Small Bowel Inflammation Research Articles

S3024 Case of a Young Adult With Small Intestine Predominant Henoch Schonlein Purpura

Introduction: Henoch Schonlein Purpura (HSP) is the most common systemic vasculitis in young children, but is less commonly seen in adults. Diagnosis is based on the presence of palpable purpura without thrombocytopenia and with at least one other disease manifestation (arthritis, renal involvement, and/or abdominal pain). Gastrointestinal (GI) manifestations rarely precede the classic rash. Here we describe a young adult who initially presented with solely GI involvement of HSP. Case Description/Methods: A 25-year-old healthy male presented with two weeks of nausea, persistent sharp peri-umbilical abdominal pain of variable severity, and melena. Labs were notable for WBC 10.9 K/uL with neutrophilic predominance, CRP 66 mg/L, ESR 4 mm/hr, creatinine 0.88 mg/dL. Abdominal X-ray with mildly dilated gas-filled small bowel loops in central abdomen. CT abdomen/pelvis was unrevealing. EGD revealed antral-predominant nodular erythematous mucosal lesions in the stomach but otherwise normal appearing gastric mucosa (Fig 1a), histologically with surface hemorrhage. In the duodenum, diffuse erythematous mucosa with spontaneous hemorrhage was seen (Fig 1b), pathology consistent with duodenitis and erosions/ulcerations. Colonoscopy revealed right-sided erythema and granularity with biopsies showing non-specific inflammation. Interestingly, the day after endoscopic evaluation the patient developed bilateral lower extremity petechial rash (Fig 1c). Punch biopsies were diagnostic of IgA-mediated leukocytoclastic vasculitis. The overall presentation was consistent with HSP without renal involvement. Further work-up showed low C3 (consistent with HSP), negative ANA screen and ANCA, normal gastrin level, negative cryoglobulins, and unremarkable infectious work up. Discussion: HSP in adults is rare, especially if it presents with isolated GI disease. However, clinicians should maintain a high index of suspicion in adults with manifestations of small bowel inflammation. HSP mainly affects the small intestine, because the villi contain end-capillaries that get obstructed by immune complexes and cause necrosis. The rest of the GI tract is generally not involved by medium-vessel vasculitis due to its redundant circulation. The skin and epiphyseal plate have similar capillaries and are therefore frequently affected by HSP. Treatment with corticosteroids is controversial as most patients improve with supportive care. In this case, decision was made to treat with corticosteroids as patient returned with worsening disease activity.Figure 1.: a) Endoscopic view of gastric antrum/pylorus with multiple small nodular erythematous mucosal lesions; b) Endoscopic view of second portion of the duodenum showing diffuse erythematous mucosa with many erosive purple-hued mucosal lesions in a diffuse distribution with associated spontaneous bleeding; c) Classic purpuric rash on medial aspect of right foot.

S1347 Comparison of Magnetic Resonance Enterography and Balloon Assisted Enteroscopy in the Detection of Active Small Bowel Inflammation in Patients with Crohn’s Disease

Introduction: There are several modalities to detect active inflammation in the small intestine in patients with Crohn’s disease. Magnetic resonance (MR) enterography is a recommended non-invasive imaging technique that can detect inflammation, strictures and fistulas. Balloon assisted enteroscopy (BAE) allows direct visualization and sampling of the small intestine. We aimed to compare MRE and BAE in the detection of active small bowel inflammation in patients with Crohn’s disease. Methods: We performed a retrospective analysis of patients with Crohn’s disease who underwent both MRE and BAE between January 2011 and March 2021. All patient charts were analyzed for MRE findings, BAE findings, age, sex, and surgical history. MRE was considered positive for active inflammation if findings included mural thickening, mucosal enhancement, mesenteric edema and lymphadenopathy. BAE was considered positive for active inflammation if ulceration seen and inflammation confirmed on pathology. Results: Retrospective review identified a total of 96 patients with both MRE and BAE performed. A total of 18 patients were excluded since the time between MRE and BAE was greater than one year. Of the remaining 78 patients, 40 patients (51.2%) had a history of prior Crohn’s related surgery. Three BAE (3.7%) were unsuccessful in reaching small intestine findings seen on MRE due to stricture or adhesions. The agreement of a lack of active inflammation between MRE and BAE findings occurred in 17 patients (21.7%). MRE and BAE agreed with the presence of active inflammation in 34 patients (43.5%). In three patients (3.7%), MRE showed active inflammation but BAE did not find any visual or pathologic evidence of active inflammation. In 19 patients (24.3%), MRE was negative for active inflammation but BAE was positive. When compared to the other groups, this group had higher rates of prior surgery (63.2%) and higher rates of inflammatory stricture (52.6%). Conclusion: In patients with Crohn’s disease, MRE and BAE are helpful modalities in detecting active inflammation in the small intestine. In patients with a history of Crohn’s related surgery, BAE may be more helpful in determining presence of active inflammation or inflammatory strictures. Despite history of surgery, BAE is successful in reaching small bowel lesions.

