Microscopic Colitis Patients Research Articles

Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.

Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.

Inflammatory eye disease is a risk factor for future microscopic colitis: A nationwide population-based matched case control study.

Microscopic colitis (MC) is an inflammatory disorder of the colon. To date, the relationship between inflammatory eye diseases and MC is unclear. To assess whether inflammatory eye disease (iridocyclitis and episcleritis) is a risk factor for MC. We conducted a nationwide matched case control study in Sweden leveraging the ESPRESSO-study (a Swedish database containing data on all biopsies from the gastrointestinal tract from 1965 to 2017). In total, we identified 14,338 patients with biopsy-verified MC (diagnosed from 1981 to 2017). Patients with MC were matched (by age, sex, county and year of birth) with 68,753 controls from the general population and the occurrence of preceding inflammatory eye diseases (defined as diagnosis of episcleritis or iridocyclitis) in the two groups was compared. Multivariable adjusted odds ratios (aORs) were calculated using conditional logistic regression conditioned on the matching variables. A majority of patients with MC were women (71.9%) and the median age at MC diagnosis was 63.3years (interquartile range (IQR)=50.7-72.6). Some 225 (1.6%) MC patients had an earlier record of inflammatory eye disease compared with 614 (0.9%) in controls. These figures corresponded to an aOR of 1.77 (95% CI=1.52-2.07) for inflammatory eye diseases in patients with MC. Compared to siblings, the aOR for previous inflammatory eye diseases in MC was 1.52 (95% CI=1.17-1.98) and patients treated with budesonide, as a proxy for clinically significant disease, had a somewhat higher aOR for previous inflammatory eye diseases. Inflammatory eye diseases are more common in patients subsequently being diagnosed with MC. Our findings highlight that these conditions may have shared causes and inflammatory pathways and are of clinical interest to gastroenterologists, ophthalmologists and general practitioners.

Exploring the association between microscopic colitis and celiac disease: A comprehensive analysis using the national in-patient data (2016-2019).

Several investigations suggested correlation between microscopic colitis (MC) and celiac disease (CD). This study aimed to examine this relationship using large-sized, population-based data with adequate control for confounding factors. This study employed the National Inpatient Sample (NIS) database over 4 years (2016-2019). Patients with/without MC in the presence/absence of CD were identified through ICD-10 codes. Univariate and multi-variate analyses involving odds ratios (OR) and 95% confidence intervals (CI) were performed. Overall, 26,836,118 patients were analyzed. Of whom, 6,836 patients had MC (n = 179 with CD and n = 6,657 without CD). The mean hospital stay was not significantly different between both groups (5.42 ± 5.44 days vs. 4.95 ± 4.66 days, P = 0.202). The univariate analysis revealed a significant association between MC and CD (OR = 22.69, 95% [19.55, 26.33], P < 0.0001). In the multi-variate analysis, which adjusted for potential confounders including age, race, hospital region, hospital teaching status, ZIP income, smoking status, alcohol overuse, hypertension, diabetes mellitus, lipidemia-related disorders, non-steroidal anti-inflammatory drug use, and selected auto-immune diseases, the association remained significant (OR = 15.71, 95% CI [13.52, 18.25], P < 0.0001). Moreover, in patients with MC, the presence of CD emerged as a significant, independent variable of in-hospital mortality in univariate (OR = 2.87, 95% [1.14, 7.21], P = 0.025) and multi-variate (OR = 3.37, 95% CI [1.32, 8.60], P = 0.011) analyses. This study establishes a probable link between MC and CD, backed by both univariate and multi-variate analyses, while also identifying CD as an independent risk factor for increased mortality among MC patients. These findings need to be validated in real-world clinical studies.

Microscopic Colitis and Risk of Incident Psoriasis: A Nationwide Population-Based Matched Cohort Study.

Microscopic colitis (MC) has been associated with several immune-mediated diseases including psoriasis, but earlier research has been limited to psoriasis occurring before MC. Data from large-scale cohort studies investigating MC and risk of future psoriasis are lacking. To examine the association between MC and psoriasis. In a nationwide, population-based, matched cohort study in Sweden from 2007 to 2021, we identified 8404 patients with biopsy-verified MC (diagnosed in 2007-2017), 37,033 matched reference individuals, and 8381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a Swedish histopathology database with nationwide coverage). Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis up until 2021. During a median follow-up of 9.2 years (interquartile range = 6.7-11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241.1 vs 131.8 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC over 10 years. After adjustment for the matching variables (birth year, sex, county of residence, and calendar period) and level of education, we computed an adjusted hazard ratio (aHR) of 1.82 (95% CI = 1.53-2.17). Stratified by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95% CI = 1.36-2.51). Patients with MC are at an almost doubled risk of psoriasis compared to the general population. Clinicians need to consider psoriasis in MC patients with skin lesions.

