Etiology and Pathogenesis of Achalasia: The Current Understanding

Department of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
The American Journal of Gastroenterology (Impact Factor: 10.76). 07/2005; 100(6):1404-14. DOI: 10.1111/j.1572-0241.2005.41775.x
Source: PubMed


Idiopathic achalasia is an inflammatory disease of unknown etiology characterized by esophageal aperistalsis and failure of LES relaxation due to loss of inhibitory nitrinergic neurons in the esophageal myenteric plexus. Proposed causes of achalasia include gastroesophageal junction obstruction, neuronal degeneration, viral infection, genetic inheritance, and autoimmune disease. Current evidence suggests that the initial insult to the esophagus, perhaps a viral infection or some other environmental factor, results in myenteric plexus inflammation. The inflammation then leads to an autoimmune response in a susceptible population who may be genetically predisposed. Subsequently, chronic inflammation leads to destruction of the inhibitory myenteric ganglion cells resulting in the clinical syndrome of idiopathic achalasia. Further studies are needed to better understand the etiology and pathogenesis of achalasia-such an understanding will be important in developing safe, effective, and possibly curative therapy for achalasia.

69 Reads
  • Source
    • "While the etiology of achalasia is not completely understood, the disorder features a loss of ganglion cells in the myenteric plexus of the esophagus, which is speculated to be caused by an inflammatory or neurodegenerative process. It has also been suggested that a viral infection or an autoimmune response may be responsible for the development of achalasia (1, 2). The global prevalence of achalasia is approximately 10/100,000 and its incidence is less than 1/100,000/yr (2). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Owing to the rarity of the disease, epidemiologic information on achalasia is limited. This study aimed to investigate the epidemiology and treatment patterns of achalasia in the population of Korea using a national healthcare database. The diagnostic code K22.0 of the International Classification of Diseases was used to identify cases of achalasia between 2007 and 2011. Treatment modalities for achalasia were identified using the electronic data interchange codes Q7642 or Q7641 for balloon dilation and QA421 or QA422 for esophago-cardiomyotomy. A total of 3,105 patients with achalasia (1,447 men; mean age, 52.5 yr) were identified between 2007 and 2011, indicating a prevalence of 6.29/100,000 (95% confidence interval [CI], 4.94-7.66) during this 5-yr period. A total of 191 incident cases of achalasia (82 men; mean age, 49.5 yr), which were not diagnosed as achalasia in the previous 4 yr, were detected in 2011, indicating an incidence of 0.39/100,000 (95% CI, 0.15-0.63) for that year. During the study period, balloon dilation therapy was performed a total of 975 times in 719 patients, and surgical esophago-cardiomyotomy was performed once per patient in 17 patients. This is the first population-based epidemiologic study of achalasia in Korea. Graphical Abstract
    Journal of Korean medical science 04/2014; 29(4):576-80. DOI:10.3346/jkms.2014.29.4.576 · 1.27 Impact Factor
  • Source
    • "Clinical symptoms of achalasia are dysphagia, regurgitation, chest pain and weight loss. The exact pathophysiology of achalasia has not been fully understood, but functional loss of myenteric plexus ganglion cells in the distal esophagus and LES, therefore causing imbalance between the excitatory and inhibitory innervation of the distal esophagus is the generally accepted mechanism.3,4 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Achalasia is classified into 3 types according to the Chicago classification. The aim of this study was to investigate characteristics and treatment outcomes of 3 achalasia subtypes in Korean patients. Fifty-five patients diagnosed with achalasia based on conventional or high-resolution esophageal manometry were consecutively enrolled. Their clinical characteristics, manometric, endoscopic and esophagographic findings and treatment responses were analyzed among the 3 subtypes of achalasia. Of 55 patients, 21 (38.2%) patients had type I, 28 (50.9%) patients had type II and 6 (10.9%) patients had type III. The median follow-up period was 22.4 (interquartile range, 3.6-67.4) months. Type III patients were older than type I and II patients (70.0 vs. 46.2 and 47.6 years, P = 0.023). The width of the esophagus in type I patients was wider with more frequent bird's beak appearance on esophagogram than the other 2 types (P = 0.010 and 0.006, respectively). Of the 50 patients who received the evaluation for treatment response at 3 months, 7 patients (36.8% vs. 26.9%) were treated with pneumatic dilatation and 4 patients (21.1% vs. 15.4%) with laparoscopic Heller's myotomy in type I and II groups, respectively. The treatment responses of pneumatic dilatation and Heller's myotomy in type I group were 71.4 and 50.0% and in type II were 85.7 and 75.0%, respectively, and all 5 patients in type III group showed good response to medical therapy. Clinical characteristics of 3 achalasia subtypes in Korean patients are consistent with other studies. Treatment outcomes are variable among 3 subtypes.
    Journal of neurogastroenterology and motility 10/2013; 19(4):485-94. DOI:10.5056/jnm.2013.19.4.485 · 2.30 Impact Factor
  • Source
    • "Impairment in nitrergic inhibitory neurotransmission results in nonrelaxing LES and aperistalsis of the esophageal body, which are typical manometric findings of achalasia.1 Those findings are presumed to be caused by the neurodegenerative insult, which is believed to be of inflammatory origin.2 However, evidence for the etiology and pathogenesis of achalasia is lacking. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The primary pathophysiologic abnormality in achalasia is known to be a loss of inhibitory myenteric ganglion cells, which may result from an immune-mediated response or neuronal degeneration. The aim of this study was to identify proteins suggestive of an immune-mediated response or neuronal degeneration in the serum of achalasia patients using a proteomic analysis. Blood samples were collected from five symptomatic achalasia patients and five sex- and age-matched healthy controls. Serum proteomic analysis was conducted, and the protein spots were identified using matrix-assisted laser desorption ionization/time-of-flight and a proteomics analyzer. The serum level of C3 was measured by enzyme-linked immunosorbent assay in nine patients with achalasia and 18 sex- and age-matched healthy controls. Of the 658 matched protein spots, 28 spots were up-regulated over 2-fold in the serum from achalasia patients compared with that from controls. The up-regulated proteins included complement C4B5, complement C3, cyclin-dependent kinase 5, transthyretin, and alpha 2 macroglobulin. The serum levels of C3 in achalasia patients were significantly higher than those of controls. The serum proteomic analysis of achalasia patients suggests an immune-mediated response or neuronal degeneration. Further validation studies in larger samples and the esophageal tissue of achalasia patients are required.
    Gut and liver 07/2013; 7(4):411-6. DOI:10.5009/gnl.2013.7.4.411 · 1.81 Impact Factor
Show more