摘要
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease of the esophagus characterized by symptoms of esophageal dysfunction such as dysphagia, food impaction, and chest pain in adults. It is associated with atopic di- seases such as allergic rhinitis, atopic dermatitis, and asthma. Diagnosis requires symptoms of esophageal dysfunction, eosinophilic inflammation in esophageal biopsies with at least 15 eosinophils per high power field, and exclusion of other causes of local or systemic eosinophilia. EoE is more common in men and has an increasing prevalence, varying globally. The pathophysiology involves TH2-mediated eosinophilic inflammation driven by food antigens, esophageal barrier dysfunction and tissue remodeling. Various therapeutic options aim for clinical and histological remission, including dietary and pharmacological treatments. Dietary therapy, topical corticosteroids and proton pump inhibitors are first-line treatments. Topical corticosteroids achieve high histological remission. Development of new therapies is ongoing. Dupilumab, an antibody against IL-4Rα, shows efficacy in achieving histological and symptomatic remission in patients unresponsive to proton pump inhibitors. Other targeted therapies with clinical trials for EoE include mepolizumab, reslizumab, cendakimab, lirentelimab, and etrasimod with variable clinical and histological results. A subgroup of patients with EoE unresponsive or with bad adherence to first line therapies or patients with multiple comorbid atopic diseases may benefit from biological therapies. This review aims to describe new therapeutic options, detailing their mechanisms, efficacy, and safety profiles.
La esofagitis eosinofílica (EEo) es una enfermedad crónica, inmunomediada del esófago, caracterizada por síntomas de disfunción esofágica como disfagia, impactación y dolor torácico en adultos. Se asocia a otras enfermedades atópicas como rinitis alérgica, dermatitis atópica y asma. El diagnóstico requiere síntomas de disfunción esofágica, inflamación eosinofílica en biopsias de esófago con al menos 15 eosinófilos por campo de aumento mayor, y exclusión de otras causas de eosinofilia local o sistémica. La EEo es más común en hombres y tiene una prevalencia en aumento. La fisiopatología incluye inflamación eosinofílica mediada por una respuesta TH2 gatillada por antígenos alimenticios, además disfunción de barrera esofágica y remodelación de tejido. Varias opciones terapéuticas tienen como objetivo la remisión clínica e histológica, incluyendo terapias dietéticas y tratamientos farmacológicos. La terapia dietética, inhibidores de bomba de protones o corticosteroides tópicos sin terapias de primera línea. Los corticosteroides tópicos alcanzan altas tasas de remisión histológica. El desarrollo de nuevas terapias se está llevando a cabo. Dupilumab, un anticuerpo contra IL-4Rα, muestra eficacia en alcanzar remisión histológica y sintomática en pacientes no responde- dores a inhibidores de bomba de protones. Otras terapias con estudios clínicos para EEo incluyen el mepolizumab, reslizumab, cendakimab, lirentelimab y etrasimod, con resultados variables. Un subgrupo de pacientes con EEo no respondedores o con mala adherencia a terapias de primera línea o con comorbilidades atópicas graves se podrían beneficiar de terapias biológicas como dupilumab. Esta revisión tiene como objetivo describir nuevas opciones tera- péuticas, detallando su mecanismo de acción, eficacia y perfil de seguridad.
Subject(s)
Humans , Male , Female , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Esophagus/pathology , Proton Pump Inhibitors/therapeutic use , Eosinophilic Esophagitis/etiology摘要
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease, induced by food allergens, clinically characterized by symptoms of esophageal dysfunction. Pathologically there is a predominant eosinophilic inflammation. This disease is relatively new, and its definitions have evolved over time. Its prevalence and incidence are increasing and causes clinical problems both in children and adults. Its symptoms include food impaction, dysphagia, symptoms that resemble gastroesophageal reflux, abdominal pain, and vomiting. It can also have extra-digestive symptoms such as rhinosinusitis, chronic cough, recurrent croup and hoarseness. EoE can be associated with other atopic conditions, such as asthma, eczema and food allergies. The diagnosis is made by the analysis of endoscopic biopsies (> 15 eosinophils per high power field). Proton pump inhibitors (PPIs) are currently accepted as a treatment for EoE. The clinical and pathological improvement with the use PPIs ceased to be a criterion to define Esophageal eosinophilia responsive to PPIs as a differential diagnosis, since this condition is currently considered within the EoE spectrum. There are three main treatment approaches for EoE: diet, drugs and dilation. Its diagnosis and early treatment are key to avoid or delay its complications, such as stenosis and severe esophageal dysfunction.
