Increased Activated Plasma Cells in Inflammatory Bowel Disease When Compared to Ischemic Acute Colitis

Introduction/Objective Inflammatory bowel disease (IBD) and acute ischemic colitis can both be involved by active colitis. IBD is characterized by crypt architectural distortion, basal lymphoplasmacytosis, and occasional granulomatous changes. However, diagnosis of IBDs is still largely by exclusion of other types of active colitis with similar changes. We previously demonstrated that glucose regulated protein 94 (grp94) is mainly expressed by activated plasma cells. We postulate that increased numbers of grp94-positive plasma cells may support diagnosis of IBDs. Here, we compared IBD and active ischemic colitis for grp94 expression in mucosal plasma cells of colectomy specimens Methods/Case Report Tissue sections from colectomy specimens with active IBD (n = 8) and ischemic colitis (n = 7) were examined for grp94 expression by immunohistochemistry (monoclonal antibody clone 9G10 at dilution of 1:200, Enzo Life Science, Inc Farmindale, NY). The staining intensity and highest number of grp94 in plasma cells per high power field was counted and recorded for each case, and combined scores were calculated as # of plasma cells multiplied by staining intensity (ranging from 0 to 3+). Unpaired student T tests were used to compare these indices between the two groups for statistical significance (p value < 0.05 was considered significantly different) Results (if a Case Study enter NA) Plasma cells in lamina propria identified by grp94 staining showed higher intensity in IBD than ischemic groups. The number of plasma cells and combined scores were also significantly higher in the IBC group than that of ischemic group Conclusion Our data indicates that active plasma cells are much more numerous in IBD than ischemic colitis, supporting the notion that active plasma cells are involved in the development of this disease process. Morphologically, active colitis with increased number of plasma cells appears to be another index favoring the diagnosis of IBD.

P211 Pseudopolyps are associated with increased fecal calprotectin levels in patients with Inflammatory Bowel Disease in clinical and endoscopic remission

Background Fecal calprotectin (FC) has become a fundamental tool in the non-invasive monitorization of activity in patients with inflammatory bowel diseases (IBD). However, there is still debate over the choice of the optimal cut-off point for the different clinical settings. The aim of this study is to analyze whether the presence of pseudopolyps and their characteristics have an impact on the value of FC and should therefore be taken into account when deciding the optimal cutoff values. Methods A single-centered, retrospective analysis including data from patients with colonic Crohn′s disease or Ulcerative colitis who underwent colonoscopy for dysplasia screening at our center between 2018 and 2019. Patients that did not have a FC registered within 8 months from to the colonoscopy, or that did not maintain clinical remission between the colonoscopy and the measurement of the FC, were excluded. Patients that had activity in the colonoscopy (Mayo endoscopic score >0, SESCD >0) were also excluded. Results 73 patients were included. 26 (35.6%) of them had pseudopolyps in the colonoscopy. The median value of the FC was significantly different in patients with pseudopolyps (110.1 µg/g, CI 95% [48.6–171.5]) compared to those without them (52.5 µg/g, CI 95% [29.9–75.1]). In 11 (42.3%) of the patients with pseudopolyps, biopsies were taken, observing histological activity in 3 of them (27.3%) and no inflammatory activity in the other 8 (72.7%). We found that FC was higher in patients with inflammatory polyps (119.0 µg/g) in comparison to those without histological activity in their pseudopolyps (96.9 µg/g); however, these results were not statistically significant. The location of the pseudopolyps had no influence over the FC in our study. In addition, no correlation was found between the presence of polyps or diverticula and FC. Conclusion In our study, the presence of pseudopolyps is associated with significantly higher levels of FC. Moreover, our results suggest a tendency towards higher FC in patients who had active colitis in the histological samples of their pseudopolyps.

P149 Application of revised Pediatric Inflammatory Bowel Disease (PIBD) classes criteria to the Korean PIBD patients

