Drug-Induced Enteropathy

Abstract

Background/Aims: Many medications can cause diarrhea by increasing motility, inflammation or enteropathy. Olmesartan and mycophenolic acid (CellCept) are drugs that are capable of increasing inflammation and enteropathy in some individuals and, if not recognized, can lead to chronic diarrhea. It is this type of drug-induced diarrhea that is the focus of this review. Methods: A summary of our findings (recent and earlier published) as well as a review of published works from other centers were conducted. Results: There is increasing evidence that olmesartan use is associated with enteropathy in a small number of individuals who use angiotensin receptor II blockers, and that this enteropathy is characterized by severe diarrhea capable of inducing severe dehydration and, in some instances, failure of organs such as the kidney. Typical patient demographics are Caucasian individuals who are older (>50 years old) and obese or overweight prior to weight loss. Prolonged exposure to olmesartan use for 1-2 years is typical, although case reports of irbesartan and valsartan have been reported as well. Discontinuing olmesartan leads to improvement of symptoms; however, the period for healing is variable, with some patients requiring steroid therapy and even prolonged parental nutrition support. In addition, many histological features of olmesartan-associated enteropathy are also present in celiac disease, including villi shortening and lymphocyte infiltration. Other drug-associated enteropathies have also been reported with mycophenolate mofetil used in transplantation. Conclusions: Of the drug-associated enteropathies discussed in this review, olmesartan can generate the most severe symptoms, albeit quite rare. Therefore, with patients who present with severe diarrhea and weight loss, one should consider olmesartan-associated enteropathy. In addition, many of the features associated with olmesartan-associated enteropathy are also found in celiac disease enteropathy; as such, one should review any celiac disease diagnosis for any use of olmesartan at the time of diagnosis.

Olmesartan-Associated Enteropathy: A Review of Clinical and Histologic Findings

“…Based on cases reported to date, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] OAE affects both men and women equally, and it most frequently affects patients in the seventh to eighth decades of life (mean age, 68 years; range, 46-91 years). Most patients with OAE present with chronic nonbloody diarrhea and weight loss.…”

“…16,19 Reported abnormal endoscopic features of the small bowel include mucosal nodularity, villous atrophy, and ulceration. 5,10,11,14,17,18,20 …”

“…Of the cases we identified in the literature with duodenal biopsies, 92 of 100 individuals (92%) had total or partial villous blunting (Figures 1 and 2). 3,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] A total of 5 biopsies (5%) had normal duodenal villous architecture, 11,14 2 of which had increased intraepithelial lymphocytes.…”

“…Colon biopsies may show increased IELs, subepithelial collagen thickening ( Figure 7), and lamina propria chronic inflammation that can resemble lymphocytic or collagenous colitis. 3,5,8,11,13,[16][17][18][19] Colonic crypt apoptoses have also been described. 8 It is unknown whether microscopic changes can be seen in the biopsies of patients with OAE prior to the development of severe diarrhea.…”

“…1 There are approximately 100 cases currently reported in the English-language literature that support olmesartan-associated enteropathy (OAE) as a distinct clinical entity. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] The aim of this article is to provide a review of clinicopathologic findings of OAE with a focus on microscopic features of gastrointestinal tract biopsies described in the literature as well as to provide a brief discussion of other entities to consider in the differential diagnosis of OAE. Original case reports and series published in the Englishlanguage literature of patients who developed enteropathy while on olmesartan therapy were identified through electronic searches in PubMed as well as manual bibliographic searches.…”