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.

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.

Microscopic colitis related to food supplement containing turmeric: a review of 3 cases.

Microscopic colitis is a chronic inflammatory disorder of the colon characterized by microscopic changes in the intestinal lining. Turmeric, a commonly used spice, is generally regarded as beneficial for digestive and articular health thanks to its anti-inflammatory properties. No cases of microscopic colitis under a food supplement containing turmeric has been previously described in the literature. This article highlights 3 cases where the consumption of a specific turmeric-based supplement caused microscopic colitis. Each of them complained about profuse watery diarrhea shortly after initiating the food supplement containing turmeric. Ileo-colonoscopies with biopsies confirmed the diagnosis of microscopic colitis, with two cases classified as lymphocytic colitis and the third as collagenous colitis. Following the discontinuation of the supplement, all patients experienced a resolution of their symptoms within a few days. Subsequent control biopsies for the three patients confirmed the resolution of microscopic colitis.

Rifaximin Treatment of Collagenous Colitis: A Randomised, Double-Blind, Placebo-Controlled Trial.

Introduction: Collagenous colitis (CC) is a disabling disease primarily affecting elderly women. Sparse, well-documented treatment modalities exist, except for budesonide. Long-term and repetitive treatment with budesonide is often necessary. Rifaximin is a poorly absorbed antibiotic with a positive modulatory effect on gut microbiota. In this randomised, double-blind, placebo-controlled single-centre trial, we test the effect of adding rifaximin in continuation to budesonide on relapse rates in CC. Methods: Eligible patients with active, biopsy-verified CC received oral budesonide during a 6-week open-label induction phase. Patients in clinical remission after 4 weeks of treatment were randomised to receive either rifaximin or placebo for 4 weeks. Results: Fifteen patients were randomised to receive either rifaximin (n = 7) or placebo (n = 8). At 12-week follow-up, 2 patients in the rifaximin group were still in remission and none in the placebo group (p = 0.2). The median number of days in remission in the rifaximin group was 42 (interquartile range [IQR] 33-126) compared to 18.5 (IQR 10.5-51.5) in the placebo group (p = 0.189). At 12-week follow-up, the relapse rate per 100 person-days in the placebo group was higher (3.25 [1.40-6.41]) than in the rifaximin group (1.33 [0.43-3.10]). Conclusion: Although not statistically significant (p = 0.0996), the study suggests a potential improvement in relapse rates within the rifaximin group compared to the placebo group. A major limitation in the study is the small sample size.

Collagenous Colitis with Escitalopram Use: A Case Report and Literature Review.

We present the case of a 42-year-old female whose escitalopram use potentially contributed to a diagnosis of collagenous colitis. The patient presented with significant watery, nonbloody diarrhea, abdominal cramping and pain, and weight loss. Established risk factors of microscopic colitis in this patient include a history of smoking and female gender. The patient underwent a colonoscopy, which confirmed histological changes consistent with collagenous colitis. Prescribed therapy included oral budesonide and omeprazole, continued for eight and twelve weeks, respectively. Escitalopram was continued, with a discussion regarding changing to an alternative therapy. Based on the patient's history of escitalopram use, this case suggests a relationship between escitalopram and microscopic colitis. Though case reports of patients diagnosed with microscopic colitis after antidepressant use are published, this case appears to be the only report of collagenous colitis without macroscopic complications following escitalopram use. This case adds further support in that antidepressants may contribute to microscopic colitis. Despite an undefined frequency of association, healthcare providers who prescribe antidepressants should be cognizant of the theorized association and understand risk factors, screening, and treatment approaches.

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

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

Clinical Implications of Microscopic Colitis Isolated to Polyps.

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.

Immune-Related Diarrhea and Colitis in Non-small Cell Lung Cancers: Impact of Multidisciplinary Management in a Real-World Setting.

INTRODUCTION: Immune-related adverse events (irAEs) constitute a challenge in the clinical management of solid tumors. This study aims to collect real-world data on the occurrence of immune-mediated diarrhea and colitis (IMDC) in advanced non-small cell lung cancer (aNSCLC) treated with immune checkpoint inhibitors (ICIs) and to assess the clinical impact of a multidisciplinary approach (MDA) on IMDC management. METHODS: We retrospectively collected data on patients with aNSCLC consecutively treated with ICIs, either as single agent or in combination with chemotherapy, between September 2013 and July 2022. Among patients developing IMDC, we conducted blinded revision of colonic biopsies and evaluated the clinical impact of the introduction of MDA through predefined indicators. RESULTS: Among the 607 patients included, 84 (13.8%) experienced IMDC. Pathological review highlighted a high prevalence of microscopic colitis (28%), with a collagenous pattern linked to longer symptoms duration (P = .01). IMDC occurred more frequently in females (P = .05) and PD-L1 expressors (P = .014) and was correlated with longer progression-free survival (17.0 vs 5.8, P < .001) and overall survival (28.3 vs 9.5, P < .001). The introduction of MDA was associated with increased employment of diagnostical tools such as fecal calprotectin test (P < .001), colonoscopy (P < .001), and gastroenterological evaluation (P = .017) and a significant decrease in both grade 3 conversion rate (P = .046) and recurrence after rechallenge (P = .016). Hospitalization rate dropped from 17.2% to 3.8% (P: ns). CONCLUSION: These findings highlight the clinical relevance of IMDC and support the incorporation of a MDA to optimize the clinical management of this irAE to improve patient care. Prospective validation has been planned.

Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of Microscopic Colitis Subtypes.

