Long-term course of untreated asymptomatic esophageal eosinophilia and minimally symptomatic eosinophilic esophagitis

 

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Abstract

Background and study aims The long-term course of untreated asymptomatic esophageal eosinophilia (aEE) and minimally symptomatic eosinophilic esophagitis (mEoE) are not well understood. This study aimed to clarify this course.

Patients and methods A total of 36 patients with EE who were endoscopically followed up for more than 5 years, and who underwent more than one endoscopy evaluation after the first diagnosis, were investigated. These patients were divided into two groups according to the presence or absence of the continuous treatment: no treatment group (NT group, n=22) and proton pump inhibitor/potassium competitive acid blocker group (Tx group, n=14). Symptoms and endoscopic and histological findings were retrospectively reviewed according to endoscopic phenotypes. Endoscopic assessment was performed using the EoE endoscopic reference score (EREFS).

Results The median follow-up period was 84.5 months in the Tx group and 92 months in the NT group. During the follow-up period, about half of the patients in the Tx-diffuse group persisted EREFS >3, while the remaining half had EREFS ≤2. The total EREFS in the NT-diffuse group remained almost unchanged (median: 2–4) without apparent exacerbation. In contrast, EREFS in the NT-localized group exhibited an unchanged or gradually decreasing trend, with statistical significance from the first diagnosis to 72 to 83 months after.

Conclusions Untreated aEE and mEoE are not likely to worsen even without treatment at least for a median follow-up of 7 years. Instead, the localized type may spontaneously improve, implying a different pathogenesis in the presence of the diffuse type. Further studies should clarify the long-term prognosis.

