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Objective To date, there are no epidemiological data on microscopic colitis (MC) in France. The aim of this study was to determine the incidence of MC in the Somme department in Northern France, to evaluate clinical characteristics, and to search for risk factors for both collagenous colitis (CC) and lymphocytic colitis (LC). Design Between January 1, 2005, and December 31, 2007, four pathology units in the Somme department recorded all new cases of MC diagnosed in patients living in the area. Colonic biopsies were reviewed by 4 pathologists together. For each incident case, demographic, clinical, endoscopic, and biological data were collected according to methodology of the EPIMAD registry. Results One hundred and thirty cases of MC, including 87 CC and 43 LC, were recorded during the three-year study. The mean annual incidence for MC was 7.9/10 5 inhabitants, 5.3/10 5 inhabitants for CC, and 2.6/10 5 inhabitants for LC. Annual standardized incidence of Crohn’s disease and ulcerative colitis in the EPIMAD registry during the same period (2005–2007) were 7.4/10 5 and 4.9/10 5 , respectively. Median age at diagnosis was 63 years for MC, 70 for CC, and 48 for LC. The female-to-male gender ratio was 3.5 for MC, 4.1 for CC, and 2.6 for LC. Median time to diagnosis was 8 weeks. Chronic diarrhea and abdominal pain were, respectively, present in 93 and 47 % of the cases. An autoimmune disease was associated in 28 % of MC cases. At diagnosis, proton pump inhibitor treatment was more often reported in CC than in LC (46 vs 16 %; p  = 0.003). Budesonide was effective on diarrhea in 77 % of patients, and thirteen percent of patients became steroid dependent. Conclusion This population-based study shows that the incidence of MC in France is high and similar to Crohn’s disease incidence and confirms that this condition is associated with female gender, autoimmune diseases, and medications.

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.

Microscopic colitis (MC) is a relatively common cause of chronic watery diarrhea, especially in older persons. Associated symptoms, including abdominal pain and arthralgias, are common. The diagnosis is based upon characteristic histological findings in the presence of diarrhea. The two types of MC, collagenous and lymphocytic colitis, share similar clinical features, with the main difference being the presence or absence of a thickened subepithelial collagen band. There are several treatment options for patients with MC, although only budesonide has been well studied in multiple controlled clinical trials. This review will describe the clinical features, epidemiology, pathophysiology, diagnostic criteria, and treatment of patients with MC.

Abstract Background For unidentified reasons, possibly due to increased immune surveillance, patients with collagenous colitis (CC) and lymphocytic colitis (LC), both forms of microscopic colitis (MC), have lower risk of colorectal cancer than controls and ulcerative colitis (UC) patients. Levels of secreted and cell-bound mediators in MC patients with active disease and in histological remission (HR) compared to UC patients and controls were investigated. Methods Median fluorescence intensity of 54 analytes in colonic biopsies from patients with active CC (n = 21), LC (n = 11), and UC (n = 19); CC-HR (n = 6), LC-HR (n = 9), UC in remission (n = 19), non-diarrhea controls (n = 48), and diarrhea controls (n = 25) was measured using Luminex. Results Granzyme B and CCL5 levels were higher in active CC than in UC, whereas CCL4 and CD163 levels were similar in CC and UC, and both groups had higher levels of matrix metalloproteinase (MMP)-1, MMP-3, and tumor necrosis factor receptor II than both control groups. APRIL, BAFF, BCMA, CCL20, CXCL8, chitinase 3-like 1, pentraxin-3, Fas, and IL-33 were higher in UC than MC. Increases in 4-1BB and perforin in MC compared to controls were lower than in UC. Levels of gp130 and IL-6Rα were decreased in MC but increased in UC compared to controls. Conclusions Microscopic colitis patients exhibit increased levels of several analytes, including some associated with CD8+ T lymphocytes, suggesting a different pathogenesis of MC compared to UC. Higher levels of MMP-1 and MMP-3 in CC than LC indicate separate disease entities. Lay Summary Microscopic colitis patients have elevated colonic levels of numerous analytes compared to controls, with some being higher than in ulcerative colitis patients and associated with CD8+ cytotoxic T lymphocytes. These differences imply distinct pathogeneses of these diseases. Graphical Abstract Graphical Abstract

