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Background and Aims: Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the clinical outcomes of microscopic colitis., Methods: We retrospectively reviewed the medical records of patients with microscopic colitis who were treated at the University of Chicago and Oregon Health & Science University between August 2010 and May 2016. Patient characteristics and treatments were evaluated as predictors of clinical outcomes using univariate and multivariate analyses. Clinical remission was defined as no symptoms associated with microscopic colitis based on physician assessment and histologic remission was defined as no evidence of histological inflammation of microscopic colitis., Results: Seventy-two patients with microscopic colitis were included in the study (28 with lymphocytic colitis and 44 with collagenous colitis). Non-steroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors were used in 23 (31.9%), 14 (19.4%) and 15 (20.8%), respectively, at the time of diagnosis. Among 46 patients with adequate follow-up data, 25 (54.3%) patients achieved clinical remission. Response to budesonide ( p  = .0002) and achieving histologic remission ( p  = .0008) were associated with clinical remission on univariate analysis. On multivariate analysis, budesonide response ( p  = .0052) was associated with clinical remission (odds ratio 25.00, 95% confidence interval 2.63-238.10). Among 22 patients who underwent a follow-up colonoscopy, five patients (22.7%) achieved histologic remission. All patients with histologic remission maintained clinical remission without medication, whereas only two patients (11.8%) were able to discontinue medical therapy when histologic inflammation was present ( p  = .0002)., Conclusions: In the present cohort of patients with microscopic colitis, a favourable response to budesonide was significantly associated with long-term clinical remission, and all patients achieving histological remission were able to maintain clinical remission without further medical therapy. Larger studies are required to confirm these findings.

Microscopic colitis is generally identified on random colon biopsies performed for chronic diarrhea, but rarely incidental polyps have histologic features of microscopic colitis. We compared patients with polypoid microscopic colitis to control patients with conventional polyps to determine the implications of polypoid microscopic colitis., Medical records were searched for patients without prior or concurrent microscopic colitis who were found to have polypoid microscopic colitis. For each patient with polypoid microscopic colitis, one patient with conventional polyps was selected as a control. We reviewed the histologic features of each polypoid microscopic colitis specimen, and evaluated endoscopic and clinical findings for polypoid microscopic colitis patients and controls., Twenty-six patients with polypoid microscopic colitis were identified with histologic features of collagenous colitis in 8 patients (31%) and lymphocytic colitis in 18 patients (69%). Polypoid microscopic colitis was unifocal in 14 patients (54%) and multifocal in 12 patients (46%). Patients with polypoid microscopic colitis were older than control patients (median age = 60 years vs 66 years, P  = .04). On follow-up 7 patients with polypoid microscopic colitis (33%) developed chronic diarrhea compared to 3 (12%) controls ( P  = .16). Of patients with follow-up biopsies, 1 patient with polypoid microscopic colitis (13%) and no control patients developed microscopic colitis ( P  = 1)., Polypoid microscopic colitis may be identified in asymptomatic patients and most patients do not develop chronic diarrhea, but some patients with polypoid microscopic colitis develop diarrhea (33% vs 12% in controls) or conventional microscopic colitis on follow-up. Thus pathologists should distinguish polypoid microscopic colitis from conventional microscopic colitis but may inform clinicians of the uncertain association with chronic diarrhea to guide decisions regarding follow-up., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Lymphocytic colitis (LC) in the pediatric population has been associated with immune dysregulation., Methods: Single-center retrospective study of pediatric LC., Results: 50 patients (35 female, 70%) with a median age of 12 years at diagnosis (interquartile range: 5.7-15.8) of LC were identified. At presentation, 11 patients (22%) had malnutrition, 16 (32%) had a known underlying immune dysregulation, 4 (8%) had celiac disease (CD), and none had a diagnosis of inflammatory bowel disease. The most common medications prior to diagnosis were non-steroidal anti-inflammatory drugs, proton pump inhibitor, and selective serotonin reuptake inhibitors (10% each). Colonic biopsies showed a median number of intraepithelial lymphocytes (IELs)/100 epithelial cells of 48 (range: 25-85), and only 10% of cases had neutrophilic cryptitis. Upper gastrointestinal tract findings included lymphocytic esophagitis (4%), and duodenal IELs without and with villous blunting (9% each) (n: 47). Ten patients (23%) had increased IELs in the terminal ileum (n: 43). Treatments including 5-ASA, budesonide, prednisone, and gluten-free diet improved symptoms in <50% of patients (n: 42), and all follow-up colonoscopies showed persistent LC (n: 13)., Conclusion: Our study supports the association of LC with immune-mediated conditions, most commonly celiac disease. Symptomatic improvement was seen in <50% of patients with none of the patients with repeat colonoscopy showing histologic improvement., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort., Methods: Women (n = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) (n = 92) and lymphocytic colitis (LC) (n = 66) or MC with one episode of the disease (n = 70) and refractory MC (n = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits., Results: MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p = 0.05) and MC with one episode (12.9% vs. 2.3%; p = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p = 0.037) and refractory MC (38.6% vs. 20.0%; p = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020-17.469; p = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042-1.506; p = 0.058)., Conclusion: Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities., (© 2024. The Author(s).)

