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Pathophysiology of fistula formation in Crohn's disease


Scharl, Michael; Rogler, Gerhard (2014). Pathophysiology of fistula formation in Crohn's disease. World Journal of Gastrointestinal Pathophysiology, 5(3):205-212.

Abstract

Fistulae represent an important complication in patient suffering from Crohn's disease (CD). Cumulative incidence of fistula formation in CD patients is 17%-50% and about one third of patients suffer from recurring fistulae formation. Medical treatment options often fail and also surgery frequently is not successful. Available data indicate that CD-associated fistulae originate from an epithelial defect that may be caused by ongoing inflammation. Having undergone epithelial to mesenchymal transition (EMT), intestinal epithelial cells (IEC) penetrate into deeper layers of the mucosa and the gut wall causing localized tissue damage formation of a tube like structure and finally a connection to other organs or the body surface. EMT of IEC may be initially aimed to improve wound repair mechanisms since "conventional" wound healing mechanisms, such as migration of fibroblasts, are impaired in CD patients. EMT also enhances activation of matrix remodelling enzymes such as matrix metalloproteinase (MMP)-3 and MMP-9 causing further tissue damage and inflammation. Finally, soluble mediators like TNF and interleukin-13 further induce their own expression in an autocrine manner and enhance expression of molecules associated with cell invasiveness aggravating the process. Additionally, pathogen-associated molecular patterns also seem to play a role for induction of EMT and fistula development. Though current knowledge suggests a number of therapeutic options, new and more effective therapeutic approaches are urgently needed for patients suffering from CD-associated fistulae. A better understanding of the pathophysiology of fistula formation, however, is a prerequisite for the development of more efficacious medical anti-fistula treatments.

Abstract

Fistulae represent an important complication in patient suffering from Crohn's disease (CD). Cumulative incidence of fistula formation in CD patients is 17%-50% and about one third of patients suffer from recurring fistulae formation. Medical treatment options often fail and also surgery frequently is not successful. Available data indicate that CD-associated fistulae originate from an epithelial defect that may be caused by ongoing inflammation. Having undergone epithelial to mesenchymal transition (EMT), intestinal epithelial cells (IEC) penetrate into deeper layers of the mucosa and the gut wall causing localized tissue damage formation of a tube like structure and finally a connection to other organs or the body surface. EMT of IEC may be initially aimed to improve wound repair mechanisms since "conventional" wound healing mechanisms, such as migration of fibroblasts, are impaired in CD patients. EMT also enhances activation of matrix remodelling enzymes such as matrix metalloproteinase (MMP)-3 and MMP-9 causing further tissue damage and inflammation. Finally, soluble mediators like TNF and interleukin-13 further induce their own expression in an autocrine manner and enhance expression of molecules associated with cell invasiveness aggravating the process. Additionally, pathogen-associated molecular patterns also seem to play a role for induction of EMT and fistula development. Though current knowledge suggests a number of therapeutic options, new and more effective therapeutic approaches are urgently needed for patients suffering from CD-associated fistulae. A better understanding of the pathophysiology of fistula formation, however, is a prerequisite for the development of more efficacious medical anti-fistula treatments.

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Additional indexing

Item Type:Journal Article, not refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:15 August 2014
Deposited On:11 Feb 2015 10:47
Last Modified:06 Aug 2017 20:47
Publisher:Baishideng Publishing Group Co. Limited
ISSN:2150-5330
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.4291/wjgp.v5.i3.205
PubMed ID:25133023

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