Drug-induced Enteropathy Research Articles

New Onset Villous Atrophy in a Patient With Celiac Disease

New Onset Villous Atrophy in a Patient With Celiac Disease

Rebleeding rate and risk factors in nonsteroidal anti-inflammatory drug-induced enteropathy.

Limited evidence is available on rebleeding due to nonsteroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy. Previous studies have primarily analyzed endoscopic findings. Therefore, there is a need to evaluate their clinical implications for patients. This study aimed to evaluate the rebleeding rate and its related risk factors in patients with NSAIDs-induced enteropathy. Of 402 patients with obscure gastrointestinal bleeding who were evaluated with capsule endoscopy, 49 were diagnosed with NSAIDs-induced enteropathy. The clinical characteristics of the patients were retrospectively analyzed. The Charlson comorbidity index was used to stratify the comorbidities. For patients who used additional drugs that influenced their tendency to bleeding, the odds ratio was calculated and used for a quantitative comparison. The rebleeding rate in patients with NSAIDs-induced enteropathy was 20.4%, within a mean duration of 23.4 months. Age ≥65 years (hazard ratio [HR] 8.628, 95% confidence interval [CI] 1.152-64.625), no additional use of mucoprotective agents (HR 11.712, 95% CI 1.278-76.098) and the continuation of NSAIDs after the first bleeding episode (HR 9.861, 95% CI 1.395-98.344) were independently related to rebleeding due to NSAIDs-induced enteropathy. The underlying comorbidities, drug-related rebleeding risk scores and therapeutic use of proton pump inhibitors were not significantly different (P = 0.209, 0.212 and 0.720, respectively). Approximately one-fifth of patients with NSAIDs-induced enteropathy showed rebleeding within 2 years. A careful long-term follow-up should be offered to elderly patients with NSAIDs-induced enteropathy who need continuous NSAID treatment without the additional use of mucoprotective medications.

Sa1169 - Deficiency of CCR7 is Responsible for the Deterioration of Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

Sa1169 - Deficiency of CCR7 is Responsible for the Deterioration of Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

Severe intestinal malabsorption associated with ACE inhibitor or angiotensin receptor blocker treatment. An observational cohort study in Germany and Italy.

PurposeThe angiotensin II receptor blocker (ARB) olmesartan has been recently associated with sprue‐like enteropathy (SLE), a gastrointestinal condition characterized by intestinal malabsorption (IM) and severe diarrhea. Whether the increased risk of SLE is substance‐specific or a class effect involving all ARBs is uncertain. The aim of this study is to assess the risk of enteropathy associated with ARBs and angiotensin converting enzyme inhibitors (ACE‐i) by using data from large administrative and claim databases.MethodsWe obtained data from Italian local health‐care units and a large German claim database and included patients treated with olmesartan, other ARBs, and ACE‐i. In the absence of a specific diagnosis code for SLE, International Classification of Diseases codes for IM were used. Analysis implemented a Poisson regression with robust error variance procedure, which allowed accounting for different clusters (local health‐care units and countries) and correctly estimating the standard error for the relative risk of rare event occurrence.ResultsPatients were divided into 3 groups: olmesartan (25.591, 5.5%), other ARBs (104.901, 22.5%), and ACE‐i patients (334.951, 72.0%). Baseline characteristics were similar overall. The incidence of unspecified IM in ACE‐i patients was not different compared with that of olmesartan, whereas a higher rate ratio was observed when comparing ARB patients with the olmesartan group (RR: 2.50, 95% CI 1.21 to 5.19, P .01). When International Classification of Diseases codes for coeliac disease were included, no differences were observed.ConclusionsWe could not confirm previous findings of a higher risk of malabsorption in olmesartan‐only patients, and drug‐induced enteropathy should be considered the result of exposure to the class of ARBs rather than a specific drug‐related effect.

Drug-Induced Flu-Like Enteropathy

Drug-Induced Flu-Like Enteropathy

Non-Steroidal Anti-Inflammatory Drug-Induced Protein-Losing Enteropathy: A Great Masquerade of Crohnʼs Disease

Non-Steroidal Anti-Inflammatory Drug-Induced Protein-Losing Enteropathy: A Great Masquerade of Crohnʼs Disease

Pediatric-onset Chronic Nonspecific Multiple Ulcers of Small Intestine: A Nationwide Survey and Genetic Study in Japan.

We performed a Japanese nationwide survey of pediatric-onset chronic nonspecific multiple ulcers of the small intestine between January 2000 and July 2013 in 176 institutions of pediatric surgery or pediatric gastroenterology and clarified the clinical features associated with genetic abnormalities in the Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1) gene. A total of 4 cases (3 girls and 1 boy) were diagnosed in this series, which had to be differentiated from Crohn disease, Behçet disease, tuberculosis, or drug-induced enteropathy. Clinical symptoms appeared in infants and accurate diagnosis required several years. Medical therapies for inflammatory bowel disease were administered in all patients; however, 2 of the 4 patients had mutation in the SLCO2A1 gene which are responsible for primary hypertrophic osteoarthopathy, and underwent strictureplasty or ileal resection after long-term follow-up. Pediatric gastroenterologists should include this new entity in the differential diagnosis of small intestinal ulcers and inflammatory bowel disease.

