Potential association between M694V homozygous mutation in familial Mediterranean fever and eosinophilic intestinal inflammation: a pediatric case series.

Familial Mediterranean fever (FMF) is the most common hereditary systemic auto-inflammatory disease. Digestive complaint is a common feature during FMF attacks. Nevertheless, digestive complaint in attack-free period has scarcely been studied. This retrospective monocentric study aimed to describe the clinical, histological, and genetic features of pediatric patients with FMF who underwent endo-colonoscopy in this setting. Out of 115 patients with a diagnosis of FMF, 10 (8, 7%) underwent endoscopy or colonoscopy. All displayed homozygote MEFV M694V mutation and presented chronic abdominal pain, iron deficiency, and/or growth retardation. On the histological level, all patients displayed low-grade mucosal inflammation, characterized by a moderate eosinophilic infiltrate in the lamina propria sometimes associated with increased crypt apoptosis. The proportion of patients explored with endoscopy or colonoscopy was 0.4 patients per year in our center, compared with 5.7 patients per year nationwide. This study identified a specific intestinal phenotype that does not respond to the criteria of classical inflammatory bowel disease: pediatric FMF pediatric patients with homozygous MEFV M694V, abdominal pain, iron deficiency, and growth retardation should benefit from specialized gastroenterological advice.

SARS-CoV-2 as a potential trigger for microscopic colitis in a young adult: A case report.

This case highlights the potential role of SARS-CoV-2 in triggering lymphocytic colitis, emphasizing the need for further research and vigilance in identifying potential post-COVID-19 GI complications. We describe a case of a young adult who experienced chronic diarrhea and abdominal pain for 10 months after a SARS-CoV-2 infection. Extensive laboratory and imaging investigations yielded no significant findings. Despite a preliminary diagnosis of irritable bowel syndrome and symptomatic treatment, symptoms persisted. Colonoscopy with biopsies revealed unremarkable colonic mucosa but confirmed moderate lymphocytic infiltration consistent with lymphocytic colitis. Treatment with budesonide achieved complete symptom resolution. The findings underscore the importance for clinicians to consider triggered microscopic colitis in patients presenting with persistent diarrhea following SARS-CoV-2 infection.

The Utility of Intestinal Ultrasound in a Case of Microscopic Colitis.

This case demonstrates the utility of intestinal ultrasound in inflammatory bowel diseases outside of Crohn's disease and ulcerative colitis. We describe the utility of intestinal ultrasound in monitoring disease activity and treatment response in a patient with microscopic colitis.

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

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

Inflammatory eye disease is a risk factor for future microscopic colitis: A nationwide population-based matched case control study.

BACKGROUND: Microscopic colitis (MC) is an inflammatory disorder of the colon. To date, the relationship between inflammatory eye diseases and MC is unclear. OBJECTIVE: To assess whether inflammatory eye disease (iridocyclitis and episcleritis) is a risk factor for MC. METHODS: We conducted a nationwide matched case control study in Sweden leveraging the ESPRESSO-study (a Swedish database containing data on all biopsies from the gastrointestinal tract from 1965 to 2017). In total, we identified 14,338 patients with biopsy-verified MC (diagnosed from 1981 to 2017). Patients with MC were matched (by age, sex, county and year of birth) with 68,753 controls from the general population and the occurrence of preceding inflammatory eye diseases (defined as diagnosis of episcleritis or iridocyclitis) in the two groups was compared. Multivariable adjusted odds ratios (aORs) were calculated using conditional logistic regression conditioned on the matching variables. RESULTS: A majority of patients with MC were women (71.9%) and the median age at MC diagnosis was 63.3 years (interquartile range (IQR) = 50.7-72.6). Some 225 (1.6%) MC patients had an earlier record of inflammatory eye disease compared with 614 (0.9%) in controls. These figures corresponded to an aOR of 1.77 (95% CI = 1.52-2.07) for inflammatory eye diseases in patients with MC. Compared to siblings, the aOR for previous inflammatory eye diseases in MC was 1.52 (95% CI = 1.17-1.98) and patients treated with budesonide, as a proxy for clinically significant disease, had a somewhat higher aOR for previous inflammatory eye diseases. CONCLUSION: Inflammatory eye diseases are more common in patients subsequently being diagnosed with MC. Our findings highlight that these conditions may have shared causes and inflammatory pathways and are of clinical interest to gastroenterologists, ophthalmologists and general practitioners.

