Medical therapy for Crohn's disease strictures.
Intestinal fibrostenosis is a frequent and debilitating complication of Crohn's disease (CD), not only resulting in small bowel obstruction, but eventually in repeated bowel resection and short bowel syndrome. Over one third of patients with CD have a clear stenosing disease phenotype, often in the absence of luminal inflammatory symptoms. Intestinal fibrosis is a consequence of chronic transmural inflammation in CD. As in other organs and tissues, phenotypic transformation and activation of resident mesenchymal cells, such as fibroblasts and smooth muscle cells, underlie fibrogenesis in the gut. The molecular mechanisms and growth factors involved in this process have not been identified. However, it is clear that inflammatory mediators may have effects on mesenchymal cells in the submucosa and the muscle layers that are profoundly different from their action on leukocytes or epithelial cells. Transforming growth factor-beta (TGF-beta), for instance, has profound anti-inflammatory activity in the mucosa and probably serves to keep physiologic inflammation at bay, but at the same time it appears to be driving the process of fibrosis in the deeper layers of the gut. Tumor necrosis factor, on the other hand, has antifibrotic bioactivity and pharmacologic inhibition of this cytokine carries a theoretical risk of enhanced stricture formation. Endoscopic management of intestinal strictures with balloon dilation is an accepted strategy to prevent or postpone repeated surgery, but careful patient selection is of paramount importance to ensure favorable long-term outcomes. Specific medical therapy aimed at preventing or reversing intestinal fibrosis is not yet available, but candidate molecules are emerging from research in the liver and in other organs.
Van Assche
Gert
G
Division of Gastroenterology, Leuven University Hospital, Herestraat 49, 3000 Leuven, Belgium. gert.vanassche@uz.kuleuven.ac.be
Geboes
Karel
K
Rutgeerts
Paul
P
D002404:Catheterization; D003113:Colonoscopy; D003424:Crohn Disease / Q000150:complications / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007415:Intestinal Obstruction / Q000150:complications / Q000473:pathology / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use
D016212:Transforming Growth Factor beta