Search

A 60-year-old man with type 2 diabetes mellitus treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor was referred to our hospital because of his refractory watery diarrhea. Ileocolonoscopy revealed increased capillary growth, fine granular mucosa, and longitudinal mucosal tears mainly in the left side of the colon. A bioptic examination revealed thickened subepithelial collagen bands, thus confirming the diagnosis of collagenous colitis. Systemic steroid therapy was initiated, but his symptoms recurred when tapering the steroid. However, withdrawal of the DPP-4 inhibitor was successful even after the cessation of steroid therapy. We therefore considered his collagenous colitis to have been caused by the DPP-4 inhibitor.

BACKGROUND: Epidemiological studies from Europe and North America report an increasing incidence of microscopic colitis (MC) in the late twentieth century followed by a plateau. This population-based study assessed recent incidence trends and the overall prevalence of MC over the past decade. METHODS: Residents of Olmsted County, Minnesota diagnosed with collagenous colitis (CC) or lymphocytic colitis (LC) between January 1, 2011 and December 31, 2019 were identified using the Rochester Epidemiology Project. Clinical variables were abstracted by chart review. Incidence rates were age- and sex-adjusted to the 2010 US population. Associations between incidence and age, sex, and calendar periods were evaluated using Poisson regression analyses. RESULTS: A total of 268 incident cases of MC were identified with a median age at diagnosis of 64 years (range, 19–90); 207 (77%) were women. The age- and sex-adjusted incidence of MC was 25.8 (95% confidence interval [CI] 22.7–28.9) cases per 100,000 person-years. The incidence of LC was 15.8 (95% CI, 13.4–18.2) and CC 9.9 (95% CI, 8.1–11.9) per 100,000 person-years. A higher MC incidence was associated with increasing age and female sex (p

Microscopic colitis (MC) is an inflammatory disease of the colon characterized by persistent watery, nonbloody diarrhea. Subtypes of MC include collagenous and lymphocytic MC. Microscopic examination of colon tissue is crucial to confirming the diagnosis because the colonic mucosa often appears normal during flexible sigmoidoscopy or colonoscopy. We aim to determine the optimal sites and minimum number of colon biopsies required to diagnose MC from published studies. We systematically searched PubMed, Web of Science, Scopus, and Cochrane databases from inception until October 2020 using the following keywords: microscopic, lymphocytic, collagenous, colitis, biopsy, and biopsies. We screened the search results for eligibility and extracted data from the included studies. We pooled the numbers of biopsies provided by each study to calculate the mean number of biopsies, SD, and SEM. We included three retrospective cohort studies with 356 patients (148 collagenous, 192 lymphocytic, and 16 mixed), and the total number of biopsies were 1854. The mean number of biopsies that were recommended by the included studies are 4, 4, and 9, respectively. The pooled mean ± SD is 5.67 ± 2.89. The included studies reported that biopsies from the ascending colon (AC) and descending colon (DC) had the highest diagnostic rates. To ensure a high level of certainty in diagnosing MC, a total of six biopsies should be taken from the AC and DC (3 AC and 3 DC). However, special care should be directed toward differentiating MC from other forms of colitis. In addition, detailed and comparative studies are needed to provide stronger recommendations to diagnose MC.

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.

Background: The association between autoimmune diseases and microscopic colitis remains uncertain. Aims: To describe the association between autoimmune diseases and microscopic colitis by using a matched case–control design based on nationwide registry data. Methods: All adult Danish patients with a diagnosis of microscopic colitis from 2001 to 2018 were identified from nationwide registries. Odds of autoimmune diseases were compared between cases with microscopic colitis and sex- and age-matched controls from the background population in a 1:10 ratio and evaluated by logistic regression calculating odds ratios (OR) with 95% confidence intervals (CI) adjusted for comorbidity. Analyses were stratified according to sex, age and the subtypes of lymphocytic and collagenous colitis. Results: We identified 15 597 cases with microscopic colitis and matched to 155 910 controls. In total, 3491 (22%) of patients with microscopic colitis had concomitant autoimmune disease compared to 16 521 (11%) of controls (OR, 2.46; 95% CI, 2.36-2.56). Adjusting for comorbidities reduced the OR to 2.09 (95% CI, 2.01-2.19). Analyses showed increased ORs with 16 different autoimmune diseases, particularly of gastrointestinal and endocrine origin, and connective tissue disorders. The highest ORs were for coeliac disease (OR = 10.15; 95% CI, 8.20-12.6), Crohn’s disease (OR = 2.47; 95% CI, 2.10-2.91) and ulcerative colitis (OR = 6.73; 95% CI, 6.20-7.30). In stratified analyses younger age at diagnosis and collagenous colitis were associated with higher odds. Conclusion: Using nationwide registry data, microscopic colitis was associated with a wide range of autoimmune diseases, especially of gastrointestinal origin. The results suggest an autoimmune predisposition to microscopic colitis.

