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Rutkowski K, Udrycka K, Włodarczyk B, Małecka-Wojciesko E. Microscopic Colitis: An Underestimated Disease of Growing Importance. J Clin Med 2024; 13:5683. [PMID: 39407743 PMCID: PMC11476874 DOI: 10.3390/jcm13195683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/18/2024] [Accepted: 09/20/2024] [Indexed: 10/20/2024] Open
Abstract
The aim of this paper is to raise awareness of MC as a clinically significant condition and to highlight its under-recognition, risk factors, diagnosis, management, and complications. This paper underlines the diagnostic and therapeutic challenges associated with the often nonspecific symptoms of MC. In order to create this article, we reviewed available articles found in the PubMed database and searched for articles using the Google Scholar platform. Microscopic colitis (MC) is a chronic inflammatory bowel disease, classified into three types: lymphocytic, collagenous, and unspecified. The average age of onset of MC is around 62-65 years and the disease is more common in women than men (nine times more common). The main symptom of MC is watery diarrhoea without blood, other symptoms include defecatory urgency, faecal incontinence, abdominal pain, nocturnal bowel movements, and weight loss. Once considered a rare disease, MC is now being diagnosed with increasing frequency, but diagnosis remains difficult. To date, a number of causative factors for MC have been identified, including smoking, alcohol consumption, medications (including NSAIDs, PPIs, SSRIs, and ICPIs), genetic factors, autoimmune diseases, bile acid malabsorption, obesity, appendicitis, and intestinal dysbiosis. It may be difficult to recognize and should be differentiated from inflammatory bowel diseases (Crohn's disease and ulcerative colitis), irritable bowel syndrome (IBS), coeliac disease, infectious bowel disease, and others. Diagnosis involves biopsy at colonoscopy and histopathological evaluation of the samples. Treatment consists of budesonide oral (the gold standard) or enema. Alternatives include bile acid sequestrants (cholestyramine, colesevelam, and colestipol), biologics (infliximab, adalimumab, and vedolizumab), thiopurines, methotrexate, and rarely, surgery.
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Affiliation(s)
- Kamil Rutkowski
- Department of Digestive Tract Disease, Medical University of Lodz, 90-647 Lodz, Poland; (K.U.); (B.W.); (E.M.-W.)
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Djembissi Fotso A, Arvanitakis M, Salame M, Gallez J, Lakis A. What do we know today about drug-induced microscopic colitis? A case of lymphocytic colitis on olmesartan. Acta Gastroenterol Belg 2023; 86:474-480. [PMID: 37814563 DOI: 10.51821/86.3.11361] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
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.
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Affiliation(s)
- A Djembissi Fotso
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
- Department of Gastroenterology, Erasme Hospital, Université Libres de Bruxelles (ULB), Brussels, Belgium
| | - M Arvanitakis
- Department of Gastroenterology, Erasme Hospital, Université Libres de Bruxelles (ULB), Brussels, Belgium
| | - M Salame
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
| | - J Gallez
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
| | - A Lakis
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
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Daferera N, Nyström S, Hjortswang H, Ignatova S, Jenmalm MC, Ström M, Münch A. Mucosa associated invariant T and natural killer cells in active and budesonide treated collagenous colitis patients. Front Immunol 2022; 13:981740. [PMID: 36591297 PMCID: PMC9798420 DOI: 10.3389/fimmu.2022.981740] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 11/28/2022] [Indexed: 12/23/2022] Open
Abstract
Introduction Collagenous colitis (CC) is an inflammatory bowel disease, which usually responds to budesonide treatment. Our aim was to study the immunological background of the disease. Methods Analyses of peripheral and mucosal MAIT (mucosa associated invariant T cells) and NK (natural killer) cells were performed with flow cytometry. Numbers of mucosal cells were calculated using immunohistochemistry. We studied the same patients with active untreated CC (au-CC) and again while in remission on budesonide treatment. Budesonide refractory patients and healthy controls were also included. The memory marker CD45R0 and activation marker CD154 and CD69 were used to further study the cells. Finally B cells, CD4+ and CD8+ T cells were also analysed. Results The percentages of circulating CD56dimCD16+ NK cells as well as MAIT cells (CD3+TCRVa7.2+CD161+) were decreased in au-CC compared to healthy controls. This difference was not seen in the mucosa; where we instead found increased numbers of mucosal CD4+ T cells and CD8+ T cells in au-CC. Mucosal immune cell numbers were not affected by budesonide treatment. In refractory CC we found increased mucosal numbers of MAIT cells, CD4+ and CD8+ T cells compared to au-CC. Discussion Patients with active collagenous colitis have lower percentages of circulating MAIT and NK cells. However, there was no change of these cells in the colonic mucosa. Most mucosal cell populations were increased in budesonide refractory as compared to au-CC patients, particularly the number of MAIT cells. This may indicate that T cell targeting therapy could be an alternative in budesonide refractory CC.