S944 Fecal Calprotectin From Ileostomy Output Is Sensitive and Specific for the Prediction of Small Bowel Inflammation in Patients With Crohn's Disease

S944 Fecal Calprotectin From Ileostomy Output Is Sensitive and Specific for the Prediction of Small Bowel Inflammation in Patients With Crohn's Disease

Assessment of a new score for capsule endoscopy in pediatric Crohn's disease (CE-CD).

Background and study aims Two scores have been implemented to standardize capsule endoscopic (CE) findings in patients with Crohn’s disease (CD): Lewis score (LS) and Capsule Endoscopy Crohnʼs Disease Activity Index (CECDAI). Both have limitations and are not well validated in the pediatric population. The aim of our study was to assess a new score (capsule endoscopy – Crohn’s disease index, CE-CD) in pediatric patients with CD and to compare it to preexisting scores. Patients and methods This was a double-center, retrospective study involving pediatric subjects with CD who underwent CE. Correlation analyses between CE-CD, endoscopy scores and noninvasive markers of disease activities were performed. The ability of different CE scores to predict clinical and endoscopic outcomes was evaluated with regression and survival analyses. Results A total of 312 subjects were analyzed. The CE-CD score showed a moderate (Pearson’s r = 0.581, P < 0.001) and strong (r = 0.909, P < 0.001) association with LS and CECDAI, respectively. CE-CD was a statistically significant predictor of hospitalization (hazard ratio [HR]1.061), treatment escalation (HR 1.062), steroid therapy (HR 1.082), clinical (HR 1.064) and endoscopic (HR 1.060) relapse over the twenty-four months ( P < 0.001). Subjects with mucosal inflammation according to CE-CD (CE-CD ≥ 9) had worse outcomes compared to patients without inflammation (CE-CD < 9) (Log rang test < 0.001). Conclusions The CE-CD score is a simple, reliable, reproducible, and predictive score for evaluation of small bowel inflammation in pediatric patients with CD. Prospective validation is needed to confirm the applicability of this new index in clinical practice.

Higher concentrations of cytokine blockers are needed to obtain small bowel mucosal healing during maintenance therapy in Crohn's disease

Several studies have reported a positive correlation between serum drug concentrations and endoscopic remission in patients with Crohn's disease. To examine the association between the concentrations of cytokine blockers (infliximab, adalimumab and ustekinumab) and endoscopic remission of small bowel lesions. This was a cross-sectional study conducted at a single tertiary referral centre. Patients with Crohn's disease who received maintenance cytokine blocker therapy were recruited from April 2018 to May 2020. We performed balloon-assisted enteroscopy and collected serum samples to measure drug concentrations. The primary endpoint was the relationship between the concentrations of cytokine blockers and endoscopic remission in the small bowel. We enrolled 143 patients, 66, 44 and 33 of whom were receiving infliximab, adalimumab and ustekinumab, respectively. Enteroscopic findings showed that the rate of endoscopic remission of small bowel lesions was significantly lower than that of colonic lesions (P<0.01). For each agent, the mean drug concentration in patients exhibiting endoscopic remission in the small bowel was higher than that observed in patients with endoscopic remission in the colon (but not in the small bowel) or with any active disease (either in the small bowel, colon or both). Patients with infliximab, adalimumab and ustekinumab concentrations >5, 14 and 4µg/mL were nearly 5.3-, 9.4- and 14.7-times more likely to exhibit endoscopic remission of the small bowel, respectively. Cytokine blocker treatment was less efficacious for small bowel inflammation than colonic inflammation. Higher serum concentrations were needed to achieve endoscopic remission of small bowel lesions.

Inter-reader agreement of the Society of Abdominal Radiology-American Gastroenterological Association (SAR-AGA) consensus reporting for key phenotypes at MR enterography in adults with Crohn disease: impact of radiologist experience.

