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Undiagnosed Microscopic Colitis: a Hidden Cause of Chronic Diarrhoea and a Frequently Missed Treatment Opportunity

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Undiagnosed Microscopic Colitis: a Hidden Cause of Chronic Diarrhoea and a Frequently Missed Treatment Opportunity EDUCATION Frontline Gastroenterol: first published as 10.1136/flgastro-2019-101227 on 5 July 2019. Downloaded from REVIEW Undiagnosed microscopic colitis: a hidden cause of chronic diarrhoea and a frequently missed treatment opportunity Andreas Münch ,1 David S Sanders,2 Michael Molloy- Bland,3 A Pali S Hungin4 1Division of Gastroenterology ABSTRACT patients and clinicians. In many national and Hepatology, Department Microscopic colitis (MC) is a treatable cause of Clinical and Experimental settings, because of downward pressure Medicine, Faculty of Health of chronic, non-bloody , watery diarrhoea, but to minimise specialist referrals and colo- Science, Linköping University, physicians (particularly in primary care) are less noscopies with histology in patients with Linköping, Sweden familiar with MC than with other causes of 2Department of seemingly normal endoscopic appear- Gastroenterology, Royal chronic diarrhoea. The colon in patients with ances, the systems for diagnosing and Hallamshire Hospital, Sheffield, MC is usually macroscopically normal. MC can managing patients with gastrointestinal UK only be diagnosed by histological examination 3Oxford PharmaGenesis, problems work against a diagnosis of MC Melbourne, Victoria, Australia of colonic biopsies (subepithelial collagen band and its effective management. 4 The Institute of Health and >10 µm (collagenous colitis) or >20 intraepithelial When first described in 1980, MC was Society, Faculty of Medical lymphocytes per 100 epithelial cells (lymphocytic 1 Sciences, Newcastle University, thought to be a rare condition. We now Newcastle upon Tyne, UK colitis), both with lamina propria inflammation). know that MC is a common form of inflam- The UK National Health Service exerts downward matory bowel disease (IBD), with one Correspondence to pressure to minimise colonoscopy referrals. recent study putting the incidence in the Professor Andreas Münch, Furthermore, biopsies are often not taken Division of Gastroenterology UK at around 18 cases per 100 000 popula- and Hepatology, Department according to guidelines. These factors work against tion/year.2 The incidence of MC in the USA of Clinical and Experimental MC diagnosis. In this review, we note the high Medicine, Faculty of and the UK has been increasing, though it incidence of MC (comparable to ulcerative colitis 2–4 Health Science, Linköping may have stabilised in the USA. Reasons University, Linkoping 581 83, and Crohn’s disease) and its symptomatic overlap for the growing incidence of MC may http://fg.bmj.com/ Sweden; Andreas. Munch@ with irritable bowel syndrome. We also highlight regionostergotland. se include greater awareness and the ageing problems with the recommendation by National population. Importantly, MC accounts for Received 14 March 2019 Health Service/National Institute for Health and approximately 10% of individuals who Revised 30 May 2019 Care Excellence guidelines for inflammatory 5 Accepted 20 June 2019 present with non- bloody diarrhoea, but bowel diseases that colonoscopy referrals should Published Online First physicians, particularly in primary care, on September 26, 2021 by guest. Protected copyright. 5 July 2019 be based on a faecal calprotectin level of ≥100 are not as aware of MC as a cause of this µg/g. Faecal calprotectin is <100 µg/g in over half symptom as they are of other IBDs and irri- of individuals with active MC, building into the table bowel syndrome (IBS). This is perhaps system a propensity to misdiagnose MC as irritable not surprising, considering that the UK bowel syndrome. This raises important questions— National Health Service (NHS)6 refers to fg. bmj. com how many patients with MC have already been MC as a ‘less common type of IBD’, despite misdiagnosed, and how do we address this silent the UK incidence being comparable to burden? Clarity is needed around pathways for ulcerative colitis and Crohn’s disease (both MC management; MC is poorly acknowledged around 10 cases per 100 000 population/ by the UK healthcare system and it is unlikely year).7 8 © Author(s) (or their employer(s)) that best practices are being followed adequately. 2020. Re- use permitted under The defining symptom of MC is chronic There is an opportunity to identify and treat CC BY- NC. No commercial re- or recurrent, non- bloody, watery diar- use. See rights and permissions. patients with MC more effectively. 