Microscopic Colitis and Celiac Disease: Sharing More than a Diagnostic Overlap.

Microscopic colitis (MC) is an emergent group of chronic inflammatory diseases of the colon, and celiac disease (CD) is a chronic gluten-induced immune-mediated enteropathy affecting the small bowel. We performed a narrative review to provide an overview regarding the relationship between both disorders, analyzing the most recent studies published at the epidemiological, clinical and pathophysiological levels. In fact, MC and CD are concomitantly prevalent in approximately 6% of the cases, mainly in the subset of refractory patients. Thus, physicians should screen refractory patients with CD against MC and vice versa. Both disorders share more than a simple epidemiological association, being multifactorial diseases involving innate and adaptive immune responses to known or unknown luminal factors based on a rather common genetic ground. Moreover, autoimmunity is a shared characteristic between the patients with MC and those with CD, with autoimmunity in the latter being quite well-established. Furthermore, CD and MC share some common clinical symptoms and risk factors and overlap with other gastrointestinal diseases, but some differences exist between both disorders. More studies are therefore needed to better understand the complex mechanisms involving the common pathogenetic ground contributing to the CD and MC epidemiological association.

Coeliac Disease and Microscopic Colitis: The Largest Study Assessing Prognosis and Risk of Hospital Admission.

Microscopic colitis (MC) and coeliac disease (CD) are common associated gastrointestinal conditions. We present the largest study assessing hospitalisation in patients with MC and the effect of a concomitant diagnosis of CD. Data were retrospectively collected between January 2007 and December 2021 from all patients diagnosed with MC and compared to a database of patients with only CD. In total, 892 patients with MC (65% female, median age 65 years (IQR: 54-74 years) were identified, with 6.4% admitted to hospital due to a flare of MC. Patients admitted were older (76 vs. 65 years, p < 0.001) and presented with diarrhoea (87.7%), abdominal pain (26.3%), and acute kidney injury (17.5%). Treatment was given in 75.9% of patients, including intravenous fluids (39.5%), steroids (20.9%), and loperamide (16.3%). Concomitant CD was diagnosed in 3.3% of patients and diagnosed before MC (57 versus 64 years, p < 0.001). Patients with both conditions were diagnosed with CD later than patients with only CD (57 years versus 44 years, p < 0.001). In conclusion, older patients are at a higher risk of hospitalisation due to MC, and this is seen in patients with a concomitant diagnosis of CD too. Patients with MC are diagnosed with CD later than those without.

Microscopic colitis found together with celiac disease in a female population is associated with one episode of lymphocytic colitis.

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.

Diagnosis and Pharmacological Management of Microscopic Colitis in Geriatric Care.

Microscopic colitis, a diagnosis under the umbrella term of inflammatory bowel disease, is a prevalent cause of watery diarrhea, often with symptoms of urgency and bloating, typically observed in older adults aged ≥ 60 years. Its incidence has been reported to exceed those of ulcerative colitis and Crohn's disease in some geographical areas. Although nonpathognomonic endoscopic abnormalities, including changes of the vascular mucosal pattern; mucosal erythema; edema; nodularity; or mucosal defects, e.g., "cat scratches" have been reported, a colonoscopy is typically macroscopically normal. As reliable biomarkers are unavailable, colonoscopy using random biopsies from various parts of the colon is compulsory. Based on the histological examination under a microscope, the disease is divided into collagenous (with a thickened subepithelial collagenous band) and lymphocytic (with intraepithelial lymphocytosis) colitis, although incomplete forms exist. In routine clinical settings, the disease has a high risk of being misdiagnosed as irritable bowel syndrome or even overlooked. Therefore, healthcare providers should be familiar with clinical features and rational management strategies. A 6-8-week oral budesonide treatment course (9 mg/day) is considered the first-line therapy, but patients often experience relapse when discontinued, or might become intolerant, dependent, or even fail to respond. Consequently, other therapeutic options (e.g., bismuth subsalicylate, biologics, loperamide, bile acid sequestrants, and thiopurines) recommended by available guidelines may be prescribed. Herein, clinically meaningful data is provided based on the latest evidence that may aid in reaching a diagnosis and establishing rational therapy in geriatric care to control symptoms and enhance the quality of life for those affected.