Follow-Up of Microscopic Colitis Patients and Diarrhea Controls at 1 Year

Background and AimsMicroscopic colitis is a common cause of chronic diarrhea, however the clinical course of this disease is poorly understood. We aimed to investigate how patients diagnosed with microscopic colitis were treated in routine clinical practice and how their symptoms compared to patients with other causes of chronic diarrhea at one year follow-up. MethodsWe conducted a case-control study of patients undergoing outpatient colonoscopy to evaluate diarrhea. The study pathologist determined whether patients were classified as microscopic colitis cases or non-microscopic colitis controls. One year after colonoscopy, we interviewed cases (n=74) and controls (n=162) about their diagnosis, medications for diarrhea, and symptom burden. ResultsAt one year follow-up after colonoscopy, 10% of microscopic colitis cases were unaware of the diagnosis, 60% had been prescribed a medication for diarrhea, 40% had fecal urgency, 32% had weight loss, and 21% had fecal incontinence. Among cases, 46% were treated with budesonide. Compared to cases, controls had worse symptoms based on the Microscopic Colitis Disease Activity Index (MCDAI) score with a median MCDAI score of 3.0 (IQR 1.9-4.2) vs 2.3 (IQR 1.4-3.2) at one year follow-up. Controls had more frequent stools, urgency, fecal incontinence, and abdominal pain. ConclusionsIn a cohort of patients with biopsy-confirmed microscopic colitis and diarrhea controls, we found that some cases remained unaware of their diagnosis, many cases had persistent symptoms, and controls had worse symptoms than cases. These findings suggest there are opportunities to improve management of this chronic disease.

Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study.

Microscopic colitis (MC) has been linked to several autoimmune conditions. Results from previous studies on the association with rheumatoid arthritis (RA) have been inconsistent. To assess the risk of future RA in MC. We conducted a nationwide matched cohort study in Sweden of 8179 patients with biopsy-verified MC (diagnosed in 2007-2017), 36,400 matched reference individuals and 8202 siblings without MC, with follow-up until 2021. Information on MC was obtained from all of Sweden's regional pathology registers (n = 28) through the ESPRESSO cohort. Data on incident RA were collected from the National Patient Register. Using Cox regression, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During a median follow-up of 9.1 years (interquartile range = 6.7-11.7), 73 MC patients and 183 reference individuals from the general population were diagnosed with RA (99 vs. 55 events per 100,000 person-years), equivalent to one extra case of RA in 226 patients with MC followed for 10 years. These rates corresponded to an aHR of 1.83 (95% CI = 1.39-2.41). The aHR was highest during the first year of follow-up (2.31 [95% CI = 1.08-4.97]) and remained significantly elevated up to 5 years after MC diagnosis (aHR 2.16; 95% CI = 1.42-3.30). Compared to siblings, without MC, the aHR was 2.04 (95% CI = 1.18-3.56). Patients with MC are at a nearly two-fold risk of developing RA compared to the general population. Knowledge of this increased risk may expedite evaluation for RA in patients with MC presenting with joint symptoms and/or arthralgia, thus preventing delay until RA diagnosis.

Autoimmune and immune-mediated inflammatory diseases after exposure to acid-suppressive medication: A systematic review and meta-analysis.

