Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Effect of topical corticosteroids on nasal patency after acute positive airway pressure exposure / Efeito dos corticosteroides tópicos na patência nasal após exposição aguda à pressão positiva nas vias aéreas

Abstract Introduction Nasal congestion and obstruction are reported in the majority of continuous positive airway pressure users and are frequently cited as reasons for noncompliance. Baseline inflammation due to allergic rhinitis could increase or exacerbate the inflammatory effect of high airflow in the nasal cavity as the result of continuous positive airway pressure and lead to greater continuous positive airway pressure intolerance. In this setting, intranasal steroids would be expected to counteract the nasal inflammation caused by allergic rhinitis and/or continuous positive airway pressure. Objective The aim of the present study is to evaluate the effects of topical corticosteroid use on nasal patency after acute exposure to positive pressure. Methods Ten individuals with allergic rhinitis were exposed to 1 h of continuous airway pressure (15 cm H2O) in the nasal cavity, delivered by a continuous positive airway pressure device. Visual analog scale, nasal obstruction symptom evaluation scale, acoustic rhinometry and peak nasal inspiratory flow were performed before and after the intervention. After 4 weeks topical nasal steroid (budesonide) application, positive pressure exposure was repeated as well as the first assessments. Results Patients reported a statistically significant improvement both on the visual analog (p = 0.013) and obstruction symptom evaluation scales (p < 0.01). Furthermore, objective measurements were improved as well, with increased nasal cavity volume on acoustic rhinometry (p = 0.02) and increased peak nasal inspiratory flow (p = 0.012), after corticosteroid treatment. Conclusion In patients with allergic rhinitis, intranasal corticosteroid therapy improved objective and subjective parameters of nasal patency after acute exposure of the nasal cavity to positive pressure.

Resumo Introdução Congestão e obstrução nasais são relatadas na maioria dos usuários de pressão positiva contínua nas vias aéreas e são frequentemente mencionadas como razões para a falta de aderência. A inflamação basal devida à rinite alérgica pode aumentar ou agravar o efeito inflamatório do alto fluxo de ar na cavidade nasal como resultado da pressão positiva contínua nas vias aéreas e aumentar a intolerância à mesma. Nesse cenário, espera-se que os esteróides intranasais neutralizem a inflamação nasal causada pela rinite alérgica e/ou pela pressão positiva contínua nas vias aéreas. Objetivo Avaliar os efeitos do uso tópico de corticosteroides na patência nasal após exposição aguda à pressão positiva. Métodos Dez indivíduos com rinite alérgica foram expostos a uma hora de pressão contínua nas vias aéreas (15 cm H2O) na cavidade nasal, fornecida por um dispositivo de pressão positiva contínua nas vias aéreas. A escala visual analógica, a escala Nasal Obstruction Symptom Evaluation, rinometria acústica e pico de fluxo inspiratório nasal foram aplicados antes e após a intervenção. Após 4 semanas de aplicação tópica de esteroide nasal (budesonida), a exposição positiva à pressão foi repetida, bem como as primeiras avaliações. Resultados Os pacientes relataram uma melhoria estatisticamente significante tanto na escala visual analógica (p = 0,013) quanto na escala Nasal Obstruction Symptom Evaluation (p < 0,01). Além disso, as medidas objetivas também foram melhoradas, com aumento do volume da cavidade nasal na rinometria acústica (p = 0,02) e aumento do pico de fluxo inspiratório nasal (p = 0,012), após o tratamento com corticosteroide. Conclusão Em pacientes com rinite alérgica, a terapia com corticosteroide intranasal melhorou os parâmetros objetivos e subjetivos da patência nasal após exposição aguda da cavidade nasal à pressão positiva.

Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels / Tratamento individualizado para a rinite alérgica baseado nas principais manifestações clínicas nasais e dos níveis de histamina e leucotrieno D4

Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

The efficacy and safety of ciclesonide for the treatment of perennial allergic rhinitis: a systematic review and meta-analysis / Eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene: uma revisão sistemática e metanálise

Abstract Introduction: Allergic rhinitis is a chronic inflammatory disease which affects 1 out of 6 individuals. Perennial allergic rhinitis accounts for 40% of AR cases. Ciclesonide is one of the relatively new intranasal steroid for allergic rhinitis. Objective: The purpose of this study was to evaluate the efficacy and safety of ciclesonide in the treatment of perennial allergic rhinitis. Methods: We searched Pubmed, Scientific Citation Index, Embase, Clinical Trial Registries for randomized controlled trials and Cochrane Central Register of Controlled Trials to find out the randomized controlled Trial comparing ciclesonide with placebo for PAR. Results: Eight studies were included. In comparison with placebo groups, ciclesonide groups significantly decreased Reflective Total Nasal Symptom Score (MD = −0.56; 95% CI −0.72 to 0.39, p < 0.00001) with heterogeneity (p = 0.19, I2 = 24%), Instantaneous Total Nasal Symptom Score (MD = −0.57; 95% CI −0.75 to −0.39, p < 0.00001) with heterogeneity (p = 0.34, I2 = 11%). A significant effect for Reflective Nasal Symptom Score Subtotal (MD = −0.15; 95% CI −0.18 to −0.13, p < 0.00001) with heterogeneity (p = 0.12, I2 = 24%) was also demonstrated. Rhinoconjunctivitis quality of life questionnaire score (RQLQs) (MD = −0.27; 95% CI −0.39 to −0.15, p < 0.00001) with heterogeneity (p = 0.58, I 2 = 0%) in the treatment of ciclesonide was also significantly reduced. In addition, the difference in Treatment-Emergent Adverse Events between the two groups was not significant. Conclusion: Ciclesonide can improve perennial allergic rhinitis without increasing adverse events. Ciclesonide may be another valuable choice for perennial allergic rhinitis in the future.

Resumo Introdução: A rinite alérgica é uma doença inflamatória crônica que afeta um a cada seis indivíduos. A rinite alérgica perene é responsável por 40% dos casos de rinite alérgica. A ciclesonida é um dos corticosteroides intranasais mais novos para o tratamento dessa condição clínica. Objetivo: Avaliar a eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene. Método: Uma busca foi feita nos bancos de dados Pubmed, Scientific Citation Index, Embase e Clinical Trial Registries por ensaios clínicos randomizados e Cochrane Central Register of Controlled Trials por estudos controlados randomizados que comparassem ciclesonida com placebo no tratamento da rinite alérgica perene. Resultados: Oito estudos foram incluídos. Em comparação com os grupos placebo, os grupos ciclesonida mostraram diminuição significante no escore do Reflective Total Nasal Symptom Score (DM = −0,56; IC 95%: −0,72 a −0,39, p < 0,00001) com heterogeneidade (p = 0,19, I2 = 24%), do Instantaneous Total Nasal Symptom Score (DM = −0,57; IC95%: −0,75 a −0,39, p < 0,00001) com heterogeneidade (p = 0,34, I2 = 11%). Um efeito significante no escore do Reflective Nasal Symptom Score Subtotal (DM = −0,15; IC 95%: −0,18 a −0,13, p < 0,00001) com heterogeneidade (p = 0,12, I2 = 24%) também foi demonstrado. O escore do Rhinoconjunctivitis Quality of Life Questionnaire score (RQLQs) (DM = −0,27; IC 95%: −0,39 a −0,15, p < 0,00001) com heterogeneidade (p = 0,58, I2 = 0%) também foi significantemente reduzido no tratamento com ciclesonida. Além disso, a diferença em relação aos eventos adversos emergentes do tratamento entre os dois grupos não foi significante. Conclusão: A ciclesonida pode melhorar a rinite alérgica perene sem aumentar os eventos adversos. Esse fármaco pode ser outra opção valiosa para a rinite alérgica perene no futuro.