To assess inter-reader agreement of key features from the SAR-AGA recommendations for the interpretation and reporting of MRE in adult patients with CD, focusing on the impact of radiologist experience on inter-reader agreement of CD phenotypes. Two experienced and two less-experienced radiologists retrospectively evaluated 99 MRE in CD patients (50 initial MRE, 49 follow-up MRE) performed from 1/1/2019 to 3/20/2020 for the presence of active bowel inflammation (stomach, proximal small bowel, ileum, colon), stricture, probable stricture, penetrating disease, and perianal disease. The MRE protocol did not include dedicated perianal sequences. Inter-rater agreement was determined for each imaging feature using prevalence-adjusted bias-adjusted kappa and compared by experience level. All readers had almost-perfect inter-reader agreement (κ > 0.90) for penetrating disease, abscess, and perianal abscess in all 99 CD patients. All readers had strong inter-reader agreement (κ: 0.80-0.90) in 99 CD patients for active ileum inflammation, proximal small bowel inflammation, and stricture. Less-experienced readers had significantly lower inter-reader agreement for active ileum inflammation on initial than follow-up MRE (κ 0.68 versus 0.96, p = 0.018) and for strictures on follow-up than initial MRE (κ 0.76 versus 1.0, p = 0.027). Experienced readers had significantly lower agreement for perianal fistula on follow-up than initial MRE (κ: 0.55 versus 0.92, p = 0.008). There was strong to almost-perfect inter-reader agreement for key CD phenotypes described in the SAR-AGA consensus recommendations including active ileum and proximal small bowel inflammation, stricture, penetrating disease, abscess, and perianal abscess. Areas of lower inter-reader agreement could be targeted for future education efforts to further standardize CD MRE reporting. Dedicated perianal sequences should be included on follow-up MRE.

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

Abstract 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.

Small bowel adenocarcinoma arising in longstanding fibrostenotic Crohn’s disease

Empirical evidence suggesting a link between neoplasia and chronic inflammation was first noted by Virchow more than a century ago, but the intricacies of the involved pathological processes have not yet been entirely elucidated. With a growing number of Crohn’s disease (CD) cases worldwide, it is only logical to consider that the complications of this entity would become proportionally more prevalent. We report a case of small bowel adenocarcinoma arising in a patient with longstanding CD and discuss the current differences in paradigms related to surgical decisions in patients with inflammatory small bowel disease. A 56-years-old male patient known with CD was admitted in emergency to our clinic for intense diffuse abdominal pain spontaneously and on palpation, Blumberg +, with signs of peritoneal irritation, episode apparently much more severe compared to the previous ones. Laboratory investigations confirmed the diagnosis of acute abdomen and immediate surgery was performed. Intraoperative findings were peritonitis due to ileal perforation and ileal adenocarcinoma with “signet ring” cells, moderately differentiated (G2), on the background of active inflammatory bowel disease (CD). Segmental enterectomy and ileostomy were performed. The postoperative outcome was relatively favorable, with resumption of digestive tolerance and of intestinal transit at ileostomy level. As increased evidence suggest causality between chronic inflammation and malignant transformation one should contemplate whether the old treatment paradigms applied for other conditions such as fistulae in anal and leg ulcers should not be translated to inflammatory bowel disease (IBD) patients. Are we doing too much or not enough surgery for IBD? Could we diagnose small bowel adenocarcinomas in CD in early stages or there is too much risk for the patients and very few to benefit from a more aggressive surveillance?

The utility of faecal and urine biomarkers for small bowel diseases.

Small bowel diseases pose a unique diagnostic and management challenge and often requires tertiary specialist referral. The use of biomarkers may provide a cheap, noninvasive tool to assess the small bowel in terms of diagnosis, offering a better way to triage referrals and select patients for early management. This review looks at the most recent evidence behind the use of several faecal and urine biomarkers for small bowel diseases. Faecal calprotectin shows the most promise, with evidence to support its role in predicting relapse postsurgery and monitoring treatment response in patients with Crohn's disease. A faecal calprotectin less than 50 μg/g may also be used as a cut-off to triage further investigation. Faecal lactoferrin also appears promising as a marker of small bowel inflammation. A positive faecal immunohistochemistry test precapsule may help to prioritize referrals for obscure bleeding. The use of biomarkers in the diagnosis and management of small bowel disease is still controversial and remains unclear. More studies are required to further develop their potential and before societal guidelines can be developed to direct their appropriate use in clinical practice.

