Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology

Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

Guía clínica chilena de urticaria crónica espontánea / Chilean guidelines for chronic urticaria

Chronic urticaria (CU) is characterized by itchy wheals, angioedema or both lasting six weeks or more. It is classified as spontaneous (CSU) and inducible urticaria (CIndU), depending whether there is an identifiable trigger or not. CSU is the predominant form, affecting more than 75% of patients, although overlaps often occur. The prevalence of CSU throughout life is around 1.8% and predominates in women at a ratio of 2:1. The higher incidence of CSU is between 20 and 40 years of age and lasts between one to five years. However, in up to 20% of patients the disease may last longer. CSU not only hampers quality of life, but also affect performance at work and school. The diagnosis of CSU is mainly clinical, and laboratory tests are required depending on the clinical history of the patient. Extensive laboratory tests are usually unnecessary. Second generation anti-histamines are used as first line treatment for CSU treatment. In refractory patients, systemic treatments, such as cyclosporine or omalizumab are suggested. We herein report the first Chilean CSU guidelines.

Pneumocystis jirovecii pneumonia induced by low-dose methotrexate in a patient with chronic urticaria

Abstract Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.

Chronic urticaria in adults: state-of-the-art in the new millennium

Chronic urticaria has been explored in several investigative aspects in the new millennium, either as to its pathogenesis, its stand as an autoimmune or auto-reactive disease, the correlation with HLA-linked genetic factors, especially with class II or its interrelation with the coagulation and fibrinolysis systems. New second-generation antihistamines, which act as good symptomatic drugs, emerged and were commercialized over the last decade. Old and new drugs that may interfere with the pathophysiology of the disease, such as cyclosporine and omalizumab have been developed and used as treatments. The purpose of this article is to describe the current state of knowledge on aspects of chronic urticaria such as, pathophysiology, diagnosis and the current therapeutic approach proposed in the literature.

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 / Argentine guidelines for urticaria and angioedema

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.

Omalizumab: opción terapéutica para la urticaria crónica espontánea de difícil control con vasculitis asociada, reporte de tres casos / Omalizumab: therapeutic option in chronic spontaneous urticaria difficult to control with associated vasculitis, report of three cases

Introducción. Aproximadamente el 50 % de los casos de urticaria crónica no mejoran adecuadamente con las dosis convencionales de antihistamínicos, por lo cual se han planteado múltiples opciones terapéuticas, entre las cuales el omalizumab es una herramienta novedosa que ahora cuenta con evidencia de alta calidad que soporta su uso en los casos difíciles, que mejora rápidamente el índice sintomático y el uso de medicamentos, y cuenta con un buen perfil de seguridad. Objetivo. Presentar tres casos de mujeres adultas con urticaria crónica espontánea de más de ocho años de evolución, que no mejoraron con el tratamiento con altas dosis de antihistamínicos, asociados a antileucotrienos e inmunomoduladores y en quienes se combinaban varios mecanismos fisiopatológicos: urticaria crónica espontánea con componente de autoinmunidad, componente de presión y urticaria vasculítica. Materiales y métodos. Se reportan los casos con sus respectivas evaluaciones clínicas y de laboratorio, los medicamentos usados y la respuesta después del inicio de omalizumab y se hace una revisión de la literatura científica sobre uso de este medicamento en la urticaria crónica. Resultados. En los tres casos presentados se obtuvo una mejoría completa de los síntomas tras el inicio del omalizumab. Conclusión. El omalizumab es una opción terapéutica exitosa en casos de urticaria crónica de difícil control con vasculitis asociada, cuando se han agotado las opciones propuestas por las guías internacionales.

