Olmesartan Associated Sprue-Like Enteropathy and Colon Perforation

Abdelghany, Mahmoud; Gonzalez, Luis S.; Slater, J. C.; Begley, Christopher

doi:10.1155/2014/494098

Cited by 20 publications

(47 citation statements)

References 8 publications

(13 reference statements)

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“…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.…”

Section: Clinical and Laboratory Findingsmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Choi

McKenna²

2015

Archives of Pathology &Amp; Laboratory Medicine

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Olmesartan is an antihypertensive medication belonging to the angiotensin II receptor blocker class of drugs that has recently been associated with severe enteropathy. Olmesartan-associated enteropathy is uncommon and may be difficult to recognize because of its clinical and histologic similarities to other clinical entities, including celiac sprue and autoimmune enteropathy. The purpose of this article is to review the clinical and histologic findings of olmesartan-associated enteropathy that have been reported in the literature and to discuss clinical entities to consider in the differential diagnosis of olmesartanassociated enteropathy.

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Section: Clinical and Laboratory Findingsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Choi

McKenna²

2015

Archives of Pathology &Amp; Laboratory Medicine

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“…The nutritional deficiencies found in patients with OAE are further detailed in a recent review [4]. One case report describes bowel perforation thought to be secondary to OAE [6]. It is therefore not surprising that patients with OAE were admitted to the hospital, sometimes multiple times.…”

Section: Olmesartan-associated Enteropathymentioning

confidence: 99%

“…Besides elevated creatinine, hypokalemia, and evidence of micronutrient deficiencies, patients had normal laboratory findings, including tTG. Abdominal imaging was normal with one exception of bowel perforation [6]. Upper endoscopy with small bowel biopsies showed findings similar to that of celiac disease [2].…”

Section: Olmesartan-associated Enteropathymentioning

confidence: 99%

Drug-Induced Enteropathy

Marietta

Cartee

Rishi

et al. 2015

Dig Dis

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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.

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“…At Mayo Clinic, 35 individuals have been diagnosed with OAE in the last 5 years, and a national study done in France identified 31 OAE patients . There have also been multiple case reports from around the world . Although the frequency for OAE appears to be low, it is imperative to rapidly identify these individuals, because complications of OAE are severe, including renal failure, and suspension of the drug leads to resolution of symptoms and mucosal healing .…”

Section: Introductionmentioning

confidence: 99%

Immunopathogenesis of olmesartan‐associated enteropathy

Marietta

Nadeau

Cartee

et al. 2015

Aliment Pharmacol Ther

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Structured Summary Background Olmesartan-associated enteropathy (OAE) is characterized by diarrhea, nausea, vomiting, abdominal pain, weight loss, and severe sprue-like enteropathy, all of which is resolved after olmesartan medoxomil discontinuation. Aim To determine the mechanistic similarities with celiac sprue. Methods Duodenal biopsies were extracted from OAE patients before (n=11) or after (n=17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were 7 “on/off” paired samples. Formalin fixed biopsies were stained for CD8, CD4, FoxP3, IL-15R, and psmad 2/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL-15, IL-15R, and ZO-1. Results In the “on olmesartan medoxomil” duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco-2 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO-1, a tight junction protein, is disrupted in olmesartan medoxomil-treated Caco-2 cells. Conclusions OAE shares many features with celiac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effect of gluten upon the epithelium of celiac patients.

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Olmesartan Associated Sprue-Like Enteropathy and Colon Perforation

Cited by 20 publications

References 8 publications

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

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

Drug-Induced Enteropathy

Immunopathogenesis of olmesartan‐associated enteropathy

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