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.

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.

Microscopic colitis.

Microscopic colitis (MC) is the common denominator for lymphocytic and collagenous colitis (CC). It is now recognized as a relatively frequent cause of diarrhea that equals the prevalence of inflammatory bowel disease. Patients are typically middle-aged women, but disease may occur at every age. Patients with MC report watery, non-bloody diarrhea in the absence of endoscopic and radiologic abnormalities. Lymphocytic colitis is characterized by an increased number of intraepithelial lymphocytes, and CC by a thickened subepithelial collagen band, whereas in both an increased mononuclear infiltration of the lamina propria is found. The pathogenesis of MC is largely unknown, but may relate to autoimmunity, adverse reactions to drugs or (bacterial) toxins, and abnormal collagen metabolism in the case of CC. Budesonide is so far the only drug that has proven efficacy in randomized controlled trials both for the induction and maintenance of remission. Patients who are nonresponsive, dependent or who experience side effects on budesonide may benefit from thiopurine or anti-TNF treatment, but these options are still experimental. The long-term prognosis of MC is good; it does not appear to predispose to malignancies and can in some cases be self-limiting. Further research and randomized clinical trials are required to expand our understanding of the natural course and the pathogenesis of MC.

Advances in knowledge on microscopic colitis: From bench to bedside.

Microscopic colitis (MC) is a general term that describes a family of chronic inflammatory bowel diseases, including lymphocytic colitis (LC) and collagenous colitis (CC). The two forms are characterized by chronic watery diarrhea with normal or near normal endoscopic colonic appearance and specific histopathological abnormalities.Data from recent epidemiological studies reported the diagnosis of MC from several different regions in the world, providing that it can be a worldwide condition. The etiopathogenesis of MC still remains unknown but it is generally accepted that MC is a multifactorial disease, probably secondary to an abnormal immune reaction in predisposed individuals, triggered by different luminal factors (infections, drugs, autoimmunity and/or bile acids). Furthermore, some studies show that the epithelial barrier function in the colonic mucosa of MC patients is also impaired. Several mucosal factors of intestinal inflammation have been studied in MC, postulating that an aberrant T-lymphocyte response may lead to a chronic gut inflammatory condition, with the infiltration of colonic mucosa by different proportion of subset of T-lymphocytes. Little is known about the specific inflammatory mediators in MC pathogenesis, but a predominant Th1 type cytokine profile has been demonstrated. Currently, a number of medical treatments have been studied in MC patients, following mainly an empirical treatment approach. Further studies are needed in order to obtain prospective and more evidence-based data. In the future, it will be possible to develop causal treatment approaches after better understanding the molecular mechanisms behind the origin of the disease.

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.

[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: clinical characteristics, treatment and outcomes in an Irish population.

BACKGROUND AND AIMS: Many aspects of microscopic colitis remain poorly understood. Our aim was to report a single centre experience with this condition. METHODS: Two hundred and twenty-two patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed, and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. RESULTS: There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98 %) while abdominal pain (24 %), weight loss (10 %), faecal incontinence (8 %) and blood PR (5 %) were also described. Twenty-eight percent had concomitant autoimmune diseases, most commonly coeliac disease. Patients were taking a variety of medications at diagnosis thought to be associated with microscopic colitis including NSAIDs (22 %), aspirin (19 %), statins (15 %), proton pump inhibitors (19 %) and SSRIs (10 %) at diagnosis. Prior to the widespread use of budesonide in our institution, 33 % of patients required two or more medications during therapy compared to 15 % following the introduction of budesonide (p = 0.001). Thirty-eight percent of patients achieved spontaneous remission with either no treatment or simple anti-diarrhoeals. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95 % CI 1.0-3.6; p = 0.04). Two patients had refractory microscopic colitis; one required a colectomy while a more recent case has responded to anti-TNFα therapy. CONCLUSION: Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment of this lesser studied inflammatory bowel disease.

Microscopic colitis: a review.

AIM: In recent years, microscopic colitis has been increasingly diagnosed. This review was carried out to evaluate demographic factors for microscopic colitis and to perform a systematic assessment of available treatment options. METHOD: Relevant publications up to December 2013 were identified following searches of PubMed and Google Scholar using the key words 'microscopic colitis', 'collagenous colitis' and 'lymphocytic colitis'. Two-hundred and forty-eight articles were identified. RESULTS: The term microscopic colitis includes lymphocytic colitis and collagenous colitis. Both have common clinical symptoms but are well defined histopathologically. The clinical course is usually benign, but serious complications, including death, may occur. A peak incidence from 60 to 70 years of age with a female preponderance is observed. Although most cases are idiopathic, associations with autoimmune disorders, such as coeliac disease and hypothyroidism, as well as with exposure to nonsteroidal anti-inflammatory drugs and proton-pump inhibitors, have been observed. The incidence and prevalence of microscopic colitis is rising and good-quality epidemiological research is needed. Treatment is currently largely based on anecdotal evidence and on results from limited clinical trials of budesonide. Long-term follow-up of these patients is not well established. CONCLUSION: The review synthesizes work on the definition of microscopic colitis and the relationship between collagenous and lymphocytic colitis. It reviews the international epidemiology and work on aetiology. In addition, it critically considers the efficacy of a range of treatments.

[Microscopic colitis: update 2014]. / Colites microscopiques--quoi de neuf?

Microscopic colitis, which includes lymphocytic colitis and collagenous colitis, represents a frequent cause of chronic watery diarrhea especially in the elderly population. Several medications, such as nonsteroidal antiinflammatory drugs, proton pump inhibitors or antidepressants, as well as cigarette smoking have been recognized as risk factors for microscopic colitis. The diagnosis of microscopic colitis is based on a macroscopically normal ileo-colonoscopy and several biopsies from the entire colon, which demonstrate the pathognomonic histopathologic findings. Therapy is mainly based on the use of budesonide. Other medications, such as mesalazine, cholestyramine and bismuth, have been evaluated as well but the evidence is less solid.

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.

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.

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.

Review of the microscopic colitides.

Microscopic colitis is a common cause of chronic diarrhea in predominantly older adults. Incidence rates of microscopic colitis (including lymphocytic and collagenous colitis) have increased over time to levels comparable to other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis is an important consideration when evaluating these patients, although this concept requires further investigation. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. In this review, we will provide an updated assessment of the epidemiology, diagnosis, and treatment of microscopic colitis.

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.

Microscopic colitis: an update.

Microscopic colitis (MC) causes chronic diarrhea, abdominal cramping, nausea, and weight loss. Colonic mucosa appears normal on endoscopy; however, biopsies show abnormalities such as intraepithelial lymphocytosis in lymphocytic colitis, and a thickened subepithelial collagen band in collagenous colitis. Epidemiologic data demonstrates that MC is a more common cause of diarrhea than previously shown. Although the etiology of this condition is unclear, certain well-defined risk factors exist. Recently there has been more research on the pathophysiology of MC, and studies on treatment have demonstrated budesonide to be most effective, although other treatments also hold promise.

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.

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.