Olmesartan-associated Enteropathy Research Articles

Olmesartan Associated Enteropathy, an easily overlooked etiology of bowel disturbance: report of three cases

Olmesartan medoxomil is one of eight marketed Angiotensin II Receptor Blocker for the treatment of high blood pressure. Olmesartan Associated Enteropathy has been described in several case reports, subsequently, the United states Food and Drug Administrationincluded severe sprue-like enteropathy as an adverse effect of Olmesartan. Olmesartan Associated Enteropathy mimics celiac disease clinically and pathologically. The pathologic findings are villous atrophy and increased intraepithelial lymphocytes. Clinical presentation of Olmesartan Associated Enteropathy includes nausea, bloating, diarrhea and weight loss. In contrast to celiac disease, tissue transglutaminase is not elevated, and there is no response to a gluten-free diet. Several case reports have described the effects of olmesartan on gut, giving rise to the term of Olmesartan Associated Enteropathy. Clinicians should always be aware that Olmesartan can cause an enteropathy clinically and histologically similar to celiac disease since replacing Olmesartan with an alternative antihypertensive drug can simplify the diagnostic workup and provide both clinical and histologic improvement. We report three cases of Olmesartan Associated Enteropathy in this article. Bangladesh Crit Care J September 2022; 10(2): 154-157

Olmesartan-associated Enteropathy with Acute Kidney Injury

Moo Jin Kang, Kyung Hwa Min, Hyung Wook Kim, Su Bum Park, Dae Hwan Kang, Cheol Woong Choi, Su Jin Kim, Hyeong Seok Nam and Dae Gon Ryu. Korean J Gastroenterol 2022;79:194. https://doi.org/10.4166/kjg.2022.007.e1

Olmesartan-associated Enteropathy

Olmesartan,an angiotensin Ⅱ receptor blocker,is a commonly used antihypertensive drug.Several case reports and cohort studies in recent years have described a severe gastrointestinal adverse event with chronic diarrhea,intestinal malabsorption,and weight loss after the administration of olmesartan.In such cases,the patients recovered after discontinuing olmesartan.This adverse effect is called olmesartan-associated enteropathy(OAE).This article reviews the potential pathogenesis and clinical characteristics of OAE,which broadens the disease spectrum for the differential diagnosis of chronic diarrhea and intestinal malabsorption.

An unusual cause of diarrhoea: case report and literature review of olmesartan-associated enteropathy

Olmesartan is an angiotensin II receptor blocker, approved in 2002 by the Food and Drug Administration for the treatment of hypertension. During chronic therapy with olmesartan, sprue-like enteropathy can occur, being mainly characterised by non-bloody diarrhoea, weight loss and variable degrees of duodenal mucosal damage, which resolved after withdrawal of olmesartan. We hereby report the case of a 77-year-old, poli-treated male patient with a 3-month history of diarrhoea, vomiting and weight loss, associated with severe intestinal villous atrophy and lymphocytic infiltration of gastric and colonic mucosa. After extensive investigations aimed at excluding other possible causes of chronic diarrhoea, a diagnosis of olmesartan-associated enteropathy was made, which was later confirmed by clinical improvement after the discontinuation of the drug. Repeated endoscopy 8 months later showed complete healing of duodenal mucosa with normal villous architecture. Villous atrophy and lymphocytic infiltration of duodenal mucosa are the most described pathologic finding, but several cases of gastric and colonic involvement have also been reported. We, therefore, reviewed the available literature, focussing on the extent of mucosal damage throughout the whole intestine and on its possible causative factors.

Olmesartan-associated enteropathy: heterogeneity of involvement along gastrointestinal tract.

Olmesartan-associated enteropathy: heterogeneity of involvement along gastrointestinal tract.

Olmesartan-associated Enteropathy Mimics Endoscopic Findings of Celiac Disease.

Olmesartan-associated Enteropathy Mimics Endoscopic Findings of Celiac Disease.

Olmesartan-Associated Enteropathy: An Unexpected Cause of Chronic Diarrhoea.

