Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2016; 22(35): 7892-7907
Published online Sep 21, 2016. doi: 10.3748/wjg.v22.i35.7892
New insights into the pathophysiology of achalasia and implications for future treatment
Janette Furuzawa-Carballeda, Samuel Torres-Landa, Miguel Ángel Valdovinos, Enrique Coss-Adame, Luis A Martín del Campo, Gonzalo Torres-Villalobos
Janette Furuzawa-Carballeda, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, CP 14080, Mexico
Samuel Torres-Landa, Luis A Martín del Campo, Gonzalo Torres-Villalobos, Department of Experimental Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, CP 14080, Mexico
Miguel Ángel Valdovinos, Enrique Coss-Adame, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, CP 14080, Mexico
Author contributions: Furuzawa-Carballeda J, Torres-Landa S, Valdovinos MA, Coss-Adame E, Martín del Campo LA and Torres-Villalobos G performed the study, and drafted and reviewed the manuscript.
Conflict-of-interest statement: The authors report no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Gonzalo Torres-Villalobos, MD, PhD, Department of Experimental Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, Mexico City, CP 14080, Mexico.
Telephone: +52-55-54070900-2501 Fax: +52-55-55732096
Received: April 1, 2016
Peer-review started: April 6, 2016
First decision: June 20, 2016
Revised: July 6, 2016
Accepted: August 5, 2016
Article in press: August 5, 2016
Published online: September 21, 2016

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.

Keywords: Achalasia, Treatment, Autoimmune disease, Pathophysiology

Core tip: Primary achalasia is associated with loss of ganglion cells in the esophagus and in the lower esophageal sphincter. In the last decade, achalasia pathophysiology has been widely studied, and investigations have aimed to expand clinical management beyond mere treatment of symptoms and towards attacking the specific cause of the disease. While the etiologies remain unclear and no cure exists, the most recent findings suggest an interaction between autoimmune and inflammatory responses, possibly triggered by viral infection, in genetically susceptible individuals. This article reviews the recent advances in understanding the disease pathogenesis with implications for improving therapeutic management.