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Affiliation(s)
- Niki Daferera
- Department of Gastroenterology, Faculty of Health Sciences, Linköping University, Linköping, Sweden,*Correspondence: Niki Daferera,
| | - Sofia Nyström
- Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden,Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden
| | - Henrik Hjortswang
- Department of Gastroenterology, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - Simone Ignatova
- Department of Pathology, Linköping University, Linköping, Sweden
| | - Maria C. Jenmalm
- Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - Magnus Ström
- Department of Gastroenterology, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - Andreas Münch
- Department of Gastroenterology, Faculty of Health Sciences, Linköping University, Linköping, Sweden
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Boivineau G, Zallot C, Zerbib F, Plastaras L, Amiot A, Boivineau L, Koch S, Peyrin-Biroulet L, Vuitton L. Biologic Therapy for Budesonide-refractory, -dependent or -intolerant Microscopic Colitis: a Multicentre Cohort Study from the GETAID. J Crohns Colitis 2022; 16:1816-1824. [PMID: 35793161 DOI: 10.1093/ecco-jcc/jjac089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Budesonide remains the backbone therapy for microscopic colitis [MC]; however, relapses are frequent, and some patients are intolerant or dependent. Anti-TNF therapy is increasingly used to treat these patients, but available evidence is still limited. The aim of this study was to evaluate the effectiveness and safety of anti-TNF therapy in MC patients failing budesonide. METHODS In a multicentre retrospective cohort study, budesonide-refractory, -dependent, or -intolerant MC patients treated with anti-TNF agents were included. Clinical remission was defined as fewer than three bowel movements per day, and clinical response was defined as an improvement in stool frequency of at least 50%. RESULTS Fourteen patients were included. Median age was 58.5 years, median disease duration was 25 months, and median follow-up was 29.5 months. Seven patients were treated with infliximab [IFX], and seven with adalimumab. Clinical remission without steroids at 12 weeks was reached in 5/14 [35.7%] patients; all of these received IFX. Clinical response at 12 and 52 weeks, was obtained in 9/14 [64.3%] and 7/14 [50%] patients, respectively. Five patients switched to another anti-TNF agent. When considering both first- and second-line anti-TNF therapies, 7 [50%] patients were in clinical remission at Week 52. Mild to moderate adverse events were reported in six ptients. Two patients were treated with vedolizumab, of whom one had clinical response; one patient treated with ustekinumab had no response. CONCLUSIONS This is the first multicentre cohort study showing that half of patients treated with anti-TNF therapy for MC achieved clinical remission in case of budesonide failure.
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Affiliation(s)
- Grégoire Boivineau
- Gastroenterology Department, Besançon University Hospital, Besançon, France
| | - Camille Zallot
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, France
| | - Franck Zerbib
- Gastroenterology Department, Bordeaux University Hospital, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Bordeaux, France
| | | | - Aurélien Amiot
- Department of Gastroenterology, Hopitaux Universitaires Bicêtre, AP-HP, Universite Paris Est Creteil, INSERM UMR1018, Le Kremlin Bicêtre, France
| | - Lucile Boivineau
- Hepatogastroenterology Department, Montpellier University Hospital, Montpellier, France
| | - Stéphane Koch
- Gastroenterology Department, Besançon University Hospital, Besançon, France
| | | | - Lucine Vuitton
- Gastroenterology Department, Besançon University Hospital, Besançon, France.,Department of Gastroenterology and UMR 1098, University Hospital of Besançon, University Bourgogne-Franche-Comté, Besançon, France
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Fărcaş RA, Grad S, Dumitraşcu DL. Microscopic colitis: an update. Med Pharm Rep 2022; 95:370-376. [PMID: 36506610 PMCID: PMC9694749 DOI: 10.15386/mpr-2389] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 01/21/2022] [Accepted: 02/05/2022] [Indexed: 12/15/2022] Open
Abstract
Microscopic colitis (MC) is an inflammatory pathology of the bowel diagnosed predominantly in older patients. MC is a cause of chronic watery, non-bloody diarrhea, that affects the older patients, mostly women, and leads to impaired health-related quality of life. The diagnosis and treatment can be often difficult. There are three main histological subtypes: collagenous colitis, lymphocytic colitis and incomplete microscopic colitis. Because of the variable nature of this pathology, the therapeutic options should be individualized for every patient. MC has a variable course, varying from occasional symptoms to recurrent or progressive symptoms. A literature search was performed on the main databases. Data on microscopic colitis was collected and presented. This comprehensive review aims to raise awareness of this pathology while providing the latest data regarding current recommendations. General practitioners and gastroenterologists should always take microscopic colitis into consideration when diagnosing a patient with chronic diarrhea.
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Affiliation(s)
- Radu A Fărcaş
- 2 Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Simona Grad
- 2 Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Dan L Dumitraşcu
- 2 Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Fedor I, Zold E, Barta Z. Microscopic colitis in older adults: impact, diagnosis, and management. Ther Adv Chronic Dis 2022; 13:20406223221102821. [PMID: 35813189 PMCID: PMC9260565 DOI: 10.1177/20406223221102821] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 04/28/2022] [Indexed: 11/18/2022] Open
Abstract
Microscopic colitis (comprising lymphocytic and collagenous colitis, albeit an incomplete variant is gaining recognition as well) is a chronic, immune-mediated inflammatory state of the lower gastrointestinal tract (colon). The diagnosis requires diagnostic colonoscopy with characteristic histopathological findings. They have a propensity to present in senior populations (above 60 years of age), particularly women - who are approximately 2.5-3 times more likely to develop microscopic colitis. Preexisting other immune-inflammatory diseases are also shown to predispose patients for the development of microscopic colitis. The classic presentation is profuse watery diarrhea, often during the night or early morning hours. Fecal incontinence and abdominal pain are frequent as well. Thus, the disease impacts patients' quality of life and well-being. The first described cases date back to the seventies and eighties of the twentieth century, thereby they can be considered fairly recently discovered disease states. Our understanding of the disease and its pathophysiology is still incomplete. Although there is a lack of unified recommendation for treatment, most clinicians prefer the use of budesonide, and most published guidelines regard this locally acting glucocorticoid as the therapy of choice. In our article, we aimed for a brief, noncomprehensive overview of the clinical significance, diagnosis, and management of microscopic colitis.