Introduction: Approximately 50% of chronic urticaria cases do not respond adequately to conventional doses of antihistamines, so a number of other therapeutic options have been suggested. Among these, omalizumab is an innovative tool, which now has high-quality evidence that supports its use in difficult cases, rapidly improving the symptom index and the use of medications with a good safety profile. Objective: To report three cases of adult women with spontaneous chronic urticaria with an evolution of more than eight years, which did not improve with high doses of antihistamines and leukotriene receptor blockers, associated with immunomodulatory therapy in which several etiologic mechanisms were combined: chronic spontaneous urticaria with autoimmune and pressure components, and vasculitis. Materials and methods: We report the cases with their clinical and laboratory evaluations, used medication, the response after the start of omalizumab and we performed a review of the literature on the use of this drug in chronic urticaria. Results: In all the presented cases, we obtained complete improvement of symptoms after starting omalizumab. Conclusion: Omalizumab is a successful treatment option in cases of difficult to control chronic urticaria with associated vasculitis in which the options proposed by international guidelines have been exhausted.

Recidiva de urticária crônica decorrente de reinfecção por Helicobacter pylori / Recurrence of chronic urticaria caused by reinfection by Helicobacter pylori / Recidiva de urticaria crónica decurrente de reinfección por Helicobacter pylori

OBJETIVO: Descrever, em uma adolescente do sexo feminino, o caso clínico de urticária crônica associado à infecção por Helicobacter pylori confirmado em dois momentos distintos, com melhora após a terapêutica antibacteriana. DESCRIÇÃO DO CASO: Paciente do sexo feminino, 13 anos, procurou atendimento médico com urticária crônica e dores epigástricas sem resposta ao tratamento medicamentoso. Os exames solicitados para investigação complementar apresentaram-se normais, exceto a endoscopia digestiva alta com biópsia, que evidenciou gastrite crônica ativa moderada associada ao Helicobacter pylori. Foi iniciado o tratamento adequado para a bactéria em questão e a paciente apresentou remissão dos sintomas. Nova endoscopia digestiva alta para controlar o tratamento após nove meses estava normal. Cinco anos depois, a paciente procurou novamente o ambulatório queixando-se de retorno do quadro de urticária e dores epigástricas. Ela se encontrava em uso de anti-histamínico, sem melhora. Foi novamente submetida a protocolo de exames para investigar urticária crônica, com resultados dentro da normalidade. Foi submetida à endoscopia digestiva alta, que apresentou teste da urease positivo. Iniciou-se então novo tratamento para Helicobacter pylori por sete dias, com desaparecimento da urticária crônica e das dores epigástricas. COMENTÁRIOS: O caso relatado sugere relação causal entre o diagnóstico positivo para o Helicobacter pylori e a ocorrência do quadro de urticária crônica, com instituição de terapêutica eficaz para tal bactéria e remissão dos sintomas. A urticária crônica é uma doença de etiopatogenia complexa e, apesar das controvérsias, as evidências do envolvimento do Helicobacter pylori com doenças extraintestinais vêm crescendo, entre elas a urticária crônica.

OBJECTIVE: To describe a case of chronic urticaria in a female adolescent associated with Helicobacter pylori infection, confirmed in two different occasions, with improvement of urticaria after the antibacterial treatment. CASE DESCRIPTION: A 13-year-old female patient sought medical care with chronic urticaria and epigastric pain unresponsive to medical treatment. Laboratorial tests for further investigation were normal except for the upper gastrointestinal endoscopy with biopsy showing moderate chronic active gastritis associated with Helicobacter pylori. After specific and appropriate treatment, the patient had remission of the symptoms. A new upper gastrointestinal endoscopy to control the treatment after nine months was normal. After five years, the patient returned with recurrence of urticaria and epigastric pain. She was taking antihistamines, without any improvement. It was again submitted to screening protocol for chronic urticaria with normal results. She was submitted to upper gastrointestinal endoscopy, which showed positive urease test. The patient started a new treatment for Helicobacter pylori with disappearance of chronic urticaria and epigastric pain within seven days. COMMENTS: The reported case suggests a causal relationship between the positive diagnosis of Helicobacter pylori and the occurrence of chronic urticaria, showing the remission of symptoms after the institution of effective therapy for this agent. Chronic urticaria is a disease of complex etiology, and although controversial, there is growing evidence of Helicobacter pylori involvement with extraintestinal diseases, including chronic urticaria.

