Diagnosis and Management of Microscopic Colitis in Pediatric Patients.

Microscopic colitis (MC) is an inflammatory disease of the colon, characterized by chronic watery diarrhea with distinguishing histologic findings despite normal endoscopic appearance of the colonic mucosa. MC is a common cause of diarrhea in older adults, though it has been infrequently reported in children and adolescents. As MC is rare in the pediatric population, and the clinical presentation is non-specific, increased awareness of this disease amongst pediatric clinicians and pathologists is essential for timely diagnosis, which requires performing colonoscopy with biopsy. The etiology of MC is incompletely understood, but current theories in pathogenesis inform management strategies. The goals of management in pediatric MC should be to achieve symptomatic improvement while minimizing adverse effects of treatment. Many patients who achieve clinical response have symptomatic recurrence after discontinuation of initial therapy, and may require maintenance medication therapy to sustain remission. This review aims to summarize the epidemiology and risk factors, clinical features, diagnosis, theories regarding pathogenesis, and suggested management approaches for MC in the pediatric population.

Quantifying risk factors for microscopic colitis: A nationwide, retrospective cohort study.

BACKGROUND: Microscopic colitis (MC) is associated with several risk factors; however, their relative risk has been variable and not thoroughly evaluated. We aimed to quantify the risk of medical comorbidities and medications associated with MC and treatment offered to these patients. METHODS: A population-based retrospective analysis in International Business Machines (IBM) Explorys (1999-2018), a pooled, de-identified database of 63 million patients in the USA, was performed. Odds ratios (OR) were calculated between MC and other diseases/medications. MC patients were also stratified by age to assess trends of MC in different age groups. RESULTS: A total of 1130 patients had MC in the database. Among medications, non-steroidal anti-inflammatory agents (OR, 20.2) and proton pump inhibitors (OR, 12.1) were associated with highest odds of MC. Among medical comorbidities, infectious gastroenteritis (OR, 26.6) and celiac disease (OR, 22.5) had the highest odds of being associated with MC. Tobacco smoking, psoriasis, Sjogren's syndrome, Clostridium difficile infection, and malabsorption syndromes all conferred odds greater than 10. CONCLUSION: Early identification of MC is critical for minimizing morbidity and mortality. Epidemiologic information can be integrated with current clinical algorithms to more rapidly identify patients at risk.

Alcohol Consumption is Associated With An Increased Risk of Microscopic Colitis: Results From 2 Prospective US Cohort Studies.

BACKGROUND: No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC. METHODS: We conducted a prospective cohort study of 209,902 participants (age range, 28.5-66.7 years) enrolled in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86-1.67) for consumers of 0.1-4.9 g/day of alcohol, 1.90 (95% CI, 1.34-2.71) for consumers of 5-14.9 g/day, and 2.31 (95% CI, 1.54-3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04-1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91-1.12) or liquor (aHR, 1.00; 95% CI, 0.92-1.09). CONCLUSIONS: Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.

Microscopic Colitis: A Concise Review for Clinicians.

Microscopic colitis (MC) is an inflammatory disease of the colon and a common cause of chronic watery diarrhea, predominantly in older patients. Microscopic colitis encompasses 2 different subtypes, lymphocytic colitis and collagenous colitis. The colon typically appears normal endoscopically in MC, and the diagnosis requires histologic evaluation. Whereas recent studies suggest that the incidence of MC has plateaued, given the aging of the population, the prevalence of MC will likely increase. Risk factors for MC include increasing age; female sex; presence of other autoimmune diseases; and possibly use of certain medications, including proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and statins. The clinical presentation of MC is nonspecific and includes watery nonbloody diarrhea, nocturnal stools, fecal urgency, abdominal pain, arthralgias, and weight loss. The disease course of MC is variable; some patients experience occasional, intermittent symptoms, and others demonstrate more chronic and even progressive symptoms. The approach to treatment is similar for both lymphocytic colitis and collagenous colitis and should be guided by the severity of the patient's symptoms. Offending medications highly associated with MC should be eliminated as clinically possible. In patients with mild symptoms, antidiarrheals such as loperamide are the initial choice; for moderate-severe disease, budesonide is recommended for induction of clinical remission. In those with recurrent symptoms, low-dose budesonide may be required for maintenance therapy with close monitoring for potential adverse effects. In rare cases, immunomodulators may be required.