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

Background: An association has been reported between celiac disease (CD) and microscopic colitis (MC). However, large, population-based cohort studies are rare., Objective: To systematically examine the association between CD and MC in a large, nationwide cohort., Methods: We conducted a nationwide population-based matched cohort study in Sweden of 45,138 patients with biopsy-verified CD (diagnosed in 1990-2016), 223,149 reference individuals, and 51,449 siblings of CD patients. Data on CD and MC were obtained from all (n = 28) pathology departments in Sweden. Adjusted hazard ratios (aHRs) were calculated using Cox regression., Results: During follow-up, 452 CD patients and 197 reference individuals received an MC diagnosis (86.1 vs. 7.5 per 100,000 person-years). This difference corresponded to an aHR of 11.6 (95% confidence interval [CI] = 9.8-13.8) or eight extra MC cases in 1000 CD patients followed up for 10 years. Although the risk of MC was highest during the first year of follow-up (aHR 35.2; 95% CI = 20.1-61.6), it remained elevated even after 10 years (aHR 8.1; 95% CI = 6.0-10.9). Examining MC subtypes lymphocytic colitis (LC) and collagenous colitis (CC) separately, the aHR was 12.4 (95% CI = 10.0-15.3) for LC and 10.2 (95% CI = 7.7-13.6) for CC. MC was also more common before CD (adjusted odds ratio [aOR] = 52.7; 95% CI = 31.4-88.4). Compared to siblings, risk estimates decreased but remained elevated (CD and later MC: HR = 6.2; CD and earlier MC: aOR = 7.9)., Conclusion: Our study demonstrated a very strong association of MC with CD with an increased risk of future and previous MC in CD patients. The magnitude of the associations underscores the need to consider the concomitance of these diagnoses in cases in which gastrointestinal symptoms persist or recur despite a gluten-free diet or conventional MC treatment. The comparatively lower risk estimates in sibling comparisons suggest that shared genetic and early environmental factors may contribute to the association between CD and MC., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied., Methods: This was a case-control study based on the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy, and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for country of birth and matching factors. Further subanalyses were made based on MC subtypes (lymphocytic colitis and collagenous colitis), follow-up time postappendectomy and severity of appendicitis., Results: The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n = 1103) and 5.1% (n = 3510), respectively, had a previous appendectomy ≥1 year prior to MC or matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR, 1.50; 95% CI, 1.40-1.61) and per the collagenous colitis subtype (OR, 1.67; 95% CI, 1.48-1.88) or lymphocytic colitis subtype (OR, 1.42; 95% CI, 1.30-1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in noncomplicated appendicitis., Conclusions: This nationwide case-control study found a modestly increased risk of developing MC following appendectomy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Microscopic colitis (MC) is a chronic inflammatory disease of colon with clinical presentations of chronic, watery, nonbloody diarrhea, and normal or almost normal endoscopic findings. Confirmation of a diagnosis of MC requires microscopic examination on colon biopsy to identify characteristic morphological features, in which 2 main subtypes of MC, lymphocytic colitis (LC) and collagenous colitis (CC), have been described. Although the pathogenesis of MC is still unclear, studies have revealed associations of MC with many risk factors and other diseases such as celiac disease, inflammatory bowel disease, and medication use. Meanwhile, variants of MC, MC incomplete, or MC-like changes in other conditions are still diagnostic dilemmas for pathologists. The goal of this paper is to systemically introduce the clinicopathologic features of MC and focus on unusual features of MC and its associations with other conditions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The number of intestinal mast cells (MC) is increased in several types of colitis, but the mucosa of patients with chronic non-bloody diarrhea has not been studied. The current study sought to determine the relationship between MC counts and degranulation and the severity of symptoms in patients with chronic loose stools. Following a negative laboratory workup for the most common causes of chronic diarrhea, patients with chronic non-bloody loose stools were included in the study. Patients with macroscopic evidence of inflammation or organic disease were excluded after endoscopy with biopsies. Biopsies from the 179 patients in the study were stained with hematoxylin and eosin and anti-CD117 c-kit antibodies. Immunohistochemistry was used to assess the degree of MC degranulation. Out of the 179 patients, 128 had normal histologic findings suggestive of irritable bowel syndrome and were used as controls. Twenty-four presented with abnormally high MC counts (≥40 MC x HPF), 23 with ≥20 intraepithelial lymphocytes x HPF suggesting lymphocytic colitis, and 4 had both (≥40 MC and ≥20 intraepithelial lymphocytes x HPF). In the patients with high MC counts, figures were significantly higher in the right colon versus the left colon (p=0.016), but degranulation did not differ in the right versus the left colon (p=0.125). No age or sex-related difference was observed (p=0.527 and p=0.859 respectively). The prevalence of abdominal pain and bloating did not differ in the three groups (p=0.959 and p=0.140, respectively). Patients with lymphocytic colitis (p=0.008) and those with high MC counts (p=0.025) had significantly higher evacuation rates compared to controls. There was no difference between these two groups (p=0.831). Mast cell degranulation was not associated with the number of evacuations, abdominal pain, or bloating (p=0.51; p=0.41; p=0.42, respectively). The finding that a significantly higher number of evacuations was linked to increased MC in the colonic mucosa of a subset of patients with otherwise normal laboratory and endoscopic findings suggests that "mastocytic colitis" may be a new clinical-pathological entity responsible for chronic non-bloody diarrhea. Prospective studies with a larger number of patients, as well as endoscopic and histological follow-up, are needed to confirm this hypothesis.