9 Published by BMJ. rhoea. Known risk factors include older age,3 female sex,3 smoking10 and the use of To cite: Münch A, Sanders DS, 11 Molloy- Bland M, et al. INTRODUCTION some drugs. The natural course of MC is Frontline Gastroenterology The underdiagnosis of microscopic colitis generally benign, with similar mortality12 2020;11:228–234. (MC) represents a lost opportunity for and colorectal cancer risk13–15 as the general 228 Münch A, et al. Frontline Gastroenterology 2020;11:228–234. doi:10.1136/flgastro-2019-101227 EDUCATION Frontline Gastroenterol: first published as 10.1136/flgastro-2019-101227 on 5 July 2019. Downloaded from containers. MC occurs in two histologically distinct Key messages forms: collagenous colitis (CC) and lymphocytic colitis (LC). In both CC and LC, inflammation in the lamina Microscopic colitis (MC) is a prevalent (comparable to ► propria is present throughout the entire colon.20 The ulcerative colitis and Crohn’s disease) but treatable cause key histological feature distinguishing CC is the pres- of chronic, non- bloody, watery diarrhoea. ► The colon is macroscopically normal in most patients ence of a broad subepithelial collagen band, >10 µm in with MC; diagnosis thus requires histological thickness, immediately underneath the surface epithe- 20 examination of colonic biopsies. lium. The key histological feature that distinguishes ► MC is less familiar to physicians (particularly in primary LC is an increased number of intraepithelial lympho- care) than other causes of chronic diarrhoea and may cytes (IEL), with >20 IELs per 100 epithelial cells be misdiagnosed because of symptomatic overlap with generally considered diagnostic.20 Another MC group irritable bowel syndrome (IBS), downward pressure not may also exist, referred to variably in the literature as to refer patients for colonoscopy and low adherence to MC not otherwise specified,21 paucicellular LC 22 or, biopsy guidelines. most recently, MC incomplete (MCi).23 In patients The UK National Health Service recommends colonoscopy ► with MCi, the collagen layer (>5 m) or number of when faecal calprotectin is ≥100 µg/g, based on National µ Institute for Health and Care Excellence guidelines IELs (>5 per 100 epithelial cells) is abnormal, but for inflammatory bowel diseases; however, faecal below the threshold for CC or LC, though there is still 20 calprotectin is <100 µg/g in over 50% of patients with inflammation in the lamina propria. active MC. Patients with CC, LC and MCi cannot be distin- ► In most cases it is possible to distinguish between IBS guished from each other based on their demographic and MC by taking a thorough history, though a more features, clinical characteristics or symptom presen- pragmatic approach is to refer patients for colonoscopy tation.23–25 Treatment guidelines do not distinguish with biopsy to assess MC if they have chronic (>4 between CC and LC,9 because differences in treat- weeks), mainly watery diarrhoea. ment outcomes have not been observed between these ► A large, hidden burden of undiagnosed and untreated subgroups.26 In addition, uncontrolled data from a MC likely exists in the UK population owing to systemic retrospective analysis indicate that MCi has a similar misdiagnosis of MC as IBS. response to treatment compared with CC and LC.23 ► Pathways for the management of MC in the UK are unclear and need to be clarified so that they can be Interestingly, in patients with CC, the degree of lamina amended and standardised where necessary. propria inflammation has been found to be a signifi- cant predictor of the degree of symptom response,27 leading to speculation that this feature may be of more population. However, chronic diarrhoea, combined diagnostic value than the criteria used to distinguish with other possible symptoms such as abdominal pain, CC, LC and MCi. It is important to note that patients fatigue, arthralgia, myalgia, urgency, faecal inconti- with MCi currently do not receive a diagnosis of MC. 16–19 nence, nocturnal defecation and weight loss, signifi- If randomised, controlled data can confirm that the http://fg.bmj.com/ cantly impairs health- related quality of life in patients response of MCi to treatment is similar to CC and LC, with MC.17 Treatment of symptomatic MC focuses on then it seems clear that patients with MCi should be improving quality of life by targeting the underlying classified as MC and treated accordingly. This would inflammation that is presumed to cause symptoms. also simplify diagnosis, because pathologists have more The underestimation of MC as a cause of diarrhoea trouble consistently discriminating MCi from CC and is creating a legacy of accumulated misdiagnoses—a LC than they do discriminating between MC/MCi and on September 26, 2021 by guest. Protected copyright. situation made even more unpalatable by the fact non- MC.28 that there is a clear path for the diagnosis and treat- Several approaches have been used to try and ment of this burdensome disease. In this article, we minimise the need for colonoscopy with biopsy for provide a brief overview of current best practice the diagnosis of MC. One approach is the devel- for the
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