Chronic Nonbloody Diarrhea Research Articles

The etiological profile of chronic organic non-bloody diarrhea in India: Emergence of inflammatory bowel disease as a dominant cause.

Chronic non-bloody diarrhea may be attributed either to functional or organic diseases. The latter category may present with malabsorption syndrome if there is extensive involvement of the small bowel, whereas diseases of the large bowel may only present with diarrhea sans malabsorption. Indian data has predominantly focussed on the etiological spectrum of malabsorption syndrome in adults. The primary aim of the current study was to evaluate etiological spectrum of chronic organic non-bloody diarrhea in India. This prospective observational study was done at a tertiary care hospital in North India. Patients ≥ 18years presenting with chronic non-bloody diarrhea of > 4weeks duration were enrolled in the study after exclusion of patients with IBS and anal incontinence. During the study period of 12months, 100 patients with chronic organic non-bloody diarrhea were evaluated. A definite etiological diagnosis was made in 97 patients (97%). The mean age of the patients was 48 ± 16.7years (58% males). The median duration of diarrhea was 5.5months (interquartile range [IQR] 3.5, 11). Inflammatory bowel disease (IBD) accounted for 45% of the cases making it the predominant cause for organic diarrhea. GI infections and adult-onset celiac disease accounted for 18% and 9% of the cases, respectively. Pancreatic disease, benign or neoplastic, accounted for 6% of the total cases. Notably, gastrointestinal (GI) malignancies manifesting as chronic non-bloody diarrhea were diagnosed in 5% of the patients. Our data suggests a paradigm shift in the etiological spectrum of chronic organic non-bloody diarrhea in India with the emergence of IBD as the predominant cause displacing GI infections.

Genomic testing identifies monogenic causes in patients with very early-onset inflammatory bowel disease: a multicenter survey in an Iranian cohort.

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multicenter study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in 1 patient, respectively. In 3 patients (18.7%), no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.

P302 Diagnostic Delayed is Associated with a Poor Prognosis in Patients with Crohn's Disease

Abstract Background The studies show that diagnostic delay, especially in Crohn’s disease (CD), is associated with a higher risk of complications and major surgery. We aimed to investigate timing of the diagnostic delay (DD) and its impact on the CD outcomes. Methods We retrospectively evaluated demographic and clinical features of CD patients between June 1993 and October 2023. Diagnostic delay was defined as the time interval from the onset of the first symptoms to the making of the CD diagnosis. The first CD related symptoms were evaluated by a review of the physician’s notes and medical record. Specific symptoms of CD included chronic or recurrent bloody or non-bloody diarrhea, and/or abdominal pain accompanied by noticeable weight loss, general weakness, and fever. Results 514 patients with CD were included in the study. The median age of disease onset was 34.14 years (16–84 years). Male sex was 299 (58.2%). DD was detected median 13 months (5-47) (14 months in male and 12 months in female). DD was 12 months for diseases with onsets before the age of 40 and 15 months for diseases with onsets after the age of 40. DD was 25 months in isolated ileal involvement, in terminal ileal involvement was 21.5 months, ileo-colonic involvement was 20 months, and colonic location was 10 months. Ileal involvement was found to have a longer duration for DD than colonic involvement. Compared to stenosing behavior (20 months) and penetrating behavior (17 months), DD was shorter in non-stenosing non-penetrating behavior (12 months). DD was longer in perianal disease (18 months) than in those without (12 months). Current smokers had a longer duration of the DD (20 months) compared to non-smokers (11.5 months) and ex-smokers (10 months). The duration of DD (18 months) was longer in CD patients with extraintestinal manifestations than in those without (12 months). Regarding the biological treatment, CD patients who experienced multiple biologics and resistance had longer DD (24 months) than those who experienced biologic monotherapy and responded (12 months). Compared to patients who had not had surgery (12 months), DD was longer in CD patients who had undergone surgery (15 months). Conclusion Our study showed that ileal involvement, stenosing-penetrating behavior, perianal disease, current smoking and existing extraintestinal manifestations were connected with DD. DD was also associated with multiple biologic needed and surgery. DD may have a role a significantly increased risk of bowel damage.

PROTON-PUMP INHIBITORS ARE ASSOCIATED WITH AN INCREASED RISK OF MICROSCOPIC COLITIS: A POPULATION-BASED STUDY AND REVIEW OF THE LITERATURE.

