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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.

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.

Secukinumab an interleukin-17 (IL-17) monoclonal antibody inhibitor is currently approved for the treatment of rheumatological conditions, such as psoriasis and ankylosing spondylitis. Lymphocytic colitis, a phenotype of microscopic colitis, is a long-term inflammatory condition, is characterized by relapsing diarrhea. The specific entity of drug-induced lymphocytic colitis has been discussed with numerous individual cases being reported from around the world. Secukinumab has been linked with exacerbation of and de novo cases of inflammatory bowel disease. However, lymphocytic colitis in association with this drug has not been documented. The management of drug-induced lymphocytic colitis is complicated, as patients frequently exhibit spontaneous remission of symptoms. Removal of the offending agent has shown some benefit; however, some patients continue to exhibit symptoms months after drug cessation and washout. Although our patient’s lymphocytic colitis was benign and responded to the cessation Secukinumab, it is an important diagnosis to consider in patients with new onset relapsing diarrhea treated with biologics.

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.

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.

Lymphocytic colitis is a subtype of microscopic colitis that is mostly seen in adults. It presents mainly as chronic nonbloody diarrhea, with the hallmark of normal or near-normal endoscopy. In this case series, we are presenting 4 pediatric patients with lymphocytic colitis with prominent apoptosis of the colonic gland epithelium. Remarkably, all the patients have genetic mutations known to be associated with autoimmune enteropathy. Three patients have a CTLA4 mutation, and 1 patient has an STAT3 mutation. These mutations were previously reported in association with inflammatory bowel disease, but a specific connection with lymphocytic colitis has not been described. This report investigates the histopathology of such lesions in children and adolescents.

In the preceding article (part 1), we proposed the third type of microscopic colitis: colitis nucleomigrans (CN). Microscopically, the nuclei of surface‐lining columnar cells were migrated in chain to the middle part of the cells, and apoptotic nuclear debris was scattered in the cytoplasm beneath the nuclei. For ultrastructural analysis, buffered formalin‐fixed biopsy tissue of CN (n = 2) was dug out of paraffin blocks. After deparaffinization, tissue blocks were prepared with conventional sequences. Ultrathin sections were stained with uranyl acetate and lead citrate. Fine morphological preservation was satisfactory even after paraffin embedding. Apoptotic nuclear debris was localized within the cytoplasm beneath the migrated nuclei of the surface‐lining columnar cells. Abnormality of cytoskeletal filaments (actin, cytokeratin and tubulin) was scarcely recognized in the epithelial cytoplasm. Macrophages located in the uppermost part of the lamina propria phagocytized electron‐dense globular materials. Intraepithelial lymphocytes with scattered dense bodies were observed among the columnar cells. We suppose that altered apoptotic processes in the colorectal surface‐lining epithelial cells may be involved in the pathogenesis of CN. Mechanisms of nuclear migration to the unusual position or impairment of nuclear anchoring to the basal situation in the surface‐lining epithelial cells remain unsettled, because cytoskeletal components showed little ultrastructural abnormality.

Microscopic colitis (MC), encompassing collagenous colitis and lymphocytic colitis, is featured by chronic diarrhea, normal-looking endoscopic findings and unique microscopic appearance. After reviewing biopsied nonspecific colitis, we propose the third type of MC: colitis nucleomigrans (CN). Histopathological criteria of CN included: (i) chained nuclear migration to the middle part of the surface-lining columnar epithelium; (ii) apoptotic nuclear debris scattered below the nuclei; and (iii) mild/moderate chronic inflammation in the lamina propria. Thirty-three patients (M:F = 20:13; median age 63 years, range 17-88) fulfilled our criteria. Seven cases demonstrated MC-like clinical/endoscopic features. Mucosal reddening with or without erosion/aphtha was endoscopically observed in the remaining 26 cases with inflammatory bowel disease (IBD)-like features: occult/gross hematochezia seen in 19, abdominal pain in two and mucin secretion in two. Cleaved caspase-3-immunoreactive apoptotic debris appeared more frequently in IBD-like CN than in MC-like CN, while CD8-positive intraepithelial lymphocytes comparably appeared in both. Proton pump inhibitors (PPIs) were administered in five (71%) cases with MC-like features, and in three diarrhea improved after drug cessation. In IBD-like CN cases, eight (31%) received PPIs. Four patients received chemotherapy against malignancies. Four patients associated immune-related disorders. Microscopic appearance of CN also appeared in a remission state of ulcerative colitis (12/20 lesions).

