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.

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    • "There is, however, little in the literature to suggest that megaesophagus is common in patients with muscular dystrophy or other myopathies. Megaesophagus occurs more frequently in severe cases of achalasia, as a consequence of inability to fully relax the LES[2,3]. It will be of interest for future studies to use electrophysiology and manometry to test if Pax7 −/− mice have a nonautonomous defect in LES function. "
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    ABSTRACT: Background: The mammalian esophageal musculature is unique in that it makes a transition from smooth to skeletal muscle, with most of this process occurring after birth. In order to better understand the mechanisms that control esophageal musculature development, we investigated the roles in this process of the paired box transcription factor, PAX7, a principal regulator of skeletal myogenic progenitor cells. Previous studies showed that Pax7 is important for determining the esophageal muscle composition. Results: We characterized the postnatal development of the esophageal musculature in Pax7 (-/-) mice by analyzing morphology, muscle composition, and the expression of markers of myogenesis, cell proliferation, and apoptosis. Pax7 (-/-) mice displayed megaesophagus with a severe defect in the postnatal developmental process whereby esophageal smooth muscle is replaced by skeletal muscle. Pax7 (-/-) esophagi have substantially reduced skeletal muscle, most likely due to diminished proliferation and premature differentiation of skeletal muscle precursor cells. This impaired the proximal-to-distal progression of skeletal myogenesis and indirectly affected the patterning of the smooth muscle-containing portion of the esophageal musculature. Conclusions: Postnatal patterning of the esophageal musculature appears to require robust, PAX7-dependent cell proliferation to drive the proximal-to-distal progression of skeletal myogenesis. This process in turn influences distal smooth muscle morphogenesis and development of the mature pattern of the esophageal musculature.
    Full-text · Article · Dec 2015 · Skeletal Muscle
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    • "It may occur at any age and has an incidence of 0.6 per 100,000 per year [1]. Although its etiology is unknown, current data suggest that achalasia is an immune-mediated disorder and is caused by a loss of inhibitory nitrinergic neurons in the esophageal myenteric plexus [2]. Dysphagia to solids and liquids, regurgitation of undigested food, and chest pain are the main symptoms in patients with achalasia. "
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    ABSTRACT: Background Achalasia is characterized by esophageal aperistalsis and a failure of lower esophageal sphincter (LES) relaxation. Combined multichannel intraluminal impedance and manometry (MII-EM) allows the simultaneous recording of esophageal peristalsis and bolus transport patterns. The aim of this study was to evaluate the feasibility of MII-EM for the assessment of esophageal motility and to characterize patterns of esophageal bolus transport in patients with achalasia with or without Heller myotomy. Materials and methods A total of nine patients (2 men and 7 women, age range 25–46 years) were enrolled in this study. Two of the patients had previously undergone Heller myotomy. All patients underwent combined MII-EM with a nine-channel esophageal function testing catheter containing four impedance measuring segments and five solid-state pressure transducers. Each patient received 10 liquid and 10 viscous swallows in a sitting position. All tracings were recorded and analyzed for esophageal contractions and bolus transit. Results None of the patients with achalasia, whether they had undergone a Heller myotomy or not, had manometrically normal esophageal peristalsis during saline or viscous swallowing. They had a normal LES resting pressure, incomplete LES relaxation, and lower distal esophageal contraction. The LES relaxation percentages in the patients who had undergone Heller myotomy (97% and 51%) were higher than those of the untreated patients (mean 47%). All patients demonstrated a low baseline impedance level in the distal esophagus. Air trapping in the proximal esophagus was also detected in nearly all of the patients. None of the patients in either group had complete bolus transit with either saline or viscous swallows. Conclusion Patients with achalasia are characterized by poor esophageal contraction and absent esophageal bolus clearance and such abnormalities are still noticeable after Heller myotomy. Although combined MII-EM can provide additional information regarding esophageal bolus transit, a low baseline impedance level and air trapping in the proximal esophagus may limit its utility in the diagnosis of esophageal dysmotility in patients with achalasia.
    Preview · Article · Jun 2014
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    • "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). "
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    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
    Full-text · Article · Apr 2014 · Journal of Korean medical science
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