Publication History

Received: 30 October 2023

Accepted after revision: 04 January 2024

Accepted Manuscript online:
04 March 2024

Article published online:
15 April 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Lucendo AJ, Molina-Infante J, Arias Á. et al. Guidelines on eosinophilic esophagitis: Evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J 2017; 5: 335-358 DOI: 10.1177/2050640616689525. (PMID: 28507746)
  CrossrefPubMedGoogle Scholar
• 2 Dellon ES, Hirano I. Epidemiology and natural history of eosinophilic esophagitis. Gastroenterology 2018; 154: 319-332.e3 DOI: 10.1053/j.gastro.2017.06.067. (PMID: 28774845)
  CrossrefPubMedGoogle Scholar
• 3 Lam AY, Lee JK, Coward S. et al. Epidemiologic burden and projections for eosinophilic esophagitis-associated emergency department visits in the United States: 2009–2030. Clin Gastroenterol Hepatol 2023; 21: 3041-3050.e3 DOI: 10.1016/j.cgh.2023.04.028.
  CrossrefPubMedGoogle Scholar
• 4 Ishimura N, Okimoto E, Shibagaki K. et al. Similarity and difference in the characteristics of eosinophilic esophagitis between Western countries and Japan. Dig Endosc 2021; 33: 708-719
  CrossrefPubMedGoogle Scholar
• 5 Fujiwara Y. Symptom-based diagnostic approach for eosinophilic esophagitis. J Gastroenterol 2020; 55: 833-845 DOI: 10.1007/s00535-020-01701-y. (PMID: 32720208)
  CrossrefPubMedGoogle Scholar
• 6 Adachi K, Mishiro T, Tanaka S. et al. Suitable biopsy site for detection of esophageal eosinophilia in eosinophilic esophagitis suspected cases. Dig Endosc 2016; 28: 139-144 DOI: 10.1111/den.12555. (PMID: 26418844)
  CrossrefPubMedGoogle Scholar
• 7 Sato H, Honma T, Nozawa Y. et al. Eosinophilic esophagitis in Japanese patients: A mild and slow-progressing disorder. PLoS One 2018; 13: e0206621 DOI: 10.1371/journal.pone.0206621. (PMID: 30388148)
  CrossrefPubMedGoogle Scholar
• 8 Tanaka F, Fukumoto S, Morisaki T. et al. Obesity and hiatal hernia may be non-allergic risk factors for esophageal eosinophilia in Japanese adults. Esophagus 2019; 16: 309-315 DOI: 10.1007/s10388-019-00662-3. (PMID: 30927164)
  CrossrefPubMedGoogle Scholar
• 9 Ronkainen J, Talley NJ, Aro P. et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: The population-based Kalixanda study. Gut 2007; 56: 615-620 DOI: 10.1136/gut.2006.107714. (PMID: 17135307)
  CrossrefPubMedGoogle Scholar
• 10 Ma X, Xu Q, Zheng Y. et al. Prevalence of esophageal eosinophilia and eosinophilic esophagitis in adults: A population-based endoscopic study in Shanghai, China. Dig Dis Sci 2015; 60: 1716-1723 DOI: 10.1007/s10620-014-3512-9. (PMID: 25599960)
  CrossrefPubMedGoogle Scholar
• 11 Dellon ES, Liacouras CA, Molina-Infante J. et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference. Gastroenterology 2018; 155: 1022-1033.e10
  CrossrefPubMedGoogle Scholar
• 12 Ishimura N, Sumi S, Okada M. et al. Is asymptomatic esophageal eosinophilia the same disease entity as eosinophilic esophagitis?. Clin Gastroenterol Hepatol 2019; 17: 1405-1407 DOI: 10.1016/j.cgh.2018.08.048. (PMID: 30144524)
  CrossrefPubMedGoogle Scholar
• 13 Kitamura H, Tanaka F, Nadatani Y. et al. Eosinophilic esophagitis and asymptomatic esophageal eosinophilia display similar immunohistological profiles. J Clin Biochem Nutr 2021; 68: 246-252 DOI: 10.3164/jcbn.20-49. (PMID: 34025028)
  CrossrefPubMedGoogle Scholar
• 14 Suzuki Y, Iizuka T, Hosoi A. et al. Clinicopathological differences between eosinophilic esophagitis and asymptomatic esophageal eosinophilia. Intern Med 2022; 61: 1319-1327
  CrossrefPubMedGoogle Scholar
• 15 Muroi K, Kakushima N, Furukawa K. et al. Subjective symptoms in patients with eosinophilic esophagitis are related to esophageal wall thickness and esophageal body pressure. Dig Dis Sci 2021; 66: 2291-2300
  CrossrefPubMedGoogle Scholar
• 16 Kanamori A, Tanaka F, Takashima S. et al. Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis. Esophagus 2023; 20: 333-341
  CrossrefPubMedGoogle Scholar
• 17 Suzuki Y, Ochiai Y, Hosoi A. et al. Mucosal and submucosal thickening of esophageal wall is a promising factor in the development of symptoms in eosinophilic esophagitis. Gut Liver 2024; 18: 50-59 DOI: 10.5009/gnl220490. (PMID: 36789578)
  CrossrefPubMedGoogle Scholar
