Skip to main content

Severe spruelike enteropathy and collagenous colitis caused by olmesartan

Abstract

Background

Olmesartan, which is an angiotensin II receptor blocker, reportedly causes spruelike enteropathy, with intestinal villous atrophy as its typical histopathological finding. Interestingly, collagenous and/or lymphocytic gastritis and colitis occur in some patients. We report the case of a 73-year-old Japanese man with a 2-month clinical history of severe diarrhea and weight loss. There were few reports in which spruelike enteropathy and collagenous colitis were both observed and could be followed up.

Case presentation

We report a case of a 73-year-old man with a 2-month clinical history of severe diarrhea and weight loss. He had taken olmesartan for hypertension treatment for 5 years. Endoscopic examination with biopsies revealed intestinal villous atrophy and collagenous colitis. Suspecting enteropathy caused by olmesartan, which was discontinued on admission because of hypotension, we continued to stop the drug. Within 3 weeks after olmesartan discontinuation, his clinical symptoms improved. After 3 months, follow-up endoscopy showed improvement of villous atrophy but not of the thickened collagen band of the colon. However, the mucosa normalized after 6 months, histologically confirming that the preexistent pathology was finally resolved.

Conclusions

This report presents a case in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. In unexplained cases of diarrhea, medication history should be reconfirmed and this disease should be considered a differential diagnosis.

Peer Review reports

Background

,1,1,1,2]. Pathological evidence of the stomach and colon suggests that olmesartan may affect the entire gastrointestinal tract. There were few reports in which spruelike enteropathy and collagenous colitis were both observed and could be followed up.

Herein, we report a case of severe enteropathy and collagenous colitis associated with olmesartan use.

Case presentation

A 73-year-old Japanese man with a history of olmesartan intake (20 mg daily for 5 years) for hypertension treatment was admitted to a local hospital complaining of watery, nonbloody diarrhea approximately 10 times daily since 2 months. In 2 months, he lost 10 kg of his weight. Blood tests, CT, and endoscopy were performed, but the cause of his diarrhea remained unknown. Hence, he was referred to our hospital for further examination. His physical examination results were unremarkable. However, laboratory results (Additional file 1) indicated anemia (hemoglobin, 10.5 g/dL) and hypoalbuminemia (3.4 g/dL). We searched DQA1 and DQB1. HLA DQ4 and DQ6 were positive. Meanwhile, stool culture, Clostridium difficile toxin, HLA-DQ2/DQ8, and IgA antibodies to tissue transglutaminase and endomysial, were all negative. Abdominal computer tomography was unremarkable. Esophagogastroduodenoscopy (EGD) revealed villous atrophy and a mosaic pattern of the duodenal mucosa (Fig. 1), while colonoscopy (CS) detected villous atrophy of the terminal ileum and diffuse slight edema of the colon (Additional file 2). The stomach, duodenum, terminal ileum, and colon were randomly biopsied. Pathological findings of the duodenum and ileum showed villous atrophy, intraepithelial lymphocyte infiltration, and collagen band, and those of the colon showed a 14 μm collagen band (Fig. 2). Moreover, capsule endoscopy displayed villous atrophy of the entire small intestine. Taken together, we suspected that the patient had olmesartan-associated spruelike enteropathy. Hence, olmesartan, which was stopped on admission because of hypotension, remained withdrawn, and was switched to amlodipine.

Fig. 1
figure 1

Esophagogastroduodenoscopy at the initial visit. a White-light imaging shows villous atrophy and a mosaic pattern of the duodenal mucosa. b Magnification endoscopy with narrow-band imaging shows villous atrophy of the duodenal mucosa

Fig. 2
figure 2

a Duodenal biopsy (hematoxylin–eosin, 0924; top: –743; width: 5205; height: 3719; visibility: visible; mso-wrap-style: square); b Duodenal biopsy (Masson trichrome, ichromeichrome eosin, 0924; top: Colonic biopsy (hematoxylin–eosin, 0924; top: − 743; width: 5205; height: 3719; visibility: visible)

Within 3 weeks after olmesartan discontinuation, his clinical symptoms improved. Three months later, diarrhea resolved, and the duodenum, terminal ileum, and colon showed a normal appearance on EGD/CS (Fig. 3). As shown in the biopsies of the duodenum and terminal ileum, the villous architecture of the duodenal and ileal mucosa almost completely recovered (Fig. 4), but in colonic biopsies, the collagen band only slightly improved (Additional file 3). Six months after discontinuing olmesartan, follow-up endoscopy showed a histologically normal colonic mucosa.

