Association of sprue-like enteropathy and angiotensin receptor-1 antagonists


Over the past 5 years several case reports and cohort studies have been published that describe a sprue-like enteropathy (SLE) with abdominal pain, chronic diarrhea and weight loss, after taking angiotensin type 1 receptor blockers (ARB). The initial case series from the Mayo Clinic, which described 22 cases of olmesartan-induced SLE, was followed by numerous case descriptions for almost all ARBs. A total of 73 case reports have been described so far that show evidence of ARB-associated enteropathy with villous atrophy and full recovery 3–12 months after discontinuation of the sartan in question. Of these, 59 cases were olmesartan-associated cases of SLE, another 14 case reports have been published for telmisartan (4), valsartan (3), losartan (2), candesartan (1) and eprosartan (1). Based on the available cohort studies, ARB-associated intestinal malabsorption occurs in 9.8–14 cases per 100,000 patients treated with ARBs, the number treated to harm is over 31,000 patient-years. Although the majority of case reports have been published with olmesartan, in the cohort studies no clear difference within the ARBs can be ruled out. The SLE is rare but must be suspected and diagnostically investigated in every patient presenting with abdominal discomfort, chronic diarrhea and weight loss who is being treated with an ARB, after other causes have been ruled out. In such cases, discontinuing the ARB leads to a full recovery.

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

Fig. 1





Angiotensin receptor‑1 antagonist








Extracellular fluid volume








Sprue-like enteropathy

TGF beta:

Transforming growth factor beta


Tumor necrosis factor alpha


  1. 1.

    Freeman HJ. Drug-induced Sprue-like intestinal disease. Int J Celiac Dis. 2014;2:49–53.

    Article  Google Scholar 

  2. 2.

    Adike A, Corral J, Rybnicek D, Sussman D, Shah S, Quigley E. Olmesartan-induced Enteropathy. Methodist Debakey Cardiovasc J. 2016;12:230–2.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Scialom S, Malamut G, Meresse B, et al. Gastrointestinal disorder associated with Olmesartan mimics Autoimmune Enteropathy. PLoS ONE. 2015;10:e125024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Ianiro G, Bibbo S, Montalto M, Ricci R, Gasbarrini A, Cammarota G. Systematic review: Sprue-like enteropathy associated with olmesartan. Aliment Pharmacol Ther. 2014;40:16–23.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Rubio-Tapia A, Herman ML, Ludvigsson JF, et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc. 2012;87:732–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Fiorucci G, Puxeddu E, Colella R, Reboldi PG, Villanacci V, Bassotti G. Severe spruelike enteropathy due to olmesartan. Rev Esp Enferm Dig. 2014;106:142–4.

    Article  PubMed  Google Scholar 

  7. 7.

    DeGaetani M, Tennyson CA, Lebwohl B, et al. Villous atrophy and negative celiac serology: a diagnostic and therapeutic dilemma. Am J Gastroenterol. 2013;108:647–53.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Dreifuss SE, Tomizawa Y, Farber NJ, Davison JM, Sohnen AE. Spruelike enteropathy associated with olmesartan: an unusual case of severe diarrhea. Case Rep Gastrointest Med. 2013;2013:1–3.

    Google Scholar 

  9. 9.

    Fabian E, Schiller D, Wenzl H, et al. Clinical-Pathological Conference Series from the Medical University of Graz: Case No 156: 82-year-old woman with chronic diarrhea and weight loss of 20 kilograms. Wien Klin Wochenschr. 2015;127:974–80.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Basson M, Mezzarobba M, Weill A, et al. Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study. Gut. 2016;65:1664–9.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Marthey L, Cadiot G, Seksik P, et al. Olmesartan-associated enteropathy: results of a national survey. Aliment Pharmacol Ther. 2014;40:1103–9.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Mondet L, Pierson-Marchandise M, Gras V, et al. Angiotensin II receptor blockers-induced enteropathy: not just olmesartan! A case report with candesartan. Fundam Clin Pharmacol. 2016;30:62.

    Google Scholar 

  13. 13.

    Maier H, Hehemann K, Vieth M. Celiac disease-like enteropathy due to antihypertensive therapy with the angiotensin-II receptor type 1 inhibitor eprosartan. Cesk Patol. 2015;51:87–8.

    PubMed  Google Scholar 

  14. 14.

    Cammarota G, Ianiro G, Bibbo S, Letter GA. telmisartan associated enteropathy—is there any class effect? Authors’ reply. Aliment Pharmacol Ther. 2014;40:570.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Negro A, Rossi GM, Santi R, Iori V, De Marco L. A case of severe Sprue-like Enteropathy associated with Losartan. J Clin Gastroenterol. 2015;49:794.

    Article  PubMed  Google Scholar 

  16. 16.

