Strictures in Crohn's Disease: From Pathophysiology to Treatment

Dig Dis Sci. 2020 Jul;65(7):1904-1916. doi: 10.1007/s10620-020-06227-0. Epub 2020 Apr 11.

Abstract

Despite recent advances aimed to treat transmural inflammation in Crohn's disease (CD) patients, the progression to a structuring behavior still represents an issue for clinicians. As inflammation becomes chronic and severe, the attempt to repair damaged tissue can result in an excessive production of extracellular matrix components and deposition of connective tissue, thus favoring the formation of strictures. No specific and accurate clinical predictors or diagnostic tools for intestinal fibrosis exist, and to date, no genetic or serological marker is in routine clinical use. Therefore, intestinal fibrosis is usually diagnosed when it becomes clinically evident and strictures have already occurred. Anti-fibrotic agents such as tranilast, peroxisome proliferator-activated receptor gamma agonists, rho kinase inhibitors, and especially mesenchymal stem cell therapy have provided interesting results, but most of the evidence has been derived from studies performed in vitro. Therefore, current therapy of fibrotic strictures relies mainly on endoscopic and surgical procedures. Although its long-term outcomes may be debated, endoscopic balloon dilation appears to be the safest and most effective approach to treat appropriately selected strictures. The use of endoscopic stricturotomy is currently limited by the expertise needed to perform it and by the few data available in the literature. Some good results have been achieved by the positioning of self-expandable metal stents (SEMS). However, there is no concordance regarding the type of stent to use and for how long it should be left in place. The development of new specific SEMS may lead to better outcomes and to an increased use of this alternative in CD-related strictures.

Keywords: Dilatation; Fibrosis; Inflammatory bowel diseases; Self-expandable metal stents; Stricture.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Constriction, Pathologic / etiology
  • Constriction, Pathologic / metabolism
  • Constriction, Pathologic / physiopathology*
  • Constriction, Pathologic / therapy*
  • Crohn Disease / complications
  • Crohn Disease / metabolism
  • Crohn Disease / physiopathology*
  • Crohn Disease / therapy
  • Dilatation
  • Endoscopy, Gastrointestinal*
  • Extracellular Matrix / metabolism
  • Fibroblasts / metabolism
  • Fibrosis / metabolism
  • Fibrosis / physiopathology
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Intestines / pathology*
  • PPAR gamma / agonists
  • Protein Kinase Inhibitors / therapeutic use
  • Self Expandable Metallic Stents*
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • ortho-Aminobenzoates / therapeutic use
  • rho-Associated Kinases / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Gastrointestinal Agents
  • PPAR gamma
  • Protein Kinase Inhibitors
  • Tumor Necrosis Factor Inhibitors
  • ortho-Aminobenzoates
  • rho-Associated Kinases
  • tranilast