Pathogenesis of Achalasia

ABSTRACT

Achalasia is a rare esophageal motilty disorder characterized by loss of myenteric neurons leading to aperistalsis of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES). Esophageal peristalsis and relaxation of the LES are mediated by myenteric neurons. Achalasia may be an autoimmune disease targeting esophageal myenteric neurons with cell-mediated and antibody-mediated attack to an unidentified antigen. It is still unknown how these immunologic attacks begin and why these are functionally limited to the esophagus. Initial immunologic reactions can begin in genetically predisposed persons who had viral infection, such as herpes simplex virus 1. The type of immune response and the intensity of the cytotoxic T-cell attack can determine the clinical presentation of the disease. Patients with Chicago Classification type III achalasia may present with chronic inflammation in the absence of neuronal loss, where as patients with Chicago Classification type I or II achalasia present with a predominantly cytotoxic immune response with progressive loss of myenteric neurons. Further well controlled researches which reveal the unknown facts of pathogenesis are needed.