Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing.

BACKGROUND & AIMS: Bile acid sequestrants (BAS) may be a treatment in microscopic colitis (MC), but efficacy data are limited. We evaluated the effectiveness of BAS in MC and assessed the utility of bile acid testing to predict response. METHODS: Adults with MC treated with BAS (2010-2020) at Mayo Clinic were identified. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs. Response was defined at 12 ± 4 weeks after BAS initiation as: complete (resolution of diarrhea), partial (≥50% improvement in diarrhea), nonresponse (<50% improvement), and intolerance (discontinuation due to side effects). Logistic regression was used to identify predictors of response to BAS. RESULTS: We identified 282 patients (median age, 59 years [range, 20-87 years]; 88.3% women) with median follow-up of 4.5 years (range, 0.4-9.1 years). Patients were treated with the following BAS: 64.9% cholestyramine, 21.6% colesevelam, and 13.5% colestipol. Clinical outcomes were: 49.3% complete response, 16.3% partial response, 24.8% nonresponse, and 9.6% intolerance. There were no differences in outcomes between those on BAS alone or BAS combined with other medications (P = .98). The dose of BAS was not associated with response (P = .51). Bile acid testing was done in 31.9% of patients, and 56.7% were positive. No predictors of response to BAS were identified. After BAS discontinuation, 41.6% had recurrence at a median of 21 weeks (range, 1-172 weeks). CONCLUSION: In one of the largest cohorts evaluating BAS treatment in MC, nearly two-thirds had a partial or complete response. Additional research is needed to determine the role of BAS and bile acid malabsorption in MC.

Regional differences in the incidence of lymphocytic and collagenous colitis over time.

BACKGROUND: In microscopic colitis (MC), the incidence has increased over the last decades. The aim of the present study was to determine the incidence of lymphocytic (LC) and collagenous colitis (CC) in the county Skåne (Scania), southern Sweden, during the period 2010-20 with focus both on the temporal and spatial variations. METHODS: The MC diagnosis was retrieved from the biopsy registries at the Departments of Pathology. Established diagnostic criteria (increased lymphocyte count, inflammation in lamina propria and in CC a collagen band) were used for diagnosis. Age, gender, date for diagnosis and municipality of residence were retrieved for all patients. RESULTS: In total 1985 patients could be identified with a mean age of 62.9 years (SD 15.7) whereof 1415 were women. The incidence for CC was stable with a total age-standardized rate (ASR) per 100 000 person-years of 6.34, (range 4.6-8.1). In LC the ASR was 7.90 (range 1.7-15.2) but increased markedly 2015-20 reaching 15.2 in 2019. Also, the northwest part of the region showed significantly higher ASR:s of LC during the last part of the decade in comparation to the whole region. CONCLUSIONS: The incidence of CC was stable during the period while LC differed substantially in a way that indicates that it most probably must be two different disease entities. In LC, in view of the marked and rapid increase, although no definitive explanation could be found, causative environmental factors could be contemplated, why further studies are indicated.

[Clinical cases of microscopic colitis: Diagnosis and treatment issues. Case report].

Currently, there is an increase in the incidence of microscopic colitis. There are difficulties in diagnosing this disease due to the variability of histological signs, variability of morphological changes in the mucous membrane of the colon in different parts of the colon, and the combination in one patient of not only various forms of microscopic colitis, but also other intestinal diseases. The article describes the differential diagnosis, an example of its staging and successful treatment of various forms of microscopic colitis with budesonide (two clinical cases presented).

Gastrointestinal Infection and Risk of Microscopic Colitis: A Nationwide Case-Control Study in Sweden.