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., (Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation (ECCO) 2022.)

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.

Objective: Microscopic colitis is a chronic inflammatory disorder characterized by a triad of chronic diarrhea, endoscopy without significant abnormality, and distinct histopathological features. Histopathologically, microscopic colitis is divided into 3 subtypes; collagenous colitis, lymphocytic colitis, incomplete microscopic colitis. The main purpose of this study was to analyze the detailed clinicopathological parameters of microscopic colitis cases in the Turkish population., Material and Method: The clinicopathological parameters were evaluated in 53 microscopic colitis cases (37 collagenous colitis, 7 lymphocytic colitis, 9 incomplete microscopic colitis) diagnosed between 2010 and 2019., Results: All cases had lymphoplasmacytosis. The presence of ≥20 eosinophils/high power field in the lamina propria was remarkable in 75.7%, 57.1%, and 11.1% of collagenous colitis, lymphocytic colitis, and incomplete microscopic colitis cases, respectively. One of the striking findings was the presence of concomitant Celiac disease in 29% of the lymphocytic colitis cases. In terms of drug use, proton pump inhibitors and nonsteroidal anti-inflammatory drugs were the most commonly used drugs., Conclusion: The mean age in our series is lower than the literature and a distinct male predominance was observed in lymphocytic colitis and incomplete microscopic colitis, contrary to the literature. These suggest that susceptibility to microscopic colitis may differ between ethnic groups. The presence of overt lymphoplasmacytosis, eosinophilic infiltration and epithelial damage are the microscopic features which should alert the pathologist for the diagnosis of complete microscopic colitis. Given that microscopic colitis is a common treatable cause of chronic diarrhea, awareness of the aforementioned histopathological features is of utmost importance for accurate diagnosis and not to miss incomplete cases.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© 2020 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

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)., (© 2020 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Objective: 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., Methods: 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., Results: 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%) ( p =0.0031). In the three cases of LC with markedly reduced AQP5 (score 1), enteric steroid treatment did not lead to significant improvement in diarrhea., Conclusions: 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., (© 2020 by the Association of Clinical Scientists, Inc.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Patients with inflammatory bowel disease (IBD) may occasionally present with lymphocytic colitis/collagenous colitis (LC/CC) either before or after the onset of IBD. Although a few reports have described a small number of such cases, the relationship between these 2 disorders is still unclear. We evaluated 27 patients with diagnosis of either ulcerative colitis (UC) or Crohn disease (CD) and LC/CC. Clinical, endoscopic, and pathological features were reviewed. Ten patients with initial diagnoses of LC (n = 2)/CC (n = 8) evolved into UC (n = 7) or CD (n = 3) after a median interval of 14 months (range, 2-44 months). Among these, 4 patients with LC/CC evolving into IBD also had recurrent CC in a quiescent phase of IBD. Seventeen patients with initial diagnosis of UC (n = 11) or CD (n = 6) developed LC (n = 6)/CC (n = 11) after a median interval of 108 months (range, 15-548 months). IBD patients with initial presentation of LC/CC were significantly older than those who developed LC/CC after onset of IBD (66.5 versus 34.0 years old, P = .001). The interval time between LC/CC to IBD was significantly shorter than that of IBD to LC/CC (14 versus 108 months, P = .007). Quiescent UC with superimposed CC was the most common pattern (n = 8). Patients with CD had shorter interval time to develop LC/CC than UC patients, although it was not statistically significant (60.5 versus 139 months, P = .14). Endoscopically, most patients that started with LC/CC had unremarkable findings, but 11 of 17 patients who developed LC/CC after IBD showed quiescent chronic colitis. Histologically, LC/CC patients with diagnosis of IBD, either before or after, more frequently show active inflammation. Chronicity was more commonly seen in biopsy of LC/CC patients with a history of IBD. Our study found that IBD patients with initial presentation of LC/CC tend to occur in older age, with shorter interval time and frequent active inflammation in initial LC/CC. These findings suggest that LC/CC may be a spectrum of IBD as the initial presentation in a subset of older IBD patients. On the other hand, IBD patients can develop LC/CC associated with chronic mucosal injury many years after the onset of IBD (typically with >10 years interval time while patients are in remission phase), for which these 2 processes seem unrelated to each other., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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) 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.

