Crypt Architectural Distortion Research Articles

Colonic stem cell from severe ulcerative colitis maintains environment-independent immune activation by altering chromatin accessibility and global m6A loss

Abstract Ulcerative colitis (UC) is a chronic inflammatory disease of colon, which is characterized by cryptarchitectural distortion. Alternation of colonic stem cell (CoSC) contributed to the occurrence of UC, yet the regulatory mechanisms remain unclear. To investigate the dysregulation of transcriptional and post-transcriptional regulation, we performed RNA-seq, ATAC-seq, and m6A meRIP-seq analysis of the cultured CoSCs that were isolated from UC patients. The transcriptome analysis revealed distinct expression signatures of UC patients in mild and severe stages. We observed abnormal activation of immune and extracellular matrix-related genes in patients affected by severe UC. The chromatin accessibility at the promoter regions of these genes was also specifically increased in the severe stage. In addition, we identified that a global loss of RNA m6A modification in the severe stage was accompanied by higher expression of the m6A demethylase FTO. The aberrant activation of a large number of immune and extracellular matrix-related genes, including IL4R, HLA-DPA1, and COL6A1, was related to both the gain of chromatin accessibility and the loss of m6A in severe UC patients. Our finding revealed an environment-independent immune activation of CoSCs in UC and provided FTO as a potential therapeutic target.

PRIMARY EOSINOPHILIC COLITIS WITH CONCOMITANT NEWLY DIAGNOSED INFLAMMATORY BOWEL DISEASE – A DIAGNOSITIC CONUNDRUM

Eosinophilic colitis (EC) is a rare primary condition characterized by eosinophilic infiltration of the colon in the absence of secondary causes. Affecting only 0.003% of people in the United States, clinical manifestations of the disease can range from abdominal pain, bloody stools, and diarrhea to colonic obstruction, intussusception, volvulus, and perforation. The diagnosis is made upon histopathological analysis of colonic biopsies with the inflammatory infiltrate consisting predominantly or exclusively of eosinophils with focal collections greater than 100 per high-power field (hpf). Unlike inflammatory bowel disease (IBD), granulomas, crypt architectural distortion, pseudopyloric metaplasia, and fibrosis are not usually present with EC, but differentiating between the two conditions has proven to be difficult over the decades.

PRIMARY EOSINOPHILIC COLITIS WITH CONCOMITANT NEWLY DIAGNOSED INFLAMMATORY BOWEL DISEASE – A DIAGNOSITIC CONUNDRUM

Abstract Eosinophilic colitis (EC) is a rare primary condition characterized by eosinophilic infiltration of the colon in the absence of secondary causes. Affecting only 0.003% of people in the United States, clinical manifestations of the disease can range from abdominal pain, bloody stools, and diarrhea to colonic obstruction, intussusception, volvulus, and perforation. The diagnosis is made upon histopathological analysis of colonic biopsies with the inflammatory infiltrate consisting predominantly or exclusively of eosinophils with focal collections greater than 100 per high-power field (hpf). Unlike inflammatory bowel disease (IBD), granulomas, crypt architectural distortion, pseudopyloric metaplasia, and fibrosis are not usually present with EC, but differentiating between the two conditions has proven to be difficult over the decades. A 33-year-old male with a history of ulcerative colitis since the age of 23 currently on mesalamine presented to the clinic for follow-up. He was officially diagnosed 10 years ago after being hospitalized with bloody bowel movements. Flexible sigmoidoscopy at the time showed confluent, erythematous, ulcerated mucosa suggestive of moderate to severe colitis seen extending from the rectum to 40cm. Rectosigmoid pathology showed distorted crypt architecture with increased lymphoplasmacytic infiltrate in the lamina propria and markedly increased neutrophils within crypt epithelial cells, indicative of ulcerative colitis. He was started on mesalamine and a prednisone taper but was poorly compliant. He presented again 5 months ago with abdominal pain and bloody diarrhea and was given steroids with follow-up colonoscopy. This time, findings showed scattered inflammation and aphthous ulcers throughout the colon with systemic loss of vascularity. Biopsies were negative for any evidence of active inflammatory bowel disease. Pathology showed mildly distorted crypts and significantly increased lamina propria eosinophils >100/hpf consistent with eosinophilic colitis. Bloodwork, including ESR and CRP, were normal. The patient was continued on mesalamine and as needed steroids with good symptom control. Our case highlights a rare phenomenon of primary eosinophilic colitis with newly diagnosed ulcerative colitis. It is difficult to ascertain which disease at which time contributed to our patient’s symptoms as the timeframe of both conditions likely overlap. His mild crypt architectural distortion and absence of lymphoplasmacytic infiltrate upon the repeat colonoscopy is indicative of well-controlled ulcerative colitis. There were no other etiologies ascertained for his colonic eosinophilia. Our case demonstrates the diagnostic obscurity of EC in its ability to masquerade as IBD. We aim to educate gastroenterologists on the timely diagnosis and effective management of this disease in order to prevent serious patient complications. Initial colonoscopy showing confluent, erythematous, ulcerated mucosa in the rectosigmoid region. Subsequent pathology confirmed ulcerative colitis. Rectosigmoid histopathology from second colonsocopy showing mildly distorted crypts and significantly increased lamina propria eosinophils >100/hpf consistent with well-controlled ulcerative colitis but active primary eosinophilic colitis. 400x magnification.