Background Microscopic colitis (MC), comprising lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel disease with increasing incidence. MC etiopathogenesis remains unknown; however, altered colonic epithelial integrity may underlie uncontrolled luminal antigen passage, triggering immuno‐inflammatory responses. Objective The aim of this study was to further define the involvement of the colonic epithelium in MC. Methods A paired transcriptomic and proteomic analysis followed by epithelial ultrastructural examination was performed on colonic biopsies from LC and CC patients, and from irritable bowel syndrome with a predominance of diarrhoea (IBS‐D) and healthy subjects (H) as control groups. The impact of budesonide therapy on the epithelial structure was also evaluated in CC. Results MC patients exhibited decreased expression of inter‐microvilli adhesion and actin‐bundling proteins, accompanied by increased expression of actin‐membrane connection proteins compared to both control groups. Distinct molecular differentiated CC and LC, which translated into differential ultrastructure abnormalities. The colonic microvilli in CC patients were shorter in length and fewer in number, with partial restoration following budesonide treatment, whereas LC showed a reduction solely in microvilli number. A negative correlation was found between daily stool frequency and SPATN1 and ATP8B1 protein levels in CC patients. Conclusions Molecular dysregulation and aberrant ultrastructure of the colonic brush border feature the colonic epithelium in LC and CC. These previously undescribed findings provide new perspectives for further defining MC pathogenesis and identifying biomarkers for diagnosis, prognosis and treatment of this debilitating and prevalent disease. Key Summary Summarise the established knowledge on this subject ◦ Microscopic colitis (MC) is a chronic immune‐mediated disease characterized by colonic mucosal inflammation and barrier dysfunction, but a deeper characterization of colonocytes is lacking. What are the significant and/or new findings of this study? ◦ This study is the first to MC identify molecular and ultrastructural alterations of the brush border in colonocytes in lymphocytic colitis (LC) and collagenous colitis (CC). ◦ The uniqueness of this study relies on the identification of a molecular phenotype of the brush border that differentiates from healthy controls and, notably, from the closest diarrhoeal disorder, irritable bowel syndrome with a predominance of diarrhoea. ◦ Given the fundamental role of the brush border in maintaining intestinal homoeostasis and regulating epithelial barrier function, our study sets the basis for the identification of new predictive diagnostic and/or prognostic biomarkers for both LC and CC, as well as new potential therapeutic targets.

Background Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort. Methods Women ( n  = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) ( n  = 92) and lymphocytic colitis (LC) ( n  = 66) or MC with one episode of the disease ( n  = 70) and refractory MC ( n  = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits. Results MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p  = 0.05) and MC with one episode (12.9% vs. 2.3%; p  = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p  = 0.037) and refractory MC (38.6% vs. 20.0%; p  = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p  = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020–17.469; p  = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042–1.506; p  = 0.058). Conclusion Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities.

Background An association has been reported between celiac disease (CD) and microscopic colitis (MC). However, large, population‐based cohort studies are rare. Objective To systematically examine the association between CD and MC in a large, nationwide cohort. Methods We conducted a nationwide population‐based matched cohort study in Sweden of 45,138 patients with biopsy‐verified CD (diagnosed in 1990–2016), 223,149 reference individuals, and 51,449 siblings of CD patients. Data on CD and MC were obtained from all (n = 28) pathology departments in Sweden. Adjusted hazard ratios (aHRs) were calculated using Cox regression. Results During follow‐up, 452 CD patients and 197 reference individuals received an MC diagnosis (86.1 vs. 7.5 per 100,000 person‐years). This difference corresponded to an aHR of 11.6 (95% confidence interval [CI] = 9.8–13.8) or eight extra MC cases in 1000 CD patients followed up for 10 years. Although the risk of MC was highest during the first year of follow‐up (aHR 35.2; 95% CI = 20.1–61.6), it remained elevated even after 10 years (aHR 8.1; 95% CI = 6.0–10.9). Examining MC subtypes lymphocytic colitis (LC) and collagenous colitis (CC) separately, the aHR was 12.4 (95% CI = 10.0–15.3) for LC and 10.2 (95% CI = 7.7–13.6) for CC. MC was also more common before CD (adjusted odds ratio [aOR] = 52.7; 95% CI = 31.4–88.4). Compared to siblings, risk estimates decreased but remained elevated (CD and later MC: HR = 6.2; CD and earlier MC: aOR = 7.9). Conclusion Our study demonstrated a very strong association of MC with CD with an increased risk of future and previous MC in CD patients. The magnitude of the associations underscores the need to consider the concomitance of these diagnoses in cases in which gastrointestinal symptoms persist or recur despite a gluten‐free diet or conventional MC treatment. The comparatively lower risk estimates in sibling comparisons suggest that shared genetic and early environmental factors may contribute to the association between CD and MC.

