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.

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.

Coexisting Th1 and Th2 cytokines in patients with collagenous gastritis and implications for its pathogenesis.

OBJECTIVES: Collagenous gastritis (CG) is a rare cause of refractory dyspepsia and anemia that frequently affects children and young adults and whose histological hallmark is chronic mucosal inflammation with a subepithelial collagen band. The etiology remains obscure, and no established treatments exist. We investigated the pathogenesis of CG by determining the expression profiles of genes related to immunity and inflammation in index biopsies. METHODS: Gastric biopsies from 10 newly diagnosed patients with CG were evaluated using the NanoString nCounter assay. Gastric biopsies from 14 normal individuals served as controls. The gene expression ratios for CG versus controls were determined in pooled samples and confirmed in individual samples by quantitative reverse transcription polymerase chain reaction. The results were compared with previously reported expression data from a cohort of patients with collagenous colitis, a colonic disorder with similar morphology, including subepithelial collagen band. RESULTS: CG biopsies featured enhanced expression of key genes encoding both Th1 (IFNγ, TNF-α, IL-2, IL-10, IL-12A, IL-12B, and IL-18) and Th2 cytokines (IL-3, IL-4, IL-5, IL-6, and IL-13). In contrast, biopsies from patients with CC exhibited upregulated Th1 cytokines only. CONCLUSIONS: We show in this first published gene expression profiling study that CG involves simultaneous upregulation of Th1 and Th2 cytokines. This finding is unique, contrasting with other types of chronic gastritis as well as with collagenous colitis, which shares the presence of a collagen band. Involvement of Th2 immunity in CG would support further investigation of potential dietary, environmental, or allergic factors to guide future therapeutic trials.

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.

Leflunomide-induced collagenous colitis: a case report and literature review.

We describe a patient with rheumatoid arthritis and Hashimoto's thyroiditis who developed chronic diarrhea and subsequently diagnosed with collagenous colitis (CC) 5 years after leflunomide initiation. Cessation of leflunomide resulted in complete resolution of diarrhea within 2 months. Although rare, leflunomide-induced colitis should be considered in patients with otherwise unexplained chronic diarrhea. Diagnosis is challenging as symptom onset can occur many years after leflunomide initiation, but diarrheal symptoms typically resolve within weeks to months of stopping the instigating drug.

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.

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.

Celiac disease and risk of microscopic colitis: A nationwide population-based matched cohort study.

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.

Meta-analysis: Placebo rates in microscopic colitis randomised trials and applications for future drug development using a historical control arm.

BACKGROUND: Effective medical therapies for patients with microscopic colitis (MC) who fail budesonide are lacking. However, conducting randomised controlled trials (RCTs) in MC has been challenging due to small sample sizes. Understanding placebo responses can help inform more efficient future trials. AIMS: The aim of this study is to estimate clinical and histologic placebo response rates and to determine factors associated with placebo response in MC. METHODS: EMBASE, MEDLINE, and CENTRAL were searched until 7 January 2022, to identify placebo-controlled RCTs in adult patients with MC. Clinical and histologic response in the placebo arms were pooled using random-effects models. Stratified analyses based on disease- and trial-level characteristics, leave-one-out meta-analysis, and cumulative meta-analysis were performed. RESULTS: Twelve RCTs enrolling a total of 391 patients (placebo n = 163) with MC were included. Pooled clinical and histologic placebo response rates were 24.4% (95% CI: 12.4%-38.4%), I2  = 60.8%, p < 0.01, and 19.9% (95% CI: 5.3%-39.0%), I2  = 66.4%, p = 0.01 (tests for heterogeneity), respectively. Clinical response to placebo was numerically higher in patients with lymphocytic compared to collagenous colitis (39.9% vs. 19.8%, p = 0.08). Heterogeneity in clinical response to placebo was significantly reduced when the Miehlke 2014 RCT was excluded in the leave-one-out meta-analysis or when a more stringent secondary definition of response based on the Hjortswang criteria was applied. CONCLUSIONS: Approximately one-quarter of patients in MC trials respond to placebo, although with substantial heterogeneity, reflecting the need for standardised outcome definitions and study designs for MC. This analysis also serves to inform future MC trials that may consider incorporating an external, historical placebo control arm, rather than directly randomising patients to placebo.

Microscopic colitis: lymphocytic colitis, collagenous colitis, and beyond.

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.

Appendectomy and Future Risk of Microscopic Colitis: A Population-Based Case-Control Study in Sweden.

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.

Frequency And Risk Factors Of Microscopic Colitis As A Cause Of Chronic Watery Diarrhoea.

BACKGROUND: Microscopic colitis (MC) is one of the most underdiagnosed conditions leading to chronic watery diarrhoea in patients worldwide. This is the first study of this kind in Pakistan and we aimed to calculate the frequency as well as study the risk factors behind the disease. METHODS: This was a prospective cross-sectional study in a tertiary care hospital in Pakistan. A total of 58 participants with chronic watery diarrhoea who had normal colonoscopy were recruited for the study and biopsies were obtained for diagnosing MC. RESULTS: 2 participants out of 58 (3.4%) had biopsy proven microscopic colitis; one patient had a lymphocytic colitis variant and the other had a collagenous colitis variant. The average score based on the MC scoring system was 7.53 in the entire study group. The patient with lymphocytic colitis had a score of 06 while the patient with collagenous colitis had a score of 8. CONCLUSIONS: The frequency of microscopic colitis was found to be 3.4% of all cases of chronic watery diarrhoea. A link between MC and autoimmune diseases was also observed. However, we had a limited sample size and encouraged future studies to employ a larger sample size to get a multifaceted look at the disease process.

Spontaneous colonic perforation with collagenous colitis in an elderly patient.

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

Cat scratch lesions as a manifestation of chronic colitis due to spirochetosis.

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

Microscopic colitis in Northern Ireland: an updated clinicopathological audit and assessment of compliance with European guidelines.

AIM: We previously reported the first population-based study of the epidemiology of microscopic colitis in Northern Ireland. The aim of the current study is to provide updated data on incidence, diagnostic methods and clinicopathological associations, following dissemination of the previous report. A further aim was to compare the findings against relevant recommendations from the 2020 European guidelines. METHOD: Study cases were identified via the Belfast Health and Social Care Trust pathology laboratory system for new cases of collagenous colitis or lymphocytic colitis diagnosed from 2017 to 2020 inclusive. Demographic and clinical information was collated from electronic healthcare records. RESULTS: Two hundred and seventeen new diagnoses of microscopic colitis were made between 2017 and 2020, comprising 89 (41%) collagenous colitis and 128 (59%) lymphocytic colitis. The overall incidence of microscopic colitis, expressed per 100,000 adult population, ranged from 7.6 to 11.5 (5.9 to 9.0 per 100,000 total population). The 2019 peak of 11.5 cases per 100,000 adult population represents a 71.6% increase in incidence compared with the mean incidence of 6.7 per 100,000 adult population from previous data for 2008-2016. There has also been a significant increase in number of cases diagnosed on separate sampling from the right and left colon (85% in 2019-2020 compared with 30% in 2008-2016; p < 0.001). Overall compliance with coeliac serology testing has improved, with 89% tested in 2017-2018 compared with 75% in 2008-2016. CONCLUSION: Clinicopathological communication has contributed to an increased incidence of microscopic colitis in Northern Ireland through better endoscopic diagnostic sampling and pathology coding practices. Coeliac serology testing has also improved, although continued clinical awareness is required of the need for coeliac serology testing in all patients diagnosed with microscopic colitis.