeutic doses of 10 and 20 mg once-daily, it had no clinically relevant adverse effects on cognitive function and psychomotor performance or on cardiovascular function. In conclusion, ebastine is an effective and generally well-tolerated treatment for allergic rhinitis and chronic idiopathic urticaria. In addition to the regular tablet formulation, ebastine is available as a FDT, providing a treatment option that is particularly convenient for patients. [source] Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicentre studyALLERGY, Issue 5 2007A. Gimenez-Arnau Background:, Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. Objective:, To study rupatadine efficacy and safety for moderate to severe CIU treatment. Methods:, This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. Results:, A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with placebo (44.9%). Both doses of rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. Conclusion:, Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU. [source] Chronic urticaria and associated coeliac disease in children: A case,control studyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2005L. Caminiti Celiac disease (CD) and chronic urticaria (CU) are both sustained by immune mechanisms, but there are so far few data on their clinical association. We performed a case,control study to determine the occurrence of CD in urticaria and matched control children, and to assess the clinical relevance of this association. Children and adolescents were diagnosed to have severe chronic idiopathic urticaria in the presence of hives for more than 6 wk poorly or not responsive to oral antihistamines. Other known causes of urticaria had to be excluded. A matched control group without urticaria was enrolled. In both groups, the presence of CD was searched by assaying antitransglutaminase and antiedomysial antibodies, and confirmed with endoscopic intestinal biopsy. Results. CD was diagnosed and confirmed in 4/79 (5.0%) of children with CU and in 17/2545 (0.67%) of the controls (p = 0.0003). In the four children with urticaria and CD the gluten free diet (GFD) lead to complete remission of urticaria within 5,10 wk, whereas the disappearance of serological markers occurred in longer times (5,9 months). Conclusions. The presence of CD in children with CU was significantly more frequent than in controls. GFD resulted in urticaria remission. CD may be regarded in such subjects as a cause of CU. [source] Diagnosis and management of idiopathic urticariaPRESCRIBER, Issue 22 2006FRCPath(Imm), Mark Gompels BSc The majority of urticaria seen in general practice is not associated with allergy. Here, the author discusses the diagnosis of idiopathic urticaria and angioedema and their recommended treatment. Copyright © 2006 Wiley Interface Ltd [source] LETTER TO THE EDITOR: Clinical efficacy of reserpine as "add-on therapy" to antihistamines in patients with recalcitrant chronic idiopathic urticaria and urticarial vasculitisTHE JOURNAL OF DERMATOLOGY, Issue 9 2010Toshio DEMITSU No abstract is available for this article. [source] The utility of mixed-effects covariate analysis in rapid selection of doses in pediatric subjects: A case study with fexofenadine hydrochlorideBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2004Rajesh Krishna Abstract Fexofenadine hydrochloride is a non-sedating antihistamine that is used in the treatment of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria. A pooled analysis of pharmacokinetic data from children 6 months to 12 years of age and adults was conducted to identify the dose(s) in children that produce exposures comparable to those in adults for the treatment of seasonal allergic rhinitis. The pharmacokinetic parameter database included peak and overall exposure data from 269 treatment exposures from 136 adult subjects, and 90 treatment exposures from 77 pediatric allergic rhinitis patients. The data were pooled and analysed using NONMEM software, version 5.0. A covariate model based on body weight and age and a power function model based on body weight were identified as appropriate models to describe the variability in fexofenadine oral clearance and peak concentration, respectively. Individual oral clearance estimates were on average 44%, 36% and 61% lower in children 6 to 12 years (n = 14), 2 to 5 years (n = 21), and 6 months to 2 years (n = 42), respectively, compared with adults. Trial simulations (n = 100) were carried out based on the final pharmacostatistical models and parameter estimates to identify the appropriate dose(s) in children relative to the marketed dose of 60 mg fexofenadine hydrochloride in adults. The trials were designed as crossover studies in 18 subjects comprising various potential dosing regimens with and without weight stratification. Pharmacokinetic parameter variability was assumed to have a log-normal distribution. Individual weights and ages were simulated using mean (SD) estimates derived from the studies used in this analysis and proportional measurement/model