Rothenberg Marc E
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Gastroenterology. 2015 May;148(6):1143-57. doi: 10.1053/j.gastro.2015.02.002. Epub 2015 Feb 7.
Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE, particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells. Susceptibility has been associated with variants at 5q22 (TSLP) and 2p23 (CAPN14), indicating roles for allergic sensitization and esophageal specific protease pathways. We propose that EoE is a unique disease characterized by food hypersensitivity; strong hereditability influenced by early-life exposures and esophageal-specific genetic risk variants; and allergic inflammation and that the disease is remitted by disrupting inflammatory and T-helper type 2 cytokine-mediated responses and through dietary elimination therapy.
嗜酸性粒细胞性食管炎(EoE)在历史上是根据组织学以及对抑酸治疗无反应与胃食管反流病相区分的,但现在人们认识到食管嗜酸性粒细胞增多可对质子泵抑制剂产生反应。遗传和环境因素会增加患EoE的风险,尤其是早期生活事件。疾病发病机制涉及上皮炎症途径的激活(嗜酸性粒细胞趋化因子-3[由CCL26编码]的产生)、屏障功能受损(由桥粒芯糖蛋白-1缺失介导)、转化生长因子-β的产生和/或活性增加,以及嗜酸性粒细胞和肥大细胞诱导的过敏性炎症。易感性与5q22(TSLP)和2p23(CAPN14)的变异有关,表明过敏致敏和食管特异性蛋白酶途径发挥了作用。我们提出,EoE是一种独特的疾病,其特征为食物超敏反应;受早期生活暴露和食管特异性遗传风险变异影响的强遗传性;以及过敏性炎症,并且该疾病可通过破坏炎症和2型辅助性T细胞细胞因子介导的反应以及通过饮食排除疗法得到缓解。