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Achalasia

Nature Reviews Disease Primers volume 8, Article number: 28 (2022) Cite this article

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Abstract

Achalasia is a rare disorder of the oesophageal smooth muscle characterized by impaired relaxation of the lower oesophageal sphincter (LES) and absent or spastic contractions in the oesophageal body. The key pathophysiological mechanism is loss of inhibitory nerve function that probably results from an autoimmune attack targeting oesophageal myenteric nerves through cell-mediated and, possibly, antibody-mediated mechanisms. Achalasia incidence and prevalence increase with age, but the disorder can affect all ages and both sexes. Cardinal symptoms consist of dysphagia, regurgitation, chest pain and weight loss. Several years can pass between symptom onset and an achalasia diagnosis. Evaluation starts with endoscopy to rule out structural causes, followed by high-resolution manometry and/or barium radiography. Functional lumen imaging probe can provide complementary evidence. Achalasia subtypes have management and prognostic implications. Although symptom questionnaires are not useful for diagnosis, the Eckardt score is a simple symptom scoring scale that helps to quantify symptom response to therapy. Oral pharmacotherapy is not particularly effective. Botulinum toxin injection into the LES can temporize symptoms and function as a bridge to definitive therapy. Pneumatic dilation, per-oral endoscopic myotomy and laparoscopic Heller myotomy can provide durable symptom benefit. End-stage achalasia with a dilated, non-functioning oesophagus may require oesophagectomy or enteral feeding into the stomach. Long-term complications can, rarely, include oesophageal cancer, but surveillance recommendations have not been established.

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Fig. 1: Normal oesophageal physiology and innervation.
Fig. 2: Oesophageal manifestations and natural history of achalasia.
Fig. 3: Achalasia subtypes based on high-resolution manometry.
Fig. 4: Two possible pathways of pathogenesis differentiate achalasia subtypes.
Fig. 5: Diagnostic and management algorithm for achalasia.
Fig. 6: Adjunctive tests in the diagnosis of achalasia.

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Acknowledgements

The authors thank the anonymous patient for their contribution in Box 2.

Author information

Authors and Affiliations

  1. Gastroenterology Unit, Azienda Ospedale Università di Padova (AOUP), Padua, Italy

    Edoardo Savarino

  2. Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Padua, Italy

    Edoardo Savarino

  3. Department of Gastroenterology, Sir HN Reliance Foundation Hospital, Mumbai, India

    Shobna Bhatia

  4. Hospices Civils de Lyon, Digestive Physiology, Hopital E Herriot, Lyon, France

    Sabine Roman

  5. Université Lyon 1, Villeurbanne, France

    Sabine Roman

  6. Inserm U1032, LabTAU, Lyon, France

    Sabine Roman

  7. Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK

    Daniel Sifrim

  8. Division of Gastroenterology, University Hospital of Leuven, Leuven, Belgium

    Jan Tack

  9. Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia

    Sarah K. Thompson

  10. Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA

    C. Prakash Gyawali

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Contributions

Introduction (E.S., C.P.G. and S.B.); Epidemiology (S.R.); Mechanisms/pathophysiology (D.S.); Diagnosis/screening/prevention (C.P.G.); Management (E.S. and S.K.T.); Quality of life (S.R.); Outlook (J.T.); Overview of the Primer (E.S.).

Corresponding author

Correspondence to Edoardo Savarino.

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Competing interests

E.S. has served as speaker for AbbVie, AGPharma, Alfasigma, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Medtronic, Novartis, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda and Unifarco; has served as consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Falk, Fresenius Kabi, Janssen, Merck & Co., Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda and Unifarco; and has received research support from Reckitt Benckiser, SILA, Sofar and Unifarco. S.B. has served as speaker for Medtronic. S.R. has served as consultant for Reckitt Benckiser and Dr Falk Pharma; and has received research support from Medtronic and Diversatek Healthcare. D.S. has served as consultant for Reckitt Benckiser UK, Jinshan Technology China and Alfasigma Italy. J.T. has served on the speaker bureau for Abbott, Mylan and Takeda; has served as consultant for Arena, Bayer, Falk, Takeda and Truvion pharmaceuticals; and has received research support from Shire, Sofar and Takeda. S.K.T. has served as a consultant for Medtronic. C.P.G. has served as speaker for Medtronic, Takeda and Johnson&Johnson, and has served as consultant for Medtronic, Diversatek, Takeda and Ironwood.

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Nature Reviews Disease Primers thanks I. Gockel; Z. Nabi; M. Patti; Y. Shimamura, who co-reviewed with Y. Fujiyoshi; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Savarino, E., Bhatia, S., Roman, S. et al. Achalasia. Nat Rev Dis Primers 8, 28 (2022). https://doi.org/10.1038/s41572-022-00356-8

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