mis-specification errors derived from the analysis were incorporated into the simulation. The results indicated that a 30 mg dose of fexofenadine hydrochloride administered to children 1 to 12 years of age and weighing >10.5 kg and a 15 mg dose administered to children 6 months and older and weighing ,10.5 kg produces exposures similar to those seen with the 60 mg dose in adults. Copyright © 2004 John Wiley & Sons, Ltd. [source] Desloratadine dose selection in children aged 6 months to 2 years: comparison of population pharmacokinetics between children and adultsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2007Samir K. Gupta What is already known about this subject ,,According to recent literature, the pathophysiologies of allergic rhinitis and chronic idiopathic urticaria are thought to be similar in adults and children. In addition, the response to antihistamine treatment is similar in adults and children, suggesting a similar concentration-response relationship. ,,However, an appropriate dose selection and the pharmacokinetics of desloratadine in children of ,6 months,,2 years old have never been addressed in the literature. What this study adds ,,This study demonstrated that desloratadine syrup offers a safe treatment option for allergic conditions in young children. ,,A suitable dose for children aged ,6 months,<1 year is 1.0 mg, while the corresponding predicted dose for children aged ,1 year,,2 years is 1.25 mg. These paediatric doses yielded similar systemic desloratadine exposures (AUC) to those seen with a typical adult dose of 5.0 mg. Aims The aim of this study was to identify the dose of desloratadine in children aged ,6 months,,2 years that would yield a single-dose target exposure (AUC) comparable with that in adults taking 5 mg desloratadine as syrup. Methods In a phase 1, single-dose, open-label, pharmacokinetic study in 58 children aged ,6 months,<1 year and ,1 year,,2 years were randomly assigned to desloratadine syrup 0.625 mg (1.25 ml) and 1.25 mg (2.5 ml), respectively. Because the volume of blood that could be collected from individual subjects was limited, a population pharmacokinetic approach was used to estimate the pharmacokinetics of desloratadine. Safety was assessed based on results of screening and postdose physical examinations, laboratory safety tests, vital signs, and adverse events. Results The apparent clearance (CL/F) of desloratadine, population estimate (%CV), in children aged ,6 months,<1 year was 27.8 l h,1 (35) and corresponding values in children ,1 year,,2 years was 35.5 l h,1 (51), compared with 137 l h,1 (58) for adults. The CL/F ratios (children to adults) indicated that doses of 1 mg for ,6 months,<1 year and 1.25 mg for ,1 year,,2 years would result in similar systemic exposure to that observed in adults receiving the recommended 5 mg dose. Desloratadine was well tolerated with no safety issues. Conclusions Doses of 1.0 and 1.25 mg in children aged ,6 months,,2 years should result in an exposure to desloratadine similar to that of adults receiving doses of 5 mg. [source] High plasma proteasome levels are detected in patients with metastatic malignant melanomaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005P-E. Stoebner Summary Background, Proteasomes, nonlysosomal proteolytic structures, are implicated in cell growth and differentiation. An abnormal expression has been described in haematopoietic malignancies and in some solid tumours. Objectives, To study the plasma proteasome levels in patients with malignant melanoma (MM) using an enzyme-linked immunosorbent assay (ELISA) technique, and to compare them with the values obtained in a normal population and in patients with severe psoriasis or chronic idiopathic urticaria (CIU). Methods, Plasma proteasome level was measured using a sandwich ELISA test in normal donors (n = 14), and in patients with stage I/II (n = 13), stage III (n = 6) and stage IV (n = 10) MM, severe psoriasis (n = 13) and CIU (n = 6). Tissue proteasome expression was also detected by immunohistology using a monoclonal antibody in paraffin-embedded samples of normal tissue, psoriasis skin and MM. Results, In normal donors, mean ± SEM plasma proteasome concentration was 2138 ± 221 ng mL,1. Patients with stages III and IV MM exhibited a significantly higher value (3373 ± 470 ng mL,1 and 8931 ± 1232 ng mL,1, respectively). Values in patients with stage I/II MM and CIU were not significantly different from those in normal volunteers. Patients with severe psoriasis also exhibited increased values (3398 ± 374 ng mL,1) but to a lesser extent than in patients with stage IV MM. There was a significant correlation of proteasome levels with serum lactate dehydrogenase in the MM group. Tissue expression as demonstrated by immunohistochemistry paralleled these findings. The strongest expression was seen on MM slides and to a lesser extent in psoriasis samples, the weakest expression being observed in normal skin. Conclusions, Proteasomes are strongly expressed in cutaneous MM; high levels of