S2772 Subcutaneous Sweet Syndrome Successfully Treated With Ustekinumab in Patient With Ulcerative Colitis

Introduction: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are well-established. Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is a reactive mucocutaneous manifestation of IBD presenting as erythematous papules/plauqes with associated fever and arthomyalgias. There is limited evidence regarding efficacy of Ustekinumab in management of EIMs of UC, particularly SS. Case Description/Methods: The patient is a 50-year-old woman with left-sided UC (Montreal classification E2) that previously failed several therapies, including mesalamine, azathioprine, infliximab, adalimumab, vedolizumab, and a fecal microbiota transplant trial. She presented with worsening abdominal pain, diarrhea/hematochezia, and bilateral lower extremity pain. She was febrile and tachycardic with tender, violaceous, and ulcerated subcutaneous nodules on the bilateral ankles with hemorrhagic bullae (FigureA). Labs revealed negative C. diff, elevated ESR/CRP, thrombocytosis, and borderline leukocytosis with neutrophilic predominance. Lower extremity MR imaging and bone biopsy revealed multifocal sterile osteomyelitis with adjacent abscess; skin biopsy demonstrated dense granulomatous/neutrophilic infiltrate in the deep dermis/subcutis without microorganisms, consistent with subcutaneous SS (FigureB). A restaging colonoscopy demonstrated severe proctosigmoid ulcerative colitis (FigureC). Given that the patient had failed several immunomodulators and biologic therapies, she was started on prednisone and Ustekinumab. Four months later, she reported complete resolution of her cutaneous SS off steroids and improving UC symptoms (less frequent and more formed stools, minimal hematochezia). Repeat MRI demonstrated resolution of the sterile osteomyelitis and abscess. Discussion: Our case highlights the novel use of Ustekinumab in the treatment of subcutaneous SS with sterile osteomyelitis in a patient with flaring UC. SS is a neutrophilic dermatosis that is a rare EIM of IBD, classically characterized by tender cutaneous lesions. There is limited evidence supporting the use of Ustekinumab in treating EIMs of CD, and a lack of data regarding its efficacy in treating EIMs of UC. Our case fills a major gap in the literature and highlights the clinical efficacy of Ustekinumab for SS and UC especially in patients that have a contraindication to, failed previous treatment with, or otherwise cannot tolerate corticosteroids and TNF-alpha antagonists.Figure 1.: 1A. Right lateral malleolus with 2.5 cm shallow erosion with slightly violaceous borders and central bright yellow fibrinous debris. There was slight atrophy of surrounding skin with mild edema and hyperpigmentation (left image). Left medial malleolus/dorsal foot with grouped irregular shallow ulcers with surrounding mild violaceous erythema (middle and right image). 1B. Left ankle biopsies showed mixed septal and lobular panniculitis with granulomatous and neutrophilic inflammation. Histologic sections show a mildly spongiotic epidermis with dense granulomatous and neutrophilic inflammatory infiltrate in the deep dermis and subcutis (left image). The inflammatory infiltrate, which consists of prominent neutrophils, histiocytes, and scattered lymphocytes, surrounds vascular and adnexal structures, as well as adipocyte lobules. Definitive features of vasculitis are not seen. PASd (periodic acid-Schiff-diastase), GMS (Grocott’s methenamine silver), Gram, and Fite staining fail to highlight microorganisms (right image). 1C. Colonoscopy demonstrated severe (Mayo Endoscopy Score 3) proctosigmoid ulcerative colitis to 30 cm (left image). Sigmoid biopsies showed significant immune cell infiltration with crypt architectural distortion concerning for severe chronic active colitis. No evidence of granulomas, dysplasia or cytomegalovirus (right image).

S2741 Ischemic Colitis Imitating Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) and ischemic colitis (IC) are two different entities that can present similarly. There have been case reports of Crohn’s disease mimicking IC in elderly population. In contrast, we present a case of a young patient whose clinical history was consistent with IBD, but he was ultimately found to have IC on biopsy results. Case Description/Methods: A 36-year-old male with a history of type I diabetes mellitus, hypothyroidism as well as family history significant for IBD presented with abdominal pain, nausea, emesis, and diarrhea. In the emergency room, he was afebrile and hemodynamically stable with BP of 121/88 mmHg and HR of 90 BPM. Labs were significant for mild leukocytosis and normal lipase. Computed tomography of abdomen pelvis with contrast revealed diffuse colonic thickening concerning for acute colitis. C. difficile and gastrointestinal pathogen panel were negative. The day after admission, he was found to have intermittent episode of hematochezia along with elevated fecal calprotectin and c-reactive protein at 2945 ug/g and 38 MG/L respectively. Patient’s elevated inflammatory marker in setting of negative infectious work up, family, and personal history of autoimmune diseases were concerning for IBD. Patient underwent colonoscopy which revealed large ulcerated, edematous, and erythematous area in the mid-distal proximal transverse colon (50-80cm from the anal verge) (Figure) with rest of colonic mucosa and terminal ileum appearing normal. Biopsies from the mid transverse colon showed paucicellular lamina propria with edema, hyalinization, vascular dilation, and congestion consistent with ischemic colitis without any significant crypt architectural distortion, basilar lymphoplasmacytosis or evidence of metaplasia. Precipitant for ischemic colitis was unclear in this patient. He was treated symptomatically for ischemic colitis and had symptomatic improvement at time of discharge. Discussion: It is essential to consider IC in a young patient with family and personal history of autoimmune disease presenting with signs and symptoms typical for IBD as IC can mimic IBD. Timely and proper diagnosis is necessary as treatment for these two disorders is completely different. IBD can require medications like biologics which may have dangerous side effects if used inappropriately where IC is managed symptomatically.Figure 1.: Colonoscopy showing large edematous and erythematous area in the mid-distal proximal transverse colon.