•The study evaluated the risk of developing microscopic colitis and its subtypes in patients on PPI therapy. •Using a large multicenter database, a retrospective cohort analysis was conducted, excluding patients with autoimmune diseases, and adjusting for confounders. •An increased risk of developing microscopic colitis was associated with female gender, smoking, and the use of PPI, SSRI, and NSAIDs. •The use of PPI represented the highest odds of developing microscopic colitis. Microscopic colitis is a relatively new diagnosis that was first described in the 1980s. Patients usually present with chronic watery and non-bloody diarrhea and are typically characterized by an unremarkable gross appearance of the colon on lower endoscopy while having evidence of lymphocytic infiltration of the lamina propria and the epithelium on histology. Two subtypes have been described in the literature: Collagenous colitis, with marked thickening of the subepithelial layer, and Lymphocytic colitis. Multiple risk factors such as female gender, older age and celiac disease have been associated with this entity. A few studies have found an association between microscopic colitis and proton-pump inhibitor (PPI). The aim of our study was to evaluate the risk of developing microscopic colitis and its subtypes for patients who are on PPI therapy. A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have been diagnosed with any autoimmune disease have been excluded. A multivariate regression analysis was performed to assess risk of developing microscopic, lymphocytic, and collagenous colitis by accounting for potential confounders including female gender, smoking history, and the use of proton pump inhibitor, nonsteroidal anti-inflammatory drugs, and selective serotonin receptor inhibitors. A two-sided P value <0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). 78,256,749 individuals were screened in the database and 69,315,150 were selected in the final analysis after accounting for inclusion and exclusion criteria. The baseline characteristics of patients with microscopic, lymphocytic, and collagenous colitis is seen in table 1. Using a multivariate regression analysis, the risk of developing microscopic, lymphocytic, and collagenous colitis was calculated and illustrated in table 2. Our study showed that the risk of microscopic colitis, lymphocytic colitis and collagenous colitis was higher in females and smokers. Although medications like SSRI and NSAIDs showed a positive correlation with colitis, the highest likelihood of developing this disease was associated with PPIs. Lansoprazole has been documented to be associated with microscopic colitis as it is believed to inhibit colonic proton pumps, and subsequently promote diarrhea and inflammation. Interestingly, the prevalence of lymphocytic colitis and collagenous colitis was similar in the cohort of patients treated with PPIs, indicating no specific predisposition to either subtype. This study further confirms the risk factors associated with microscopic colitis. It can help guide physicians to recognize and eliminate these risk factors prior to initiating treatment for this disease. Future studies can focus on identifying the incidence of microscopic colitis with the different types of PPIs in the market.

Is mastocytic colitis a specific clinical-pathological entity?

The number of intestinal mast cells (MC) is increased in several types of colitis, but the mucosa of patients with chronic non-bloody diarrhea has not been studied. The current study sought to determine the relationship between MC counts and degranulation and the severity of symptoms in patients with chronic loose stools. Following a negative laboratory workup for the most common causes of chronic diarrhea, patients with chronic non-bloody loose stools were included in the study. Patients with macroscopic evidence of inflammation or organic disease were excluded after endoscopy with biopsies. Biopsies from the 179 patients in the study were stained with hematoxylin and eosin and anti-CD117 c-kit antibodies. Immunohistochemistry was used to assess the degree of MC degranulation. Out of the 179 patients, 128 had normal histologic findings suggestive of irritable bowel syndrome and were used as controls. Twenty-four presented with abnormally high MC counts (≥40 MC x HPF), 23 with ≥20 intraepithelial lymphocytes x HPF suggesting lymphocytic colitis, and 4 had both (≥40 MC and ≥20 intraepithelial lymphocytes x HPF). In the patients with high MC counts, figures were significantly higher in the right colon versus the left colon (p=0.016), but degranulation did not differ in the right versus the left colon (p=0.125). No age or sex-related difference was observed (p=0.527 and p=0.859 respectively). The prevalence of abdominal pain and bloating did not differ in the three groups (p=0.959 and p=0.140, respectively). Patients with lymphocytic colitis (p=0.008) and those with high MC counts (p=0.025) had significantly higher evacuation rates compared to controls. There was no difference between these two groups (p=0.831). Mast cell degranulation was not associated with the number of evacuations, abdominal pain, or bloating (p=0.51; p=0.41; p=0.42, respectively). The finding that a significantly higher number of evacuations was linked to increased MC in the colonic mucosa of a subset of patients with otherwise normal laboratory and endoscopic findings suggests that "mastocytic colitis" may be a new clinical-pathological entity responsible for chronic non-bloody diarrhea. Prospective studies with a larger number of patients, as well as endoscopic and histological follow-up, are needed to confirm this hypothesis.