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., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: Lymphocytic colitis is a common cause of chronic, nonbloody diarrhea. However, the effects of treatment are unclear and randomized placebo-controlled trials were requested in a Cochrane review. We performed a randomized, placebo-controlled, multicenter study to evaluate budesonide and mesalazine as induction therapy for lymphocytic colitis., Methods: Patients with active lymphocytic colitis were randomly assigned to groups given budesonide 9 mg once daily (Budenofalk granules), mesalazine 3 g once daily (Salofalk granules), or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as ≤21 stools (including ≤6 watery stools), in the 7 days before week 8., Results: The final analysis included 57 patients (19 per group). Most patients were female (72%) and the mean age was 59 years. The proportion of patients in clinical remission at week 8 was significantly higher in the budesonide group than in the placebo group (intention-to-treat analysis, 79% vs 42%; P = .01). The difference in proportions of patients in clinical remission at week 8 between the mesalazine (63%) and placebo groups was not significant (P = .09). The proportion of patients with histologic remission at week 8 was significantly higher in the budesonide group (68%) vs the mesalazine (26%; P = .02) or placebo (21%; P = .008) groups. The incidence of adverse events was 47.4% in the budesonide group, 68.4% in the mesalazine group, and 42.1% in the placebo group., Conclusions: In a randomized multicenter study, we found oral budesonide 9 mg once daily to be effective and safe for induction of clinical and histologic remission in patients with lymphocytic colitis, compared with placebo. Oral mesalazine 3 g once daily was not significantly better than placebo. ClinicalTrials.gov no: NCT01209208., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Some authors have found increase of neuroendocrine cells in microscopic colitis and ulcerative colitis., Objective: The aim of this study is to evaluate the presence of neuroendocrine cells in ulcerative colitis and lymphocytic colitis and collagenous colitis., Materials and Methods: Immunohistochemistry was performed to identify neuroendocrine cells through marker chromogranin A (CgA). The study included 10 cases of each diagnosis of Lymphocytic colitis, collagenous colitis and ulcerative colitis., Results: There was statistically significant difference in the count of neuroendocrine cells, between lymphocytic colitis and control (p=0.019104), and between ulcerative colitis and controls (p=0.0077). In collagenous colitis there was an increase in neuroendocrine cells but we failed to find statistical differences., Conclusion: We could observe neuroendocrine cell hyperplasia in lymphocytic colitis and ulcerative colitis compared with controls, which confirm previous studies.

Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine- N -acetyltransferase (AANAT), and N -acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis. The study included 30 healthy subjects (group C), 30 patients with severe ulcerative colitis (group UC), and 30 patients with lymphocytic colitis (group LC). The diagnosis was based on endoscopic, histological, and laboratory examinations. Biopsy specimens were collected from right, transverse, and left parts of the colon. The levels of mRNA expression, TPH1, AANAT, and ASMT were estimated in the colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by the photometric method. The expression of TPH1, AANAT, and ASMT in colonic mucosa in UC and LC patients was significantly higher than in healthy subjects. Significant differences were found in the urinary aMT6s excretion: group C-13.4 ± 4.8 µg/24 h, group UC-7.8 ± 2.6 µg/24 h ( p < 0.01), group LC-19.2 ± 6.1 µg/24 h ( p < 0.01). Moreover, a negative correlation was found between fecal calprotectin and MT6s-in patients with UC - r = -0.888 and with LC - r = -0.658. These results indicate that patients with UC and those with LC may display high levels of melatonin-synthesizing enzymes in their colonic mucosa, which could possibly be related to increased melatonin synthesis as an adaptive antioxidant activity., Competing Interests: The authors declare no conflict of interest.

Microscopic colitis (MC) is still an underestimated cause of chronic, non-bloody watery diarrhea. It is typically manifested in elderly patients with a female predominance. The incidence of microscopic colitis has been increasing. The aetiology and pathophysiology remain unclear. Conditions associated with it include autoimmune diseases. There may be a genetic predisposition, as familial cases have been described. As implicated by the name microscopic colitis, the diagnosis is found by histological examination. There are mainly two subtypes, the lymphocytic colitis (LC) and the collagenous colitis (CC). Even if the condition's long-term course is benign, a chronic recurrent course of the symptoms is frequent. Due to the symptoms, there is an impairment of patient's health-related quality of life. A correct diagnosis and therapy is therefore mandatory. The aim of this paper is to create awareness for microscopic colitis.

Introduction: Lymphocytic colitis and microscopic enteritis are relatively common causes of chronic diarrhea and it is characterized by an intraepithelial lymphocytic infiltrate. There have been no previous reports of coexistence between these 2 pathologies., Objective: To describe histological and clinical characteristic in patients with coexistence of lymphocytic colitis and microscopic enteritis., Material and Methods: All cases with simultaneous diagnosis of lymphocytic duodenosis and lymphocytic colitis were reevaluated during lapse time 2010-2016 in hospital Daniel Carrion. The slides were reviewed by 3 pathologists and clinical information was obtained from clinical records. Expression of CD3 and CD8 was detected in 6 cases by immunohistochemical assays., Results: A total of 35 patients with coexistence of lymphocytic duodenitis and lymphocytic colitis were selected of the pathology archives, 80% were females, Anemia was identified in 28.5% of patients. Blastocysitis hominis infestation was identified in 31.8%. The mean intraepithelial lymphocyte CD8 and CD3 positive was 40% in microscopic enteritis, while the mean intraepithelial lymphocyte CD3 positive was 37.2% and CD8 positive was 29.2% Additionally, lymphocytic ileitis was diagnosed in 11 of our cases. Eosinophilic colitis was diagnosed in 9 cases of lymphocytic colitis Conclusion: We found that lymphocytic colitis, microscopic enteritis and even lymphocytic ileitis can coexist in a group of patients with chronic diarrhea. These findings bring the question if this concurrence of both pathologies constituted a more generalized gastrointestinal disorder, involving both the large and the small intestines.

