Urticária Crônica Espontânea: abordagem clínico-laboratorial e manejo terapêutico

Contexto: Urticária crônica caracteriza-se pela presença de urticas e/ou angioedema, com tempo de evolução superior a 6 semanas. Classifica- se em urticária crônica espontânea (UCE), com causas conhecidas ou não conhecidas e urticária crônica induzida (UCI). Objetivo: Esta revisão de UCE visa abordar os aspectos clínico-laboratoriais e indicações terapêuticas, de acordo com as diretrizes brasileira e internacional. Métodos: para esta revisão de UCE foi realizada pesquisa nas bases de dados PubMed, Embase, Google Acadêmico e Web of Science. Resultados: Foram incluídos artigos em inglês publicados entre 2018 e 2024, de acordo com sua relevância. Discussão: A patogênese da UCE engloba mecanismos imunológicos do tipo I e IIb. O diagnóstico da afecção é clínico, podendo ser realizados exames laboratoriais complementares, incluindo hemograma, VHS, D-dímero, PCR, anticorpos anti-peroxidase tireoidiana e IgE total. O diagnóstico diferencial da UCE apresenta diversas condições clínicas com morfologia semelhante à UCE. O tratamento indicado da UCE envolve medidas como suspensão de eventuais fatores desencadeantes e abordagem farmacológica, com utilização de anti-histamínicos não-sedantes, omalizumabe e uso eventual de ciclosporina. Conclusões: O impacto da UCE para os pacientes e para o sistema de saúde é de extrema relevância e avanços nas pesquisas permitirão um tratamento individualizado, com melhores perspectivas em relação à terapêutica e qualidade de vida dos pacientes.

The Role of Adjuvant Therapy in the Management of Chronic Urticaria / El papel de la terapia adyuvante en el tratamiento de la urticaria crónica espontánea

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitamin D, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU (AU)

Las directrices actuales para el tratamiento de la urticaria crónica recomiendan los antihistamínicos H1 de segunda generación como tratamiento de primera línea, con un aumento de hasta 4 veces la dosis si no se controla. Sin embargo, la terapia en la urticaria crónica espontánea suele ser decepcionante, por lo que es necesario un tratamiento adyuvante adicional para mejorar la eficacia de la terapia, especialmente en los pacientes que son refractarios a dosis mayores de antihistamínicos. Las investigaciones más recientes recomiendan varias modalidades de tratamiento adyuvante para la urticaria crónica espontánea, como los agentes biológicos, los inmunosupresores, los antagonistas de los receptores de leucotrienos, los antihistamínicos H2, las sulfonas, la terapia con suero autólogo, la fototerapia, la vitamina D, los antioxidantes y los probióticos. Esta revisión bibliográfica presenta estudios recientes sobre la eficacia de diversas terapias adyuvantes en el tratamiento de la urticaria crónica espontánea (AU)

[Artículo traducido] El papel de la terapia adyuvante en el tratamiento de la urticaria crónica espontánea / The Role of Adjuvant Therapy in the Management of Chronic Urticaria

Las directrices actuales para el tratamiento de la urticaria crónica recomiendan los antihistamínicos H1 de segunda generación como tratamiento de primera línea, con un aumento de hasta 4 veces la dosis si no se controla. Sin embargo, la terapia en la urticaria crónica espontánea suele ser decepcionante, por lo que es necesario un tratamiento adyuvante adicional para mejorar la eficacia de la terapia, especialmente en los pacientes que son refractarios a dosis mayores de antihistamínicos. Las investigaciones más recientes recomiendan varias modalidades de tratamiento adyuvante para la urticaria crónica espontánea, como los agentes biológicos, los inmunosupresores, los antagonistas de los receptores de leucotrienos, los antihistamínicos H2, las sulfonas, la terapia con suero autólogo, la fototerapia, la vitamina D, los antioxidantes y los probióticos. Esta revisión bibliográfica presenta estudios recientes sobre la eficacia de diversas terapias adyuvantes en el tratamiento de la urticaria crónica espontánea (AU)

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitamin D, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU (AU)

The Role of Adjuvant Therapy in the Management of Chronic Urticaria. / [Artículo traducido] El papel de la terapia adyuvante en el tratamiento de la urticaria crónica espontánea.