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

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

The Metabolomic Profile of Microscopic Colitis Is Affected by Smoking but Not Histopathological Diagnosis, Clinical Course, Symptoms, or Treatment.

Microscopic colitis (MC) is classified as collagenous colitis (CC) and lymphocytic colitis (LC). Genetic associations between CC and human leucocyte antigens (HLAs) have been found, with smoking being a predisposing external factor. Smoking has a great impact on metabolomics. The aim of this explorative study was to analyze global metabolomics in MC and to examine whether the metabolomic profile differed regarding the type and course of MC, the presence of IBS-like symptoms, treatment, and smoking habits. Of the 240 identified women with MC aged ≤73 years, 131 completed the study questionnaire; the Rome III questionnaire; and the Visual Analog Scale for Irritable Bowel Syndrome (VAS-IBS). Blood samples were analyzed by ultra-high-performance liquid chromatograph mass spectrometry (UHLC-MS/UHPLC-MSMS). The women, 63.1 (58.7-67.2) years old, were categorized based on CC (n = 76) and LC (n = 55); one episode or refractory MC; IBS-like symptoms or not; use of corticosteroids or not; and smoking habits. The only metabolomic differences found in the univariate model after adjustment for false discovery rate (FDR) were between smokers and non-smokers. Serotonin was markedly increased in smokers (p < 0.001). No clear patterns appeared when conducting a principal component analysis (PCA). No differences in the metabolomic profile were found depending on the type or clinical course of the disease, neither in the whole MC group nor in the subgroup analysis of CC.

Factors associated with long-term clinical outcome in microscopic colitis.

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 Secondary to Leflunomide: A Case Report.

Microscopic colitis (MC) is characterized by chronic watery diarrhea that requires histological examination for diagnosis. Here, we present a case of a 63-year-old female with rheumatoid arthritis who developed persistent diarrhea following leflunomide initiation. Despite a normal colonoscopy, random colonic biopsies confirmed MC. Discontinuation of leflunomide led to symptom resolution, implicating it as the causative agent. Leflunomide-induced MC is exceedingly rare, with limited documented cases. Understanding its variability in presentation and timely recognition is crucial. This case underscores the importance of thorough medication history assessment and consideration of drug-induced colitis in patients presenting with unexplained diarrhea, facilitating prompt management and resolution.

Number of intraepithelial lymphocytes and presence of a subepithelial band in normal colonic mucosa differs according to stainings and evaluation method.

Chronic watery diarrhea is a frequent symptom. In approximately 10% of the patients, a diagnosis of microscopic colitis (MC) is established. The diagnosis relies on specific, but sometimes subtle, histopathological findings. As the histology of normal intestinal mucosa vary, discriminating subtle features of MC from normal tissue can be challenging and therefore auxiliary stainings are increasingly used. The aim of this study was to determine the variance in number of intraepithelial lymphocytes (IELs) and presence of a subepithelial band in normal ileum and colonic mucosa, according to different stains and digital assessment. Sixty-one patients without diarrhea referred to screening colonoscopy due to a positive feacal blood test and presenting with endoscopically normal mucosa were included. Basic histological features, number of IELs, and thickness of a subepithelial band was manually evaluated and a deep learning-based algorithm was developed to digitally determine the number of IELs in each of the two compartments; surface epithelium and cryptal epithelium, and the density of lymphocytes in the lamina propria compartment. The number of IELs was significantly higher on CD3-stained slides compared with slides stained with Hematoxylin-and-Eosin (HE) (p<0.001), and even higher numbers were reached using digital analysis. No significant difference between right and left colon in IELs or density of CD3-positive lymphocytes in lamina propria was found. No subepithelial band was present in HE-stained slides while a thin band was visualized on special stains. Conclusively, in this cohort of prospectively collected ileum and colonic biopsies from asymptomatic patients, the range of IELs and detection of a subepithelial collagenous band varied depending on the stain and method used for assessment. As assessment of biopsies from patients with diarrhea constitute a considerable workload in the pathology departments digital image analysis is highly desired. Knowledge provided by the present study highlight important differences that should be considered before introducing this method in the clinic.