Background the rare occurrence of collagenous gastritis (CG) makes its epidemiology difficult to investigate. We designed a study to determine the demographic and clinical characteristics as well as the associations of CG with other upper gastrointestinal diseases in a large national clinicopathological database. Methods from the IDEA database we extracted all patients with histopathologically documented CG and, in a case-control study, we compared 168 subjects with and 1,286,165 subjects without CG using odds ratios (OR) with their 95% confidence intervals (CI). Results the prevalence of CG was 13 per 100,000 EGDs. CG was significantly more common among female than male patients (OR: 1.69, 95% CI: 1.20–2.39) and was characterized by a bi-modal age distribution (first peak in patients aged 10–19, second peak primarily in females aged >60 years). CG patients presented with diarrhea (18%), anemia (12%), weight loss (11%), and vomiting (10%). CG was significantly associated with other lymphocytic disorders of the upper gastrointestinal tract, including celiac sprue (2.12, 1.55–2.88), duodenal intraepithelial lymphocytosis (3.71, 2.30–5.98), and lymphocytic gastritis (23.2, 10.9–49.5). CG persisted in 69% of patients who underwent multiple consecutive endoscopies. Conclusions the epidemiologic features of collagenous gastritis reflect on different etiologies contributing to its occurrence in children and adults.

Background Olmesartan, which is an angiotensin II receptor blocker, reportedly causes spruelike enteropathy, with intestinal villous atrophy as its typical histopathological finding. Interestingly, collagenous and/or lymphocytic gastritis and colitis occur in some patients. We report the case of a 73-year-old Japanese man with a 2-month clinical history of severe diarrhea and weight loss. There were few reports in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. Case presentation We report a case of a 73-year-old man with a 2-month clinical history of severe diarrhea and weight loss. He had taken olmesartan for hypertension treatment for 5 years. Endoscopic examination with biopsies revealed intestinal villous atrophy and collagenous colitis. Suspecting enteropathy caused by olmesartan, which was discontinued on admission because of hypotension, we continued to stop the drug. Within 3 weeks after olmesartan discontinuation, his clinical symptoms improved. After 3 months, follow-up endoscopy showed improvement of villous atrophy but not of the thickened collagen band of the colon. However, the mucosa normalized after 6 months, histologically confirming that the preexistent pathology was finally resolved. Conclusions This report presents a case in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. In unexplained cases of diarrhea, medication history should be reconfirmed and this disease should be considered a differential diagnosis.

Background Collagenous colitis (CC) is an inflammatory bowel disease where chronic diarrhoea is the main symptom. Diagnostic markers distinguishing between CC and other causes of chronic diarrhoea remain elusive. This study explores neutrophil gelatinase-associated lipocalin (NGAL) and its mRNA lipocalin2 (LCN2) as histological and faecal disease markers in CC. Methods NGAL/LCN2 were studied in colonic biopsies from CC patients before and during budesonide treatment using RNA sequencing (n = 9/group), in situ hybridization (ISH) (n = 13–22/group) and immunohistochemistry (IHC) (n = 14–25/group). Faecal samples from CC (n = 3–28/group), irritable bowel syndrome diarrhoea (IBS-D) (n = 14) and healthy controls (HC) (n = 15) were assayed for NGAL and calprotectin. Results NGAL/LCN2 protein and mRNA expression were upregulated in active CC vs HC, and vs paired samples of treated CC in clinical remission. IHC and ISH localized increased NGAL/LCN2 mainly to epithelium of active CC, compared to almost absence in HC and treated CC. In contrast, calprotectin was solely expressed in immune cells. Despite great individual differences, faecal NGAL was significantly increased in active CC compared to HC, IBS-D and treated CC and had high test sensitivity. Faecal calprotectin levels were variably increased in active CC, but the values remained below usual clinical cut-offs. Conclusion NGAL/LCN2 is upregulated in the epithelium of active CC and reduced during budesonide-induced clinical remission to the level of HC and IBD-S. This was reflected in NGAL faecal concentrations. We propose NGAL as an IHC marker for disease activity in CC and a potential faecal biomarker discriminating CC from HC and IBS-D.

AimWe 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.MethodStudy 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.ResultsTwo 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 ConclusionClinicopathological 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.

Patients with chronic diarrhea often undergo colonoscopy evaluation, however, the performance of biopsies or ileoscopy remains controversial.To evaluate the usefulness of colonoscopy plus biopsies in the study of patients with chronic diarrhea.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.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 (p0.001), 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).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.

