Clinical difference between single subtype and mixed subtype chronic urticaria: A retrospective study

Background: The subtypes of chronic urticaria share a common clinical expression, but may show differences phenotypically. Meanwhile, two or more different subtypes of chronic urticaria can coexist in any given patient which may involve different phenotypes. Aims: The study aims to compare the two phenotypes in terms of demographics, clinical profile and treatment response. Methods: In this retrospective study, 2678 chronic urticaria patients were divided into the single subtype chronic urticaria group and mixed subtype chronic urticaria group as was appropriate.The differences in the clinical features, possible causes, urticaria activity score of seven days, dermatology life quality index score, laboratory investigations and response to treatments were evaluated among the two groups. Results: An obvious female predominance was detected in chronic urticaria, especially in mixed subtype chronic urticaria patients. Of the 2678 chronic urticaria patients, there were 837(31.25%) mixed subtype chronic urticaria. Chronic spontaneous urticaria combined with symptomatic dermographism was the most common group in the mixed subtype chronic urticaria. Patients with mixed subtype chronic urticaria were more likely to have associated chest tightness/shortness of breath and showed greater urticaria activity. In patients with single subtype chronic urticaria, the positive rate of family history with allergic rhinitis, asthma or urticaria was lower. Based on evaluation of the treatment, control with second-generation antihistamines at licensed doses was achieved in only 38.83% of mixed subtype chronic urticaria patients, compared with 56.32% of patients with single subtype. Limitations: First, this study was a single-center design retrospective study. Second, omalizumab treatment was not included. Third, the differences between different subtypes of mixed subtype chronic urticaria were not discussed in detail. Conclusion: This study showed that mixed subtype chronic urticaria had some distinct features. Comprehensive knowledge about it may help us define effective therapeutic strategies and improve symptom control and the quality of life for chronic urticaria patients

Urticária aquagênica: relato de caso e revisão de literatura / Aquagenic urticaria: a case report and literature review

A urticária aquagênica é uma forma rara de urticária crônica induzida (UCInd) desencadeada por um estímulo específico. A patogênese não é totalmente compreendida, mas os sintomas se iniciam minutos após a exposição cutânea à água, independentemente de sua temperatura, e as urticas têm o padrão foliculocêntricas. O diagnóstico é confirmado através do teste de provocação, e o tratamento de primeira linha são os anti-histamínicos de segunda geração. Neste artigo, relatamos um caso de urticária aquagênica e fazemos uma breve revisão da literatura sobre o tema.

Aquagenic urticaria is a rare form of chronic inducible urticaria (CIndU) triggered by a specific stimulus. Pathogenesis is not fully understood, but symptoms appear minutes after cutaneous exposure to water, regardless of temperature, and wheals have a folliculocentric pattern. The diagnosis of CIndU is confirmed by provocation testing using established protocols, and first-line treatment is second-generation antihistamines. In this article, we report a case of aquagenic urticaria and provide a brief review of the relevant literature.

Effect of clemastine fumarate on TLR4/PI3K/Akt signaling pathway during hypoxia-reoxygenation in rat cardiomyocytes / 中华麻醉学杂志

Objective To evaluate the effect of clemastine fumarate on Toll-like receptor 4/phosphatidylinositol-3-kinase/serine-threonine kinase (TLR4/PI3K/Akt) signaling pathway during hypoxia-reoxygenation (H/R) in rat cardiomyocytes.Methods H9C2 cells of rats cultured in vitro were seeded in culture wells or dishes at a density of 1×105 cells/ml and divided into 3 groups (n=11 each) by using a random number table method:control group (group C),H/R group and clemastine fumarate group (CF group).Cardiomyocytes were exposed to 5％ CO2-95％ N2in a low-glucose DMEM medium at 37℃ for 4 h followed by 4 h reoxygenation.At 4 h of reoxygenation,the cell viability was detected by CCK-8 assay,the ultrastructure was observed with a transmission electron microscope,the expression of TLR4,PI3K,phosphorylated Akt (p-Akt) and caspase-3 was detected by Western blot,and the expression of TLR4,PI3K and caspase-3 was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the expression of TLR4 and caspase-3 was up-regulated,and the expression of PI3K and p-Akt was down-regulated in group H/R (P＜0.05).Compared with group H/R,the cell viability was significantly increased,the expression of TLR4 and caspase-3 was down-regulated,the expression of PI3K and p-Akt was up-regulated (P＜0.05),and the mitochondrial damage was significantly attenuated in group CF.Conclusion The mechanism by which clemastine fumarate alleviates H/R injury to rat cardiomyocytes may be related to inhibiting TLR4 expression and activating PI3K/Akt signaling pathway.

