Esophageal hyposensitivity in achalasia cardia: Do we finally have an answer?

We thank Tustumi and colleagues for their interest in our manuscript. Gastroesophageal reflux disease (GERD) is common after per-oral endoscopic myotomy (POEM).¹ However, symptomatic GERD is uncommon compared to erosive esophagitis and increased esophageal acid exposure.² We speculated that submucosal tunneling and mucosal denervation during POEM may contribute to relative esophageal hyposensitivity. It is important to note that robust studies are required to support this hypothesis.

Tustumi et al. postulated that esophageal hyposensitivity may be a feature of achalasia itself rather than the effect of treatment. The reasons for primary esophageal hyposensitivity include nervous degeneration, failure of longitudinal muscles to contract, and central desensitization. In addition, mechanical stimulus may not be effective in generating symptoms due to pre-existing esophageal distension in cases with achalasia. Although the proposition by Tustumi et al. is intriguing, it is not substantiated by quality trials and there are several arguments against it.

First, the symptoms of GERD, especially heartburn and chest pain, are not uncommon in cases with untreated achalasia.³ The majority of these symptoms subside after treatment irrespective of the presence or absence of reflux esophagitis. Second, the spectrum of achalasia is quite wide according to the degree of neuronal loss.⁴ It is generally believed that type I or classic achalasia is a more advanced form of disease with no post-deglutitive contractility, which is likely the consequence of nearly complete aganglionosis.⁴ In contrast, the degree of neuronal loss is less severe in cases with type II achalasia and there is at least some conserved contraction of longitudinal and circular smooth muscle contraction.⁵ If neuronal degeneration or the absence of longitudinal muscle contractility were to determine esophageal hyposensitivity, the symptoms of reflux would have varied according to the degree of neuronal degeneration. In contrast, the rate of symptomatic GERD after treatment does not appear to be different across sub-types of achalasia.⁶ The same argument holds for central desensitization, which is more likely in cases with long-standing achalasia. Based on this hypothesis it may be speculated that the duration of the disease and the degree of esophageal dilatation should affect esophageal sensitivity. Quite the reverse, the response of the esophagus to mechanical and chemical stimuli did not differ according to disease duration, sub-type of achalasia, and the type of treatment in a recent well-conducted study.⁶ Third, the phenomenon of esophageal hyposensitivity may not be universal after POEM. In contrast to the lack of symptoms in a majority of the patients, those with post-POEM reflux symptoms demonstrate esophageal hypersensitivity to chemical and mechanical stimuli.⁶ Moreover, the outcomes of the acid perfusion test have been found to be similar between healthy controls and asymptomatic patients with achalasia after treatment.

In conclusion, “one size does not fit all” and the hypothesis of esophageal hyposensitivity before or after treatment in cases with achalasia needs to be substantiated in future studies.