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González-Castro AM, Fernández-Bañares F, Zabana Y, Farago-Pérez G, Ortega-Barrionuevo J, Expósito E, Guagnozzi D. Microscopic Colitis and Celiac Disease: Sharing More than a Diagnostic Overlap. Nutrients 2024; 16:2233. [PMID: 39064676 PMCID: PMC11279699 DOI: 10.3390/nu16142233] [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: 06/02/2024] [Revised: 07/01/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
Microscopic colitis (MC) is an emergent group of chronic inflammatory diseases of the colon, and celiac disease (CD) is a chronic gluten-induced immune-mediated enteropathy affecting the small bowel. We performed a narrative review to provide an overview regarding the relationship between both disorders, analyzing the most recent studies published at the epidemiological, clinical and pathophysiological levels. In fact, MC and CD are concomitantly prevalent in approximately 6% of the cases, mainly in the subset of refractory patients. Thus, physicians should screen refractory patients with CD against MC and vice versa. Both disorders share more than a simple epidemiological association, being multifactorial diseases involving innate and adaptive immune responses to known or unknown luminal factors based on a rather common genetic ground. Moreover, autoimmunity is a shared characteristic between the patients with MC and those with CD, with autoimmunity in the latter being quite well-established. Furthermore, CD and MC share some common clinical symptoms and risk factors and overlap with other gastrointestinal diseases, but some differences exist between both disorders. More studies are therefore needed to better understand the complex mechanisms involving the common pathogenetic ground contributing to the CD and MC epidemiological association.
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Affiliation(s)
- Ana María González-Castro
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
- Neuro-Immuno-Gastroenterology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain
| | - Fernando Fernández-Bañares
- Gastroenterology Department, University Hospital Mútua Terrassa, 08221 Terrassa, Spain (Y.Z.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Instituto Carlos III), 28029 Madrid, Spain
| | - Yamile Zabana
- Gastroenterology Department, University Hospital Mútua Terrassa, 08221 Terrassa, Spain (Y.Z.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Instituto Carlos III), 28029 Madrid, Spain
| | - Georgina Farago-Pérez
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
| | - Jonathan Ortega-Barrionuevo
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
| | - Elba Expósito
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
- Neuro-Immuno-Gastroenterology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain
| | - Danila Guagnozzi
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
- Neuro-Immuno-Gastroenterology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Instituto Carlos III), 28029 Madrid, Spain
- Gastroenterology Department, University Hospital Vall d’Hebron, 08035 Barcelona, Spain
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Raju SA, Rawcliffe ME, Bowker-Howell FJ, Shiha MG, Kaur KE, Griffin J, Cross SS, Sanders DS. Coeliac Disease and Microscopic Colitis: The Largest Study Assessing Prognosis and Risk of Hospital Admission. Nutrients 2024; 16:2081. [PMID: 38999829 PMCID: PMC11243059 DOI: 10.3390/nu16132081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/21/2024] [Accepted: 06/25/2024] [Indexed: 07/14/2024] Open
Abstract
Microscopic colitis (MC) and coeliac disease (CD) are common associated gastrointestinal conditions. We present the largest study assessing hospitalisation in patients with MC and the effect of a concomitant diagnosis of CD. Data were retrospectively collected between January 2007 and December 2021 from all patients diagnosed with MC and compared to a database of patients with only CD. In total, 892 patients with MC (65% female, median age 65 years (IQR: 54-74 years) were identified, with 6.4% admitted to hospital due to a flare of MC. Patients admitted were older (76 vs. 65 years, p < 0.001) and presented with diarrhoea (87.7%), abdominal pain (26.3%), and acute kidney injury (17.5%). Treatment was given in 75.9% of patients, including intravenous fluids (39.5%), steroids (20.9%), and loperamide (16.3%). Concomitant CD was diagnosed in 3.3% of patients and diagnosed before MC (57 versus 64 years, p < 0.001). Patients with both conditions were diagnosed with CD later than patients with only CD (57 years versus 44 years, p < 0.001). In conclusion, older patients are at a higher risk of hospitalisation due to MC, and this is seen in patients with a concomitant diagnosis of CD too. Patients with MC are diagnosed with CD later than those without.
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Affiliation(s)
- Suneil A Raju
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Megan E Rawcliffe
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Freya J Bowker-Howell
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Mohamed G Shiha
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Kamaldeep E Kaur
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Jonathan Griffin
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Simon S Cross
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - David S Sanders
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
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González IA, Conrad M, Weinbrom S, Patel T, Kelsen JR, Russo P. Clinicopathologic Characterization of Lymphocytic Colitis in the Pediatric Population. Pediatr Dev Pathol 2024; 27:156-168. [PMID: 38160439 PMCID: PMC11972057 DOI: 10.1177/10935266231215117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
BACKGROUND Lymphocytic colitis (LC) in the pediatric population has been associated with immune dysregulation. METHODS Single-center retrospective study of pediatric LC. RESULTS 50 patients (35 female, 70%) with a median age of 12 years at diagnosis (interquartile range: 5.7-15.8) of LC were identified. At presentation, 11 patients (22%) had malnutrition, 16 (32%) had a known underlying immune dysregulation, 4 (8%) had celiac disease (CD), and none had a diagnosis of inflammatory bowel disease. The most common medications prior to diagnosis were non-steroidal anti-inflammatory drugs, proton pump inhibitor, and selective serotonin reuptake inhibitors (10% each). Colonic biopsies showed a median number of intraepithelial lymphocytes (IELs)/100 epithelial cells of 48 (range: 25-85), and only 10% of cases had neutrophilic cryptitis. Upper gastrointestinal tract findings included lymphocytic esophagitis (4%), and duodenal IELs without and with villous blunting (9% each) (n: 47). Ten patients (23%) had increased IELs in the terminal ileum (n: 43). Treatments including 5-ASA, budesonide, prednisone, and gluten-free diet improved symptoms in <50% of patients (n: 42), and all follow-up colonoscopies showed persistent LC (n: 13). CONCLUSION Our study supports the association of LC with immune-mediated conditions, most commonly celiac disease. Symptomatic improvement was seen in <50% of patients with none of the patients with repeat colonoscopy showing histologic improvement.