Synergistic Effect of H1-Antihistamines on Topical Corticosteroids for Pruritus in Atopic Dermatitis: A Systematic Review and Meta-Analysis

BACKGROUND: Although oral antihistamines (H1-histamine receptor antagonists) are the main treatment option for pruritus in general skin dermatosis, their effect in treating pruritus of atopic dermatitis (AD) has not yet been established. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the effectiveness of combined therapy of H1-antihistamines and topical steroids. METHODS: We systematically searched MEDLINE, Embase, and CENTRAL databases for articles published from 1967 to 2015. We identified 1,206 studies and assessed their titles, abstract, and full-text. Random effects meta-analysis was used to calculate mean differences (MD) with 95% confidence intervals (CI). RESULTS: Two studies satisfying the inclusion criteria of antihistamine therapy with mandatory topical steroid use were selected. Comparing antihistamine monotherapy with combination therapy, patients treated with the addition of antihistamine to topical corticosteroids showed a statistically significant clinical improvement (standard MD, −0.24; 95% CI, −0.42 to −0.05; p=0.01). CONCLUSION: H1-antihistamines may have a synergistic effect when combined with topical steroids by influencing various associative factors of chronic pruritus in AD.

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p <0.03).. Study limitations: A single-center study evaluating only aspects related to histamine. Conclusions: Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.

Application of antihistamines in special populations / 中华皮肤科杂志

Antihistamines,a group of drugs most commonly used for the treatment of allergic diseases in dermatology,exert favorable efficacy and are well tolerated in most people.Due to their wide application,the safety of medication is particularly important.When they are used in some special populations with allergic diseases,such as children,pregnant and lactating women,the elderly and people with hepatic or renal insufficiency,their pharmacodynamics,metabolic characteristics and interactions with other drugs should be fully considered,and profits of medication and potential adverse effects should be well weighed before choosing relatively safe antihistamines.In addition,decreasing the routine dose or prolonging intervals between the administration of antihistamines may also be attempted to achieve maximum safety.

Efficacy of clemastine fumarate in antagonizing atracurium-induced release of histamine in patients undergoing surgery under general anesthesia / 中华麻醉学杂志

Objective To evaluate the efficacy of clemastine fumarate in antagonizing atracuriuminduced release of histamine in the patients undergoing surgery under general anesthesia.Methods Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 21-59 yr,with body mass index of 17-26 kg/m2,scheduled for elective modified radical mastectomy,were divided into 2 groups (n=40 each) using a random number table:control group (group C) and clemastine fumarat group (group CF).Clemastine fumarate 2 mg was injected intramuscularly at 20 min before induction of anesthesia.Anesthesia was induced with iv midazolam 0.1 mg/kg,etomidate 0.3 mg/kg,fentanyl 4-6 μg/kg and atracurium 0.8 mg/kg.The patients were mechanically ventilated after insertion of the larygeal mask airway.Anesthesia was maintained with inhalation of 2％ sevoflurane.Before administration of clemastine fumarate,at 20 min after administration,immediately before administration of atracurium,and at 2,5,10 and 20 min after administration of atracurium,arterial blood samples were taken for determination of plasma histamine concentrations,and the peak airway pressure and degree of cutaneous color were recorded.The development of histaminemia and adverse cardiovascular events was assessed.Steward recovery scores and Ramsay sedation scores were recorded at 10 min after removal of the laryngeal mask airway.Results The incidence of histaminemia was 60％ and 8％ in C and CF groups,respectively.Compared with group C,the plasma histamine concentrations,incidence of histaminemia,degree of cutaneous color,and incidence of hypotension and tachycardia were significantly decreased (P＜0.05),and no significant change was found in the peak airway pressure,Steward recovery scores and Ramsay sedation scores in group CF (P＞0.05).Conclusion For atracurium-induced release of histamine in the patients undergoing surgery under general anesthesia,clemastine fumarate 2 mg injected intramuscularly before operation can not only antagonize histamine at H1 level,but also reduce histamine release,and exerts no influence on recovery from anesthesia and produces good antihistamine efficacy.