• 18 Kon T, Abe Y, Sasaki Y. et al. Clinical features of esophageal eosinophilia according to endoscopic phenotypes. Intern Med 2020; 59: 2971-2979 DOI: 10.2169/internalmedicine.4447-20. (PMID: 32759578)
  CrossrefPubMedGoogle Scholar
• 19 Ishibashi F, Fukushima K, Onizuka R. et al. Risk of progression to eosinophilic esophagitis in patients with asymptomatic esophageal eosinophilia: A retrospective pilot study. JGH Open 2020; 4: 422-428
  CrossrefPubMedGoogle Scholar
• 20 Schoepfer AM, Safroneeva E, Bussmann C. et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 2013; 145: 1230-6.e1
  CrossrefPubMedGoogle Scholar
• 21 Dellon ES, Kim HP, Sperry SLW. et al. A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc 2014; 79: 577-85.e4
  CrossrefPubMedGoogle Scholar
• 22 Lipka S, Kumar A, Richter JE. Impact of diagnostic delay and other risk factors on eosinophilic esophagitis phenotype and esophageal diameter. J Clin Gastroenterol 2016; 50: 134-140 DOI: 10.1097/MCG.0000000000000297. (PMID: 25710524)
  CrossrefPubMedGoogle Scholar
• 23 Hirano I, Moy N, Heckman MG. et al. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: Validation of a novel classification and grading system. Gut 2013; 62: 489-495 DOI: 10.1136/gutjnl-2011-301817. (PMID: 22619364)
  CrossrefPubMedGoogle Scholar
• 24 Cotton CC, Woosley JT, Moist SE. et al. Determination of a treatment response threshold for the Eosinophilic esophagitis Endoscopic Reference Score. Endoscopy 2022; 54: 635-643 DOI: 10.1055/a-1675-7860. (PMID: 34674209)
  Article in Thieme ConnectPubMedGoogle Scholar
• 25 Dellon ES, Khoury P, Muir AB. et al. A clinical severity index for eosinophilic esophagitis: Development, consensus, and future directions. Gastroenterology 2022; 163: 59-76 DOI: 10.1053/j.gastro.2022.03.025. (PMID: 35606197)
  CrossrefPubMedGoogle Scholar
• 26 Sawada A, Hashimoto A, Uemura R. et al. Association between endoscopic findings of eosinophilic esophagitis and responsiveness to proton pump inhibitors. Endosc Int Open 2019; 7: E433-E439
  Article in Thieme ConnectPubMedGoogle Scholar
• 27 Safroneeva E, Straumann A, Coslovsky M. et al. Symptoms have modest accuracy in detecting endoscopic and histologic remission in adults with eosinophilic esophagitis. Gastroenterology 2016; 150: 581-590.e4
  CrossrefPubMedGoogle Scholar
• 28 Alexander R, Alexander JA, Ravi K. et al. Measurement of observed eating behaviors in patients with active and inactive eosinophilic esophagitis. Clin Gastroenterol Hepatol 2019; 17: 2371-2373
  CrossrefPubMedGoogle Scholar
• 29 Straumann A, Spichtin HP, Grize L. et al. Natural history of primary eosinophilic esophagitis: A follow-up of 30 adult patients for UP to 11.5 years. Gastroenterology 2003; 125: 1660-1669 DOI: 10.1053/j.gastro.2003.09.024. (PMID: 14724818)
  CrossrefPubMedGoogle Scholar
• 30 Bohm M, Jacobs JW, Gupta A. et al. Most children with eosinophilic esophagitis have a favorable outcome as young adults. Dis Esophagus 2017; 30: 1-6
  CrossrefPubMedGoogle Scholar
• 31 Podboy AJ, Lavey C, Mara K. et al. Eosinophilic esophagitis is rarely continually symptomatic 10 years after an initial treatment course in adults. Dig Dis Sci 2019; 64: 3568-3578 DOI: 10.1007/s10620-019-05636-0. (PMID: 31065898)
  CrossrefPubMedGoogle Scholar
• 32 Yamamoto M, Nagashima S, Yamada Y. et al. Comparison of nonesophageal eosinophilic gastrointestinal disorders with eosinophilic esophagitis: A nationwide survey. J Allergy Clin Immunol Pract 2021; 9: 3339-3349
  CrossrefPubMedGoogle Scholar
• 33 Schreiner P, Biedermann L, Greuter T. et al. How to approach adult patients with asymptomatic esophageal eosinophilia. Dis Esophagus 2021; 34: 1-7
  Google Scholar
• 34 Okimoto E, Ishimura N, Ishihara S. Clinical characteristics and treatment outcomes of patients with eosinophilic esophagitis and eosinophilic gastroenteritis. Digestion 2021; 102: 33-40 DOI: 10.1159/000511588. (PMID: 33202408)
  CrossrefPubMedGoogle Scholar
• 35 Lucendo AJ, Molina-Infante J. Current treatment options and long-term outcomes in patients with eosinophilic esophagitis. Expert Rev Clin Immunol 2022; 18: 859-872 DOI: 10.1080/1744666X.2022.2096591. (PMID: 35770955)
  CrossrefPubMedGoogle Scholar

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