Les colites microscopiques.

Microscopic colitis is frequently found as a cause of chronic watery diarrhea in women after menopause. The disease can be associated with a medication side effect in half of the patients (non-steroidal anti-inflammatory drugs or proton pump inhibitors for instance). Colonic biopsies are mandatory for the diagnosis of microscopic colitis and should be performed in several locations of the colon. Management of microscopic colitis is first based on avoiding iatrogenic factors and smoking together with symptomatic treatment of diarrhea (loperamide, cholestyramine). In case of failure or severe symptoms, budesonide is the key treatment. The aim of the treatment is to achieve clinical remission, defined as less than 3 liquid stools per day, to improve quality of life. After a first course of budesonide, recurrence of diarrhea is frequent and a maintenance therapy can be prescribed for several months. In case of intolerance or refractoriness, second-line therapy (immunosuppressants, biological therapy, surgery) should be discussed in multidisciplinary team meeting.

Colonic Manifestations and Complications Are Relatively Under-Reported in Systemic Sclerosis: A Systematic Review.

OBJECTIVES: Although systemic sclerosis (SSc) is known to affect the gastrointestinal (GI) tract, most of the literature focuses on esophageal, small intestinal, or anorectal manifestations. There have been no reviews focused on large bowel SSc complications in over 30 years. The aim of this study is to perform a systematic review of colonic manifestations and complications of SSc. METHODS: An experienced librarian conducted a search of databases, including English and Spanish articles. The search used keywords including "systemic sclerosis," "scleroderma," and "colon." A systematic review was performed using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Case reports/series were screened for validity by adapting from criteria published elsewhere. RESULTS: Of 1,890 articles, 74 met selection criteria. Fifty-nine of the 77 articles were case reports/series. The most common article topics on colonic SSc complications were constipation/dysmotility (15), colonic volvulus (8), inflammatory bowel disease (7), microscopic colitis (6), megacolon (6), and telangiectasia (6). Colonic manifestations constituted 24% of articles on GI complications of SSc. There were a total of 85 cases (84% women, with a median age of onset of colon complication of 52 years). Limited cutaneous SSc phenotype (65.6%) was more common than diffuse (26.2%). Patients frequently had poor outcomes with high mortality related to colonic complications (27%). Recent studies explore contemporary topics such as the microbiome in SSc and prucalopride for chronic constipation in SSc. DISCUSSION: Colonic complications comprise a large proportion of the published reports on GI symptoms afflicting patients with SSc and require raised diagnostic suspicion and deliberate action to avoid potentially serious complications including death.

Budesonide treatment for microscopic colitis from immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (CPIs) are effective against a variety of malignancies but can be limited by inflammatory toxicities such as enterocolitis. Enterocolitis is typically treated with systemically active glucocorticoids. Endoscopy can stratify patients by the severity of mucosal inflammation, including identifying patients with colitis in the absence of visible mucosal changes: microscopic colitis. Whether patients with CPI microscopic colitis could be managed differently from colitis with more severe mucosal involvement is unclear. The objective of this study was to describe outcomes in CPI microscopic colitis focusing on the response to first line treatment with budesonide. METHODS: We evaluated data from a retrospective cohort from a single-center large academic hospital. The participants were all adult patients evaluated by endoscopy for suspected CPI enterocolitis between 3/2017 and 3/2019. The exposures were: Mayo Endoscopic Score (range 0-3). The subset was: oral budesonide, maximum dose 12 mg daily, administered minimum of 5 weeks. The main outcomes and measures were: Primary: time from first CPI exposure to first glucocorticoid use; use of systemic glucocorticoids; time from symptom onset to resolution; continuation of CPI therapy; number of additional CPI infusions received. Secondary: admissions for symptom control; novel irAE development; need for second-line immunosuppression; oncologic outcomes. RESULTS: We identified 38 patients with biopsy confirmed CPI enterocolitis, 13 in the microscopic colitis cohort, and 25 in the non-microscopic colitis cohort. Budesonide use was higher in the microscopic colitis cohort (12/13 vs 3/25, p < 0.001), and systemic glucocorticoid use was higher in non-microscopic colitis (22/25 vs. 3/13, p < 0.001). Time from symptom onset to resolution did not differ. Microscopic colitis patients more frequently remained on CPI after developing (entero)colitis (76.9% vs 16.0%, p < 0.001). Microscopic colitis patients tolerating further CPI received, on average, 4.2 CPI infusions more than non-microscopic colitis patients tolerating CPI (5.8 vs 1.6, p = 0.03). Microscopic colitis was associated with increased time-to-treatment-failure (HR 0.30, 95% CI 0.14-0.66) and progression-free survival (HR 0.22, 95% CI 0.07-0.70). CONCLUSIONS: Gastrointestinal mucosal inflammation without visible mucosal injury is a distinct, prevalent CPI enterocolitis subset that can be diagnosed by endoscopy. First-line budesonide appears effective in controlling "microscopic colitis" symptoms and prolonging immunotherapy duration. These findings present a compelling rationale for routine endoscopic evaluation of suspected CPI enterocolitis and suggest an alternative glucocorticoid-sparing treatment strategy for a subset of such patients.