S2704 A New Protein Losing Enteropathy: Autoimmune Cryptolytic Enterocolitis

Introduction: Protein losing enteropathy (PLE) can be classified into erosive, non-erosive, and increased interstitial pressure PLE. Presenting signs are often chronic non-bloody diarrhea, anasarca, abdominal pain, and weight loss. We present a complex case of a PLE presentation with a novel diagnosis. Case Description/Methods: A 30-year-old woman with a history of migraines presented with severe abdominal pain and chronic diarrhea. She was on long-term combined estrogen-progestin oral contraceptive pills (OCP) and chronic high dose non-steroidal anti-inflammatory (NSAID) medications. She was exposed to mycoplasma pneumoniae one month prior to presentation, without other infectious exposures. Laboratory tests were notable for hemoglobin 6 g/dL, albumin 0.5 g/dL, stool pathogen PCR negative, and fecal calprotectin >3000µg/g. Extensive infectious work up only revealed Mycoplasma IgM+. Inflammatory markers and alpha-1 anti-trypsin clearance were elevated, and she was found to have warm autoimmune hemolytic anemia. CT angiography excluded ischemia and vasculitis (autoimmune serologies were negative), revealing diffuse enterocolitis, confirmed on magnetic resonance enterography with ileal ulcers. Endoscopic evaluation revealed diffuse superficial ulcerations terminal ileum and colon with diffuse mucosal sloughing. Histopathology revealed diffusely injured crypts with crypt drop-out and minimal inflammation, without any findings to suggest infection, inflammatory bowel disease (IBD) or autoimmune enteritis (Figure). Normal B-cell switching studies excluded common variable immunodeficiency (CVID). Due to profound anasarca and inability to tolerate oral intake, albumin infusions and total parenteral nutrition were started. There was minimal response to systemic or topical steroids. Diarrhea was mildly improved with albumin repletion, and she was empirically started on vedolizumab. Discussion: Given the absence of classic IBD findings, negative infectious and immunological testing, we present the first case of autoimmune cryptolytic enterocolitis, a histopathologic diagnosis of unclear etiology and pathogenesis. The patient has responded to vedolizumab infusions as an empiric treatment for an IBD-like entity. Nevertheless, supporting the autoimmune component of this entity, is a possible concomitant potential pathway of molecular mimicry in the setting of post-mycoplasma infection along with chronic high dose NSAID and OCP exposure.Figure 1.: Terminal Ileum and Sigmoid Colon with Diffuse Crypt Dropout.

A Rare Case of Synchronous Severe Duodenal Ulcers and Acute Colitis in Sartan-Induced Enteropathy: A Case Report and Review of Literature

Sartan induced sprue-like enteropathy (SIE) was initially reported as a side effect of chronic Olmesartan use in 2012 and is characterized by chronic diarrhoea and weight loss. The diagnosis is often difficult and requires ruling out of other causes of enteropathy including infectious gastroenteritis, autoimmune enteropathy and celiac disease. A 51 – year – old Caucasian male was admitted to our hospital because of chronic non-bloody diarrhoea associated with severe acute renal failure and electrolyte imbalances. His medical history was only positive for hypertension for which he was on Olmesartan Medoxomil and Lacidipine, both of which were discontinued due to hypotension at admittance. Stool cultures and search for C. Difficile toxin resulted negative, whilst a Colonscopy showed endoscopic and histological signs of aspecific acute colitis. After having responded to i.v. hydration with normalization of the renal function the patient was discharged home with the same medications he was on before admittance. His diarrhoea relapsed and he was readmitted shortly afterwards with acute renal failure and electrolyte imbalances; the anti-hypertensive medications were again discontinued. After having excluded all other causes of diarrohea, including celiac disease and HIV, Sartan – induced enteropathy (SIE) was suspected and then confirmed with an esophagogastroduodenoscopy which revealed a severe erosive duodenitis with multiple duodenal ulcers. The patient again responded to i.v. hydration with normalization of the renal function and Olmesartan was held also at discharge without further relapse of the symptoms. SIE is a rare cause of chronic diarrhoea, weight loss and possible severe renal failure. It could affect the whole gastrointestinal tract and in cases of unexplained non-bloody diarrhea, suspecting SIE is fundamental and should be considered in the differential diagnosis. Discontinuation of the drug is generally sufficient for symptom resolution: in suspected cases with a positive medical history for chronic angiotensin receptor blocker (ARB) use, stopping the drug ex-juvantibus should be undertaken. Further research on the immunopathological mechanisms and how to recognize patients at higher risk of developing this condition is deemed necessary.