Collagenous colitis (CC) is a variant of microscopic colitis that causes chronic, non-bloody, and watery diarrhea. The natural history of CC is generally benign and serious complications are rare. Perforation, especially spontaneous perforation, is a particularly rare complication. A 90-year-old woman presented with acute abdominal pain. She was diagnosed with peritonitis due to colonic perforation, and partial colectomy was performed. Macroscopic findings showed well-circumscribed longitudinal ulcer, and a pathological examination revealed descending colon perforation with CC. She had no history of examination and the case was considered to be spontaneous. The postoperative course was uneventful and she had no recurrence of CC after changing from the suspected drug (lansoprazole) to an H2-blocker. The characteristics of perforation by CC are characteristic longitudinal ulcer and micro-perforation. If it can be diagnosed accurately, conservative treatment may be an option. In spontaneous cases, the history of medication and the site of perforation may assist in this decision.

Background In a subgroup of patients with microscopic colitis [MC], its histopathology changed from lymphocytic [LC] to collagenous colitis [CC] and vice versa. Previous studies have also observed histopathological transitions between MC and inflammatory bowel disease [IBD]. Aims The aim of the present study was to analyse the prevalence of such transitions in a large population of MC patients. Methods The Inform Diagnostics database is an electronic repository of histopathology records of patients distributed throughout the USA. In a cross-sectional study, we analysed the prevalence of changes in MC histology. Each prevalence was expressed as the rate per 100 MC patients with its 95% Poisson confidence interval. Results In a total population of 29 307 MC patients, our cross-sectional study focused on a subgroup of 4363 patients who underwent two or more consecutive colonoscopies between December 2008 and March 2020. Overall, 1.6% [95% CI 1.2–2.0%] of patients changed their MC phenotype from LC to CC, and 0.5% [0.3–0.7%] from CC to LC. Of 4363 MC patients, 414 [9.5%] were also diagnosed with IBD. In 2.9% [2.4–3.5%], MC and IBD were diagnosed as synchronous mucosal lesions. In 2.1% [1.7–2.6%], MC changed to IBD, and in 4.5% [3.9–5.2%] IBD changed to MC. Conclusions The analysis confirmed the synchronous occurrence of MC and IBD and transitions between the two diagnoses. In patients who fail therapy for either one of the two diseases, the gastroenterologist should search for changes in the underlying phenotype as a possible explanation.

PURPOSE: The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon.METHODS: Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases.RESULTS: In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC.CONCLUSION: Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.

Objectives: Crohn's disease and ulcerative colitis are associated with an increased risk to develop anemia, cutaneous diseases, liver diseases, malignancy, osteoporosis, rheumatic diseases, thromboembolism and uveitis. The association between these diseases and microscopic colitis (MC) is not known. The aim of the present systematic review was to examine associations between MC and diseases observed in association with Crohn's disease and ulcerative colitis.Material and methods: According to the review protocol, original articles which described the prevalence of abovementioned diseases in relation to MC, were searched for in PubMed, Embase and Web of Science.Results: After exclusion of duplicates, 928 articles remained. Based on relevancy of their title, abstract or type of article, 16 articles were ordered in full text and after assessment, nine articles could be included in the review. A second research strategy with individual diseases rendered further two articles. Seven articles covered malignancy/neoplasia, where four showed no association with malignancy and three a reduced association compared with controls. Four articles covering rheumatic diseases showed an association between these diseases and MC. One study showed an association between MC and osteoporosis, whereas one did not. One study showed an association between MC and cutaneous diseases, whereas anemia, eye diseases and thromboembolism showed no associations.Conclusions: Due to short follow-up time in small studies, with selection bias due to exclusion of former or prevalent malignancy in an older population, no conclusions can be drawn concerning the true association between MC and malignancy. Rheumatic diseases seem to be associated with MC.

Barotrauma or cat scratch is an unusual finding on colonoscopy. The etiology is unknown, but insufflation associated with increased rigidity of the colonic wall due to various pathological processes has been postulated as a pathogenic mechanism. Some authors observed the same associated with collagenous colitis, IBD(Inflammatory Bowel Diseases), intestinal ischemia, shunt colitis and intake of NSAIDs (Non-steroidal anti-inflammatory drugs). In all the cases described, Co2 was used for insufflation.

