Letter on “Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders”

We read with great interest the study by Reddy et al1Reddy C.A. et al.Clin Gastroenterol Hepatol. 2024; 22: 34-41.e2Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar on the risk of eosinophilic esophagitis (EoE) and other allergic disorders in patients with achalasia. The authors reported that patients with achalasia could have high prevalence of EoE and other allergic disorders, indicating that achalasia could potentially be associated with allergic disorders. The results have important clinical implications because they inform clinicians regarding further assessments needed before conducting invasive achalasia treatments. However, we would like to raise some issues regarding the study. First, to validate the achalasia diagnosis by International Classification of Diseases-9 or -10 diagnosis codes, the authors checked high-resolution manometry studies from patients. Although these manometric criteria are essential, we believe that endoscopy findings could also be applied as part of the definition algorithm because these were recommended as additional criteria in some guidelines, such as American College of Gastroenterology Clinical Guidelines2Vaezi M.F. et al.Am J Gastroenterol. 2020; 115: 1393-1411Crossref PubMed Scopus (181) Google Scholar and the 2018 International Society for Diseases of the Esophagus achalasia guideline. Upper endoscopy can allow excluding neoplastic pseudoachalasia or other mechanical obstruction and is easier to observe moderate to severely dilated esophagus.3Zaninotto G. et al.Dis Esophagus. 2018; 31Crossref Scopus (228) Google Scholar Therefore, we suggest that endoscopy records could be included while confirming the diagnosis of achalasia for stricter definition to avoid potential misclassification bias. Second, the authors conducted age stratification analyses based on a cutoff point of 40 years. However, EoE can also occur in younger adults and children. In terms of symptoms, children with EoE often present with vomiting, failure to thrive, and regurgitation, whereas adults present with heartburn, dysphagia, and food impaction. Endoscopic features and treatments also vary considerably between children and adult patients.4Markowitz J.E. et al.Gastrointest Endosc Clin N Am. 2018; 28: 59-75Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Consequently, it will be clinically meaningful to discuss the risk of EoE in younger patients with achalasia in further studies. Third, it was reported that asthma might be worse in approximately 40% of pregnant women and more symptoms occur during labor in about 10% of pregnant patients. Moreover, the treatment must be more careful, because it could have a serious impact on fetal development.5Bravo-Solarte D.C. et al.Allergy Asthma Proc. 2023; 44: 24-34Crossref PubMed Scopus (4) Google Scholar As such, we suggest that the authors perform another subgroup analysis for the association between asthma and pregnant women with achalasia. Finally, the relative risk of allergic disorders in the current study was compared with patients matched for birthyear and sex. Nevertheless, there are still some confounders that should be considered. Studies have reported that the environment is likely to affect EoE development,6Dowling P.J. et al.Clin Rev Allergy Immunol. 2019; 57: 330-339Crossref PubMed Scopus (16) Google Scholar whereas alcohol is more prevalent in EoE cases.7Koutlas N.T. et al.Dis Esophagus. 2018; 31: 1-7Crossref PubMed Scopus (26) Google Scholar Hence, we believe that environmental factors and alcohol consumption should be taken into consideration for addressing potential confounding bias. All in all, the results of the Reddy et al1Reddy C.A. et al.Clin Gastroenterol Hepatol. 2024; 22: 34-41.e2Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar study demonstrated associations between achalasia, EoE, and other allergic disorders, and could be essential for clinicians managing these patients. Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic DisordersClinical Gastroenterology and HepatologyVol. 22Issue 1PreviewAchalasia has been assumed to be an autoimmune disease targeting esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes might be allergy-driven, caused by a form of eosinophilic esophagitis (EoE) in which activated eosinophils and/or mast cells infiltrating esophageal muscle release products that disrupt motility and damage myenteric neurons. To seek epidemiologic support for this hypothesis, we identified patients with achalasia in the Utah Population Database, and explored their frequency of having EoE and other allergic disorders. Full-Text PDF ReplyClinical Gastroenterology and HepatologyVol. 22Issue 5PreviewThis letter to the editor is in response to a letter from Yun-Feng Li and Shuo-Yan Gau regarding the Clinical Gastroenterology and Hepatology paper entitled "Achalasia is Strongly Associated with Eosinophilic Esophagitis and Other Allergic Disorders" (corresponding author Stuart Spechler). We thank Drs Li and Gau for their kind comments regarding the importance of our study, and for their thoughtful suggestions. As they note, we validated the accuracy of International Classification of Diseases codes for achalasia based on high-resolution manometry studies showing the essential achalasia characteristics of impaired deglutitive lower esophageal sphincter relaxation and aperistalsis. Full-Text PDF