BACKGROUND AND AIMS: Gastrointestinal infections have been linked to changes in the composition and function of gut microbiome and development of inflammatory bowel diseases. We therefore sought to examine the relationship between gastroenteritis and risk of microscopic colitis (MC). METHODS: We conducted a case-control study of all adult patients with MC diagnosed between 1990 and 2016 in Sweden matched to up to 5 general population controls according to age, sex, calendar year, and county. Cases of MC were identified using Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, a cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden. We used logistic regression modeling to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Through December of 2016, we matched 13,468 MC cases to 64,479 controls. The prevalence of previous diagnosed gastrointestinal infection was 7.5% among patients with MC, which was significantly higher than in controls (3.0%, Pcomparison < .001). After adjustment, gastroenteritis was associated with an increased risk of MC (aOR 2.63; 95% CI 2.42-2.85). Among specific pathogens, Clostridioides difficile (aOR 4.39; 95% CI 3.42-5.63), Norovirus (aOR 2.87; 95% CI 1.66-4.87), and Escherichia species (aOR 3.82; 95% CI 1.22-11.58), but not Salmonella species, were associated with an increased risk of MC. The association between gastrointestinal infections and risk of MC was stronger for collagenous subtype (aOR 3.23; 95% CI 2.81-3.70) as compared with lymphocytic colitis (aOR 2.51; 95% CI 2.28-2.76; Pheterogeneity = .005). The associations remained significant after adjustment for immune-mediated conditions and polypharmacy and when compared with unaffected siblings. CONCLUSION: In a nationwide study, we found that gastrointestinal infection, particularly Clostridioides difficile, is associated with an increased risk of subsequent MC. This study was approved by the Regional Ethics Committee, Stockholm, Sweden (Protocol no. 2014/1287-31/4).

Transient Lymphocytic Colitis After SARS-CoV2 mRNA Vaccine.

This is the first scientific report describing lymphocytic colitis after administration of the Pfizer severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) messenger RNA (mRNA) vaccine. The patient developed liquid stools, abdominal pain, and nausea within 24 hours of receiving the second dose. Symptoms were persistent for 3 months but improved 113 days after onset. Laboratory profiles and gastrointestinal polymerase chain reaction were normal. Esophagogastroduodenoscopy and colonoscopy performed 98 days after onset revealed patchy erythema in the descending colon and rectosigmoid. Mucosal evaluation revealed lymphocytic colitis. Review of the Vaccine Adverse Event Reporting System revealed 5 cases of microscopic colitis after the second mRNA dose. This report and Vaccine Adverse Event Reporting System cases suggest providers should consider microscopic colitis in the differential diagnosis of patients with severe, persistent diarrhea after the SARS-CoV2 mRNA vaccine.

Prevalence of Microscopic Colitis in Diarrhea-predominant Irittable Bowel Syndrome Patients: Cohort Study From Upper Egypt.

BACKGROUND AND AIM: There is controversy about colonoscopy and taking biopsy from the normal colonic mucosa in patients with a clinical diagnosis of diarrhea-predominant irritable bowel syndrome (D-IBS). This study aims to estimate the prevalence of microscopic colitis (MC) in D-IBS patients and to select patients without the well-known alarming features who will benefit from colonoscopy and biopsies from the normal colonic mucosa. PATIENTS AND METHODS: We performed a cohort cross-sectional study over 6 months duration in a total of 129 patients with Rome III criteria of D-IBS after excluding cases with features of organic diseases. Cases were subjected to colonoscopy and biopsies from the colonic mucosa that seemed normal. RESULTS: Histopathologic examination of biopsies taken from cases with normal colonic mucosa revealed 86 (71.66%) cases with nonspecific colitis, 26 (21.66%) cases with MC and 8 (6.66%) cases with ulcerative colitis. Concomitant immunologic diseases (P=0.00005) and triggering drugs intake (P=0.006) were significantly more common in the MC group. The mean duration of diarrhea in MC patients was significantly longer than that of nonspecific colitis and ulcerative colitis patients (P=0.0006). CONCLUSIONS: Prevalence of MC in D-IBS patients from Upper Egypt is relatively high (21.66%). Concomitant immunologic diseases, possible triggering drugs intake, and long duration of diarrhea are significant risk factors for undiagnosed MC in D-IBS patients.