Fig. 3
figure 3

Esophagogastroduodenoscopy showed a normal appearance of the duodenum 3 months after olmesartan discontinuation

Fig. 4
figure 4

Biopsy showed an almost complete recovery of the villi on the duodenal mucosa 3 months after olmesartan discontinuation (hematoxylin–eosin, redof)

Discussion and conclusion

Olmesartan-associated spruelike enteropathy is a type of enteropathy induced by olmesartan administration. It is characterized by severe diarrhea and weight loss. The duration of olmesartan exposure before the onset of diarrhea varies from months to years [1,3,1,1,1,4]. HLA-DQ2 or DQ8 haplotypes were present in 71% of patients with olmesartan-associated spruelike enteropathy [3,1,5,6,2,

,2]. CS or capsule endoscopy may reveal villous atrophy and ulceration in the jejunum and ileum [2,

,7,8,9,

,1,10,11,12,

,13,14,1,15,16,17,15]. Some patients with collagenous colitis showed a typical histology but had no symptoms [18,

Hence, this report presents a rare case in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. Villous atrophy of the small intestine may have a greater effect on diarrhea caused by olmesartan even in cases with collagenous colitis.

In conclusion, both the large and small intestines should be assessed for villous atrophy and other abnormalities.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ARBs:

Angiotensin II receptor blockers

CS:

Colonoscopy

EGD:

Esophagogastroduodenoscopy

References

  1. Rubio-Tapia A, Herman ML, Ludvigsson JF, Kelly DG, Mangan TF, Wu TT, Murray JA. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc. 2012;87:732–8. https://doi.org/10.1016/j.mayocp.2012.06.003,PMID22728033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Marthey L, Cadiot G, Seksik P, Pouderoux P, Lacroute J, Skinazi F, et al. Olmesartan-associated enteropathy: results of a national survey. Aliment Pharmacol Ther. 2014;40:1103–9. https://doi.org/10.1111/apt.12937,PMID25199794.

    Article  CAS  PubMed  Google Scholar 

  3. Ianiro G, Bibbò S, Montalto M, Ricci R, Gasbarrini A, Cammarota G. Systematic review: sprue-like enteropathy associated with olmesartan. Aliment Pharmacol Ther. 2014;40:16–23. https://doi.org/10.1111/apt.12780,PMID24805127.

    Article  CAS  PubMed  Google Scholar 

  4. Matt P, Schoenhoff F, Habashi J, Holm T, Van Erp C, Loch D, et al. Circulating transforming growth factor-beta in Marfan syndrome. Circulation. 2009;120:526–32. https://doi.org/10.1161/CIRCULATIONAHA.108.841981,PMID19635970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shahzad MA, Harding D, Ruszkiewicz A, Tran E, England G, Philpott H. Gastrointestinal: olmesartan-induced enteropathy. J Gastroenterol Hepatol. 2018;33:1691. https://doi.org/10.1111/jgh.14317,PMID29968297.

    Article  CAS  PubMed  Google Scholar 

  6. Choi EY, McKenna BJ. Olmesartan-associated enteropathy: a review of clinical and histologic findings. Arch Pathol Lab Med. 2015;139:1242–7. https://doi.org/10.5858/arpa.2015-0204-RA,PMID26414468.

    Article  CAS  PubMed  Google Scholar 

  7. Badreldin R, Barrett P, Wooff DA, Mansfield J, Yiannakou Y. How good is zoom endoscopy for assessment of villous atrophy in coeliac disease? Endoscopy. 2005;37:994–8. https://doi.org/10.1055/s-2005-870245,PMID16189773.

    Article  CAS  PubMed  Google Scholar 

  8. Eusébio M, Caldeira P, Antunes AG, Ramos A, Velasco F, Cadillá J, et al. Olmesartan-induced enteropathy: an unusual cause of villous atrophy. GE Port J Gastroenterol. 2016;23:91–5. https://doi.org/10.1016/j.jpge.2015.09.005,PMID28868439.

    Article  PubMed  Google Scholar 

  9. Rondonotti E, Spada C, Cave D, Pennazio M, Riccioni ME, De Vitis I, et al. Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study. Am J Gastroenterol. 2007;102:1624–31. https://doi.org/10.1111/j.1572-0241.2007.01238.x,PMID17459022.

