Coeliac disease enteropathy and symptoms may be aggravated by angiotensin receptor blockers in patients on a gluten-free diet

United European Gastroenterol J. 2021 Oct;9(8):973-979. doi: 10.1002/ueg2.12117. Epub 2021 Jun 29.

Abstract

Background: Angiotensin receptor blocker-associated enteropathy (ARB-e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD). There is evidence to suggest immune-mediated mucosal injury in ARB-e with a high prevalence of DQ2/DQ8; however, as IgA anti-tissue transglutaminase (anti-TTG) is usually negative, an insult other than TTG-mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known.

Objective: To assess the effect of ARB exposure on patients with established CD.

Methods: A patient record search of 1142 individual patients attending a dedicated coeliac clinic from 2010 to the present identified 59 patients treated with ARB. Those with CD confirmed by serology (TTG + ve/EMA + ve) and histopathology (Marsh criteria) were included (n = 40, 0.52%). Data collected included disease duration, compliance with gluten-free diet (GFD), reported symptoms (diarrhoea, weight loss and abdominal pain), surrogate markers of absorption (Vitamin D, Iron, Calcium and Haemoglobin), in addition to anti-TTG titre and histological grade at last follow up. Patients were age and sex-matched in a 1:2 ratio with CD patients not taking ARBs (controls), with comparable rates of disease duration and compliance with GFD.

Results: The ARB and control groups were matched in terms of age (mean 66.2 years) and gender (female 63%). Strict compliance with GFD was reported in 55% and 56%, respectively. Persistent symptoms were reported in 10/40 (25%) of the ARB group compared with 7/82 (9%) of controls (p = 0.0181). There were lower rates of mucosal healing (Marsh grade 0) in the ARB group (36% n = 11) compared to controls (55%, n = 33). There was no significant difference in anti-TTG titres. Surrogate markers of absorption were comparable across the groups, except for Vitamin D which was lower in those taking olmesartan (p = 0.0015).

Conclusions: ARBs may aggravate the enteropathy and lead to increased symptoms in patients with bone fide diagnosed CD following a GFD.

Keywords: ARB-enteropathy; MARSH; angiotensin receptor blocker; anti-TTG; coeliac disease; enteropathy; gluten-free diet.

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / adverse effects*
  • Autoantibodies / blood
  • Celiac Disease / chemically induced*
  • Celiac Disease / diet therapy
  • Celiac Disease / physiopathology*
  • Diet, Gluten-Free
  • Female
  • Humans
  • Immunoglobulin A / immunology
  • Intestinal Mucosa / pathology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transglutaminases / immunology
  • Wound Healing / drug effects*

Substances

  • Angiotensin Receptor Antagonists
  • Autoantibodies
  • Immunoglobulin A
  • Transglutaminases