Sprue-like histology in patients with abdominal pain taking olmesartan compared with other angiotensin receptor blockers Stephen M Lagana, 1 Eric D Braunstein, 2 Carolina Arguelles-Grande, 2 Govind Bhagat, 1 Peter H R Green, 2 Benjamin Lebwohl 2 1 Department of Pathology and Cell Biology, Columbia University and New York Presbyterian Hospital, New York, New York, USA 2 Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York, New York, USA Correspondence to Dr Stephen M Lagana, Department of Pathology and Cell Biology, Columbia University and New York Presbyterian Hospital, 630 W 168th St., VC15-202, New York, NY 10032, USA; Sml2179@cumc.columbia.edu Received 15 August 2014 Revised 18 September 2014 Accepted 30 September 2014 Published Online First 23 October 2014 To cite: Lagana SM, Braunstein ED, Arguelles- Grande C, et al. J Clin Pathol 2015;68:29–32. ABSTRACT Aims A severe syndrome characterised by life-threatening diarrhoea and severe sprue-like histology has been described in patients taking the angiotensin receptor blocker (ARB) olmesartan. It is unknown whether there are any histopathological changes in patients without severe diarrhoea exposed to this medication. It is also unknown whether other ARBs cause sprue-like histology. Methods Retrospective cohort study of patients with abdominal pain undergoing upper gastrointestinal endoscopy with duodenal biopsy who were taking ARBs. Patients taking olmesartan (n=20) and a non-olmesartan ARB (n=20) were compared with age and sex-matched controls. Histological features (classic sprue-like and other inflammatory changes) were analysed. Results No single histopathological finding was significantly more common in olmesartan-using patients than controls. However, 10 of 20 olmesartan patients had one or more sprue-like histological features compared with 4 of 20 age-matched and sex-matched controls not taking ARBs (p=0.10). Patients taking ARBs other than olmesartan were not more likely than controls to have one or more of these sprue-like histological features (9/20 vs. 12/20, p=0.34). Conclusions There were no statistically significant differences between olmesartan users with abdominal pain and controls for any single histopathological abnormality. However, there were trends towards significance for individual abnormalities as well as for a composite outcome of sprue-like changes. This raises the possibility that there is a spectrum of histological changes associated with olmesartan use. INTRODUCTION Olmesartan medoxomil is a commonly used antihy- pertensive medication, which acts by blocking angio- tensin receptors. Recently, a series of cases were described in which 22 patients presented with debili- tating diarrhoea and had a sprue-like enteropathy on histological examination due to olmesartan. The diar- rhoea was so severe that 14 patients required hospi- talisation and 4 required total parenteral nutrition. Serological testing for coeliac disease was negative in all cases and none improved with a gluten-free diet. All had biopsies, which showed severe sprue-like changes (villous atrophy, lamina propria inflamma- tion and intraepithelial lymphocytosis (IEL)). Seven of the patients had collagenous sprue. All patients had dramatic improvement, with resolution of their diarrhoea following cessation of olmesartan. 1 As a major referral centre for coeliac disease, we have subsequently encountered a number of such cases and several other case series and reports have been published, which demonstrate similar clinical and histopathological findings. 2–12 At present, this adverse drug reaction is thought to be a rare occur- rence. A recent case–control study did not show an association between olmesartan use and chronic diar- rhoea in patients presenting for oesophagogastroduo- denoscopy (OGD) or colonoscopy. 13 While it is unusual to encounter severe villous atrophy in non-coeliac patients, milder changes which may overlap with sprue-like enteropathies (such mild or focal IEL) are common. 2 14 Medication reactions, particularly non-steroidal anti-inflammatory drugs, are commonly listed in the differential of such pathological findings. 15 Other drugs also enter the differential, but it is unknown whether olmesartan exposure should be considered when encountering such findings. It is also unknown whether other angiotensin receptor block- ers (ARBs) may cause histopathological changes. Because it is unclear whether the severe sprue- like enteropathy seen in a few patients taking olme- sartan is the severe end of a spectrum of intestinal injury, we identified patients taking olmesartan who had undergone endoscopy for abdominal pain with duodenal biopsy and systematically studied the biopsies. We also identified patients with abdominal pain taking other ARBs who had duodenal biopsy and examined their biopsies to determine whether the changes were specific for olmesartan. We identi- fied those patients whose indication for the proced- ure was abdominal pain to avoid those whose symptom was diarrhoea. METHODS We performed a retrospective cohort study using the electronic medical record of Columbia University Medical Center endoscopy unit (ProVation Medical Systems, Wolters Kluwer Health, New South Wales, Australia). This record includes all home medication use reported by out- patients undergoing OGD. This list of medications is ascertained by a trained nurse during an inter- view immediately preceding the procedure. We queried the medical record for patients in whom the indication for OGD was abdominal pain (self- reported, no formal diagnostic criteria employed) and identified 20 outpatients who listed olmesartan as one of their medications. We then matched each patient by age and gender to a control patient who did not report any ARB when listing his/her medi- cations. Using the same process, we identified Lagana SM, et al. J Clin Pathol 2015;68:29–32. doi:10.1136/jclinpath-2014-202615 29 Original article on April 24, 2020 by guest. Protected by copyright. http://jcp.bmj.com/ J Clin Pathol: first published as 10.1136/jclinpath-2014-202615 on 23 October 2014. Downloaded from