OBJETIVO: Describir, en una adolescente del sexo femenino, el caso clínico de urticaria crónica asociado a la infección por Helicobacter pylori confirmado en dos momentos distintos, con mejora después de la terapéutica antibacteriana. DESCRIPCIÓN DEL CASO: Paciente del sexo femenino, 13 años, buscó atención médica con urticaria crónica y dolores epigástricas sin respuesta al tratamiento medicamentoso. Los exámenes solicitados para investigación complementar se presentaron normales, excepto por la endoscopía digestiva alta con biopsia, que evidenció gastritis crónica activa moderada asociada al Helicobacter pylori. Se inició el tratamiento adecuado para la bacteria en cuestión, y la paciente presentó remisión de los síntomas. Nueva endoscopía digestiva alta para controlar el tratamiento después de nueve meses estaba normal. Tras cinco años, la paciente buscó nuevamente el ambulatorio quejándose de retorno del cuadro de urticaria y dolores epigástricos. Ella estaba en uso de anti-histamínicos, sin mejoría. Fue nuevamente sometida al protocolo de exámenes para investigar urticaria crónica, con resultados dentro de la normalidad. Fue sometida a la endoscopía digestiva alta, que presentó prueba de ureasa positiva. Se inició entonces nuevo tratamiento para Helicobacter pylori por siete días, con desaparición de la urticaria crónica y de los dolores epigástricos. COMENTARIOS: El caso relatado sugiere relación causal entre el diagnóstico positivo para el Helicobacter pylori y la ocurrencia del cuadro de urticaria crónica, con institución de terapéutica eficaz para tal bacteria y remisión de los síntomas. La urticaria crónica es una enfermedad de etiopatogenía compleja y, a pesar de las controversias, las evidencias de la implicación del Helicobacter pylori con enfermedades extraintestinales vienen creciendo, entre ellas la urticaria crónica.

Urticária: diagnóstico e tratamento / Urticaria: diagnosis and treatment

A urticária apresenta-se com diversas formas clínicas e causas distintas. Constitui uma das dermatoses mais frequentes: 15% a 20% da população têm pelo menos um episódio agudo da doença em sua vida. A urticária é classificada do ponto de vista de duração da evolução temporal em aguda (inferior a seis semanas) ou crônica (superior a seis semanas). O tratamento da urticária pode compreender medidas não farmacológicas e intervenções medicamentosas, as quais são agrupadas em tratamentos de primeira (anti-histamínicos), segunda (corticosteróides e antileucotrienos) e terceira linha (medicamentos imunomoduladores). Essa entidade clínica acarreta importante perda na qualidade de vida e deve ser prontamente tratada pelo profissional de saúde.

The urticaria presents itself with diverse clinical forms and distinct causes. It is one of the most common dermatosis: 15% to 20% of the population has at least one acute episode of illness in their life. Urticaria is classified based on its temporal evolution as acute (less than 6 weeks) or chronic (more than 6 weeks). Management strategies may involve nonpharmacological measures and drug interventions, which are grouped into first-(antihistamines), second (corticosteroids and antileukotrienes) and third-line therapies (immunomodulators). This clinical entity has a major loss in quality of life and should be promptly treated by a health professional.

Diagnóstico de urticaria crónica en Guayaquil / Diagnosis of chronic urticaria in Guayaquil

La urticaria crónica es una entidad que se caracteriza por la presencia de ronchas, la mayoría de las veces pruriginosas; los síntomas persisten más de 6 semanas. El diagnóstico etiológico puede demostrarse hasta en un 40% a pesar de una historia clinica y exámenes detallados. En nuestro estudio retrospectivo se incluyeron 161 pacientes que consultaron por urticaria crónica en el servicio de alergia. La etiología más frecuente fue la idiopática (57%) seguida por la urticaria vasculítica (12%). Se observó una alta frecuencia de esta patología en el sexo femenino (76,4%) en comparación con el sexo masculino (23,9%). En cuanto al tratamiento, la gran mayoría de pacientes respondió favorablemente a los antihistamínicos de primera o segunda generación. En cambio, en otros se utilizó terapia combinada con anti-H1 y bloqueantes anti-H2. En un pequeño grupo de pacientes hubo que asociar fármacos como levotiroxina, corticoesteroides, inmunorreguladores, antileucotrienos y gammaglobulina endovenosa.