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Affiliation(s)
- Iván A. González
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Maire Conrad
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Sarah Weinbrom
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Trusha Patel
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Judith R. Kelsen
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Pierre Russo
- Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, PA, USA
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Bergman D, Roelstraete B, Sun J, Ebrahimi F, Askling J, Ludvigsson JF. Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study. Aliment Pharmacol Ther 2023; 58:1028-1040. [PMID: 37727878 DOI: 10.1111/apt.17708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/19/2023] [Accepted: 08/26/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND Microscopic colitis (MC) has been linked to several autoimmune conditions. Results from previous studies on the association with rheumatoid arthritis (RA) have been inconsistent. AIM To assess the risk of future RA in MC. METHODS We conducted a nationwide matched cohort study in Sweden of 8179 patients with biopsy-verified MC (diagnosed in 2007-2017), 36,400 matched reference individuals and 8202 siblings without MC, with follow-up until 2021. Information on MC was obtained from all of Sweden's regional pathology registers (n = 28) through the ESPRESSO cohort. Data on incident RA were collected from the National Patient Register. Using Cox regression, we calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS During a median follow-up of 9.1 years (interquartile range = 6.7-11.7), 73 MC patients and 183 reference individuals from the general population were diagnosed with RA (99 vs. 55 events per 100,000 person-years), equivalent to one extra case of RA in 226 patients with MC followed for 10 years. These rates corresponded to an aHR of 1.83 (95% CI = 1.39-2.41). The aHR was highest during the first year of follow-up (2.31 [95% CI = 1.08-4.97]) and remained significantly elevated up to 5 years after MC diagnosis (aHR 2.16; 95% CI = 1.42-3.30). Compared to siblings, without MC, the aHR was 2.04 (95% CI = 1.18-3.56). CONCLUSION Patients with MC are at a nearly two-fold risk of developing RA compared to the general population. Knowledge of this increased risk may expedite evaluation for RA in patients with MC presenting with joint symptoms and/or arthralgia, thus preventing delay until RA diagnosis.
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Affiliation(s)
- David Bergman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Jiangwei Sun
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Fahim Ebrahimi
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Johan Askling
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Orebro University Hospital, Orebro, Sweden
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
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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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Haraikawa M, Shibuya T, Kurosawa T, Ito K, Nomura K, Haga K, Nomura O, Takeda T, Fukushima H, Murakami T, Ishikawa D, Hojo M, Yao T, Nagahara A. Differential diagnosis of ulcerative colitis with increased diarrhea; collagenous colitis or irritable bowel syndrome? A case report. J Int Med Res 2022; 50:3000605221140686. [PMID: 36474409 PMCID: PMC9732797 DOI: 10.1177/03000605221140686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 11/04/2022] [Indexed: 12/12/2022] Open
Abstract
A 50-year-old man with a 20-year history of left-sided ulcerative colitis (UC) presented to our hospital with sudden onset of watery diarrhea. To this point, he had been treated with mesalazine 2.0 g/day for UC and had maintained remission. We considered that the UC had worsened. We immediately performed surveillance colonoscopy, which revealed a normal mucous membrane. The results of blood laboratory examinations were normal. Histopathology of colonic biopsies revealed new-onset collagenous colitis (CC), with a thickened subepithelial collagen band (SECB) and inactive UC. We herein report the importance of random colonic biopsies to diagnose CC even when the endoscopic appearance of the colon is normal in patients with inflammatory bowel disease with worsened diarrhea.
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Affiliation(s)
- Mayuko Haraikawa
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Taro Kurosawa
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Kentaro Ito
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Kei Nomura
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Keiichi Haga
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Osamu Nomura
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Tsutomu Takeda
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Hirofumi Fukushima
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Takashi Murakami
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Mariko Hojo
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of
Medicine, 3-1-1 Hongo, Bunkyo-ku, Tokyo, Japan
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Le C, Zeffren N, Kramer N, Rosenstein ED. Rheumatologic Associations of Microscopic Colitis: A Narrative Review. Mod Rheumatol 2022; 33:441-447. [PMID: 35993773 DOI: 10.1093/mr/roac080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/22/2022] [Accepted: 07/31/2022] [Indexed: 11/12/2022]
Abstract
Extra-intestinal manifestations are frequent complications of the classical inflammatory bowel diseases, Crohn's disease and ulcerative colitis. However, in addition to the classical diseases, there is a spectrum of conditions, often termed "microscopic colitis", in which extra-intestinal manifestations are less well described. Our objective was to review the literature regarding the extra-intestinal manifestations complicating microscopic colitis and describe the association with systemic autoimmune rheumatic diseases. A comprehensive search and review of peer-reviewed English-language and international journals and reports was completed based on key terms, including "microscopic colitis", "lymphocytic colitis", "collagenous colitis", "inflammatory bowel disease", "extraintestinal manifestations", and the specific disease associations utilizing the PubMed Central database and MEDLINE. A broad spectrum of rheumatologic manifestations has been reported in patients with microscopic colitis. The identification of rheumatoid arthritis and limited scleroderma as co-morbidities with microscopic colitis was noteworthy. Inflammatory arthropathy was frequently seen in microscopic colitis, usually preceding or occurring in conjunction with the onset of gastrointestinal symptoms. A variety of presentations of associated arthritis were reported: migratory, symmetric or asymmetric, peripheral or axial, oligoarticular or polyarticular, erosive or non-erosive. There was a high incidence of autoantibodies in these patients, supporting a potential autoimmune association. On the basis of these anecdotal reports, we would suggest development of a clinical registry to help define the incidence of extra-intestinal manifestations and systemic autoimmune rheumatic diseases among microscopic colitis patients to help elucidate shared predispositions, pathogenic mechanisms and therapeutic opportunities.
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Affiliation(s)
- Christopher Le
- Department of Medicine, Bayonne Medical Center, CarePoint Health, Bayonne, NJ, USA
| | - Noam Zeffren
- Department of Medicine, Bayonne Medical Center, CarePoint Health, Bayonne, NJ, USA
| | - Neil Kramer
- Institute for Rheumatic & Autoimmune Diseases, Overlook Medical Center, Atlantic Health System, Summit, USA.,Division of Rheumatology, Department of Medicine, NYU Langone Medical Center, New York, USA
| | - Elliot D Rosenstein
- Institute for Rheumatic & Autoimmune Diseases, Overlook Medical Center, Atlantic Health System, Summit, USA.,Division of Rheumatology, Department of Medicine, NYU Langone Medical Center, New York, USA
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Jk L, B R, B O, K S. Lack of autoantibodies against collagen and related proteins in collagenous colitis. BMC Immunol 2022; 23:29. [PMID: 35668375 PMCID: PMC9171945 DOI: 10.1186/s12865-022-00504-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 06/01/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction Collagenous colitis (CC) is a common cause of chronic diarrhea and is characterized by a subepithelial thickened collagen layer in the colonic mucosa. It shares many of the characteristics found in autoimmune diseases, but no autoantibodies have been identified. In CC, an imbalance in collagen turnover is evident. The purpose of the present study was to investigate whether any collagen-associated autoantibodies or other antibodies such as TPO and ASCA were present, and if levels of total IgE were increased. Methods Sera from women with active CC were analysed with ELISA for detection of autoantibodies against collagen type III and IV (Col III and IV), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and tenascin-C (TNC). Sera were also analysed for TPO, ASCA and total IgE. Healthy female blood donors served as controls. The cut-off value in the control group was defined as relative units > 97.5th percentile. Results Sixty-six women were included (mean age 60 years; range 31–74, mean disease duration 6 years; range 1–22). No autoantibody was significantly overexpressed in the CC population compared to controls. The mean disease duration was lower (p = 0.03) in the subjects who expressed collagen-associated autoantibodies (3.7 years; range 1–14), compared to those who did not (6.4 years; range 1–22). Treatment with budesonide was not associated with any of these autoantibodies. Conclusion No increased presence of the investigated antibodies could be found in the present study of CC. Neither could antibodies against ASCA or TPO, or elevated levels of IgE, be found. Consequently, no association was found between CC and these proteins, even though this may not be generalizable to other compounds in the collagen layer.