Double-headed small-bowel capsule endoscopy: Real-world experience from a multi-centre British study

IntroductionCapsule endoscopy (CE) is well established the investigation of small-bowel (SB) pathology. We compared the use of double-headed (DH) capsules, to conventional single-headed (SH), in a real-world patient cohort in the first multicentre British study. MethodsOver 9 months, patients referred for routine SBCE at 4 tertiary referral centres in the UK underwent DH CE instead of conventional SH using MiroCamⓇ MC2000 as per local protocols. One head (L/R) was chosen at random and reported by an expert reviewer. The DH recordings, anonymised and randomised, reported by another expert or re-read after a 4-week interval. For each CE, numbers and types of findings and overall conclusion/diagnosis were compared between SH and DH examinations. Results211 CEs were performed. 7 failed to reach the SB; 204 analysed. Indications were: SB bleeding (n = 94); ?SB inflammation or reassessment of known inflammatory bowel disease (IBD) (n = 84); ?SB neoplasia including suspicious radiological imaging (n = 15); and, others e.g. ?celiac disease (n = 11). For SB bleeding: 27/94 (28.7%) examinations reported differences between SH and DH readings. In 17 (18.1%) the findings were clinically significant. SH CE missed angiectasias (5 pts), SB inflammation (7 pts), oesophagitis (2 pts) and SB masses (2 pts). In 1 patient, the extent of angiectasias seen was greater on the DH reading. For IBD: findings differed in 30/84 (35.7%) of CEs; 11 (13.1%) were clinically significant. In 5, signs of active inflammation were missed by the SH reading. In 6, assessment of extent/severity differed. For?SB neoplasia findings differed in 2/15 (13.3%) of examinations. Both were clinically significant. For others: 1/11 (9.1%) examinations differed; however, not deemed clinically significant. Overall, use of DH CE impacted the diagnosis in 30/204 (14.7%). ConclusionsThe use of DH CE provides more information with the potential to change clinical diagnosis and therefore management. Therefore, the routine adoption of DH CE in SB assessment should be considered.

ROLE OF MAGNETIC RESONANCE ENTEROGRAPHY IN THE DIAGNOSTICS OF ACTIVE CROHN’S DISEASE IN CHILDREN

Abstract Background Crohn’s disease (CD) is an idiopathic inflammatory bowel disease of the gastrointestinal tract. It is more common in the developed and industrialized countries, particularly in the Western Europe and North America. Up to 20–30% of patients present first symptoms during childhood or adolescence. Traditionally it is diagnosed by clinical indicates, endoscopy and histological findings. Assessment of the disease activity and location along the gastrointestinal tract are of crucial importance for diagnosis and implementation of the proper treatment. Active inflammation can manifest as mural thickening, edema, ulcerations, abscesses or fistulas. Magnetic resonance enterography (MRE) is the most modern radiological method in depicting all of these manifestations of CD. Objective The aim of the study was to assess the value of MRE in evaluation of Crohn’s disease in pediatric patients. Materials and Methods 18 children (8 boys, 10 girls) with confirmed diagnosis of Crohn’s disease, were included in the study. Each patient underwent MR enterography with intravenous administration of a contrast agent. All studies were performed using a 1.5T scanner according to a local study protocol. Results All MRE findings were associated with small bowel inflammation. All patients showed asymmetric ileal wall thickening and edema. Edematous ileocecal valve was visible in 8 patients. In 7 cases reactive lymphadenopathy was detected (lymph nodes ≥ 10 mm in short axis). In 4 patients small intestine fistulas were found, whereas abscess was observed in another 4 patients. In contrast-enhanced images, a vivid enhancement of the affected bowel section was revealed in all patients and in 10 children inflammatory infiltration of periintestinal fat was depicted. Conclusion MRE is a reliable tool in diagnosis, evaluation of the disease activity and assessment of potential complications of Crohn’s disease. Due to the lack of ionizing radiation MRE exhibits beneficial safety profile and can be offered to patients who repeatedly require follow-up examinations, especially in pediatric patients.

Intake of Lactobacillus delbrueckii (pExu:hsp65) Prevents the Inflammation and the Disorganization of the Intestinal Mucosa in a Mouse Model of Mucositis.