Olmesartan-associated enteropathy is a rare cause of severe enteropathy that should be considered in the differential diagnosis of patients with unexplained chronic diarrhoea. It may be difficult to recognise because of its clinical and histologic similarities to other clinical entities. The authors present the case of a 72-year-old woman with a 6-month clinical history of non-bloody diarrhoea and weight loss. Discontinuation of olmesartan resulted in clinical and histologic recovery, and therefore, physicians need to be aware of olmesartan-associated enteropathy in order to avoid unnecessary testing. Although rare, it is considered an emerging and underdiagnosed enteropathy.LEARNING POINTSOlmesartan-associated enteropathy is characterised by chronic diarrhoea (often severe) and weight loss that is unresponsive to a gluten-free diet.When a patient presents with unexplained chronic diarrhoea, a detailed medication review is needed. If duodenal biopsies reveal villous atrophy and coeliac disease is excluded, drug-induced enteropathy is likely.Clinical response and histologic improvement are expected after olmesartan is withdrawn.

Duodenal Villous Atrophy and Diarrhea Associated with Chronic Olmesartan Intake

Olmesartan is an angiotensin II receptor blocker (ARB) approved for the treatment of hypertension since 2002. Olmesartan-associated enteropathy (OAE), first described in 2012 by Rubio-Tapia, has seldom been considered as a diagnosis in patients with villous atrophy and negative serology for celiac disease. The clinical presentation could be extremely heterogenous. In contrast to celiac disease, there is no response to a gluten-free diet. The exact mechanism of intestinal injury still remains unknown. The histological pattern, at the upper gastrointestinal endoscopy, usually reveals a variable degree of villous atrophy and a moderate infiltration of lymphocytes at mucosal level. Symptoms usually improve upon olmesartan discontinuation and the repeat endoscopy could demonstrate complete resolution of inflammatory change with normal villous architecture. The differential diagnosis for this kind of clinical and pathological features include celiac disease, tropical sprue, autoimmune enteropathy, inflammatory bowel disease, and drug induced enteropathy. With this background, we report the case of a patient with a clinical picture compatible with seronegative celiac disease and symptoms that rapidly improved clinically and histologically after olmesartan discontinuation. In conclusion, although this condition is rare, physicians should be consider this medication in the differential diagnosis of this enteropathy.

Dehydration Secondary to Acute Olmesartan Associated Enteropathy with Concomitant Lymphocytic Colitis

Introduction: Olmesartan is an angiotensin II receptor blocker recently described to cause a spruelike enteropathy. Duodenal biopsies are identical to those of Celiac disease (CD), however the patient will be negative for transglutaminase. Unlike Olmesartan associated enteropathy (OAE), CD has been associated with lymphocytic colitis (LC). LC can cause significant diarrhea, although it typically does not cause dehydration. Case Report: 84-year-old Caucasian female with a past medical history of dementia and hypertension was hospitalized for diarrhea. She was noted to have an acute kidney injury (AKI) with a creatinine of 1.79 mg/dL. Her C. diff screen was positive and the patient was treated with oral vancomycin. Her AKI resolved with rehydration and she was discharged home. At home she began to have 20 liquid bowel movements daily and was taken to another local hospital. Repeat C. diff screening was negative; however, she was again treated with oral Vancomycin. She was discharged home despite still having diarrhea. Outpatient esophagogastroduodenoscopy and colonoscopy were performed for follow up evaluation. Further, she was noted to have been recently started on Olmesartan which was discontinued prior to endoscopic evaluation. Endoscopy revealed negative gross evaluation of the duodenum and biopsy revealed blunted villous architecture with increased intraepithelial lymphocytes and focal neutrophilic infiltrates. Colonic biopsies revealed lymphocytic colitis. Shortly after, the patient had altered mental status and hypotension and was sent to the emergency department. Initial vital signs were significant for temperature of 91.7 °F and a blood pressure of 72/57 mm Hg. Physical exam was unremarkable besides altered mentation. Initial bloodwork revealed an AKI with a creatinine of 7.74 mg/dL. She continued to have profound diarrhea and outpatient biopsy results were not immediately available. Repeat C. diff screening, stool cultures, Shiga toxins, and ova and parasites were checked and found to be negative. Computer tomography of the abdomen showed diverticulosis. With the duodenal biopsy results transglutaminase IgA and IgG were checked and were negative. The AKI resolved with rehydration and the diarrhea improved with budesonide. Discussion: Celiac sprue enteritis is associated with LC, OAE has not been described to be associated with it. Clinicians should suspect a concomitant process in patients with LC presenting with dehydration.