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitaminD, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.

The Role of Adjuvant Therapy in the Management of Chronic Urticaria.

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitamin D, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.

Guia prático do tratamento com omalizumabe para urticária crônica espontânea / Practical guide to omalizumab treatment for chronic spontaneous urticaria

A urticária crônica é uma doença com grande impacto socioeconômico e na qualidade de vida do indivíduo. O adequado conhecimento de formas de tratamento eficazes e com perfil de segurança satisfatório, assim como dos mecanismos preditores de resposta ao tratamento, são essenciais para que se alcance um controle adequado da doença. O omalizumabe é um anticorpo monoclonal anti-IgE com eficácia reconhecida e bom perfil de segurança no tratamento da urticária crônica. Objetivamos elucidar questões envolvidas no manejo desta medicação, através da revisão em literatura de estudos atuais e com relevância clínica. Foi realizado levantamento de questões importantes e pouco elucidadas, buscando respostas baseadas nestes estudos. Com isso, foram abordados aspectos práticos do tratamento com o omalizumabe, esclarecendo desde os fenótipos dos pacientes e conduta adequada para estas diferentes situações, trazendo possíveis fatores preditores de resposta ao tratamento e contemplando também um novo anticorpo monoclonal anti-IgE no manejo destes pacientes.

Chronic urticaria is a disease with great socioeconomic impact on people's quality of life. Adequate knowledge of effective treatments with a satisfactory safety profile as well as of the predictive mechanisms of response to treatment are essential for achieving adequate disease control. Omalizumab is an anti-IgE monoclonal antibody with recognized efficacy and a good safety profile in the treatment of chronic urticaria. We aim to elucidate issues involving the management of this medication through a literature review of current studies with clinical relevance. A survey of important and unclear questions was conducted, and the answers were sought in the studies. Thus, practical aspects of omalizumab treatment were addressed, including the phenotypes of patients and appropriate approaches for different situations. Possible predictive factors of response to treatment and a new anti-IgE monoclonal antibody for the management of these patients were also reported.

A influência do tratamento do Helicobacter pylori no paciente com urticária crônica espontânea / The influence of Helicobacter pylori treatment on patients with chronic spontaneous urticaria

Introdução: A urticária crônica espontânea (UCE) é considerada atualmente uma condição autoimune, onde o mastócito é a célula central e sua ativação envolve a participação de autoanticorpos IgG e/ou IgE. Entretanto, várias outras condições podem estar associadas ao não controle da UCE, como a infecção pelo Helicobacter pylori (Hp), embora os dados na literatura sejam controversos. O objetivo deste estudo foi avaliar a influência do tratamento do Hp no controle clínico da UCE. Métodos: Estudo retrospectivo de prontuários eletrônicos de pacientes com UCE que foram submetidos à pesquisa de Hp devido a sintomas gastroesofágicos. Foram avaliados os dados demográficos e a refratariedade aos anti-histamínicos destes pacientes. Posteriormente, a positividade ao Hp e a influência do tratamento do Hp sobre o controle clínico da UCE também foram avaliados. A UCE foi considerada controlada quando o UAS7 < 6, juntamente com a redução do uso de medicamentos para UCE. Resultados: Foram incluídos 50 pacientes, a maioria do sexo feminino (84%), e com idade média de 56,0 anos. A positividade para o Hp foi observada em 18 pacientes (36%), porém, o tratamento para erradicação do Hp foi realizado em apenas 13 pacientes, e, destes, 9 (69,2%) apresentaram melhora dos sintomas da UCE, avaliados em média 5,6 meses após este tratamento. Não houve associação da infecção pelo Hp com a gravidade da UCE e nem com o tempo de doença. Conclusões: Embora a UCE tenha a autoimunidade como a principal hipótese para ativação do mastócito, outras situações estão associadas ao não controle da UCE, como a infecção pelo Hp. Este estudo encontrou que a frequência de positividade do Hp nos pacientes com UCE foi mais baixa do que a encontrada na literatura, porém, cerca de 70% dos pacientes tratados para erradicação do Hp apresentaram melhora clínica da UCE.