Subject(s)
Humans , Gastroesophageal Reflux , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Proton Pump Inhibitors/therapeutic use摘要
Abstract Objective: The objective of this review is to provide an overview of the practical diagnostic and therapeutic approaches to eosinophilic esophagitis and to increase the visibility of the disease among pediatricians. Sources: A search of the MEDLINE, Embase, and CINAHL databases and recent consensus statements and guidelines were performed. Summary of the findings: The definition of eosinophilic esophagitis is based on symptoms and histology. It is important to rule out other diseases associated with esophageal eosinophil-predominant inflammation. It is not yet clear whether the increased prevalence is due to a real increase in incidence or a result of increased awareness of the disease. Various options for management have been used in pediatric patients, including proton pump inhibitors, dietary restriction therapies, swallowed topical steroids, and endoscopic dilations. More recently, proton pump inhibitor-responsive esophageal eosinophilia and eosinophilic esophagitis have been contemplated on the same spectrum, and proton pump inhibitors should be considered the initial step in the treatment of these patients. Conclusions: Eosinophilic esophagitis is a relatively new disease with a remarkable progression of its incidence and prevalence in the past two to three decades, and diagnostic criteria that are constantly evolving. It is important to better understand the pathogenesis of the disease, the predisposing factors, the natural history, and the categorization of varying phenotypes to develop diagnostic and therapeutic strategies that meet the clinical needs of patients.
Resumo Objetivo: Fornecer uma visão geral do diagnóstico e do tratamento da esofagite eosinofílica na prática clínica e aumentar a visibilidade da doença entre os pediatras. Fontes dos dados: Foi feita uma busca na literatura relevante nos bancos de dados Medline, Embase, CINAHL e consensos e diretrizes recentes foram revisados. Síntese dos dados: A definição de esofagite eosinofílica é baseada nos sintomas e na histologia. É importante excluir outras doenças associadas com inflamação esofágica predominantemente eosinofílica. Ainda não está claro se o aumento na prevalência é devido a um real aumento da incidência ou se é o resultado da maior suspeição diagnóstica. Várias opções para tratamento, inclusive inibidores de bomba de prótons, restrições dietéticas, esteroides tópicos deglutidos e dilatações endoscópicas têm sido usadas em pacientes pediátricos. Mais recentemente a eosinofilia esofágica responsiva a inibidores de bomba de prótons e a esofagite eosinofílica têm sido contempladas no mesmo espectro e os inibidores de bomba de prótons devem ser considerados como opção inicial no tratamento desses pacientes. Conclusões: A esofagite eosinofílica é uma doença relativamente nova com uma notável progressão da incidência e prevalência nas últimas 2-3 décadas e critérios diagnósticos estão em evolução constante. É importante entender melhor a patogênese dessa doença, os fatores predisponentes, a história natural e a categorização dos diferentes fenótipos para desenvolver estratégias diagnósticas e terapêuticas que vão ao encontro das necessidades clínicas dos pacientes.
Subject(s)
Humans , Child , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Esophagoscopy , Dilatation , Proton Pump Inhibitors/therapeutic use , Anti-Inflammatory Agents/therapeutic use摘要
Background: Eosinophilic esophagitis (EE) is a clinicopathologic primary disease of the esophagus, characterized by dense eosinophilic infiltration and it is currently identified as an emerging global entity capable of producing dysphagia and food impaction in adults. Objective: Review of the literature and analysis of the current evidence related to eosinophilic esophagitis in adults. Methods: An electronic search was performed in PubMed to identify relevant literature regarding epidemiology, pathogenesis, clinical presentation, diagnosis, treatment and prognosis of EE. The MeSH terms: Eosinophilic esophagitis AND adults, were used including studies from 1975 to 2012, in English and Spanish written papers. Results: A total of 467 articles were identified in PubMed, where 374 correspond to adults. Eighty percent of the papers were published during the last six years, being mostly case reports or series. Although the pathogenesis is unknown, our review suggests a multifactorial cause, with an altered immune response and genetic component associated to it. At the same time, it was found that adult patients often have a long history of intermittent dysphagia or food impaction. Currently, there is no established consensus for histological diagnosis; however, eosinophilic infiltration of 15 per high power field is accepted. The most commonly used treatment in adults is topical corticosteroids. Although EE is a chronic disease, it does not seem to have a significant impact on morbimortality. Conclusions: Eosinophilic esophagitis is a chronic inflammatory disease with immunoallergic compromise, which requires clinical and histological diagnosis. A multidisciplinary approach to understand its natural history is suggested, thus developing future therapeutic approaches.
