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Although urticaria is not a life-threatening disease, its impact on quality of life in children should not be overlooked. A systematic search of online databases, including Medline, was performed to inform a review aiming to equip clinicians with an evidence-based approach to all aspects of pediatric urticaria. This review hinges on an illustrative case and includes a summary table of studies pertaining to disease management in children. The multiple issues faced by patients, their families, and treating clinicians are highlighted, and the current literature on the presentation, natural history, investigation, and management of this poorly understood condition is assessed.

OBJECTIVE: To review clinical trial data to determine the benefits of using montelukast alone or as combination therapy in the treatment of urticaria. DATA SOURCES: MEDLINE (1966-March 2006) and International Pharmaceutical Abstracts (1970-October 2005) were searched to find clinical trial publications that addressed the use of montelukast in urticaria. DATA SYNTHESIS: Six clinical trials were identified. Montelukast was compared alone and as combination therapy with nonsedating histamine1-receptor antagonists to determine efficacy and safety. Patients had chronic or physical urticaria. The results were mixed. Some studies demonstrated that montelukast can decrease urticarial symptoms with minimal adverse effects, while others found no differences. CONCLUSION: Large-scale, controlled trials are needed to determine which patients would likely benefit from treatment with montelukast.

BACKGROUND: Urticaria is a common skin disease characterised by itching weals or hives, which can occur almost anywhere on the body. There are a number of different subtypes and a range of available treatment options. There is lack of agreement on the efficacy of H2-receptor antagonists used in the treatment of urticaria. OBJECTIVES: To assess the safety and effectiveness of H2-receptor antagonists in the treatment of urticaria. SEARCH METHODS: We searched the following databases up to 7 October 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 4), MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched online trials registries for ongoing trials. SELECTION CRITERIA: Randomised controlled trials of H2-receptor antagonists in people with a clinical diagnosis of urticaria of any duration or of any subtype. Studies including H1-antihistamines for chronic urticaria are the topic of a separate Cochrane review; thus, they were not included in this review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted and analysed data. MAIN RESULTS: Four studies of a relatively small size, involving 144 participants, were included in this review. A combination of ranitidine with diphenhydramine was more effective at improving the resolution of urticaria than diphenhydramine administered alone (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.07 to 2.36). Although there was a similar improvement in itching, weal size, and intensity, cimetidine provided no statistically significant greater overall improvement in symptoms of urticaria when compared to diphenhydramine. However, a combination of these medications was more effective than diphenhydramine alone (RR 2.02, 95% CI 1.03 to 3.94). Adverse events were reported with several of the interventions, i.e. ranitidine and diphenhydramine, causing drowsiness and sedation, but there was no significant difference in the level of sedation from baseline with either famotidine or diphenhydramine. AUTHORS' CONCLUSIONS: The very limited evidence provided by this review was based on a few old studies of a relatively small size, which we categorised as having high to unclear risk of bias. Thus, at present, the review does not allow confident decision-making about the use of H2-receptor antagonists for urticaria. Although some of these studies have reported a measure of relief of symptoms of urticaria and rather minimal clinical improvement in some of the participants, the evidence was weak and unreliable. We have emphasised the lack of precision and limitations in the reported data where appropriate in this review.

Resumen: la urticaria crónica espontánea es una enfermedad que produce gran compromiso en la calidad de vida del paciente y de la que aún se desconocen, en gran parte, los mecanismos fisiopatológicos asociados, ya que no son generalizables en todos los individuos. Existen factores intrínsecos y extrínsecos implicados en el desarrollo y persistencia de la enfermedad, los cuales pueden actuar de forma individual o coexistente. En esta revisión se proponen algunos cambios en la clasificación actual de la enfermedad, donde se incluye una subdivisión dentro de la urticaria crónica denominada urticaria crónica mixta, la cual hace referencia a los casos donde coexisten factores intrínsecos y extrínsecos para la aparición de la enfermedad en el mismo individuo. Algunos procesos infecciosos virales, bacterianos y parasitarios se han asociado en el desarrollo o severidad de los síntomas de la urticaria crónica en un subgrupo de pacientes, por lo tanto, son incluidos como factores extrínsecos del individuo dentro de las urticarias crónicas inducibles no físicas. Estas modificaciones son propuestas con el fin de optimizar el diagnóstico y manejo de los pacientes con urticaria crónica mixta. (AU)

