Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto SP 14049-900, Brazil.
Correspondence Address: Dr. Roberto Oliveira Dantas, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Av Bandeirantes 3900, Ribeirão Preto SP 14049-900, Brazil. E-mail:
Dr. Roberto Oliveira Dantas, is a Senior Associate Professor at the Department of Medicine, Division of Gastroenterology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. He is a Member of the Advisory Board of the journal Gastroenterology and the Editorial Advisory Board of the journal Dysphagia. In addition, he is also a member of the Board of Directors of the International Dysphagia Diet Standardisation Initiative (IDDSI).
This is an open access article licensed under the terms of Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original author is credited and the new creations are licensed under the identical terms.
Idiopathic and Chagas’ disease achalasia are characterized by absent or partial lower esophageal sphincter relaxation, absence of peristaltic esophageal contraction, food retenction in the esophagus and esophageal dilatation. The most frequent symptoms are dysphagia, regurgitation, heartburn, weight loss and non-cardiac chest pain. The diagnosis is made by radiologic examination and esophageal manometry, which is considered the most accurate exam to characterized achalasia. In both diseases there is destruction of the esophageal myenteric plexus. Despite similarities in clinical and manometric presentation there is evidence of greater loss of inhibitory neurons of the myenteric plexus in idiopathic achalasia, whereas in Chagas’ disease there is a loss of both excitatory and inhibitory neurons. Such differences, though do not affect patients’ clinical presentation, and hence treatment options should be the same for both diseases.
Achalasia, Chagas’ disease, megaesophagus, dysphagia, esophageal denervation
The most common symptoms are dysphagia, regurgitation, heartburn, weight loss and non-cardiac chest pain. The diagnosis is made by radiologic examination of the esophagus and esophageal manometry, which is the most accurate exam to characterized achalasia. In this test, achalasia is characterized by increased integrated relaxation pressure of the lower esophageal sphincter and absence of peristaltic contraction in the esophageal body. Using high resolution manometry achalasia patients may be classified as type I, when there are no contractions in esophageal body during swallows, type II, characterized by pan-esophageal pressurization, or type III when there are high-amplitude simultaneous contractions in the distal esophagus.
The etiology of achalasia is unknown in most cases around the world, and may be multifactorial, including autoimmune, genetic and viral factors. 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. The disease occurs with an annual incidence of 1 in 100,000 and a prevalence of 10 in 100,000.
Achalasia may be caused by infection by the hemoflagellate protozoan Trypanosoma cruzi[5,6] which affects millions of people in Latin America and has been increasingly reported in the United States and Europe. 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, 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. It is estimated that 300,000 infected immigrants are living in United States. From 7% to 10% of the infected individuals will have achalasia.
Although both diseases cause the same alteration in the esophagus, including absent or partial relaxation of the lower esophageal sphincter, esophageal aperistlsis, and megaesophagus the loss of esophageal intrinsic innervations may not be the same[11-13].
While in idiopathic achalasia neural destruction has been suggested to be more intense in inhibitory nerves than in excitatory nerves, in achalasia caused by Trypanosoma cruzi infection neural impairment involves both inhibitory and excitatory innervations. Consequently lower esophageal sphincter pressure is frequently increased in idiopathic achalasia[14-17] and frequently decreased in Chagas’ disease[16-19] which may explain the variation in the lower esophageal sphincter pressure, and the heterogeneity seen in these patients.
Previous studies have reported differences in esophageal response to gastrin[14,15,18] and to atropine[15,22]. These mechanisms have not been completely elucidated in Chagas’ disease[11,13] [Table 1]. Although studies on idiopathic achalasia have demonstrated a partial opening of the upper esophageal sphincter with increased residual pressure during swallow, these features have not been fully demonstrated in Chagas’ disease[12,13]. The time between pharyngeal contraction and proximal esophageal contraction (5 cm distance) after wet swallows in patients with megaesophagus is increased in Chagas’ disease but not in idiopathic achalasia. Contractions in the esophageal body are not of the same intensity, and tend to be more intense in patients with idiopathic achalasia[19,25]. In addition epiphrenic diverticula is more frequent on idiopathic achalasia (3.6% to 7.4%) than in Chagas’ disease (1.5%). Also, high prevalence of circulating antibodies against M2 acethilcholine muscarinic receptor has been found in Chagas’ disease patients with achalasia (84%), compared with patients with idiopathic achalasia (28%).
