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.

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.

Clinicopathologic Characterization of Lymphocytic Colitis in the Pediatric Population.

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.

Acquired Ichthyosis Revealing Lymphocytic Colitis.

A 69-year-old patient with no personal or family history of ichthyosis consulted our dermatology department for diffused cutaneous xerosis with intense pruritus evolving for 3 weeks. Physical examination revealed diffused ichthyosis of large polygonal fine scales on the skin without erythema (Figure 1). The lesions spared the face. Examination of the mucous membranes, hair, and nails revealed no abnormalities. There was no fever or adenomegaly. A skin biopsy revealed an orthokeratotic hyperkeratosis with thinning of granular layer (Figure 2). The initial diagnosis of acquired ichthyosis was maintained. The patient also reported a change in bowel habits since 2 weeks with watery, non-bloody diarrhea and mild steatorrhea. His laboratory investigations presented low serum vitamin B12 level, mild anemia, hypoalbuminemia, and fecal leukocytes; however, antinuclear antibodies, perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), rheumatoid factor, and complement components C3 and C4 were normal. A colonoscopy performed was also normal without any abnormalities. Colon biopsies revealed histologic aspects of lymphocytic colitis with more than 20% increase in lymphocytes in the surface epithelium of colorectal mucosa. Laboratory investigations excluded neoplasia, hemopathies, or autoimmune-associated diseases. The patient was treated with salazopyrin with a remarkable lessening of diarrhea and cutaneous manifestations within 4 weeks (Figure 3).

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.

Reduced Intake of Dietary Tryptophan Improves Beneficial Action of Budesonide in Patients with Lymphocytic Colitis and Mood Disorders.

Lymphocytic colitis (LC) is a gastrointestinal (GI) tract disease with poorly known pathogenesis, but some environmental and lifestyle factors, including certain dietary components, may play a role. Tryptophan is an essential amino acid, which plays important structural and functional roles as a component of many proteins. It is important in the development and maintenance of the body, in which it is metabolized in two main pathways: kynurenine (KYN) and serotonin. In this work, we explored the effect of reducing of TRP in the diet of patients with LC with mood disorders. We enrolled 40 LC patients who had a normal diet, 40 LC patients with the 8-week diet with TRP content reduced by 25% and 40 controls. All LC patients received budesonide at 9 mg per day, and the severity of their GI symptoms was evaluated by the Gastrointestinal Symptoms Rating Scale. Mood disorders were evaluated by the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA), in urine were determined. Budesonide improved the GI and mental states of LC patients, and the diet with reduced TRP content further amended these symptoms. Dietary intervention decreased the concentration of 5-HIAA by about 50% (3.4 vs. 6.3) and QA by about 45% (3.97 vs. 7.20). These changes were correlated with a significant improvement in the profitable action of budesonide on gastrointestinal and mental health of LC patients as they displayed significantly lower GSRS, HAM-A and HAM-B scores after than before the intervention-10.5 vs. 32, 11.0 vs. 21 and 12 vs. 18, respectively. In conclusion, a reduction in TRP intake in diet may improve GI and mental symptoms in LC patients treated with budesonide and these changes may be mediated by the products of TRP metabolism.

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.

Type 1 diabetes and microscopic colitis: A nationwide matched case-control study in Sweden.

BACKGROUND AND AIMS: Microscopic colitis (MC) is a colonic inflammatory condition associated with autoimmune dysfunction. Type 1 diabetes (T1D) is a chronic disease induced by autoimmune destruction of pancreatic ß-cells. We aimed to examine the association between T1D and MC. METHODS: A matched case-control study was conducted using the nationwide ESPRESSO cohort as study base. All biopsy-confirmed MC patients born after 1940 were identified and compared to biopsy-free individuals matched from the general population for T1D diagnosis using the Swedish National Patient Register. The T1D-MC association was estimated as odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models, considering differences by sex and MC subtype. Full sibling comparison and adjustment for MC-associated medications were also performed. RESULTS: We identified 352 (3.7%) and 945 (2.0%) T1D diagnoses from 9,600 MC cases and 47,870 matched population controls, respectively, which corresponded to an overall OR of 1.79 (95% CI: 1.56-2.05). The association was stronger for collagenous colitis (OR, 2.15; 95% CI: 1.70-2.71) than lymphocytic colitis (OR, 1.62; 95% CI: 1.37-1.92) and remained statistically significant in full sibling comparison (OR, 1.46; 95%: 1.18-1.81). Medication adjustment attenuated the association to null among females (OR: 1.02; 95% CI: 0.82-1.27) but not among males (OR: 1.45; 95% CI: 1.11-1.90). CONCLUSION: T1D diagnosis was almost 80% more prevalent in MC patients compared to general population. This positive association did not seem to be spurious due to residual confounding shared by full siblings but may relate to consumption of medications associated with MC onset.

Lymphocytic colitis with macroscopic findings.

The clinical case of a patient in the fifth decade of life with a diagnosis of lymphocytic colitis is presented, who comes for chronic diarrhea, which receives treatment with Budesonide with partial response.

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.

[Lymphocytic colitis caused by medicine ingredient modification].

A 49-year-old woman was referred to our hospital for further evaluation and treatment of diarrhea. Colonoscopic findings revealed indistinct vascular patterns and extensive edema in a colon segment, and white granular mucosa and crack-like appearance in the sigmoid colon and rectum. She was diagnosed with lymphocytic colitis (LC) based on lymphocytic infiltration into the epithelium on histopathological examination. Diarrhea symptoms resolved after long-term medication withdrawal. This medicine's composition was changed 4 years ago and this modification possibly triggered LC.

Is mastocytic colitis a specific clinical-pathological entity?

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.