De Novo Diagnosis of Lymphocytic Colitis After SARS-CoV-2 Vaccination

ABSTRACTSARS-CoV-2 mRNA vaccines are safe and effective for most patients. Gastrointestinal complications reported after vaccination have included gastroparesis and inflammatory bowel disease flares. In this study, we present a unique case of lymphocytic colitis that occurred in a healthy middle-aged man after Moderna SARS-CoV-2 mRNA vaccination. This reveals an unexpected complication of a mRNA vaccine that presented as worsening diarrhea after vaccination in a dose-dependent pattern. Caregivers should be aware of lymphocytic colitis as a possible complication of the Moderna vaccine and monitor those patients closely for symptom resolution.

Diversion colitis in inflammatory bowel disease (IBD) is distinct from that in non-IBD: Reappraisal of diversion colitis

The significant histologic overlap between diversion colitis and inflammatory bowel disease (IBD) poses a diagnostic challenge. We aimed to identify histologic features that are characteristic of diverted colon segments among patients with IBD and compare them with histologic features identified in IBD colectomies. Archived slides from resected diverted colon segments from patients with (n=79) and without (n=80) IBD and the corresponding prior colectomies (n=52) of the IBD patients were reviewed. Clinical and endoscopic data were collected, and a series of histologic features were evaluated and graded. Compared to the non-IBD group, IBD patients were more likely to be symptomatic and present with abnormal endoscopic findings (P<.05). The severity of inflammatory activity, crypt architectural distortion, mucosal atrophy, transmural inflammation, intramucosal lymphoid aggregates (IMLAs), and transmural lymphoid aggregates (TMLAs) were significantly greater in diverted segments in IBD cases than controls (P<.001). The severity of inflammatory activity, IMLAs, TMLAs, and transmural inflammation and the presence of ulcer(s) in the diverted colon segments of IBD patients were associated with the histologic features reflective of IBD activity such as inflammatory activity, transmural inflammation and ulcer(s) in the preceding colectomies (P<.05). Diversion colitis developing in the setting of IBD is endoscopically and histologically distinct from that observed among individuals without IBD. Inflammatory activity, presence of ulcer(s), IMLAs, TMLAs, and transmural inflammation in diverted colon segments of IBD patients may, in part, reflect the severity of underlying IBD rather than pure diversion colitis.

Utility of colon allograft biopsies in surveillance of patients with small intestinal transplantation – A systematic study of 129 biopsies

Abstract Introduction/Objective A segment of right colon is sometimes included with small intestinal allografts to preserve the ileocecal valve and maintain water reabsorption. We correlated pathological findings of colon allograft biopsies obtained during surveillance colonoscopies with clinical, endoscopic, and microbiologic findings. Methods/Case Report All colon allograft biopsies from surveillance colonoscopies over a 3-year period were reviewed for crypt apoptotic activity, cryptitis, lamina propria inflammation, ulceration, and crypt architectural distortion. Clinical and endoscopic findings, and positive cultures a week before and after the biopsies were recorded. Results (if a Case Study enter NA) There were 129 colon biopsies from 29 patients; 98 were histologically normal, whereas 28 showed rare apoptoses (n=14), focal cryptitis (n=8), increased intraepithelial lymphocytes (n=2), moderate acute rejection (n=1), and crypt architectural distortion (n=2). Of these 29 patients, 8 had abnormal endoscopic findings, 21 were normal. Out of 8 patients with abnormal endoscopic exams, 50% had normal histology on biopsy. Twenty-one biopsies were associated with positive cultures in the blood (n=5), urine (n=16) or wound, peritoneal, stool (n=6); 3 had abnormal endoscopies, and 4, abnormal histology. One patient with C.difficle toxin had normal endoscopy and focal cryptitis, whereas another with CMV DNA in blood showed endoscopically congested mucosa and rare apoptoses on biopsy. Of 12 biopsies (7 patients) with abnormal endoscopic findings, (erythema, congestion, ulceration), 4 biopsies had no pathologic findings, 8 had rare apoptosis, and one each had focal cryptitis and chronic colitis. Paired small intestinal biopsies were present with 59 biopsies; 10 showed rare apoptosis and 2, focal cryptitis. Of 70 without paired small intestinal biopsies, there were 5 with rare apoptotic bodies, 5 with focal cryptitis, and 2 with crypt architectural distortion. Conclusion The correlation of histologic, endoscopic, and microbiologic findings in colonic allograft surveillance biopsies is inconsistent. Colon allograft biopsies have limited utility in the follow-up of patients, particularly in absence of paired small intestinal biopsies.

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

Abstract 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 &amp;lt; 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.

Gastrointestinal: Autoimmune enteropathy associated with thymoma.