Differences between idiopathic achalasia and Chagas' disease
|Idiopathic achalasia||Chagas’ disease|
|Dopamine D2 receptors||Decreased||Not investigated|
|LES basal pressure||Increased||Decreased|
|Bothinun toxin response||LES pressure reduction (32% to 45%)||LES pressure reduction (23%)|
|Edrophonium response||Increase in esophageal pressure||Increase in esophageal pressure|
|Anti M2R antibody||Low prevalence (28%)||High prevalence (84%)|
|Epiphrenic diverticula||3.6% to 7.4%||1.5%|
Despite differences in pathophysiology of Chagas’ disease-related and idiophatic achalasia, the clinical presentation in both diseases is the same, with dysphagia as a common complaint, affecting more than 90% of the patients. However, the symptoms occurs later in patients with Chagas’ disease achalasia, a long time after the infection, and may be associated with aging-related changes in esophageal motility in addition to impairment of esophageal myenteric plexus caused by the disease. In the evaluation of the water ingestion dynamics patients with dysphagia caused by Chagas’ disease or idiopathic achalasia have the same behavior.
Taken together, both Chagas’ disease-related and idiopathic achalasia have similar clinical and radiologic manifestations, including nonrelaxing or partially relaxing lower esophageal sphincter and esophageal aperistalsis, although the pathophysiology of the diseases should not be the same. Therefore, treatment of both conditions is similar, and include pneumatic dilation of the esophageal-gastric transition, laparoscopic Heller myotomy and, the more recent peroral endoscopic myotomy (POEM)[28-30]. Drugs and botulinum toxin may be used in special cases and esophagectomy for advanced cases. There is no cure for the disease, and the objective of treatment is relieve the symptoms and permit an adequate food ingestion. Drugs cause benefit for a short time and have side effects which may be intense. The remission of the symptoms with pneumatic dilatation may least for 5 to 10 years, but the most effective treatment is laparoscopic or endoscopic myotomy, with an improvement of the symptoms for 6 to 10 years. The patients who have a better response to treatment, pneumatic dilation or Heller myotomy, are them who has isobaric panesophageal pressurization after swallowing.
R.O. Dantas contributed solely to the paper.Financial support and sponsorship
None.Conflicts of interest
There are no conflicts of interest.Patient consent
Not applicable.Ethics approval
1. Jeon HH, Kim JH, Youn YH, Park H, Conklin JL. Clinical characteristics of patients with untreat achalasia. J Neurogastroenterol Motil 2017;23:370-7.DOIPubMedPMC
2. Pressman A, Behar J. Etiology and pathogenesis of idiopathic achalasia. J Clin Gastroenterol 2017;51:1195-201.
3. Crespin OM, Tatum RP, Xiao K, Martin AV, Khandelwal S, Pellegrini CA, Oelschlager BK. The relationship between manometric subtype and outcomes of surgical treatments for patients with achalasia. Surg Endosc 2017; doi: 10.1007/s00464-017-5570-5.DOI
4. Pandolfino JE, Kahrilas PJ. Presentation, diagnosis, and management of achalasia. Clin Gastroenterol Hepatol 2013;11:887-97.DOIPubMed
5. Oliveira RB, Troncon LEA, Dantas RO, Meneghelli UG. Gastrointestinal manifestations of Chagas' disease. Am J Gastroenterol 1998;93:884-9.DOIPubMed
6. Matsuda NM, Miller SM, évora PRB. The chronic gastrointestinal manifestations of Chagas' disease. Clinics 2009;64:1219-24.DOIPubMedPMC
7. Bern C, Montgomery SP, Herwaldt BL, Rassi A Jr, Marin-Neto JA, Dantas RO, Magure JH, Acquatella H, Morillo C, Kirchhoff LV, Gilman RH, Reyes PA, Salvatella R, Moore AC. Evaluation of treatment of Chagas' disease in the United States. A systematic review. JAMA 2007;298:2171-81.DOIPubMed
8. Sánches-Montalvá A, Moris M, Mego M, Salvador F, Accarino A, Ramirez K, Azpiroz F, Ruiz de Leon A, Molina I. High resolution esophageal manometry in patients with Chagas' disease: a cross-sectional evaluation. PLoS Negl Trop Dis 2016;10:e0004416.DOIPubMedPMC