Efficacy of fexofenadine hydrochloride tablets at tapering doses for the treatment of chronic spontaneous ;urticaria:a clinical observation / 中华皮肤科杂志

Objective To evaluate the efficacy of fexofenadine hydrochloride tablets at tapering doses for the treatment of chronic spontaneous urticaria. Methods After receiving evaluation of medical history and undergoing autologous serum skin test (ASST), 80 patients with chronic spontaneous urticaria were randomly divided into two groups:conventional dose group administrating fexofenadine hydrochloride tablets 120 mg/d for 12 consecutive weeks, tapering dose group administrating fexofenadine hydrochloride tablets 120 mg/d for the first 4 weeks followed by dose tapering of fexofenadine hydrochloride tablets by 30 mg at the 5th and 9th weeks. The urticaria activity score(UAS) and dermatology life quality index(DLQI)were evaluated before the treatment(baseline)as well as after 4?, 8?and 12?week treatment, and the total dose of fexofenadine hydrochloride was calculated. Results A total of 76 patients completed the 12?week treatment, including 37 patients in the conventional dose group and 39 patients in the tapering dose group. After 4?, 8?and 12?week treatment, a significant decrease was observed in the UAS in the conventional dose group(0.64 ± 0.82, 0.37 ± 0.68 and 0.27 ± 0.56 vs. 4.08 ± 0.79, all P0.05). After 8?and 12?week treatment, symptoms were controlled in 71.79%(28/39)and 82.05%(32/39)of patients in the tapering dose group, respectively, with the total dose of fexofenadine hydrochloride being significantly lower in the tapering dose group than in the conventional dose group (both P<0.001). Conclusion After 4- 8 weeks of treatment with fexofenadine hydrochloride, the tapering dose regimen and conventional dose regimen show similar clinical efficacy in patients with chronic spontaneous urticaria.

Gynecomastia induced by H1-antihistamine (ebastine) in a patient with idiopathic anaphylaxis

H1-antihistamine is generally a well-tolerated and safe drug. However, in resemblance with all other drugs, H1-antihistamines can also prompt adverse drug reactions (ADRs). We recently encountered the very unusual ADR of H1-antihistamine-induced gynecomastia. A 21-year-old man with idiopathic anaphylaxis was treated with ebastine (Ebastel), a second-generation H1-antihistamine, for the prevention of anaphylaxis. Three months later, the patient remained well without anaphylaxis, but had newly developed gynecomastia. Because anaphylaxis recurred after the cessation of H1-antihistamine, the preventive medication was changed to omalizumab. A few months later, his gynecomastia had entirely disappeared. Physicians should be aware of this exceptional ADR of H1-antihistamine.