Background In 2017, Porto group of ESPGHAN published the PIBD classes criteria, a diagnostic classification criteria for PIBD by conducting multi-center study, and the revised PIBD classes criteria were released in 2020 after multi-center verification. Consisting of 19 items classified into a total of 3 classes, this criteria classifies PIBD into UC, atypical UC, CD, and IBD-U through an algorithm. The purpose of this study is to examine the appropriateness of diagnosis and criteria by applying the revised PIBD classes-criteria for PIBD patients diagnosed in a certified tertiary hospital. Methods Among 156 new patients aged 1–18 years old diagnosed with PIBD at Seoul National University Children’s Hospital from January 1, 2014 to August 18, 2020, 102 patients who had no underlying disease, did not administer drugs that affect the immune system, whose key items of PIBD class criteria (upper and lower gastrointestinal endoscopy, gastrointestinal imaging, pathology, etc.) and basic demographic characteristics were verified were analyzed retrospectively through electronic medical records. Results Of the 102 PIBD patients, 85 (83%) were initially diagnosed with CD, 15 (15%) with UC, and 2 (2%) with IBD-U by clinicians. Of the 102 patients, 69 (68%) were male, and the age of first diagnosis was 11.5±3.7 years. After applying the revised PIBD classes criteria, the diagnosis was changed to CD for 2 IBD-U patients, IBD-U for 7 UC patients, and CD for 1 UC patient. Finally, the diagnosis was changed to 86 (84%) CD, 8 (8%) UC and 7 (7%) IBD-U. The two patients whose diagnosis was changed from IBD-U to CD satisfied the items of Class 1, so the diagnosis was changed. All 7 patients whose diagnosis changed from UC to IBD-U did not satisfy all the items of Class 1, but most of the items ‘Focal active colitis on histology in more than one biopsy’ (6/7) and ‘Focal enhanced gastritis on histology’ (7/7) of class 3 criteria were satisfied, and the diagnosis has changed. Conclusion As a result of applying the PIBD class criteria, there was no significant change in the diagnosis of CD, but the diagnosis of UC decreased by 73% and the diagnosis of IBD-U increased by 5 times. In this study group, the positive rates of items ‘Fistulising disease’, ‘‘Thickened jejunal or ileal bowel loops on radiology or other evidence of significant small bowel inflammation on capsule endoscopy’, ‘Focal active colitis on histology in more than one biopsy’ and ‘Focal enhanced gastritis on histology’ tended to be significantly higher than those of the previous study. So, Further validation and confirmation are needed.

Colonisation of the colonic mucus gel layer with butyrogenic and hydrogenotropic bacteria in health and ulcerative colitis

Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others may inhibit butyrate, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL). Mucosal brushings were obtained from 20 healthy controls (HC), 20 patients with active colitis (AC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann–Whitney-U and Kruskall-Wallis tests. Butyrogenic R. hominis was more abundant in health than UC (p < 0.005), prior to normalisation against total bacteria. Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p < 0.005). An inverse correlation existed between inflammation and R. hominis (ρ − 0.460, p < 0.005) and B. wadsworthia (ρ − 0.646, p < 0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.

A195 A RARE CAUSE OF SEVERE REFRACTORY DIARRHEA IN A PATIENT WITH COMMON VARIABLE IMMUNE DEFICIENCY ASSOCIATED INTESTINAL ENTEROPATHY

Background CVID is the most common type of severe antibody deficiency. Gastrointestinal manifestations affect approximately 20–50% of patients. Boland et al. described in a case series that 2/3 CVID patients were able to achieve clinical and endoscopic remission with Vedolizumab. This α4β7 integrin antagonist inhibits intestinal T cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte mediated inflammation. However, despite its novel use for this indication, limited data is available on the consequences of this therapy in patients with CVID. Aims To report on a case assessing the efficacy and outcomes of Vedolizumab for the treatment of CVID associated autoimmune enteropathy. Methods We present the case of a 50-year-old male presenting with severe refractory diarrhea and malnutrition. A colonoscopy demonstrated patchy ulceration and biopsies revealed ulcerated active colitis, negative for CMV. He was treated with Vedolizumab and Total Parental Nutrition (TPN). His diarrhea resolved, he gained 20 kg and he was weaned off TPN. In 2019, he re-presented with severe diarrhea. Subsequently endoscopic evaluation revealed patchy edematous colonic mucosa and biopsies demonstrated minimally active colitis, negative for CMV. He again responded to Vedolizumab re-induction, however shortly after, his diarrhea returned aggressively. CT enterography demonstrated active jejunal inflammation. Subsequently, an EGD revealed multiple duodenal ulcers and luminal narrowing. Biopsies of the small bowel were sent to histopathology. Results CMV superinfection was diagnosed on pathology (image 1). This patient’s diarrhea completely resolved with IV Gancyclovir and he was discharged on maintenance treatment with oral Valganciclovir. Conclusions This represents the first reported case of CMV enteritis secondary to Vedolizumab for the treatment of CVID associated autoimmune enteropathy. In this case, clinical and endoscopic remission was observed with Vedolizumab, however subsequently hampered by CMV reactivation. Hommel et al., published a positive correlation in a single centre retrospective cohort study of CMV reactivation in patients with ulcerative colitis treated with Vedolizumab. A large retrospective review of data from a multicenter consortium database of over 1000 Vedolizumab treated IBD patients reported CMV colitis in only 4 patients. CMV reactivation appears to be an exceptionally rare but important event in patients treated with Vedolizumab. Based on this report, patients with CVID associated enteropathy and refractory diarrhea should be carefully screened for CMV when treated with Vedolizumab. Further prospective data assessing the incidence of CMV reactivation in patients with Vedolizumab therapy is required to further define these findings. Funding Agencies None

A case of pneumoperitoneum after diagnostic colonoscopy for ulcerative colitis managed conservatively: a rare but possible complication

