Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Achalasia: Pathogenesis, clinical manifestations, and diagnosis

Stuart J Spechler, MD
Section Editor
Nicholas J Talley, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH


Achalasia results from progressive degeneration of ganglion cells in the myenteric plexus in the esophageal wall, leading to failure of relaxation of the lower esophageal sphincter, accompanied by a loss of peristalsis in the distal esophagus. This topic will review the etiology, pathogenesis, clinical manifestations, and diagnosis of achalasia. The management of achalasia is discussed separately. (See "Overview of the treatment of achalasia" and "Pneumatic dilation and botulinum toxin injection for achalasia" and "Surgical myotomy for achalasia".)


Achalasia is an uncommon disorder with an annual incidence of approximately 1.6 cases per 100,000 individuals and prevalence of 10 cases per 100,000 individuals [1]. Men and women are affected with equal frequency. The disease can occur at any age, but onset before adolescence is rare. Achalasia is usually diagnosed in patients between the ages of 25 and 60 years.

Achalasia may occur in association with adrenal insufficiency and alacrima in patients with triple A syndrome or Allgrove syndrome, a rare autosomal recessive genetic disorder [2,3]. (See "Unusual causes of adrenal insufficiency", section on 'Triple A (Allgrove syndrome)'.)


The etiology of primary or idiopathic achalasia is unknown. Secondary achalasia is due to diseases that cause esophageal motor abnormalities similar or identical to those of primary achalasia (table 1). In Chagas disease, which occurs predominantly in Central and South America, esophageal infection with the protozoan parasite Trypanosoma cruzi can result in a loss of intramural ganglion cells, leading to aperistalsis and incomplete lower esophageal sphincter relaxation [4]. Other diseases that have been associated with achalasia-like motor abnormalities include amyloidosis, sarcoidosis, neurofibromatosis, eosinophilic esophagitis, multiple endocrine neoplasia type 2B, juvenile Sjögren syndrome, chronic idiopathic intestinal pseudo-obstruction, and Fabry disease [5-11]. (See "Chagas disease: Pathology and pathogenesis".)