9. Bern C. Chagas' disease. N Engl J Med 2015;373:456-66.DOIPubMed
10. Köberle F. Chagas' disease and Chagas' syndromes: the pathology of American trypanosomiais. Adv Parasitol 1968;6:63-116.DOI
11. Dantas RO. Idiopathic achalasia and chagasic megaesophagus. J Clin Gastroenterol 1988;10:13-5.DOIPubMed
12. Dantas RO. Comparison between idiopathic achalasia and achalasia caused by Chagas' disease: a review about the pathophysiology of the diseases. Arq Gastroenterol 2003;40:126-30.DOIPubMed
13. Herbella FAM, Oliveira DRFC, Del Grande JC. Are idiopathic and chagasic achalasia two different diseases? Dig Dis Sci 2004;49:353-60.DOIPubMed
14. Cohen S, Lipshutz W, Hughes W. Role of gastrin supersensitivity in the pathogenesis of the lower esophageal sphincter hypertension in achalasia. J Clin Invest 1971;50:1241-7.DOIPubMedPMC
15. Holloway RH, Dodds WJ, Helm JF, Hogan WJ, Dent J, Arndorfer RC. Integrity of cholinergic innervations to the lower esophageal sphincter in achalasia. Gastroenterology 1986;90:924-9.DOI
16. Dantas RO, Godoy RA, Oliveira RB, Meneghelli UG, Troncon LEA. Lower esophageal sphincter pressure in Chagas' disease. Dig Dis Sci 1990;35:508-12.DOIPubMed
17. Lemme EMO, Domingues GR, Pereira VLC, Firman CG, Pantoja J. Lower esophageal sphincter pressure in idiopathic achalasia and Chagas' disease-related achalasia. Dis Esophagus 2001;14:232-4.DOIPubMed
18. Padovan W, Godoy RA, Dantas RO, Meneghelli UG, Oliveira RB, Troncon LEA. Lower oesophageal sphincter response to pentagastrin in chagasic patients with megaesophagus and megacolon. Gut 1980;21:85-90.DOIPubMedPMC
19. Dantas RO, Deghaide NHS, Donadi EA. Esophageal motility of patients with Chagas' disease and idiopathic achalasia. Dig Dis Sci 2001;46:1200-6.DOIPubMed
20. Hirano I. Pathophysiology of achalasia. Curr Gastroenterol Rep 1999;1:198-202.DOIPubMed
21. Hirano I, Tatum RP, Shi G, Sang Q, Joehl RJ, Kahrilas PJ. Manometric heterogeneity in patients with idiopathic achalasia. Gastroenterology 2001;120:789-98.DOIPubMed
22. Dantas RO, Godoy RA, Oliveira RB, Meneghelli UG, Troncon LEA. Effect of isosorbide dinitrate and atropine on the lower esophageal sphincter pressure in chagasic patients. Acta Physiol Pharmacol Latinoam 1988;38:151-8.PubMed
23. Dudnick RS, Castell JA, Castell DO. Abnormal upper esophageal sphincter function in achalasia. Am J Gastroenterol 1992;87:1712-5.PubMed
24. Ramos RI, Varrica LMM, Dantas RO. Differences in response of the proximal esophagus to wet swallows in patients of Chagas' disease and idiopathic achalasia. Dis Esophagus 2006;19:401-5.DOIPubMed
25. Dantas RO, Aprile LRO. Esophageal contractions in Chagas' disease and in idiopathic achalasia. Dig Dis Sci 2005;39:863-8.DOI
26. Goin JC, Sterin-Borda L, Bilder CR, Varrica LM, Iantorno G, Rios MC, Borda E. Functional implications of circulating muscarinic cholinergic receptor autoantibodies in chagasic patients with achalasia. Gastroenterology 1999;117:798-805.DOI
27. Dantas RO, Santos CM, Cassiani LMT, Nascimento WV. Postfundoplication dysphagia causes similar water ingestion dynamics as achalasia. Arq Gastroenterol 2016;53:98-102.DOIPubMed
28. Awaiz A, Yunus RM, Khan S, Memon B, Memon MA. Systematic review and meta-analysis of perioperative outcomes of peroral endoscopic myotomy (POEM) and laparoscoic Heller myotomy (LHM) for achalasia. Surg Laparosc Endosc Percutan Tech 2017;27:123-31.DOIPubMed
29. Kahrilas PJ, Pandolfino JE. Treatments for ahcalasia in 2017: how to choose among them. Curr Opin Gastroenterol 2017;33:270-6.DOIPubMed
30. Stavros NS, Friedel D, Modayil R, Parkman HP. Diagnosis and management of esophageal achalasia. BMJ 2016;353:i2785.DOIPubMed
31. Patel DA, Lappas BM, Vaezi MF. An overwiew of achalasia and its subtypes. Gastroenterol Hepatol 2017;13:411-21.