Incapacitating solar urticaria: successful treatment with omalizumab

Abstract: Solar urticaria is a rare form of physical urticaria mediated by immunoglobulin E. The lesions appear immediately after the sun exposure, interfering with the patient's normal daily life. Omalizumab, a monoclonal anti-IgE antibody, has been recently approved for the treatment of chronic spontaneous urticaria, and the latest reports support its role also in the treatment of solar urticaria. Hereby, we report a case of solar urticaria refractory to conventional treatment strategies, with an excellent response to treatment with omalizumab and phototesting normalization.

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.

Omalizumab para la rinosinusitis crónica / Omalizumab for chronic rhinosinusitis

Resumen INTRODUCCIÓN: La rinosinusitis crónica es una enfermedad inflamatoria crónica de alta prevalencia que compromete la mucosa de la cavidad nasal y senos paranasales. La inmunoglobulina E es un mediador inflamatorio que juega un rol etiopatogénico en esta condición, por lo que se ha planteado que omalizumab, un anticuerpo monoclonal anti-inmunoglobulina E, podría constituir una alternativa de tratamiento. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyeron cinco estudios primarios, de los cuales dos corresponden a ensayos controlados aleatorizados. Concluimos que en pacientes con rinosinusitis crónica, no está claro si omalizumab lleva a una mejoría en la escala de pólipos nasales, la calidad de vida, el bienestar general o los síntomas nasales porque la certeza de la evidencia es muy baja. Por otra parte, el uso de omalizumab probablemente se asocia a efectos adversos frecuentes.

Abstract INTRODUCTION: Chronic rhinosinusitis is a high prevalence chronic inflammatory disease that involves nasal mucosa and paranasal sinuses. Immunoglobulin E is an inflammatory mediator that plays an etiopathogenic role in this condition, so omalizumab, an anti-immunoglobulin E monoclonal antibody, might be a therapeutic alternative. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified five systematic reviews that included five primary studies overall, of which two correspond to randomized trials. We concluded it is not clear whether omalizumab leads to an improvement in the nasal polyps scale, quality of life, general well-being or nasal symptoms in patients with chronic rhinosinusitis, because the certainty of the evidence is very low. On the other hand, omalizumab is probably associated with frequent adverse effects.

Mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis: a non-inferiority study (PUMA) / Furoato de mometasona no tratamento de rinite alérgica persistente leve, moderada ou grave: estudo de não inferioridade (PUMA)

ABSTRACT INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.

Resumo Introdução: A rinite alérgica é considerada a doença respiratória mais prevalente no Brasil e em todo o mundo, com grande impacto na qualidade de vida; além de, afetar a vida social, o sono e também o desempenho na escola e no trabalho. Objetivo: Comparar a eficácia e segurança de duas formulações contendo furoato de mometasona no tratamento da rinite alérgica persistente leve, moderada ou grave por um período de quatro semanas. Método: Trata-se de um estudo nacional aberto de fase III, randomizado, de não inferioridade de comparação do furoato de mometasona em duas apresentações (medicação de controle e fármaco sob investigação). O ponto final primário foi o percentual de pacientes com redução mínima de 0,55 no escore de índice nasal (EIN) após quatro semanas de tratamento. Os desfechos secundários foram: escore NIS total após 4 e 12 semanas de tratamento; escores individuais para sintomas de obstrução nasal, rinorréia, espirros e prurido nasal, bem como escores para prurido, lacrimejamento e hiperemia conjuntival após 4 e 12 semanas de tratamento. O estudo foi registrado em clinicaltrials.gov com o número de referência NCT01372865. Resultados: A análise de eficácia primária demonstrou não inferioridade do fármaco sob investigação em relação à medicação de controle, visto que o limite superior do intervalo de confiança (IC) de 95% para a diferença entre os percentuais de sucesso após quatro semanas de tratamento (12,6%) situava-se abaixo da margem de não inferioridade proporcionada durante a determinação do tamanho da amostra (13,7%). Eventos adversos foram pouco frequentes e de leve intensidade na maioria dos casos. Conclusão: A eficácia e a segurança de um fármaco experimental no tratamento da rinite alérgica persistente foram similares às do produto de referência, o que demonstrou sua não inferioridade.