Introduction Collagenous colitis (CC) is a common cause of chronic diarrhea and is characterized by a subepithelial thickened collagen layer in the colonic mucosa. It shares many of the characteristics found in autoimmune diseases, but no autoantibodies have been identified. In CC, an imbalance in collagen turnover is evident. The purpose of the present study was to investigate whether any collagen-associated autoantibodies or other antibodies such as TPO and ASCA were present, and if levels of total IgE were increased. Methods Sera from women with active CC were analysed with ELISA for detection of autoantibodies against collagen type III and IV (Col III and IV), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and tenascin-C (TNC). Sera were also analysed for TPO, ASCA and total IgE. Healthy female blood donors served as controls. The cut-off value in the control group was defined as relative units > 97.5th percentile. Results Sixty-six women were included (mean age 60 years; range 31–74, mean disease duration 6 years; range 1–22). No autoantibody was significantly overexpressed in the CC population compared to controls. The mean disease duration was lower (p = 0.03) in the subjects who expressed collagen-associated autoantibodies (3.7 years; range 1–14), compared to those who did not (6.4 years; range 1–22). Treatment with budesonide was not associated with any of these autoantibodies. Conclusion No increased presence of the investigated antibodies could be found in the present study of CC. Neither could antibodies against ASCA or TPO, or elevated levels of IgE, be found. Consequently, no association was found between CC and these proteins, even though this may not be generalizable to other compounds in the collagen layer.

The role of surgery for collagenous colitis (CC) is unexplored. Either diverting stoma, subtotal colectomy with ileo-rectal anastomosis, and proctocolectomy with ileal pouch-anal anastomosis (IPAA) have been proposed. However, the optimal surgical strategy still needs to be defined. The aim of this short report is to report our experience with two cases of IPAA for CC. Two patients affected by histologically proven CC with watery diarrhea refractory to several lines of medical treatment underwent a laparoscopic proctocolectomy with IPAA at a tertiary referral hospital for the treatment of Inflammatory Bowel Disease in Belgium. A longer rectal cuff was left in place because of the absence of macroscopic inflammation of the rectal mucosa and the consequent negligible risk of cuffitis. No postoperative complications (90 days) occurred. Definitive pathological examination confirmed the diagnosis of CC. At six months, pouchoscopy revealed no signs of inflammation. One year after surgery, mean Öresland and Pouch Functional Score were 10.5 (8-13) and 11.5 (9-14). Functional outcomes after IPAA for CC were barely satisfactory. A high stool frequency not responding to high doses of anti-diarrheals was observed. This has also previously been reported for CC patients receiving a diverting stoma. Proctocolectomy and IPAA for medical refractory CC leads to acceptable short-term gastrointestinal functional outcomes which seems to be particularly affected by high stool frequency. For this reason, pouch surgery might not be the optimal indication for collagenous colitis.

Background Microscopic colitides are chronic immune-inflammatory bowel diseases. The typical presentation is chronic, watery diarrhoea. Inflammation mostly cannot be visualized via macroscopic inspection. The diagnosis thus requires histologic sampling. The clinical picture can vary. New investigations can prove valuable in setting up recommendations. Patients A total of 103 patients with microscopic colitis (MC) [28 lymphocytic colitis (LC) 27.2%, 75 collagenous colitis (CC) 72.8%] in the Clinical Centre of the University of Debrecen (tertiary care centre) were included, diagnosed between 1993 and 2020. We aimed for a retrospective analysis characterizing Hungarian MC patients. We sought to compare two subgroups of patients (with either LC or CC). Our investigation focussed on dominant alteration of stool habits, autoimmune and allergic comorbidities. Autoimmune diseases were diagnosed in 39% (40) of the patients, allergic diseases in 26.2% (27) of patients and 22.2% of tested patients had alimentary hypersensitivity to certain foods (18 cases out of 81 tested). Results Age of diagnosis was younger in LC (44.5 years, SD: 5.3 vs. 51.9 years, SD: 12.8, difference= 7.4 years p = .0151). Autoimmune diseases were equally frequent in the two groups (LC: 10 patients 36%, CC: 30 patients, 40%, difference: 4%, p = .7124). Food-linked hypersensitivities were more common in CC (LC: 1 patient, CC: 17 patients). Difference in allergic diseases (asthma, rhinitis, urticaria) did not differ between groups (LC: 6 patients, 21%; CC: 21 patients, 28%, difference: 7% p = .4739). One-third of the patients did not complain about chronic diarrhoea. These patients had chronic constipation as the main symptom (34 patients, 33%). Conclusion Pre-existing autoimmune and allergic diseases were common in patients with MC. Chronic watery diarrhoea is not experienced in many cases. The absence of certain symptoms should not be used to rule out the condition.