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Affiliation(s)
- Istvan Fedor
- Department of Public Health and Epidemiology,
Faculty of Medicine, University of Debrecen, Kassai Street 26., Debrecen
4012, Hungary
- Department of Clinical Immunology, Doctoral
School of Clinical Immunology and Allergology, Institute of Internal
Medicine, Faculty of Medicine, University of Debrecen, Moricz Zs. Street
22., Debrecen 4004, Hungary
| | - Eva Zold
- Department of Clinical Immunology, Doctoral
School of Clinical Immunology and Allergology, Institute of Internal
Medicine, Faculty of Medicine, University of Debrecen, Debrecen,
Hungary
| | - Zsolt Barta
- GI Unit, Department of Infectology, Doctoral
School of Clinical Immunology and Allergology, Faculty of Medicine,
University of Debrecen, Debrecen, Hungary
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Khushal S, Oliva-Hemker M. Diagnosis and Management of Microscopic Colitis in Pediatric Patients. Paediatr Drugs 2022; 24:217-233. [PMID: 35501559 DOI: 10.1007/s40272-022-00504-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/27/2022] [Indexed: 11/27/2022]
Abstract
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.
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Affiliation(s)
- Salina Khushal
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Maria Oliva-Hemker
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Mihaly E, Patai Á, Tulassay Z. Controversials of Microscopic Colitis. Front Med (Lausanne) 2021; 8:717438. [PMID: 34712675 PMCID: PMC8546222 DOI: 10.3389/fmed.2021.717438] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/11/2021] [Indexed: 11/21/2022] Open
Abstract
Microscopic colitis (MC) has become a disease with increased awareness due to the availability of new data about the pathogenesis, diagnosis and therapy of this disease. The incidence of MC is increasing, reaching the incidence of the inflammatory bowel disease (IBD) in some populations. However, some aspects of MC are still controversial. It is unknown whether the changes of microbiome play a role in the pathogenesis and what is in the background of the different subtypes of disease that can transform into each other. Is there a connection between MC and IBD or why the histological changes do not follow the clinical activity? We do not know what the etiology of the incomplete MC is, and what its natural course is. The association of MC with celiac disease is well-known- is there a common pathogenesis? The MC treatment is budesonide. Its effectiveness is high, but the relapse rate is high, as well. Why would biologics be effective in these cases when budesonide is not? This mini-review makes an attempt to summarize the data about MC and highlight that there are still unanswered questions in the pathogenesis, diagnosis and therapy of the disease, which can initiate further investigations in the future.
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Affiliation(s)
- Emese Mihaly
- Gastroenterology Unit, Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
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9
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Abstract
Microscopic colitis (MC) is an inflammatory disease of the large intestine associated with urgent watery diarrhoea. MC may occur in people of all ages, although the disease primarily affects older women. Once believed to be rare, MC is now known to be a common cause of chronic watery diarrhoea in high-income countries, affecting 1 in 115 women and 1 in 286 men during their lifetime in Swedish population-based estimates. An inappropriate immune response to disturbances in the gut microenvironment is implicated in the pathogenesis of MC. Evidence also supports an underlying genetic basis for disease. The diagnosis of MC relies on clinical symptoms and microscopic assessment of colonic biopsy samples. MC is categorized histologically into collagenous colitis, lymphocytic colitis and their incomplete forms. The mainstay of treatment includes the use of budesonide, with or without adjunctive therapies, and withdrawal of offending drugs. Emerging studies suggest a role for biologicals and immunosuppressive therapies for the management of budesonide-refractory or budesonide-dependent disease. MC can have a substantial negative effect on patient quality of life. The outlook for MC includes a better understanding of the immune response, genetics and the microbiome in disease pathogenesis along with progress in disease management through robust clinical trials.
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Affiliation(s)
- Kristin E Burke
- Gastroenterology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
| | - Mauro D'Amato
- Gastrointestinal Genetics Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Siew C Ng
- Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, LK Institute of Health Science, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Paediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
| | - Hamed Khalili
- Gastroenterology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
- Institute of Environmental Medicine, Nutrition Epidemiology, Karolinska Institutet, Solna, Sweden.
