Skip to main content

Advertisement

SpringerLink
Log in

Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Backgrounds

Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan.

Methods

A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE.

Results

Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone.

Conclusions

Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Miller JB, Gandhi N, Clarke J, et al. Gastrointestinal involvement in systemic sclerosis: an update. J Clin Rheumatol. 2018;24:328–37.

    Article  PubMed  Google Scholar 

  2. Omair MA, Lee P. Effect of gastrointestinal manifestations on quality of life in 87 consecutive patients with systemic sclerosis. J Rheumatol. 2012;39:992–6.

    Article  PubMed  Google Scholar 

  3. Matsuzaki T, Sugiyama T, Sekiguchi T, et al. Reflux esophagitis in progressive systemic sclerosis. (1) Nocturnal gastroesophageal motility in recumbent position. Jpn J Gastro-Enterol. 1983;80:2329–38.

    CAS  Google Scholar 

  4. Marie I, Dominique S, Levesque H, et al. Esophageal involvement and pulmonary manifestations in systemic sclerosis. Arthritis Rheum. 2001;45:346–54.

    Article  CAS  PubMed  Google Scholar 

  5. Roman S, Hot A, Fabien N, et al. Esophageal dysmotility associated with systemic sclerosis: a high-resolution manometry study. Dis Esophagus. 2011;24:299–304.

    Article  CAS  PubMed  Google Scholar 

  6. Tang DM, Pathikonda M, Harrison M, et al. Symptoms and esophageal motility based on phenotypic findings of scleroderma. Dis Esophagus. 2013;26:197–203.

    Article  CAS  PubMed  Google Scholar 

  7. Kimmel JN, Carlson DA, Hinchcliff M, et al. The association between systemic sclerosis disease manifestations and esophageal high-resolution manometry parameters. Neurogastroenterol Motil. 2016;28:1157–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Crowell MD, Umar SB, Griffing WL, et al. Esophageal motor abnormalities in patients with scleroderma: heterogeneity, risk factors, and effects on quality of life. Clin Gastroenterol Hepatol. 2017;15(207–13): e1.

    Google Scholar 

  9. Abozaid HSM, Imam HMK, Abdelaziz MM, et al. High-resolution manometry compared with the University of California, Los Angeles Scleroderma Clinical Trials Consortium GIT 2.0 in Systemic Sclerosis. Semin Arthritis Rheum. 2017;47:403–8.

    Article  PubMed  Google Scholar 

  10. Kuribayashi S, Motegi SI, Hara K, et al. Relationship between esophageal motility abnormalities and skin or lung involvements in patients with systemic sclerosis. J Gastroenterol. 2019;54:950–62.

    Article  PubMed  Google Scholar 

  11. Matsuzaki T, Sugiyama T, Sekiguchi T, et al. A study on reflux esophagitis in progressive systemic sclerosis (PSS): second report. Nocturnal gastroesophageal motility and esophageal pH in supine position. Jpn J Gastro-Enterol. 1985;82:1300–7.

    CAS  Google Scholar 

  12. Marie I, Ducrotte P, Denis P, et al. Oesophageal mucosal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy. Aliment Pharmacol Ther. 2006;24:1593–601.

    Article  CAS  PubMed  Google Scholar 

  13. Stern EK, Carlson DA, Falmagne S, et al. Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients. Neurogastroenterol Motil. 2018;30. https://doi.org/10.1111/nmo.13247.

    Article  PubMed  Google Scholar 

  14. Iwakiri K, Fujiwara Y, Manabe N, et al. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021. J Gastroenterol. 2022;57:267–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tabuchi M, Minami H, Akazawa Y, et al. Use of vonoprazan for management of systemic sclerosis-related gastroesophageal reflux disease. Biomed Rep. 2021;14:25.

    Article  CAS  PubMed  Google Scholar 

  16. Shirai Y, Kawami N, Iwakiri K, et al. Use of vonoprazan, a novel potassium-competitive acid blocker, for the treatment of proton pump inhibitor-refractory reflux esophagitis in patients with systemic sclerosis. J Scleroderma Relat Disord. 2022;7:57–61.

    Article  PubMed  Google Scholar 

  17. Eba J, Nakamura K. Overview of the ethical guidelines for medical and biological research involving human subjects in Japan. Jpn J Clin Oncol. 2022;52:539–44.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kahrilas PJ, Bredenoord AJ, Fox M, et al. The Chicago classification of esophageal motility disorders v3.0. Neurogastroenterol Motil. 2015;27:160–74.

    Article  CAS  PubMed  Google Scholar 

  19. Kuribayashi S, Iwakiri K, Kawada A, et al. Variant parameter values-as defined by the Chicago Criteria-produced by ManoScan and a new system with Unisensor catheter. Neurogastroenterol Motil. 2015;27:188–94.

    Article  CAS  PubMed  Google Scholar 

  20. Kuribayashi S, Iwakiri K, Shinozaki T, et al. Clinical impact of different cut-off values in high-resolution manometry systems on diagnosing esophageal motility disorders. J Gastroenterol. 2019;54:1078–82.

