Management of Microscopic Colitis: Challenges and Solutions
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University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2019-02-27 Management of microscopic colitis: challenges and solutions Julia Shor University of Massachusetts Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Digestive System Diseases Commons, Gastroenterology Commons, and the Therapeutics Commons Repository Citation Shor J, Churrango G, Hosseini N, Marshall C. (2019). Management of microscopic colitis: challenges and solutions. Open Access Articles. https://doi.org/10.2147/CEG.S165047. Retrieved from https://escholarship.umassmed.edu/oapubs/3771 Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Journal name: Clinical and Experimental Gastroenterology Article Designation: Review Year: 2019 Volume: 12 Clinical and Experimental Gastroenterology Dovepress Running head verso: Shor et al Running head recto: Shor et al open access to scientific and medical research DOI: http://dx.doi.org/10.2147/CEG.S165047 Open Access Full Text Article REVIEW Management of microscopic colitis: challenges and solutions Julia Shor1 Abstract: Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by Gustavo Churrango1 nonbloody diarrhea in the setting of normal appearing colonic mucosa. MC has two main subtypes Nooshin Hosseini2 based on histopathologic features, collagenous colitis and lymphocytic colitis. Management of Christopher Marshall1 both subtypes is the same, with treatment goal of reducing the number of bowel movements and improving consistency. First-line treatment involves counseling the patient about decreasing 1Department of Gastroenterology, University of Massachusetts Medical their risk factors, like discontinuing smoking and avoiding medications with suspected associa- School, Worcester, MA, USA; tion such as NSAIDs, proton pump inhibitor, ranitidine, and sertraline. Starting loperamide for 2 Department of Gastroenterology, immediate symptomatic relief is used as an adjunct to therapy with glucocorticoids. Budesonide Mount Sinai Hospital, New York, NY, USA is considered first-line treatment for MC given its favorable side effect profile and good efficacy, For personal use only. though relapse rates are high. Systemic glucocorticoids should be reserved to patients unable to take budesonide. In glucocorticoid refractory disease, medications that have been tried include cholestyramine, bismuth salicylate, antibiotics, probiotics, aminosalicylates, immunomodula- tors, and anti-tumor necrosis factor-alpha inhibitors. More research is needed for the creation of a systematic stepwise approach for relapsing and refractory disease. Keywords: microscopic colitis, diarrhea, collagenous colitis, lymphocytic colitis, management, inflammatory colitis Introduction Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by nonbloody diarrhea in the setting of normal appearing colonic mucosa and distinct histopathologic features. It has a preponderance for middle-aged women and is associ- ated with various autoimmune disorders, as well as widely used medications includ- Clinical and Experimental Gastroenterology downloaded from https://www.dovepress.com/ by 146.189.228.139 on 10-May-2019 ing NSAIDs.1 MC has two main subtypes, collagenous colitis (CC) and lymphocytic colitis (LC), as well as an incomplete variant. Although MC has been well-described in the medical literature since the 1970s, many aspects of this disease remain poorly understood and few high-quality studies are available to guide therapy. There have been promising advancements in the understanding of MC, as several international medical societies have published recent statements and guidelines on the diagnosis and treatment of MC, and various studies are on the horizon exploring new therapies such as novel biologics and even fecal transplant.2,3 Correspondence: Julia Shor Department of Gastroenterology, General overview University of Massachusetts Medical Epidemiology School, 55 N Lake Ave, Worcester, MA Based on a recent meta-analysis, the annual overall incidence of CC is 4.14 per 100,000 01605, USA Email [email protected] person-years and 4.85 per 100,000 person-years for LC. The overall prevalence of CC submit your manuscript | www.dovepress.com Clinical and Experimental Gastroenterology 2019:12 111–120 111 Dovepress © 2019 Shor et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work http://dx.doi.org/10.2147/CEG.S165047 you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Shor et al Dovepress is 49.21 cases per 100,000 person-years and 63.05 cases per Pathophysiology 100,000 person-years for LC.4 It is important to note that The exact mechanism of diarrhea in MC remains largely most of the data about the incidence and prevalence of MC unknown but is thought to be multifactorial. Mucosal inflam- are from the developed Western world, namely the USA, mation has been proposed as the most pathophysiologic Canada, Spain, the Netherlands, and Denmark. Data from mechanism of the diarrhea. This may be due to mucosal the developing world are lacking. Age increases the risk of changes due to inflammation that lead to reduced sodium and MC with an OR of 8.3 for age >65 years compared with chloride absorption, inhibition of the chloride/bicarbonate <65 years.5,6 The incidence is higher in women than in men, exchange channels, and a decrease in passive permeability.15 with a female-to-male incidence ratio of 3.05 for CC and These changes consequently lead to a secretory diarrhea. An 1.92 for LC.4 osmotic element has also been studied and is supported by the finding that periods of fasting decrease fecal weight.16 Risk factors Bile salt malabsorption may also play a factor, as bile acid While the etiology of MC is still unknown, various indepen- sequestrants have successfully been used to treat diarrhea dent risk factors, broadly including medications, tobacco, in MC. In one study, a selenium-labeled homocholic acid and autoimmune conditions, have been identified, which taurine test was used to study bile acid malabsorption in are implicated in both developing and flaring of MC. The patients with CC, and 44% (12/27) were found to have an widely used medications include proton pump inhibitors, abnormal test.17 Mucosal injury from luminal contents has NSAIDs, beta-blockers, statins, and selective serotonin also been proposed as another factor leading to diarrhea. This reuptake inhibitors.7 In fact, a recent Danish case–control was evidenced by studying patients who underwent diverting study of 10,652 patients found a strong association of pro- ileostomy, who were found to have histologic improvement of ton pump inhibitors with both CC (OR 6.98) and LC (OR the MC. This improvement later reverted when the ileostomy 3.95), with the strongest association being with the current was reversed.18 The microbiome has also been implicated in use of lansoprazole.8 In addition to the classically described For personal use only. the pathogenesis of MC, with an identified increase in the medications thought to have association with MC, new proinflammatory sulfur-reducing bacterial family Desul- medications, namely novel chemotherapeutic agents immune fovibrionales and a decrease in Coriobacteriaceae, which checkpoint inhibitors (ICPIs), have been implicated in caus- is seen in abundance in the healthy gastrointestinal tract.19 ing histologically proven MC. It is important to distinguish Additionally, given that the disease is most prevalent in this entity as patients on ICPIs had a more aggressive course postmenopausal women, hormones are thought to play a often requiring hospitalization and were treated with more role in the pathophysiology of MC. In a pooled analysis by aggressive immunosuppression such as oral and intravenous the Nurses’ Health Study, exogenous oral contraceptive and corticosteroids and infliximab as well as vedolizumab.9 While menopausal hormone therapy use were associated with the medications are classically thought of as being causative for increased risk of MC, thereby implicating estrogen in playing MC, evidence to this fact remains present only in certain a role in inflammation of the gastrointestinal tract.20 individual cases with larger scale studies unable to replicate the cause and effect relationship.10 Smoking has also been Symptoms Clinical and Experimental Gastroenterology downloaded from https://www.dovepress.com/ by 146.189.228.139 on 10-May-2019 found to have an association with MC, leading to the onset The hallmark symptom of MC is chronic, nonbloody, watery of disease >10 years earlier