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 <6 months, weight loss, abdominal pain and use of proton pump inhibitors, statins, or non-steroidal anti-inflammatory drugs. In individuals with right- and left-sided biopsies taken, 98.2% had diagnostic features in both. However, rectal biopsies were only positive in 88.7%., 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.

The relationship between Microscopic Colitis and Inflammatory Bowel Disease is unclear. However, when both are diagnosed they seem to be part of a broader spectrum of the same disease, more than just a coincidence. We report a 55 years old woman with Ulcerative Colitis limited to the rectum with complete clinical and endoscopic response to standard treatment and adequate surveillance for 13 years, who abandoned treatment and control. After eight years, she consulted for mild-to-moderate non-bloody diarrhea lasting several months. Colonoscopy and basic laboratory did not show any alterations. Nevertheless, random biopsies had a characteristically pattern compatible with Lymphocytic Colitis. After the first week of treatment with budesonide the patient was asymptomatic and still in clinical remission, with negative fecal calprotectin at 6 months’ follow-up.

Background: Lymphocytic colitis (LC) causes watery diarrhea. We aimed to identify mechanisms of altered Na absorption and regulatory inputs in patients with LC by examining the epithelial Na channel (ENaC) function as the predominant Na transport system in human distal colon., Methods: Epithelial Na channel function and regulation was analyzed in biopsies from sigmoid colon of patients with LC and in rat distal colon in Ussing chambers. ENaC-subunit expression was measured by real-time PCR and RNA sequencing. Correction factors for subepithelial resistance contributions were determined by impedance spectroscopy. Upstream regulators in LC were determined by RNA sequencing., Results: Epithelial Na channel-mediated electrogenic Na transport was inhibited despite aldosterone stimulation in human sigmoid colon of patients with LC. The increase in γ-ENaC mRNA expression in response to aldosterone was MEK1/2-dependently reduced in LC, since it could be restored toward normal by MEK1/2 inhibition through U0126. Parallel experiments for identification of signaling in rat distal colon established MEK1/2 to be activated by a cytokine cocktail of TNFα, IFNγ, and IL-15, which were identified as the most important regulators in the upstream regulator analysis in LC., Conclusions: In the sigmoid colon of patients with LC, the key effector cytokines TNFα, IFNγ, and IL-15 inhibited γ-ENaC upregulation in response to aldosterone through a MEK1/2-mediated pathway. This prevents ENaC to reach its maximum transport capacity and results in Na malabsorption which contributes to diarrhea.

The mucosa of the esophagus, the stomach, the small intestine, the large intestine and rectum are unremittingly challenged by adverse micro-environmental factors, such as ingested pathogenic and non-pathogenic bacteria, and harsh secretions with digestive properties with disparate pH, as well as bacteria and secretions from upstream GI organs. Despite the apparently inauspicious mixture of secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To by-pass the tough microenvironment, the epithelia of the GI react by speeding-up cell exfoliation, by increasing peristalsis, eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial enzymes (lysozyme) and host defense peptides (defensin-5). Lysozyme was recently found up-regulated in Barrett's esophagitis, in chronic gastritis, in gluten-induced atrophic duodenitis (celiac disease), in collagenous colitis, in lymphocytic colitis and in Crohn's colitis. This up-regulation is a response directed towards the special types of bacteria thriving in the microenvironment in each of the aforementioned clinical inflammatory maladies. The purpose of that up-regulation is to protect the mucosa affected by the ongoing chronic inflammation. Bacterial antibiotic resistance continues to exhaust our supply of effective antibiotics. The future challenge is how to solve the increasing menace of bacterial resistance to anti-bacterial drugs. Further research on natural anti-bacterial enzymes such as lysozyme, appears mandatory., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: Microscopic colitis (MC) includes two main types: collagenous colitis (CC) and lymphocytic colitis (LC). Previous studies have indicated an increasing incidence, but these have mainly been based on regional databases. We found it important to study the epidemiology based on a comprehensive nationwide cohort., Material and Methods: We studied the epidemiological data of MC in Denmark from 2002 to 2011. The cohort consisted of all patients with a recorded diagnosis of either CC or LC in the Danish Pathology Register during the study period. Data on all patients with a registered colon biopsy were also included., Results: A total of 7777 patients, 4749 (61%) with CC and 3028 (39%) with LC, were identified. Over the study period, the annual incidence of diagnosed cases of CC increased from 2.9/10(5) to 14.9/10(5) and of LC from 1.7/10(5) to 9.8/10(5). In 2011, the incidence of MC was 24.7/10(5) inhabitants. The age-specific incidence showed that the risk of both CC and LC increased with age. The female/male ratio, distribution of the type of colitis and mean age at diagnosis were relatively stable during the study period. The annual number of registered colon biopsies in the pathology register increased from 21.583 in 2002 to 39.733 in 2011, indicating an increased diagnostic activity., Conclusion: In a nationwide cohort study, the incidence of CC and LC continued to increase from 2002 to 2011. An increased diagnostic activity could in part explain the increase in the number of diagnosed cases.