Gabapentin in treatment for pruritus and insomnia among patients with hemodialysis / 中华全科医师杂志

This paper aimed to study clinical effectiveness of gabapentin in the treatment for pruritus and insomnia among patients with hemodialysis. Eighty patients with severe pruritus and insomnia during regular hemedialysis in Jiaozhou People's Hospital, Jiangsu were randomly divided into two groups with 40 patients each. Gahapentin 0. 1 g were given each patient every night for 4 weeks in one group and a modified-re]ease capsule of 8 mg chiorphenamine maleate was given each patient daffy for 4 weeks in the other group. Effectiveness of treatment was evaluated by improvement of itching symptoms and Pittsburgh Sleep Quality Index (PSQI) scores for insomnia in the patients. Itching improvement was observed in 85%(34/40) of the patients and PSQI scores obviously lowered in them four weeks after gabapentin treatment.However, itching improvement was observed only in 42% ( 17/40 ) of the patients and little change was observed in PSQI scores in them four weeks after chlorphenamine treatment It suggests that gabapentin can significantly improve quality of sleeping and itching symptoms in patients with hemodialysis and it is worthy popularizing in those with it.

Revisão sobre a efícacia e segurança dos anti-histamínicos de primeira e segunda geração / Revision on efficacy and safety of antihistamines of first and second generation

Objetivo: Revisar a eficácia e segurança dos principais anti-histamínicos de primeira e segunda geração. Os anti-histamínicos correspondem a um grupo extenso de medicamentos que vêm apresentando grandes avanços no conhecimento de suas ações e estão entre os agentes mais utilizados na prática clínica em diversas doenças alérgicas. Método: Levantamento bibliográfico nos bancos de dados PubMed, Medline, LILACS, SCIELO e capítulos de livros nos últimos 10 anos, sendo incluídos artigos históricos. Resultados: Nessa revisão são destacadas as principais características da histamina, as diferenças entre os receptores de histamina, o desenvolvimento dos anti-histamínicos de primeira e segunda geração, sua classificação e os principais efeitos colaterais de cada grupo de anti-histamínicos. Conclusão: A presente revisão não pretende esgotar o assunto sobre eficácia e segurança dos anti-histamínicos, mas destaca a falta de estudos bem conduzidos sobre eficácia dos anti-histamínicos de primeira geração e o número crescente de metanálises sobre farmacodinâmica, potência, eficácia e segurança dos anti-histamínicos de segunda geração.

Objective: To review the efficacy and safety of the main antihistamines of first and second generation. The antihistamines represent an extensive group of drugs that are showing great advances in knowledge of their actions and are among the most common agents used in clinical practice in various allergic diseases. Method: Searches in PubMed, Medline, LILACS, SCIELO database and book chapters in the last 10 years, including historic articles. Results: This review highlights the main features of histamine, the differences between histamine receptors, development of first and second generation antihistamines, their classification, and the main side effects of each group of antihistamines. Conclusion: The present review is not intended to exhaust the subject on efficacy and safety of antihistamine, but it highlights the lack of well conducted studies of the efficacy of first-generation antihistamine and the rising number of meta-analysis of pharmacodynamics, potency, efficacy and safety of second-generation antihistamines.

Histamina, receptores de histamina e anti-histamínicos: novos conceitos / Histamine, histamine receptors and antihistamines: new concepts

As drogas com ação anti-histamínica estão entre as medicações mais comumente prescritas na prática dermatológica diária, tanto em adultos como em crianças. Este artigo aborda os novos conceitos da função dos receptores de histamina (receptores H1) e discute os efeitos anti-inflamatórios dessas drogas. A segunda geração de anti-histamínicos difere da primeira geração devido a sua elevada especificidade e afinidade pelos receptores H1 periféricos e devido a seu menor efeito no sistema nervoso central, tendo como resultado menores efeitos sedativos. Embora a eficácia dos diferentes anti-histamínicos H1 (anti-H1) no tratamento de doentes alérgicos seja similar, mesmo quando se comparam anti-H1 de primeira e de segunda geração, eles são muito diferentes em termos de estrutura química, farmacologia e propriedades tóxicas. Consequentemente o conhecimento de suas características farmacocinéticas e farmacodinâmicas é importante para a melhor prática médica, especialmente em gestantes, crianças, idosos e doentes com comorbidades.

Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors) and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.