Lymphocytic colitis (LC) is characterized by chronic watery diarrhea and unremarkable endoscopic findings. Only one case of LC presenting as multiple colonic polyps has been reported. We report a case series of histologic LC pattern of injury (LCPI), presenting as endoscopic polyps, and compare them with typical LC cases. Eighteen archived (2009-2019) polypoid LCPI cases without an associated cause of polyp, such as adenoma, hyperplastic change, or lymphoid aggregate, were retrieved from 17 (12 female and 5 male) patients. The clinical history and endoscopic findings were noted. A total of 40 conventional LC cases were used as controls. Fisher's exact test was performed to evaluate associations between two variables. The mean age of the patients was 61.1 years. The indication for colonoscopy was chronic watery diarrhea (56%), screening/surveillance (33%), and rectal bleeding (11%). The mean number and size of the polyps was 1.6 and 2.9 mm, respectively. Seventy-six percent were located in the left colon, and 48% were sessile. When biopsied (14/18; 78%), the background colonic mucosa showed LCPI. There was no significant difference in age, gender, and the average number of lymphocytes in the two groups. Hypertension and history of malignancy was more common in the polypoid LCPI group than in the control LC group (P 0.05). LCPI may present as endoscopic polyps, frequently in patients with hypertension and history of malignancy. Polypoid LCPI may be a harbinger of LCPI in the background nonpolypoid colonic mucosa. A subset of polypoid LCPI (56%) cases represents true LC.

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.

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.

In response to the report of Ong and colleagues of a series of patients with levodopa/dopa decarboxylase inhibitor associated microscopic colitis, we report a case of entacapone associated microscopic colitis. We agree that chronic diarrhoea in patients with Parkinson's disease should prompt consideration of drug-induced microscopic colitis as the cause.

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

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

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

Teriflunomide is an oral monotherapy used to treat relapsing multiple sclerosis. Although teriflunomide may be associated with gastrointestinal symptoms, these events are mild and self-limiting. We present a 39-year-old female who developed severe diarrhea and lost 20 pounds within 3 weeks of starting teriflunomide. Despite discontinuing teriflunomide and undergoing cholestyramine washout, her symptoms persisted. Celiac disease on genetic testing was positive, but no anti-transglutaminase and anti-endomysial antibodies were detected. She underwent colonoscopy and biopsy was consistent with lymphocytic colitis. Remission was achieved within days of starting budenoside. Our case describes a rare, but serious, gastrointestinal adverse event of teriflunomide.

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.

Lymphocytic colitis (LC) and LC incomplete (LCi) are common causes of chronic watery diarrhea. The diagnosis relies on clinical findings and histopathologic evaluation. The diagnostic criteria of LC are based on hematoxylin and eosin (HE) staining. However, supplementary immunohistochemical staining for highlighting the lymphocytes in borderline cases is now widely used. This change in diagnostics could lead to incorrectly diagnosing patients with LC and LCi if the present histologic criteria are used. The number of intraepithelial lymphocytes (IELs) was estimated and categorized in intervals based on HE- versus CD3-stained slides from patients with an HE diagnosis of normal colonic mucosa (n = 19), mucosa with nonspecific reactive changes (n = 24), LCi (n = 24), and LC (n = 40). The number of IELs was compared with clinical symptoms. Overall, the number of IELs was higher with CD3 stain compared with HE stain in 73% of cases, unchanged in 26% of cases, and lower in 1 case. The number of IELs detected was higher using the CD3 stain in 53%, 79%, 79%, and 75% of cases included as normal colonic mucosa, nonspecific reactive changes, LCi, and LC, respectively. Based on CD3 stain, 58% of the cases with nonspecific reactive changes fulfilled the HE criteria for LCi, and 79% of the cases with LCi fulfilled the HE criteria for LC. Automated image analysis of CD3-stained slides resulted in even higher numbers of IELs in all 4 diagnostic groups. Conclusively, our data support considering increased cutoff values for LCi and LC when assessed in CD3-stained specimens.

Patient: Male, 59 Final Diagnosis: Olmesartan associated enteropathy Symptoms: Diarrhea and weight loss Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Unusual or unexpected effect of treatment Background: Olmesartan, an angiotensin receptor blockade class of antihypertensive medication has recently been associated with a seronegative sprue like enteropathy. Patients typically present with diarrhea and weight loss often prompting exhaustive diagnostic workup. Discontinuation of the drug leads to dramatic recovery and hence, physicians need to be aware of olmesartan associated enteropathy (OAE) in order to avoid unnecessary testing. Case Report: A 59-year-old Caucasian male was admitted to the hospital with complaints of intractable diarrhea, vomiting and considerable weight loss. Medical history was notable for hypertension being treated with olmesartan. Workup for all potential infectious causes and celiac disease was negative. Eventually, a colonoscopy was performed due to his persistent symptoms and biopsy revealed lymphocytic colitis. An upper endoscopy was also performed, and histopathology of the duodenum revealed total villous blunting. In light of negative serology for celiac disease and after a detailed review of the patient’s medications, the possibility of olmesartan induced enteropathy was considered. Olmesartan was stopped and his symptoms resolved. A follow-up endos-copy done a few months later showed normal small bowel mucosa. Conclusions: This case demonstrates the need for a thorough medication review by healthcare providers especially after a full workup for the patient’s symptoms has already been performed. It also reiterates that having an awareness of rare side effects of common medications mitigates the need for extensive diagnostic testing.

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.

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 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.

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.