Background Epidemiological studies of microscopic colitis have shown varying but increasing incidence rates. Aim To assess the incidence of microscopic colitis in Sweden. Methods Nationwide cohort study performed in 1995-2015 based on biopsy reports. Age-specific and age-standardised incidence rates were calculated. Results We identified 13 844 patients with an incident diagnosis of microscopic colitis. Lymphocytic colitis (n = 9238) constituted 67% and collagenous colitis (n = 4606) 33% of microscopic colitis. The mean age at time of diagnosis of microscopic colitis was 60.2 years (58.6 for lymphocytic colitis, 63.3 for collagenous colitis). The lifetime risk of developing microscopic colitis was 0.87% in women (95% confidence interval, CI: 0.85-0.88) and 0.35% in men (95% CI: 0.34-0.36). From 2006, the overall incidence of microscopic colitis was approximately 10.5 cases per 100 000 person-years (95% CI: 9.8-11.3) with higher rates in women (72% of cases, incidence rate ratio = 2.4 (95% CI: 2.3-2.5) and the elderly with increasing rates up to 75-79 years. From 2006-2015, there was a significant increase of 1% per year (P = 0.02) in the overall microscopic colitis incidence rate in women; the estimated annual percent change was similar, although not statistically significant, in men (P = 0.15). Conclusions In Sweden, the incidence of microscopic colitis is still increasing in women, although the rate appears to be stabilising. The incidence is particularly high in women and the elderly up to age 75-79 years. Finally, across a lifetime, 1 in 115 females and 1 in 286 males are expected to be diagnosed with microscopic colitis and thus posing a considerable disease burden.

Collagenous colitis is a relatively rare disorder affecting mainly middle-aged women where they present with chronic non-bloody diarrhea. Both with lymphocytic colitis they compose microscopic colitis. The exact cause of collagenous colitis is still unknown however; many potential pathophysiologic mechanisms have been proposed but no convincing mechanism has been identified. Collagenous colitis has been linked to medications mainly NSAIDs, SSRIs, and PPIs. It is also believed that collagenous colitis is autoimmune disease and there are weak believe it could have some genetic inheritance. We reported before two cases of collagenous colitis developed in patients with Crohn's disease and ulcerative colitis while they were in complete mucosal remission after being treated with tumor necrosis factors-α inhibitors. In this article we will try to explain how collagenous colitis can develop in patients with inflammatory bowel disease especially those on tumor necrosis factors-α inhibitors.

Objective: Chronic watery diarrhoea is a classical symptom of collagenous colitis (CC). However, in some cases, the typical histologic findings of CC can be found in patients without this symptom. In this study we have performed a follow up on patients with a confirmed histological diagnosis of CC without the typical symptom watery diarrhoea Patients and methods: A structured medical record follow-up was performed on the subgroup of patients without watery diarrhoea but diagnosed with the typical CC histologic appearance in a previous study of microscopic colitis. Results: At follow up after a median time of 8 years (range: 0.33-12 years), five of these fifteen patients developed bowel symptoms but only two developed characteristic CC symptoms with watery diarrhoea. Conclusion: The majority of patients without chronic watery diarrhoea at diagnosis remained free from this symptom during follow up and only in a few cases symptoms attributed to CC developed.

Leflunomide belongs to the group of disease-modifying anti-rheumatic drugs (DMARDs) used in the treatment of psoriatic, rheumatoid, and reactive arthritis. Approximately 20% of patients will experience some adverse event, highlighting weight loss, abdominal pain and diarrhea. We describe the clinical, endoscopic, and histological findings in a patient with psoriatic arthritis (PA) who developed severe chronic diarrhea after drug use.

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

Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti-PD-1 (programmed cell death protein 1), and PD-L1 (programmed cell death protein-ligand 1) are emerging drugs that have radically changed treatment and prognosis of different types of tumors. However, despite their considerable benefits, immune checkpoint inhibitors are associated with numerous side effects involving several organs. Gastrointestinal toxicities represent some of these most common adverse events. While clinical presentation usually ranges from mild diarrhea to life-threatening colitis, typical endoscopic and histologic findings of immune-mediated colitis often resemble those of inflammatory bowel diseases. However, less common patterns are lymphocytic colitis and, rarely, collagenous colitis. Physician and pathologists must be aware of the wide spectrum of clinical and histological findings that may be encountered in immune-related gastro-intestinal toxicities. We report a rare and atypical case of collagenous colitis occurred in a woman affected by stage IV lung adenocarcinoma, on atezolizumab therapy.

Background and Aims The pathophysiology of the inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of mucosal samples from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and control subjects to gain insight into CC pathophysiology, identify genetic signatures linked to CC, and uncover potentially druggable disease pathways. Methods We performed whole transcriptome sequencing of CC samples from patients before and during treatment with the corticosteroid drug budesonide, CC steroid-refractory patients, UC patients, and healthy control subjects (n = 9–13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell (IEC) gene expression were analyzed by gene set enrichment and gene set variation analyses to identify significant pathways and cells, respectively, altered in CC. Leading genes and cells were validated using reverse-transcription quantitative polymerase chain reaction or immunohistochemistry. Results We identified an activation of the adaptive immune response to bacteria and viruses in active CC that could be mediated by dendritic cells. Moreover, IECs display hyperproliferation and increased antigen presentation in active CC. Further analysis revealed that genes related to the immune response (DUOX2, PLA2G2A, CXCL9), DNA transcription (CTR9), protein processing (JOSD1, URI1), and ion transport (SLC9A3) remained dysregulated even after budesonide-induced remission. Budesonide-refractory CC patients fail to restore normal gene expression, and displayed a transcriptomic profile close to UC. Conclusions Our study confirmed the implication of innate and adaptive immune responses in CC, governed by IECs and dendritic cells, respectively, and identified ongoing epithelial damage. Refractory CC could share pathomechanisms with UC., Graphical abstract

