New insights into the pathophysiology of achalasia and implications for future treatment.
New insights into the pathophysiology of achalasia and implications for future treatment.
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DOI：
10.3748/wjg.v22.i35.7892
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发表时间：
2016-09-21
影响因子：
4.3
通讯作者：
Torres-Villalobos G
中科院分区：
文献类型：
--
作者：
Furuzawa-Carballeda J;Torres-Landa S;Valdovinos MÁ;Coss-Adame E;Martín Del Campo LA;Torres-Villalobos G
特发性贲门失弛缓症是一种典型的食管运动障碍，导致进食能力明显受损，生活质量下降。这种情况的病理生理基础是食管扩张的丧失和下食管括约肌（LES）松弛不足。临床表现包括固体和液体吞咽困难、食管内容物反流、胸骨后胸痛、咳嗽、误吸、体重减轻和胃灼热。尽管特发性贲门失弛缓症在300多年前首次被描述，但研究人员现在才开始解开其复杂的病因和分子病理学。最新的研究结果表明，存在自身免疫成分，如循环抗肌间神经丛自身抗体的存在，和遗传易感性，如观察到的与其他明确的遗传综合征，如Allgrove综合征和多发性内分泌瘤2型B综合征的相关性。病毒因子（疱疹、水痘带状疱疹）也被认为是致病和促进因素。不幸的是，今天可用的治疗方法不能解决疾病的原因，并且仅针对所涉及的组织的相应变化，例如LES的破坏，而不是恢复或改变潜在的病理学。新的治疗方法应该旨在在早期阶段阻止疾病，从而防止随之而来的变化发展并抑制永久性损害。本文综述了特发性贲门失弛缓症的已知特征，这将有助于促进对其发病机制的理解，并改善治疗管理，以积极影响患者的生活质量。
Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient’s quality of life.