Smoking and Risk of Microscopic Colitis: A Systematic Review and Meta-analysis.

BACKGROUND: The association between smoking and inflammatory bowel disease has long been recognized, but its role in the development of microscopic colitis is less well defined. This systematic review and meta-analysis was conducted with the aims to identify all available studies on the association between smoking and risk of microscopic colitis and to synthesize their results. METHODS: The MEDLINE and EMBASE databases were searched from inception to May 2018 for cohort studies and case-control studies that compared the risk of microscopic colitis among current/former smokers vs individuals who have never smoked. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted from the included studies and pooled together using a random-effects model, generic inverse variance method of DerSimonian and Laird. Between-study heterogeneity was quantified using the Q statistic and I2. Publication bias was assessed using funnel plots. RESULTS: Seven studies (2 cohort studies and 5 case-control studies) with 262,312 participants met the eligibility criteria and were included in the meta-analysis. Relative to never-smokers, current smokers had significantly increased odds of microscopic colitis, with a pooled OR of 2.99 (95% CI, 2.15-4.15; I2, 64%). Former smokers also had significantly higher odds of microscopic colitis compared with never-smokers, with a pooled OR of 1.63 (95% CI, 1.37-1.94; I2, 0%). Funnel plots were symmetric and did not provide suggestive evidence of publication bias for both analyses. CONCLUSIONS: The current systematic review and meta-analysis found a significantly higher risk of microscopic colitis among current smokers compared with never-smokers. The risk attenuated among former smokers but remained significantly higher among never-smokers.

[Microscopic Colitis]. / Mikroskopische Kolitis.

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

Prevalence, Pathogenesis, Diagnosis, and Management of Microscopic Colitis.

Microscopic colitis (MC), which is comprised of lymphocytic colitis and collagenous colitis, is a clinicopathological diagnosis that is commonly encountered in clinical practice during the evaluation and management of chronic diarrhea. With an incidence approaching the incidence of inflammatory bowel disease, physician awareness is necessary, as diagnostic delays result in a poor quality of life and increased health care costs. The physician faces multiple challenges in the diagnosis and management of MC, as these patients frequently relapse after successful treatment. This review article outlines the risk factors associated with MC, the clinical presentation, diagnosis and histologic findings, as well as a proposed treatment algorithm. Prospective studies are required to better understand the natural history and to develop validated histologic endpoints that may be used as end points in future clinical trials and serve to guide patient management.

Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study.