Introduction: Chronic spontaneous urticaria (CSU) is currently considered an autoimmune disorder, where mast cells are the key cells and their activation is associated with IgG and/ or IgE autoantibodies. However, many other conditions may be associated with uncontrolled CSU, such as Helicobacter pylori (Hp) infection, although the literature is controversial in this regard. The aim of this study was to evaluate the influence of Hp treatment on CSU control. Methods: We retrospectively reviewed the medical records of patients with CSU who underwent Hp screening because of gastroesophageal symptoms. Data on demographics and antihistamine resistance were assessed in these patients. Hp positivity and the influence of Hp treatment on CSU control were also evaluated. CSU was considered controlled if UAS7 <6 and the medication for CSU control was reduced. Results: Fifty patients were included in the study; most were women (84%) and the mean age was 56.0 years. Hp infection was observed in 18 patients (36%), although only 13 were treated for Hp eradication; of these, 9 (69.2%) showed improvement in CSU symptoms, reassessed at a mean of 5.6 months after treatment. There was no association of Hp infection with CSU severity or disease duration. Conclusions: Although the main hypothesis for mast cell activation in CSU is autoimmunity, other conditions are associated with uncontrolled CSU, such as Hp infection. This study found a lower rate of Hp positivity than that reported in the literature, but about 70% of patients with CSU treated for Hp eradication showed clinical improvement.

Omalizumabe no tratamento da urticária crônica espontânea: análise de custo-efetividade e impacto orçamentário / Omalizumab in the treatment of chronic spontaneous urticaria: cost-effectiveness analysis and budgetary impact

Objetivos: Determinar a relação custo-efetividade da adição do omalizumabe (Oma) no tratamento da urticária crônica espontânea (UCE) refratária aos tratamentos convencionais, bem como o impacto orçamentário no contexto da saúde suplementar (SS) no Brasil. Métodos: Na análise econômica, utilizou-se o modelo de Markov baseado no Urticaria Activity Score for 7 days (UAS7), considerando- se os desfechos clínicos: anos de vida salvos com doença controlada (UAS7 = 0 ou UAS7 ≤ 6), e anos de vida ajustados à qualidade (QALY). Três razões de custo-efetividade incremental (RCEI) foram calculadas. O impacto orçamentário foi calculado com base em dados da SS, população elegível e o horizonte de 5 anos. Resultados: As RCEI calculadas para o desfecho anos de vida salvos com doença controlada nos horizontes de 3 e 5 anos foram R$ 108.935,42 e R$ 166.977,29, respectivamente. O impacto orçamentário, do primeiro ao quinto ano, da incorporação do Oma à SS para o tratamento de pacientes com UCE refratária variou entre R$ 65 milhões e R$ 157 milhões, que equivaleria a R$ 1,38/assistido no primeiro ano incorporação. Sendo assim, ao analisar os custos adicionais por desfecho adicional salvo, nota-se que a RCEI também se mostrou menor que três vezes o PIB per capita no Brasil, podendo-se dizer que o tratamento com Oma é custo-efetivo em comparação ao tratamento atual também neste desfecho. Conclusão: A análise econômica demonstrou que o tratamento com Oma da UCE refratária ao tratamento com antihistamínicos H1 em doses elevadas é custo-efetivo no cenário nacional, e a sua incorporação na SS é viável.

Objectives: To determine the cost-effectiveness of adding omalizumab (Oma) to the treatment of chronic spontaneous urticaria (CSU) refractory to conventional treatments, as well as its budgetary impact in the context of private health insurance (PHI) in Brazil. Methods: In the economic analysis, the Markov model based on the Urticaria Activity Score over 7 days (UAS7) was used considering the following clinical outcomes: life years saved with controlled disease (UAS7 = 0 or UAS7 ≤ 6) and quality-adjusted life years (QALYs). Three incremental cost-effectiveness ratios (ICERs) were calculated. The budgetary impact was calculated using PHI data, eligible population, and 5-year horizon. Results: The estimated ICERs for life years saved with controlled disease in 3- and 5-year horizons were R$ 108,935.42 and R$ 166,977.29, respectively. The budgetary impact from the first to the fifth year of the incorporation of Oma into PHI for the treatment of patients with refractory CSU ranged from R$ 65 million to R$ 157 million, equivalent to R$ 1.38/assisted patient in the first year of incorporation. When additional costs were analyzed per additional outcome saved, ICER was shown to be less than three times the GDP per capita in Brazil. Thus, Oma is cost-effective compared to the current treatment in this outcome as well. Conclusion: The economic analysis demonstrated that treatment with Oma of CSU refractory to the treatment with H1 antihistamines in high doses is cost-effective in the Brazilian setting and its incorporation into the PHI system is feasible.