Abnormal findings on abdominopelvic cross-sectional imaging in patients with microscopic colitis: a retrospective, multicenter study.

OBJECTIVES: Patients with microscopic colitis may have subtle macroscopic findings on colonoscopy such as erythema, edema, or altered vascular pattern; however, radiographic abnormalities on cross-sectional imaging have not been investigated. We aimed at identifying the abdominopelvic radiographic abnormalities in patients with microscopic colitis, as well as possible correlation with endoscopic findings and the need for extended duration of treatment. MATERIALS AND METHODS: This was a retrospective study of patients with biopsy-proven microscopic colitis at two tertiary centers between 1 January 2010 and 30 April 2020. Patients underwent computed tomography scan or magnetic resonance imaging within 30 days of a diagnostic flexible sigmoidoscopy or colonoscopy. Patients with colon ischemia and other causes of colitis were excluded. Radiographic abnormalities from imaging reports included bowel wall thickening, mucosal hyperenhancement and mesenteric fat stranding. Univariate and multivariable logistic regression models were used to identify predictors of radiographic abnormalities. RESULTS: 498 patients with microscopic colitis underwent abdominopelvic cross-sectional imaging within 30 days of flexible sigmoidoscopy/colonoscopy. Lymphocytic colitis was diagnosed in 54.6% of patients, and collagenous colitis in 45.4%. Endoscopic and radiographic abnormalities were identified in 16.1% and 12.4% of patients, respectively. Radiographic abnormalities were associated with the need for budesonide therapy (p = .029) and budesonide therapy long-term (p = .0028). Budesonide therapy long-term (p = .047) was associated with radiographic abnormalities in multivariate analysis. CONCLUSIONS: Radiographic abnormalities may be present on abdominopelvic cross-sectional imaging in a minority of patients with biopsy-proven microscopic colitis, suggesting cross-sectional imaging has low clinical value in the evaluation and treatment of this disease.

Microscopic colitis in Northern Ireland: an updated clinicopathological audit and assessment of compliance with European guidelines.

AIM: We previously reported the first population-based study of the epidemiology of microscopic colitis in Northern Ireland. The aim of the current study is to provide updated data on incidence, diagnostic methods and clinicopathological associations, following dissemination of the previous report. A further aim was to compare the findings against relevant recommendations from the 2020 European guidelines. METHOD: Study cases were identified via the Belfast Health and Social Care Trust pathology laboratory system for new cases of collagenous colitis or lymphocytic colitis diagnosed from 2017 to 2020 inclusive. Demographic and clinical information was collated from electronic healthcare records. RESULTS: Two hundred and seventeen new diagnoses of microscopic colitis were made between 2017 and 2020, comprising 89 (41%) collagenous colitis and 128 (59%) lymphocytic colitis. The overall incidence of microscopic colitis, expressed per 100,000 adult population, ranged from 7.6 to 11.5 (5.9 to 9.0 per 100,000 total population). The 2019 peak of 11.5 cases per 100,000 adult population represents a 71.6% increase in incidence compared with the mean incidence of 6.7 per 100,000 adult population from previous data for 2008-2016. There has also been a significant increase in number of cases diagnosed on separate sampling from the right and left colon (85% in 2019-2020 compared with 30% in 2008-2016; p < 0.001). Overall compliance with coeliac serology testing has improved, with 89% tested in 2017-2018 compared with 75% in 2008-2016. CONCLUSION: Clinicopathological communication has contributed to an increased incidence of microscopic colitis in Northern Ireland through better endoscopic diagnostic sampling and pathology coding practices. Coeliac serology testing has also improved, although continued clinical awareness is required of the need for coeliac serology testing in all patients diagnosed with microscopic colitis.