Mo1898 - Vonoprazan, a Novel Active Potassium-Competitive Acid Blocker, and Rabeprazole Induce Small Intestinal Dysbiosis and Exacerbate the Non-Steroidal Anti-Inflammatory Druginduced Small Intestinal Enteropathy

Mo1898 - Vonoprazan, a Novel Active Potassium-Competitive Acid Blocker, and Rabeprazole Induce Small Intestinal Dysbiosis and Exacerbate the Non-Steroidal Anti-Inflammatory Druginduced Small Intestinal Enteropathy

Su1852 - Deficiency of CCR7 Deteriorates Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

Su1852 - Deficiency of CCR7 Deteriorates Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

Mo1882 - Rebleeding Rate and Related Risk Factors for Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy

Mo1882 - Rebleeding Rate and Related Risk Factors for Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy

Non-steroidal anti-inflammatory drug-induced enteropathy.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to be associated with serious upper gastrointestinal complications, such as peptic ulcer, bleeding, perforation, and obstruction. Recently, attention has been mainly focused on the small bowel injuries caused by NSAIDs, and new endoscopic techniques such as capsule endoscopy and double balloon endoscopy can help in detecting such injuries. This article reviewed the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of small bowel injuries caused by NSAIDs. Small bowel injures by NSAIDs might occur with a similar frequency and extent as those observed in the upper gastrointestinal tract. The pathogenesis of NSAID-induced enteropathy is complex and not clearly understood. The various lesions observed in the small bowel, including petechiae, reddened folds, loss of villi, erosions, and ulcers can be detected by capsule endoscopy. A drug that could prevent or treat NSAID-induced enteropathy has not yet been developed. Therefore, further investigations should be performed to elucidate the pathogenesis of such enteropathy and develop suitable preventive and treatment strategies.

Practice patterns and clinical significance of use of capsule endoscopy in suspected and established Crohn's disease.

Background/AimsAlthough the role of capsule endoscopy (CE) in Crohn's disease (CD) has expanded, CE is not used routinely for diagnosing and evaluating CD in Korea. We aimed to investigate current patterns of practice and evaluate the clinical significance of the use of CE in CD in Korean patients.MethodsAmong 651 CE procedures performed for various indications, we retrospectively analyzed the medical records of patients who underwent CE in 57 cases of suspected CD (sCD) and 14 cases of established CD (eCD).ResultsIn the sCD group, CE was most commonly used for the initial diagnosis of CD (54.4%). Capsule retention was found in only 1 patient in the eCD group (1/71, 1.4%). In the sCD group, 28.1% of patients were diagnosed with CD on the basis of CE findings; other diseases diagnosed included tuberculous enteritis (7.0%), non-steroidal anti-inflammatory drug-induced enteropathy (5.3%), and other enteritis (17.5%). Only 11.5% of patients with eCD (14/122) underwent CE. The indication for CE in the 14 patients with eCD was to assess disease extent and activity. The overall diagnostic yield of CE was 59.7%. Therapeutic strategies were changed in 70.2% of patients in the sCD group and 50% of those in the eCD group based on CE findings.ConclusionsIn clinical practice, CE was most commonly indicated for the initial diagnosis of CD and was not generally performed in patients with eCD. CE appears to be an effective diagnostic modality for evaluating sCD and is useful for determining therapeutic strategies for patients with sCD and those with eCD.

In vivo effects of s-pantoprazole, polaprenzinc, and probiotic blend on chronic small intestinal injury induced by indomethacin.

Treatment and prevention methods for non-steroidal anti-inflammatory drug-induced enteropathy have not yet been established. We tested the preventive effects of s-pantoprazole sodium trihydrate (PAN), polaprezinc (PZ), and probiotics on an indomethacin (Indo)-induced small intestinal injury in a rat model. Rats were randomised into 6 groups to receive: normal saline (control), Indo (6 mg/kg), PZ plus Indo, PAN plus Indo, or probiotics plus Indo (at 108 and 109 cfu/head) for 2 weeks. We measured body weight, food intake, severity of small intestinal damage, haemoglobin (Hb) levels in the small intestinal fluid, intestinal inflammatory cytokines, and a few groups of faecal bacteria. The experimental groups were found to have the following survival rates: 0% for the Indo, PZ, and PAN groups; 50% for both probiotic groups; and 100% for control. Treatment with probiotics of different concentrations reduced small intestinal lesion scores and intestinal fluid Hb as compared with the Indo group, while these parameters did not reduce in the PZ and PAN groups. The anti-inflammatory marker interleukin 10 increased in both probiotic groups. Analysis of a few groups of faecal bacteria revealed that Indo-induced a significant increase in Gram-negative bacteria and decreases in Bifidobacterium and Lactobacillus. Similar changes were also observed in the PZ and PAN groups. However, opposite effects were found in both probiotic groups. The use of probiotics appeared to be beneficial in preventing Indo-induced chronic small intestinal injury.

Tu1888 Deficiency of CCR7 Exacerbates Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

Tu1888 Deficiency of CCR7 Exacerbates Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge.

Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

Severe apoptotic enteropathy caused by methotrexate treatment for rheumatoid arthritis

The folic acid antagonist methotrexate is a cornerstone treatment of rheumatoid arthritis. Its use is limited chiefly by gastrointestinal toxicity, which is among the main reasons for methotrexate discontinuation. Here, we report the case of a 40-year-old man on chronic methotrexate therapy in whom life-threatening apoptotic enteropathy with watery diarrhea and hypovolemic shock developed after he was switched from the oral to the intramuscular route, with no change in dosage. Colonic biopsies suggested drug-induced colitis, showing a nonspecific, mildly inflammatory infiltrate of lymphocytes and plasma cells, dilated damaged crypts, and a marked increase in basal crypt apoptosis (>20 apoptotic bodies/100 crypts). Clinicians should be aware that methotrexate can cause life-threatening apoptotic enteropathy. Increased basal crypt apoptosis in colonic biopsies with more than 5 apoptotic bodies/100 crypts should routinely suggest drug-induced enteropathy.

Peyerʼs Patches Play a Protective Role in Nonsteroidal Anti-inflammatory Drug-induced Enteropathy in Mice

Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. Wild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina propria (LP) of the small intestine were measured. WT and PP-null mice were given antibiotics before indomethacin treatment to evaluate enteropathy. Naive CD4 T cells were co-cultured with CD103 or CD103 dendritic cells (DCs) to analyze the interleukin (IL)-10 expression levels. Finally, WT mice adoptively transferred with CD103 or CD103 DCs were injected with indomethacin. The proportion of CD103 DCs in PPs and MLNs and IL-10-expressing CD4 T cells of PPs and the LP increased after indomethacin treatment. The PP-null mice showed greater indomethacin-induced enteropathy, fewer CD103 DCs in their MLNs, and lower proportion of IL-10-expressing CD4 T cells of their LP than WT mice, regardless of commensal bacteria. Naive splenic CD4 T cells co-cultured with CD103 DCs isolated from the MLNs of indomethacin-injected WT mice produced a higher amount of IL-10 compared with those co-cultured with CD103 DCs. Moreover, WT mice that received CD103 DCs showed milder enteropathy than those that received CD103 DCs. PPs play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy, and this protection is associated with an increase in CD103 DCs and IL-10-producing CD4 T cells in the intestine, independent of the commensal bacteria.

Increased Gap Density Predicts Weakness of the Epithelial Barrier In Vivo by Confocal Laser Endomicroscopy in Indomethacin-Induced Enteropathy

The intestinal epithelial barrier plays an important role in the pathogenesis of non-steroidal anti-inflammatory drug-induced enteropathy, and its disruption is often associated with increased cell shedding. The purpose of this report is to observe the gap density in indomethacin-induced small intestinal damage by confocal laser endomicroscopy (CLE) and to investigate the mechanisms involved in this process and how mucosal protectants improve intestinal epithelial barrier dysfunction. CLE is expected to provide a new way for evaluating non-steroidal anti-inflammatory drugs-induced enteropathy in humans and assessing drug efficacy. Using the new technique of CLE, we established a method to evaluate, in real time, intestinal damage after the administration of indomethacin in Wistar rats by investigating the gap density in the small intestine. The mucosal protectant teprenone and acid-suppressant rabeprazole were then given by gavage before and after the administration of indomethacin, and the mechanisms affecting the intestinal epithelial barrier were investigated. Using CLE, gaps could be clearly observed and easily distinguished from goblet cells. Gap density was increased after the administration of indomethacin. During this process, the expression of tumor necrosis factor-α, nuclear factor-κB, and caspase-3 was up-regulated and the expression of tight junctions was down-regulated, which led to the damage of the epithelial barrier. Teprenone and rabeprazole could intervene in this pathway and protect the integrity of the epithelial barrier. CLE can be objective, accurate, and real time in investigating gap density. Teprenone and rabeprazole can prevent indomethacin-induced intestinal lesions and protect the epithelial barrier by intervening in the tumor necrosis factor-α pathway. Gap density was expected to be an indicator of evaluating intestinal inflammation and drug efficacy.

Meckel's diverticulum detected by virtual enteroscopy in a patient with nonsteroidal anti-inflammatory drug-induced enteropathy

Meckel's diverticulum detected by virtual enteroscopy in a patient with nonsteroidal anti-inflammatory drug-induced enteropathy

Endoscopic diagnosis of small intestinal diseases.

The technological development in endoscopy is directed toward improved accuracy of the diagnoses of novel diseases. The capsule endoscope and balloon-assisted endoscope are examples of such technological development. By these novel technologies, the small intestine can be examined in more detail. Therefore, an increasing number of novel diseases have been discovered, requiring the establishment of diagnosis and treatment strategies for these unknown diseases. In particular, obscure gastrointestinal bleeding, Crohn's disease, and nonsteroidal anti-inflammatory drug-induced enteropathy are of great interest to endoscopists. The capsule endoscope is the best method for screening the small intestine; however, the development of supporting methods such as the patency capsule is eagerly desired.