Case Presentation: A 70-year-old man presented with 3-months of profuse watery diarrhea and 40 lb. weight loss. Two months prior, he was seen at an outside facility where he underwent extensive non-diagnostic work-up of his symptoms with lab testing, imaging, esophagogastroduodenoscopy (EGD), and colonoscopy. At that time, his serum pancreatic elastase-1 level was low, prompting a possible diagnosis of pancreatic insufficiency and initiation of supplemental pancreatic enzymes with minimal improvement in his symptoms. On presentation, his temperature was 36.8 degrees Celsius, blood pressure was 108/78 mmHg, and pulse was 103 bpm. Physical exam revealed no abdominal tenderness, rebound, guarding, or hepatosplenomegaly. Medications included lipase-protease-amylase, Olmesartan, amlodipine, dicyclomine, and loratadine. An extensive work-up was pursued: stool electrolytes consistent with osmotic diarrhea (osmotic gap 112 mOsm/kg); elevated fecal calprotectin (84.3 mcg/g); elevated serum chromogranin A (527 ng/mL), gastrin (169 pg/mL), pancreatic elastase (69 mcg/g); positive serum Strongyloides antibody; normal fecal alpha-1-anti-trypsin; negative stool Helicobacter pylori antigen, comprehensive ova and parasite panel, Clostridium difficile assay; normal serum 5-hydroxyindoleacetic acid, thyroid stimulating hormone, free T4, vitamins B3 / B12 / D, tryptase, tissue transglutaminase IgA, vasoactive intestinal peptide, immunoglobulins, human immunodeficiency virus antigen / antibody, glucagon, C-reactive protein, somatostatin, hepatitis A / B / C serologies, and cytomegalovirus IgM / IgG. Colonoscopy and EGD were both grossly normal. Duodenal biopsies showed acute and chronic duodenitis with mucosal desquamation and ulceration, few intact villi with blunting, increased intraluminal lymphocytes, and a few neutrophils imparting a sprue-like pattern. Olmesartan associated enteropathy (OAE), celiac disease, and autoimmune enteropathy can all cause sprue-like enteropathy. The patient had negative celiac serologies and anti-enterocyte antibody. Olmesartan cessation and a steroid taper resulted in complete symptom resolution.
Discussion: OAE as a rare cause of chronic diarrhea and weight loss. Olmesartan medoxomil acts as an angiotensin-II receptor blocker (ARB). Though mostly well-tolerated, Olmesartan can cause OAE with non-bloody diarrhea, weight loss, abdominal pain, and vomiting. Patients may develop enteropathy months-to-years after drug initiation.1 Although Olmesartan is the most common ARB to cause enteropathy, studies suggest other ARBs may cause similar complications.2 Diagnosis is often delayed due to unfamiliarity of OAE; normal appearing endoscopic findings prompting no biopsy; and nonspecific symptoms. EGD with biopsy is essential to the diagnosis, showing sprue-like enteropathy with intestinal villous atrophy and mucosal inflammation, similar to celiac disease and autoimmune enteropathy but with negative serologies.3 Treatment requires Olmesartan cessation and addition of steroids for severe cases. Clinical improvement occurs days to a week after discontinuation.4
Conclusions: In this case, only after an extensive work-up was the OAE diagnosis established. Given frequent Olmesartan use, increasing OAE occurrence, and the wide spectrum of symptoms, it is crucial for internists to recognize OAE and consider early Olmesartan cessation to avoid further intestinal damage, protracted symptoms, and unnecessary diagnostics.