Aquaporin-5 (AQP5) is a member of a family of water channel proteins involved in the bidirectional transfer of water across cell membranes. Lymphocytic colitis (LC) and collagenous colitis (CC) are clinically similar diseases characterized by chronic watery diarrhea in patients with usually unremarkable colonic mucosa on colonoscopy. The aim of this study was to determine whether AQP5 expression in colonic epithelium is altered in LC and CC.Sections of formalin-fixed and paraffin-embedded colorectal biopsies from three control patients (CTL), 8 patients with chronic non-bloody diarrhea with biopsies negative for active inflammation or significant distortion (CTL-D), 8 patients with LC, and 5 with CC were stained for AQP5 using immunohistochemistry. The staining intensity was scored as 3 (strong), 2 (intermediate), 1 (weak), or 0 (no staining). Statistical analysis was performed using Prism 7 Statistical Soft-ware.AQP5 was strongly expressed (score 3) in the epithelial cells in all three CTL cases and all 8 CTL-D cases. In the 5 cases of CC, 3(60%) had score 3 and 2(40%) had score 2, but none had a score of 1 or 0. Of the 8 LC cases, 2(25%) had score 3, 3 had score 2(37.5%), and 3 had score 1(37.5%) (Colorectal AQP5 expression is reduced in most cases of LC. Markedly reduced AQP5 expression in LC may identify a subset of patients with suboptimal response to enteric steroid treatment. Additional larger studies are needed to confirm these findings.This abstract was presented in part at Digestive Diseases Week in San Diego, CA, May 2019.

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 MC patients diagnosed between 1990–2016 in Sweden matched to up to 5 general population controls according to age, sex, calendar year, and county. Cases of MC were identified using SNOMED codes from the ESPRESSO 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% 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 MC patients which was significantly higher than in controls (3.0%, P(comparison)

Summary Microscopic colitis (MC) is characterized by chronic watery diarrhea, endoscopically normal findings, and abnormal histology. While mostly encountered in adults, pediatric cases are rare and may show varying presentations. Our pathology data system was searched from 1984 to 2019 for patients ≤18 years of age with a lymphocytic colitis (LC) or collagenous colitis (CC) pattern of injury. Twenty-seven cases (23 LC and 4 CC) were retrieved. LC was more prevalent than CC (85% vs 15%, respectively) and affected slightly younger individuals (mean, 9.8 years versus 12.25 years). Immune dysregulation was documented in 11 (41%) patients. Most patients presented with watery diarrhea (n = 26, 96%) and either abdominal pain (n = 18, 67%), nausea/vomiting (n = 5, 19%), flatulence (n = 6, 22%), and/or weight loss (n = 1, 4%). A subset of patients (n = 10, 37%) demonstrated endoscopic abnormalities. Histologically, some patients with LC and CC displayed focal cryptitis or crypt abscess formation (n = 7, 26%) and focally increased crypt apoptosis (n = 9, 33%) in the absence of chronic injury. Clinical follow-up data were available for 23 (85%) patients with variable clinical responses recorded. Only 8 patients experienced complete symptom resolution. Twelve patients (11 LC and 1 CC) had subsequent biopsy material; of which, one developed histologic features of inflammatory bowel disease and another was found to have a CTLA-4 deficiency. Our study shows that pediatric patients with MC may have atypical clinical, histologic, and endoscopic findings and variable clinical responses. Underlying inflammatory and/or genetic conditions may be eventually unmasked, and genetic testing may be helpful in a small subset of patients.

There is an unmet need in investigating corticosteroid-sparing treatments for induction and maintenance of remission in microscopic colitis (MC). The authors' aim was to evaluate the outcomes of patients with MC treated with bile acid sequestrants (BAS).MC is a common chronic diarrheal illness. Budesonide is effective induction therapy, but relapses are high after cessation of treatment.Our cohort consisted of patients enrolled in our institutional MC registry, a biorepository of histology-confirmed diagnoses of MC. Patients receiving BAS for the treatment of MC were reviewed at each clinical visit for efficacy or ability to decrease budesonide maintenance dosing.The authors included 79 patients (29 collagenous colitis and 50 lymphocytic colitis) with a median follow-up period of 35 months (range, 1 to 120). Most patients were female individuals (78%) and the median age was 69 years (range, 29 to 87). BAS therapy was used in 21 patients who were budesonide-naive, with a response rate of 76% (16/21). In patients treated previously with budesonide, 46 patients were budesonide-dependent and given BAS as maintenance therapy. Of these patients, 23 (50%) were able to decrease their budesonide dosing and 9 (20%) were able to stop budesonide completely. Seven of 46 patients (15%) stopped BAS because of intolerance, perceived lack of benefit, or treatment of concomitant diarrhea illness.BAS may be an effective corticosteroid-sparing option in the treatment of MC and should be considered after budesonide induction. Larger controlled studies are needed to confirm the efficacy for long-term maintenance and tolerability of BAS in patients with MC.