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Affiliation(s)
- Larsson Jk
- Department of Clinical Sciences, Department of Gastroenterology and Nutrition, Lund University, Skåne University Hospital, Malmö, Sweden.
| | - Roth B
- Department of Clinical Sciences, Department of Gastroenterology and Nutrition, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Ohlsson B
- Department of Clinical Sciences, Department of Medicine, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Sjöberg K
- Department of Clinical Sciences, Department of Gastroenterology and Nutrition, Lund University, Skåne University Hospital, Malmö, Sweden
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9
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Zabana Y, Tontini G, Hultgren-Hörnquist E, Skonieczna-Żydecka K, Latella G, Østvik AE, Marlicz W, D'Amato M, Arias A, Mielhke S, Münch A, Fernández-Bañares F, Lucendo AJ. Pathogenesis of Microscopic Colitis: A Systematic Review. J Crohns Colitis 2022; 16:143-161. [PMID: 34272945 DOI: 10.1093/ecco-jcc/jjab123] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Whereas the exact aetiology of microscopic colitis [MC] remains unknown, a dysregulated immune response to luminal factors or medications is the most accepted pathogenesis hypothesis. METHODS We conducted a systematic review of the pathogenesis of MC. We applied the Joanna Briggs Institute methodologies and the PRISMA statement for the reporting of systematic reviews [PROSPERO Trial Identifier: CRD42020145008]. Populations, Exposure of interest, and Outcome [PEO] questions were used to explore the following topics in MC: 1] intestinal luminal factors; 2] autoimmunity; 3] innate immunity; 4] adaptive immunity; 5] extracellular matrix; 6] genetic risk factors; and 7] mechanism of diarrhoea. A search was done in PubMed, Embase, and Web of Science up to February 2020. A narrative description was performed explaining the findings for each aspect of MC aetiopathogenesis. RESULTS Thirty-eight documents provided evidence for PEO1, 100 for PEO2, 72 for PEO3 and 4, 38 for PEO5, 20 for PEO6, and 23 for PEO7. The majority of documents were cohorts, case reports, and case series, with a few case-control and some experimental studies. Consistency among data provided by different studies was considered to support pathogenetic hypotheses. MC is a multifactorial disease believed to involve innate and adaptive immune responses to luminal factors, genetic risk, autoimmunity, and extracellular matrix alterations, all contributing by varied mechanisms to watery diarrhoea. CONCLUSIONS This is the first systematic review on the aetiology of MC supporting the notion that MC is a multifactorial disease. However, high-profile studies are lacking, and most evidence derives from small heterogeneous studies.
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Affiliation(s)
- Yamile Zabana
- Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - Gian Tontini
- Department of Pathophysiology and Transplantation, University of Milan and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | | | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Ann Elisabeth Østvik
- Department of Clinical and Molecular Medicine [IKOM], Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
- Centre for Digestive Diseases Endoklinika, Szczecin, Poland
| | - Mauro D'Amato
- Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Angel Arias
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
- Research Unit, Hospital General Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| | - Stephan Mielhke
- Centre for Digestive Diseases, Internal Medicine Centre Eppendorf & Endoscopy Centre, University Hospital Hamburg Eppendorf, Hamburg, Germany
| | - Andreas Münch
- Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden
| | - Fernando Fernández-Bañares
- Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - Alfredo J Lucendo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
- Gastroenterology Department, Hospital General de Tomelloso-Spain and Instituto de Investigación Sanitaria Princesa [IIS-IP], Madrid, Spain
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10
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Wildt S, Munck LK, Winther-Jensen M, Jess T, Nyboe Andersen N. Autoimmune diseases in microscopic colitis: A Danish nationwide case-control study. Aliment Pharmacol Ther 2021; 54:1454-1462. [PMID: 34653278 DOI: 10.1111/apt.16614] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/26/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND The association between autoimmune diseases and microscopic colitis remains uncertain. AIMS To describe the association between autoimmune diseases and microscopic colitis by using a matched case-control design based on nationwide registry data. METHODS All adult Danish patients with a diagnosis of microscopic colitis from 2001 to 2018 were identified from nationwide registries. Odds of autoimmune diseases were compared between cases with microscopic colitis and sex- and age-matched controls from the background population in a 1:10 ratio and evaluated by logistic regression calculating odds ratios (OR) with 95% confidence intervals (CI) adjusted for comorbidity. Analyses were stratified according to sex, age and the subtypes of lymphocytic and collagenous colitis. RESULTS We identified 15 597 cases with microscopic colitis and matched to 155 910 controls. In total, 3491 (22%) of patients with microscopic colitis had concomitant autoimmune disease compared to 16 521 (11%) of controls (OR, 2.46; 95% CI, 2.36-2.56). Adjusting for comorbidities reduced the OR to 2.09 (95% CI, 2.01-2.19). Analyses showed increased ORs with 16 different autoimmune diseases, particularly of gastrointestinal and endocrine origin, and connective tissue disorders. The highest ORs were for coeliac disease (OR = 10.15; 95% CI, 8.20-12.6), Crohn's disease (OR = 2.47; 95% CI, 2.10-2.91) and ulcerative colitis (OR = 6.73; 95% CI, 6.20-7.30). In stratified analyses younger age at diagnosis and collagenous colitis were associated with higher odds. CONCLUSION Using nationwide registry data, microscopic colitis was associated with a wide range of autoimmune diseases, especially of gastrointestinal origin. The results suggest an autoimmune predisposition to microscopic colitis.
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Affiliation(s)
- Signe Wildt
- Section of Gastroenterology, Medical Department, Zealand University Hospital, Køge, Denmark
| | - Lars Kristian Munck
- Section of Gastroenterology, Medical Department, Zealand University Hospital, Køge, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Matilde Winther-Jensen
- Centre for Clinical Research and Prevention, Frederiksberg and Bispebjerg Hospital, Copenhagen, Denmark
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Nynne Nyboe Andersen
- Department of Medical Gastroenterology and Hepatology, Rigshospitalet, Copenhagen, Denmark
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11
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Hussain MS, Balagoni H, Dwivedi S, Piper M. Macroscopic to Microscopic - A Case of Crohn's Disease Progressing to Collagenous Colitis. Cureus 2021; 13:e18299. [PMID: 34722074 PMCID: PMC8547377 DOI: 10.7759/cureus.18299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2021] [Indexed: 11/30/2022] Open
Abstract
The association between microscopic colitis (MC) and inflammatory bowel disease (IBD) is uncertain and infrequently reported. Rare cases in the literature consist of simultaneous MC and IBD, or progression of one condition to the other. We present a unique case of clinically and endoscopically diagnosed and successfully treated IBD that revealed MC on histology months later due to reappearance of diarrhea. Common pathophysiologic mechanisms, such as tumor necrosis factor α and T helper type 1 cells, may explain the MC and IBD relationship. During endoscopy, a prompt biopsy should be taken if suspicious for MC, thus decreasing the duration of patient's symptoms and saving healthcare costs.