Pharmacovigilance risk signals have proposed a relationship between the use of acid-suppressive medications and the development of certain autoimmune and immune-mediated inflammatory diseases. A systematic review and a meta-analysis was performed. We reviewed MEDLINE (Ovid) and Scopus for comparative observational studies between these diseases and previous exposure to proton-pump inhibitors (PPI), H2-receptor antagonists (H2RA), and antacids. The protocol was registered on the PROSPERO database (CRD42020192715). From 3,191 citations, 25 articles were eligible and covered 16 diseases. Microscopic colitis (MC) was studied the most (7 studies). In a random-effects meta-analysis, there was low certainty evidence (GRADE approach) of a non-significant relationship between exposure to any PPIs and MC (meta-OR 3.28, 95% CI 0.98-11.0, I2 98.2%, six studies, 4,436 PPI-exposed MC patients). Moderate certainty evidence pointed towards large odds of collagenous colitis after exposure to lansoprazole (meta-OR 14.5, 95% CI 9.37-22.3, I2 10.2%, three studies, 1,725 lansoprazole-exposed patients). After PPI exposure, the risk of rheumatoid arthritis was slightly increased based on low certainty evidence from two cohort studies totaling 475 diagnoses (meta-RR 1.62, 95% CI 1.12-2.34, I2 34.5%). In patients with MC, it would be reasonable to carefully review the indication of PPI, especially in CC patients using lansoprazole.

Clinical Implications of Microscopic Colitis Isolated to Polyps.

Microscopic colitis is generally identified on random colon biopsies performed for chronic diarrhea, but rarely incidental polyps have histologic features of microscopic colitis. We compared patients with polypoid microscopic colitis to control patients with conventional polyps to determine the implications of polypoid microscopic colitis. Medical records were searched for patients without prior or concurrent microscopic colitis who were found to have polypoid microscopic colitis. For each patient with polypoid microscopic colitis, one patient with conventional polyps was selected as a control. We reviewed the histologic features of each polypoid microscopic colitis specimen, and evaluated endoscopic and clinical findings for polypoid microscopic colitis patients and controls. Twenty-six patients with polypoid microscopic colitis were identified with histologic features of collagenous colitis in 8 patients (31%) and lymphocytic colitis in 18 patients (69%). Polypoid microscopic colitis was unifocal in 14 patients (54%) and multifocal in 12 patients (46%). Patients with polypoid microscopic colitis were older than control patients (median age = 60 years vs 66 years, P = .04). On follow-up 7 patients with polypoid microscopic colitis (33%) developed chronic diarrhea compared to 3 (12%) controls ( P = .16). Of patients with follow-up biopsies, 1 patient with polypoid microscopic colitis (13%) and no control patients developed microscopic colitis ( P = 1). Polypoid microscopic colitis may be identified in asymptomatic patients and most patients do not develop chronic diarrhea, but some patients with polypoid microscopic colitis develop diarrhea (33% vs 12% in controls) or conventional microscopic colitis on follow-up. Thus pathologists should distinguish polypoid microscopic colitis from conventional microscopic colitis but may inform clinicians of the uncertain association with chronic diarrhea to guide decisions regarding follow-up.

Fecal calprotectin level in microscopic colitis: a systematic review and meta-analysis

Background There are no specific biomarkers for microscopic colitis (MC), and the diagnosis depends on histopathological tissue obtained during colonoscopy. Studies on the role of fecal calprotectin (FCP) in MC are limited. A literature search of PubMed, Embase, and Scopus was conducted from each database’s inception through September 2022. Methods A DerSimonian-Liard random-effects meta-analysis was performed to examine the standardized mean difference (SMD) in FCP levels between patients with MC and control patients with chronic diarrhea. Results Six studies with 96 active MC patients and 200 controls were included in the meta-analysis. Random effects meta-analysis revealed that FCP was significantly and moderately elevated in patients with MC compared to the control group (SMD = 0.6 [95% CI 0.3, 1.0], P = 0.001). Imputing one effect size confirmed the observation that FCP is significantly higher in patients with MC than control subjects with chronic diarrhea (SMD = 0.5 [95% CI 0.2, 0.9], P = 0.004). Study heterogeneity between the SMDs was not significant (I2 = 41%, P = 0.1). Conclusion These results indicate that FCP levels in patients with chronic diarrhea can help identify patients with MC. More studies with serial measurements of FCP would provide a better understanding of its utility in MC.

Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study

Inflammatory diseases are associated with an increased risk of incident major adverse cardiovascular events (MACE). However, data on MACE are lacking in large population-based histopathology cohorts of microscopic colitis (MC). This study included all Swedish adults with MC without previous cardiovascular disease (1990-2017; N = 11,018). MC and subtypes (collagenous colitis and lymphocytic colitis) were defined from prospectively recorded intestinal histopathology reports from all pathology departments (n= 28) in Sweden. MC patients were matched for age, sex, calendar year, and county with up to 5 reference individuals (N= 48,371) without MC or cardiovascular disease. Sensitivity analyses included full sibling comparisons, and adjustment for cardiovascular medication and healthcare utilization. Multivariable-adjusted hazard ratios for MACE (any of ischemic heart disease, congestive heart failure, stroke, and cardiovascular mortality) were calculated using Cox proportional hazards modelling. Over a median of 6.6 years of follow-up, 2181 (19.8%) incident cases of MACE were confirmed in MC patients and 6661 (13.8%) in reference individuals. MC patients had a higher overall risk of MACE outcomes compared with reference individuals (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.21-1.33) and higher risk of its components: ischemic heart disease (aHR, 1.38; 95% CI, 1.28-1.48), congestive heart failure (aHR, 1.32; 95% CI, 1.22-1.43), and stroke (aHR, 1.12; 95% CI, 1.02-1.23) but not cardiovascular mortality (aHR, 1.07; 95% CI, 0.98-1.18). The results remained robust in the sensitivity analyses. Compared with reference individuals, MC patients had a 27% higher risk of incident MACE, equal to 1 extra case of MACE for every 13 MC patients followed for 10 years.

Type 1 diabetes and microscopic colitis: A nationwide matched case-control study in Sweden.

Microscopic colitis (MC) is a colonic inflammatory condition associated with autoimmune dysfunction. Type 1 diabetes (T1D) is a chronic disease induced by autoimmune destruction of pancreatic β-cells. We aimed to examine the association between T1D and MC. A matched case-control study was conducted using the nationwide ESPRESSO cohort as study base. All biopsy-confirmed MC patients born after 1940 were identified and compared to biopsy-free individuals matched from the general population for T1D diagnosis using the Swedish National Patient Register. The T1D-MC association was estimated as odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models, considering differences by sex and MC subtype. Full sibling comparison and adjustment for MC-associated medications were also performed. We identified 352 (3.7%) and 945 (2.0%) T1D diagnoses from 9,600 MC cases and 47,870 matched population controls, respectively, which corresponded to an overall OR of 1.79 (95% CI: 1.56-2.05). The association was stronger for collagenous colitis (OR, 2.15; 95% CI: 1.70-2.71) than lymphocytic colitis (OR, 1.62; 95% CI: 1.37-1.92) and remained statistically significant in full sibling comparison (OR, 1.46; 95%: 1.18-1.81). Medication adjustment attenuated the association to null among females (OR: 1.02; 95% CI: 0.82-1.27) but not among males (OR: 1.45; 95% CI: 1.11-1.90). T1D diagnosis was almost 80% more prevalent in MC patients compared to general population. This positive association did not seem to be spurious due to residual confounding shared by full siblings but may relate to consumption of medications associated with MC onset.

A180 PLACEBO RATES IN MICROSCOPIC COLITIS RANDOMIZED TRIALS: APPLICATIONS FOR FUTURE DRUG DEVELOPMENT USING A HISTORICAL CONTROL ARM