Background/aims: Although normal endoscopic findings are, as a rule, part of the diagnosis of microscopic colitis, sev-eral cases of macroscopic lesions (MLs) have been reported in collagenous colitis, but hardly in lymphocytic colitis (LC). The aim of this study was to investigate the endoscopic, clini-cal, and histopathologic features of LC with MLs., Methods: A total of 14 patients with LC who were diagnosed between 2005 and 2010 were enrolled in the study. Endoscopic, clini-cal, and histopathologic findings were compared retrospec-tively according to the presence or absence of MLs., Results: MLs were observed in seven of the 14 LC cases. Six of the MLs exhibited hypervascularity, three exhibited exudative bleeding and one exhibited edema. The patients with MLs had more severe diarrhea and were taking aspirin or pro-ton pump inhibitors. More intraepithelial lymphocytes were observed during histologic examination in the patients with MLs compared to the patients without MLs, although this difference was not significant. The numbers of mononuclear cells and neutrophils in the lamina propria were independent of the presence or absence of MLs., Conclusions: LC does not always present with normal endoscopic findings. Hyper-vascularity and exudative bleeding are frequent endoscopic findings in patients with MLs. (Gut Liver, 2015;9197-201).

Background: Lymphocytic and collagenous colitis are emerging as common findings in subjects undergoing colonoscopy for chronic non-bloody diarrhea (CNBD). Data concerning microscopic colitis (MC) are still limited and affected by controversial epidemiological evidences. Recent converging lines of evidence suggest that MC correlates a lower risk of colorectal neoplasia. Accordingly, we prospectively assessed MC prevalence in a multicenter cohort of subjects submitted to colonoscopy for CNBD, thereby defining whether MC influences the risk of colorectal neoplasia., Methods: Consecutive patients with CNBD of unknown origin underwent pan-colonoscopy with multiple biopsies. The prevalence of neoplastic patients in MC was compared with that observed in negative CNBD subjects., Results: Among 8006 colonoscopy, 305 subjects were enrolled for CNBD. Patients with CNBD were more likely to be women than men (odds ratio = 1.5; P = 0.001). Histopathology detected high prevalence of MC (16%) with a clear predominance of collagenous colitis (70%). A striking age-dependent rise in MC-associated risk was observed, depicting outstanding differences among varying age groups, as in the number needed to screen 1 new case. Gender distribution was balanced within MC patients (Female/Male = 1.5/1), especially among lymphocytic colitis (Female/Male = 1.2/1). MC patients were negatively associated with the risk of neoplastic polyps compared with negative CNBD subjects (odds ratio = 0.22; P = 0.035)., Conclusions: MC is the first cause of CNBD in subjects submitted to colonoscopy. Multiple biopsies are strongly recommended, even in the case of uneventful endoscopic inspection, especially for age ≥40 years. MC has a reduced risk of colorectal neoplasia, suggesting that this model of chronic inflammation plays a protective effect against colorectal carcinogenesis.

Background: Chronic non-bloody diarrhoea affects up to 5% of the population. Microscopic colitis is one of the most common causes, encompassing the subtypes collagenous colitis and lymphocytic colitis. The diagnosis of microscopic colitis is made by histological examination of colonic mucosal biopsy specimens. The aim of this investigation was to determine whether laboratory parameters or questions about disease history or concomitant disease could be helpful in discriminating patients with MC from those with a histologically normal colonic mucosa., Findings: Patients admitted for colonoscopy because of chronic non-bloody diarrhoea (>2 loose stools for >3 weeks) at endoscopy units in Malmö during 2007 and 2009, were enrolled. A total number of 78 patients were included (60 women, 18 men, median age 59, IQR 45-69 years). Out of these 78, 15 patients (19%) had microscopic colitis (CC; n = 10, LC; n = 5). MC was especially prevalent in patients above the age of 50 (25%). No differences were found between those with normal histology and MC in laboratory analyses (inflammatory and liver parameters). Neither were differences shown in questions regarding symptoms, environmental factors or concomitant diseases except for an association with celiac disease (p = 0.019) and a trend maybe indicating an inverse association with appendectomy (p = 0.057)., Conclusions: Microscopic colitis is associated with female gender, celiac disease and consumption of NSAIDs. Trends were observed indicating that age above 50 years, acute onset and absence of appendectomy may be associated with MC. No associations were observed with other symptoms, calprotectin levels or liver parameters.

Background/aims: The etiopathogenesis of inflammatory bowel disease (IBD) is multifactorial and not well explained. Environmental, genetic, and dietary factors play an important role. The aim of the study was the evaluation of lactase, saccharase, and maltase activity in patients with IBD., Materials and Methods: The study comprised 65 children, aged 3-18 years. During a routine endoscopy, we took biopsies from the descending part of the duodenum. In these biopsies, we determined disaccharidase activity using Dahlquist's method., Results: Decreased lactase activity in the biopsies taken from the small intestine mucosa was most frequently observed in patients with Crohn's disease (5/15-33%) and least frequently seen in children with lymphocytic colitis (in 1/10-10%). The lowest mean values of lactase activity were found in the children with Crohn's disease and ulcerative colitis (1.7-2.5 U/1 g). Decreased saccharase activity in the biopsies obtained from the small intestine mucosa was most frequently observed in patients with lymphocytic colitis (in 5/10-50%) and ulcerative colitis (9/20-45%) and least frequently seen in children with non-specific undetermined colitis (in 7/20-35%). Decreased maltase activity in the small bowel mucosa was the most frequently observed in patients with Crohn's disease (in 5/15-33%) and least frequently seen in children with ulcerative colitis (in 3/20-15%). The lowest mean values of maltase activity were found in the children with Crohn's disease (5.4 U/1 g)., Conclusion: Therefore, it seems reasonable to perform diagnostic examinations aimed at lactose, saccharose, and maltose intolerance and to initiate a dietary regimen in children with IBD.