What is the incidence of celiac disease in patients with microscopic colitis? Why are these two diseases related?

Introduction: Although there are studies in the literature showing that celiac disease (CD) is more common in patients with microscopic colitis (MC), there are publications to the contrary. The pathophysiologies of both diseases are different from each other. Aim: To investigate the frequency of CD in MC patients, the different features of these 2 diseases, and the relationship between them. Material and methods: In our prospective and cross-sectional analytical study, the presence of CD was investigated in 90 patients diagnosed with MC by colonoscopy and biopsy due to chronic diarrhoea between September 2011 and December 2021. Results: We detected MC in 102 (9.3%) of 1096 patients investigated for chronic diarrhoea. We detected CD in 1 (1.1%) of 90 patients with MC who participated in the study. Only 10% of the patients were positive for AGA IgA, 3.3% for EMA IgA, and 2.2% for Anti-TG2 IgA. There was no difference in autoantibody titre in treatment-responsive and treatment-resistant MC patients. HLA DQ2 was positive in 32.2% (n = 29) of the MC patients, and HLA DQ8 was found in 5.5% (n = 5). Intraepithelial lymphocyte increase was remarkable in the duodenal biopsies of MC patients who did not respond to treatment (40% vs. 11.4%; p = 0.007). Conclusions: We did not reach the conclusion that CD is more common in MC patients. An increase in IEL may also occur in the small intestine in patients with MC who do not respond to treatment.

Follow-Up of Microscopic Colitis Patients and Diarrhea Controls at 1 Year.

BACKGROUND AND AIMS: Microscopic colitis (MC) is a common cause of chronic diarrhea; however, the clinical course of this disease is poorly understood. We aimed to investigate how patients diagnosed with MC were treated in routine clinical practice and how their symptoms compared to patients with other causes of chronic diarrhea at one year follow-up. METHODS: We conducted a case-control study of patients undergoing outpatient colonoscopy to evaluate diarrhea. The study pathologist determined whether patients were classified as MC cases or non-MC controls. One year after colonoscopy, we interviewed cases (n = 74) and controls (n = 162) about their diagnosis, medications for diarrhea, and symptom burden. RESULTS: At 1-year follow-up after colonoscopy, 10% of MC cases were unaware of the diagnosis, 60% had been prescribed a medication for diarrhea, 40% had fecal urgency, 32% had weight loss, and 21% had fecal incontinence. Among cases, 46% were treated with budesonide. Compared to cases, controls had worse symptoms based on the Microscopic Colitis Disease Activity Index score with a median score of 3.0 (interquartile range 1.9-4.2) vs 2.3 (interquartile range 1.4-3.2) at 1-year follow-up. Controls had more frequent stools, urgency, fecal incontinence, and abdominal pain. CONCLUSION: In a cohort of patients with biopsy-confirmed MC and diarrhea controls, we found that some cases remained unaware of their diagnosis, many cases had persistent symptoms, and controls had worse symptoms than cases. These findings suggest there are opportunities to improve management of this chronic disease.

Microscopic Colitis and Risk of Incident Psoriasis: A Nationwide Population-Based Matched Cohort Study.

Background: Microscopic colitis (MC) has been associated with several immune-mediated diseases including psoriasis, but earlier research has been limited to psoriasis occurring before MC. Data from large-scale cohort studies investigating MC and risk of future psoriasis are lacking. Objective: To examine the association between MC and psoriasis. Methods: In a nationwide, population-based, matched cohort study in Sweden from 2007 to 2021, we identified 8404 patients with biopsy-verified MC (diagnosed in 2007-2017), 37,033 matched reference individuals, and 8381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a Swedish histopathology database with nationwide coverage). Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis up until 2021. Results: During a median follow-up of 9.2 years (interquartile range = 6.7-11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241.1 vs 131.8 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC over 10 years. After adjustment for the matching variables (birth year, sex, county of residence, and calendar period) and level of education, we computed an adjusted hazard ratio (aHR) of 1.82 (95% CI = 1.53-2.17). Stratified by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95% CI = 1.36-2.51). Conclusion: Patients with MC are at an almost doubled risk of psoriasis compared to the general population. Clinicians need to consider psoriasis in MC patients with skin lesions.