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Affiliation(s)
| | - Harika Balagoni
- Gastroenterology, Ascension Providence Hospital, Southfield, USA
| | - Sankalp Dwivedi
- Gastroenterology, Ascension Providence Hospital, Southfield, USA
| | - Marc Piper
- Gastroenterology, Ascension Providence Hospital, Southfield, USA
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12
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Collagenous Gastritis in Children: Incidence, Disease Course, and Associations With Autoimmunity and Inflammatory Markers. Clin Transl Gastroenterol 2021; 11:e00219. [PMID: 32955189 PMCID: PMC7431242 DOI: 10.14309/ctg.0000000000000219] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients.
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13
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Khalili H, Burke KE, Roelstraete B, Sachs MC, Olén O, Ludvigsson JF. Microscopic Colitis and Risk of Inflammatory Bowel Disease in a Nationwide Cohort Study. Gastroenterology 2020; 158:1574-1583.e2. [PMID: 31926169 DOI: 10.1053/j.gastro.2019.12.028] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/11/2019] [Accepted: 12/28/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Microscopic colitis shares pathogenetic mechanisms with inflammatory bowel disease (IBD). We studied the association between microscopic colitis and risk of incident IBD using data from a nationwide cohort study. METHODS We conducted a prospective cohort study of all adults who received a diagnosis of microscopic colitis from 1990 through 2017 in Sweden and risk of incident IBD. Cases of microscopic colitis (n= 13,957) were identified through Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, which included gastrointestinal pathology reports from all of Sweden's 28 centers. Individuals with microscopic colitis were matched to 5 general population controls (n = 66,820) and to unaffected siblings (n =13,943). Cox regression was used to estimate adjusted hazard ratio (aHRs) and 95% confidence intervals (CIs). RESULTS Through December of 2017, we identified 323 incident cases of ulcerative colitis (UC) and 108 incident cases of Crohn's disease (CD) in patients with microscopic colitis compared with 94 UC and 42 CD cases in population comparators. Mean times from diagnosis of microscopic colitis to diagnosis of CD was 3.3 ± 3.2 years and to diagnosis of UC was 3.2 ± 3.5 years. In multivariable models, microscopic colitis was associated with an aHR of 12.6 (95% CI 8.8-18.1) for CD, 17.3 (95% CI 13.7-21.8) for UC, and 16.8 (95% CI 13.9-20.3) for IBD. The 10-year absolute excess risks of CD and UC were 0.9 (95% CI 0.7-1.1) and 2.6 (95% CI 2.2-2.9) percentage points, respectively. In sensitivity analyses, comparing patients with microscopic colitis with their unaffected siblings, the aHRs of CD and UC were 5.4 (95% CI 3.2-9.2) and 9.4 (95% CI 6.4-13.8), respectively. CONCLUSIONS In a population-based study in Sweden, we found a significant increase in risk of incident IBD among patients with microscopic colitis. Future studies should focus on potential mechanisms underlying these observed associations.
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Affiliation(s)
- Hamed Khalili
- Massachusetts General Hospital, Crohn's and Colitis Center and Harvard Medical School, Boston, Massachusetts; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
| | - Kristin E Burke
- Massachusetts General Hospital, Crohn's and Colitis Center and Harvard Medical School, Boston, Massachusetts
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Michael C Sachs
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Ola Olén
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
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14
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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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15
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Liu Q, Harpaz N. Expression Profiling of Inflammatory and Immunological Genes in Collagenous Colitis. J Crohns Colitis 2019; 13:764-771. [PMID: 31131860 PMCID: PMC6535503 DOI: 10.1093/ecco-jcc/jjy224] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 11/27/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Collagenous colitis [CC] is a common idiopathic cause of chronic watery diarrhoea. We investigated its pathogenesis by means of gene expression analysis. METHODS We analysed the expression of genes implicated in immunological and inflammatory pathways in paired colonic biopsies of histologically involved and uninvolved mucosa from five patients with histologically patchy CC, in pooled colonic biopsies of eight other patients with diffuse CC, and in pooled biopsies of eight normal controls. Analyses were performed with the Nanostring nCounter system. Expression ratios were generated and confirmed by quantitative reverse transcription PCR. RESULTS CC mucosa was characterized by enhanced expression of nitric oxide synthase 2; of matrix metalloproteinases 3 and 9 and tissue inhibitor of metalloproteinase 1, but not transforming growth factor β1; of mediators of T-helper 1 immunity including interleukins 12A [IL12A], 12B, IL12 receptor B1 and interferon γ; of immune mediators of the leukocyte immunoglobulin-like receptor subfamily B; and of multiple T cell cytokines and their receptors. The mitogen-activated protein kinase signalling pathway was unchanged. There were no increases in IL22, IL22RA2 or tumour necrosis factor α, which are reportedly elevated in chronic inflammatory bowel disease. In four of five patients with patchy CC, similar gene expression profiles were observed in histologically involved and uninvolved mucosa. CONCLUSIONS CC is characterized by altered expression of a limited repertoire of genes involved in nitric oxide synthesis, extracellular matrix remodelling, T-helper 1 immunity and immune modulation. The abnormal gene expression in patchy CC may be expressed in mucosa with and without histological disease manifestations.
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Affiliation(s)
- Qingqing Liu
- The Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Noam Harpaz
- The Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA,Corresponding author: Noam Harpaz, MD, PhD, Department of Pathology, Annenberg 15-38E, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA. Tel: [212) 241-6692; Fax: [212) 828-4188;
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16
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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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17
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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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18
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Valluri M, Akhondi H, Hyndman M. Moyamoya complicated by thrombotic cerebrovascular accident in a Caucasian woman with collagenous colitis. Neurol Sci 2018; 39:2007-2009. [PMID: 30094527 DOI: 10.1007/s10072-018-3519-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 08/01/2018] [Indexed: 11/28/2022]
Affiliation(s)
- Manshi Valluri
- , Las Vegas, USA.,Internal Medicine Residency, MountainView Hospital Center, Las Vegas, NV, USA
| | - Hossein Akhondi
- Department of Internal Medicine, Mountain View Hospital Center, 2880 N Tenaya Way, Las Vegas, NV, 89128, USA.