5-Fluorouracil (5-FU) is an antineoplastic drug that causes, as a side effect, intestinal mucositis, acute inflammation in the small bowel. The Heat Shock Protein (Hsp) are highly expressed in inflammatory conditions, developing an important role in immune modulation. Thus, they are potential candidates for the treatment of inflammatory diseases. In the mucositis mouse model, the present study aimed to evaluate the beneficial effect of oral administration of milk fermented by Lactobacillus delbrueckii CIDCA 133 (pExu:hsp65), a recombinant strain. This approach showed increased levels of sIgA in the intestinal fluid, reducing inflammatory infiltrate and intestinal permeability. Additionally, the histological score was improved. Protection was associated with a reduction in the gene expression of pro-inflammatory cytokines such as Tnf, Il6, Il12, and Il1b, and an increase in Il10, Muc2, and claudin 1 (Cldn1) and 2 (Cldn2) gene expression in ileum tissue. These findings are corroborated with the increased number of goblet cells, the electronic microscopy images, and the reduction of intestinal permeability. The administration of milk fermented by this recombinant probiotic strain was also able to reverse the high levels of gene expression of Tlrs caused by the 5-FU. Thus, the rCIDCA 133:Hsp65 strain was revealed to be a promising preventive strategy for small bowel inflammation.

A rare primary presentation of crohn's disease: Enterocutaneous fistula with abdominal abscess

Crohn's disease (CD) is defined as a chronic gastrointestinal tract inflammatory disease which most commonly affects the distal ileum. It might present with a wide range of unspecific symptoms such as diarrhoea, abdominal pain and anorectal pathologies. In this article, we report the case of a 57-year-old man who presented solely with an abdominal abscess associated with low-grade fever. Radiological studies revealed an enterocutaneous fistula and severely inflamed small bowel loops, which were all managed surgically. The patient was stable post-operatively, and final laboratory results confirmed the diagnosis of CD and he was treated accordingly.

Is the Mixed Use of Magnetic Resonance Enterography and Computed Tomography Enterography Adequate for Routine Periodic Follow-Up of Bowel Inflammation in Patients with Crohn's Disease?

ObjectiveComputed tomography enterography (CTE) and magnetic resonance enterography (MRE) are considered substitutes for each other for evaluating Crohn's disease (CD). However, the adequacy of mixing them for routine periodic follow-up for CD has not been established. This study aimed to compare MRE alone with the mixed use of CTE and MRE for the periodic follow-up of small bowel inflammation in patients with CD.Materials and MethodsWe retrospectively compared two non-randomized groups, each comprising 96 patients with CD. One group underwent CTE and MRE (MRE followed by CTE or vice versa) for the follow-up of CD (interval, 13–27 months [median, 22 months]), and the other group underwent MRE alone (interval, 15–26 months [median, 21 months]). However, these two groups were similar in clinical characteristics. Three independent readers from three different institutions determined whether inflammation had decreased, remained unchanged, or increased within the entire small bowel and the terminal ileum based on sequential enterography of the patients after appropriate blinding. We compared the two groups for inter-reader agreement and accuracy (terminal ileum only) using endoscopy as the reference standard for enterographic interpretation.ResultsThe inter-reader agreement was greater in the MRE alone group for the entire small bowel (intraclass correlation coefficient [ICC]: 0.683 vs. 0.473; p = 0.005) and the terminal ileum (ICC: 0.656 vs. 0.490; p = 0.030). The interpretation accuracy was higher in the MRE alone group without statistical significance (70.9%–74.5% vs. 57.9%–64.9% in individual readers; adjusted odds ratio = 3.21; p = 0.077).ConclusionThe mixed use of CTE and MRE was inferior to MRE alone in terms of inter-reader reliability and could probably be less accurate than MRE alone for routine monitoring of small bowel inflammation in patients with CD. Therefore, the consistent use of MRE is favored for this purpose.

Diagnostic Accuracy of Fecal Calprotectin for the Detection of Small Bowel Crohn's Disease through Capsule Endoscopy: An Updated Meta-Analysis and Systematic Review.

