Etiology and Pathogenesis of Idiopathic Achalasia

Abstract

This review examines the etiology and pathogenesis of idiopathic achalasia. This disease is clinically characterized by dysphagia of solids and liquids due to the presence of simultaneous or absent esophageal contractions and impaired or absent relaxation of the lower esophageal sphincter. It includes a review of (a) etiology and pathogenesis of this inflammatory process that damage the ganglion cells of the Auerbach plexus that is limited to the esophagus; (b) genetic abnormalities and polymorphisms associated with this disease that may help explain its heterogeneity expressed by the different motility abnormalities of its phenotypes as well as differences in its clinical progression. These different genetic abnormalities may be responsible for the slow progression of types I or II phenotypes; (c) indirect evidence of viruses present in these patients that may initiate its development; (d) the abnormalities of the muscle layer that may be responsible for the dilation of the body of the esophagus that ultimately causes the sigmoid-like esophagus in the very last phase of this disease. This progression to the end-stage phase tends to occur in about 5% of patients. And, (e) the chronic inflammatory abnormalities in the squamous mucosa that may be the cause of the dysplastic and neoplastic changes that may lead to squamous cell carcinoma whose incidence in this disease is increased. These mucosal abnormalities are usually present in patients with markedly dilated body of the esophagus and severe food stasis.

Differences between idiopathic and chagasic achalasia

“…The etiology of achalasia is unknown in most cases around the world, and may be multifactorial, including autoimmune, genetic and viral factors [2] . In idiopathic achalasia, there are evidences of autoimmune, genetic and viral etiology, due to the presence of specific autoantibodies associated with neuronal damage, occasional incidence in members of the same family, and presence of previous viral infection in these patients [2] .…”

“…In idiopathic achalasia, there are evidences of autoimmune, genetic and viral etiology, due to the presence of specific autoantibodies associated with neuronal damage, occasional incidence in members of the same family, and presence of previous viral infection in these patients [2] . The disease occurs with an annual incidence of 1 in 100,000 and a prevalence of 10 in 100,000 [4] .…”

“…This parasitic infection is the cause of Chagas' disease, and is characterized by myenteric inflammation, absent myenteric ganglion cells and myenteric neural fibrosis. These lesions are restricted to the esophagus in idiophatic achalasia [2] , and may be seen in all digestive tract in Chagas' disease [5,6,9,10] . In Latin America Chagas' disease has an incidence from 1,000 in 100,000 to 4,000 in 100,000, however the number is decreasing, as 18 million in 1991 to 5.7 million in 2010 [9] .…”

“…Achalasia is a disease characterized by absent or partial relaxation of the lower esophageal sphincter, absence of peristaltic esophageal contraction, food retention and esophageal dilation [1,2] .…”

Laparoscopic Heller Myotomy: A Fundoplication Is Necessary to Control Gastroesophageal Reflux

“…5,6 The most common form of achalasia is idiopathic. 7,8 The pathophysiology of achalasia is due to a defect on the esophageal myenteric plexus (Auerbach's plexus) that contains parasympathetic and sympathetic fibers and supplies both the circular and longitudinal muscle layers with motor innervation. Because of a degeneration on the inhibitory nerves, both esophageal peristalsis and LES relaxation are severely affected.…”