Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Clin Gastroenterol Hepatol. 2020 Apr;18(4):767-776. doi: 10.1016/j.cgh.2019.07.015. Epub 2019 Jul 15.
Gastroesophageal reflux disease (GERD) is now one of the most common diagnoses made in a gastroenterology practice. From a conventional pathophysiological perspective, GERD is conceptualized as incompetence of the antireflux barrier at the esophagogastric junction; the more severe that incompetence, the worse the disease. However, it is increasingly clear that many presentations of GERD represent distinct phenotypes with unique predisposing cofactors and pathophysiology outside of this paradigm. Three major consensus initiatives have grappled with this dilemma (the Montreal Consensus, The Rome Foundation, and the Lyon Consensus), each from a different perspective. Montreal struggled to define the disease, Rome sought to characterize its functional attributes, while Lyon examined its physiological attributes. Here, we merge the 3 perspectives, developing the concept that what has come to be known as GERD is actually a family of syndromes with a complex matrix of contributing pathophysiology. A corollary to this is that the concept of one size fits all to therapeutics does not apply, and that although escalating treatment with proton pump inhibitors (PPIs) may be pertinent to healing esophagitis, its applicability beyond that is highly questionable. Similarly, failing to recognize the modulating effects of anxiety, hypervigilance, and visceral and central hypersensitivity on symptom severity has greatly oversimplified the problem. That oversimplification has led to excessive use of PPIs for everything captured under the GERD umbrella and shown a broad spectrum of syndromes less amenable to PPI therapy in any dose. It is with this in mind that we delineate this precision medicine concept of GERD.
胃食管反流病(GERD)现在是消化科最常见的诊断之一。从传统的病理生理学角度来看,GERD 被认为是食管胃交界处的抗反流屏障功能不全;这种功能不全越严重,疾病越严重。然而,越来越明显的是,GERD 的许多表现代表了独特的表型,具有独特的易患因素和该范式之外的病理生理学。三项主要的共识倡议已经在努力解决这一困境(蒙特利尔共识、罗马基金会和里昂共识),它们各自从不同的角度来看待这个问题。蒙特利尔努力定义疾病,罗马试图描述其功能属性,而里昂则检查其生理属性。在这里,我们合并了这三个视角,提出了一个概念,即所谓的 GERD 实际上是一组综合征,其病理生理学有一个复杂的矩阵。这一概念的推论是,一种治疗方法适合所有情况的概念并不适用,虽然用质子泵抑制剂(PPI)升级治疗可能与食管炎的愈合有关,但超出这个范围的适用性是非常值得怀疑的。同样,未能认识到焦虑、过度警觉以及内脏和中枢敏感性对症状严重程度的调节作用,大大简化了这个问题。这种简化导致了 PPI 被过度用于 GERD 伞状下的所有疾病,并显示出广泛的综合征对任何剂量的 PPI 治疗都不太有效。正是基于这一点,我们阐述了 GERD 的精准医疗概念。