Celiac Disease Is Associated with Microscopic Colitis in Refractory Cases in Adults: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Microscopic colitis and Celiac disease have been shown to occur concomitantly, but their relationship has yet to be systematically evaluated. Some patients with refractory microscopic colitis may have simultaneous celiac disease, and the converse is also true. AIMS: We performed a systematic review and meta-analysis of observational studies to assess the prevalence and possible association between these two conditions. METHODS: PubMed, Embase, Cochrane, Web of Science, SciELO, and CINAHL Plus were systematically searched through January 26, 2021, to include relevant observational studies assessing the prevalence of microscopic colitis in celiac disease population or vice versa. DerSimonian-Laird approach using random effects was used to pool data and compare outcomes. Pooled prevalence, 95% confidence interval (CI), and p values (where applicable) were calculated. RESULTS: Five studies (with 2589 patients, age range 39.5-52 years and females 66.6%) and 21 studies (with 7186 patients, age range 46.4-65.8 years and females 76.3%) were included assessing the prevalence of microscopic colitis in refractory celiac disease and celiac disease in refractory microscopic colitis cohort. The overall prevalence was 4.5% (2.6-6.3%) and 6.7% (5.2-8.1%), respectively. Five studies showed higher odds of celiac disease diagnosis in the refractory microscopic colitis population compared to the control group (OR 8.12, CI 4.92-13.41, p < 0.001). CONCLUSION: Celiac disease and microscopic colitis are concomitantly prevalent in a subset of population with either refractory diagnosis. Clinicians should explore alternate diagnosis when one condition has been appropriately treated and patients continue to have refractory symptoms.

Clinical Characteristics and Treatment Response in Microscopic Colitis Based on Age at Diagnosis: A Multicenter Retrospective Study.

BACKGROUND: Microscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce. AIMS: To compare clinical characteristics and treatment response by age at diagnosis. METHODS: This retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were 'younger' if age at diagnosis was ≤ 50 years and 'older' if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered 'responders' if they had remission or response and 'non-responders' if they had non-response or intolerance. RESULTS: We included 295 patients (52 younger, 243 older). There were no differences in sex, race, MC subtype, and diarrhea severity between groups (all P > 0.05). Younger patients were more likely to have celiac disease (17.3% vs. 5.8%, P = 0.01), while older patients had higher BMI (mean 25.0 vs. 23.8 kg/m2, P = 0.04) were more likely smokers (53.9% vs. 34.6%, P = 0.01) and use NSAIDs (48.6% vs. 15.4%, P < 0.01) and statins (22.6% vs. 3.8%, P < 0.01). Overall treatment response was highest for budesonide (88.3%) and did not differ when comparing older to younger patients (90.6% vs. 77.8%, P = 0.12) or by MC subtype (LC, 81.5% vs. CC, 92.9%, P = 0.07). CONCLUSIONS: There are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age.

Increasing Incidence of Microscopic Colitis in a Population-Based Cohort Study in Switzerland.

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, nonbloody watery diarrhea and only few or no endoscopic abnormalities. Histologic examination discriminates lymphocytic colitis (LyC; presence of ≥20 intraepithelial lymphocytes per 100 surface epithelial cells) and collagenous colitis (CC; colonic subepithelial collagen band >10 µm in diameter).1,2 MC not otherwise specified describes a subgroup of patients who do not fulfill the diagnostic criteria for either CC or LyC.1,2 Population-based epidemiologic data regarding MC are scarce. We aimed to evaluate the clinical presentation at diagnosis, incidence, and prevalence of MC in Cantons of Vaud and Fribourg, Switzerland.

A 5-year clinicopathological study on microscopic colitis at a Malaysian tertiary hospital.