Achalasia results from inflammation and degeneration of neurons in the esophageal wall (figure 1) [12]. The cause of the inflammatory degeneration of neurons in primary achalasia is not known. The observations that achalasia is associated with variants in the HLA-DQ region and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia is an autoimmune disorder [13-15]. Some investigators have proposed that the inflammatory attack on esophageal neurons in achalasia is triggered by an antibody response to viral infections (eg, herpes zoster, measles viruses), but data have been inconclusive [16,17]. A study evaluating T cells in patients with achalasia found reactivity to HSV-1, suggesting that achalasia may be triggered by HSV-1 infection [18]. A genetic predisposition to the inflammatory degeneration of ganglion cells in achalasia is suggested by its association with variants in the HLA-DQ region and by its occurrence in genetic syndromes such as Allgrove syndrome. (See 'Epidemiology' above and "Unusual causes of adrenal insufficiency", section on 'Triple A (Allgrove syndrome)'.)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Aug 18, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Sadowski DC, Ackah F, Jiang B, Svenson LW. Achalasia: incidence, prevalence and survival. A population-based study. Neurogastroenterol Motil 2010; 22:e256.
  2. Allgrove J, Clayden GS, Grant DB, Macaulay JC. Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet 1978; 1:1284.
  3. Verma S, Brown S, Dakkak M, Bennett JR. Association of adult achalasia and alacrima. Dig Dis Sci 1999; 44:876.
  4. de Oliveira RB, Rezende Filho J, Dantas RO, Iazigi N. The spectrum of esophageal motor disorders in Chagas' disease. Am J Gastroenterol 1995; 90:1119.
  5. Costigan DJ, Clouse RE. Achalasia-like esophagus from amyloidosis. Successful treatment with pneumatic bag dilatation. Dig Dis Sci 1983; 28:763.
  6. Dufresne CR, Jeyasingham K, Baker RR. Achalasia of the cardia associated with pulmonary sarcoidosis. Surgery 1983; 94:32.
  7. Foster PN, Stewart M, Lowe JS, Atkinson M. Achalasia like disorder of the oesophagus in von Recklinghausen's neurofibromatosis. Gut 1987; 28:1522.
  8. Cuthbert JA, Gallagher ND, Turtle JR. Colonic and oesophageal disturbance in a patient with multiple endocrine neoplasia, type 2b. Aust N Z J Med 1978; 8:518.
  9. Similä S, Kokkonen J, Kaski M. Achalasia sicca--juvenile Sjögren's syndrome with achalasia and gastric hyposecretion. Eur J Pediatr 1978; 129:175.
  10. Schuffler MD. Chronic intestinal pseudo-obstruction syndromes. Med Clin North Am 1981; 65:1331.
  11. Roberts DH, Gilmore IT. Achalasia in Anderson-Fabry's disease. J R Soc Med 1984; 77:430.
  12. Reynolds JC, Parkman HP. Achalasia. Gastroenterol Clin North Am 1989; 18:223.
  13. Wong RK, Maydonovitch CL, Metz SJ, Baker JR Jr. Significant DQw1 association in achalasia. Dig Dis Sci 1989; 34:349.
  14. Verne GN, Sallustio JE, Eaker EY. Anti-myenteric neuronal antibodies in patients with achalasia. A prospective study. Dig Dis Sci 1997; 42:307.
  15. Verne GN, Hahn AB, Pineau BC, et al. Association of HLA-DR and -DQ alleles with idiopathic achalasia. Gastroenterology 1999; 117:26.
  16. Niwamoto H, Okamoto E, Fujimoto J, et al. Are human herpes viruses or measles virus associated with esophageal achalasia? Dig Dis Sci 1995; 40:859.
  17. Birgisson S, Galinski MS, Goldblum JR, et al. Achalasia is not associated with measles or known herpes and human papilloma viruses. Dig Dis Sci 1997; 42:300.
  18. Facco M, Brun P, Baesso I, et al. T cells in the myenteric plexus of achalasia patients show a skewed TCR repertoire and react to HSV-1 antigens. Am J Gastroenterol 2008; 103:1598.
  19. Goldblum JR, Whyte RI, Orringer MB, Appelman HD. Achalasia. A morphologic study of 42 resected specimens. Am J Surg Pathol 1994; 18:327.
  20. Goldblum JR, Rice TW, Richter JE. Histopathologic features in esophagomyotomy specimens from patients with achalasia. Gastroenterology 1996; 111:648.
  21. Holloway RH, Dodds WJ, Helm JF, et al. Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia. Gastroenterology 1986; 90:924.
  22. Qualman SJ, Haupt HM, Yang P, Hamilton SR. Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease. Gastroenterology 1984; 87:848.
  23. Sodikoff JB, Lo AA, Shetuni BB, et al. Histopathologic patterns among achalasia subtypes. Neurogastroenterol Motil 2016; 28:139.
  24. Massey BT, Hogan WJ, Dodds WJ, Dantas RO. Alteration of the upper esophageal sphincter belch reflex in patients with achalasia. Gastroenterology 1992; 103:1574.
  25. Mearin F, Papo M, Malagelada JR. Impaired gastric relaxation in patients with achalasia. Gut 1995; 36:363.
  26. Eckardt VF, Köhne U, Junginger T, Westermeier T. Risk factors for diagnostic delay in achalasia. Dig Dis Sci 1997; 42:580.
  27. Howard PJ, Maher L, Pryde A, et al. Five year prospective study of the incidence, clinical features, and diagnosis of achalasia in Edinburgh. Gut 1992; 33:1011.