Background/AimsThe diagnosis of small bowel Crohn’s disease with negative ileocolonoscopic findings has been challenging. Fecal calprotectin (FC) has been used to detect colonic inflammation, but its efficacy for detecting small bowel inflammation is less established. We performed an updated meta-analysis to evaluate the diagnostic accuracy of FC to detect active small bowel inflammation observed during capsule endoscopy.MethodsWe conducted a systematic literature search for studies that evaluated the correlation between small bowel inflammation and FC in patients with suspected/established Crohn’s disease. We calculated the pooled sensitivity, specificity, and diagnostic odds ratios (DORs) and constructed hierarchical summary receiver operating characteristic curves for FC cutoffs of 50, 100, and 200 µg/g.ResultsFourteen studies were eligible for the final analysis. The DORs of all FC cutoffs were significant. The highest DOR was observed at 100 µg/g (sensitivity, 0.73; specificity, 0.73; and DOR, 7.89) and was suggested as the optimal diagnostic cutoff. If we analyzed only studies that included patients with suspected Crohn’s disease, the DOR was 8.96. If we analyzed only studies that included patients with a Lewis score ≥135 as a diagnostic criterion for active disease, the DOR was 10.90.ConclusionsFC has significant diagnostic accuracy for detecting small bowel inflammation, and an FC cutoff of 100 µg/g can be used as a tool to screen for small bowel Crohn’s disease. (Gut Liver 2021;15-741)

Altered Intestinal ACE2 Levels Are Associated With Inflammation, Severe Disease, and Response to Anti-Cytokine Therapy in Inflammatory Bowel Disease

The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls. Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n= 495; n= 387 UC; n= 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted. ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti-tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders. Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection andpotentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.

S1580 Gallstone Ileus in a 67-Year-Old Male

INTRODUCTION: There are several causes of small bowel obstructions. About 4% of all cases of mechanical intestinal obstructions are caused by gallstones. This increases to 25% in the elderly (age > 65 years) with a heavy female predominance (male:female ratio 3.5:6.0). This clinical vignette presents a case of gallstone ileus in a 67 year old male and aims to increase the priority of gallstone ileus on the differential list due to suspicion of an increase in prevalence of this condition. CASE DESCRIPTION/METHODS: 67M presents with 4.5 hours of sharp periumbilical and epigastric pain that has been progressively worsening and associated with intermittent spasms. Pt denies previous abdominal surgeries and no reported history of gallbladder issues. Physical exam revealed generalized tenderness most prominent in the epigastric, RUQ and periumbilical region with rebound tenderness. No distension, rigidity or guarding were noted. Abdominal CT revealed mild small bowel dilatation and inflammation. Pt was admitted for an SBO and initially managed conservatively. Pt's symptoms continued to worsen such that he vomited 4000 cc of bilious emesis and NGT output was 2600cc in 24 hours. He was not passing flatus or having BMs. Surgery decided to proceed with an exploratory laparotomy. Intraoperatively, pt was found to have a loop of bowel in the mid jejunum that was twisted, dilated and associated with patchy necrosis. A 3 cm stone was noted just distal to this segment and was causing a complete SBO with transition zone. The source of the stone was felt to be of gallbladder origin. However, gallbladder was contracted and firm without inflammation. No portal vein gas was noted on CT, but there was not another source seen for the stone. No large duodenal diverticulum based on CT. GI recommended a CT enterography, which revealed intraluminal gallbladder air that may relate to a biliary enteric fistula. Thickening of the first portion of the duodenum that made contact with the gallbladder was also noted. DISCUSSION: Prevalence of gallstone ileus may be increasing, and the ratio between males and females may be more evenly distributed than prior. Two subsequent cases of gallstone ileus in males were seen at the same hospital in the following months. It will be beneficial to have this condition higher on the differential list in patients presenting with a bowel obstruction. Patients over the age of 65 found to have asymptomatic gallstones may benefit from elective cholecystectomy to prevent gallstone ileus and its complications.Figure 1.: Three centimeter gallstone with segment of mid-jejunum removed intra-operatively.Figure 2.: Intraluminal gallbladder air noted on CT enterography.Figure 3.: Thickened first portion of the duodenum along the right lateral aspect which contacts the gallbladder.

S2118 Angiographic Diagnosis and Treatment of Adult GI Bleeding from Meckel’s Diverticulum

