Yamile Zabana1,2, Gian Tontini3, Elisabeth Hultgren-Hörnquist4, Karolina Skonieczna-Żydecka5, Giovanni Latella6, Ann Elisabeth Østvik7,8, Wojciech Marlicz9,10, Mauro D'Amato11,12, Angel Arias2,13, Stephan Mielhke14, Andreas Münch15, Fernando Fernández-Bañares1,2, Alfredo J Lucendo2,16. 1. Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Barcelona, Spain. 2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. 3. Department of Pathophysiology and Transplantation, University of Milan and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy. 4. School of Medical Sciences, Örebro University, Örebro, Sweden. 5. Department of Biochemical Sciences, Pomeranian Medical University, Szczecin, Poland. 6. Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy. 7. Department of Clinical and Molecular Medicine [IKOM], Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. 8. Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway. 9. Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland. 10. Centre for Digestive Diseases Endoklinika, Szczecin, Poland. 11. Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain. 12. Ikerbasque, Basque Foundation for Science, Bilbao, Spain. 13. Research Unit, Hospital General Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain. 14. Centre for Digestive Diseases, Internal Medicine Centre Eppendorf & Endoscopy Centre, University Hospital Hamburg Eppendorf, Hamburg, Germany. 15. Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden. 16. Gastroenterology Department, Hospital General de Tomelloso-Spain and Instituto de Investigación Sanitaria Princesa [IIS-IP], Madrid, Spain.
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.
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.