Ulcerative colitis is a chronic disease characterized by recurring episodes of inflammation of the colonic mucosae. Patients with ulcerative colitis are at an increased risk of perforations due to friability of colonic mucosa. Colonoscopy is usually regarded as a safe procedure, but complications may occur. Perforations associated with colonoscopy are dreaded complications. Most patients with pneumoperitoneum require surgical intervention, with associated major postoperative morbidity and mortality. This case report describes a 30 year old female presenting with an extensive pneumoperitoneum 2 days after colonoscopy done for her complaint of melena for one week. Colonoscopy was suggestive of severe active colitis in background of chronic ulcerative colitis. Histopathological reports s/o inflammatory bowel disease ulcerative colitis likely. CT Abdomen was s/o diffuse concentric thickening of the large bowel more predominantly seen in rectosigmoid colon, ascending colon, caecum, IC junction and consistent with inflammatory bowel disease and moderate pneumoperitoneum noted. The patient remained stable despite intraperitoneal free air. Patient was managed conservatively and no surgical intervention needed.

Case report: Unusual manifestation of gastric mucormycosis in patient with rheumathoid arthritis

Introduction: Mucormycosis is an opportunistic life-threatening infection whose incidence has significantly risen during the last two decades. Gastrointestinal form is very rare, with the stomach as the most common site of infection, followed by the colon and ileum. Risk factors include uncontrolled diabetes mellitus, corticosteroid use, organ transplantation. We report a patient with a history of rheumatoid arthritis who has developed gastrointestinal mucormycosis. To the best of our knowledge, this is the first such case reported in the literature. Case report: A 53-year-old female patient with a prior medical history of rheumatoid arthritis was admitted to the hospital due to persisting diarrhea. Physical examination revealed diffuse abdominal tenderness to palpation, without meteorism and peritoneal signs. Laboratory results demonstrated systemic inflammation, so antibiotic therapy was administered. An abdominal computed tomography findings revealed inflammation of the rectum and the left colon. Colonoscopy findings were indicative of Crohn?s disease. Additionally, the patient had developed profuse rectal bleeding and consequently underwent emergency surgery. Subtotal colectomy with ileostomy and partial gastrectomy was performed. Patient?s condition rapidly worsened after operation and she died due to multi-organ failure. Histologic findings of resection specimens discovered chronic active colitis and extensive gastric necrosis associated with dense mixed inflammatory infiltration and numerous nonseptate and 90-degree branching hyphae. Diagnosis of invasive gastric mucormycosis was obtained, but unfortunately, several days after the patient?s death. Conclusion: It is very important to obtain high awareness among clinicians of this deadly infection to achieve a prompt diagnosis and effective therapy.

Colonisation of the Colonic Mucus Gel Layer With Butyrogenic and Hydrogenotropic Bacteria in Health and Ulcerative Colitis

Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others have an inhibitory effect, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL).Mucosal brushings were obtained from 20 patients with active colitis (AC), 20 healthy controls (HC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann-Whitney-U and Kruskall-Wallis tests.Butyrogenic R. hominis was more abundant in health than UC (p<0.005). Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p<0.005). An inverse correlation existed between inflammation and R. hominis (ρ -0.460, p >0.005) and B. wadsworthia (ρ -0.646, p >0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic and some species of hydrogenotropic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.

Checkpoint Inhibitor-Induced Colitis: A Case Series

Introduction/Objective Checkpoint inhibitors are novel immune-stimulating antibodies that have revolutionized the management and prognosis of several malignancies. The primary targets are cytotoxic T-lymphocyte–associated antigen-4 (anti-CTLA-4; e.g. pembrolizumab) and programmed cell death-1 receptor (anti-PD-1; e.g. ipilimumab and nivolumab). In spite of the significant advantages, many immune-related adverse effects have been identified. One of which is checkpoint inhibitor-induced colitis (CIC). Although there is awareness of the histopathologic features of anti- CTLA-4 induced colitis, there is much to be discovered about the pathologic features of anti-PD-1 colitis. Methods We herein report three cases of CIC. There were two women and 1 male (age range, 50 to 73-years-old, mean 64-years-old) who presented with diarrhea and/or hematochezia after multiple cycles of pembrolizumab or ipilimumab/ nivolumab combination therapy. Endoscopic examination was abnormal in all of these cases. Results The histologic features were similar in two cases, with moderate active chronic colitis and one case with focal active colitis. Two of the three patient were given steroids in addition to their regular medications with symptom improvement. One patient was removed off all medications and enrolled into hospice due to disease progression. CIC has been an increasingly recognized immune-related adverse effect that has a wide spectrum of clinical presentations ranging from mild diarrhea and abdominal pain to severe colitis and intestinal perforation. However, it is thought to be underestimated. Histologically, CIC can mimic inflammatory bowel disease, microscopic colitis and active colitis. Our cases showed histopathologic features mimicking those of ulcerative colitis. Conclusion Awareness of CIC is crucial for the multidisciplinary management essential for these patients. The histopathologic pattern coupled with the clinical history can allow pathologists to confirm the diagnosis of CIC and facilitate timely diagnosis and treatment.