The diagnosis of microscopic colitis (MC) is based on histologic findings and includes collagenous colitis (CC) and lymphocytic colitis (LC). Incomplete MC (MCi) denotes patients with chronic diarrhea and a normal endoscopy and morphological changes that do not completely meet the histologic criteria of LC or CC. The aim of this study was to investigate the intraobserver and interobserver agreement on the MC subtypes of CC, LC, and MCi and the ability to discriminate MCi from normal and inflammatory bowel disease/nonspecific reactive changes. A single hematoxylin and eosin-stained specimen from biopsies of the following 5 groups were randomly selected and blinded: CC, LC, MCi, inflammatory bowel disease, and normal. Three pathologists independently reviewed the specimens. The specimens were relabeled and reinterpreted 4 months later. Intraobserver and interobserver agreement was evaluated by κ statistics. κ values for intraobserver agreement were good for 5 diagnostic groups varying from 0.70 to 0.83 and very good when simplifying to only 3 diagnostic groups varying from 0.88 to 0.96, separating MC/MCi from non-MC. κ values for interobserver agreement varied from 0.60 to 0.75 for 5 diagnostic groups and 0.81 to 0.89 for 3 diagnostic groups. The study shows that the intraobserver and interobserver agreement is high for discriminating between MC/MCi and non-MC, whereas the ability to discriminate MCi from CC and LC is lower. A revision and consensus on the histologic criteria of the MC subtypes seem warranted., (© 2013.)

Background and Aims: Microscopic colitis (MC), encompassing the subgroups collagenous colitis (CC) and lymphocytic colitis (LC), is characterized by macroscopically normal or near-normal colonic mucosa, and an increased number of intraepithelial lymphocytes (IELs) and mononuclear cell infiltration in the underlying lamina propria (LP), in addition to an increased collagen layer in CC. This study aimed to characterize the inflammatory cells involved in mucosal inflammation, using immunohistochemistry., Methods: Paraffin-embedded biopsies from 23 untreated patients with MC (CC=13, LC=10) and 17 controls were stained with antibodies against CD3, CD4, CD8, CD20, CD30, Foxp3, CD45RO and Ki67. Computerized image analysis was used to calculate areas of stained lymphocytes in the surface and crypt epithelia as well as in the LP., Results: In CC and LC, an increase of predominantly CD8(+) lymphocytes was seen in both the epithelium and the lamina propria, whereas a decreased amount of CD4(+) lymphocytes was found in the lamina propria. CD45RO(+) and Foxp3(+) cells were more abundant in all areas in both patient groups compared to controls, as were CD20(+) areas, although more scarce. Ki67(+) areas were only more abundant in the epithelium, whereas CD30(+) areas were more abundant in the lamina propria of both patient groups compared to controls., Conclusions: This study confirms an increased amount of CD8(+) lymphocytes in the epithelium. Lymphocytic proliferation and activation markers were more abundant, whereas a decreased amount of CD4(+) lymphocytes was seen in the LP. Further studies are needed to reveal the underlying mechanism(s)., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Objective: Microscopic colitis (MC) is prevalent in adults investigated for chronic watery diarrhea, yet characterization of pediatric MC is limited., Methods: Our pathology database was searched from 1995 to 2011 for pediatric cases of lymphocytic colitis (LC) or collagenous colitis (CC). Those with diarrhea persisting for >2 weeks and visually normal colonoscopy were accepted as cases. Demographics, laboratory results, medication use within 3 months of presentation, medical and family history of autoimmune disease, and response to treatment were abstracted., Results: A total of 27 cases were histologically consistent with MC on biopsy; 5 with concomitant enteric infection or isolated abdominal pain were excluded. Twenty-two cases of MC (female patients, 59%; median age at diagnosis, 15.3 years) were included (19 LC and 3 CC). Two had type 1 diabetes mellitus, 2 were anti-nuclear antibody positive, and 2 had common variable immunodeficiency. Of 20 patients who underwent an esophagogastroduodenoscopy, 1 had collagenous sprue and 4 had celiac disease. One presented after the clearance of recurrent Clostridium difficile infection. Previous drug exposures included nonsteroidal anti-inflammatory drugs (n = 7), proton pump inhibitors (n = 6), and selective serotonin reuptake inhibitors (n = 3). Common symptoms in addition to diarrhea included abdominal pain (77.3%) and weight loss (27.3%). Of 17 patients with follow-up, all of the 8 treated with steroids had some response: 57.1% (4/7) responded to mesalamine and 42.9% (3/7) responded to bismuth subsalicylate., Conclusions: In this cohort of pediatric patients, LC was much more common than CC. As described in adults, we observed associations with celiac disease, type 1 diabetes mellitus, and medications; we additionally saw an association with immunodeficiency. Our patients showed greater response to steroids than mesalamine or bismuth.