INTRODUCTION: Meckel's diverticulum is the most common gastrointestinal anomaly resulting from a persistent omphalomesenteric duct. It is usually discovered in children when gastrointestinal (GI) bleeding occurs. This case demonstrates the use of provocative angiography for both the diagnosis and treatment of a bleeding Meckel's diverticulum in an adult. CASE DESCRIPTION/METHODS: A 22-year-old woman with no known past medical history presented to the emergency department with a chief complaint of black stool, lightheadedness and weakness. On exam, her abdomen was soft and non-tender. Rectal exam showed black stool with bloody mucus. Labs were significant for a Hgb of 6.1 (MCV 90.1) from 12.1 one week prior. During her hospitalization she underwent several studies to determine the location of her bleed. Esophagogastroduodenoscopy, colonoscopy, tagged red blood cell scan, and Meckel’s Scan were all normal. Video capsule endoscopy visualized blood in the terminal ileum and cecum mixed with stool, however no lesions were identified in these areas on colonoscopy. Magnetic resonance enterography was without evidence of small bowel inflammation. A visceral arteriogram was performed by interventional radiology, which was negative for bleeding until provocation was done using direct intra-arterial thrombolytic infusion (tissue plasminogen activator) that demonstrated active bleeding in an superior mesenteric artery branch which appeared to be serving a Meckel's diverticulum. Successful embolization was performed with a 3 mm coil and no further bleeding episodes occurred during her hospital stay. One month later she returned for surgical resection. Pathology confirmed Meckel's diverticulum with focal ulceration, underlying granulation tissue, and gastric heterotopia. DISCUSSION: Tc-99m pertechnetate scintigraphy (Meckel's Scan) is helpful in diagnosis of a Meckel’s diverticulum as pertechnetate is taken up by mucin-secreting cells of ectopic gastric tissue. This scan has high sensitivity and specificity in children but is drastically lower in adults as hemorrhage due to ectopic gastric mucosa is primarily a pediatric disease. For adults with suspected bleeding from a Meckel's diverticulum with multiple negative imaging modalities including a Meckel's scan, it is important to continue pursuit of the diagnosis using all means available. This case demonstrates the vital importance of provocation angiography in diagnosis of a Meckel's diverticulum that would have otherwise been missed and therefore left untreated.Figure 1.: Negative Meckel’s Scan. No heterotopic gastric mucosa visualized.Figure 2.: Angiogram before tPA administration. Red arrow indicates suspected Meckel diverticulum served by superior mesenteric artery branch.Figure 3.: Angiogram after tPA administration. Red arrow indicates area of extravasation and active bleeding.

S2856 New Onset Esophagitis and Ulcerative Duodenitis in a Patient With Acute SARS-CoV-2 Infection

INTRODUCTION: The novel coronavirus SARS-CoV-2 has infected nearly 6 million people globally and resulted in over 350,000 deaths thus far. While primarily a respiratory illness, gastrointestinal (GI) manifestations have been described in up to 50.5% of patients. In a subgroup of patients, GI symptoms may be the only evidence of infection. Understanding the full spectrum of GI manifestations is crucial for recognizing affected patients and maintaining the safety of both clinicians and the public. CASE DESCRIPTION/METHODS: A 27-year-old woman with lupus presented to the emergency room with three days of abdominal pain and three weeks of cough, fevers, and malaise. Physical examination was notable for severe pain with epigastric palpation but without rebound or guarding. An abdominal CT revealed segments of small bowel wall thickening concerning for possible ischemia. An abdominal angiogram showed no evidence of mesenteric ischemia, however, exhibited small bowel inflammation. An esophagogastroduodenoscopy found atrophic, friable esophagus and circumferential ulceration of the distal duodenum. Biopsies revealed fibrin-rich thrombi within the lamina propria, and submucosa associated with mucosal necrosis. No cellular infiltration was observed to suggest vasculitis. SARS-CoV-2 nasopharyngeal PCR from admission returned positive. Rheumatology was consulted and determined that the patient’s lupus was not clinically active and that microthrombi were likely related to the SARS-CoV-2 infection. The patient was discharged home on pantoprazole and apixaban with GI follow-up and instructions to self-isolate. DISCUSSION: This is the first case to date describing ulceration of the GI tract in the setting of acute SARS-CoV-2 infection. Pathology suggests the mechanism of injury to be microthrombi causing mucosal necrosis. Autopsies of recently deceased patients have similarly revealed microthrombi affecting the pulmonary and renal vasculature and it is hypothesized to be the mechanism of organ damage. Optimal medical management for hypercoagulability in the setting of SARS-CoV-2 infection remains unclear. Some authors recommend anticoagulation for 3–6 months only if venous thromboembolism (VTE) is present, while others endorse a prophylactic strategy by discharging all patients on 4–6 weeks of treatment. As SARS-CoV-2 becomes increasingly prevalent, it should be considered in the differential diagnosis of patients presenting with new onset ulcerative esophagitis or duodenitis.Figure 1.: Lower third of the esophagus. Mucosa is atrophic and friable.Figure 2.: Distal duodenum. Congested, friable mucosa with circumferential ulceration.