OBJECTIVES: Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited. AIM: The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis. METHODS: A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality. RESULTS: Some 212 patients and 627 controls participated in the study. There was an association with a family history of microscopic colitis in both CC [odds ratio (OR): 10.3; 95% confidence interval (CI): 2.1-50.4, P=0.004] and LC (OR not estimated, P=0.008). Current smoking was associated with CC [OR: 4.7; 95% CI: 2.4-9.2, P<0.001) and LC (OR: 3.2; 95% CI: 1.6-6.7, P=0.002). The median age at diagnosis was around 10 years earlier in ever-smokers compared with never-smokers.CC was associated with a history of ulcerative colitis (UC) (OR: 8.7, 95% CI: 2.2-33.7, P=0.002), thyroid disease (OR: 2.3; 95% CI: 1.1-4.5, P=0.02), coeliac disease (OR: 13.1; 95% CI: 2.7-62.7, P=0.001), rheumatic disease (OR 1.9; 95% CI: 1.0-3.5, P=0.042) and previous appendicectomy (OR: 2.2; 95% CI: 1.3-3.8, P=0.003), and LC with UC (OR: 6.8; 95% CI: 1.7-28.0, P=0.008), thyroid disease (OR: 2.4; 95% CI: 1.1-5.4, P=0.037) and coeliac disease (OR: 8.7; 95% CI: 2.8-26.7, P<0.001). CONCLUSION: Association with a family history of microscopic colitis indicates that familial factors may be important. The association with a history of UC should be studied further as it may present new insights into the pathogenesis of microscopic colitis and UC.

Differences in the socio-economic distribution of inflammatory bowel disease and microscopic colitis.

AIM: Inflammatory bowel disease (IBD) and microscopic colitis are characterized by different geographical distributions across the USA. In this cross-sectional study we utilized demographic and socio-economic information associated with individual ZIP codes to further delineate the epidemiological characteristics of the two diseases. METHOD: A total of 813 057 patients who underwent colonoscopy between 2008 and 2014 were extracted from an electronic database of histopathology reports. The prevalence of patients with IBD or microscopic colitis was expressed as percentage of the population associated with specific demographic (age, sex, ethnicity) and socio-economic characteristics (population size, housing value, annual income, tertiary education). RESULTS: Both diseases were more common among subjects from ZIP codes with predominantly White residents and less common among subjects from ZIP codes with predominantly non-White residents such as Black, Hispanic and Asian. These ethnic variations were more pronounced in microscopic colitis than IBD. Markers of affluence, such as average residential house value and annual income, were positively associated with IBD and negatively with microscopic colitis. The prevalence of both diseases was positively correlated with tertiary education. CONCLUSION: The occurrence of both IBD and microscopic colitis is influenced by environmental risk factors. The differences in the demographic, ethnic and socio-economic distributions of the two diseases suggest that different sets of risk factors affect the two diseases and that their aetiology is unrelated.

Trends in Irritable Bowel Syndrome Incidence among Taiwanese Adults during 2003-2013: A Population-Based Study of Sex and Age Differences.

BACKGROUND: No population-based irritable bowel syndrome (IBS) incidence data among Taiwanese adults are available. Whether IBS is associated with risk of organic colonic diseases remains unanswered. We investigated 1) the sex- and age-stratified trends in the annual incidence of IBS, and 2) the risk of selected organic diseases in patients with IBS compared with those without IBS among Taiwanese adults during 2003-2013. METHODS: Medical claims data for 1 million randomly selected beneficiaries were obtained and analyzed. Patients with IBS were considered eligible for enrollment if they aged between 20 and 100 and had at least two medical encounters with IBS codes within 1 year. To test whether there was a linear secular trend in IBS incidence over time, multivariate Poisson regression with generalized estimating equation model was conducted. The risk of selected organic diseases associated with IBS was examined using multivariate Cox proportional hazard regression. RESULTS: From 2003 to 2013, the incidence of IBS significantly decreased over time [adjusted incidence rate ratio (IRR) = 0.97, p< 0.001]; the incidence of IBS significantly increased with age (adjusted IRR = 1.03, p < 0.001) and was significantly higher in women than in men (adjusted IRR = 1.14, p< 0.001). IBS significantly associated with increased risk of microscopic colitis, inflammatory bowel disease, and colorectal cancer during a 10-year follow-up period. CONCLUSIONS: The incidence of IBS increased with age and was slightly higher in women than in men among Taiwanese adults. During 2003-2013, IBS incidence gradually decreased over time. IBS may increase risk of several colonic organic diseases.

The association between the intake of specific dietary components and lifestyle factors and microscopic colitis.