Microscopic colitis (MC) is the umbrella term for the conditions termed lymphocytic colitis (LC) and collagenous colitis (CC). LC with thickening of the subepithelial collagen band or CC with increased number of intraepithelial T- lymphocytes (IELs) is often seen in MC and may lead to difficulties in correct histological classification. We investigated the extent of overlapping features of CC and LC in 60 cases of MC by measuring the exact thickness of the subepithelial collagen band in Van Gieson stained slides and quantifying number of IELs in CD3 stained slides by digital image analysis. A thickened collagen band was observed in nine out of 29 cases with LC (31%) and an increased number of IELs in all 23 cases of CC (100%). There was no correlation between the thickness of the collagen band and number of IELs. Due to the increased number of IELs in all cases of CC we consider the lymphocytic inflammatory infiltration of the mucosa to be the essential histopathological feature of MC. However, although LC and CC are related due to the lymphocytic inflammation, the non-linear correlation of number of IELs and thickness of the collagenous band indicate differences in their pathogenesis.

Objective: Microscopic colitis (MC) is classically associated with normal or near-normal endoscopic appearances. However, non-specific macroscopic findings have been described, the importance of biopsy location for confirming a diagnosis of MC is unclear, and reported incidence data from the United Kingdom are limited. This study was designed to assess macroscopic features, incidence, demographics, and location and positivity of biopsy samples in MC. Materials and methods: Retrospective, cross-sectional study of individuals with newly diagnosed MC. Results: From 2010 to 2015, 540 cases of MC were reported. Macroscopic findings occurred in 16.5% (n = 89) cases, with trends towards increased frequency of ulceration or linear scarring in collagenous colitis (CC). The mean incidence of MC was 11.3 per 100,000 population/year, including 291 (53.9%) with CC (incidence 6.1 per 100,000/year), 203 (37.6%) with lymphocytic colitis (incidence 4.2 per 100,000/year) and 46 (8.5%) with MC, not otherwise specified. Most individuals were female (70.2%). Common features in patients with MC included symptom duration Conclusions: One in six patients with MC demonstrated distinct macroscopic findings at colonoscopy. Our data confirm a female preponderance in MC, a relatively short symptom duration and use of certain drugs as common features. Both right- and left-sided biopsies were frequently positive, suggesting flexible sigmoidoscopy and biopsy could confirm a diagnosis in certain individuals.

Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis. We describe here the histopathologic findings in 8 patients who developed colitis while on anti-PD-1 monotherapy. The most common pattern of injury observed (5/8 cases) was an active colitis with neutrophilic crypt microabscesses and with prominent crypt epithelial cell apoptosis and crypt atrophy/dropout. These latter features are reminiscent of other colitides with prominent apoptosis such as acute graft-versus-host disease or certain drug-induced colitides. The remainder of cases (3/8) showed a lymphocytic colitis-like pattern, characterized by increased intraepithelial lymphocytes and surface epithelial injury. Apoptosis was also often increased in these cases but crypt atrophy/dropout was not present. In patients who experienced recurrence of anti-PD-1 colitis, histologic features were similar to the initial insult but, in addition, features of chronicity developed that mimicked inflammatory bowel disease (basal lymphoplasmacytosis and crypt architectural irregularity, and Paneth cell metaplasia in 1 case). Awareness of the clinical scenario, however, should allow pathologists to suggest anti-PD-1 colitis. Interestingly, recurrent colitis was observed in patients who had been off anti-PD-1 therapy for many months. As anti-PD-1 agents are increasingly used in oncology, we present this series to increase awareness of anti-PD-1 colitis among pathologists, to facilitate its timely diagnosis and treatment.

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.

Microscopic colitis (MC) includes lymphocytic colitis (LC) and collagenous colitis (CC). Microscopic changes are required to establish these diagnoses. While criteria exist, interobserver variability has been reported previously. This has not been evaluated in the context of subspecialty signout (SSSO) or a consensus conference. We identified 133 colon biopsies diagnosed as LC, CC, MC, or normal but with mild changes insufficient for MC. All predated the introduction of SSSO at our institution. They were independently reviewed by three gastrointestinal (GI) pathologists. Cases lacking independent consensus were reviewed by the same pathologists in consensus conference to establish a final diagnosis. Individual diagnoses were compared with the consensus diagnoses, and consensus diagnoses were compared with original diagnoses made by GI and non-GI pathologists. Consensus diagnoses were normal (n = 34), LC (n = 57), and CC (n = 42). “Normal” was the diagnosis most commonly agreed upon independently (27/34 cases, P = 0.0073 versus LC, P = 0.0172 versus CC). The reviewing pathologists independently agreed with 80%, 80%, and 94% of consensus diagnoses (κ = 0.70, 0.69, and 0.91). The group consensus agreed with the diagnoses in 49 of 58 (84%) cases originally signed out by non-GI pathologists (κ = 0.77) and in 44 of 57 (77%) cases originally signed out by GI pathologists (κ = 0.63). Good interobserver agreement exists for MC, though whether GI subspecialty training improves agreement remains unclear. Group consensus may aid in diagnosis of difficult/borderline MC cases.