Abstract Background The term “incomplete microscopic colitis” (MCi) has been suggested to define patients with chronic watery diarrhea not fulfilling the complete histologic criteria for MC. There are inconsistent data on the epidemiology of MCi and the optimal management of these patients. Methods A systematic search of randomized control trials (RCTs) and observational studies of adults with biopsy-proven MCi (incomplete lymphocytic colitis and collagenous colitis) was conducted using Cochrane, Medline, Scopus, and Embase from inception to May 6, 2025. Data were extracted on (1) incidence and prevalence of MCi, (2) patient features and risk factors, (3) clinical response with treatment, and (4) relapse after treatment cessation. Data were pooled using the random-effects model to calculate weighted pooled estimates and 95% confidence intervals (CIs). Results Of 136 potentially relevant publications identified, 49 passed abstract screening, and 17 studies (1 RCT and 16 observational) were included, with a total of 1370 patients with MCi (median age of 62 years and 69.6% women). The incidence rate of MCi ranged from 0.96 to 5.0 cases per 100 000 person-years. The pooled proportion of concurrent autoimmune disease with MCi was 18% (95% confidence interval [CI], 0.07-0.28; I2 = 95%), and 46% (95% CI, 0.28-0.64; I2 = 95%) were on medications associated with microscopic colitis (MC). The pooled clinical remission rate with any induction therapy was 78% (95% CI, 0.68-0.89; I2 = 81%) and 85% (95% CI, 0.72-0.98; I2 = 88%) with budesonide. Conclusions Patients with MCi share similar characteristics with full MC including demographics, risk factors, and response to therapy, indicating that the histologic criteria for MC should potentially be broadened. Lay Summary This systematic review and meta-analysis includes 17 studies evaluating the clinical characteristics and treatment response of patients with incomplete microscopic colitis. We demonstrate that these patients share similar demographics, risk factors, and response to therapy compared with complete microscopic colitis.

Microscopic colitis is an inflammatory bowel disease (IBD) comprising two clinically undiscernible entities: collagenous colitis and lymphocytic colitis. Collagenous colitis associates with HLA genes and displays a Th1/Tc1–Th17/Tc17 profile with pericryptal myofibroblast activity, water malabsorption and secondary fluid loss due to altered osmoregulation. Conversely, lymphocytic colitis lacks genetic associations and displays a Th1/Th2 profile and paracellular/transcellular permeability. Lymphocytic colitis subclassifies into channelopathic lymphocytic colitis due to unique alteration of ion and organic acid transport that could result from drug exposure, and inflammatory lymphocytic colitis due to the involvement of moderate immune responses compared to collagenous colitis. As microscopic colitis mucosa remains intact and immune cells seem to stay inactive, microscopic colitis is an ideal model to explore early stages of IBD if collagenous colitis and lymphocytic colitis are studied as distinct entities. Exploiting multiomic approaches and established biobanks will ensure validation of microscopic colitis patient stratification, and deepening into pathomechanisms which could enable precision medicine.

BackgroundMicroscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce.AimsTo compare clinical characteristics and treatment response by age at diagnosis.MethodsThis 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.ResultsWe 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).ConclusionsThere 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.