BACKGROUND: Chronic spontaneous urticaria (CSU) is characterised by the development of crops of red, itchy, raised weals or hives with no identifiable external cause. OBJECTIVES: To assess the effects of H1-antihistamines for CSU. SEARCH METHODS: We searched the following databases up to June 2014: Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 5), MEDLINE (from 1946), EMBASE (from 1974) and PsycINFO (from 1806). We searched five trials registers and checked articles for references to relevant randomised controlled trials. SELECTION CRITERIA: We included randomised controlled trials of H1-antihistamines for CSU. Interventions included single therapy or a combination of H1-antihistamines compared with no treatment (placebo) or another active pharmacological compound at any dose. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. Our primary outcome measures were proportion of participants with complete suppression of urticaria: 'good or excellent' response, 50% or greater improvement in quality of life measures, and adverse events. We present risk ratios (RR) with 95% confidence intervals (CIs). MAIN RESULTS: We identified 73 studies (9759 participants); 34 studies provided data for 23 comparisons. The duration of the intervention was up to two weeks (short-term) or longer than two weeks and up to three months (intermediate-term). Cetirizine 10 mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). For this same outcome, comparison of desloratadine versus placebo in the intermediate term (5 mg) (RR 37.00, 95% CI 2.31 to 593.70) and in the short term (20 mg) (RR 15.97, 95% CI 1.04 to 245.04) favoured desloratadine, but no differences were seen between 5 mg and 10 mg for short-term treatment. Levocetirizine 20 mg per day (short-term) was more effective for complete suppression of urticaria compared with placebo (RR 20.87, 95% CI 1.37 to 317.60), and at 5 mg was effective in the intermediate term (RR 52.88, 95% CI 3.31 to 843.81) but not in the short term, nor was 10 mg effective in the short term. Rupatadine at 10 mg and 20 mg in the intermediate term achieved a 'good or excellent response' compared with placebo (RR 1.35, 95% CI 1.03 to 1.77). Loratadine (10 mg) versus placebo (RR 1.86, 95% CI 0.91 to 3.79) and loratadine (10 mg) versus cetirizine (10 mg) (RR 1.05, 95% CI 0.76 to 1.43) over short-term and intermediate-term treatment showed no significant difference for 'good or excellent response' or for complete suppression of urticaria, respectively. Loratadine (10 mg) versus desloratadine (5 mg) (intermediate-term) showed no statistically significant difference for complete suppression of urticaria (RR 0.91, 95% CI 0.78 to 1.06) or for 'good or excellent response' (RR 1.04, 95% CI 0.64 to 1.71). For loratadine (10 mg) versus mizolastine (10 mg) (intermediate-term), no statistically significant difference was seen for complete suppression of urticaria (RR 0.86, 95% CI 0.64 to 1.16) or for 'good or excellent response' (RR 0.88, 95% CI 0.55 to 1.42). Loratadine (10 mg) versus emedastine (2 mg) (intermediate-term) showed no statistically significant difference for complete suppression (RR 1.04, 95% CI 0.78 to 1.39) or for 'good or excellent response' (RR 1.09, 95% CI 0.96 to 1.24); the quality of the evidence was moderate for this comparison. No difference in short-term treatment was noted between loratadine (10 mg) and hydroxyzine (25 mg) in terms of complete suppression (RR 1.00, 95% CI 0.32 to 3.10). When desloratadine (5 to 20 mg) was compared with levocetirizine (5 to 20 mg), levocetirizine appeared to be the more effective (P value < 0.02). In a comparison of fexofenadine versus cetirizine, more participants in the cetirizine group showed complete suppression of urticaria (P value < 0.001). Adverse events leading to withdrawals were not significantly different in the following comparisons: cetirizine versus placebo at 10 mg and 20 mg (RR 3.00, 95% CI 0.68 to 13.22); desloratadine 5 mg versus placebo (RR 1.46, 95% CI 0.42 to 5.10); loratadine 10 mg versus mizolastine 10 mg (RR 0.38, 95% CI 0.04 to 3.60); loratadine 10 mg versus emedastine 2 mg (RR 1.09, 95% CI 0.07 to 17.14); cetirizine 10 mg versus hydroxyzine 25 mg (RR 0.78, 95% CI 0.25 to 2.45); and hydroxyzine 25 mg versus placebo (RR 3.64, 95% CI 0.77 to 17.23), all intermediate term. No difference was seen between loratadine 10 mg versus mizolastine 10 mg in the proportion of participants with at least 50% improvement in quality of life (RR 3.21, 95% CI 0.32 to 32.33). AUTHORS' CONCLUSIONS: Although the results of our review indicate that at standard doses of treatment, several antihistamines are effective when compared with placebo, all results were gathered from a few studies or, in some cases, from single-study estimates. The quality of the evidence was affected by the small number of studies in each comparison and the small sample size for many of the outcomes, prompting us to downgrade the quality of evidence for imprecision (unless stated for each comparison, the quality of the evidence was low). No single H1-antihistamine stands out as most effective. Cetirizine at 10 mg once daily in the short term and in the intermediate term was found to be effective in completely suppressing urticaria. Evidence is limited for desloratadine given at 5 mg once daily in the intermediate term and at 20 mg in the short term. Levocetirizine at 5 mg in the intermediate but not short term was effective for complete suppression. Levocetirizine 20 mg was effective in the short term, but 10 mg was not. No difference in rates of withdrawal due to adverse events was noted between active and placebo groups. Evidence for improvement in quality of life was insufficient.