Urticaria crónica: características, diagnóstico y tratamiento / Cronic urticaria: characteristics, diagnosis and treatment

La urticaria y el angioedema son afecciones dermatológicas frecuentes en la consulta diaria de alergología, son un problema grave de salud ya que hasta en 90 por ciento de los casos no se determina su causa y en un porcentaje similar el resultado del tratamiento es insatisfactorio, tanto para el paciente como para el médico tratante. Con el fin de conocer algunas características de la urticaria crónica en nuestra región, se estudiaron prospectivamente 45 pacientes con esta afección que acudieron a la consulta de alergología del Hospital General Regional y de zona número seis del Instituto Mexicano del Seguro Social de Ciudad Madero, Tamaulipas en un periodo de tiempo determinado. Se incluyeron personas de todas las edades, de ambos sexos. A todos se les realizó historia clínica alergológica completa, una batería completa de exámenes de laboratorio y gabinete complementarios para intentar llegar al diagnóstico etiológico, tratándose a los pacientes en dos grupos con cuatro tipos de antihistamínicos considerados dentro del cuadro básico de la institución. En este estudio se demuestra que la urticaria y el angioedema juntos se presentan con mayor frecuencia (81.25 por ciento), afectando más al sexo femenino (81.25 por ciento) entre los 20 y 39 años de edad; la causa sólo se pudo determinar en 37.77 por ciento de los casos predominando la parasitosis. Llama la atención que en 56.25 por ciento de los mismos había el antecedente de alguna enfermedad alérgica respiratoria no diagnosticada. Se observó una mejor reacción cuando se combinaron dos antihistamínicos HI y aplicó tratamiento específico con inmunoterapia con buenos resultados.

Urticárias agudas e crônicas / Acutes and cronics urticarias

A urticária é uma das condiçöes médicas mais freqüentemente encontrada nos consultórios de alergia, clínica médica e emergências. Ao redor de 20% da populaçäo ao largo já teve urticária uma vez na vida. É mais freqüentemente vista nas mulheres (60% dos casos) na idade de 20/50 anos e muito raramente após a idade de 70 anos. A urticária por si própria näo é uma doença, mas uma síndrome com uma variedade de processo etiológicos. Pode-se apresentar como urticária angiodérmica idiopática, urticária com angioderma mediada por complemento ou uma reaçäo a administraçäo de produtos sangüíneos. É freqüentemente descrita como uma reaçäo com pápula-eritema-edema, localizada ou disseminada na pele e/ou mucosa de curta duraçäo (duas horas, exceto na urticária devido a vasculite que dura três ou quatro dias

Mequitazina no tratamento da urticária crônica / Mequitazina in the treatment of chronic urticaria

A eficácia e a segurança de mequitazina no tratamento de urticária crônica foram avaliadas neste estudo aberto, näo-comparativo, onde 50 pacientes adultos ambulatoriais foram tratados com mequitazina comprimidos de 5 mg duas vezes por dia, por um período de 14 dias. Os pacientes foram avaliados, inicialmente, no 3§, 7§ e 14§ dia de tratamento, procurando-se observar: o estado geral, as características dermatológicas das lesöes, a intensidade dos sintomas, o efeito terapêutico e a ocorrência de efeitos colaterais. Observou-se significativa diminuiçäo na intensidade dos sintomas e na regressäo das lesöes características do quadro (p<0,001). O efeito terapêutico foi considerado como excelente e bom em 98% dos casos, tanto na opiniäo do investigador como na dos pacientes. Os efeitos colaterais observados foram de leve intensidade, näo havendo necessidade de retirar nenhum paciente do estudo. A sonolência foi correlacionada ao tratamento em apenas dois casos (4%). Nossa opiniäo, baseada nos resultados obtidos é que mequitazina é um medicamento eficaz e seguro, passando a ser uma nova opçäo terapêutica para o tratamento da urticária crônica