  28. Eckardt VF, Stauf B, Bernhard G. Chest pain in achalasia: patient characteristics and clinical course. Gastroenterology 1999; 116:1300.
  29. Fisichella PM, Raz D, Palazzo F, et al. Clinical, radiological, and manometric profile in 145 patients with untreated achalasia. World J Surg 2008; 32:1974.
  30. Spechler SJ, Souza RF, Rosenberg SJ, et al. Heartburn in patients with achalasia. Gut 1995; 37:305.
  31. Burke CA, Achkar E, Falk GW. Effect of pneumatic dilation on gastroesophageal reflux in achalasia. Dig Dis Sci 1997; 42:998.
  32. Seeman H, Traube M. Hiccups and achalasia. Ann Intern Med 1991; 115:711.
  33. Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol 2013; 108:1238.
  34. Carter M, Deckmann RC, Smith RC, et al. Differentiation of achalasia from pseudoachalasia by computed tomography. Am J Gastroenterol 1997; 92:624.
  35. Spechler SJ. American gastroenterological association medical position statement on treatment of patients with dysphagia caused by benign disorders of the distal esophagus. Gastroenterology 1999; 117:229.
  36. Pandolfino JE, Ghosh SK, Rice J, et al. Classifying esophageal motility by pressure topography characteristics: a study of 400 patients and 75 controls. Am J Gastroenterol 2008; 103:27.
  37. Kahrilas PJ, Ghosh SK, Pandolfino JE. Esophageal motility disorders in terms of pressure topography: the Chicago Classification. J Clin Gastroenterol 2008; 42:627.
  38. Pandolfino JE, Kwiatek MA, Nealis T, et al. Achalasia: a new clinically relevant classification by high-resolution manometry. Gastroenterology 2008; 135:1526.
  39. Roman S, Zerbib F, Quenehervé L, et al. The Chicago classification for achalasia in a French multicentric cohort. Dig Liver Dis 2012; 44:976.
  40. Salvador R, Costantini M, Zaninotto G, et al. The preoperative manometric pattern predicts the outcome of surgical treatment for esophageal achalasia. J Gastrointest Surg 2010; 14:1635.
  41. Pratap N, Reddy DN. Can achalasia subtyping by high-resolution manometry predict the therapeutic outcome of pneumatic balloon dilatation?: author's reply. J Neurogastroenterol Motil 2011; 17:205.
  42. Min M, Peng LH, Yang YS, et al. Characteristics of achalasia subtypes in untreated Chinese patients: a high-resolution manometry study. J Dig Dis 2012; 13:504.
  43. Spechler SJ, Castell DO. Classification of oesophageal motility abnormalities. Gut 2001; 49:145.
  44. Hirano I, Tatum RP, Shi G, et al. Manometric heterogeneity in patients with idiopathic achalasia. Gastroenterology 2001; 120:789.
  45. Hirano I.. Pathophysiology of achalasia and diffuse esophageal spasm. GI Motility Online 2006; 10.1038/gimo22.
  46. Goldenberg SP, Burrell M, Fette GG, et al. Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings. Gastroenterology 1991; 101:743.
  47. Pasricha PJ, Rai R, Ravich WJ, et al. Botulinum toxin for achalasia: long-term outcome and predictors of response. Gastroenterology 1996; 110:1410.
  48. Miller LS, Liu JB, Barbarevech CA, et al. High-resolution endoluminal sonography in achalasia. Gastrointest Endosc 1995; 42:545.
  49. Kahrilas PJ, Kishk SM, Helm JF, et al. Comparison of pseudoachalasia and achalasia. Am J Med 1987; 82:439.
  50. Campos CT, Ellis FH Jr, LoCicero J 3rd. Pseudoachalasia: a report of two cases with comments on possible causes and diagnosis. Dis Esophagus 1997; 10:220.
  51. Eckardt VF, Hoischen T, Bernhard G. Life expectancy, complications, and causes of death in patients with achalasia: results of a 33-year follow-up investigation. Eur J Gastroenterol Hepatol 2008; 20:956.
  52. Vela MF, Richter JE, Wachsberger D, et al. Complexities of managing achalasia at a tertiary referral center: use of pneumatic dilatation, Heller myotomy, and botulinum toxin injection. Am J Gastroenterol 2004; 99:1029.
  53. Sandler RS, Nyrén O, Ekbom A, et al. The risk of esophageal cancer in patients with achalasia. A population-based study. JAMA 1995; 274:1359.
  54. Csendes A, Braghetto I, Burdiles P, et al. Very late results of esophagomyotomy for patients with achalasia: clinical, endoscopic, histologic, manometric, and acid reflux studies in 67 patients for a mean follow-up of 190 months. Ann Surg 2006; 243:196.
  55. Streitz JM Jr, Ellis FH Jr, Gibb SP, Heatley GM. Achalasia and squamous cell carcinoma of the esophagus: analysis of 241 patients. Ann Thorac Surg 1995; 59:1604.
  56. Leeuwenburgh I, Scholten P, Alderliesten J, et al. Long-term esophageal cancer risk in patients with primary achalasia: a prospective study. Am J Gastroenterol 2010; 105:2144.
  57. Zendehdel K, Nyrén O, Edberg A, Ye W. Risk of esophageal adenocarcinoma in achalasia patients, a retrospective cohort study in Sweden. Am J Gastroenterol 2011; 106:57.
  58. Zaninotto G, Rizzetto C, Zambon P, et al. Long-term outcome and risk of oesophageal cancer after surgery for achalasia. Br J Surg 2008; 95:1488.