The Effectiveness of Omalizumab Treatment in Real-Life is Lower in Patients with Chronic Urticaria Longer than 18 Months' Evolution and Prior Immunosuppressive Treatment. / La efectividad del tratamiento con omalizumab en la vida real es menor en pacientes con urticaria crónica de más de 18 meses de evolución y tratamiento inmunosupresor previo.

BACKGROUND: The efficacy of omalizumab in the treatment of chronic spontaneous urticaria has been demonstrated in phase iii clinical trials, but limited information is available regarding real-life effectiveness using the weekly Urticarial Activity Score (UAS7). The aim of the study was to assess clinical response (UAS7≤6) and complete response (UAS7=0) rates at weeks 12 and 24 in a real-life cohort and to identify possible predictors of response to omalizumab. METHODS: Clinical records of consecutive patients with moderate-to-severe chronic spontaneous urticaria (UAS≥16) treated with omalizumab at a university-affiliated reference dermatology department in Barcelona, Spain, from February 2014 to September 2017 were retrospectively reviewed. UAS7 values and patients' evolution were assessed according to a predefined protocol. Statistical analysis of data was done using SPSS 18 statistical package (SPSS 18 Inc., Chicago, IL, USA) software. RESULTS: Forty-eight patients were included in the study. All of them completed at least 24-weeks of treatment and follow-up. At week 12, clinical response rates (UAS7<6) were 70.8% and complete response rates (UAS7=0) were 47.9%. At week 24, clinical response rates were 64.6% and complete response rates were 52.1%. PATIENTS: with long-term urticaria (≥18 months' duration) were less likely to achieve a clinical response at week 12 (odds ratio: 0.25; 95% confidence interval 0.06-0.96). Previous immunosuppressive treatment tended to be associated with a lower probability of complete response at week 12 (odds ratio: 0.27 95% confidence interval: 0.07-1.02). H1-antihistamine treatment was associated with lower probability of response at week 24 (odds ratio: 0.1 95% 95% confidence interval: 0.01-0.88) CONCLUSIONS: The effectiveness and safety of omalizumab in real life are similar to efficacy and safety in clinical trials. Duration of disease, previous immunosuppressive therapy and requirement for concomitant H1-antihistamine treatment may be helpful in predicting response to omalizumab treatment.

Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab. / Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea.

BACKGROUND AND OBJECTIVE: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. MATERIAL AND METHODS: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. RESULTS: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7days, the Urticaria Control Test, or both. CONCLUSIONS: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse.

Urticária crônica espontânea refratária aos anti-histamínicos: opção por ciclosporina / Antihistamine-refractory chronic spontaneous urticaria: opting for cyclosporine