| | - Mark Hyndman
- Core Faculty, Internal Medicine Residency, Mountain View Hospital Center, Las Vegas, NV, USA
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19
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Setia N, Alpert L, van der Sloot KWJ, Colussi D, Stewart KO, Misdraji J, Khalili H, Lauwers GY. Lymphocytic colitis: pathologic predictors of response to therapy. Hum Pathol 2018; 78:1-7. [DOI: 10.1016/j.humpath.2018.02.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Revised: 01/27/2018] [Accepted: 02/01/2018] [Indexed: 12/22/2022]
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20
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Westerlind H, Mellander MR, Bresso F, Munch A, Bonfiglio F, Assadi G, Rafter J, Hübenthal M, Lieb W, Källberg H, Brynedal B, Padyukov L, Halfvarson J, Törkvist L, Bjork J, Andreasson A, Agreus L, Almer S, Miehlke S, Madisch A, Ohlsson B, Löfberg R, Hultcrantz R, Franke A, D'Amato M. Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis. Gut 2017; 66:421-428. [PMID: 26525574 DOI: 10.1136/gutjnl-2015-309934] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 10/11/2015] [Accepted: 10/12/2015] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role. DESIGN Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin. RESULTS Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10-10 for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10-11; OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis). CONCLUSIONS HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.
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Affiliation(s)
- Helga Westerlind
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Marie-Rose Mellander
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Francesca Bresso
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Andreas Munch
- Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden
| | - Ferdinando Bonfiglio
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Ghazaleh Assadi
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Joseph Rafter
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Matthias Hübenthal
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Wolfgang Lieb
- Institute of Epidemiology and Biobank POPGEN, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Henrik Källberg
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Boel Brynedal
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Leonid Padyukov
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Leif Törkvist
- Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Jan Bjork
- Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Andreasson
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Lars Agreus
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Sven Almer
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Stephan Miehlke
- Center for Digestive Diseases, Internal Medicine Center Eppendorf, Hamburg, Germany
| | - Ahmed Madisch
- Clinic for Gastroenterology, Endoscopy and Interventional Diabetology, Siloah Hospital, Hannover, Germany
| | - Bodil Ohlsson
- Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden
| | - Robert Löfberg
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Sophiahemmet Hospital, Stockholm, Sweden
| | - Rolf Hultcrantz
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Mauro D'Amato
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
- BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
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21
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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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22
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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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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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Abstract
Microscopic colitis (MC) is described as an inflammatory bowel disease characterized by chronic, bloodless diarrhea with normal or close to normal endoscopic findings. Histopathological examination reveals two subtypes: collagenous colitis (CC) and lymphocytic colitis (LC), which are indistinguishable clinically. The disease debuts typically in middle-aged patients, but can occur at all ages, including children. A female predominance is found in both CC and LC, but is not confirmed by others in LC. The etiology is unclear, but the disease has been assumed to be of autoimmune origin. However, several etiologies may render a microscopic inflammation in the mucosa; this is a common, universal reaction to a variety of irritants in contact with the intestinal lumen. Furthermore, some patients with a microscopic inflammation in their colonic mucosa have no symptoms, or are suffering from constipation or abdominal pain, rather than diarrhea. Recently, a discussion was initiated calling into question the overdiagnosing of symptoms and pointing out the danger of exacerbating people's perception of their ailments, of weakening their eligibility in health insurance, of overprescription of drugs, and thus the increasing cost to the society of health care. In the light of this discussion, this review will highlight histopathological and clinical features of MC, and discuss the diagnosis and management of this disease. Perhaps, the intestinal mucosa has no other mode by which to react than an inflammatory response, irrespective of the presence or absence of autoimmunity. Thus, to better identify and classify subgroups of MC, and to clarify and correctly handle the inflammatory changes, this field of research stands to benefit from a review of the results and experience gained to date.
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Affiliation(s)
- Bodil Ohlsson
- Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Inga Marie Nilssons Street 32, S-205 02 Malmö, Sweden
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26
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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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Garner C, Ahn R, Ding YC, Steele L, Stoven S, Green PH, Fasano A, Murray JA, Neuhausen SL. Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus. PLoS One 2014; 9:e101428. [PMID: 24999842 PMCID: PMC4084811 DOI: 10.1371/journal.pone.0101428] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 06/03/2014] [Indexed: 12/20/2022] Open
Abstract
We performed a genome-wide association study (GWAS) of 1550 North American celiac disease cases and 3084 controls. Twelve SNPs, distributed across four regions (3p21.31, 4q27, 6q15, 6q25), were significantly associated with disease (p-value <1.0×10−7), and a further seven SNPs, across four additional regions (1q24.3, 10p15.1, 6q22.31, 17q21.32) had suggestive evidence (1.0×10−7 < p-value < 1.0×10−6). This study replicated a previous suggestive association within FRMD4B (3p14.1), confirming it as a celiac disease locus. All four regions with significant associations and two regions with suggestive results (1q24.3, 10p15.1) were known disease loci. The 6q22.31 and 10p11.23 regions were not replicated. A total of 410 SNPs distributed across the eight significant and suggestive regions were tested for association with dermatitis herpetiformis and microscopic colitis. Preliminary, suggestive statistical evidence for association with the two traits was found at chromosomes 3p21.31, 6q15, 6q25, 1q24.3 and 10p11.23, with future studies being required to validate the reported associations.
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Affiliation(s)
- Chad Garner
- Epidemiology Department, School of Medicine, University of California Irvine, Irvine, California, United States of America
- * E-mail:
| | - Richard Ahn
- Epidemiology Department, School of Medicine, University of California Irvine, Irvine, California, United States of America
| | - Yuan Chun Ding
- Population Sciences Department, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Linda Steele
- Population Sciences Department, Beckman Research Institute of City of Hope, Duarte, California, United States of America
| | - Samantha Stoven
- Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Rochester, MN, United States of America
| | - Peter H. Green
- Celiac Disease Center, Columbia University, New York City, New York, United States of America
| | - Alessio Fasano
- Center for Celiac Research, MassGeneral Hospital for Children, Boston, MA, United States of America
| | - Joseph A. Murray
- Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Rochester, MN, United States of America
| | - Susan L. Neuhausen
- Population Sciences Department, Beckman Research Institute of City of Hope, Duarte, California, United States of America
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Ingle SB, Adgaonkar BD, (Ingle) CRH. Microscopic colitis: Common cause of unexplained nonbloody diarrhea. World J Gastrointest Pathophysiol 2014; 5:48-53. [PMID: 24891975 PMCID: PMC4024520 DOI: 10.4291/wjgp.v5.i1.48] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Microscopic colitis (MC) is characterized by chronic, watery, secretory diarrhea, with a normal or near normal gross appearance of the colonic mucosa. Biopsy is diagnostic and usually reveals either lymphocytic colitis or collagenous colitis. The symptoms of collagenous colitis appear most commonly in the sixth decade. Patients report watery, nonbloody diarrhea of a chronic, intermittent or chronic recurrent course. With collagenous colitis, the major microscopic characteristic is a thickened collagen layer beneath the colonic mucosa, and with lymphocytic colitis, an increased number of intraepithelial lymphocytes. Histological workup can confirm a diagnosis of MC and distinguish the two distinct histological forms, namely, collagenous and lymphocytic colitis. Presently, both forms are diagnosed and treated in the same way; thus, the description of the two forms is not of clinical value although this may change in the future. Since microscopic colitis was first described in 1976 and only recently recognized as a common cause of diarrhea, many practicing physicians may not be aware of this entity. In this review, we outline the epidemiology, risk factors associated with MC, its etiopathogenesis, the approach to diagnosis and the management of these individuals.