Urticária aquagênica familiar: relato de dois casos e revisão da literatura / Familial aquagenic urticaria: report of two cases and literature review

Urticária aquagênica é forma rara de urticária física caracterizada por aparecimento de urticas após o contato com água, independente da temperatura. Há poucos casos descritos de urticária aquagênica e, destes, somente cinco da forma familiar. Apresentamos o primeiro relato de urticária aquagênica familiar no Brasil, acometendo mãe e filha. Ambas apresentavam urticas, principalmente após banho de chuveiro, independentemente da temperatura da água. A mãe referia ter o quadro há quatro anos, e a filha, desde o nascimento. Para diagnóstico, foram realizados testes de provocação com água, com aparecimento de lesões em ambas, e testes com dermografômetro, com cubo de gelo envolvido em plástico e de provocação para urticária colinérgica, sem o aparecimento de lesões, excluindo assim outras formas de urticária física.

Aquagenic urticaria is a rare form of physical urticaria, characterized by pruritic wheals that appear following contact with water, independently of its temperature. There are few reports of cases of aquagenic urticaria, and only five include the familial form. We present the first case of familial aquagenic urticaria in Brazil (mother and daughter). Both patients presented wheals following contact with water, especially when showering, regardless of its temperature. The mother reported onset of urticaria four years before and the daughter presented wheals since birth. For diagnostic purposes, they were submitted to a challenge test with water, and both subjects presented wheals, as well as to tests using ice cubes in plastic bag with dermographometer and challenge tests for cholinergic urticaria, with no appearance of lesions, excluding other forms of physical urticaria.

Dapsona como alternativa no tratamento de urticária crônica não responsiva a anti-histamínicos / Dapsone as an alternative to the treatment of chronic urticaria non-responsive to antihistamines

FUNDAMENTOS: A urticária crônica é dermatose que interfere negativamente na qualidade de vida de seus portadores. O tratamento clássico com anti-histamínicos muitas vezes é ineficaz. OBJETIVO: Avaliar a eficácia e a segurança do uso da dapsona no tratamento da urticária crônica não responsiva a anti-histamínicos. METÓDOS: Realizou-se estudo retrospectivo mediante a revisão de prontuários de pacientes atendidos em ambulatório especializado em urticária entre novembro de 1996 e março de 2007. RESULTADOS: Foram avaliados 20 pacientes com urticária crônica de difícil controle, que receberam tratamento com dapsona na dose de 100mg/dia. Associados à dapsona, foram mantidos anti-histamínicos em altas doses, que, isoladamente, não controlavam os sintomas. Quatorze pacientes (70 por cento) responderam com melhora do quadro, observada tanto na diminuição ou desaparecimento das lesões quanto na redução do prurido; três (15 por cento) não obtiveram nenhum sucesso com a medicação; e três (15 por cento) tiveram o tratamento suspenso em decorrência de efeitos colaterais. CONCLUSÃO: Neste estudo, conclui-se que a dapsona é opção segura e eficaz para pacientes com urticária crônica grave não responsiva a anti-histamínicos.

BACKGROUND: Chronic urticaria is a dermatosis that negatively interferes in quality of life of affected individuals. The classic treatment with antihistamines is many times ineffective. OBJECTIVE: To evaluate the efficacy and safety of using dapsone in the treatment of chronic urticaria non-responsive to antihistamines. METHODS: A retrospective study was carried out by reviewing the medical charts of patients seen at an outpatient’s clinic specialized in urticaria, between November 1996 and March 2007. RESULTS: Twenty patients with difficult to control chronic urticaria and who were treated with 100 mg/day of dapsone were evaluated. High doses of antihistamines were maintained and associated with dapsone. Antihistamines alone did not control symptoms. Fourteen patients (70 percent) presented good results, observed in the reduction or disappearance of lesions as well as in reduced pruritus; three patients (15 percent) did not get any success with the medication; and three (15 percent) had the treatment interrupted due to side effects. CONCLUSION: In this study it can be concluded that dapsone is a safe and efficient option for patients presenting severe chronic urticaria non-responsive to antihistamines.