Introdução: Anti-histamínico de segunda geração (AH1 2ªG) é o tratamento de escolha para pacientes com urticária crônica espontânea (UCE). Porém, cerca de 50% dos pacientes não responde a este tratamento. A ciclosporina é uma opção para os quadros mais graves. A ciclosporina tem propriedades imunossupressoras potentes, mas, apesar de sua eficácia, seu uso é limitado devido a diversos efeitos colaterais importantes. Objetivo: O objetivo deste estudo foi avaliar a resposta à ciclosporina em pacientes com UCE refratária aos anti-histamínicos. Método: Estudo retrospectivo baseado no prontuário eletrônico de pacientes com UCE refratária aos AH1 2ªG e que não responderam à introdução de outros medicamentos para controle da urticária. A ciclosporina foi indicada para todos os pacientes. A dosagem de D-dímero foi realizada em alguns pacientes. Resultados: Trinta pacientes participaram do estudo. Desses pacientes, 80% eram do sexo feminino, e a média de idade era de 42,8 anos. Previamente à introdução da ciclosporina, todos estavam em uso de AH1, 60% de AH2, 67% de montelucaste, 33,3% de hidroxicloroquina, e 56,7% de corticoide oral. A mediana de tempo de uso da ciclosporina foi de 11,5 meses. Em relação à eficácia, 40% dos pacientes apresentaram melhora dos sintomas, 40% não responderam ao tratamento, e em 20% dos pacientes a resposta não foi avaliada por suspensão da ciclosporina devido a efeitos colaterais, ou não foi introduzida devido a alterações clínicas ou laboratoriais prévias. Houve aumento dos níveis pressóricos em 9 pacientes (30%), e nefrotoxicidade em 5 pacientes (16,7%). Conclusões: Embora a ciclosporina seja uma boa opção terapêutica para pacientes com UCE refratária aos AH1, os efeitos colaterais são frequentes e devem ser monitorados.

Introduction: Second-generation antihistamines (sgAH1) are the treatment of choice for patients with chronic spontaneous urticaria (CSU). However, about 50% of the patients do not respond to this treatment. Cyclosporine is an option for more severe presentations. This drug has potent immunosuppressive properties. Despite its effectiveness, use is limited due to several serious side effects. Objective: The aim of this study was to assess response to cyclosporine in patients with antihistamine-refractory CSU. Method: This retrospective study was based on the electronic records of patients with sgAH1-refractory CSU who did not respond to the introduction of other drugs to control urticaria. Cyclosporine was indicated for all patients. D-dimer dosage was performed in some patients. Results: Thirty patients participated in the study. Of these, 80% were female and the mean age was 42.8 years. Prior to the introduction of cyclosporine, all patients were using AH1, 60% AH2, 67% montelukast, 33.3% hydroxychloroquine, and 56.7% oral corticosteroids. Median time of cyclosporine use was 11.5 months. Regarding efficacy, 40% of the patients showed improvement of symptoms, 40% did not respond to treatment, and in 20% response was not evaluated because the medication was withdrawn due to side effects or was not introduced based on previous clinical or laboratory abnormalities. There was an increase in blood pressure levels in 9 patients (30%) and nephrotoxicity in 5 (16.7%). Conclusions: Even though cyclosporine is a good therapeutic option for patients with AH1-refractory CSU, side effects are frequent and should be monitored.

Improvement in the quality of life of patients with chronic spontaneous urticaria treated with omalizumab in real life. / Mejora de la calidad de vida de los pacientes con urticaria crónica espontánea tratados con omalizumab en vida real.

OBJECTIVE: Evaluation of the impact on the quality of life (QOL) relating to health in patients with chronic urticaria (CSU) treated with omalizumab. METHOD: Longitudinal descriptive observational study of quality of life based on18 patients with chronic urticaria ≥12 years treated with omalizumab. Changes in QOL examined at 1 month (T1), at 6 months (T6) and 12 months (T12), by: Visual Analogical Scale (UAS), specific urticaria QOL questionnaire (CU-Q2oL), general health questionnaire (SF-36) and activity of urticaria questionnaire (Score UAS7). RESULTS: The most disabling symptoms for patients were: pruritus (61.1%); decrease in health and physical activity (55.5%), wheals, swelling and nervousness (50%); depression and shame of marks (38.89%); side effects to drugs (33.33%); sleepiness and tiredness (27.78%); work (22.22%); "choosing clothes and pain" 16.67% and social relations (11.11%). Statistically significant differences were observed in T1, T6 and T12. In T1, UAS -4.72 (p=.001); CU-Q2oL -16.38 (p<.001); SF-36 15.44 (p=.006); UAS7 wheals -7.27 (p=.001), UAS7 pruritus -8.72 (p=.003). In T6, UAS -4.26 (p=.001); CU-Q2oL -18.94 (p<.001); SF-36 15.41 (p<.001); UAS7 wheals -7.41 (p=.001), UAS7 pruritus -7.11 (p=.001). In T12 UAS -9.61 (p=.004); CU-Q2oL -21.38 (p=.01); SF-36 17.53 (p=.04); UAS7 wheals -8.23 (p=.004), UAS7 pruritus -10.69 (p=.004). CONCLUSIONS: There was a very good response in T1, which was maintained in T6 and T12. Patients with chronic urticaria treated with omalizumab presented good results with a reduction of CUE activity and improvement of their QOL.