    Article  PubMed  Google Scholar 

  10. Fujisawa M, Matsushima M, Ueda T, Kaneko M, Fujimoto R, Sano M, et al. Celiac disease complicated by rhabdomyolysis. Intern Med. 2021;60:217–22. https://doi.org/10.2169/internalmedicine.5358-20,PMID32921688.

    Article  PubMed  Google Scholar 

  11. Yamamoto Y, Yamada T, Akutsu D, Sugaya A, Murashita T, Matsuda K, et al. Collagenous sprue diagnosed by double balloon endoscopy. Case Reports Dig Endosc. 2014;26:108–12. https://doi.org/10.1111/den.12007,PMID23368698.

    Article  PubMed  Google Scholar 

  12. Jansson-Knodell CL, Hujoel IA, Rubio-Tapia A, Murray JA. Not all that flattens villi is celiac disease: a review of enteropathies. Mayo Clin Proc. 2018;93:509–17. https://doi.org/10.1016/j.mayocp.2017.10.025,PMID29622097.

    Article  PubMed  Google Scholar 

  13. Uehara T, Ikusaka M, Ohira Y, Noda K, Suzuki S, Shikino K, et al. Olmesartan-induced enteropathy manifesting as Wernicke-Korsakoff syndrome. Intern Med. 2016;55:3675–8. https://doi.org/10.2169/internalmedicine.55.7388,PMID27980272.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fukushima M, Kitamoto H, Inokuma T, Imai Y. Severe spruelike enteropathy associated with olmesartan observed by double-balloon enteroscopy. Gastrointest Endosc. 2016;83:269–70. https://doi.org/10.1016/j.gie.2015.06.004,PMID26149710.

    Article  PubMed  Google Scholar 

  15. Bashari DR. Severe sprue-like enteropathy and colitis due to olmesartan: lessons learned from a rare entity. Gastroenterology Res. 2020;13:150–4. https://doi.org/10.14740/gr1301,PMID32864026.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ebrahim VS, Martin J, Murthy S, Odstrcil E, Huang H, Polter D. Olmesartan-associated enteropathy. Proc (Bayl Univ Med Cent). 2017;30:348–50. https://doi.org/10.1080/08998280.2017.11929644,PMID28670083.

    Article  Google Scholar 

  17. Costetti M, Schiepatti A, Fraticelli S, Costa S, Maimaris S, Lenti MV, et al. Dig Liver Dis. 2021;S1590–8658:371–6. https://doi.org/10.1016/j.dld.2021.07.002,PMID34330666.

    Article  Google Scholar 

  18. Thörn M, Sjöberg D, Holmström T, Rönnblom A. Collagenous colitis without diarrhoea at diagnosis – a follow up study. Scand J Gastroenterol. 2019;54:194–7. https://doi.org/10.1080/00365521.2019.1570325,PMID30782025.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the technical and clerical assistance of Dr. Fujita of the Department of Endoscopy of Aiiku Hospital in Sapporo, in the preparation of the manuscript. The authors also would like to thank Enago (www.enago.jp) for the English language review.

Funding

No funding was received to accomplish this work.

Author information

Authors and Affiliations

Authors

Contributions

SK contributed to conceptualization, data curation, resource collection, and writing of the original manuscript. KM contributed to conceptualization, data curation, resources, original draft writing, and review and editing. YM, SS, KK, AN, MY, NE, and MU contributed to conceptualization, data curation, and resource collection. HK contributed to data curation and resources. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Kana Matsuda.

Ethics declarations

Ethics approval and consent to participate

Ethics approval by committee was not required for this case report. It was conducted in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent for study participation was obtained from the patient.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

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

Supplementary Information

Additional file 1.

Initial Laboratory Studies.

Additional file 2.

Colonoscopy showed a diffuse slight edema of the colon.

Additional file 3.

Biopsy showed slight improvement of the collagen band in the colon 3 months after olmesartan discontinuation (Masson trichrome).

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaneko, S., Matsuda, K., Mizuta, Y. et al. Severe spruelike enteropathy and collagenous colitis caused by olmesartan. BMC Gastroenterol 21, 350 (2021). https://doi.org/10.1186/s12876-021-01926-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12876-021-01926-y

Keywords