INTRODUCTION: Microscopic colitis (MC) is a well-recognised cause of chronic diarrhoea in Western countries. It is classically associated with normal endoscopic findings and a higher prevalence among patients with autoimmune disease. Local information regarding this disease remains scarce. We identified patients diagnosed with MC over a five-year period, and then proceeded to analyse the clinical characteristics of these cases. MATERIALS AND METHODS: A retrospective study was conducted by identifying all histologically confirmed colitis cases diagnosed at Hospital Universiti Sains Malaysia from January 2015 until December 2019. Clinicodemographic data was retrieved from case notes of patients. RESULTS: Of the 299 cases with histological colitis, 23 (7.7%) were initially identified as MC. Two cases had incomplete data, while two others were excluded as the diagnoses were revised to inflammatory bowel disease. An incidence of 14 MC cases/1000 case-year was obtained using the 21 MC cases seen within the five-year period. MC subtypes for the 19 analysed cases i.e., lymphocytic colitis and collagenous colitis accounted for 13 (68.4%) and 6 (31.6%) cases, respectively. Eleven patients (57.9%) were females (M:F ratio 1:1.5) with a median age of 51 years. Only nine (47.3%) presented with diarrhoea; one subject (5.4%) had an autoimmune condition (Hashimoto thyroiditis). Normal endoscopic findings were found in 89.5% of patients. CONCLUSION: Approximately half of the subjects in our study who had histologically confirmed MC did not present with diarrhoea. Adequate biopsy samples despite normal colonoscopy findings are important in order to not miss the diagnosis of MC.

[Diagnostic utility of colonoscopy and histological evaluation in the study of patients with chronic diarrhea]. / Utilidad diagnóstica de la colonoscopia y evaluación histológica en el estudio de pacientes con diarrea crónica.

INTRODUCTION: Patients with chronic diarrhea often undergo colonoscopy evaluation, however, the performance of biopsies or ileoscopy remains controversial. OBJECTIVE: To evaluate the usefulness of colonoscopy plus biopsies in the study of patients with chronic diarrhea. MATERIALS AND METHODS: We retrospectively reviewed patients with chronic diarrhea who underwent colonoscopy between 2015 and 2019. Patients with incomplete data, HIV infection, abnormal endoscopic findings, colonoscopy without blind assessment, being on empiric treatment for diarrhea, and poor diagnosis were excluded. preparation. A descriptive analysis of the characteristics of the patients, histopathological findings and comparison of signs and symptoms according to histopathological finding was performed. RESULTS: 535 patients with chronic diarrhea were evaluated, of these, 283 (52.8%) underwent biopsies. In 55.1% (n=156) of the biopsies some final histopathological diagnosis was obtained. Histopathological diagnoses corresponded to ulcerative colitis (n=3), Crohn's disease (n=5), lymphocytic colitis (n=6), collagenous colitis (n=12), eosinophilic colitis (n=13), infectious colitis (n=13), Melanosis coli (n=15), nonspecific colitis (n=57) and other histological changes (n=32). Crohn's disease was only documented in biopsies of the ileum (p<0.001), ulcerative colitis was only diagnosed in biopsies of the sigmoid rectum (p=0.007), infectious colitis in its highest proportion (30.7%) was documented in biopsies of the right colon (p=0.028). CONCLUSION: Colonoscopy and biopsies are useful in the investigation of patients with chronic diarrhea, obtaining a histological diagnosis in 55% of patients. Ileoscopy complemented colonoscopy findings to a lesser extent.

High risk of microscopic colitis after Campylobacter concisus infection: population-based cohort study.