Abstract Background There remains a need to develop effective medical therapies for patients with microscopic colitis (MC) who do not respond, are intolerant, or relapse on budesonide. Conducting randomized trials in MC is logistically and ethically challenging: budesonide is highly effective, and therefore, some institutional review boards have not allowed trials that randomize MC patients to placebo. However, comparing an investigational drug to budesonide is statistically infeasible: powering a non-inferiority study against a budesonide comparator arm with 90% power for a 10% non-inferiority margin would require over 700 subjects, yet fewer than 400 patients have been randomized in all historical MC trials. Therefore, alternative trial designs should be explored in MC, including the use of a historical control arm. Purpose To conduct a systematic review and meta-analysis to determine the proportion of placebo responders in MC trials that will inform future trials using a historical placebo comparator, and evaluate factors associated with placebo response. Method EMBASE, MEDLINE, and CENTRAL were searched from inception to January 7, 2022, and supplemented with conference abstracts to identify randomized controlled trials (RCTs) using a placebo comparator in adult patients with confirmed MC (either lymphocytic, collagenous, or mixed populations but excluding incomplete MC). The proportion of clinical and histologic responders in the placebo arms were pooled using random-effect models, statistical heterogeneity was evaluated using the I2 method, and the Freeman-Tukey double arcsine transformation was used to compute 95% confidence intervals (CI) using the score statistic and exact binomial method. All analyses were conducted in Stata 17.0. Result(s) Twelve placebo controlled RCTs were included, evaluating a total of 391 patients (163 randomized to placebo). The pooled placebo clinical response rate was 24.4% [95% CI 12.4%, 38.4%] (Figure 1), with substantial heterogeneity (I2=60.8%, p&amp;lt;0.01). The pooled histologic response rate was 19.9% [95% CI: 5.3%, 39.0%], with substantial heterogeneity (I2=66.4%, p&amp;lt;0.01). Subgroup analysis demonstrated higher placebo responses in lymphocytic colitis (39.9% [95% CI: 23.9%, 56.7%]) compared to collagenous colitis (19.8% [95% CI: 5.9%, 37.8%]), but not by allowance of baseline anti-diarrheals. Leave-one-out meta-analysis showed a reduction in heterogeneity after removal of Miehlke et al. 2014 (placebo response 21.0% [95% CI: 11.5%, 32.1%], I2=28.6%, p=0.17). Image Conclusion(s) Approximately 1 in 4 patients in MC trials will respond clinically to placebo and 1 in 5 will demonstrate a histologic response, although with substantial heterogeneity. T his highlights the need for standardized outcome definitions in MC trials and can serve to inform a Bayesian prior estimate for future trials that may consider using a historical placebo comparator. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest P. Hamilton: None Declared, K. Buhler: None Declared, G. Kaplan Grant / Research support from: Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire, Consultant of: AbbVie, Janssen, Pfizer, Amgen, Takeda, and Gilead, C. Lu Consultant of: Abbvie, Janssen, Ferring, and Takeda, Speakers bureau of: Janssen and Abbvie, C. Seow Consultant of: Advisory Boards: Janssen, Abbvie, Takeda, Ferring, Shire, Pfizer, Sandoz, Pharmascience, Fresenius Kabi, Amgen, Speakers bureau of: Janssen, Abbvie, Takeda, Ferring, Shire, Pfizer, Pharmascience, K. Novak Grant / Research support from: AbbVie and Janssen, Consultant of: Advisory board fees from AbbVie, Janssen, Pfizer, Ferring, and Takeda, speaker’s fees from AbbVie, Janssen, and Pfizer, R. Panaccione Consultant of: Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, UCB. Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, Speakers bureau of: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals, C. Ma Grant / Research support from: Ferring, Pfizer, Consultant of: AbbVie, Alimentiv, American College of Gastroenterology, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Sanofi/Regeneron, Takeda, Pendopharm, Pfizer, Roche, Speakers bureau of: : AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer

Case-control study of the concurrence of coeliac disease with inflammatory bowel disease.

Previous studies suggested that inflammatory bowel disease (IBD) is associated with an increased prevalence of comorbid coeliac disease. Our case-control study aimed to test this association using a large histopathology database. The Inform Diagnostics database is a repository of histopathologic records from patients distributed throughout the United States. In a case-control study among patients with bidirectional endoscopy, we compared the occurrence of coeliac disease in case subjects with IBD or microscopic colitis (MC) and control subjects without inflammatory colitis, calculating odds ratios (OR) and their 95% confidence intervals (CI) adjusted to the varying age, gender and ethnic distributions of case and control subjects. The study population was split into 12,816 IBD cases and 6486 MC cases, who were compared to 345,733 control subjects without colitis. A total of 2892 patients were diagnosed with coeliac disease. Of 12,816 IBD patients, 57 patients (0.4%) harboured coeliac disease compared to 0.7% (2548/345,733) in the control population. The prevalence of coeliac disease among MC patients was 4.4% (288/6486). The corresponding ORs were significantly decreased in IBD (OR: 0.50, CI: 0.38-0.64) and significantly increased in MC patients (6.78, 5.96-7.69). Further stratification of the case populations into subtypes of IBD (Crohn's disease or ulcerative colitis) and MC (collagenous or lymphocytic colitis) similarly revealed significantly decreased and increased ORs for each subtype. The previously reported positive association between coeliac disease and IBD may have been possibly biased by the inclusion of MC cases in the IBD patient population.

What is the incidence of celiac disease in patients with microscopic colitis? Why are these two diseases related?