Introducción: La esofagitis eosinofílica (EE) es una enfermedad clínico-patológica primaria del esófago, caracterizada por infiltración eosinofílica densa y actualmente identificada como una entidad emergente a nivel mundial, capaz de producir disfagia e impactación alimentaria en adultos. Objetivo: Revisión de la literatura y análisis de la evidencia actual de EE en el adulto. Metodología: Se realizó una búsqueda electrónica en PubMed para identificar literatura relevante sobre epidemiología, patogenia, presentación clínica,diagnóstico, tratamiento y pronóstico. Se utilizaron los términos MeSH: Eosinophilic esophagitis AND adults, incluyendo estudios publicados desde 1975 a 2012, en idiomas inglés y español. Resultados: Un total de 467 artículos se identificaron en PubMed, donde 374 corresponden a adultos. Durante los últimos seis años se publicó el 80 por ciento de ellos, siendo en su mayoría informes de casos o series de casos. Aunque la patogenia es desconocida, la presente revisión sugiere que es multifactorial, con alteración de la respuesta inmune y componente genético. Se encontró que los pacientes adultos presentan frecuentemente una larga historia de disfagia o impactación alimentaria. Actualmente, no existe un consenso establecido para el diagnóstico histológico, sin embargo, la infiltración eosinofílica de 15/campo de gran aumento es aceptada. El tratamiento más comúnmente indicado en adultos son los corticoesteroides tópicos. Aunque la EE es una patología crónica, no parece impactar significativamente la morbimortalidad. Conclusiones: La EE es una enfermedad inflamatoria crónica con compromiso inmunoalérgico, que requiere un diagnóstico clínico e histológico. Se sugiere un enfoque multidisciplinario con el fin de comprender su historia natural, desarrollando así futuros enfoques terapéuticos.
Subject(s)
Humans , Adult , Endoscopy, Digestive System/methods , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/pathology , Eosinophilic Esophagitis/therapy , Review Literature as Topic摘要
Eosinophilic esophagitis is a clinico pathologic entity that has been increasingly recognized over the past two decades. It affects all ages, preferably men, with a history of atopy and is characterized by eating disorders, dysphagia and heartburn. It has elements in common with gastroesophageal reflux disease and the distinction between them can be a challenge for the clinician. It has several typical endoscopic features, such as longitudinal grooves, rings, plaques and stenosis, but none of them is pathognomonic of the disease. The correlation of history, endoscopic and histology are essential for a correct diagnosis. Management includes a period of use of proton pump inhibitors to rule out concomitant reflux disease. Treatment with topical corticosteroids such as fluticasone and budesonide are successful in the short term, but recurrence is common. Some cases may require endoscopic dilatation. Data is still insufficient to establish optimal management at short and long-term, therefore therapeutic decisions should be evaluated on a case-by-case basis.
La esofagitis eosinofílica es una entidad clínico patológica que ha sido reconocida en forma cada vez más frecuente en las últimas dos décadas. Afecta a todas las edades, de preferencia a hombres con antecedentes de atopia y se caracteriza por presentar trastornos alimentarios, disfagia y pirosis. Presenta elementos comunes con la enfermedad por reflujo gastroesofágico y la distinción entre ellas puede ser un desafío para el médico. Tiene varias características endoscópicas típicas, como los surcos longitudinales, anillos, placas y estenosis, pero ninguna de ellas es patognomónica de la enfermedad. La correlación de la historia, imagen endoscópica e histología son imprescindibles para el diagnóstico correcto. El manejo incluye un período de uso de inhibidores de la bomba de protones para descartar una enfermedad por reflujo concomitante. El tratamiento con corticoides tópicos como la fluticasona y budesonida da buenos resultados a corto plazo, pero la recidiva es frecuente. Algunos casos pueden requerir dilatación endoscópica. Faltan datos para establecer un manejo óptimo a corto y largo plazo, por lo que las decisiones terapéuticas deben ser evaluadas caso a caso.