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30
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Vigren L, Tysk C, Ström M, Kilander AF, Hjortswang H, Bohr J, Benoni C, Larson L, Sjöberg K. Celiac disease and other autoimmune diseases in patients with collagenous colitis. Scand J Gastroenterol 2013; 48:944-50. [PMID: 23800241 DOI: 10.3109/00365521.2013.805809] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. METHODS Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. RESULTS A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. CONCLUSION Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.
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Affiliation(s)
- Lina Vigren
- Department of Clinical Sciences, Division of Gastroenterology, Skåne University Hospital, Lund University, Malmö, Sweden.
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Auto-antibodies and their association with clinical findings in women diagnosed with microscopic colitis. PLoS One 2013; 8:e66088. [PMID: 23776613 PMCID: PMC3679050 DOI: 10.1371/journal.pone.0066088] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Accepted: 05/07/2013] [Indexed: 12/22/2022] Open
Abstract
Background Microscopic colitis (MC) is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings. Methods and Findings Women with MC verified by biopsy and younger than 73 years, at any Department of Gastroenterology, in the district of Skåne, between 2002 and 2010 were invited to participate in this study. The patients were asked to complete both a questionnaire describing their medical history and the Gastrointestinal Symptom Rating Scale (GSRS). Blood samples were collected. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), and antibodies against glutamic acid decarboxylase (anti-GAD), islet antigens-like insulin 2 (anti-IA2), thyroid peroxidase (anti-TPO), and thyrotropin receptor (TRAK) were analysed. Of 240 women identified, 133 were finally included in the study, median age 63 (59–67) years. Apart from the MC diagnosis, 52% also suffered from irritable bowel syndrome, 31% from hypertension and 31% from allergy. The prevalence of ANA (14%), ASCA IgG (13%), and anti-TPO antibodies (14%) for these patients was slightly higher than for the general population, and were found together with other concomitant diseases. Patients had more of all gastrointestinal symptoms compared with norm values, irrespective of antibody expression. Conclusions Women with MC have a slightly increased prevalence of some auto-antibodies. These antibodies are not associated with symptoms, but are expressed in patients with concomitant diseases, obscuring the pathophysiology and clinical picture of MC.
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El-Salhy M, Gundersen D, Hatlebakk JG, Hausken T. Clinical presentation, diagnosis, pathogenesis and treatment options for lymphocytic colitis (Review). Int J Mol Med 2013; 32:263-70. [PMID: 23695201 DOI: 10.3892/ijmm.2013.1385] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2013] [Accepted: 04/29/2013] [Indexed: 12/16/2022] Open
Abstract
Lymphocytic colitis (LC) is characterized by chronic or relapsing non-bloody watery diarrhea and a macroscopically normal colon. However, histopathological examination of colonic biopsy samples reveals an increased intraepithelial infiltration of lymphocytes (≥20/100 enterocytes), and increased inflammatory cells within the lamina propria, but with a normal mucosal architecture. The reported prevalence of LC varies from 14.2 to 45 per 100,000 individuals, while its reported incidence is between 0.6 and 16 per 100,000 individuals. LC has a high rate of spontaneous symptomatic remission and is not associated with an increased risk of colon cancer or inflammatory bowel disease. The diagnosis is based on the histopathological findings. The density of colonic chromogranin A-positive cells provides an effective diagnostic tool with high sensitivity and specificity in both the right and left colon. Gastrointestinal infections, drugs, and/or autoimmunity may trigger chronic colonic low-grade inflammation. Colonic nitric oxide, serotonin and peptide YY (PYY) cell densities are markedly increased in patients with LC. It has been hypothesized that the low-grade inflammation in LC through the endocrine-immune axis causes this increase. It has been postulated further that these abnormalities in the neuroendocrine system of the colon are responsible for the diarrhea observed in patients with LC. The benign course and rate of spontaneous remission of LC denotes that drugs with severe side-effects should be avoided if possible. The drug cost and drug coverage may also be limiting factors for some patients. These aspects should be taken into account when making decisions regarding treatment options.
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Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, Stord, Norway
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DiGiacomo D, Santonicola A, Zingone F, Troncone E, Caria MC, Borgheresi P, Parrilli G, Ciacci C. Human leukocyte antigen DQ2/8 prevalence in non-celiac patients with gastrointestinal diseases. World J Gastroenterol 2013; 19:2507-2513. [PMID: 23674852 PMCID: PMC3646141 DOI: 10.3748/wjg.v19.i16.2507] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Revised: 12/31/2012] [Accepted: 02/07/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease.
METHODS: HLA DQ2/8 status was assessed in 443 patients from three ambulatory gastroenterology clinics in Southern Italy (University of Federico II, Naples, Loreto Crispi Hospital, Ruggi D’Aragona Hospital, Salerno). Patients were grouped based on disease status [pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)] and DQ2/8 alleles, which correspond to a celiac disease genetic risk gradient. Subject allele frequencies were compared to healthy Italian controls.
RESULTS: One hundred and ninety-six out of four hundred and forty-three (44.2%) subjects, median age 56 years and 42.6% female, were DQ2/8 positive. When stratifying by disease we found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Furthermore, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Compared to healthy controls those with functional upper GI diseases disorders had a 1.8 times higher odds of DQ2/8 positivity. Those with liver disease had 1.3 times the odds, albeit not statistically significant, of DQ2/8 positivity. Both those with IBS and IBD had a lower odds of DQ2/8 positivity compared to healthy controls.
CONCLUSION: The proportion of individuals HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD as compared to general population estimates.
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Storr MA. Microscopic colitis: epidemiology, pathophysiology, diagnosis and current management-an update 2013. ISRN GASTROENTEROLOGY 2013; 2013:352718. [PMID: 23691336 PMCID: PMC3654232 DOI: 10.1155/2013/352718] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/10/2013] [Accepted: 03/28/2013] [Indexed: 12/14/2022]
Abstract
Microscopic colitis is a common cause of chronic diarrhea. Over the last years the incidence and the prevalence of microscopic colitis are rising and this rise is largely attributed to a rising awareness, and concomitantly an increasing number of diagnoses are made. Patients with microscopic colitis report watery, nonbloody diarrhea of chronic, intermittent, or chronic recurrent course. Following an unremarkable physical examination the diagnosis of microscopic colitis is made by colonoscopy, which shows essentially a normal colonic mucosa. Biopsies taken during the colonoscopy procedure will then finally establish the correct diagnosis. Histological workup can then confirm a diagnosis of microscopic colitis and can distinguish the two distinct histological forms, namely, collagenous colitis and lymphocytic colitis. Presently both forms are diagnosed and treated in the same way; thus the description of the two forms is not of clinical value, though this may change in future. Depending on the patients age and gender 10-30% of patients investigated for chronic diarrhea will be diagnosed with microscopic colitis if biopsies are taken. Microscopic colitis is most common in older patients, especially in female patients and is frequently associated with autoimmune disorders and the consumption of several drugs. This review summarizes the present knowledge of the epidemiology, the pathophysiology, and the diagnosis of microscopic colitis and discusses the former and the present treatment options.