Uncommon Cause of Emesis and Diarrhea in a Nonverbal Elderly Patient

Question: An 80-year-old nonverbal man presented to the emergency department accompanied by his sister who provided the history of his recent illness. Three days before his visit, the patient started to experience nausea, vomiting, diarrhea, abdominal bloating, fatigue, dyspnea, and fever (100.1°F). His appetite was unchanged. Physical examination showed abdominal distension with no abdominal tenderness and breath sounds were normal. There was no history of recent travel, trauma or exposure to COVID-19. Past medical history was significant for type 2 diabetes, hyperlipidemia, hypertension, chronic kidney disease stage 3, and deafness. Laboratory studies on admission, including complete blood count with differential and basic metabolic panel were unrevealing, except for elevated blood glucose level (448 mg/dL). A computed tomography scan of abdomen and pelvis showed diverticulosis but was negative for inflammation, distention or obstruction of small bowel or colon. Due to the persistence of his symptoms, upper endoscopy was performed. Representative images of the lower third of esophagus (Figure A), stomach body (Figure B), and small bowel (Figure C) are shown. Biopsies were obtained. Representative histologic images from the small bowel are shown (Figure D, E). Testing for COVID-19 was obtained and stool sample was sent to microbiology for stool multiplex polymerase chain reaction (PCR) panel (BioFire FilmArray GI panel), which detects 21 gastrointestinal pathogens. Based on the clinical presentation and images what is the most likely etiology for patient’s diarrhea and emesis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Upper endoscopy showed reflux esophagitis (Figure A), gastric polyps (Figure B), and unremarkable small bowel (Figure C). The biopsy from the small bowel revealed villous blunting and lamina propria chronic inflammation at low power (Figure D). High magnification demonstrated intracellular organisms in the apical enterocytes consistent with Cyclospora cayetanensis (Figure E, arrows). The organisms were in multiple life stages. Some enterocytes had meronts containing banana shaped merozoites (Figure E, bottom left), whereas others contained gametocytes (Figure E, bottom right). Stool multiplex PCR was also positive for Cyclospora cayetanensis. A nasopharyngeal swab tested by a laboratory developed severe acute respiratory syndrome coronavirus-2 reverse transcriptase polymerase chain reaction was negative. The patient was started on trimethoprim/sulfamethoxazole (TMP 160–SMX 800 mg every 12 hours for 7 days) and his symptoms improved. Cyclosporiasis is an intestinal illness caused by the protozoan parasite, Cyclospora cayetanensis.1Almeria S. Cinar H.N. Dubey J.P. Cyclospora cayetanensis and cyclosporiasis: an update.Microorganisms. 2019; 7: 317Crossref Scopus (57) Google Scholar,2Giangaspero A. Gasser R.B. Human cyclosporiasis.Lancet Infect Dis. 2019; 19: e226-e236Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Infection is acquired via consumption of food (commonly leafy vegetables, berries, basil, and cilantro) or water contaminated by sporulated oocysts. Infected individuals shed unsporulated (noninfective) oocysts (8–10 μm in diameter) in the stool. These require 1–2 weeks of favorable environmental conditions to sporulate and become infective; therefore, direct person-to-person transmission is not thought to occur. As a result, this parasite is seen primarily in settings with poor sanitation and inadequate waste disposal facilities. The parasite is endemic in tropical and subtropical regions of Central and South America, Asia, and Africa, and is rare in the United States, where most of the cases are related to international travel or ingestion of imported fresh produce from Latin America. There was a recent cyclosporiasis outbreak in the United States linked to a bagged salad mix, which is the presumed exposure in our patient. After the ingestion of sporulated oocysts, the oocysts excyst in the gastrointestinal tract, freeing the sporozoites, which then invade the enterocytes of the small intestine. Inside the cells they undergo asexual multiplication into type I meronts (containing 8–12 merozoites 3–4 μm long) and type II meronts (containing 4 merozoites 12–15 μm long). Merozoites from type II meronts undergo sexual development into macrogametocytes and microgametocytes upon invasion of another host cell.3J T Nhieu F Nin J Fleury-Feith et al.Identification of intracellular stages of cyclospora species by light microscopy of thick sections using hematoxylin.Hum Pathol. 1996; 27: 1107-1109Crossref PubMed Scopus (19) Google Scholar Fertilization occurs, and the zygote develops into an oocyst which is released from the host cell and shed in the stool. Trimethoprim/sulfamethoxazole given twice a day for 7–10 days is the treatment of choice.