BACKGROUND/OBJECTIVES: The incidence of microscopic colitis (MC) has increased over the previous decades. In addition to smoking and drugs, currently unidentified environmental factors may have a role. The aim of this study was to determine whether specific dietary or other lifestyle factors were associated with the development of MC. SUBJECT/METHODS: The population-based cohort Malmö Diet and Cancer Study of 28 095 individuals was examined. Information about dietary habits was collected by a modified diet history method. Data on anthropometry were measured, and socio-economic and lifestyle factors were collected by questionnaires. Cases of MC were identified in medical registers. Associations were estimated using Cox regression analysis. RESULTS: During a 22-year period, 135 patients were diagnosed with MC. Intakes of protein, carbohydrates, sucrose, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 or omega-6 fatty acids, fibre and zinc were not associated with MC. We could verify the previously reported association between MC and smoking (hazard ratio (HR): 2.29; 95% confidence interval (CI): 1.66-3.84) and the female gender (HR: 3.57; 95% CI: 2.22-5.74). High alcohol consumption was associated with an increased risk for MC (HR: 1.89 for the highest quartile; 95% CI: 0.82-4.33, P for trend=0.032). In a post hoc analysis, alcohol intake including all patients independently of consumption seemed to reduce the smoking-related risk. CONCLUSIONS: Despite a large cohort and a long follow-up period, we could not detect any dietary risk factors for MC. The aetiological mechanisms behind the positive impact of smoking and alcohol on MC risk should be investigated.

Diagnosis and treatment of microscopic colitis.

Microscopic colitis (MC) designates two types of chronic diarrhea diseases, which are lymphocytic colitis and collagenous colitis. The prevalence of microscopic colitis is increasing in both Western and Eastern countries, possibly due to the high incidence of colonoscopic survey in chronic diarrhea patients. Although the overall prognosis of MC patients is mostly good, it should be noted that appropriate diagnosis and choice of treatment is required to assure a good clinical outcome for MC patients. Also, a certain population of MC patients may take a severe and refractory clinical course, and thus require advanced clinical care using medications supported by less evidence. In this review, we would like to feature the essential points regarding the diagnosis of MC, and also describe the current standard of treatments for MC patients. In addition, we would like to add some findings from the national survey and research carried out in Japan, to compare those data with the western countries.

[MICROSCOPIC COLITIS: CURRENT STATE-OF-THE-ART].

The aim of the study was to analyse publications on practical aspects of the management of microscopic colitis (MC) as a common manifestation of diarrheic syndrome in aged subjects. Many etiopathogenetic issues remain debatable. Major difficulties are encountered in differential diagnostics. Of special importance is the relationship between MC, autoimmune and inflammatory intestinal diseases. Approaches to MC therapy vary from the use of antidiarrheal agents to comprehensive immunosuppressive treatment.

Microscopic colitis: A review of etiology, treatment and refractory disease.

Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor (TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis.

Drug consumption and additional risk factors associated with microscopic colitis: Case-control study.

BACKGROUND: Microscopic colitis has now emerged as a common cause of chronic diarrhoea, but its aetiology remains unknown. Some studies suggest that commonly prescribed drugs and other additional risk factors may be triggers. AIMS: To evaluate the effects of drug intake and other risk factors on microscopic colitis patients. METHODS: A prospective, case-control study with all consecutive adult patients referred to the Hospital General de Tomelloso (Ciudad Real, Spain) for chronic watery diarrhoea (from 2008 to 2011) was performed. Microscopic colitis was diagnosed following the commonly accepted histopathological criteria. RESULTS: 46 consecutive new cases of microscopic colitis and 317 chronic diarrhoea controls were recruited. Five independent risk factors significantly associated with microscopic colitis were identified: Abdominal pain (OR 3.25; 95%CI, 1.49-7.08), weight loss (OR 2.67; 95%CI, 1.16-6.15), celiac disease (OR 15.3; 95%CI, 3.70-63.5), topiramate intake (OR 13.6; 95%CI, 1.84- 100.8), and older age at diagnosis (OR 1 year increase 1.022; 95%CI, 1.002-1.042). Use of non-steroidal anti-inflammatory drugs was associated with microscopic colitis in the subgroup of patients who fulfilled irritable bowel syndrome criteria (38.5% vs. 10.8%; p < 0.017). CONCLUSIONS: Microscopic colitis is associated with autoimmune disease, an increased age at diagnosis, topiramate intake and only in a sub-group of irritable bowel disease patients with non-steroidal anti-inflammatory drugs.