    Article  CAS  PubMed  Google Scholar 

  21. Hill LD, Kozarek RA, Kraemer SJ, et al. The gastroesophageal flap valve: in vitro and in vivo observations. Gastrointest Endosc. 1996;44:541–7.

    Article  CAS  PubMed  Google Scholar 

  22. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999;45:172–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy. 1969;1:87–97.

    Article  Google Scholar 

  24. Miyazaki H, Igarashi A, Takeuchi T, et al. Vonoprazan versus proton-pump inhibitors for healing gastroesophageal reflux disease: a systematic review. J Gastroenterol Hepatol. 2019;34:1316–28.

    Article  CAS  PubMed  Google Scholar 

  25. Kusano M, Shimoyama Y, Sugimoto S, et al. Development and evaluation of FSSG: frequency scale for the symptoms of GERD. J Gastroenterol. 2004;39:888–91.

    Article  PubMed  Google Scholar 

  26. Kusano M, Hosaka H, Kawada A, et al. Development and evaluation of a modified frequency scale for the symptoms of gastroesophageal reflux disease to distinguish functional dyspepsia from non-erosive reflux disease. J Gastroenterol Hepatol. 2012;27:1187–91.

    Article  PubMed  Google Scholar 

  27. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988;15:202–5.

    CAS  PubMed  Google Scholar 

  28. Clements PJ, Lachenbruch PA, Seibold JR, et al. Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993;20:1892–6.

    CAS  PubMed  Google Scholar 

  29. Sakaguchi M, Oka H, Hashimoto T, et al. Obesity as a risk factor for GERD in Japan. J Gastroenterol. 2008;43:57–62.

    Article  PubMed  Google Scholar 

  30. Bassotti G, Battaglia E, Debernardi V, et al. Esophageal dysfunction in scleroderma: relationship with disease subsets. Arthritis Rheum. 1997;40:2252–9.

    Article  CAS  PubMed  Google Scholar 

  31. Kaye SA, Siraj QH, Agnew J, et al. Detection of early asymptomatic esophageal dysfunction in systemic sclerosis using a new scintigraphic grading method. J Rheumatol. 1996;23:297–301.

    CAS  PubMed  Google Scholar 

  32. Ebert EC. Esophageal disease in scleroderma. J Clin Gastroenterol. 2006;40:769–75.

    Article  PubMed  Google Scholar 

  33. Ntoumazios SK, Voulgari PV, Potsis K, et al. Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem. Semin Arthritis Rheum. 2006;36:173–81.

    Article  PubMed  Google Scholar 

  34. Ho SC, Chang CS, Wu CY, et al. Ineffective esophageal motility is a primary motility disorder in gastroesophageal reflux disease. Dig Dis Sci. 2002;47:652–6.

    Article  PubMed  Google Scholar 

  35. Carlson DA, Crowell MD, Kimmel JN, et al. Loss of peristaltic reserve, determined by multiple rapid swallows, is the most frequent esophageal motility abnormality in patients with systemic sclerosis. Clin Gastroenterol Hepatol. 2016;14:1502–6.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Shaker A, Stoikes N, Drapekin J, et al. Multiple rapid swallow responses during esophageal high-resolution manometry reflect esophageal body peristaltic reserve. Am J Gastroenterol. 2013;108:1706–12.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The English language was reviewed by a native English speaker (NAI Inc., Yokohama, Japan).

Funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI for Early-Career Scientists Grant Number JP18K15772.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi Maebashi, Gunma, 371-8511, Japan

    Shiko Kuribayashi, Fumihiko Nakamura, Hiroko Hosaka & Toshio Uraoka

  2. Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Sei-Ichiro Motegi, Akiko Sekiguchi, Mai Ishikawa & Yukie Endo

  3. Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Kenichiro Hara & Koichi Yamaguchi

  4. Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Tomonari Harada, Hidemi Sorimachi & Masaru Obokata

  5. Department of Public Health, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Mitsuo Uchida

Authors
  1. Shiko Kuribayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumihiko Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sei-Ichiro Motegi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenichiro Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroko Hosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akiko Sekiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mai Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yukie Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tomonari Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hidemi Sorimachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masaru Obokata
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mitsuo Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Koichi Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Toshio Uraoka
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SK is responsible for study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, statistical analysis, obtained funding. FN is responsible for drafting of the manuscript. SM and KH are responsible for study concept and design, acquisition of data, interpretation of data, and critical revision of the manuscript. HH, AS, MI, YE, TH, HS, MO, and MU are responsible for acquisition of data, interpretation of data, and critical revision of the manuscript. TU is responsible for study supervision.

Corresponding author

Correspondence to Shiko Kuribayashi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuribayashi, S., Nakamura, F., Motegi, SI. et al. Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan. J Gastroenterol 59, 179–186 (2024). https://doi.org/10.1007/s00535-024-02076-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-024-02076-0

Keywords

Search

Navigation