Background: It is unknown whether the subtypes of microscopic colitis (MC) represent distinct nosologic entities or related presentations of the same disease. Our aim was to search for epidemiologic differences among its various histopathologic subtypes., Methods: In a computerized database of 789,568 colon pathology reports, we compared the characteristics of 8,745 MC patients with those of the remaining population., Results: MC was diagnosed as three distinct histopathologic subtypes: lymphocytic colitis (LC) in 51 %, collagenous colitis (CC) in 43 %, and incomplete colitis (IC) in 6 % of patients. Only 0.65 % was simultaneously diagnosed with more than one subtype of MC. The prevalence of all three subtypes showed an age-dependent rise, with the average age (SD) being 63.3 (14.3) years in LC, 66.4 (12.1) years in CC, and 67.3 (12.7) years in IC (p < 0.0001). There was a striking female predominance in all three subtypes, the female fraction being 72 % in LC, 82 % in CC, and 79 % in IC (p < 0.0001). All three subtypes showed similar geographic distributions among different US states. They were similarly associated with diarrhea and weight loss, the odds ratios for all MC being 45.92 (43.35-48.63) and 5.12 (4.68-5.60), respectively, compared to control patients without MC. All three subtypes also harbored significantly less colonic adenomas, the overall odds ratio being 0.11 (0.10-0.12)., Conclusion: MC comes in three distinct histopathologic entities, which show striking similarities of their general epidemiologic features. The slight differences in their demographic characteristics could point at varying sets of environmental influences that affect the occurrence of subtypes.

Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC., Methods: Lamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n=7), LC (n=6), as well as LC or CC patients in histopathological remission, (LC-HR) (n=6) and CC-HR (n=4) and non-inflamed controls (n=10) were phenotypically characterized by four-color flow cytometry., Results: The proportions of CD8(+) IELs were increased in CC and LC (p<0.01) compared to controls. Increased proportions of CD45RO(+)CD8(+) IELs and LPLs were observed in LC and even more in CC patients (p<0.01). Both CC (p<0.05) and LC patients had elevated proportions of CD4(+)8(+) IELs and LPLs compared to controls. The proportions of CD45RO(+) cells were increased in CD4(+)8(+) IELs and LPLs (p<0.05) in CC and LC patients compared to controls. Both CC (p<0.05) and LC patients had higher proportions of Ki67(+)CD8(+) IELs and LPLs compared to controls. In contrast, decreased proportions of CD4(+) LPLs were observed in CC and LC as well as CD4(+) IELs in LC compared to controls. Increased proportions of Ki67(+)CD4(+) IELs and LPLs (p<0.05) were observed in CC and LC patients. CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively., Conclusion: LC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67(+) and CD45RO(+) CD8(+) and CD4(+)8(+) mucosal T cells., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Microscopic colitis (MC) is a chronic inflammatory bowel disorder of unknown aetiology comprising collagenous colitis (CC) and lymphocytic colitis (LC). Data on the local cytokine profile in MC is limited. This study investigated the T helper (Th) cell and cytotoxic T lymphocyte (CTL) mucosal cytokine profile at messenger and protein levels in MC patients., Methods: Mucosal biopsies from CC (n=10), LC (n=5), and CC or LC patients in histopathological remission (CC-HR, n=4), (LC-HR, n=6), ulcerative colitis (UC, n=3) and controls (n=10) were analysed by real-time PCR and Luminex for expression/production of IL-1β, -4, -5, -6, -10, -12, -17, -21, -22, -23, IFN-γ, TNF-α, T-bet and RORC2., Results: Mucosal mRNA but not protein levels of IFN-γ and IL-12 were significantly up regulated in CC, LC as well as UC patients compared to controls. Transcription of the Th1 transcription factor T-bet was significantly enhanced in CC but not LC patients. mRNA levels for IL-17A, IL-21, IL-22 and IL-6 were significantly up regulated in CC and LC patients compared to controls, albeit less than in UC patients. Significantly enhanced IL-21 protein levels were noted in both CC and LC patients. IL-6 protein and IL-1β mRNA levels were increased in CC and UC but not LC patients. Increased mucosal mRNA levels of IFN-γ, IL-21 and IL-22 were correlated with higher clinical activity, recorded as the number of bowel movements per day, in MC patients. Although at lower magnitude, IL-23A mRNA was upregulated in CC and LC, whereas TNF-α protein was increased in CC, LC as well as in UC patients. Neither mRNA nor protein levels of IL-4, IL-5 or IL-10 were significantly changed in any of the colitis groups. LC-HR and especially CC-HR patients had normalized mRNA and protein levels of the above cytokines compared to LC and CC patients. No significant differences were found between LC and CC in cytokine expression/production., Conclusion: LC and CC patients demonstrate a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile., (Copyright © 2013 Elsevier Ltd. All rights reserved.)