Bile Acid Diarrhea in Adults and Adolescents.

Bile acids are central to enterohepatic signaling pathways activated through natural receptors, farnesoid X receptor [FXR mediates synthesis of fibroblast growth factor-19 (FGF-19)], and G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Although bile acid diarrhea (BAD) is more commonly encountered in ileal resection or disease, there is evidence documenting "idiopathic" BAD in about 20% of adolescents and 30% of adults presenting with chronic, non-bloody diarrhea often attributed to irritable bowel syndrome. Mechanism(s) leading to increased hepatic synthesis and colonic bile acid levels in "idiopathic" BAD include reduced synthesis of FGF-19 by the ileal mucosa, or genetic variation in hepatocyte proteins klotho β and FGF receptor 4 (FGFR4) that mediate negative feedback of bile acid synthesis. The objective of this review is to summarize the diagnosis of BAD in adults and adolescents. In addition to 75 SeHCAT retention for diagnosis of BAD, studies have validated fasting serum 7αC4 and FGF-19, respectively, by-product and inhibitor of hepatic bile acid synthesis, as well as fecal bile acid measurements. These assays are widely available through reference laboratories, and they are being simplified (eg, measurement of primary fecal bile acids in a random stool sample). BAD has also been identified as a co-factor contributing to persistent diarrhea in other diseases in remission including inflammatory bowel disease, microscopic colitis, celiac disease, and neuroendocrine tumors. In summary, advances in diagnosis of BAD provide opportunities for generalists and pediatric and adult gastroenterologists to provide targeted treatment for BAD presenting as chronic non-bloody diarrhea.

Small bowel hemorrhage from check point inhibitor enteritis: a case report

BackgroundThere is rising utilization of immune checkpoint inhibitors (ICI) for a growing number of metastatic malignancies. While gastrointestinal side effects of ICI are common, isolated ICI-induced enteritis leading to small bowel hemorrhage is rare.Case presentationA 71-year-old man with a previously resected right colon adenocarcinoma on atezolizumab and recently treated Clostridioides difficile presented with acute on chronic abdominal pain and non-bloody diarrhea. A CT scan revealed enteritis of the duodenum and jejunum without colitis. Initial endoscopic work-up revealed many clean-based non-bleeding duodenal ulcers to the third portion of the duodenum and normal rectosigmoid mucosa. The patient initially improved on steroids but was readmitted on day after discharge with hematochezia and hemorrhagic shock. Repeat CT showed improvement in enteritis; however, repeat push enteroscopy revealed multiple duodenal and jejunal ulcers, two with visible vessels requiring endoscopic intervention. He continued to have significant hemorrhage requiring transfusions despite IV methylprednisolone. Conventional angiogram revealed multiple sites of active extravasation, and he underwent small bowel resection and subsequent IR embolization due to persistent bleeding. He was then started on infliximab 10 mg/kg with resolution of his small bowel hemorrhage and diarrhea.ConclusionsSevere isolated ICI-enteritis is rare and can lead to clinically significant gastrointestinal hemorrhage. Patients with severe ICI-enteritis on endoscopy should be carefully monitored for steroid refractory disease for consideration of step-up therapy such as infliximab.

Treating chronic diarrhea: A systematic review on Immunoproliferative Small Intestinal Disease (IPSID).

Immunoproliferative Small Intestinal Disease (IPSID) is a disease characterized by extra-nodal marginal zone B-cell lymphoma with villous atrophy in the small intestine, causing chronic intermittent non-bloody diarrhea. Although originally associated with the Mediterranean region, this disease is present in many countries worldwide and may have been underreported due to its complicated diagnosis and scarce scientific literature, especially in regards to treatment. This study aims to review IPSID clinical features, therapeutic options, and treatment outcomes to help physicians identify and treat IPSID. Using PRISMA guidelines, a systematic review of articles was conducted on PubMed database with search terms including IPSID, therapy, treatment, and outcomes. Inclusion and exclusion criteria were used to select 33 English language articles published from the year 2000–2020 that included relevant clinical information about IPSID treatment. Data were extracted independently by at least two authors to reduce the introduction of potential bias. There were 22 case reports, 7 reviews, 1 research article, 1 prospective study, 1 letter to the editor and 1 memoriam in which 76 patients were identified. Epidemiological analysis showed a mean patient age of 32 years old, 2.4:1 mal to female ratio and heterogeneous ethnicities, with 16 Europeans (43.2%) and 12 Asians (32.4%). Chief symptoms included chronic diarrhea (53/76, 69.7%), weight loss (49/76, 64.4%), malabsorption (38/76, 50%), abdominal pain (32/76, 42.1%), and finger clubbing (24/76, 31.6%). Patients stratified into the early disease stage (Galian A) were treated with tetracycline antibiotics, corticosteroids, and non-pharmacological supplements with mostly with complete or partial remission. Late stages (Galian B or C), were treated mostly with anthracycline-based chemotherapy, and occasionally surgery, radiotherapy, or rituximab. This work offers a targeted approach to diagnosing and treating IPSID to aid physicians and serve as a treatment guideline recommendation for future public policies and clinical studies.