New Onset Villous Atrophy in a Patient With Celiac Disease

New Onset Villous Atrophy in a Patient With Celiac Disease

Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by interference of the sympathetic inhibitory pathway in hypertensive rat

Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompanied by chronic diarrhea, there have been no studies of olmesartan-induced hypermotility. Intestinal motility should be well regulated by the enteric nervous system, but degeneration of enteric neurons has been reported in patients with chronic diarrheal diseases, such as irritable bowel syndrome, suggesting a connection between OAE and intestinal hypermotility. In this study, interference with this inhibitory pathway was analyzed in a model of olmesartan-induced intestinal hypermotility (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing stress. The effects of the potent inhibitory neurotransmitters norepinephrine (NE) and sodium nitroprusside (SNP), which act via different pathways, were assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent in OAE, including atrophy of the intestinal epithelium and weight loss, were observed in these rats. Interestingly, olmesartan significantly elevated heart rate while lowering blood pressure in OIH rats. These abnormal conditions were prevented by adding linalyl acetate (LA), while the blood pressure-lowering effects of olmesartan were maintained. These findings suggest that olmesartan induces intestinal hypermotility by interfering with the sympathetic inhibitory pathway, and reduces epithelial cell size or body weight in hypertensive rats. As LA prevented these effects, combination treatment with olmesartan plus LA may provide better antihypertensive efficacy without inducing OAE.

A Case of Olmesartan-associated Sprue-like Enteropathy

A Case of Olmesartan-associated Sprue-like Enteropathy

Olmesartan is not associated with the risk of enteropathy: a Korean nationwide observational cohort study.

Background/AimsOlmesartan, a widely used angiotensin II receptor blocker (ARB), has been linked to sprue-like enteropathy. No cases of olmesartan-associated enteropathy have been reported in Northeast Asia. We investigated the associations between olmesartan and other ARBs and the incidence of enteropathy in Korea.MethodsOur retrospective cohort study used data from the Korean National Health Insurance Service to identify 108,559 patients (58,186 females) who were initiated on angiotensin converting enzyme inhibitors (ACEis), olmesartan, or other ARBs between January 2005 and December 2012. The incidences of enteropathy were compared among drug groups. Changes in body weight were compared after propensity score matching of patients in the ACEis and olmesartan groups.ResultsAmong 108,559 patients, 31 patients were diagnosed with enteropathy. The incidences were 0.73, 0.24, and 0.37 per 1,000 persons, in the ACEis, olmesartan, and other ARBs groups, respectively. Adjusted rate ratios for enteropathy were: olmesartan, 0.33 (95% confidential interval [CI], 0.10 to 1.09; p = 0.070) and other ARBs, 0.34 (95% CI, 0.14 to 0.83; p = 0.017) compared to the ACEis group after adjustment for age, sex, income level, and various comorbidities. The post hoc analysis with matched cohorts revealed that the proportion of patients with significant weight loss did not differ between the ACEis and olmesartan groups.ConclusionsOlmesartan was not associated with intestinal malabsorption or significant body weight loss in the general Korean population. Additional large-scale prospective studies of the relationship between olmesartan and the incidence of enteropathy in the Asian population are needed.

Olmesartan-Associated Enteropathy

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.

Short article: Mortality and differential diagnoses of villous atrophy without coeliac antibodies.

Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed. Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients. Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

Olmesartan-Associated Enteropathy Without Chronic Diarrhea: An Atypical Presentation of a Difficult Diagnosis