A 50-year-old gentleman presented with 4 months of chronic watery, non-bloody diarrhea up to 10 times a day, and weight loss. He had a history of a thymoma first diagnosed 7 years earlier, which was resected with positive histological margins. There was no macroscopic residual disease or vascular invasion. He did not receive any adjuvant treatment and developed recurrent Masaoka-Koga stage IVa thymoma with pleural, pericardial, and lung invasion requiring further treatment with resection, chemotherapy (3 cycles of cisplatin, doxorubicin, and cyclophosphamide), and radiotherapy (54 Gy in 30 fractions). There was no mediastinal lymph node involvement or evidence of distant hematogenous metastasis. Histopathology demonstrated multiple nodules of mixed WHO type B1 and B2, but predominantly type B1 thymoma. His diarrhea commenced after his thymoma recurrence. He did not have any features suggesting other autoimmune diseases associated with thymoma including myasthenia gravis. Physical examination and initial laboratory investigations were unremarkable. Stool cultures were negative for bacterial, viral, and parasitic infections. A computed tomography (CT) scan of the abdomen revealed wall thickening and fat stranding affecting the small intestine and colon (Fig. 1a). Correspondingly, mild patchy erythematous colitis in the rectum and sigmoid colon was seen on colonoscopy (Fig. 1b). Histologically, colonic biopsies showed active colitis with prominent regenerative changes. Goblet cells were noticeably absent, and there was prominent apoptosis, features typical of autoimmune enteropathy (Fig. 1c). Patient serum was incubated with frozen sections of normal small intestinal mucosa, showing strong staining by immunofluorescence for human IgA and IgG with a goblet cell distribution (Fig. 2). A diagnosis of thymoma-associated autoimmune enteropathy was made, and the patient was commenced on a weaning dose of prednisone starting at 25 mg daily leading to resolution of his symptoms. Thymomas are associated with concomitant autoimmune diseases in up to 30% of patients, possibly due to defective immune regulation. Differentials for thymoma-associated autoimmune conditions causing diarrhea include autoimmune enteropathy and Good's syndrome (thymoma-associated hypogammaglobulinemia). Thymoma-associated autoimmune enteropathy is rare with only five reported cases in the literature. Proposed diagnostic criteria include chronic diarrhea lasting over 6 weeks, malabsorption, and abnormal histology of the small bowel (villous blunting, deep crypt lymphocytosis, minimal intraepithelial lymphocytosis, and increased crypt apoptotic bodies). A spectrum of changes can be seen in the colon including increased mononuclear inflammatory infiltrate, active inflammation including neutrophilic cryptitis and microabscesses, intraepithelial lymphocytosis, and increased crypt epithelial apoptosis. Changes of chronicity including crypt architectural distortion and Paneth cell metaplasia have also been described. The presence of anti-enterocyte or anti-goblet antibodies is supportive, but the sensitivity and specificity of these markers are unknown. Steroids are the first-line management for autoimmune enteropathy; however, further immunosuppression (azathioprine, cyclosporin, tacrolimus, or infliximab) may be required in up to 90% of cases. For patients with thymoma-associated autoimmune enteropathy, resection of the thymoma may also improve symptoms.

S2458 Can SARS-CoV-2 Enterocolitis Trigger New Onset Inflammatory Bowel Disease ?

Introduction: Prevalence of gastrointestinal symptoms in patients infected with SARS-CoV-2 virus is 6.8% - 61.3%. Most common symptoms include diarrhea (8.1% - 33.7%), nausea/vomiting (1.5% - 26.4%), anorexia (12.1% - 26.4%), and abdominal pain (0 – 14.5%). Management involves treating respiratory manifestation of COVID-19, treating co-existing infections, and supportive care. We present a case of severe hemorrhagic enterocolitis managed with a biologic. Case Description/Methods: 47-year-old woman with COVID-19 pneumonia was admitted for extracorporeal membrane oxygenation. She developed copious amounts of watery diarrhea followed by bloody diarrhea. Stool work-up was negative for infectious causes of diarrhea. Colonoscopy revealed diffusely erythematous and friable mucosa with epithelial loss involving the entire colon and distal ileum. She was managed with rectal tube, blood transfusions, parenteral nutrition. Despite escalating doses of numerous anti-diarrheals, topical as well as systemic steroids, copious volumes of bloody diarrhea continued. Repeat colonoscopic biopsies demonstrated CMV-like inclusions with borderline elevated serologic titers. Despite successful eradication of CMV with prolonged courses of ganciclovir and foscarnet, hemorrhagic diarrhea continued. Several upper and lower endoscopies suggested worsening mucosal erythema and friability, predominantly involving small bowel and colon. Given COVID enterocolitis refractory to all the above treatments, induction therapy with a biologic was considered to treat possible de novo inflammatory bowel disease (IBD) versus immune mediated effects of COVID-19 enterocolitis. After induction doses of Ustekinumab, an IL-12 and IL-23 inhibitor, volume of diarrhea reduced and bloody diarrhea resolved, facilitating removal of rectal tube, resumption of oral nutrition, discontinuation of anti-diarrheals. Patient was discharged on maintenance Ustekinumab. Follow-up endoscopic evaluation demonstrated mucosal healing, with epithelial regeneration and chronic inflammatory changes of crypt distortion. Discussion: SARS-CoV-2 infection triggered an inflammatory cascade in the intestinal tract leading to altered or increased immune response, probably on a background of genetic predisposition, in our patient. Initiation of Ustekinumab, IL-23/IL-12 inhibitor, likely resulted in suppression of the severe systemic inflammatory response, resulting in clinical, endoscopic and pathological response.Figure 1.: (a) demonstrates endoscopic appearance of transverse colon with erythema, friability and hemorrhages prior to treatment with biologic (b) demonstrates epithelial denudation with minimal acute inflammation in colonic mucosa prior to treatment with biologic (c) demonstrates endoscopic appearance of transverse colon with resolving erythema after treatment with biologic (d) demonstrates chronic inflammatory changes with crypt architectural distortion and pyloric gland metaplasia after induction of remission with biologic, many months after initial presentation.