Microscopic Colitis: A Diagnostic Challenge in Patients with Irritable Bowel Syndrome.

BACKGROUND AND AIMS: Irritable Bowel Syndrome (IBS) is one of the most frequently diagnosed gastrointestinal disease with a prevalence of 4.1% in the general population. It is diagnosed using the Rome IV criteria. Microscopic colitis (MC), collagenous/lymphocytic colitis is a cause of chronic, watery, non-bloody diarrhea. It is a real challenge to diagnose MC in patients with IBS. The aims of the study were to determine the prevalence of MC in patients initially diagnosed with IBS, as well as to correlate fecal calprotectin levels with the endoscopic findings and microscopic inflammation in MC. METHODS: This is a retrospective study conducted in a single tertiary center with over 89 IBS patients for a period of 4 years. The patients included were patients diagnosed with IBS predominant diarrhea (IBS-D) and mixed IBS (IBS-M) using the Rome IV criteria. Total colonoscopy was performed in these patients, multiple biopsies being taken and calprotectin levels were measured. RESULTS: Out of a total of 89 IBS-D patients, 58 patients (65.2%) had no microscopic lesions, 12 patients (13.5%) had diverticular disease, 9 patients (10.1%) had non-specific chronic inflammation of the colon mucosa and 10 patients (11.2%) were diagnosed with MC. The calprotectin levels ranged from 49 µg/g to 213 µg/g. Of a total of 10 patients diagnosed with MC, 6 (60%) of them had calprotectin levels <100 µg/g and 4 (40%) had calprotectin levels >100 µg/g. The fecal calprotectin levels were higher in patients diagnosed with MC compared to those who had no microscopic lesions at the histological exam and it was also correlated with the grade of colonic microscopic inflammation. CONCLUSIONS: Microscopic colitis is less familiar to physicians and can be clinically misdiagnosed as IBS-D. An early and correct diagnosis is important for an accurate therapy.

[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).

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

BACKGROUND: Microscopic colitis (MC) has been linked to several autoimmune conditions. Results from previous studies on the association with rheumatoid arthritis (RA) have been inconsistent. AIM: To assess the risk of future RA in MC. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Dietary Calcium and Risk of Microscopic Colitis.

BACKGROUND: Microscopic colitis (MC) is an increasingly common cause of watery diarrhea particularly in older individuals. The role of diet in MC has received little study. METHODS: We conducted a case-control study at a single institution enrolling patients referred for elective outpatient colonoscopy for diarrhea. Patients were classified as cases with MC or non-MC controls after a review of colon biopsies by 1 research pathologist. Study subjects were interviewed by a trained telephone interviewer using a validated food frequency questionnaire. Adherent microbes were evaluated from colonic biopsies using 16s rRNA sequencing. RESULTS: The study population included 106 cases with MC and 215 controls. Compared with controls, the cases were older, better educated, and more likely to be female. Cases with MC had lower body mass index and were more likely to have lost weight. Subjects in the highest quartile of dietary calcium intake had a lower risk of MC compared with those in the lowest quartile (adjusted odds ratio 0.22, 95% confidence interval 0.07-0.76). The findings were not explained by dairy intake, body mass index, or weight loss. We found that dietary calcium intake had significant associations with the abundance of Actinobacteria and Coriobacteriales in the microbial community of colonic biopsies. DISCUSSION: Compared with patients with diarrhea, cases with MC had a lower intake of dietary calcium. Diet can be associated with alterations in the gut microbiota and with luminal factors that could affect the risk of MC.

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

BACKGROUND AND AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Predominant Antibody Deficiency and Risk of Microscopic Colitis: a Nationwide Case-Control Study in Sweden.