Microscopic Colitis Patients Possess a Perturbed and Inflammatory Gut Microbiota.

Microscopic colitis (MC), an inflammatory disease of the colon, is characterized by chronic non-bloody diarrhea with characteristic inflammation and for some, collagen deposits in mucosal biopsies. The etiology of MC is unclear, although previous findings implicate luminal factors and thus the gut microbiome. However, the relationships between fecal microbiota and MC are relatively unexplored. Stool microbiota of MC (n = 15) and healthy controls (HC; n = 21) were assessed by 16S rRNA V4 amplicon sequencing and analysis performed in QIIME. Gut microbiota functions were predicted using Piphillin and inflammatory potential assessed using an in vitro HT29 colonocyte cell assay. MC patient fecal microbiota were less diverse (Faiths index; p < 0.01) and compositionally distinct (PERMANOVA, weighted UniFrac, R2 = 0.08, p = 0.02) compared with HC subjects. MC microbiota were significantly depleted of members of the Clostridiales, enriched for Prevotella and more likely to be dominated by this genus (Chi2 = 0.03). Predicted pathways enriched in MC microbiota included those related to biosynthesis of antimicrobials, and sphingolipids, to glycan degradation, host defense evasion, and Th17 cell differentiation and activation. In vitro, exposure of cultured colonocytes to cell-free products of MC patient feces indicates reduced gene expression of IL-1B and occludin and increased GPR119 and the lymphocyte chemoattractant CCL20. MC gut microbiota are distinct from HC and characterized by lower bacterial diversity and Prevotella enrichment and distinct predicted functional pathways. Limited in vitro experiments indicate that compared with cell-free products from healthy fecal microbiota, MC microbiota induce distinct responses when co-cultured with epithelial cells, implicating microbiota perturbation in MC-associated mucosal dysfunction.

P659 Colonoscopic screening of symptomatic patients suggests an emerging inflammatory bowel disease (IBD) in urban and rural south India

Abstract Background Recent studies suggest that IBD is on the rise in the developing world. This is also the region with limited access to healthcare facilities, poor physician and patient awareness of the disease and diagnostic dilemmas with the infectious bacterial diarrheas preventing adequate diagnosis. There is very limited data on the relative prevalence of IBD compared to the infectious diarrhoeas. We screened symptomatic patients to assess the diagnostic profile in the real world settings with free of cost service to people below poverty line and the un-insured. Methods The study is being conducted in a large tertiary care centre in Southern India from March 2020 till date. We present the results of an interim analysis. Symptomatic patients with diarrhea, unintentional weight loss, bleeding per rectum, chronic abdominal pain and unexplained anemia were screened with a blood test (Haemogram, liver function, serum protein), abdominal ultrasound and colonoscopy/ileoscopy to ensure an early diagnosis and initiation of treatment. Data including the demographics of the patients, predominant symptoms, rural/urban residence, investigations, biopsy and final diagnosis were entered into an excel spreadsheet and analysed. Results 6878 patients, 2188 female (32%), median 44 years (1–82 years) were screened between March 2020 to January 2021. Bloody diarrhoea was noted in 1212(18%), chronic non-bloody diarrhoea in 887 (13%), altered bowel habits in 2381 (35%), pain abdomen in 4030 (59%), un-intentional weight loss in 648 (10%) and anemia in188 (3%). IBD was diagnosed in 397 patients (6%) of which 169 (2.5%) were UC and 228 (3.3%) were CD. Infective etiology including intestinal tuberculosis was seen in 577 (8.3%). Colorectal cancer was diagnosed in 251 (3.6%), polyps in 614 (8.9%). Overall, 4921 (71.5%) were urban and 1957 (28.5%) rural. The proportion of UC (2.3% rural vs 2.5% urban, p=0.65) and CD (3.6% rural and 3.2% urban, p=0.43) were not different in rural and urban groups. There was significantly higher proportion of infectious colitis in the rural subgroup (p=0.01)(Table 1). Conclusion This interim analysis indicates a rising IBD in both urban and rural India vis a vis the infectious diarrheas. However, proportion of infectious colitis was significantly higher in the rural subgroup compared to the urban.