Olmesartan-associated enteropathy (OAE) is a recently identified sprue-like enteropathy and clinical syndrome that presents primarily with chronic diarrhea and significant weight loss accompanied by abdominal pain, nausea, vomiting, bloating or fatigue. This report describes an atypical clinical presentation of olmesartan-associated enteropathy. An 82-year-old woman presented to clinic with approximately 5 months of poor appetite followed by sudden onset of frequent nausea, vomiting, epigastric abdominal pain and 40-pound weight loss. She had no diarrhea. She had several previous admissions at other hospitals with extensive work-up that was ultimately unrevealing (included multiple abdominal CTs, multiple EGDs, and colonoscopy). Olmesartan was on her home medication list but had been replaced by another hospital formulary angiotensin receptor blocker (ARB) on admission. While endoscopically unrevealing, duodenal biopsy at this admission demonstrated marked villous blunting and chronic inflammation. Serologies for celiac disease were negative, which was consistent with OAE. All ARBs were discontinued and the patient's nausea and abdominal pain improved. This case differed from the clinical pattern of symptoms noted in prior reports of OAE as the patient was entirely without diarrhea. A literature review identified numerous cases with nausea, vomiting and abdominal pain in addition to diarrhea and weight loss, but to our knowledge this is the first described case of OAE without symptoms of diarrhea (although constipation is not uncommon in celiac disease). Additionally, this case calls attention to a standard practice that influences the potential for missed diagnoses related to medication side effects. The admission process of substituting medications to comply with hospital formularies creates an opportunity for medications, such as olmesartan, to be overlooked. This case emphasizes the importance of thorough medication reconciliation at the time of a new hospitalization. Rubio-Tapia, Alberto, et al. “Severe spruelike enteropathy associated with olmesartan.” Mayo Clinic Proceedings. Vol. 87. No. 8. Elsevier, 2012. Marietta, E. V., et al. “Immunopathogenesis of olmesartan-associated enteropathy.” Alimentary pharmacology & therapeutics 42.11-12 (2015): 1303-1314. Burbure, Nina, et al. “Olmesartan associated sprue-like enteropathy: a systematic review with emphasis on histopathology.” Human Pathology (2015).Figure 1

Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis on histopathology

Sprue-like enteropathy associated with the angiotensin II receptor blocker (ARB) olmesartan was first described in 2012, and a number of cases have since been reported. This syndrome is characterized by severe diarrhea and sprue-like histopathologic findings in the intestine, often with increased subepithelial collagen. The incidence of this adverse drug reaction is not entirely clear, although it is thought to be rare. It is also not well established if other ARBs cause such a syndrome, although case reports suggest they can. The histopathologic features of olmesartan-related injury have only been described in a limited number of cases, and there are no guidelines regarding the histopathologic distinction of olmesartan-associated enteropathy from other causes of sprue (eg, celiac disease, tropical sprue). Herein, we review the histopathologic changes and clinical observations described in recent reports of olmesartan-associated sprue-like enteropathy comprising case series and isolated reports, other relevant literature, and our experience at a referral center specializing in small intestinal disorders. We will review recent literature suggesting other ARBs can be associated with a similar phenotype. Lastly, we will discuss the histopathologic differential diagnosis and provide clues to distinguish this entity from other entities which can cause sprue-like histopathology.

Potential coeliac disease markers and autoimmunity in olmesartan induced enteropathy: A population-based study

Aims(1) Assess the population-based incidence of severe olmesartan-associated enteropathy. (2) To describe patients of the Spanish registry. (3) Evaluate markers of potential coeliac disease and associated autoimmunity. MethodsCrude incidence rates in the area of Terrassa (Catalonia) were calculated. Clinical characteristics of patients in the Spanish registry were collected. Duodenal lymphocyte subpopulations and anti-TG2 IgA deposits were assessed in a subset of patients. ResultsAnnual incidence rates (2011–2014) ranged from 0 to 22 cases per 104 treated patients. Twenty patients were included in the Spanish registry. Nineteen (95%) exhibited villous atrophy and 16 (80%) had severe enteropathy. Lupus-like disease occurred during olmesartan treatment in 3 patients. HLA-DQ2/DQ8 was positive in 64%. Markers of potential coeliac disease were present in 4 out of 8 patients (positive anti-TG2 deposits and/or increased CD3+gammadelta+ intraepithelial lymphocytes and reduced CD3−). Histopathological changes and clinical manifestations including autoimmune disorders improved after olmesartan discontinuation but not after gluten-free diet, irrespective of the presence or absence of coeliac markers. ConclusionsIncidence of severe olmesartan-associated enteropathy was low. Autoimmune phenomena were present in a subset of cases and reversed after olmesartan removal. A genetic coeliac disease background and the presence of potential coeliac markers might uncover predisposing factors.

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

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 olmesartan-associated enteropathy.

Immunopathogenesis of olmesartan-associated enteropathy.

Olmesartan-associated enteropathy (OAE) is characterised by diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue-like enteropathy, all of which are resolved after discontinuation of olmesartan medoximil. To determine the mechanistic similarities of OAE with coeliac sprue. 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 seven '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. 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. Olmesartan-associated enteropathy shares many features with coeliac 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 effects of gluten upon the epithelium of coeliac patients.