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.

Effects of Punica granatum on milk-induced leucocytosis and eosinophilia in mice / Efecto de Punica granatum en ratas con leucocitosis y eosinofilia inducida por leche

Punica granatum Linn. (Punicaceae) commonly known as Pomegranate is a dark greenish large deciduous shrub or small tree, about 5-10 m height. Flower buds are traditionally used in the treatment of asthma and allergy. The aim of this study was to validate the traditional antiallergic property using milk-induced leucocytosis and milk-induced eosinophilia in rats. Flower buds of the plant were extracted successively using various solvents to obtain the respective extracts. These extracts were administered to mice at the dose of 50 and 100 mg/kg, orally. Only the ethanol extract showed significant reduction in leukocyte and eosinophil count, these results are a validation of the use of the extract of polar compounds of P. granatum flower buds as an antiallergic agent.

Punica granatum Linn. (Punicaceae) comúnmente conocida como granada es un pequeño árbol o arbusto grande de hoja caduca, de unos 50-10 m de altura y de color verde oscuro. Los botones florales se utilizan tradicionalmente en el tratamiento del asma y la alergia. El objetivo de este estudio fue validar la propiedad tradicional antialérgica utilizando ratas con leucocitosis y eosinofilia inducida por leche. Los botones florales de la planta se extrajeron sucesivamente con varios solventes para obtener los extractos respectivos. Estos extractos se administraron a los ratones a dosis de 50 y 100 mg / kg, por vía oral. Sólo el extracto obtenido con etanol mostró una reducción significativa en el recuento de leucocitos y eosinófilos, estos resultados son una validación del uso del extracto de compuestos polares de los botones florales de P. granatum como un agente antialérgico.

Anaphylaxis in Latin America: a report of the online Latin American survey on anaphylaxis (OLASA)

OBJECTIVES: The aims of the Online Latin American Survey of Anaphylaxis (OLASA) were to identify the main clinical manifestations, triggers, and treatments of severe allergic reactions in patients who were seen by allergists from July 2008 to June 2010 in 15 Latin American countries and Portugal (n =634). RESULTS: Of all patients, 68.5 percent were older than 18 years, 41.6 percent were male, and 65.4 percent experienced the allergic reaction at home. The etiologic agent was identified in 87.4 percent of cases and predominantly consisted of drugs (31.2 percent), foods (23.3 percent), and insect stings (14.9 percent). The main symptom categories observed during the acute episodes were cutaneous (94.0 percent) and respiratory (79.0 percent). The majority of patients (71.6 percent) were treated initially by a physician (office/emergency room) within the first hour after the reaction occurred (60.2 percent), and 43.5 percent recovered in the first hour after treatment. Most patients were treated in an emergency setting, but only 37.3 percent received parenteral epinephrine alone or associated with other medication. However, 80.5 percent and 70.2 percent were treated with corticosteroids or antihistamines (alone or in association), respectively. A total of 12.9 percent of the patients underwent reanimation maneuvers, and 15.2 percent were hospitalized. Only 5.8 percent of the patients returned to the emergency room after discharge, with 21.7 percent returning in the first 6 hours after initial treatment. CONCLUSION: The main clinical manifestations of severe allergic reactions were cutaneous. The etiologic agents that were identified as causing these acute episodes differed according to age group. Following in order: drugs (31.2 percent), foods (23.3 percent and insect stings (14.9 percent) in adults with foods predominance in children. Treatment provided for acute anaphylactic reactions was not appropriate. It is necessary to improve educational programs in order to enhance the knowledge on this potentially fatal emergency.

Evaluation of anti-allergic activity of gossypin and suramin in mast cell-mediated allergy model.