Although there are studies in the literature showing that celiac disease (CD) is more common in patients with microscopic colitis (MC), there are publications to the contrary. The pathophysiologies of both diseases are different from each other. To investigate the frequency of CD in MC patients, the different features of these 2 diseases, and the relationship between them. In our prospective and cross-sectional analytical study, the presence of CD was investigated in 90 patients diagnosed with MC by colonoscopy and biopsy due to chronic diarrhoea between September 2011 and December 2021. We detected MC in 102 (9.3%) of 1096 patients investigated for chronic diarrhoea. We detected CD in 1 (1.1%) of 90 patients with MC who participated in the study. Only 10% of the patients were positive for AGA IgA, 3.3% for EMA IgA, and 2.2% for Anti-TG2 IgA. There was no difference in autoantibody titre in treatment-responsive and treatment-resistant MC patients. HLA DQ2 was positive in 32.2% (n = 29) of the MC patients, and HLA DQ8 was found in 5.5% (n = 5). Intraepithelial lymphocyte increase was remarkable in the duodenal biopsies of MC patients who did not respond to treatment (40% vs. 11.4%; p = 0.007). We did not reach the conclusion that CD is more common in MC patients. An increase in IEL may also occur in the small intestine in patients with MC who do not respond to treatment.

Microscopic colitis is a risk factor for low bone density: a systematic review and meta-analysis.

Microscopic colitis (MC) is a chronic inflammatory disease of the large bowel characterized by watery diarrhea, substantially decreasing the patient's quality of life. Scarce data suggest that MC is associated with low bone density (LBD). We aimed to assess whether MC is a risk factor for LBD and the proportion of patients with MC having LBD. A systematic review and meta-analysis of studies reporting bone density measurements in MC patients. We systematically searched five databases from inception to October 16, 2021 (Pubmed, Embase, Cochrane, Scopus, and Web of Science). We used the random-effect model to calculate pooled odds ratios (ORs) and pooled event rates with 95% confidence intervals (CIs). To ascertain the quality of evidence of our outcomes, we followed the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. The systematic search yielded a total of 3046 articles. Four articles were eligible for quantitative synthesis. All of them used age- and sex-matched controls to evaluate LBD occurrence among patients with MC. The odds of having LBD were twofold increased (OR = 2.13, CI: 1.42-3.20) in the presence of MC, the odds of osteopenia occurrence were 2.4 (OR = 2.45, CI: 1.11-5.41), and of osteoporosis 1.4 (OR = 1.42, CI: 0.65-3.12). The proportion of LBD was 0.68 (CI: 0.56-0.78), osteopenia was 0.51 (CI: 0.43-0.58), and osteoporosis was 0.11 (CI: 0.07-0.16) among the MC population. Our findings' certainty of the evidence was very low following the GRADEPro guideline. Our data demonstrate that MC is associated with a twofold risk for LBD. Based on our findings, we suggest screening patients for bone mineral density upon diagnosis of MC. Further prospective studies with higher patient numbers and longer follow-up periods on this topic are needed. Our protocol was prospectively registered with PROSPERO (CRD42021283392).