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019

Low prevalence of colorectal neoplasia in microscopic colitis: A large prospective multi-center study

Background and AimsMicroscopic colitis (MC) is the most frequent condition in subjects undergoing ileocolonoscopy for chronic non-bloody diarrhea (CNBD) in Western countries. Emerging evidence has shown a negative association between MC and colorectal cancer. Within this prospective multi-center study we have evaluated the risk of colorectal neoplasia in MC and non-MC patients with CNBD receiving ileocolonoscopy with high-definition plus virtual chromoendoscopic imaging and histopathological assessment. MethodsPatients with CNBD of unknown origin were prospectively enrolled in 5 referral centers in Northern Italy for ileocolonoscopy with high-definition and digital/optical chromoendoscopy plus multiple biopsies in each segment. The prevalence of colorectal neoplasia (cancer, adenoma, serrated lesion) in MC was compared to that observed in a control group including CNBD patients negative for MC, inflammatory bowel disease or eosinophilic colitis. ResultsFrom 2014 and 2017, 546 consecutive CNBD patients were recruited. Among the 492 patients (mean age 53±18 years) fulfilling the inclusion criteria against the exclusion critieria, MC was the predominant diagnosis at histopathological assessment (8.7%: N=43, 28 CC, 15 LC). The regression model adjusted for age and gender showed a significant negative association between the diagnosis of CM and colorectal neoplasia (OR=0.39; 95% CI 0.22−0.67, p <0.001) with a 60% decreased risk of adenomatous and neoplastic serrated polyps as compared to the control group (n=412). ConclusionThis multi-center study confirms MC as a low-risk condition for colorectal neoplasia. No surveillance colonoscopy program is to be performed for MC diagnosis.

Checkpoint Inhibitor Colitis Masked by Multi-drug Effect

Abstract Casestudy: The utilization of checkpoint inhibitors such as programmed cell death protein 1 (PD-1/PD-L1) inhibitors (nivolumab) and cytotoxic T-lymphocyte antigen 4 inhibitors (ipilimumab) for treatment of certain malignancies has steadily gained popularity. Medication related colitis is uncommon, with a reported incidence of 1–9% depending on the checkpoint inhibitor used, and the histologic features have been characterized in recent literature. Because of the immunomodulating effect of these drugs, infectious colitis is in the differential diagnosis of enteritis. Multi-drug therapy in many of these patients further complicates identification of the culprit drug. We present the case of a 63-year-old male with metastatic renal cell carcinoma being treated with both nivolumab and ipilimumab who presented with acute on chronic non-bloody diarrhea. His clinical course was complicated by hypotension, acidosis and coagulopathy. The clinical differential for his colitis was cytomegalovirus infection versus a checkpoint inhibitor colitis. Colonoscopy revealed continuous circumferential loss of vascularity and diffuse erythema throughout the colon. Histology showed acute colitis with prominent apoptosis, cryptitis, crypt abscesses, and rare ringed mitotic figures, but without architectural distortion. Occasional smooth purple crystals consistent with pill material were present in the mucosa, but without significant tissue reaction. No pathogenic organisms were identified, and a cytomegalovirus immunostain was negative. These histologic findings in concert with the clinical history are consistent with checkpoint inhibitor colitis and multi-drug effect. A review of the patient’s chart showed cholestyramine was added to the patient’s regimen during hospitalization, which was consistent with the morphologic appearance of the crystals. Given the acute complications of checkpoint inhibitor induced enterocolitis and potential for increased morbidity (rare cases of bowel perforation and subsequent resection), accurate diagnosis is imperative. Management of checkpoint inhibitor associated colitis ranges from initiation of immunosuppression to checkpoint inhibitor cessation. When these findings are masked by multi-drug effect, accurate diagnosis can be difficult.