The mast cell-mediated allergic reactions are involved in many allergic diseases, such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells initiates the process of degranulation, resulting in the release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of gossypin (a biflavonoid) and suramin (a synthetic polysulphonated naphtylurea) on the mast cell-mediated allergy model, and studied the possible mechanism of their action. Both gossypin and suramin inhibited (P<0.001) compound 48/80-induced systemic anaphylaxis reactions, antiprurities (P<0.001) and reduced the histamine release in rats. Further, both showed significant (P<0.001) protection against rat peritoneal mast cells activated by compound 48/80. Thus, our findings provide evidence that gossypin and suramin inhibit mast cell-derived allergic reactions.

Xerostomía y uso de medicamentos en adultos / Xerostomia and the use of drugs in adults

OBJETIVO: determinar la prevalencia de xerostomía en relación con el uso de medicamentos en los adultos de 20 años y más del Consultorio Médico 64-02 de Guanabacoa, de julio a diciembre del año 2007. MÉTODOS: se realizó un estudio descriptivo y se utilizó muestreo bietápico. La presencia de xerostomía, basada en definición utilizada por otros autores, se determinó con 3 preguntas, además: edad, sexo, uso, cantidad y tipos de medicamentos, según cuestionario. RESULTADOS: se procesó la información en Excel, utilizando el porcentaje para resumirla. Los resultados se presentan en tablas. Se relacionaron las variables, con la X² y diferencia de proporciones (p<0,05), con el programa Epidat. De 511 individuos estudiados, 176 (34,4 por ciento) percibieron xerostomía. El sexo femenino fue el más afectado, se incrementa con la edad, fue mayor en el grupo de 60 años y más. CONCLUSIONES: los medicamentos más utilizados fueron: antihipertensivos y antiasmáticos. Todos los que usaron hipoglicemiantes y antialérgicos, percibieron xerostomia, y se incrementó según el número de medicamentos usados(AU)

OBJECTIVE: to determine the prevalence of xerostomia in connection with the use of drugs in adults aged 20 and over at the Family Physician's office 64-02 in Guanabacoa from July to December 2007. METHODS: a descriptive study was undertaken and a bistage sampling was used. The presence of xerostomia based on the definition used by other authors was determined by 3 questions in addition to age, sex, use, amount and type of drugs according to the questionnaire. RESULTS: the information was processed in Excel, using percentage to resume it. The results were presented in tables. The variables were related to X2 and the difference of proportions (p<0.05) by using the Epidat program. Of 511 studied individuals, 176 (34.4 percent) perceived xerostomia. Females were the most affected. It increases with age, and the group aged 60 and over was the most affected. CONCLUSIONS: the most used drugs were the antihypertensive and antiasthma drugs. All those who took glycemia-lowering and antiallergic drugs perceived xerostomia and it rose according to the number of drugs used(AU)

Colitis eosinofílica: a propósito de 3 casos y revisión de la literatura / Eosinophilic colitis: report of three cases and literature review

