Professor El-Omar has chosen Dr Ilyssa O. Gordon and Dr Florian Rieder to do the next #GUTBlog. Dr Ilyssa O. Gordon is Associate Professor in the Department of Pathology at the Cleveland Clinic, Cleveland, Ohio, USA. Her research focus is the diagnosis and categorization of intestinal fibrosis in inflammatory bowel diseases.  Dr Florian Rieder is Vice Chair of the Department of Gastroenterology, Hepatology and Nutrition at the Cleveland Clinic, Cleveland, Ohio, USA. His work focuses on pathogenesis, prediction, and clinical trials of intestinal fibrosis.  The #GUTBlog focusses on the latest paper “International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease” which was published in paper copy in GUT in March 2022.  Dr Ilyssa O. Gordon is the first author on this paper.

Dr Ilyssa O. Gordon and Dr Florian Rieder write:

“In patients with inflammatory bowel diseases, who suffer from chronic relapsing and remitting inflammation of the intestinal tract, symptomatic bowel obstruction occurs in a large proportion. This is particularly true for Crohn’s disease patients that due to small bowel strictures suffer from obstruction and have to undergo endoscopic or surgical interventions.

No therapy exists to specifically treat this complication with medical therapies, but multiple initiatives are now underway to test anti-stricture therapies. Cross sectional imaging, such as computed tomography or magnetic resonance enterography will be important endpoints in these trials. To validate these endpoints, studies are necessary comparing them to a histopathologic gold standard. Endoscopic mucosal biopsies are superficial and only assess the surface of the intestinal wall. Crohn’s disease and Crohn’ disease strictures in the small bowel, however, affect the entire intestinal wall and thorough histopathology validation studies therefore need to include the entire thickness of the intestine.

Strikingly, no validated scoring systems for full thickness intestinal histopathology for small bowel stricturing Crohn’s disease exist, despite this being a large unmet medical need.

To address this, we compiled a group of international gastrointestinal histopathology and gastroenterology experts and first reviewed any published paper that assessed full thickness histopathology in small bowel Crohn’s disease strictures. The result of this exercise was identification of a larger number of scoring systems, none of which has been properly developed or validated.

We concluded that a new validated histopathology scoring system is needed. As a second step we then developed items describing inflammation, fibrosis, and muscle changes in the strictured small intestinal wall and had our international panel rank those based on appropriateness. The process used the RAND/UCLA methodology and included two voting rounds with an interposed expert discussion.

Key findings included features on gross morphology consistent with strictures, such as wall thickness, internal circumference, and luminal diameter. The group furthermore devised definitions for the fat wrapping linked with strictures, called ‘creeping fat’. On histopathology the panel assembled necessary features of small bowel strictures such as increased wall thickness, accumulation of extracellular matrix in the intestinal wall or a thickening of the muscle layer. In addition, characteristics for active and chronic inflammation were identified. The panel thoroughly assessed the existing histopathologic scoring systems and none of them was found to be appropriate for use as a gold standard. Finally, the group also commented on technical parameters of sample preparation and staining techniques.

This work now for the first time established commonly accepted definitions and components of Crohn’s disease associated small bowel strictures. This included a focus on components related to fibrosis, muscle changes and active and chronic inflammation. In addition to strictures, this program may also provide guidance for inflammation scoring of the entire depth of the intestinal wall in non-strictured segments.

Next steps are already under way. The created statements of this consensus are currently being tested in central reading reliability exercises prior to construction of a full thickness histopathology index for small bowel strictures in Crohn’s disease. The final goal is a global score for use in clinical trials and drug development. We hope this new scoring system will enable the development of novel biomarkers and support construction of imaging endpoints for clinical trials in stricturing Crohn’s disease.”

Dr Ilyssa O. Gordon

Dr Floran Rieder @IBD_FloMD