Management of Chronic Spontaneous Urticaria in Routine Clinical Practice Following the EAACI/GA(2)LEN/EDF/WAO Guidelines. / Manejo de la urticaria crónica espontánea en la práctica clínica diaria siguiendo las indicaciones de la guía EAACI/GA(2)LEN/EDF/WAO.

INTRODUCTION: Chronic spontaneous urticaria is a prevalent and difficult-to-treat condition that has a very negative impact on patient quality of life. OBJECTIVE: To describe the epidemiological and clinical characteristics of patients presenting with chronic spontaneous urticaria and the response to treatment administered according to the EAACI/GA(2)LEN/EDF/WAO consensus guideline. MATERIAL AND METHOD: Descriptive cross-sectional study of all the patients with chronic spontaneous urticaria who consulted a skin allergy unit in the dermatology department of a tertiary hospital in Spain between July 2011 and July 2015. RESULTS: The study included 100 patients with chronic spontaneous urticaria; inducible urticaria was present in 43% of cases, and angioedema in 40%. On diagnosis, 53% of patients were taking nonsteroidal anti-inflammatory drugs. All patients were treated with second generation H1-antihistamines, but the standard dose was sufficient in only 18% of cases. Higher doses (up to 4 times the standard dose) achieved control of the urticaria in 74% of the patients studied. Higher doses of second generation H1-antihistamines were required to control the condition in patients with angioedema, and the presence of angioedema was associated with a lack of response to treatment with these drugs (OR, 6.1%; P<.001). One in 4 patients failed to respond to second generation H1-antihistamines and required treatment with omalizumab or ciclosporin to control their condition. CONCLUSIONS: Doses of H1-antihistamines higher than the standard dose are required in most cases to achieve control of chronic spontaneous urticaria. Angioedema is associated with failure to respond to treatment with antihistamines. In refractory cases, control of the condition can be achieved with omalizumab or ciclosporin. Patients with chronic spontaneous urticaria do not generally avoid the use of nonsteroidal anti-inflammatory agents.

Urticaria crónica espontánea: revisión de la literatura / Spontaneous chronic urticaria: A literature 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)

Abstract: Chronic spontaneous urticaria is a disease that produces a great compromise in patient's quality of life. The associated pathophysiological mechanisms are still largely unknown because they are not generalizable to all individuals. There are intrinsic and extrinsic factors involved in the development and persistence of the disease that can act individually or coexist. In this review are proposing some changes in the current classification of the disease, which includes a subdivision into the chronic urticaria called mixed chronic urticaria that makes reference to cases where intrinsic and extrinsic factors coexist for the onset of the disease in the same individual. Some viral, bacterial and parasite infectious processes have been associated with the development or severity of chronic urticaria symptoms in a subgroup of patients, therefore, they are included as extrinsic factors to the individual within chronic inducible urticaria non-physical. These modifications are proposed in order to optimized the diagnosis and treatment of patients with chronic spontaneous urticaria. (AU)