Background and Aim Increased frequencies of T regulatory (Treg) cells, key players in immune regulation, have been reported in inflammatory bowel diseases, including collagenous colitis (CC). However, traditional Treg identification techniques might have misinterpreted the frequencies of Treg cells in CC. Thus, we investigated the presence of genuine Treg cells in CC. Methods Treg cells were analyzed in mucosal and peripheral blood samples of CC patients before and during treatment with the corticosteroid drug budesonide and in healthy controls. Samples were analyzed by flow cytometry by classifying CD3+CD4+ cells as activated FoxP3highCD45RA- Treg cells, resting FoxP3dimCD45RA+ Treg cells, and nonsuppressive FoxP3dimCD45RA- T helper cells. Traditional gating strategies that classified Treg cells as CD25highCD127low, FoxP3+CD127low, and CD4+CD25+FoxP3+ were also used to facilitate comparison with previous studies. Results Activated and resting Treg cell frequencies did not change in active CC mucosa or peripheral blood and were not affected by budesonide treatment. Instead, nonsuppressive FoxP3dimCD45RA- T helper cells were increased in active CC mucosa, and budesonide helped restore them to normal levels. In contrast, traditional Treg cell gating strategies resulted in increased Treg cell frequencies in active CC mucosa. No alterations were found in peripheral blood samples, independently of patient treatment or gating techniques. Conclusion Previously reported increase of Treg cells is a result of incomplete Treg phenotyping, which included nonsuppressive FoxP3dimCD45RA- T helper cells. Because budesonide did not affect Treg percentage, its therapeutic effect in CC might involve alternative mechanisms.

Immunotherapy has improved the overall survival of patients with metastatic melanoma. Inflammatory bowel disease-like colitis is the most frequent gastrointestinal serious adverse event in patients treated with immune-checkpoint inhibitors. Collagenous colitis is microscopic colitis. Only two cases of immune-checkpoint inhibitors induced collagenous colitis have been reported. A man in his early 70s was referred for a metastatic melanoma treated with nivolumab as the fourth line of treatment. During the 21st cycle, the patient complained of watery, nonbloody diarrhea (around six times per day). Rectosigmoidoscopy showed no mucosal lesion. A thickened subepithelial collagen band was evidenced by trichrome staining, which was suggestive of collagenous colitis. Nivolumab was stopped and the patient was treated with budesonide 9 mg/day in combination with loperamide and cholestyramine, leading to improvement of diarrhea. However, worsening of digestive symptoms during tapering of corticosteroid dose required the permanent discontinuation of nivolumab. Due to the very low number of cases reported to date and their different evolution under corticosteroids, it is not clear whether or not immune checkpoint inhibitors can be restarted in these patients.

BACKGROUND The long-term natural history of microscopic colitis remains uncertain. AIM To describe the mortality in a large unselected cohort of patients with microscopic colitis. METHODS All Danish patients above 18 years with an incident diagnosis of microscopic colitis from 2001 to 2018 were identified from nationwide registries and compared to age- and sex-matched controls (variable 1:10 ratio). Patients were categorised according to subtypes: lymphocytic colitis and collagenous colitis. The relative risk of death by any cause was analysed with Cox regression models estimating both crude and comorbidity-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Cause-specific death was evaluated with cumulative incidence functions. An E-value was calculated to address the impact of unmeasured confounding. RESULTS The final cohort consisted of 14 024 patients with microscopic colitis. The mean follow-up was 5.8 (standard deviation SD, 2.9) years and the mean age at diagnosis was 61.1 (SD 13.9) years, 70% were women and 41% were diagnosed with lymphocytic colitis. The main results showed a 25% increased risk of all-cause death in patients with microscopic colitis; however, the relative risk was attenuated to 9% when adjusting for comorbidities (95% CI, 1.05-1.14). The E-value indicates that unmeasured confounding could explain the residual observed increased all-cause mortality. Mortality was significantly increased in patients with both lymphocytic colitis (HR 1.15; 95% CI, 1.08-1.23) and collagenous colitis (HR 1.06; 95% CI, 1.01-1.12) in fully adjusted analyses. The absolute difference in death between patients with microscopic colitis and matches was 0.9% at 1 year, 2.8% at 5 years, 5.0% at 10 years and 3.0% at 15 years. Cumulative incidence functions showed that patients with microscopic colitis were more likely to die due to smoking-related diseases including ischemic heart and lung diseases, but had a significant decreased risk of death due to colorectal cancers (P

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.