S1640 Primary Colonic Lymphoma Manifesting as Colovesical Fistula

INTRODUCTION: Gastrointestinal (GI) tract is the most common extranodal site of Non-Hodkin lymphoma (NHL) and constitutes about 4% of all GI malignancies. The most common sites of involvement in the GI tract are stomach followed by the small intestine. We report a case of primary colonic lymphoma manifesting with colovesical fistula in a patient with human immunodeficiency virus (HIV) infection. CASE DESCRIPTION/METHODS: A 50-year-old male with a history of HIV on antiretroviral therapy with undetectable viral load and a CD4 count of 260 cells/µL, presented with burning micturition, intermittent passage of air and feculent material in urine, on and off for one year. He has chronic nonbloody diarrhea and noticed thirty-pound weight loss over the past three months. At admission, he was afebrile, hypotensive, and had sinus tachycardia (114/min). Physical examination was significant for palpable, tender left lower quadrant mass but no hepatosplenomegaly, bowel distention, or peripheral lymphadenopathy. Laboratory data revealed anemia (HB 8.5 g/dl), leukocytosis (WBC 14000/µl), mildly elevated platelet count (422,000/µl), acute kidney injury (serum creatinine 2.50, baseline 0.81 mg/dL) and normal CEA level. Urine was brown, turbid with microscopy showing RBC and WBC ( >180/hpf). CT scan of abdomen and pelvis with contrast revealed a large circumferential mass measuring 14.5 cm × 10 cm in sigmoid colon with a fistulous communication to the urinary bladder suggestive of colovesical fistula. Colonoscopy confirmed a partially obstructing, large circumferential, ulcerated mass within the proximal sigmoid colon. Pathology was consistent with diffuse large B-cell lymphoma (+BCL2, +MYC). PET-CT scan showed increased FDG uptake in the sigmoid colon along with adrenal gland and bone but no involvement of lymph nodes, liver, or spleen. A diverting colostomy was performed and subsequently, he was started on dose-adjusted R-EPOCH Regimen. The patient received 5 cycles of chemotherapy and a repeat PET-CT scan showed resolution of activity in the sigmoid colon, bone, and adrenal gland. Retroperitoneal ultrasound during chemotherapy showed persistence of colovesical fistula. DISCUSSION: HIV-AIDS predisposes patients to different malignancies including NHL in about 10% of patients. Colonic involvement of primary NHL is exceedingly rare. High viral load and low CD4 counts (< 100) are risk factors for NHL in HIV patients. We describe here an unusual presentation of NHL manifesting as colovesical fistula, in a patient with HIV.Figure 1.: Computed tomographic scan of abdomen & pelvis in sagittal view showing large sigmoid mass (long arrow). Air-fluid level of orally administered contrast noted in the urinary bladder. (short arrow).Figure 2.: Colonoscopy shows a fungating, ulcerating mass in the sigmoid colon, nearly obstructing the lumen.Figure 3.: Initial PET tumor imaging whole body.

S1724 Colonic Histoplasmosis: An Uncommon Presentation of Disseminated Histoplasmosis in an Immunocompetent Patient

INTRODUCTION: Histoplasmosis is an invasive mycosis caused by inhaling the spores formed by the environmental mold Histoplasma capsulatum. It occurs commonly in immunodeficient patients however, healthy hosts can be affected if a large number of conidia is inhaled. Here we present an intricate case of disseminated histoplasmosis in an immunocompetent patient. CASE DESCRIPTION/METHODS: An 83-year-old man with a history of coronary artery disease, atrial fibrillation, diabetes complicated by gastroparesis, and COPD who presented with a 6-month history of unintentional weight loss, normocytic anemia, abdominal crampings, and chronic non-bloody diarrhea. Previous studies included an upper endoscopy 9 years prior, showing hiatal hernia but otherwise normal with a negative H pylori test at that time. Colonoscopy 7 years prior evidencing internal hemorrhoids, diverticulosis, and one tubular adenoma in the ascending colon.He underwent extensive workup upon admission, including negative stool culture, ova and parasites, HIV screen, Giardia ELISA, and C. difficile PCR; normal C reactive protein, stool lactoferrin, TSH and celiac panel. Colonoscopy showed one 9 mm polyp in the ascending colon (Figure A), 1 polyp in the transverse colon, diverticulosis coli, and internal hemorrhoids. Biopsy of the ascending polyp revealed fragments of tubular adenoma and focally eroded colonic mucosa with mixed histiocytes-rich mucosal inflammation including intracellular organisms, favoring Histoplasma capsulatum (Figures B and C). Computed tomography (CT) abdomen showed 1.7 cm left adrenal nodule, concerning for disseminated infection. CT neck was performed for evaluation of jaw pain and swelling that showed parotitis and multiple brain lesions, confirmed by MRI. The diagnosis of disseminated histoplasmosis was confirmed with a positive urinary Histoplasma antigen. The patient was started on liposomal amphotericin B but given advanced age, multiple comorbidities, and progressive disease at the time of diagnosis, the patient opted for comfort care measures. DISCUSSION: Histoplasmosis is the most common endemic fungal disease in both healthy and immunocompromised patients with more than several thousand infections reported yearly. GI histoplasmosis is unusual in immunocompetent hosts accounting for 0.05% of cases however in 50% to 70% of cases, it occurs in disseminated form. We believe that early diagnosis and proper management prevents the progression of the disease and potentially death.Figure 1Figure 2Figure 3

Test Strategies to Predict Inflammatory Bowel Disease Among Children With Nonbloody Diarrhea.