S230 Baseline Characteristics of Patient Admitted With Microscopic Colitis

Introduction: Microscopic colitis (MC) is a chronic inflammatory disease of the colon causing frequent watery diarrhea, abdominal pain, nocturnal diarrhea, urgency and fecal incontinence. Once known to be rare now MC is one of the most common causes of chronic watery diarrhea in adult population which leads to poor quality of life and increase health care cost burden. So, we decide to identify baseline characteristics and incidence of microscopic colitis in adult population. Methods: Adult patients admitted with MC were analyzed from 2016 - 2019 using the National Inpatient Sample database. The primary outcome was to determine the baseline characteristics of patients admitted with MC. Secondary outcome was to determine the disease burden in hospitalized patient population. SAS 9.4 software was used for statistical analysis. (Figure) Results: Total 35,685 patients were admitted with MC during our study period. MC cohort comprise of predominantly elders, with mean age of 71.2 ± 13.7 yrs. MC was found to be more prevalent in Caucasian (89.6%) females (77.4%) compared to male (22.6%). We also observed significant increasing trend in hospitalization secondary to MC through 2016 to 2019. Comorbidities like hypertension (62.8%), coronary artery disease (25.3%), smoking (44.7%), hypothyroidism (25.2%) and Depression (24.8%) are some of the higher prevalent ones associated with MC. Concurrent IBS (2.4%), Celiac Disease (2.6%), Rheumatoid Arthritis (9.3%) and C.diff infection (4.5%) were noted among MC patients. Majority of the hospitalization were noted to be emergent (86.7%) and primary insurance in majority of the hospitalized was found to be Medicare (74.5%). (Table) Conclusion: Our study showed increasing prevalence of MC among the elderly, Caucasians and females throughout the study period. Study also showed increased association between depression and MC. Throughout the years MC has shown an increasing hospitalization trend which potentially increases healthcare cost burden. More detailed studies are warranted in this field to better understand pathophysiology, immune response, gut microbiome along with disease management to improve quality of life among MC patients and decrease the health care cost burden especially on Medicare.Figure 1.: Trend of Microscopic Colitis Table 1. - Baseline characteristics and comorbidities of Microscopic colitis patients admitted between January 2016 and December 2020 Microscopic colitis N = 35,685 Age, in years (Mean ± SD*) 71.2 ± 13.7 Age groups, % 18 - 34 years 1.9% 35 – 49 years 5.9% 50 – 64 years 18.3% 65 - 79 43.3% >79 years 30.4% Gender, % Male 22.6% Female 77.4% Race, % Caucasians 89.6% African Americans 2.5% Others 7.9% Comorbidities, % Hypertension 62.8% Diabetes mellitus 18.7% Congestive heart failure 18.4% CAD* 25.3% Peripheral vascular disease 9.3% COPD* 25.1% Renal failure 19.8% Coagulopathy 6.1% Obesity 9.9% Drug abuse 2.1% Alcohol abuse 4.1% Smoking 44.7% Cdiff * infection 4.5% IBS* 2.4% Celiac disease 2.6% Rheumatoid arthritis/collagen vascular disease 9.3% Hypothyroidism 25.2% Depression 24.8% Admission Type, % Emergent 86.7% Elective 13.3% Insurance type, % Medicare 74.5% Medicaid 4.7% Private 18.4% Other 2.4% Location/Teaching status of the hospital, % Rural 8.9% Urban nonteaching 20.7% Urban teaching 70.3% *Abbreviations (SD - Standard deviation, CAD - Coronary artery disease, COPD - Chronic obstructive pulmonary disease, cdiff - clostridium difficile, IBS - Irritable Bowel Syndrome)

S2150 Triangle of Lymphocytic Colitis, Epstein-Barr Virus, and Lymphoma: Is There Any Association?

Introduction: Epstein–Barr virus (EBV), is linked to range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. EBV-positive diffuse large B cell lymphoma (DLBCL) not otherwise specified is a variant of DLBCL seen in patients without known immunodeficiency or prior lymphoma. In few reports EBV infection was more commonly detected in colonic mucosa of patients with Microscopic Colitis (MC), but it remains unclear if this translates to higher incidence of lymphoma in this subgroup of people. Here, we describe a case of DLBCL in patient with MC associated with EBV infection in context of recent findings. Case Description/Methods: 77-year-old female with history of COPD, diabetes underwent colonoscopy for chronic diarrhea of 4-month duration. She suffered from 3-4 loose stools/day, and had normal celiac panel, fecal elastase, and infectious workup. Colonoscopy was unremarkable except for 4 mm Paris Is polyp in sigmoid colon removed with cold snare. On pathology, the random colon biopsies were positive for lymphocytic colitis along and polyp showed DLBCL (non-germinal center phenotype) along with positive EBV infection (Figure). Discussion: It is widely believed that overall risk of malignancy is not increased in MC. However, theoretically MC should increase risk of lymphoma as it is more likely to be associated with oncogenic EBV than Ulcerative colitis or irritable bowel syndrome (90 % vs 66 % vs 0 % respectively). EBV increases the risk of lymphoma due to protein expression in transformed infected lymphocytes that results in immune evasion and suppression of apoptosis. Earlier studies have shown no evidence of higher risk of lymphoma in MC, however recently Bergman et al. (2021) analyzed data from Sweden´s pathology departments and from the Swedish Cancer Register and included 11758 patients with incident MC and found an increased risk of lymphoma (adjusted HR 1.43 [1.06–1.92]). Studies are needed to explore risk of lymphoma in subgroup of MC patients with EBV infection as inflammation cause by MC and concomitant EBV infection enhance the overall malignant potential. In conclusion, MC may not be as benign entity as it was once thought to be as it is more likely to harbor oncogenic EBV virus. Even diminutive polyps in MC can potentially harbor lymphoma and should be removed and submitted for analysis rather than being discarded.Figure 1.: Colonoscopy image showing small polyp (left) and schematic (right) of triangle between CMV, microscopic colitis and lymphoma error.