OBJECTIVE: Microscopic colitis (MC) encompasses the two histopathological distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). In this Danish population-based cohort study, we examined the risk of MC following stool culture with Campylobacter concisus, C. jejuni, non-typhoidal Salmonella or a culture-negative stool test. DESIGN: We identified patients with a first-time positive stool culture with C. concisus, C. jejuni, non-typhoidal Salmonella or negative stool test, from 2009 through 2013 in North Denmark Region, Denmark, and matched each with 10 population comparisons. All subjects were followed up until 1 March 2018 using Systematised Nomenclature of Medicine codes from The Danish Pathology Register for incident diagnoses of CC and LC. We computed risk and adjusted HRs with 95% CIs for MC among patients and comparisons. RESULTS: We identified 962 patients with C. concisus, 1725 with C. jejuni, 446 with Salmonella and 11 825 patients with culture-negative stools. The MC risk and HR versus comparisons were high for patients with C. concisus (risk 6.2%, HR 32.4 (95% CI 18.9 to 55.6)), less for C. jejuni (risk 0.6%, HR 3.7 (95% CI 1.8 to 7.7)), low for Salmonella (risk 0.4%, HR 2.2 (95% CI 0.5 to 10.8)) and for patients with negative stool testing (risk 3.3%, HR 19.6 (95% CI 16.4 to 23.4)). After exclusion of the first year of follow-up, the HRs were 9.3 (95% CI 4.1 to 20.1), 2.2 (95% CI 0.9 to 5.4), 1.3 (95% CI 0.2 to 11.1) and 5.6 (95% CI 4.6 to 7.2), respectively. CONCLUSION: A high risk of MC was observed following C. concisus in stools. Further studies are needed to elucidate any underlying biological mechanisms.

Biopsies From Ascending and Descending Colon Are Sufficient for Diagnosis of Microscopic Colitis.

BACKGROUND & AIMS: Lymphocytic and collagenous colitis are types of microscopic colitis (MC) that commonly cause chronic watery diarrhea, but there are no macroscopic features of MC that can be detected during colonoscopy. Endoscopists therefore often collect multiple random colonic biopsies, potentially oversampling, increasing times of colonoscopy and slide review. We sought to identify sites from which biopsies could be taken and analyzed to identify patients with MC with a high level of sensitivity and determine the appropriate number of biopsies to take at these sites. METHODS: We performed a retrospective study using biopsies from 101 consecutive patients with MC (52 cases of collagenous colitis, 42 cases of lymphocytic colitis, 7 combined cases), without comorbidities, from 2017 through 2018. Slides were reviewed, and the proportion of biopsies that were diagnostic of MC were calculated at each biopsy site. RESULTS: The proportions of biopsy fragments from each site of the colon found to be positive for MC were as follows: cecum, 90.0%; ascending colon, 96.9%; hepatic flexure, 77.8%; transverse colon, 95.7%; splenic flexure, 75.0%; descending colon, 85.0%; sigmoid colon, 90.9%; and rectum, 82.2%. For biopsies labeled random, 95.7% were positive for MC. When findings from ascending and descending colon biopsies were combined, 100% of MC cases were detected. CONCLUSIONS: MC can be detected with certainty by analyzing biopsies from the ascending and descending colon. Fewer biopsies than were collected from our cases are sufficient for diagnosis. We propose a Western protocol (taking 2 biopsies from each of the ascending and descending colon) in evaluation of patients for MC.

Microscopic Colitis Is Characterized by Intestinal Dysbiosis.

The critical role of the gut microbiome in microscopic colitis (MC) is evident by the observation that fecal diversion is associated with resolution of mucosal inflammation while restoration of fecal stream is associated with recurrence of disease.1 Characterization of the composition and function of the gut microbiome in MC therefore could provide insights into disease pathogenesis.

Microscopic Colitis: A Challenging Disorder.

BACKGROUND: The clinical importance of microscopic colitis (MC) is increasing. This is explained by both the increasing incidence and the challenges posed by the disease. However, recent MC data also reveal a number of doubts and uncertainties. SUMMARY: This review focuses on current knowledge of MC and highlights the various controversies and criticisms regarding the clinical data about definitions, subtypes, pathogenesis, diagnosis, and treatment of this condition. Key Messages: The diagnosis of MC is based on histology, which distinguishes 2 subtypes. However, transitional forms often cause misclassification, which calls into question the reality (specificity, meaning) of the distinction between the 2 forms. The location of the colon biopsy is not defined by international consensus. There is no credible, clear explanation for the incidence increase. The pathogenesis is unknown, probably multifactorial, but the importance of the immunological background is increasing. The natural history of the disease and the underlying cause of relapses are unclear. It is suggested that MC would be the prelude of IBD. Further data collection is needed to clarify these issues.