Guía Argentina de urticaria y angioedema

Se actualiza el diagnóstico de la urticaria crónica (UC) y los conceptos, definiciones y sugerencias basados en la evidencia para su tratamiento. La urticaria ocurre en al menos 20% de la población en algún momento de la vida. Su etiología difiere en la forma aguda (menos de 6 semanas), y en la crónica. No es posible pronosticar si las formas agudas evolucionarán a UC, ya que todas son agudas al comienzo. La UC ocurre como espontánea (UCE) o inducible (UCI). El diagnóstico es sencillo, pero incluye un minucioso estudio para descartar diagnósticos diferenciales; para UCI son útiles las pruebas de provocación en la caracterización y manejo. Los estudios complementarios se deben limitar y orientar según sospecha clínica. El tratamiento se divide en tres enfoques: evitación, eliminación o tratamiento del estímulo desencadenante o de la causa, y tratamiento farmacológico. Recientemente éste se modificó, con empleo de antihistamínicos de segunda generación como primera línea y aumento de dosis de antihistamínicos H1 no sedantes, hasta 4 veces, como segunda línea. Los antihistamínicos son fundamentales para tratar la UC; sin embargo, un 40% de los pacientes no logra un buen control pese al aumento de dosis y requiere otro medicamento adicional. La evidencia más reciente considera que un grupo de fármacos puede utilizarse como tercera línea en estos casos, para mejorar la calidad de vida y limitar la toxicidad por el uso frecuente o crónico de esteroides sistémicos. Se recomiendan para esta tercera línea solo 3 fármacos: omalizumab, ciclosporina A o antileucotrienos.

This interdisciplinary paper summarizes the news in the diagnosis and treatment of chronic urticaria (CU), and provides concepts, definitions and evidence-based suggestions for its management. Urticaria occurs in at least 20% of the population at some point in their lives. Acute urticaria (less than 6 weeks' duration), differs from CU in its etiology, but the onset of this disease is always acute. CU may occur as spontaneous (SCU) or induced (ICU). The diagnosis is simple, although a careful evaluation is necessary for differential diagnosis. ICU´s diagnosis is mainly clinical, even if provocation tests can be useful. Supplementary studies should be limited and based on the clinical suspicion. Treatment may be divided into three approaches: avoidance, elimination or treatment of the cause, and pharmacological treatment. Recently treatment has been modified with the use of second-generation antihistamines as first-line and increased doses of nonsedating H1 antihistamines, up to 4 times, as second line. Antihistamines are essential to treat CU; however, 40% of patients do not achieve good control despite increased doses and require additional treatment. The most recent evidence indicates a group of drugs to be used as third line in these cases, to improve quality of life and to limit toxicity from frequent or chronic use of systemic steroids. Only 3 drugs are recommended as third line: omalizumab, cyclosporin A or anti-leukotrienes.

Guía Argentina de urticaria y angioedema

Se actualiza el diagnóstico de la urticaria crónica (UC) y los conceptos, definiciones y sugerencias basados en la evidencia para su tratamiento. La urticaria ocurre en al menos 20% de la población en algún momento de la vida. Su etiología difiere en la forma aguda (menos de 6 semanas), y en la crónica. No es posible pronosticar si las formas agudas evolucionarán a UC, ya que todas son agudas al comienzo. La UC ocurre como espontánea (UCE) o inducible (UCI). El diagnóstico es sencillo, pero incluye un minucioso estudio para descartar diagnósticos diferenciales; para UCI son útiles las pruebas de provocación en la caracterización y manejo. Los estudios complementarios se deben limitar y orientar según sospecha clínica. El tratamiento se divide en tres enfoques: evitación, eliminación o tratamiento del estímulo desencadenante o de la causa, y tratamiento farmacológico. Recientemente éste se modificó, con empleo de antihistamínicos de segunda generación como primera línea y aumento de dosis de antihistamínicos H1 no sedantes, hasta 4 veces, como segunda línea. Los antihistamínicos son fundamentales para tratar la UC; sin embargo, un 40% de los pacientes no logra un buen control pese al aumento de dosis y requiere otro medicamento adicional. La evidencia más reciente considera que un grupo de fármacos puede utilizarse como tercera línea en estos casos, para mejorar la calidad de vida y limitar la toxicidad por el uso frecuente o crónico de esteroides sistémicos. Se recomiendan para esta tercera línea solo 3 fármacos: omalizumab, ciclosporina A o antileucotrienos.(AU)

