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Location is important: differentiation between ileal and colonic Crohn’s disease

Abstract

Crohn’s disease can affect any part of the gastrointestinal tract; however, current European and national guidelines worldwide do not differentiate between small-intestinal and colonic Crohn’s disease for medical treatment. Data from the past decade provide evidence that ileal Crohn’s disease is distinct from colonic Crohn’s disease in several intestinal layers. Remarkably, colonic Crohn’s disease shows an overlap with regard to disease behaviour with ulcerative colitis, underlining the fact that there is more to inflammatory bowel disease than just Crohn’s disease and ulcerative colitis, and that subtypes, possibly defined by location and shared pathophysiology, are also important. This Review provides a structured overview of the differentiation between ileal and colonic Crohn’s disease using data in the context of epidemiology, genetics, macroscopic differences such as creeping fat and histological findings, as well as differences in regard to the intestinal barrier including gut microbiota, mucus layer, epithelial cells and infiltrating immune cell populations. We also discuss the translation of these basic findings to the clinic, emphasizing the important role of treatment decisions. Thus, this Review provides a conceptual outlook on a new mechanism-driven classification of Crohn’s disease.

Key points

  • Emerging data from fields including clinical behaviour, epidemiology, genetics and the gut microbiota strongly suggest that ileal and colonic Crohn’s disease should be regarded as at least two subtypes of this disease entity.

  • Creeping fat, which represents hyperplasia of the mesenteric fat and wrapping of inflamed intestinal segments, is unique to small-intestinal Crohn’s disease and absent in colonic Crohn’s disease.

  • Predictive models applying a genetic risk score are able to differentiate between ileal and colonic Crohn’s disease.

  • The ileum in Crohn’s disease is characterized by a type 1 or type 17 helper T cell profile, whereas the colon is characterized by a type 1 profile.

  • There is an observable trend that patients with Crohn’s disease with isolated ileal manifestation are less likely to respond to biological therapies than patients with colonic disease.

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Fig. 1: Site-specific changes of the mesentery in Crohn’s disease.
Fig. 2: Site-specific changes in Crohn’s disease.

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Acknowledgements

R.A. and B.S. are supported by the research initiatives CRC-TRR 241, SI 749/10-1 and SPP1656 (B.S.), CRC1181 (R.A.), and CRC1340 and CRC1449 (B.S.) of the German Research Foundation (DFG). The DFG funds the Heisenberg Professorship of R.A.

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B.S. has served as a consultant for Abbvie, Boehringer, Celgene, Falk, Janssen, Lilly, Pfizer, Prometheus, Takeda and has received speaker’s fees from Abbvie, CED Service GmbH, Falk, Ferring, Janssen, Novartis and Takeda as a representative of Charité – Universitätsmedizin Berlin. R.A. has served as a speaker, or consultant, or received research grants from AbbVie, Biogen, Boehringer Ingelheim, Celgene, Dr. Falk Pharma, Ferring, InDex Pharmaceuticals, Janssen-Cilag, MSD Sharp & Dome, Pfizer, Roche Pharma, Samsung Bioepis and Takeda.

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Atreya, R., Siegmund, B. Location is important: differentiation between ileal and colonic Crohn’s disease. Nat Rev Gastroenterol Hepatol 18, 544–558 (2021). https://doi.org/10.1038/s41575-021-00424-6

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