S1898 Clostridioides difficile Colitis Masquerading as Colorectal Malignancy

Introduction: Clostridioides difficile (C. diff) is an enteric pathogen typically associated with the use of antimicrobials that disrupt the normal gut microbiome. Its endoscopic appearance ranges from patchy erythema, edema to large segmental pseudomembranes to sharply demarcated ulcers. We present a case of C. diff colitis masquerading as a friable mass concerning for malignancy. Case description/methods: This is a 60-year-old female with history of Lynch Syndrome without recent colonoscopy who presented with 3 weeks of right lower quadrant abdominal pain with profuse diarrhea, early satiety and unintentional weight loss. She had been hospitalized 2 weeks prior for septic shock with initial CT demonstrating pneumatosis intestinalis within the ascending colon. She was treated non-operatively and left against medical advice after subjective improvement in her symptoms. On repeat imaging, there was evidence of long segment terminal ileal wall thickening with resolution of her pneumatosis intestinalis. She was found to be C. diff positive and started on oral vancomycin therapy. A diagnostic ileocolonoscopy demonstrated circumferential sloughing and erythematous friable mucosa with narrowing in the terminal ileum and a large, lateral spreading, ulcerative mass in the sigmoid colon with associated stricture. Biopsies showed colonic mucosa with ulcer and crypt architectural distortion without dysplasia and malignancy. A repeat colonoscopy done 1 month after treatment given her history of Lynch Syndrome demonstrated complete resolution of her previous endoscopic findings. Discussion: While the endoscopic appearance of C diff colitis is well-described and variable, this is the first case, to our knowledge, of it mimicking as focal malignancy. C. diff may be endoscopically indistinct from acute infectious colitis or present as pseudomembrane colitis, a non-specific term used to describe acute endothelial damage characterized by multiple discrete, raised yellow plaques distributed over erythematous mucosa. It shares a pathogenic mechanism with ischemic colitis where blood flow and tissue oxygenation is disrupted with overlapping endoscopic features wherein the punctate pseudomembranes coalesce and form large segmental membranes. If focal, the edema and ulceration can resemble colonic adenocarcinoma with luminal narrowing by a lobulated mass effect. This clinical case highlights the importance of confirmatory histology and endoscopic re-evaluation.Figure 1.: Panel A: Initial CT demonstrated pneumatosis intestinalis in the ascending colon. Panel B: Repeat CT 2 showed terminal ileal wall thickening. Panel C: Ulcerative mass in the sigmoid colon with luminal narrowing Panel D: Circumferential sloughing and friable mucosa in the terminal ileum Panel E: Repeat colonoscopy with complete resolution of mucosal changes between previously tattooed sites Panel F: Repeat colonoscopy with healthy appearing terminal ileum mucosa.

S2438 COVID-19: A Potential Trigger for Inflammatory Bowel Disease?

Introduction: Coronavirus Disease 2019 (COVID-19) has been shown to infect gastrointestinal tissues, and a wide variety of gastrointestinal manifestations have been described including alterations in the composition of the intestinal microbiome. Microbiome changes have been implicated in the pathogenesis of inflammatory bowel disease (IBD), but a clear relationship between viral infection and IBD has not been established. Case description/methods: Case 1 A 45-year-old woman presented to clinic with painless hematochezia and fecal urgency 2 weeks after developing anosmia and being diagnosed with COVID-19. She had a history of constipation but no other gastrointestinal problems. Her vital signs were normal and her exam was unremarkable. Her labs showed iron deficiency anemia with hemoglobin 10.2 and ferritin < 2. Colonoscopy showed 10cm of moderately friable rectal mucosa with erosions and loss of vascular pattern. Rectal pathology showed chronic active proctitis. She was diagnosed with ulcerative proctitis and treated with mesalamine suppositories with resolution of her symptoms. Case 2 A 48-year-old woman was admitted for five months of watery, bloody bowel movements that developed after an initial hospitalization for COVID-19 pneumonia. She reported 10-15 bowel movements daily, diffuse abdominal pain, nausea, and 10kg weight loss. She was initially diagnosed with C. difficile at another hospital but her symptoms did not improve with oral vancomycin. She was mildly tachycardic, but her exam was otherwise unremarkable. Labs showed hemoglobin 6.7, CRP 6.9, ESR 50, and fecal calprotectin 1880. C. difficile testing was negative. Colonoscopy showed pancolitis with moderate inflammation, edema, erosions, erythema, and friability most severe in the distal colon with ileal sparing. Pathology showed crypt architectural distortion and branching with cryptitis and crypt abscesses consistent with ulcerative colitis. After not responding to prednisone, she achieved clinical remission with infliximab. Discussion: Prior research has described the role of abnormal immune response to intestinal microbiota in the pathogenesis of IBD. Some studies have found an increased risk of IBD after infectious gastroenteritis, but no specific causal link has been demonstrated and the role of specific infections in the development of the dysregulated immune response is incompletely understood. These cases of new ulcerative colitis diagnosed after COVID-19 infection have implications for understanding potential viral triggers of IBD.

S2266 Terminal Ileitis: It’s Not Always Inflammatory Bowel Disease

Introduction: Terminal ileitis is most classically associated with Crohn’s disease (CD). Here, we present a case of a young, Active Duty solider with acute terminal ileitis suspected to be infectious in origin. Case Description/Methods: A 26 year-old male with a history of recent TIA while deployed to Kuwait was admitted for a three day history of fever with headache without associated gastrointestinal symptoms. Vital signs were remarkable only for fever to 102 degrees F. Neurologic and abdominal examination revealed no abnormalities and initial lab work was unremarkable. CT scan on admission incidentally revealed nodular wall thickening of the terminal ileum (TI) with adjacent mesenteric lymphadenopathy. Over the course of admission, the patient developed progressive mild leukopenia and thrombocytopenia. Infectious and hematologic work-up, including lumbar puncture, blood and urine cultures, hypercoagulable evaluation, peripheral flow studies and bone marrow biopsy were unrevealing. Colonoscopy was notable for edema and erythema of the ileocecal valve as well as a patch of nodular friable mucosa in the distal TI. Biopsies were negative for EMV, CMV, fungal elements and dysplasia but did demonstrate cryptitis and mild crypt architectural distortion. Colonoscopy performed 6 weeks later showed endoscopic improvement. Repeat biopsies were still notable for active terminal ileitis but again negative for the aforementioned processes. Given interval resolution of the patient’s fever and lab abnormalities with endoscopic improvement, we suspect the etiology for his terminal ileitis was infectious in origin. Follow-up colonoscopy is planned to ensure complete resolution. Discussion: Terminal ileitis has a broad differential diagnosis and is not always representative of underlying CD. Alternate causes of terminal ileitis include lymphoma, NSAID use and infections such as Yersiniosis and intestinal tuberculosis. In this young male with recent TIA, unexplained fevers with cytopenias, and prominent mesenteric lymphadenopathy, there was initial concern for lymphoma. Ultimately, the patient demonstrated clinical improvement without intervention, suggesting a self-limited, possibly viral infection. This case highlights the importance of having a broad differential for terminal ileitis with thorough diagnostic evaluation, particularly when the patient presentation and clinic course is not consistent with common causes such as CD, as the misdiagnosis may lead to unnecessary treatment exposure and procedures.