We evaluated 4 diagnostic strategies to predict the presence of inflammatory bowel disease (IBD) in children who present with chronic nonbloody diarrhea and abdominal pain. We conducted a prospective cohort study including 193 patients aged 6 to 18 years who underwent a standardized diagnostic workup in secondary or tertiary care hospitals. Each patient was assessed for symptoms, C-reactive protein (>10 mg/L), hemoglobin (<-2 SD for age and sex), and fecal calprotectin (≥250 μg/g). Patients with rectal bleeding or perianal disease were excluded because the presence of these findings prompted endoscopy regardless of their biomarkers. Primary outcome was IBD confirmed by endoscopy or IBD ruled out by endoscopy or uneventful clinical follow-up for 6 months. Twenty-two of 193 (11%) children had IBD. The basic prediction model was based on symptoms only. Adding blood or stool markers increased the AUC from 0.718 (95% confidence interval [CI]: 0.604-0.832) to 0.930 (95% CI: 0.884-0.977) and 0.967 (95% CI: 0.945-0.990). Combining symptoms with blood and stool markers outperformed all other strategies (AUC 0.997 [95% CI: 0.993-1.000]). Triaging with a strategy that involves symptoms, blood markers, and calprotectin will result in 14 of 100 patients being exposed to endoscopy. Three of them will not have IBD, and no IBD-affected child will be missed. Evaluating symptoms plus blood and stool markers in patients with nonbloody diarrhea is the optimal test strategy that allows pediatricians to reserve a diagnostic endoscopy for children at high risk for IBD.

Issue Highlights

Issue Highlights

170 The Efficacy of Uceris in the Treatment of Microscopic and Allergic Colitides

INTRODUCTION: Chronic non-bloody diarrhea is a common complaint seen by gastrointestinal physicians. About 10–20% of these cases are secondary to the microscopic colitides (MC), which include collagenous colitis and lymphocytic colitis, and 30% are due to allergic colitides (AC), including eosinophilic colitis and mast cell enteropathy. Entocort has previously been studied as a treatment option for MC with remission rates as high as 96%. Uceris is a budesonide formulation that does not dissolve in acid and is therefore released at a controlled rate throughout the colon. This study aimed to determine whether Uceris would provide symptomatic response in patients with MC. Additionally, this study aimed to determine whether Uceris would be effective in treating AC, which currently does not have any well-established treatment options. METHODS: This was a retrospective study using the electronic medical record (EMR) and an established database of histologic findings on biopsies obtained during colonoscopies performed at Rush University Medical Center. The EMR was used to obtain demographic data and to identify what treatment medication was used (Uceris, Entocort, H1/H2 blockers, other – anti-diarrheal and stool bulking agents). Eligible subjects were contacted by telephone and asked about symptom severity pre- and post-treatment for colitis using the Modified Harvey Bradshaw Index (MHBI, Table 1). Data was analyzed using SPSS analysis of variances. RESULTS: There were 50 subjects enrolled in this study. Demographics are listed in Table 2. The mean total MHBI score for the MC subjects was 9.75 pre-treatment with all therapeutic agents and 2.13 post-treatment, and for the AC subjects was 6.83 pre-treatment and 2.89 post-treatment. There was a greater improvement in MHBI scores in the MC group compared to the AC group (P &lt; 0.031, F = 4.97, df = 1,48). For each treatment drug, there was an improvement in MHBI scores after therapy for both MC and AC (Table 3). CONCLUSION: For subjects with MC, there was greater improvement in MHBI scores with Entocort. However, the mean MHBI pre-treatment scores for MC subjects were greatest in those treated with Uceris. It is possible that Uceris was reserved for subjects with more significant symptoms or for those who failed treatment with other agents. There was a greater improvement in MHBI scores in subjects with AC that received Entocort and Uceris, suggesting that steroids may be helpful in controlling symptoms. This study was limited by small sample size and recall bias.