This interdisciplinary paper summarizes the news in the diagnosis and treatment of chronic urticaria (CU), and provides concepts, definitions and evidence-based suggestions for its management. Urticaria occurs in at least 20% of the population at some point in their lives. Acute urticaria (less than 6 weeks duration), differs from CU in its etiology, but the onset of this disease is always acute. CU may occur as spontaneous (SCU) or induced (ICU). The diagnosis is simple, although a careful evaluation is necessary for differential diagnosis. ICU´s diagnosis is mainly clinical, even if provocation tests can be useful. Supplementary studies should be limited and based on the clinical suspicion. Treatment may be divided into three approaches: avoidance, elimination or treatment of the cause, and pharmacological treatment. Recently treatment has been modified with the use of second-generation antihistamines as first-line and increased doses of nonsedating H1 antihistamines, up to 4 times, as second line. Antihistamines are essential to treat CU; however, 40% of patients do not achieve good control despite increased doses and require additional treatment. The most recent evidence indicates a group of drugs to be used as third line in these cases, to improve quality of life and to limit toxicity from frequent or chronic use of systemic steroids. Only 3 drugs are recommended as third line: omalizumab, cyclosporin A or anti-leukotrienes.(AU)

Update on the treatment of chronic urticaria.

Chronic spontaneous urticaria, also known as chronic idiopathic urticaria or simply chronic urticaria, is a common disorder that has a prevalence in the general population that ranges between 0.5% and 1%. This condition negatively affects the patient's quality of life and has considerable impact on direct and indirect health-related costs. Chronic urticaria is difficult to manage. Nonsedating H1 antihistamines are the first line of therapy, but fewer than 50% of patients experience relief at recommended dosages. Although guidelines call for increasing the dosage when response is inadequate, some patients still do not achieve adequate control of symptoms. New treatment alternatives, with proven efficacy under the standards of evidence-based medical practice, must therefore be developed.

Avanços recentes no emprego de imunobiológicos nas doenças alérgicas / Recent advances in the use of biologicals in allergic diseases

O uso de imunobiológicos, já consagrados como importantes avanços terapêuticos na Reumatologia, para o tratamento de pacientes com doenças autoimunes do tecido conjuntivo, e na Gastroenterologia, no manejo de pacientes com doenças intestinais inflamatórias, inicia uma trajetória também muito promissora no controle mais eficaz de várias condições em Alergia-Imunologia, incluindo asma grave eosinofílica, urticária crônica espontânea, dermatite atópica, e esofagite eosinofílica. É possível que futuramente, tal como na Oncologia, possam ser empregadas várias combinações de drogas visando um melhor controle da alergia, baseado sempre que possível na caracterização dos diversos endótipos e fenótipos estabelecidos. No presente artigo, é feita uma revisão objetiva e atualizada de vários agentes imunobiológicos em Alergia: omalizumabe (anti-IgE), anti-IL-5 (mepolizumabe, reslizumabe e benralizumabe), dupilumabe (anti-subunidade alfa do receptor de IL-4), quilizumabe (anti-receptor M1 prime de membrana da IgE nas células-alvo), anti-TSLP (AMG 157), e lebrikizumabe (anti-IL-13). Futuramente, novos agentes imunoterapêuticos poderão surgir, com potencial de melhorar as atuais estratégias para tratamento das doenças alérgicas mais complexas e graves, de difícil controle...

The use of biologicals, currently recognized as an important therapeutic advance in the fields of rheumatology – in the treatment of patients with autoimmune connective tissue disorders – and gastroenterology – in the management of patients with inflammatory bowel disease – has also shown promising results in terms of a more effective control of different conditions in the field of allergy and immunology, including severe eosinophilic asthma, chronic spontaneous urticaria, atopic dermatitis and eosinophilic esophagitis. Similarly to what has been seen in oncology, it is possible that, in the future, several drug combinations can be used with the aim of better controlling atopic conditions, whenever possible based on the characterization of established endotypes and phenotypes. This article presents an objective, up-to-date review of the use of different biologicals in allergy, namely, omalizumab (anti-IgE), anti-IL-5 (mepolizumab, reslizumab,and benralizumab), dupilumab (anti-alpha subunit of the IL-4 receptor), quilizumab (anti-M1 prime membrane receptor of IgE in target cells), anti-TSLP (AMG 157), and lebrikizumab (anti-IL-13). In the future, other biological agents may be developed, with the potential to improve the treatment strategies currently available for more severe, complex, difficult-to-control allergic diseases...