Assessment of extraintestinal manifestations in inflammatory bowel diseases: A systematic review and a proposed guide for clinical trials

United European Gastroenterol J. 2020 Aug 10;2050640620950093.doi: 10.1177/2050640620950093. Online ahead of print.

Lucas Guillo 1, Ferdinando D'Amico 2 3, Mélanie Serrero 1, Karine Angioi 4, Damien Loeuille 5, Antonio Costanzo 2 6, Silvio Danese 2 7, Laurent Peyrin-Biroulet 3


Author information

  • 1Department of Gastroenterology, University Hospital of Marseille Nord, University of Aix-Marseille, Marseille, France.
  • 2Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • 3Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France.
  • 4Department of Ophthalmology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
  • 5Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, University of Lorraine and University Hospital of Nancy, