Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Aug 13;12(8):1839.
doi: 10.3390/biomedicines12081839.

Extraintestinal Manifestations in Inflammatory Bowel Disease: From Pathophysiology to Treatment

Ilaria Faggiani  1   2 , Jacopo Fanizza  1   2 , Ferdinando D'Amico  1 , Mariangela Allocca  1 , Alessandra Zilli  1 , Tommaso Lorenzo Parigi  1   2 , Alberto Barchi  1   2 , Silvio Danese  1   2 , Federica Furfaro  1
Affiliations
Review

Extraintestinal Manifestations in Inflammatory Bowel Disease: From Pathophysiology to Treatment

Ilaria Faggiani et al. Biomedicines. .

Abstract

The inflammatory bowel diseases (IBDs) are systemic conditions that affect not only the gastrointestinal tract but also other parts of the body. The presence of extraintestinal manifestations can significantly impact the quality of life in IBD patients. Peripheral arthritis, episcleritis, and erythema nodosum are frequently associated with active intestinal inflammation and often improve with standard treatment targeting intestinal inflammation. In contrast, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis typically occur independently of disease flares. The incidence of these conditions in individuals with IBD can reach up to 50% of patients over the course of their lifetime. In addition, some advanced therapies utilized for the treatment of IBD potentially result in side effects that may resemble extraintestinal manifestations. This review provides a thorough analysis of the pathophysiology and treatment of extraintestinal manifestations associated with Crohn's disease and ulcerative colitis.

Keywords: Crohn’s disease; extraintestinal manifestation; inflammatory bowel diseases; ulcerative colitis.

PubMed Disclaimer

Conflict of interest statement

F Furfaro received consulting fees from Amgen, AbbVie and lecture fees from Janssen and Pfizer, F D’Amico has served as a speaker for Abbvie, Ferring, Sandoz, Janssen, Galapagos, Takeda, Tillotts, and Omega Pharma; he also served as an advisory board member for Abbvie, Ferring, Galapagos, Janssen, and Nestlè. M Allocca has received consulting fees from Nikkiso Europe, Mundipharma, Janssen, AbbVie, Ferring, and Pfizer. S Danese has served as a speaker, consultant, and advisory board member for Schering–Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor. I Faggiani, J Fanizza, A Zilli, TL Parigi, and A Barchi declare no conflicts of interest.

Figures

Figure 1
Figure 1
Potential pathophysiology of EIMs. Extension of immune responses from the intestine: (A) ectopic expression of adhesion molecules and chemokines, such as the abnormal expression of MAdCAM-1 and CCL25 in the vascular endothelium of the portal tract; (B) microbial antigen cross-reactivity, such as molecular mimicry, occurs between enteric bacteria and self-antigens presented by host’s major histocompatibility complex molecules; (C) microbial antigen translocation [8]. EIMs as independent inflammatory events: (D) shift in inflammatory tone influenced by genetic, environmental, or microbial factors, or by a systemic increase in key inflammatory mediators; (E) systemic changes in innate immune function, for example, neutrophil priming; (F) gut microbiota-induced distant inflammation driven by microbial products such as lipopolysaccharide, through changes in gut permeability and microbiota-derived metabolites [8]. MAdCAM-1: mucosal vascular addressin cell adhesion molecule 1; CCL25: chemokine (C-C motif) ligand 25; CCR9: C-C motif chemokine receptor 9; VEGF: vascular endothelial growth factor; IL-6: interleukin-6; TNFα: tumor necrosis factor α; INFγ: interferon γ; LPS: lipopolysaccharide.
Figure 2
Figure 2
Main extraintestinal manifestations observed in patients with inflammatory bowel disease.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Rogler G., Singh A., Kavanaugh A., Rubin D.T. Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management. Gastroenterology. 2021;161:1118–1132. doi: 10.1053/j.gastro.2021.07.042. - DOI - PMC - PubMed
    1. Gordon H., Burisch J., Ellul P., Karmiris K., Katsanos K., Allocca M., Bamias G., Barreiro-de Acosta M., Braithwaite T., Greuter T., et al. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J. Crohn’s Colitis. 2024;18:1–37. doi: 10.1093/ecco-jcc/jjad108. - DOI - PubMed
    1. Kim J.M., Cheon J.H. Pathogenesis and clinical perspectives of extraintestinal manifestations in inflammatory bowel diseases. Intest. Res. 2020;18:249–264. doi: 10.5217/ir.2019.00128. - DOI - PMC - PubMed
    1. Bhat S., Click B., Regueiro M. Safety and Monitoring of Inflammatory Bowel Disease Advanced Therapies. Inflamm. Bowel Dis. 2024;30:829–843. doi: 10.1093/ibd/izad120. - DOI - PubMed
    1. Berlin C., Berg E.L., Briskin M.J., Andrew D.P., Kilshaw P.J., Holzmann B., Weissman I.L., Hamann A., Butcher E.C. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993;74:185–195. doi: 10.1016/0092-8674(93)90305-A. - DOI - PubMed

LinkOut - more resources