Colitis due to cancer treatment with immune check-point inhibitors - review of literature and presentation of clinical cases.

Treatment with immune checkpoint inhibitors is effective in various cancers, but may be associated with immune-mediated side effects in other organs. Among the more common ones is gastrointestinal tract involvement, especially colitis. In most patients, colitis is mild or responds to corticosteroid treatment. A smaller proportion of patients, more often those treated with cytotoxic T lymphocyte antigen-4 inhibitors, may have a more severe course of colitis, even life-threatening complications. In these patients, prompt action, timely diagnosis with endoscopic evaluation and early treatment with high-dose corticosteroids and, if ineffective, rescue therapy with biologic agents such as infliximab and vedolizumab are needed. We present three cases from our clinical practice, data on incidence and clinical presentation, current recommendations regarding diagnostic approach and treatment of immune checkpoint inhibitors induced colitis.

The association between drugs and repeated treatment with budesonide in patients with microscopic colitis: a retrospective observational study.

Background: Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC). Objectives: We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC. Design: Retrospective observational study. Methods: All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied. Results: Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th-75th percentile 4-10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06-12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39-2.90), PPIs (OR: 1.09, 95% CI: 0.45-2.63), SSRI (OR: 1.41, 95% CI: 0.82-2.44), or statins (OR: 0.83, 95% CI: 0.35-1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis. Conclusion: The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins.

The use of drugs and the odds for patients with microscopic colitis of having a second course of budesonide Microscopic colitis is a common cause of chronic diarrhea. Previous studies have shown that the use of non-steroidal anti-inflammatory drugs, acetylsalicylic acid, proton-pump inhibitors, serotonin reuptake inhibitors and statins are used more often in patients who later develop microscopic colitis. We aimed to study if these drugs also had an association to an increased risk of disease flares treated with budesonide in 183 patients with known microscopic colitis. Oral budesonide for 6-8 weeks are recommended for disease flares of microscopic colitis. In our study, 90 patients (49%) were prescribed a second course of budesonide probably due to a disease flare. We found a higher odds for being prescribed a second course of budesonide in patients with microscopic colitis who were prescribed non-steroidal anti-inflammatory drugs but no higher risk for the other 'risk drugs' for microscopic colitis.

Lymphocytic colitis can be transcriptionally divided into channelopathic and inflammatory lymphocytic colitis.

BACKGROUND: The pathobiology of the non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways. METHODS: We performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n = 4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data with a previous cohort of ulcerative colitis and Crohn's disease patients (n = 4 per group) to distinguish non-destructive from classic IBD. RESULTS: LC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation, and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD. Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared with CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation. CONCLUSIONS: We conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention.

Concomitant Lymphocytic Colitis With Recurrent Clostridium difficile Infection.

Microscopic colitis is a clinicopathological diagnosis that is characterized by chronic microscopic inflammation of the colon and presents with chronic watery diarrhea. There are following two subtypes of microscopic colitis: lymphocytic colitis and collagenous colitis. This is a case of a 70-year-old female with a history of Clostridium difficile infections who presented with persistent watery diarrhea and was diagnosed with lymphocytic colitis in the setting of a concomitant C. difficile infection. Given her clinical presentation, the patient was initiated on empiric treatment for C. difficile infection and showed a lack of clinical improvement with persistent watery diarrhea and elevated white blood cell count. The patient's symptoms resolved upon the confirmatory diagnosis and treatment of lymphocytic colitis. This study illustrates the importance of assessing for, diagnosing, and treating lymphocytic colitis in patients with chronic non-resolving watery diarrhea, especially in the setting of concomitant or recurrent C. difficile infections. Additionally, it emphasizes the need for further characterization of the relationship between C. difficile infection and microscopic colitis.