Unusual Severe Side Effect of a Commonly Used Drug

Hypertension affects approximately 24% of adults in the United States. Angiotensin receptor blockers are commonly used to treat hypertension. Common side effects include dizziness and hyperkalemia. A 74-year-old Caucasian gentleman with a history of atrial fibrillation, hypertension, and chronic obstructive pulmonary disease was admitted for evaluation of recurrent diarrhea requiring multiple hospital admissions. His symptoms had started a month ago and had gradually worsened, so that he had to be admitted for severe dehydration and acute renal failure. Findings from stool examination were negative. He responded to fluid resuscitation and was discharged on a trial of oral metronidazole. He improved initially but the diarrhea returned in a few days and he had to be admitted again for severe dehydration. During the second hospitalization, he reported weight loss and a family history of celiac disease (CD). Results from serologic testing revealed a tissue transglutaminase immunoglobulin A (IgA) level of <1.2 U/mL in the presence of normal serum IgA. Human leukocyte antigen testing for CD was not performed because of family history of CD and the high likelihood of positivity in the patient. Stool lactoferrin was positive, pointing towards an inflammatory process. Endoscopic evaluation and biopsies were performed. Duodenum showed focally intense acute and chronic inflammation with variable villous flattening. Although results from CD-specific serologic testing were negative, it was thought that seronegative CD could be a possibility. The patient was started on a trial of glutenfree diet. Unfortunately, the patient did not improve and presented again for a third hospitalization. At this point, a comprehensive literature search was performed to solve this diagnostic dilemma, which showed a recently described association between olmesartan and enteropathy. Review of medications showed that the patient was taking olmesartan. The culprit medication was stopped and the diarrhea improved. In retrospect, the transient improvements in symptoms were associated with times during which olmesartan was held because of acute kidney injury, with relapse occurring after the drug was resumed following normalization of renal function. Enteropathy induced by olmesartan is a rare event, the pathogenesis of which is unknown. Patients usually have been taking olmesartan for several months, and may present with severe diarrhea, dehydration, and acute renal failure. Results from CD-specific serologic testing is negative in these patients. Clinical and histologic improvement is the rule following discontinuation of the offending drug, and reintroduction is associated with relapse. Olmesartan-induced enteropathy should be in the differential diagnosis for patients who present with severe unexplained chronic diarrhea and weight loss. Moreover, in patients with a working diagnosis of CD but negative CD-specific serology or lack of response to a gluten-free diet, a review of current medications is desirable before resorting to other expensive investigations.