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Janssens L, Ji H, Khanna S. 74-Year-Old Woman With Chronic Diarrhea. Mayo Clin Proc 2021; 96:770-775. [PMID: 33673924 DOI: 10.1016/j.mayocp.2020.07.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/24/2020] [Accepted: 07/02/2020] [Indexed: 12/31/2022]
Affiliation(s)
- Laurens Janssens
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Hyun Ji
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Sahil Khanna
- Advisor to Residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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Miehlke S, Guagnozzi D, Zabana Y, Tontini GE, Kanstrup Fiehn A, Wildt S, Bohr J, Bonderup O, Bouma G, D'Amato M, Heiberg Engel PJ, Fernandez‐Banares F, Macaigne G, Hjortswang H, Hultgren‐Hörnquist E, Koulaouzidis A, Kupcinskas J, Landolfi S, Latella G, Lucendo A, Lyutakov I, Madisch A, Magro F, Marlicz W, Mihaly E, Munck LK, Ostvik A, Patai ÁV, Penchev P, Skonieczna‐Żydecka K, Verhaegh B, Münch A. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United European Gastroenterol J 2021; 9:13-37. [PMID: 33619914 PMCID: PMC8259259 DOI: 10.1177/2050640620951905] [Citation(s) in RCA: 123] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/27/2020] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. METHODS Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. RESULTS These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. CONCLUSION These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.
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12
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Rojo E, Casanova MJ, Gisbert J. Treatment of microscopic colitis: the role of budesonide and new alternatives for refractory patients. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 112:53-58. [PMID: 31880163 DOI: 10.17235/reed.2019.6655/2019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes: collagenous colitis and lymphocytic colitis. Due to the increasing incidence and awareness of this disease over the last decades, several international guidelines have been recently published. However, there is still significant heterogeneity in the management of these patients, and treatments without solid scientific evidence support are often used in clinical practice. This article reviews the therapeutic role of budesonide in microscopic colitis and summarizes the current evidence regarding other treatments available for this disease, especially for the management of refractory patients. Finally, an updated treatment algorithm is proposed.
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Affiliation(s)
- Eukene Rojo
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, España
| | - María José Casanova
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, España
| | - Javier Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, España
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13
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Abstract
Microscopic colitis encompasses both collagenous and lymphocytic colitis and is a relatively common condition with rising incidence. Diagnosis is by colonoscopy (which is usually normal but may show some mild changes) and biopsies which reveal characteristic histological findings. Symptoms include non-bloody diarrhoea with urgency which may be associated with faecal incontinence and abdominal pain. Microscopic colitis is associated with a reduced health-related quality of life, and treatment is aimed at symptom control. Medications linked with the development of microscopic colitis, including proton pump inhibitors, non-steroidal anti-inflammatory drugs and selective serotonin-reuptake inhibitors, should be discontinued. If symptoms persist, budesonide is a licensed treatment for microscopic colitis which has been shown to be effective in clinical trials and real-world practice.
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Affiliation(s)
- Omer F Ahmad
- Department of Gastroenterology, University College Hospital, London, UK
| | - Ayesha Akbar
- Department of Gastroenterology, St Mark's Hospital, LNWH Trust, Harrow, UK
- Department of Surgery, Imperial College London, London, UK
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14
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Rivière P, Zerbib F. Les colites microscopiques. Rev Med Interne 2020; 41:523-528. [PMID: 32674898 DOI: 10.1016/j.revmed.2020.05.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 04/13/2020] [Accepted: 05/04/2020] [Indexed: 11/18/2022]
Abstract
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.
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Affiliation(s)
- P Rivière
- Service d'Hépato-gastroentérologie et Oncologie digestive, Centre Médico-chirurgical Magellan, CHU de Bordeaux, 33600 Pessac, France.
| | - F Zerbib
- Service d'Hépato-gastroentérologie et Oncologie digestive, Centre Médico-chirurgical Magellan, CHU de Bordeaux, 33600 Pessac, France
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15
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Miehlke S, Verhaegh B, Tontini GE, Madisch A, Langner C, Münch A. Microscopic colitis: pathophysiology and clinical management. Lancet Gastroenterol Hepatol 2020; 4:305-314. [PMID: 30860066 DOI: 10.1016/s2468-1253(19)30048-2] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 01/18/2019] [Accepted: 01/18/2019] [Indexed: 12/12/2022]
Abstract
Microscopic colitis is a chronic inflammatory disease of the colon that frequently causes chronic watery diarrhoea that might be accompanied by abdominal pain, nocturnal diarrhoea, urgency, and faecal incontinence. These symptoms lead to poor quality of life and increased health-care costs. Diagnosis relies on histological examination of multiple biopsy samples from the colonic mucosa, which often show no or only few abnormalities on endoscopy. Two major histological subtypes can be distinguished-collagenous colitis and lymphocytic colitis-but incomplete and variant forms with fewer characteristic features have been reported. Here we summarise the latest evidence on epidemiology, pathogenesis, and risk factors, and discuss established and novel therapeutic options for clinical remission. Finally, we propose an updated treatment algorithm. Further prospective studies are needed to clarify the natural history of microscopic colitis, supported by validated criteria for the assessment of disease activity.
