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Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn’s disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.

INTRODUCTION: Outcomes and safety of budesonide maintenance therapy in microscopic colitis (MC) are not well known. METHODS: Adult residents of Olmsted County, Minnesota, diagnosed with MC (2002–2019) and treated with budesonide were identified using the Rochester Epidemiology Project. Response was assessed at 12 ± 4 weeks after initiation of therapy and defined as complete (resolution of diarrhea), partial (≥50% improvement in the number of bowel movements), nonresponse (<50% improvement), and intolerance (discontinued because of side effects). For safety outcomes, cases (budesonide maintenance) and MC controls (no budesonide therapy) were matched by sex and age at diagnosis (±2 years). RESULTS: A total of 450 patients were identified, of whom 162 (36.0%) were treated with budesonide for induction of clinical remission (median age 67 [23–91] years and 126 women [77.8%] ). Clinical outcomes for induction were as follows: 130 (80.2%) complete response, 22 (13.6%) partial response, 8 (4.9%) no response, and 2 (1.2%) intolerance. After induction, 96 (63.2%) had recurrence after discontinuation, of whom 27 (28.1%) required further budesonide induction treatment without maintenance, 56 (58.3%) required long-term budesonide maintenance, and 13 (13.5%) were treated with other therapies. Of those receiving budesonide maintenance, all responded (55 [98.2%] complete and 1 [1.8%] partial). No patient stopped maintenance from adverse events. The median duration of follow-up was 5.6 years (0.3–18.9). There was no significant difference between cases and controls in the incidence of osteopenia/osteoporosis, diabetes mellitus, hypertension, glaucoma, or cataracts. DISCUSSION: The long-term use of budesonide in MC seems to be effective and generally well tolerated with limited adverse effects.

Abstract Background Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC. Methods A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response. Results Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment. Conclusions MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series.

Background: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridioides difficile infection (CDI). Data on FMT for CDI in patients with underlying inflammatory bowel disease (IBD) are emerging but conflicting. We performed a systematic review and meta-analysis to describe the efficacy and safety of FMT for CDI in IBD and its impact on IBD outcomes. Methods: A systematic search of multiple databases including Embase, Scopus, and Web of Science was performed. Our primary analysis focused on pooled rate of CDI resolution after single and multiple FMTs in IBD patients. Additional analyses included rates of IBD-associated outcomes (flare, surgery, symptom improvement) after FMT. The random-effects model was used to calculate pooled rates. Results: Among 457 adult patients, 363 had CDI resolution after first FMT with a pooled cure rate of 78% [95% confidence interval (CI): 73%-83%; I 2=39%]. Overall pooled rate cure rate with single and multiple FMTs was 88% (95% CI: 81%-94%; I 2=73%). The pooled rate of an IBD flare after FMT was 26.8% (95% CI: 22.5%-31.6%; I 2=9%) and of colectomy was 7.3% (95% CI: 4.7%-10.5%; I 2=56%). Among 141 pediatric patients, 106 had CDI resolution after first FMT with pooled cure rate of 78% (95% CI: 58%-93%; I 2=59%). Overall pooled cure rate with single and multiple FMTs was 77% (95% CI: 50%-96%; I 2=63%). The pooled rate of an IBD flare after FMT was 10.8% (95% CI: 5.7%-18.5% I 2=43%), and of colectomy was 10.3% (95% CI: 2.1%-30.2% I 2=23%). Conclusions: FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs.

Abstract Background Accurate diagnosis of rCDI is challenging because of limitations in test performance and alternative causes of recurrent diarrhea, such as post-infectious irritable bowel syndrome (IBS). Stool enzyme immunoassay (EIA) toxin testing (TOX) is the best predictor of active disease, but may miss cases of CDI when toxins are below the limit of detection. In contrast, glutamate dehydrogenase (GDH) or PCR have high sensitivity but cannot differentiate colonization from infection, leading to possible overdiagnosis due to low specificity. In ECOSPOR III, SER-109, an investigational purified microbiome therapeutic, was superior to placebo in reducing rCDI (12.4% vs 39.8%, respectively; p-value &lt; 0.001). We examined diagnostic testing patterns among screened subjects. Methods Patients with ≥2 prior episodes and ≥3 unformed bowel movements over 48 hours were screened. To ensure enrollment of patients with active CDI, toxin testing was required at entry via a local certified or central lab (Eurofins; Framingham, MA). Subjects with discordant GDH+/TOX- tests at the central lab had reflex confirmatory testing with a cell cytotoxicity neutralization assay (CCNA), considered the “gold standard” for toxin testing. Results The leading reason for screen failure among 281 subjects screened was a negative toxin test (50/99; 50.5%). Of 182 patients enrolled, 59 (32.4%) qualified with EIA TOX+ at the local lab (33 TOX+; 25 GDH+/TOX+) and 122 (67.0%) qualified by the central lab (Table 1). Of these 122 subjects, 87 qualified by GDH+/TOX+ but 35 required additional reflex testing by CCNA due to discordant GDH+/TOX-results; all 35 were positive. Diagnostic Testing for Qualifying C. difficile Episode in ITT Population Conclusion These diagnostic testing patterns suggest a subset of patients with suspected rCDI have toxin concentrations below the EIA threshold for detection or may have an alternative cause of diarrhea, such as post-infectious IBS. Thus, the limitations of EIA toxin testing need to be considered in clinical practice when evaluating patients with compatible symptoms of rCDI and a high prior probability of infection. In contrast, in trials of investigational agents, toxin testing assures enrollment of patients with active disease and accurate estimates of efficacy. Disclosures Matthew Sims, MD, PhD, FACP, FIDSA, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor) Sahil Khanna, MBBS, MS, Seres (Grant/Research Support) Darrell Pardi, MD, seres (Consultant)Vedanta (Consultant) Paul Feuerstadt, MD, FACG, Ferring/Rebiotix Pharmaceuticals (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Finch Pharmaceuticals (Scientific Research Study Investigator)Merck and Co (Speaker's Bureau)SERES Therapeutics (Consultant, Scientific Research Study Investigator)Takeda Pharmaceuticals (Consultant) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)

LINKED CONTENTThis article is linked to Wildt et al paper. To view this article, visit https://doi.org/10.1111/apt.16614