Baylor University Medical Center Proceedings July 2017 - 348

Olmesartan-associated enteropathy
Vivian S. Ebrahim, MD, Jason Martin, MD, Stacey Murthy, MD, Elizabeth Odstrcil, MD, He Huang, MD, and Daniel Polter, MD

Olmesartan, an angiotensin-receptor blocker frequently prescribed for
hypertension, has been commercially available since 2002. In 2012,
olmesartan-associated enteropathy was described, and the Food and
Drug Administration now requires a black-box warning for olmesartan
regarding severe diarrhea. The disorder can be life-threatening and often
requires hospitalization. We present three cases that represent different
aspects of this disorder, as well as some unusual features.

severe form of intestinal injury with chronic diarrhea
due to olmesartan was described by Rubio-Tapia et al
in 2012 (1). They reported 22 patients with severe diarrhea, unexplained despite an extensive evaluation, who
were found to have varying degrees of duodenal villous atrophy and mucosal inﬂammation throughout the gastrointestinal
tract. The patients did not respond to a gluten-free diet. All
were on olmesartan, and upon discontinuing this agent, their
symptoms resolved or signiﬁcantly improved with histologic
recovery. Other reports of olmesartan-associated enteropathy
have since appeared in the gastroenterology literature (2-4).
Patients typically present with severe chronic diarrhea accompanied by abdominal bloating and cramping, usually with
weight loss, nausea, and vomiting, and frequently require hospitalization for intravenous hydration. An extensive and costly
medical evaluation often is pursued, including serologic tests
for celiac disease, search for infections, endoscopic procedures,
stool studies, and various medication trials. If esophagogastroduodenoscopy (EGD) is performed and biopsies are obtained,
duodenal villous atrophy may be found. The following three
cases illustrate the variety of clinical manifestations that may
occur with olmesartan-associated enteropathy.
CASE 1
A 57-year-old man presented with a 4-month history of
nonbloody diarrhea with four to ﬁve voluminous stools per
day. He described abdominal cramps, bloating, and a 70-lb
weight loss as well as joint pain and swelling, despite a glutenfree diet. Biopsies obtained during EGD revealed collagenous
gastritis, duodenal villous blunting, and intraepithelial lymphocytosis (Figure 1a). A quantitative stool collection showed
severe secretory diarrhea. Colonic biopsies obtained by ﬂexible
348

sigmoidoscopy revealed lymphocytic and collagenous colitis
(Figure 1b). The patient had been taking olmesartan-amlodipinehydrochlorothiazide (Tribenzor, 40 mg-10 mg-25 mg) daily for
2 years prior to the onset of diarrhea. Symptoms resolved within
1 week of discontinuing this medication. The patient regained
57 lb over 4 months. Repeat biopsies obtained endoscopically
at that time revealed normal gastric and duodenal mucosa and
resolution of collagenous and lymphocytic colitis.
CASE 2
A 69-year-old woman presented with a 2-month history of
daily watery diarrhea, increased midabdominal pain, nausea,
vomiting, and a 12-lb weight loss. EGD revealed gastric erosions, and biopsies showed lymphocytic gastritis and marked
villous atrophy. A quantitative stool collection showed secretory
diarrhea. The patient had been taking olmesartan 40 mg daily
for 2.5 years. Upon discontinuation, her diarrhea promptly and
dramatically improved. Repeat EGD 1 week later revealed complete resolution of the previous duodenal inﬂammation. Followup quantitative stool fat collection after the diarrhea resolved
showed marked improvement of the steatorrhea. Olmesartan
was resumed 3 weeks later with an immediate return of diarrhea
after only one dose. Olmesartan was then permanently discontinued. She regained her weight and otherwise felt well. Recent
EGD and colonoscopy revealed normal stomach, duodenum,
and colon with normal biopsies.
CASE 3
A 72-year-old man was given olmesartan brieﬂy in 2013
for hypertension. Diarrhea ensued and resolved after stopping
the medication. Three years later, olmesartan 40 mg daily was
again prescribed for hypertension. Diarrhea promptly recurred
with 20 large-volume, nonbloody stools per day and a 16-lb
weight loss, despite a gluten-free and lactose-free diet. EGD
revealed patchy gastritis with focal erosions; biopsies showed
From the Division of Gastroenterology, Department of Internal Medicine (Ebrahim,
Martin, Odstrcil, Polter) and the Department of Pathology (Murthy, Huang), Baylor
University Medical Center, Dallas, Texas.
Corresponding author: Vivian S. Ebrahim, MD, Division of Gastroenterology,
Department of Internal Medicine, Baylor University Medical Center, 3500 Gaston
Avenue, Dallas, TX 75246 (e-mail: vivian.ebrahim@bswhealth.org).
Proc (Bayl Univ Med Cent) 2017;30(3):348-350

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