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Affiliation(s)
- Stephan Miehlke
- Centre for Digestive Diseases, Internal Medicine Centre Eppendorf, Hamburg, Germany; Centre for Oesophageal Disorders, University Hospital Eppendorf, Hamburg, Germany.
| | - Bas Verhaegh
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Gian Eugenio Tontini
- Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Ahmed Madisch
- Department of Gastroenterology, CRH Clinic Siloah, Hannover, Germany
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Andreas Münch
- Department of Gastroenterology, Linköping University, Linköping, Sweden
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Townsend T, Campbell F, O’Toole P, Probert C. Microscopic colitis: diagnosis and management. Frontline Gastroenterol 2019; 10:388-393. [PMID: 31656564 PMCID: PMC6788131 DOI: 10.1136/flgastro-2018-101040] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 11/15/2018] [Accepted: 11/18/2018] [Indexed: 02/04/2023] Open
Abstract
Microscopic colitis (MC) is a common cause of chronic, non-bloody, watery diarrhoea in older patients. The diagnosis depends on characteristic histological findings. Bile acid malabsorption and autoimmune conditions, including coeliac disease, are more frequently found in patients with MC, but colorectal neoplasia and mortality are not increased. Non-steroidal anti-inflammatory drugs, proton-pump inhibitors, selective serotonin reuptake inhibitors and smoking tobacco confer an increased risk of developing MC. Although a so-called benign disease, which rarely causes serious complications, it does have an impact on the quality of life. Several treatment options exist, but budesonide is the only treatment proven in randomised-controlled trials to be effective and safe for induction and maintenance of remission. This article provides a practical overview for the gastroenterologist looking after patients with MC.
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Affiliation(s)
- Tristan Townsend
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Fiona Campbell
- Department of Pathology, Royal Liverpool University Hospital, Liverpool, UK
| | - Paul O’Toole
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Chris Probert
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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Daferera N, Hjortswang H, Ignatova S, Münch A. Single-centre experience with anti-tumour necrosis factor treatment in budesonide-refractory microscopic colitis patients. United European Gastroenterol J 2019; 7:1234-1240. [PMID: 31700636 DOI: 10.1177/2050640619871750] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 07/23/2019] [Indexed: 01/10/2023] Open
Abstract
Background Microscopic colitis is an inflammatory bowel disease that causes chronic, watery diarrhoea. Microscopic colitis is usually effectively treated with budesonide, but some patients are refractory. Data on alternative treatments are sparse. Aims The purpose of this study was to retrospectively evaluate outcome of microscopic colitis patients receiving anti-tumour necrosis factor therapy at our centre. Methods Treatment results, including side effects, for all microscopic colitis patients receiving anti-tumour necrosis factor therapy were registered at week 12 and at end of follow-up. Clinical remission was defined as a mean of <3 stools and <1 watery stools/day/week and clinical response as a 50% reduction of mean stool frequency/day/week. Induction and maintenance treatment was either adalimumab or infliximab. Results The study cohort comprised 18 patients; mean age at diagnosis was 47 years (range 19-77). Ten and eight patients, respectively, received adalimumab and infliximab as first-line anti-tumour necrosis factor; seven patients received second-line anti-tumour necrosis factor due to non-response, loss of response or side effects. At week 12, 9/18 patients had achieved remission, 6/18 were responders and 3/18 were non-responders. Of the nine remission patients, 3/18 (16%) had long-lasting clinical remission post-induction therapy alone. Five patients (28%) (one first-line, four second-line anti-tumour necrosis factor) were in remission and one patient (6%) responded to maintenance treatment; follow-up was mean 22 (range 4-60) months. Six patients (33%) had minor, reversible side effects. Conclusions Over half of budesonide-refractory microscopic colitis patients can achieve clinical remission or response on anti-tumour necrosis factor agents. Prospective studies are mandatory to evaluate the efficacy and safety of anti-tumour necrosis factor treatments in budesonide-refractory microscopic colitis.
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Affiliation(s)
- Niki Daferera
- Department of Gastroenterology, Linköping University, Linköping, Sweden
| | - Henrik Hjortswang
- Department of Gastroenterology, Linköping University, Linköping, Sweden
| | - Simone Ignatova
- Department of Pathology, Linköping University, Linköping, Sweden
| | - Andreas Münch
- Department of Gastroenterology, Linköping University, Linköping, Sweden
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Sebastian S, Wilhelm A, Jessica L, Myers S, Veysey M. Budesonide treatment for microscopic colitis: systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2019; 31:919-927. [PMID: 31211724 DOI: 10.1097/meg.0000000000001456] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Microscopic colitis (MC), encompassing lymphocytic and collagenous colitis, is a common cause for chronic nonbloody diarrhoea, which impacts significantly on the quality of life for patients. Despite increasing awareness of the condition and its treatment, there is considerable variation in therapeutic approaches. To conduct a systematic review and meta-analysis on the efficacy and safety of budesonide in the treatment of MC. We searched Medline, Embase and Central databases using predefined search methodology for randomised trials using budesonide in the treatment of MC. We extracted data, on the efficacy and safety of budesonide, from studies identified that met the feasibility for analysis criteria. These data were pooled with a fixed effects model. Nine studies met the inclusion criteria for analysis. The pooled odds ratios (ORs) for a response to budesonide therapy at induction and maintenance were 7.34 [95% confidence interval (CI): 4.08-13.19] and 8.35 (95% CI: 4.14-16.85) respectively. Histological response rates were superior in budesonide-treated patients compared to placebo following induction (OR: 11.52; 95% CI: 5.67-23.40) and maintenance treatment (OR: 5.88; 95% CI: 1.90-18.17). There was no difference in adverse events. Significant relapse rates (>50%) were observed following treatment cessation with no difference noted between the budesonide or the placebo-treated patients. Budesonide is an effective treatment option for MC for achieving induction and maintenance of both clinical and histological response. High relapse rates on treatment cessation were observed.