INTRODUCTION: Chronic idiopathic urticaria is a frequent disease witch treatment is often disappointing. Psychological factors seem to be frequently associated to it. In what cases consider psychological treatment? And according to what modalities? METHOD: Review of the literature in search of articles in both French and English concerning psychological factors associated to chronic urticaria, either as responsible factors, or as aggravating factors, or as a consequence of the urticaria, with the study of the impact on the quality of life. We also studied articles analyzing various types of psychology-targeted treatments. We use a serie of keywords on following data banks: Medline (1970-2002), Embase, Pascal and Cochrane Library (period 1995-2002). RESULTS: Very few controlled studies were published.: Various studies are found reporting an association between stress, anxiety or depressive symptomatology and CIU, but none can assert a causality. Three controlled opened studies show significantly more anxiety and\or depression in the chronic urticaria patients. Three studies analyze the psychopathological personalities of the patients with urticaria. Two studies focus specifically on the impact of the CIU on the quality of life. Various psychotropic drugs (mainly tricyclic antidepressants) have been tested, mostly because of their anti-H1 activity. There is no study on psychological support, psychotherapies, behavioral therapies, technique of biofeedback and group therapies. A particular attention is focused to hypnosis and relaxation techniques because of the improvement of the urticarial wheals reported in studies of cutaneous ability to react in subcutaneous injections of histamine. CONCLUSION: A complementary psychological treatment of patients suffering from CIU seems necessary, because of the high frequency of psychological symptoms. Published studies concern essentially the prescription of psychotropic drugs and the use of therapies with suggestion or relaxation under hypnosis. Prospective studies on the impact of an adapted psychological treatment on the CIU evolution are not available.