International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease

ObjectiveEffective medical therapy and validated trial outcomes are lacking for small bowel Crohn’s disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques....

A187 ASSOCIATION OF IL-17 INHIBITOR TREATMENT WITH NEW OR WORSENING INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract Background Interleukin 17 (IL-17) inhibitors, monoclonal antibodies that target IL-17A (secukinumab, ixekizumab) or the IL-17 receptor (brodalumab), are effective treatments for patients with psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). IL-17A inhibitors are rarely associated with new or worsening inflammatory bowel disease (IBD), with an estimated incidence rate of 1.1/1000 patient-exposure years in Crohn’s disease (CD) and 1.0/1000 patient-exposure years in ulcerative colitis. Aims Describe 3 patients treated with IL-17 inhibitors who developed IBD. Methods Case series. Results Case 1: 50 year-old male with PsO developed bloody diarrhea after 2 months of ixekizumab therapy. Colonoscopy showed proctitis with a cobblestone appearance and anal ulceration. He failed topical 5-ASA and repeat colonoscopy 1 month later showed chronic inflammatory changes in the transverse colon and rectum. Patient was hospitalized for a right colonic perforation requiring hemicolectomy and loop ileostomy. Pathology showed mucosal ulcerations with acute transmural inflammation of the cecum, ascending colon, and ileum, with crypt architectural distortion and no granulomas. Colonoscopy 6 months later showed chronic mild patchy active colitis with granulomas. Infliximab and methotrexate were started with clinical remission of his CD and partial response of his PsO. Case 2: 39 year-old male with AS who failed golimumab and etanercept started on secukinumab, and reported acute worsening of diarrhea and abdominal pain. Colonoscopy after a year of persistent symptoms showed ulceration of the ileum and ileocecal valve. Biopsies showed mild active chronic ileitis, and architectural distortion with reactive lymphoid follicles in the right colon. He was treated with adalimumab with partial clinical response of his CD and AS. Case 3: 63 year-old female with PsA reported a 3 week history of diarrhea, abdominal pain, and fever. She was maintained on ixekizumab for 4 months and previously failed adalimumab, secukinumab, and etanercept. CT showed diffuse circumferential pancolonic wall thickening and terminal ileal involvement. Stool cultures and C. difficile were negative. CRP was 154.9 mg/L and fecal calprotectin was 1710 mcg/g. Colonoscopy showed patchy erythema and aphthous ulcers in the colon. Terminal ileal biopsies showed crypt architectural distortion and patchy acute inflammation. She started on infliximab therapy. Her diarrhea resolved prior to treatment, with no clinical improvement of her arthritis. Conclusions IL-17 inhibitors are effective in the treatment of PsO, PsA, and AS, however, in all cases described, it is unclear whether IL-17 inhibition led to new-onset IBD, or an exacerbation of previously asymptomatic IBD. Patients being considered for IL-17 inhibition with baseline gastrointestinal symptoms should be investigated for IBD. Funding Agencies None

Can COVID-19 Trigger De Novo Inflammatory Bowel Disease?