circulating proteasomes are detected in patients with metastatic MM with a high melanoma burden, and at a lesser extent in psoriatic patients, which suggests proteasomes represent a marker more of nonspecific inflammation than of early cancer. [source] Inhibition of the histamine-induced weal and flare response: a valid surrogate measure for antihistamine clinical efficacy?CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2007P. Devillier Summary Histamine plays a central role in allergic responses. Inhibition of the weal and flare response to histamine is a traditional pharmacodynamic tool to measure the activity of H1 -receptor antagonists. The time course and duration of cutaneous weal and flare inhibition are often used as surrogate measures of clinical efficacy. Pharmacodynamic differences among antihistamines are often interpreted to indicate differences in clinical efficacy. A systematic review of literature from 1980 to 2006 regarding the histamine induced weal and flare was undertaken. Search terms included ,histamine', ,skin test', ,weal', ,flare', and ,antihistamine'; retrieved articles were searched for relevant studies not identified initially. Data from human studies on the inhibition of the weal and flare by second-generation antihistamines were extracted and assessed. A literature search from 1980 to 2006 was undertaken for comparative studies of second-generation antihistamines in the clinical settings of allergic rhinitis (AR) and chronic idiopathic urticaria; data extracted from these studies underwent systematic review. Differences were noted among second-generation antihistamines in terms of their ability to inhibit the histamine-induced weal and flare. Corresponding differences in terms of clinical efficacy in AR and chronic urticaria were not identified following a systematic review. The reasons for the disconnect between pharmacodynamic effects and clinical efficacy may include differences between the route and concentration of histamine, the involvement of mediators other than histamine in the allergic response, and the short time course of pharmacodynamic studies. The histamine-induced weal and flare response is a pharmacodynamic test that should not be used to compare the clinical efficacy of different antihistamines, and is not an adequate alternative to clinical end-point assessments in AR or chronic idiopathic urticaria. [source] Evidence of in vivo basophil activation in chronic idiopathic urticariaCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2006K. Vasagar Summary Background Approximately 40% of chronic idiopathic urticaria (CIU) subjects have autoantibodies to either Fc,RI, or IgE. The effect of such autoantibodies on circulating basophil activation status is unknown. Objective The expression of cell surface activation markers on basophils from CIU, non-allergic, and allergic subjects were compared. Further, the relationship between marker expression and serum factors reported in CIU, such as histamine-releasing activity (HRA) and immunoreactivity to Fc,RI, were examined. Methods Peripheral blood was obtained from CIU, allergic, and non-allergic donors and fractionated by density gradients. Enriched basophils (1,12%) were analysed by flow cytometry for expression of activation markers including CD63, CD69, and CD203c. Dilutions of serum (5,50%) were analysed for HRA on basophils from a normal donor. Serum was tested for immunoreactivity by western blotting to a standard cell lysate prepared from an RBL-SX38 cell line transfected with human Fc,RI,. Results CIU subjects (n=9) and allergic subjects (n=8) exhibited enhanced expression of CD63 and CD69, as compared with non-allergic subjects (n=7); however, no difference was seen among groups for CD203c expression. Five CIU and two non-allergic subjects had evidence of significant serum HRA (>20%), whereas two CIU, two allergic, and three non-allergic subjects had evidence of serum immunoreactivity to Fc,RI,. Serum HRA and serum immunoreactivity to Fc,RI, were not associated with enhanced surface marker expression. Conclusion Basophil activation marker expression is increased in CIU subjects and is not associated with serum factors. In addition, serum HRA and Fc,RI, immunoreactivity are not unique to CIU, or related to enhanced circulating basophil marker expression. [source] Is there a role for antileukotrienes in urticaria?CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2006G. Di Lorenzo Summary In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, i.e. leukotriene receptor antagonists and synthesis inhibitors, are a new class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma. We searched the MedLine database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin or food additive hypersensitivity or with autoreactivity to intradermal serum injection when taken with an antihistamine but not in moderate chronic idiopathic urticaria. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angio-oedema, and exercise-induced anaphylaxis. [source] | |||||||||||||||||||||||||