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Affiliation(s)
- Martin Alexander Storr
- Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, Campus Grosshadern, Marchioninistr 15, 81377 Munich, Germany
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Dey I, Beck PL, Chadee K. Lymphocytic colitis is associated with increased pro-inflammatory cytokine profile and up regulation of prostaglandin receptor EP4. PLoS One 2013; 8:e61891. [PMID: 23613969 PMCID: PMC3629156 DOI: 10.1371/journal.pone.0061891] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Accepted: 03/18/2013] [Indexed: 12/25/2022] Open
Abstract
Microscopic colitis (MC) is comprised of two entities, lymphocytic (LC) and collagenous colitis. Up to 20% of patients with chronic diarrhea that have a normal appearing colonoscopy will be diagnosed with MC. Since MC was first described less than 40 years ago, little is known about the mechanisms involved in disease pathogenesis. Nonsteroidal anti-inflammatory drugs are associated with an increased risk of MC and some reports suggest a dysregulation in prostaglandin production. Recent genome wide screens have found an association between prostaglandin receptor EP4 expression and inflammatory bowel disease; however, EP4 expression has never been studied in MC. The aim of this study was to assess colonic mucosal inflammatory cytokine profiles in patients with LC and to assess expression of the prostaglandin receptor EP4. Colonic mucosal biopsies were obtained from patients undergoing colonoscopy for investigation of diarrhea and in those undergoing colon cancer screening. Following histological assessment, expression of cytokines and the prostaglandin receptor EP4 was analyzed using real-time reverse transcriptase-PCR and immunohistochemistry. Patients with LC had markedly increased mRNA expression for TNF-α, IFN-γ and IL-8 compared to normal controls (p<0.001). No significant differences were noted for IL-1β, IL-4, IL-10 or IL-12/23. Interestingly, those with LC had increased EP4 receptor expression, which positively correlated with increased TNF-α expression. This is the first report to demonstrate that LC is associated with increased TNF-α, INF-γ and IL-8 concurrent with a marked up-regulation of EP4. These findings add to our knowledge on the pathogenesis of LC and may give rise to possible new therapeutic and/or diagnostic tools in the management of MC.
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Affiliation(s)
- Indranil Dey
- Departments of Microbiology, Immunology and Infectious Disease, Health Sciences Centre, Snyder Institute for Chronic Inflammation, University of Calgary, Calgary, Alberta, Canada
| | - Paul L. Beck
- Division of Gastroenterology, Health Sciences Centre, Snyder Institute for Chronic Inflammation, University of Calgary, Calgary, Alberta, Canada
| | - Kris Chadee
- Departments of Microbiology, Immunology and Infectious Disease, Health Sciences Centre, Snyder Institute for Chronic Inflammation, University of Calgary, Calgary, Alberta, Canada
- * E-mail:
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Münch A, Aust D, Bohr J, Bonderup O, Fernández Bañares F, Hjortswang H, Madisch A, Munck LK, Ström M, Tysk C, Miehlke S. Microscopic colitis: Current status, present and future challenges: statements of the European Microscopic Colitis Group. J Crohns Colitis 2012; 6:932-45. [PMID: 22704658 DOI: 10.1016/j.crohns.2012.05.014] [Citation(s) in RCA: 160] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Accepted: 05/18/2012] [Indexed: 02/06/2023]
Abstract
Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials.
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Affiliation(s)
- A Münch
- Div. of Gastroenterology and Hepatology, Dept. of Clinical and Experimental Medicine, Faculty of Health Science, Linköping University, Sweden.
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Cerilli LA, Greenson JK. The Differential Diagnosis of Colitis in Endoscopic Biopsy Specimens: A Review Article. Arch Pathol Lab Med 2012; 136:854-64. [DOI: 10.5858/arpa.2012-0205-ra] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—A variety of inflammatory disorders may affect the colon, with widely differing clinical outcomes and management. These conditions encompass a spectrum of acute and chronic conditions.
Objective.—Review the pathology of the major colitides and highlight the most diagnostically useful features.
Data Sources.—Review of recent literature supplemented with personal experience in the field of gastrointestinal pathology.
Conclusions.—The etiologies associated with the various types of colitis are diverse and the range of histologic changes is somewhat limited. Nevertheless, the combination of clinical and endoscopic data coupled with histopathology allows for accurate classification in the majority of cases.
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Affiliation(s)
- Lisa A. Cerilli
- From the Department of Pathology, University of Michigan Medical School, Ann Arbor
| | - Joel K. Greenson
- From the Department of Pathology, University of Michigan Medical School, Ann Arbor
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Hautala N, Kauma H, Rajaniemi SM, Sironen T, Vapalahti O, Pääkkö E, Karttunen A, Ilonen J, Rytky S, Vainio O, Vaheri A, Hautala T. Signs of general inflammation and kidney function are associated with the ocular features of acute Puumala hantavirus infection. ACTA ACUST UNITED AC 2012; 44:956-62. [DOI: 10.3109/00365548.2012.700119] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Khor TS, Fujita H, Nagata K, Shimizu M, Lauwers GY. Biopsy interpretation of colonic biopsies when inflammatory bowel disease is excluded. J Gastroenterol 2012; 47:226-48. [PMID: 22322659 DOI: 10.1007/s00535-012-0539-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Accepted: 01/18/2012] [Indexed: 02/04/2023]
Abstract
The interpretation of colonic biopsies related to inflammatory conditions can be challenging because the colorectal mucosa has a limited repertoire of morphologic responses to various injurious agents. Only few processes have specific diagnostic features, and many of the various histological patterns reflect severity and duration of the disease. Importantly the correlation with endoscopic and clinical information is often cardinal to arrive at a specific diagnosis in many cases.
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Affiliation(s)
- Tze S Khor
- Gastrointestinal Pathology Service, Department of Pathology, Massachusetts General Hospital, Warren 219, Boston, MA, USA.