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Affiliation(s)
- Shaji Sebastian
- IBD Unit, Hull and East Yorkshire NHS Trust
- Hull York Medical School, Hull
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Rivière P, Münch A, Michetti P, Chande N, de Hertogh G, Schoeters P, Ferrante M, Vermeire S, Van Assche G. Vedolizumab in Refractory Microscopic Colitis: An International Case Series. J Crohns Colitis 2019; 13:337-340. [PMID: 30329034 DOI: 10.1093/ecco-jcc/jjy169] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Evidence for second-line therapy in patients with microscopic colitis [MC] failing budesonide is scarce, although anti-tumour necrosis factors [anti-TNFs], methotrexate and azathioprine have been reported to be effective in small cohort studies. Vedolizumab, a monoclonal antibody targeting α4β7-integrin, prevents homing of T-cells to the gut. We evaluated clinical remission with vedolizumab in budesonide-refractory MC patients. METHODS We solicited gastroenterologists in Europe and Canada for cases of MC treated with vedolizumab. Vedolizumab 300 mg IV was administered at weeks 0, 2 and 6, and then every 8 weeks. Clinical remission and histological remission were defined as less than three stools per day and normalization of histology, respectively, after induction treatment. RESULTS Eleven cases were retrieved (nine females, lymphocytic colitis [LC] n = 5, collagenous colitis [CC] n = 6). Median [interquartile range] disease duration at vedolizumab initiation was 51 [29-70] months. Nine of 11 patients had failed one immunosuppressant and ten of 11 at least one anti-TNF agent. After three infusions of vedolizumab, clinical remission was observed in 5/11 patients [two LC and three CC] of whom three remained well with maintenance therapy [median duration of 13 months]. Biopsies were obtained from 9/11 patients. Histological remission was observed in 3/4 patients with clinical remission [2/3 CC, 1/1 LC] and 0/5 patients without clinical improvement. CONCLUSION In a series of highly refractory MC patients, vedolizumab induced clinical remission in 5/11 subjects, of whom 75% showed normalized histology. Larger randomized trials are needed to assess the efficacy of vedolizumab in patients with MC.
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Affiliation(s)
- Pauline Rivière
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat, Leuven, Belgium
| | - Andreas Münch
- Division of Gastroenterology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - Pierre Michetti
- Gastro-entérologie La Source-Beaulieu, Lausanne, Switzerland
| | - Nilesh Chande
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | - Gert de Hertogh
- Department of Pathology, University Hospitals Leuven, KU Leuven, Herestraat, Leuven, Belgium
| | | | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat, Leuven, Belgium
| | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat, Leuven, Belgium
| | - Gert Van Assche
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat, Leuven, Belgium
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Shor J, Churrango G, Hosseini N, Marshall C. Management of microscopic colitis: challenges and solutions. Clin Exp Gastroenterol 2019; 12:111-120. [PMID: 30881078 PMCID: PMC6398419 DOI: 10.2147/ceg.s165047] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by nonbloody diarrhea in the setting of normal appearing colonic mucosa. MC has two main subtypes based on histopathologic features, collagenous colitis and lymphocytic colitis. Management of 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 their risk factors, like discontinuing smoking and avoiding medications with suspected association such as NSAIDs, proton pump inhibitor, ranitidine, and sertraline. Starting loperamide for immediate symptomatic relief is used as an adjunct to therapy with glucocorticoids. Budesonide is considered first-line treatment for MC given its favorable side effect profile and good efficacy, 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, immunomodulators, and anti-tumor necrosis factor-alpha inhibitors. More research is needed for the creation of a systematic stepwise approach for relapsing and refractory disease.
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Affiliation(s)
- Julia Shor
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
| | - Gustavo Churrango
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
| | - Nooshin Hosseini
- Department of Gastroenterology, Mount Sinai Hospital, New York, NY, USA
| | - Christopher Marshall
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
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21
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Gentile N, Yen EF. Prevalence, Pathogenesis, Diagnosis, and Management of Microscopic Colitis. Gut Liver 2018; 12:227-235. [PMID: 28669150 PMCID: PMC5945253 DOI: 10.5009/gnl17061] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 03/24/2017] [Accepted: 03/24/2017] [Indexed: 12/12/2022] Open
Abstract
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.