Question: On March, 2020 an otherwise young female never smoker presented to the emergency department with a seven-day episode of fever up to 38°C, sore throat, myalgia, dyspnea, and bloodless watery diarrhea (6–7 stools per day). Laboratory tests showed a leucocyte count of 14,000/μL, lymphocyte count of 1200/μL, C-reactive protein of 26.8 mg/dL, d-dimer of 1769 ng/mL, and lactate dehydrogenase of 670 U/L; other laboratory results were unremarkable. A nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A chest radiograph showed bilateral infiltrates and the patient was admitted. During hospitalization, the patient was treated with hydroxychloroquine, lopinavir/ritonavir, and azithromycin. Her symptoms improved significantly, and peripheral oxygen saturation while breathing ambient air was 98%. Markers of systemic inflammation dropped progressively, and lymphocyte count increased. On day 7 a new nasopharyngeal reverse transcriptase polymerase chain reaction swab was negative, and she was discharged from hospital. Between April and June, watery diarrhea (3–4 stools per day) persisted, with no other common symptoms of coronavirus disease-2019 (COVID-19). In July, her diarrhea worsened, with blood in all bowel movements. A chest radiograph and laboratory tests were normal, with IgG positive and IgM negative SARS-CoV-2 antibodies. Stool cultures ruled out common pathogens, including Clostridium difficile. Fecal calprotectin concentration was elevated (460 μg/g). In August, after a negative nasopharyngeal reverse transcriptase polymerase chain reaction swab, an ileocolonoscopy showed confluent colonic involvement extending for 35 cm from the anal verge, with granularity, edema, friability, and ulcers (Figure A). The rest of the colon and 5 cm of terminal ileum were normal. Histopathology showed widespread crypt architectural distortion, superficial erosions, a diffuse transmucosal inflammatory infiltrate, cryptitis, and mucin depletion (Figure B, stain: hematoxylin and eosin; original magnification ×4 large picture, ×40 small picture; courtesy of Dr. María Suárez). Immunohistochemistry excluded cytomegalovirus infection. Given this history, clinical presentation, and endoscopic and histology findings, what is your diagnostic suspicion? Look on page 1030 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. Treatment with oral and topical mesalamine was started. On day 10, the patient achieved remission (partial Mayo score of 0). Based on clinical data, endoscopic, and histology findings, incident ulcerative colitis (UC) was diagnosed in a patient with no prior gastrointestinal symptoms. Because there is no pathognomonic feature for diagnosis of a first flare of UC, we consider the presence of a second flare with repeat endoscopy necessary to confirm the diagnosis. The exact etiology of UC is unknown, although the disease is thought to be triggered by an interaction between genetic and environmental factors. Infectious gastroenteritis (GE) has been associated with an increased risk of incident inflammatory bowel disease (IBD).1García Rodríguez L.A. Ruigómez A. Panés J. Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease.Gastroenterology. 2006; 130: 1588-1594Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar The observation that the incidence rate of IBD after a documented bacterial GE was similar to the incidence after episodes of GE with negative stool culture, in which a significant proportion of cases are probably of viral origin, suggests the possibility that both bacterial and viral infections can trigger IBD. However, no specific bacterial or viral pathogens have been confirmed as a cause of IBD as per Koch’s postulates. Available evidence indicates that IBD patients are not at a greater risk of acquiring COVID-19,2Taxonera C. et al.Gastroenterology. 2020 Jul 17; ([Epub ahead of print])Google Scholar but data on SARS-CoV-2 infection in triggering IBD are lacking. Initial intestinal inflammation may arise owing to SARS-CoV2 infection. This response overshoot or defective down-regulation of mucosal immune response could lead to chronic intestinal inflammation. A case of incident UC during SARS-CoV-2 infection has been reported, but unlike our patient, COVID-19 and UC were diagnosed simultaneously, making it difficult to determine whether endoscopic and histologic alterations were related to UC or to SARS-CoV2 by itself.3Calabrese E. Zorzi F. Monteleone G. Del Vecchio Blanco G. Onset of ulcerative colitis during SARS-CoV-2 infection.Dig Liver Dis. 2020; 52: 1228-1229Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar In our case, it is not possible to rule out that the patient had UC at the time of diagnosis of the SARS-CoV-2 infection, but the absence of previous gastrointestinal symptoms and the appearance within hours of watery diarrhea as a presenting symptom of COVID -19 makes this possibility highly unlikely. In conclusion, in clinical practice, we should be vigilant to the possibility that COVID-19 may trigger de novo UC, although large population studies would be necessary to confirm a causal link.

S1741 Diffuse Colitis After an Exacerbation of Lupus Nephritis

INTRODUCTION: Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used in organ and bone marrow transplant recipients as well as in autoimmune disorders like systemic lupus erythematosus(SLE). Gastrointestinal side effects occur in about 45% of patients using MMF, manifesting as nausea, vomiting, diarrhea, and abdominal pain. Here we illustrate a case of diffuse colitis induced by MMF diagnosed by colonoscopy and histology. CASE DESCRIPTION/METHODS: 55-year old woman presented to hospital due to asymptomatic severe anemia. She reported having increased flatus and abdominal bloating for the past three weeks but denied any abdominal pain, weight changes, hematochezia, melena or hematuria. Past medical history were hypertension, diabetes mellitus, SLE and lupus nephritis requiring hemodialysis. One month prior to her presentation she experienced a flare of lupus nephritis that was managed with prednisone and MMF. Vital signs and physical exams were unremarkable. Complete blood count showed severe anemia with hemoglobin at 4.6 g/dL, normal MCV 86.9 fL and increased RDW 16.4% and normal white cells and platelet counts, indicative of normocytic anemia. Comprehensive metabolic panel were significant for increased BUN 41 mg/dL and creatinine 6.12 mg/dL with decreased total bilirubin level 0.2 mg/dL. Fecal occult blood test was negative and no blood in urine. Upper endoscopy showed chronic gastric ulcer and duodenitis without hemorrhage or perforation. Colonoscopy demonstrated the entire colon appeared inflamed, edematous and erythematous mucosa with loss of vascularity. Histopathologic exam revealed pan-colonic crypt architectural distortion with increased apoptotic bodies with endocrine cell hyperplasia and focal cryptitis (Figure A-B), which were indicative of MMF induced colitis. Subsequently, MMF was discontinued resulting in improvement and resolution of the patient’s symptoms. DISCUSSION: MMF-induced colitis is an uncommon however debilitating complication with only few case reports and no current guidelines in the literature. Histologic features of MMF-induced colitis include crypt architectural distortion, inflammatory cell infiltration, lamina propria edema and increased crypt epithelial apoptosis, which can mimic ischemic colitis, inflammatory bowel disease or graft-versus-host disease. Colitis is seen in around 9% of patients on MMF. Discontinuing MMF leads to spontaneous resolution of symptoms.Figure 1.: Colonoscopy images showing the entire colon appeared inflamed; the mucosa was edematous and erythematous with loss of vascularity (A). Hematoxylin and eosin stain (original magnification ×400) showing crypt architectural distortion with increased apoptotic bodies (B: red arrows).