Introducción: Existen afecciones inflamatorias que afectan el colon en forma infrecuente, con amplia variedad en su presentación clínica. Entre ellas, las colitis colágena, indeterminadas, infecciosas, císticas y eosinofílicas, entre otras. La colitis eosinofílica es una enfermedad crónica inflamatoria de etiología desconocida caracterizada por la infiltración masiva de eosinófilos en un segmento del tubo digestivo. Objetivo: Analizar los hallazgos clínicos, histológicos y terapéuticos asociados a la colitis eosinofílica. Diseño: Presentación de casos. Revisión de la literatura. Métodos: Revisión de registros en bases MEDLINE, LILACS y registros de AMA. Pacientes: Se analizaron 3 casos de presentación en los últimos 12 meses. Resultados: Caso 1: femenino, 40 años, dolor abdominal cólico y diarrea. Tomografía Computada: engrosamiento de colon derecho. Colonoscopía: colitis localizada en colon derecho con enantema, congestión sin ulceras. Parasitológico negativo. Caso 2: femenino 26 años, diarrea severa con deshidratación. Parasitológico positivo. Tratamiento con metronidazol sin respuesta. Colonoscopía: pancolitis moderada. Inicia tratamiento con corticoides. Caso 3: femenino 33 años, diarrea, pujo y tenesmo. Perdida de peso. VEDA normal. Colon por enema: dolicocolon. Colonoscopía: tiflitis con ileon normal. Parasitológico negativo. Tratamiento con mesalazina con buena respuesta. Todos tuvieron eosinofilia mayor al 8%. Todas las biopsias fueron del colon derecho y revelaron colitis crónica eosinofílica. Conclusiones: El diagnóstico definitivo es de necesidad para diferenciarlas de enfermedades inflamatorias del colon mediante colonoscopía y biopsia (en especial Enfermedad de Crohn). El tratamiento es sintomático y comprende una variedad de drogas (ketotifeno, corticoides, antihistamínicos, metronidazol, etc.)... (TRUNCADO)

Introduction: There is uncommon colitis with unfrequented presentation. Eosinophilic colitis is an inflammatory chronic bowel disease with unknown etiology. Objective: To evaluate clinical, histological and therapeutic findings and differential diagnosis of chronic eosinophilic colitis. Design: Case report and literature review. Patients: To analyze 3 cases in last 12 months. Results: Case 1: female, 40y, abdominal pain and diarrhea. CT: right colon involvement. Endoscopy: unspecific colitis. Positive Biopsy and negative parasitologic exam. Case 2: female, 26y, severe diarrhea, dehidratation. Positive parasitologic exam. Treatment with metronidazole without reponse. Endoscopy: mild pancolitis with positive biopsy. Treatment with steroids is instaured. Case 3: female, 33y, diarrhea and tenesmus, lost of weight. Upper endoscopy normal, lower endoscopy: cecal inflamation with positive biopsy. Negative parasitologic exam. All patients presented elevated blood eosinophilia and the biopsy were taken from right colon. Conclusions: Symptomatic treatment should be instituted with several drugs according to literature, steroids seems to be the better choice, but with secondary effects. Differential diagnosis should be done always, principally with Crohn’s disease. Current allergic exposition plus environment contamination could represent the physiopathology in some of these cases.

Tratamiento de la rinitis alérgica en la embarazada / Treatment of allergic rhinitis during pregnancy

El tratamiento de la rinitis alérgica (RA) en la paciente embarazada se ve obstaculizado por el temor que el especialista experimenta al intentar utilizar medicamentos que podrían provocar problemas en el desarrollo del feto. Este dilema es especialmente acentuado cuando la embarazada está en sus primeros meses de embarazo. Sin embargo, la persistencia de síntomas y las molestias que la rinitis alérgica le ocasiona a la paciente coloca al especialista en una disyuntiva importante: cómo tratar a la enferma sin provocar daños en el niño en gestación. La FDA ha clasificado los medicamentos que en estos casos pueden utilizarse y el metaanálisis de estudios realizados en embarazadas avala la prescripción de los fármacos que aquí se aconsejan. Es factible, además, realizar algunos procedimientos quirúrgicos durante el embarazo sin que ello involucre riesgo en la paciente ni en el feto.

Rinite alérgica: diagnóstico e tratamento / Alergic rhinitis: diagnosis and treatment

A rinite alérgica é uma doença crônica cujos sintomas variam quanto à freqüêncai e à severidade. Está presente em crianças e adultos, geralmente diminuindo a qualidade de vida. O diagnóstico depende de uma história clínica minuciosa, apoiada no exame físico e nos exames complementares. O tratamento é complexo, pois inclui medidas educativas, controle do ambiente, medicamentos diversos e, em alguns casos, imunoterapia específica e cirurgia. Esta revisão pretende abordar de forma prática como diagnosticar, classificar e tratar a rinite alérgica.