PURPOSE : Predominant antibody deficiency (PAD) disorders, including common variable immunodeficiency (CVID), have been linked to increased risk of gastrointestinal infections and inflammatory bowel diseases. However, there are limited data on the relationship between PAD, specifically CVID, and risk of microscopic colitis (MC). METHODS: We performed a nationwide case-control study of Swedish adults with MC diagnosed between 1997 and 2017 (n = 13,651). Data on biopsy-verified MC were retrieved from all of Sweden's pathology departments through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study. We defined predominant antibody deficiency using International Union of Immunologic Societies (IUIS) phenotypic classification. Individuals with MC were matched to population controls by age, sex, calendar year, and county. We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: The prevalence of PAD in MC was 0.4% as compared to 0.05% in controls. After adjustment for potential confounders, this corresponded to an aOR of 7.29 (95%CI 4.64-11.63). The magnitude of the association was higher for CVID (aOR 21.01, 95% 5.48-137.44) compared to other antibody deficiencies (aOR 6.16, 95% CI 3.79-10.14). In exploratory analyses, the association between PAD and MC was particularly strong among males (aOR 31.73, 95% CI 10.82-135.04). CONCLUSION: In this population-based study, predominant antibody deficiency was associated with increased risk of MC, particularly among males. Clinicians who encounter these patients should consider a detailed infectious history and screening for antibody deficiency.

Microbiome Composition in Microscopic Colitis: A Systematic Review.

Believed to be a rare cause of chronic diarrhoea, microscopic colitis (MC) is a condition with rising incidence. Many prevalent risk factors and the unknown pathogenesis of MC rationalise the need for studies on microbiota composition. PubMed, Scopus, Web of Science and Embase were searched. Eight case-control studies were included. The risk of bias was assessed with the Newcastle-Ottawa Scale. Clinical details on the study population and MC were poor. The most consistent result among the studies was a decreased Akkermansia genus in faecal samples. Other results were inconsistent due to the different taxonomic levels of the outcomes. Possible changes in different taxa were observed in patients who suffered from MC compared to healthy controls. The alpha diversity compared between MC and the diarrhoea control may suggest potential similarities. The beta diversity in MC compared to healthy and diarrhoeal populations showed no significant outcomes. The microbiome composition in MC possibly differed from the healthy control, but no agreement regarding taxa was made. It might be relevant to focus on possible factors influencing the microbiome composition and its relationship with other diarrhoeal diseases.

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

BACKGROUND AND AIMS: 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 ß-cells. We aimed to examine the association between T1D and MC. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Celiac disease and risk of microscopic colitis: A nationwide population-based matched cohort study.

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.

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

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Occurrence of Gastritis in Microscopic Colitis and Inflammatory Bowel Disease.

Multiple studies have shown that Helicobacter pylori infection is associated with a lower prevalence of inflammatory bowel disease (IBD).1,2 Besides chronic active gastritis (CAG) resulting from gastric infection with H pylori, pathologists have noticed another form of CAG, which is unrelated to H pylori infection and seems to cluster in patients with IBD.3-5 The aim of the present study was to compare the prevalence of H pylori-negative and H pylori-positive CAG in patients with IBD, and microscopic colitis (MC).

Drug Exposure and Risk of Microscopic Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by watery diarrhoea and a normal radiological and endoscopic appearance. Concern regarding a potential association between drug exposure and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association. METHODS: A systematic review and meta-analysis were performed to evaluate the incidence of MC associated with exposure to drug. The PubMed and Embase databases were searched to identify potential studies for inclusion. RESULTS: Twelve case-control studies were included in the meta-analysis. The results showed exposure to NSAID (OR, 1.64; 95% CI: 1.14-2.37; p < 0.001), PPI (OR, 2.36; 95% CI: 1.59-3.52; p < 0.001), SSRI (OR, 2.16; 95% CI: 1.5-3.13; p < 0.001), or aspirin (OR, 2.84; 95% CI: 1.4-5.76; p < 0.001) was related to the incidence of MC; however, such relationships in PPI and SSRI may be modulated by the selection of controls. Furthermore, we did not found a positive association with other drug exposure and MC. CONCLUSION: This meta-analysis indicated that NSAID, PPI, SSRI, or aspirin consumption may increase the risk for MC. Further studies exploring drug-induced microscopic colitis should include control groups with diarrhoea and not only healthy controls.