    Herman ML, Rubio-Tapia A, Wu TT, Murray JA. A case of severe Sprue-like Enteropathy associated with Valsartan. Acg Case Rep J. 2015;2:92–4.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Sawant AP, Spoletini G, Etherington C. Losartan-associated spruelike enteropathy in a post-lung transplant cystic fibrosis patient. J Cyst Fibros. 2017;16:135.

    Article  Google Scholar 

  18. 18.

    Cyrany J, Vasatko T, Machac J, Nova M, Szanyi J, Kopacova M. Letter: telmisartan-associated enteropathy—is there any class effect? Aliment Pharmacol Ther. 2014;40:569–70.

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Mandavdhare HS, Sharma V, Prasad KK, Kumar A, Rathi M, Rana SS. Telmisartan-induced sprue-like enteropathy: a case report and a review of patients using non-olmesartan angiotensin receptor blockers. Intest Res. 2017;15:419–21.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    De Bortoli N, Ripellino C, Cataldo N, Marchi S. Unspecified intestinal malabsorption in patients treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers: a retrospective analysis in primary care settings. Expert Opin Drug Saf. 2017;16:1221–5.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Malfertheiner P, Ripellino C, Cataldo N. Severe intestinal malabsorption associated with ACE inhibitor or angiotensin receptor blocker treatment. An observational cohort study in Germany and Italy. Pharmacoepidemiol Drug Saf. 2018;27(6):581–586.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    You SC, Park H, Yoon D, Park S, Joung B, Park RW. Olmesartan is not associated with the risk of enteropathy: a Korean nationwide observational cohort study. Korean J Intern Med. 2019;34(1):90-98.

    Article  PubMed  Google Scholar 

  23. 23.

    Levens NR. Control of intestinal absorption by the renin-angiotensin system. Am J Physiol. 1985;249:G3–15.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Fandriks L. The renin-angiotensin system and the gastrointestinal mucosa. Acta Physiol (oxf). 2011;201:157–67.

    Article  CAS  Google Scholar 

  25. 25.

    Fandriks L. The angiotensin II type 2 receptor and the gastrointestinal tract. J Renin Angiotensin Aldosterone Syst. 2010;11:43–8.

    Article  PubMed  Google Scholar 

  26. 26.

    Hallersund P, Elfvin A, Helander HF, Fandriks L. The expression of renin-angiotensin system components in the human gastric mucosa. J Renin Angiotensin Aldosterone Syst. 2011;12:54–64.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Hallersund P, Helander HF, Casselbrant A, Edebo A, Fandriks L, Elfvin A. Angiotensin II receptor expression and relation to Helicobacter pylori-infection in the stomach of the Mongolian gerbil. Bmc Gastroenterol. 2010;10:3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Marietta EV, Nadeau AM, Cartee AK, et al. Immunopathogenesis of olmesartan-associated enteropathy. Aliment Pharmacol Ther. 2015;42:1303–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Esteve M, Temino R, Carrasco A, et al. Potential coeliac disease markers and autoimmunity in olmesartan induced enteropathy: a population-based study. Dig Liver Dis. 2016;48:154–61.

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Ebrahim VS, Martin J, Murthy S, Odstrcil E, Huang H, Polter D. Olmesartan-associated enteropathy. Proc (bayl Univ Med Cent). 2017;30:348–50.

    Article  Google Scholar 

  31. 31.

    Burbure N, Lebwohl B, Arguelles-Grande C, Green PH, Bhagat G, Lagana S. Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis on histopathology. Hum Pathol. 2016;50:127–34.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Sun L, Wang W, Xiao W, Liang H, Yang Y, Yang H. Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA‑6 and the Bax pathway. Biochem Biophys Res Commun. 2012;424:663–8.

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Palmquist S, Mathews B. Isolated intestinal type angioedema due to ACE-inhibitor therapy. Clin Case Rep. 2017;5:707–10.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Locascio EJ, Mahler SA, Arnold TC. Intestinal angioedema misdiagnosed as recurrent episodes of gastroenteritis. West J Emerg Med. 2010;11:391–4.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Talbot GH. Small bowel histopathologic findings suggestive of celiac disease in an asymptomatic patient receiving olmesartan. Mayo Clin Proc. 2012;87:1231–2. author reply 2.

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Cartee AK, Genere RJP, Oxentenko AS. New onset villous atrophy in a patient with celiac disease. Baillieres Clin Gastroenterol. 2018;155:988–9.

    Google Scholar 

  37. 37.

    Menne J, Haller H. Olmesartan and intestinal adverse effects in the ROADMAP study. Mayo Clin Proc. 2012;87:1230–1. author reply 2.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Theophile H, David XR, Miremont-Salame G, Haramburu F. Five cases of sprue-like enteropathy in patients treated by olmesartan. Dig Liver Dis. 2014;46:465–9.