BACKGROUND AND AIMS: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. METHODS: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. RESULTS: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 × 10-23, odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rg = 0.77; p = 0.048] and oesophageal diseases [rg = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 × 10-8, OR = 1.31]. No significant association was detected for LC. CONCLUSION: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.

[Clinical cases of microscopic colitis: Diagnosis and treatment issues. Case report].

Currently, there is an increase in the incidence of microscopic colitis. There are difficulties in diagnosing this disease due to the variability of histological signs, variability of morphological changes in the mucous membrane of the colon in different parts of the colon, and the combination in one patient of not only various forms of microscopic colitis, but also other intestinal diseases. The article describes the differential diagnosis, an example of its staging and successful treatment of various forms of microscopic colitis with budesonide (two clinical cases presented).

Microscopic Colitis: A Review Article.

Microscopic colitis (MC) is a chronic inflammatory disease that affects the older population. Its clinical presentation includes a variety of gastrointestinal manifestations. The main symptom is chronic watery, nonbloody diarrhea. The disease has a female predominance. The diagnosis might be challenging since the symptoms are similar to other differential diagnoses, such as celiac disease, irritable bowel syndrome, Crohn's disease, bacterial overgrowth, and infectious colitis. The golden diagnostic tool for diagnosis is performing colonoscopy to obtain the colonic biopsy, which demonstrates the characteristic histological evidence needed for diagnosis. The treatment starts with an accurate diagnosis and trial of any possible offending medications. Alternatively, there are many medications, such as bismuth or budesonide, which are very effective in treating this disease. The primary objective of this detailed review is to enhance knowledge and understanding of this condition among healthcare providers to guide them with detailed information regarding epidemiology, clinical presentation, diagnosis, and appropriate management. In the assessment of individuals presenting with persistent chronic diarrhea, it is essential for healthcare providers to consider MC as a probable differential diagnosis.

The Utility of Fecal Calprotectin in the Diagnosis and Management of Microscopic Colitis.

Background: The incidence of microscopic colitis has increased over time. To date, there is no specific biomarker for microscopic colitis, and the diagnosis relies on histopathological tissue obtained during colonoscopy which is an invasive and costly procedure. Unlike Crohn's disease and ulcerative colitis, the utility of fecal calprotectin in diagnosing or monitoring microscopic colitis has not been established, and studies on the role of fecal calprotectin in microscopic colitis are limited. In this retrospective study, we analyzed the utility of this biomarker in the diagnosis of microscopic colitis. Methods: The medical records of patients who have been diagnosed with collagenous colitis and lymphocytic colitis aged 18-89 years old were retrospectively reviewed. Patient characteristics were recorded in those who had fecal calprotectin measured. Results: There were 198 patients who were diagnosed with collagenous colitis and lymphocytic between October 1, 2015, and July 31, 2022. Twenty-three patients had fecal calprotectin levels measured and were included in this study. The mean age was 51.7 ± 7.8 years in all groups. Thirteen patients were female. Six patients (26.1%) were diagnosed with collagenous colitis, and 17 patients (73.9%) were diagnosed with lymphocytic colitis. The fecal calprotectin cut-off in this lab is 50 µg/g stool. Median fecal calprotectin levels were 30.1 µg/g (15.6, 122.5), 19.5 µg/g (16.5, 64.6), and 33.2 µg/g (15.6, 134.9) in all groups, collagenous colitis, and lymphocytic colitis, respectively. Conclusion: The utility of fecal calprotectin in diagnosing microscopic colitis is limited. Our study suggests the diagnosis should be based on histopathology tissue obtained during colonoscopy.

What do we know today about drug-induced microscopic colitis? A case of lymphocytic colitis on olmesartan.

Microscopic colitis is part of the differential diagnosis of chronic watery diarrhea. Colonoscopy discloses a normal looking mucosa, therefore its diagnosis is based on histology of colonic biopsies. Two main phenotypes are distinguished: collagenous colitis and lymphocytic colitis. A third entity, incomplete microscopic colitis or unspecified microscopic colitis has been reported in the literature. It affects preferentially women over 60 years of age and its association with certain drugs is increasingly established. In case of suspected drug-induced microscopic colitis, identification of the responsible drug is a key to management. After discontinuation of the suspected drug, the gold standard of treatment is budesonide both for induction and for maintenance in case of clinical relapse, as is often the case after discontinuation. Therapy with immunomodulators, biologics, or surgery is reserved for refractory forms of microscopic colitis after multidisciplinary consultation. Through the clinical case of colitis on olmesartan, we will review the latest recommendations on drug-induced microscopic colitis.

Colon perforation due to collagenous colitis: A case report.

Collagenous colitis (CC) is generally benign, and serious complications are rare. It is important to note that spontaneous perforation of CC is a possible complication. In the case of colon perforation of unknown origin, CC should be considered.

Regional differences in the incidence of lymphocytic and collagenous colitis over time.

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.

Adult-Onset Still's Disease (AOSD) Associated With Collagenous Colitis (CC) and Basedow's Disease: A Case Report.

Adult-onset Still's disease (AOSD) is a rare auto-inflammatory syndrome of unknown etiology. Basedow's disease is a common cause of auto-immune hyperthyroidism. Collagenous colitis (CC) is a form of microscopic colitis (MC) affecting predominantly young women. While the etiology of the disease remains unclear, some studies suggest the role of auto-immunity. The association between AOSD and Basedow's disease has been reported in previous cases, suggesting auto-inflammation as a potential trigger of relapsing thyroid dysfunction. Although the co-existence of AOSD with inflammatory gastrointestinal disorders such as Crohn's disease and ulcerative colitis has also been described, we did not find any correlation with MC in the literature. We here describe the case of a woman having AOSD associated with Basedow's disease and CC.