Background and Aims Diarrhoea is a common, debilitating symptom of gastrointestinal disorders. Pathomechanisms probably involve defects in trans-epithelial water transport, but the role of aquaporin [AQP] family water channels in diarrhoea-predominant diseases is unknown. We investigated the involvement of AQPs in the pathobiology of collagenous colitis [CC], which features chronic, watery diarrhoea despite overtly normal intestinal epithelial cells [IECs]. Methods We assessed the expression of all AQP family members in mucosal samples of CC patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory CC patients and healthy controls. Samples were analysed by genome-wide mRNA sequencing [RNA-seq] and quantitative real-time PCR [qPCR]. In some patients, we performed tissue microdissection followed by RNA-seq to explore the IEC-specific CC transcriptome. We determined changes in the protein levels of the lead candidates in IEC by confocal microscopy. Finally, we investigated the regulation of AQP expression by corticosteroids in model cell lines. Results Using qPCR and RNA-seq, we identified loss of AQP8 expression as a hallmark of active CC, which was reverted by budesonide treatment in steroid-responsive but not refractory patients. Consistently, decreased AQP8 mRNA and protein levels were observed in IECs of patients with active CC, and steroid drugs increased AQP8 expression in model IECs. Moreover, low APQ8 expression was strongly associated with higher stool frequency in CC patients. Conclusion Down-regulation of epithelial AQP8 may impair water resorption in active CC, resulting in watery diarrhoea. Our results suggest that AQP8 is a potential drug target for the treatment of diarrhoeal disorders.

Background Evidence for second-line therapy in patients with microscopic colitis [MC] failing budesonide is scarce, although anti-tumour necrosis factors [anti-TNFs], methotrexate and azathioprine have been reported to be effective in small cohort studies. Vedolizumab, a monoclonal antibody targeting α4β7-integrin, prevents homing of T-cells to the gut. We evaluated clinical remission with vedolizumab in budesonide-refractory MC patients. Methods We solicited gastroenterologists in Europe and Canada for cases of MC treated with vedolizumab. Vedolizumab 300 mg IV was administered at weeks 0, 2 and 6, and then every 8 weeks. Clinical remission and histological remission were defined as less than three stools per day and normalization of histology, respectively, after induction treatment. Results Eleven cases were retrieved (nine females, lymphocytic colitis [LC] n = 5, collagenous colitis [CC] n = 6). Median [interquartile range] disease duration at vedolizumab initiation was 51 [29-70] months. Nine of 11 patients had failed one immunosuppressant and ten of 11 at least one anti-TNF agent. After three infusions of vedolizumab, clinical remission was observed in 5/11 patients [two LC and three CC] of whom three remained well with maintenance therapy [median duration of 13 months]. Biopsies were obtained from 9/11 patients. Histological remission was observed in 3/4 patients with clinical remission [2/3 CC, 1/1 LC] and 0/5 patients without clinical improvement. Conclusion In a series of highly refractory MC patients, vedolizumab induced clinical remission in 5/11 subjects, of whom 75% showed normalized histology. Larger randomized trials are needed to assess the efficacy of vedolizumab in patients with MC.

Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands. Two phenotypes of the disease have been described: a pediatric-onset and an adult-onset type. The adult-onset form is associated with collagenous colitis and autoimmune disorders. No effective treatment has been identified to date.We aim to describe the clinical features and outcomes of patients in our cohort and provide a summary of published pediatric cases with collagenous gastritis and colitis reported to date to gather information that will contribute to improved knowledge of this rare condition.A retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Children's Hospital, Melbourne, was performed. A literature review was also conducted.A total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%) patients had associated collagenous colitis. The most common clinical presentation was iron deficiency anemia. Nine (75%) patients were followed up, and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved in all patients on oral iron supplementation. Histologic improvement was only identified in one patient with the adult phenotype who had been treated with oral corticosteroids and azathioprine.Collagenous gastritis is a rare condition in children. A small proportion of children develop features of the "'adult" phenotype at a very young age. Patients with collagenous gastritis require long-term follow-up and monitoring of their disease. Further randomized clinical trials are needed to establish an effective therapeutic strategy.

Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes: collagenous colitis and lymphocytic colitis. Due to the increasing incidence and awareness of this disease over the last decades, several international guidelines have been recently published. However, there is still significant heterogeneity in the management of these patients, and treatments without solid scientific evidence support are often used in clinical practice. This article reviews the therapeutic role of budesonide in microscopic colitis and summarizes the current evidence regarding other treatments available for this disease, especially for the management of refractory patients. Finally, an updated treatment algorithm is proposed.