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Lymphocytic colitis and collagenous colitis: a review of clinicopathologic features and immunologic abnormalities. Adv Anat Pathol 2012; 19:28-38. [PMID: 22156832 DOI: 10.1097/pap.0b013e31823d7705] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Lymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of microscopic colitis, were recognized as rare disease entities 4 decades ago. An increasing body of evidence accumulated in the past 40 years reveals increasing incidence and prevalence rates, a wide spectrum of clinical presentations, and several histologic variants. Although several recent randomized clinical trials confirmed the efficacy of oral budesonide in treating LC and CC, disease relapse after a short-duration treatment is common. Despite their common clinical presentations and well-defined histologic diagnostic criteria, there are only few studies on the immunologic abnormalities in colonic tissue. The aim of this review is to (1) familiarize the pathologists in general practice with histomorphology of LC and CC, including the rare histologic variants and the clinical implication associated with these 2 diagnoses, (2) summarize the data from recent randomized clinical trials of oral budesonide, and (3) review immunological studies on colonic tissue. Overall, immunologic abnormalities of colonic tissue seem to explain for the histomorphologic features and the clinical symptomatology of LC and CC. Advances in the understanding of the underlying immunologic abnormalities in the colonic tissue may help develop novel and effective therapies for these 2 diseases.
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Cytokine gene polymorphism in microscopic colitis association with the IL-6-174 GG genotype. Eur J Gastroenterol Hepatol 2011; 23:607-13. [PMID: 21527852 DOI: 10.1097/meg.0b013e328346f5be] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Microscopic colitis (MC) is a chronic inflammatory disease with unknown pathogenesis. Very little is known about polymorphisms in the cytokine genes in MC. We have investigated the occurrence of well-characterized polymorphisms of interleukins (IL-6, IL-1β, IL-1 receptor antagonist, IL-10) and CD14 in MC. We also determined the serum IL-6 levels. METHODS We genotyped 81 patients with MC and 178 controls for polymorphisms of IL-6-174, IL-1β-511, IL-1β-3953, IL-1 receptor antagonist, IL-10-1082 and CD14-159. Serum concentration of IL-6 was measured in 72 patients. RESULTS Genotype GG of IL-6-174 was more prevalent in MC compared with the controls (P=0.030; odds ratio: 1.941; confidence interval: 1.078-3.495), and the frequency of allele G of IL-6-174 was higher in MC (0.55 vs. 0.47; P=0.036; odds ratio: 1.514; confidence interval: 1.041-2.203). However, after correction for multiple comparisons, the difference became nonsignificant. IL-6 genotype and the serum IL-6 concentration showed no association. The concentration of IL-6 was higher in patients with collagenous colitis than in those with lymphocytic colitis (median 1.73 vs. 1.34 pg/ml, P=0.011). No association between polymorphisms of other cytokine genes and MC was seen. CONCLUSION The IL-6-174 gene polymorphism has a possible association with MC, as the IL-6 GG genotype was more frequent in patients with the disease. As this genotype may be linked with an enhanced IL-6 production, we speculate that this polymorphism can influence the pathogenesis of MC by evoking a proinflammatory bias in the mucosal cytokines. The enhanced concentration of IL-6 in collagenous colitis compared with lymphocytic colitis supports a difference in the pathogenetic mechanisms between the two subgroups of MC.
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Koskela RM, Niemelä SE, Lehtola JK, Bloigu RS, Karttunen TJ. Gastroduodenal mucosa in microscopic colitis. Scand J Gastroenterol 2011; 46:567-76. [PMID: 21291294 DOI: 10.3109/00365521.2011.551889] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND We have assessed gastroduodenal, endoscopical and histopathological findings in a series of patients with microscopic colitis (MC). METHODS We studied 75 patients with MC, 27 with collagenous colitis (CC) and 48 with lymphocytic colitis (LC), and 60 controls. Data of endoscopical findings were collected and biopsies were assessed. RESULTS Helicobacter pylori infection rate was 15% in MC and 28% in the controls (p = 0.088). Age at diagnosis of MC was higher in H. pylori positive than negative patients (63.4 ± 9.6 vs. 54.4 ± 13.1 years; p = 0.034). Gastric endoscopic erosions were more prevalent in CC than in LC (25.9% vs. 6.2%; p = 0.030) and associated with thick body glands and antral predominance of gastritis in H. pylori positive patients. Rates of focal gastritis (5.6% vs. 6.9%) and lymphocytic gastritis (5.6% vs. 10%) were similar in MC and controls. LC was associated with gastric epithelial lymphocytosis and lymphocytic gastritis. Fifteen patients (20%) had celiac disease. CONCLUSIONS Unlike LC, CC is associated with endoscopic erosions, likely related with the high acid secretion capacity as indicated by the ample body glands and antral predominance of gastritis in H. pylori associated cases of CC. The presence of some divergent gastroduodenal features in LC and CC, and in comparison with those reported in inflammatory bowel disease (IBD), supports the concept that these two conditions differ not only from IBD but also from each other. The findings also suggest the presence of pathogenetic links between colorectal and gastroduodenal abnormalities.
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Williams JJ, Beck PL, Andrews CN, Hogan DB, Storr MA. Microscopic colitis -- a common cause of diarrhoea in older adults. Age Ageing 2010; 39:162-8. [PMID: 20065357 DOI: 10.1093/ageing/afp243] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Diarrhoeal diseases are common in older populations and often markedly affect their quality of life. Although there are numerous potential causes, microscopic colitis (MC) is increasingly recognised as a major diagnostic entity in older individuals. MC is comprised of two distinct histological forms - collagenous colitis and lymphocytic colitis, both of which frequently occur in older populations. Recent studies suggest that between 10 and 30% of older patients investigated for chronic diarrhoea with an endoscopically normal appearing colon will have MC. It is unclear why MC is more common in older populations, but it is associated with both autoimmune disorders and several drugs that are commonly used by seniors. A definitive diagnosis can only be made with colonic biopsies. Since MC was first described in 1976 and only recently recognised as a common cause of diarrhoea, many practising physicians may not be aware of this entity. In this review, we outline the epidemiology, risk factors associated with MC, its pathophysiology, the approach to diagnosis and the management of these individuals.
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Affiliation(s)
- Jennifer J Williams
- Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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Abstract
Microscopic colitis (MC) causes chronic diarrhea, abdominal cramping, nausea, and weight loss. Colonic mucosa appears normal on endoscopy; however, biopsies show abnormalities such as intraepithelial lymphocytosis in lymphocytic colitis, and a thickened subepithelial collagen band in collagenous colitis. Epidemiologic data demonstrates that MC is a more common cause of diarrhea than previously shown. Although the etiology of this condition is unclear, certain well-defined risk factors exist. Recently there has been more research on the pathophysiology of MC, and studies on treatment have demonstrated budesonide to be most effective, although other treatments also hold promise.
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Tysk C, Bohr J, Nyhlin N, Wickbom A, Eriksson S. Diagnosis and management of microscopic colitis. World J Gastroenterol 2008; 14:7280-8. [PMID: 19109861 PMCID: PMC2778111 DOI: 10.3748/wjg.14.7280] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2008] [Revised: 12/03/2008] [Accepted: 12/10/2008] [Indexed: 02/06/2023] Open
Abstract
Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.
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