    Article  PubMed  Google Scholar 

  39. 39.

    Eusebio M, Caldeira P, Antunes AG, et al. Olmesartan-induced Enteropathy: an unusual cause of villous atrophy. Ge Portuguese J Gastroenterol. 2016;23:91–5.

    Article  Google Scholar 

  40. 40.

    Basson M, et al. Gut. 2015;0:1–6.

    Google Scholar 

  41. 41.

    Ripellino C, Cataldo N, Scarpignato C. Unspecified intestinal malabsortion associated with angiotensin receptor blocker therapy (Abstract). Quintiles IMS, 2016,

  42. 42.

    Marild K, Lebwohl B, Green PH, Murray JA, Ludvigsson JF. Blockers of Angiotensin other than Olmesartan in patients with villous atrophy: a nationwide case-control study. Mayo Clin Proc. 2015;90:730–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Mondet L, Pierson-Marchandise, Gras V, Sevester H, Lawson P, Andrejak M, Masmoudi K. Angiotensin II receptor blcokers-induced enteropathy: not just olmesartan! A case report with candesartan. Fund Clin Pharmacol. 2016;30:67

    Google Scholar 

  44. 44.

    Famularo G, Minisola G. Relapsing Olmesartan-Associated Ileitis. Ann Pharmacother. 2016;50:1070.

    Article  PubMed  Google Scholar 

  45. 45.

    van Gils T, Robijn RJ, Bouma G, Neefjes-Borst EA, Mulder CJJ. A pitfall in suspected (refractory) celiac disease: Losartan-induced Enteropathy. Am J Gastroenterol. 2017;112:1754–5.

    Article  PubMed  Google Scholar 

  46. 46.

    Negro A, De Marco L, Cesario V, Santi R, Boni MC, Zanelli M. A case of moderate Sprue-like Enteropathy associated with Telmisartan. J Clin Med Res. 2017;9:1022–5.

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Zanelli M, Negro A, Santi R, et al. Letter: sprue-like enteropathy associated with angiotensin II receptor blockers other than olmesartan. Aliment Pharmacol Ther. 2017;46:471–3.

    Article  CAS  PubMed  Google Scholar 

  48. 48.

    Dong YH, Jin Y, Tsacogianis TN, He M, Hsieh PH, Gagne JJ. Use of olmesartan and enteropathy outcomes: a multi-database study. Aliment Pharmacol Ther. 2018;47:792–800.

    Article  CAS  PubMed  Google Scholar 

  49. 49.

    Greywoode R, Braunstein ED, Arguelles-Grande C, Green PH, Lebwohl B. Olmesartan, other antihypertensives, and chronic diarrhea among patients undergoing endoscopic procedures: a case-control study. Mayo Clin Proc. 2014;89:1239–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Kamal A, Fain C, Park A, et al. Angiotensin II receptor blockers and gastrointestinal adverse events of resembling sprue-like enteropathy: a systematic review. Gastroenterol Rep (oxf). 2019;7:162–7.

    Article  Google Scholar 

  51. 51.

    Mondet I, Pierson-Marchandise M, Gras V, H. S, Lawsan P. Angiotensin II receptor blockers-induced enteropathy: not just olmesartan! Fundam Clin Pharmacol. 2016;30:47–62.

    Google Scholar 

  52. 52.

    Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet. 1991;337:867–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2018;390:2769–78.

    Article  PubMed  Google Scholar 

  54. 54.

    Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ. Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res. 2007;100:520–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Warrington R, Watson W, Kim HL, Antonetti FR. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. 2011;7(Suppl 1):1.

    Article  CAS  Google Scholar 

  56. 56.

    Cummins AG, Roberts-Thomson IC. Prevalence of celiac disease in the Asia-Pacific region. J Gastroenterol Hepatol. 2009;24:1347–51.

    Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Univ.-Doz. Dr. René R. Wenzel M.D..

Ethics declarations

Conflict of interest

R.R. Wenzel: For the following companies there is a conflict of interest with the presented data due to consultancy fees or sponsoring: Actelion, Astra-Zeneca, Abbott, Bayer, Daichii-Sankyo, Gepamed, Medtronic, Menarini, Novartis, Speedel Pharma, St Jude Medical and Takeda. C. Datz declares that he has no competing interests.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wenzel, R.R., Datz, C. Association of sprue-like enteropathy and angiotensin receptor-1 antagonists. Wien Klin Wochenschr 131, 493–501 (2019).

Download citation


  • Malabsorption
  • Hypertension
  • Renin-Angiotensin-System
  • Diarrhea
  • AT1-receptor-antagonist