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Affiliation(s)
- Nicole Gentile
- NorthShore University HealthSystem, University of Chicago, Evanston, IL, USA
| | - Eugene F Yen
- NorthShore University HealthSystem, University of Chicago, Evanston, IL, USA
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Cotter TG, Kamboj AK, Hicks SB, Tremaine WJ, Loftus EV, Pardi DS. Immune modulator therapy for microscopic colitis in a case series of 73 patients. Aliment Pharmacol Ther 2017; 46:169-174. [PMID: 28488312 DOI: 10.1111/apt.14133] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 03/16/2017] [Accepted: 04/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments. AIM To evaluate the outcomes of patients with active MC treated with immune modulators. METHODS All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified. Patients treated with an immune modulator of interest were selected and clinical outcomes recorded. RESULTS Seventy-three MC patients (50 collagenous colitis and 23 lymphocytic colitis) with a median disease duration of 24 months (range, 7-60) were included. The indications for treatment were budesonide-refractoriness in 66%, budesonide dependence in 29%, and budesonide intolerance in 5%. Median age was 51.8 years (range, 43.4-63.1) and 61 (84%) were female. Thiopurines were used in 49 patients (67%) for a median of 4 months (range, 1.5-15). Complete and partial response occurred in 43% and 22% respectively. Adverse effects resulting in therapy cessation occurred in 17 patients (35%). Twelve patients (16%) were treated with methotrexate for a median of 14 months (3-18.8). Complete and partial response occurred in 58% and 17%, respectively. Anti-TNF therapy was used in 10 patients (14%) for a median of 4 months (range, 2.3-5.5). Complete response occurred in four patients and partial response in four patients. CONCLUSIONS The majority of patients with active MC responded to thiopurines, methotrexate, or anti-TNF therapy. Larger controlled studies are required to confirm the efficacy and safety of these medications in MC.
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Affiliation(s)
- T G Cotter
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - A K Kamboj
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - S B Hicks
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - W J Tremaine
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - E V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - D S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Abstract
PURPOSE OF REVIEW Microscopic colitis is a common cause of chronic watery diarrhea, particularly in the elderly. The accompanying symptoms, which include abdominal pain and fatigue, can markedly impair patients' quality of life. Diagnosis is based upon characteristic histologic findings of the colonic mucosa. This review focuses on the current approach to evaluation and management of patients with microscopic colitis. RECENT FINDINGS Although the incidence of microscopic colitis has been increasing over time, recent epidemiological studies show stabilization at 21.0-24.7 cases per 100,000 person-years. Recent research has further expanded our knowledge of the underlying pathophysiology and emphasized the entity of drug-induced microscopic colitis and the association with celiac disease. Two recent randomized studies have confirmed the effectiveness of oral budesonide for both induction and maintenance treatment of microscopic colitis and is now endorsed by the American Gastroenterological Association as first-line treatment. The incidence of microscopic colitis has stabilized at just over 20 cases per 100,000 person-years. Celiac disease and drug-induced microscopic colitis should be considered in all patients diagnosed with microscopic colitis. There are a number of treatments available for patients with microscopic colitis; however, budesonide is the only option well studied in controlled trials and is effective for both induction and maintenance treatment.
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24
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Pardi DS. Diagnosis and Management of Microscopic Colitis. Am J Gastroenterol 2017; 112:78-85. [PMID: 27897155 DOI: 10.1038/ajg.2016.477] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 09/01/2016] [Indexed: 12/11/2022]
Abstract
Microscopic colitis (MC) is a relatively common cause of chronic watery diarrhea, especially in older persons. Associated symptoms, including abdominal pain and arthralgias, are common. The diagnosis is based upon characteristic histological findings in the presence of diarrhea. The two types of MC, collagenous and lymphocytic colitis, share similar clinical features, with the main difference being the presence or absence of a thickened subepithelial collagen band. There are several treatment options for patients with MC, although only budesonide has been well studied in multiple controlled clinical trials. This review will describe the clinical features, epidemiology, pathophysiology, diagnostic criteria, and treatment of patients with MC.
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Affiliation(s)
- Darrell S Pardi
- Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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25
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Kia YH, Ting AYS, Dowling D. Letter: oral low-dose methotrexate for collagenous colitis. Aliment Pharmacol Ther 2016; 44:97. [PMID: 27250588 DOI: 10.1111/apt.13638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Y H Kia
- Department of Gastroenterology, University Hospital Geelong, Geelong, Vic., Australia.
| | - A Y S Ting
- Department of Gastroenterology, University Hospital Geelong, Geelong, Vic., Australia
| | - D Dowling
- Department of Gastroenterology, University Hospital Geelong, Geelong, Vic., Australia.,School of Medicine, Deakin University, Geelong, Vic., Australia
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Abstract
Collagenous colitis (CC) is an increasingly recognized cause of chronic inflammatory bowel disease characterized by watery non-bloody diarrhea. As a lesser studied inflammatory bowel disease, many aspects of the CC's natural history are poorly understood. This review discusses strategies to optimally manage CC. The goal of therapy is to induce clinical remission, <3 stools a day or <1 watery stool a day with subsequent improved quality of life (QOL). Antidiarrheal can be used as monotherapy or with other medications to control diarrhea. Budesonide therapy has revolutionized treatment and is superior to prednisone, however, the treatment is associated with high-relapse rates and the management of refractory disease is challenging. Ongoing trials will address the safety and efficacy of low-dose maintenance therapy. For those with refractory disease, case reports and case series support the role of biologic agents. Diversion of the fecal stream normalizes colonic mucosal changes and ileostomy may be considered where anti-tumor necrosis factor (TNF)-α agents are contraindicated. Underlying celiac disease, bile salt diarrhea, and associated thyroid dysfunction should be ruled out. The author recommends smoking cessation as well as avoidance of nonsteroidal anti-inflammatories as well as other associated medications.