Omalizumab (Xolair) is intended to be used as second line therapy for the treatment of chronic spontaneous urticaria (CSU) that is refractory to H1 antihistamines. If licensed, it would provide an alternative treatment option beyond antihistamines, the only licensed treatment for CSU. Omalizumab is a recombinant, human monoclonal antibody that selectively binds to human immunoglobulin E (IgE) preventing binding to high affinity receptors on the surface of mast cells and basophils, thus reducing receptor expression and the release of inflammatory mediators. It is currently licensed as add-on therapy to improve asthma control in patients with severe, persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen. In the UK, approximately 15% of people experience urticaria at some time in their lives, with a chronic urticaria point prevalence of 1-5 per 1,000. CSU symptoms may be short-lived, resolving completely after a few months; however symptoms can persist for more than 10 years. Patients with chronic urticaria often have a severely impaired quality of life, with negative effects on sleep, daily activities, school or work life, and social interactions. Treatment options for CSU refractory to antihistamines include leukotriene receptor antagonists (i.e. montelukast, zafirlukast), dapsone and immunomodulatory medication (i.e. cyclosporin A, sulfasalazine, hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil intravenous immunoglobulin, corticosteroids). Omalizumab is currently in phase III clinical trials comparing its effect on weekly itch scores against treatment with placebo. The trials are expected to complete in June 2013.

BACKGROUND: Chronic urticaria (CU) imposes profound impairment on quality of life. Up to 60% of idiopathic CU is associated with autoimmune phenomena, and may respond to immunomodulation. Hydroxychloroquine offers potential efficacy for CU and is relatively benign compared with most other therapeutic approaches. OBJECTIVE: The aim of the chronic autoimmune urticaria study and evaluation was to evaluate the efficacy of hydroxychloroquine in patients with chronic idiopathic urticaria. METHODS: Twenty-one patients referred to the Immunology and Allergy Unit at John Hunter Hospital, New South Wales, Australia, with idiopathic CU were randomised to receive treatment with standard urticaria therapies (corticosteroids, H2-antihistamines, H1--antihistamines, doxepin) with or without hydroxychloroquine. Markers of autoimmunity, thyroid disease and mast-cell autoreactivity (autologous serum skin-prick testing (ASPT)) were assessed. Measures of urticaria control were compared at baseline and at 12 weeks for the 18 individuals who completed the study. These included urticaria scores, medication scores and quality-of-life indices. RESULTS: The hydroxychloroquine-treated group achieved significant improvements in quality of life as assessed by the global symptom severity score and the LAMY-7 (a quality of life index designed by Lamy, 7th revision) at 12 weeks (P < 0.01 and P < 0.05, respectively). No significant treatment effect on medication requirements or urticaria score was detected, although differences between treatment groups approached statistical significance for urticaria score and medication requirements (0.05 < P < 0.10). ASPT-reactivity did not correlate to hydroxychloroquine-responsiveness. Hydroxychloroquine was well tolerated. CONCLUSION: Immunomodulation with hydroxychloroquine is safe and appears to offer some efficacy as an intervention in CU.

BACKGROUND: The association between urticaria and virus infections has rarely been reported in the literature. The lack of reported cases is probably due to the difficulty in establishing a cause-and-effect relationship. It is not possible to challenge the patient with an etiologic agent. OBJECTIVE: The purpose of this work was to perform a systematic review on the association between urticaria and virus infections. METHODS: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for articles from January 1, 2008, through May 2015, by using two key terms related to urticaria and virus diseases, "urticaria" and one key term related to virus infections, "virus disease," then "urticaria" and the name of each virus family, and of the most representative virus serotypes. RESULTS: We reported cases of patients affected either by acute or chronic urticaria with a concurrent virus infection. Previous other causes of urticaria had to be excluded. Herpesviridae infections and urticaria were the most frequently reported associations in children. However, hepatitis virus infections would appear to be the most-frequent cause of urticaria in adults. CONCLUSIONS: Data obtained indicated viral infection as a potential trigger and sometimes as the main etiologic agent in causing acute or chronic urticaria. In every case, urticarial manifestation cleared up after either healing or controlling of the viral infection. However, prospective studies and well-structured research is needed to better clarify the role of viruses in the pathogenesis of urticaria and their relative prevalence.