S1639 Graft vs Host Disease of the Upper and Lower Gastrointestinal Tracts After an Autologous Bone Marrow Transplant: Report of an Unusual Case

INTRODUCTION: Gastrointestinal autologous graft-versus-host disease (GVHD) has been reported in 13% of autologous stem cell transplant (auto-HCT) recipients in comparison to 40% of those who underwent allogenic-HCT. Involvement of both upper and lower GI tracts is a unique phenomenon in auto-GVHD. Herein, we present a case of biopsy-proven GVHD of the duodenum and colon after auto-HCT. CASE DESCRIPTION/METHODS: A 59-year-old male with newly diagnosed multiple myeloma of the lumbar spine received palliative radiation, followed by four cycles of chemotherapy with lenalidomide, bortezomib, and dexamethasone. He subsequently underwent auto-HCT. One month after auto-HCT, he was admitted with fever, nausea, vomiting, early satiety, diarrhea and generalized abdominal pain. Initial laboratory findings included a normal leukocyte count and mild acute kidney injury. Stool testing for infectious etiologies were negative. Additional studies were negative for Epstein–Barr virus, cytomegalovirus (CMV), parvovirus, and his thyroid function was normal. Computed tomography was remarkable for diffuse wall thickening with mucosal hyperenhancement of the entire large and small intestine. Subsequent upper endoscopy revealed atrophic, erythematous, flattened mucosa with petechia in the stomach and diffuse mucosal erythema of the duodenal bulb. Flexible sigmoidoscopy was notable for friable mucosa with altered vasculature, erythema and erosions. Histologic examination of the duodenal mucosa showed villous atrophy with increased number of crypt apoptosis and cryptitis, and active inflammation with the presence of crypt architecture distortion and numerous apoptotic bodies in the crypts of the colon. Immuno-stains for adenovirus and CMV were negative. The constellation of histomorphological features was consistent with GVHD and the patient was subsequently treated with a methylprednisolone taper, which resulted in almost complete resolution of his symptoms. DISCUSSION: GVHD represents an immunocompromised state as it reduces bowel integrity and may lead to severe infections with or without immune suppressive therapy treatment. Certain chemotherapy agents including lenalidomide, inhibit the proliferation and function of regulatory T cells, predisposing patients to GI auto-GVHD. As patients with GI auto-GVHD present with a variety of both upper and lower GI symptoms, we recommend performing endoscopic evaluation of both upper and lower GI tracts to ensure a timely diagnosis.Figure 1.: (A-B) Duodenum. A: Histologic sections of the duodenum shows abnormal villous architecture (arrows) consisting of shortening and widening. Lamina propria (star) cellularity is increased (hematoxylin and eosin stain; original magnification ×40). B: Higher magnification shows the crypts with increased number of apoptosis (arrows) (original magnification ×200). (C-D) Colon. C: Section of the colon shows marked crypt architectural distortion with the presence of acrypt abscesses (arrow). These features are those of chronic colitis with moderate activity (original magnification ×20). D: Colonic crypts show increased number of apoptosis (arrows) (origincal magnification ×200).

S1584 Autoimmune Exocrine Pancreatic Insufficiency: A Novel Paraneoplastic Mechanism for Diarrhea in Patients With Thymoma

INTRODUCTION: Paraneoplastic syndromes are an exceedingly rare cause of chronic diarrhea. Thymomas have been associated with two known paraneoplastic diarrheal syndromes, namely in the context of hypogammaglobulinemia (Good’s syndrome) or a graft-versus-host disease (GVHD)-like condition. However, exocrine pancreatic insufficiency has yet to be reported as a cause of diarrhea in patients with thymoma. CASE DESCRIPTION/METHODS: A 36-year-old woman with no known medical morbidities presented with postprandial watery diarrhea, emesis, and 100-lb unintentional weight loss over two years. Labs were notable for lymphocytosis up to 8,100/mL with normal flow cytometry and no abnormalities on blood smear. Celiac disease serologies and stool infectious studies were negative. Immunoglobulin G levels were elevated at 3,010 mg/dL, and stool pancreatic elastase levels were low (< 15 mg/g). Additional labs were consistent with fat soluble vitamin deficiency: vitamin A < 5 mcg/dL, 25-hydroxyvitamin D < 4 ng/dL, vitamin E 7 mg/L, vitamin K 69 pg/mL. Computed tomography (CT) of the chest revealed an 11-cm anterior mediastinal mass with pleural and nodal metastases, and biopsy was suggestive of malignant thymoma (Figure 1). CT of the abdomen revealed a normal-appearing pancreas. Subsequent endoscopy and colonoscopy showed healthy-appearing mucosa with no abnormalities (Figure 2). However, colonic biopsies were notable for mild diffuse inflammatory changes including scattered intraepithelial lymphocytes and neutrophils, increased apoptotic bodies, and crypt architectural distortion. Her diarrhea ultimately improved after four cycles of induction chemotherapy. DISCUSSION: GVHD-like colitis in patients with malignant thymoma has been reported in several instances. This has been attributed to alterations in the thymic microenvironment, which lead to dysregulation and loss of anergy. Autoreactive T-cells can mount an immune response that impacts a number of organs, especially in the gastrointestinal tract. Although our patient had histopathological changes reflective of colitis secondary to GVHD, the severity of her diarrhea was out-of-proportion to these findings. The postprandial nature of her symptoms and markedly low stool pancreatic elastase were suggestive of possible pancreatic insufficiency, likely secondary to an autoimmune phenomenon impacting the exocrine glands of the pancreas. This case proposes a possible novel paraneoplastic mechanism for diarrhea in patients with thymoma.Figure 1.: Cross-section image of anterior mediastinal mass.Figure 2.: Normal-appearing duodenal mucosa.