Colonic bacterial diversity and dysbiosis in active microscopic colitis as compared to chronic diarrhoea and healthy controls: effect of polyethylene glycol after bowel lavage for colonoscopy

BackgroundMost microbiota studies in microscopic colitis patients are performed after diagnostic colonoscopy without considering the potential effect of colonic lavage. Patients may achieve clinical remission after colonoscopy and it is unknown whether lavage-induced changes play a role.AimTo assess the effect of polyethylene glycol (PEG) colonic lavage on clinical remission rate, microbial diversity, microbial dysbiosis index and specific microbial changes in patients with active microscopic colitis as compared to other diarrhoeal diseases and healthy controls.MethodsFifty-five consecutive patients presenting chronic watery diarrhoea and 12 healthy controls were included. Faecal samples were collected three days before and 30 days after PEG in patients and controls for microbiome analysis.ResultsClinical remission was observed in 53% of microscopic colitis patients, and in 32% of non-microscopic colitis patients (p = 0.16). Considering patients with persisting diarrhoea after colonoscopy, 71% of non-microscopic colitis patients had bile acid diarrhoea. Baseline Shannon Index was lower in diarrhoea groups than in healthy controls (p = 0.0025); there were no differences between microscopic colitis, bile-acid diarrhoea and functional diarrhoea. The microbial dysbiosis index was significantly higher in microscopic colitis than in bile acid diarrhoea plus functional diarrhoea (p = 0.0095), but no bacterial species showed a significantly different relative abundance among the diarrheal groups.ConclusionsDysbiosis is a feature in active microscopic colitis, but loss of microbial diversity was similar in all diarrheal groups, suggesting that faecal microbial changes are not due to microscopic colitis itself but associated with stool form. A considerable number of microscopic colitis patients achieved clinical remission after colonoscopy, but we were unable to demonstrate related PEG-induced changes in faecal microbiome.

Quantifying risk factors for microscopic colitis: A nationwide, retrospective cohort study.

Microscopic colitis (MC) is associated with several risk factors; however, their relative risk has been variable and not thoroughly evaluated. We aimed to quantify the risk of medical comorbidities and medications associated with MCand treatment offered to these patients. A population-based retrospective analysis in International Business Machines (IBM) Explorys (1999-2018), a pooled, de-identified database of 63 million patients in the USA, was performed. Odds ratios (OR) were calculated between MC and other diseases/medications. MC patients were also stratified by age to assess trends of MC in different age groups. A total of 1130 patients had MC in the database. Among medications, non-steroidal anti-inflammatory agents (OR, 20.2) and proton pump inhibitors (OR, 12.1) were associated with highest odds of MC. Among medical comorbidities, infectious gastroenteritis (OR, 26.6) and celiac disease (OR, 22.5) had the highest odds of being associated with MC. Tobacco smoking, psoriasis, Sjogren's syndrome, Clostridium difficile infection, and malabsorption syndromes all conferred odds greater than 10. Early identification of MC is critical for minimizing morbidity and mortality. Epidemiologic information can be integrated with current clinical algorithms to more rapidly identify patients at risk.

MICROSCOPIC COLITIS IS ASSOCIATED WITH DECREASED BONE DENSITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract INTRODUCTION Although, microscopic colitis (MC) can be considered as spectrum of inflammatory bowel disease (IBD), MC is very different in many aspects; in terms of risk factors, symptoms, course of disease, treatment, and complication. Low bone mineral density (BMD) is previously known as complication of IBD. There are few data about MC and risk of bone density loss. We conduct this systematic review and meta-analysis to determine the association between MC and low BMD. METHODS A comprehensive literature review was conducted using the MEDLINE, and EMBASE databases through October 2021 to identify studies that demonstrated association between clinical outcomes of interest, MC and low BMD. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS After two rounds of review, four studies met our eligibility criteria and were included in analysis. The result showed statistically significant association between MC and low bone density (pooled OR = 2.15, 95% CI: 1.06 - 4.38, p = 0.03) The forest plots and funnel plots are shown below. CONCLUSIONS Our meta-analysis found significant association between MC and low bone density. Therefore, this data may suggest that BMD screening could be applied for MC patients, and such patients may have benefit from calcium and vitamin D supplementation. Further studies should be done to determine the significance of this issue.