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27
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Fernández-Bañares F, Casanova MJ, Arguedas Y, Beltrán B, Busquets D, Fernández JM, Fernández-Salazar L, García-Planella E, Guagnozzi D, Lucendo AJ, Manceñido N, Marín-Jiménez I, Montoro M, Piqueras M, Robles V, Ruiz-Cerulla A, Gisbert JP. Current concepts on microscopic colitis: evidence-based statements and recommendations of the Spanish Microscopic Colitis Group. Aliment Pharmacol Ther 2016; 43:400-26. [PMID: 26597122 DOI: 10.1111/apt.13477] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 10/01/2015] [Accepted: 10/23/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. AIM To develop an evidence-based clinical practice guide on MC current concepts. METHODS Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. RESULTS Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. CONCLUSIONS This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence.
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Affiliation(s)
- F Fernández-Bañares
- Hospital Universitari Mutua Terrassa, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - M J Casanova
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
| | | | - B Beltrán
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
- Hospital La Fe, Valencia, Spain
| | - D Busquets
- Hospital Doctor Josep Trueta, Girona, Spain
| | - J M Fernández
- Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | | | | | | | - A J Lucendo
- Hospital General de Tomelloso, Ciudad Real, Spain
| | - N Manceñido
- Hospital Infanta Sofía, San Sebastián de los Reyes, Spain
| | - I Marín-Jiménez
- Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | | | - V Robles
- Hospital Vall d'Hebron, Barcelona, Spain
| | | | - J P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
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Jauregui-Amezaga A, Vermeire S, Geboes K. Contemporary methods for the diagnosis and treatment of microscopic colitis. Expert Rev Gastroenterol Hepatol 2016; 10:47-61. [PMID: 26470823 DOI: 10.1586/17474124.2016.1096197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Microscopic colitis is a common cause of chronic diarrhea. It is characterized by non-bloody watery diarrhea with macroscopically normal colonic mucosa. Its specific histological characteristics confirm the diagnosis. Two distinct histological forms can be identified, namely, collagenous colitis and lymphocytic colitis. In collagenous colitis, a thick colonic subepithelial collagenous deposit can be observed, whereas in lymphocytic colitis, a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band can be identified. Microscopic colitis occurs more frequently in elderly females and its etiology is believed to be multifactorial, although smoking and consumption of several drugs have been identified as risks factors for the development of the disease. The treatment is based on avoiding the risks factors and administration of oral budesonide.
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Affiliation(s)
| | | | - Karel Geboes
- b 2 University Hospitals Leuven, Pathology, Leuven, Belgium
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29
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Park T, Cave D, Marshall C. Microscopic colitis: A review of etiology, treatment and refractory disease. World J Gastroenterol 2015; 21:8804-8810. [PMID: 26269669 PMCID: PMC4528022 DOI: 10.3748/wjg.v21.i29.8804] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 06/09/2015] [Accepted: 06/16/2015] [Indexed: 02/06/2023] Open
Abstract
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.
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Abstract
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.
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Münch A, Langner C. Microscopic colitis: clinical and pathologic perspectives. Clin Gastroenterol Hepatol 2015; 13:228-36. [PMID: 24407107 DOI: 10.1016/j.cgh.2013.12.026] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/19/2013] [Accepted: 12/19/2013] [Indexed: 02/07/2023]
Abstract
Microscopic colitis is a chronic inflammatory bowel disease characterized by chronic nonbloody diarrhea and specific histopathology features. Active disease, defined as 3 or more stools or 1 or more watery stools per day, significantly reduces quality of life. Epidemiologic studies have found the incidence and prevalence of microscopic colitis to be comparable with those of Crohn's disease and ulcerative colitis. Nevertheless, microscopic colitis is still under-recognized in clinical practice-most health care workers know little about its etiology and pathophysiology. Furthermore, there are many challenges to the diagnosis and treatment of patients. We review the epidemiologic and clinical features of this disorder and discuss its pathogenesis. We also outline the criteria for histopathologic evaluation of microscopic colitis, recently published by the European Consensus on Inflammatory Bowel Disease, and discuss a treatment algorithm created by the European Microscopic Colitis Group. Treatment options for patients with budesonide-refractory disease are discussed.
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Affiliation(s)
- Andreas Münch
- Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden.
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
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Farrukh A, Mayberry JF. Microscopic colitis: a review. Colorectal Dis 2014; 16:957-64. [PMID: 25039699 DOI: 10.1111/codi.12716] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 05/17/2014] [Indexed: 12/14/2022]
Abstract
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.
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Affiliation(s)
- A Farrukh
- Digestive Disease Centre, University Hospitals of Leicester, Leicester, UK
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Bohr J, Wickbom A, Hegedus A, Nyhlin N, Hultgren Hörnquist E, Tysk C. Diagnosis and management of microscopic colitis: current perspectives. Clin Exp Gastroenterol 2014; 7:273-84. [PMID: 25170275 PMCID: PMC4144984 DOI: 10.2147/ceg.s63905] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of microscopic colitis.
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Affiliation(s)
- Johan Bohr
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
| | - Anna Wickbom
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
| | - Agnes Hegedus
- Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, Sweden
| | - Nils Nyhlin
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
| | | | - Curt Tysk
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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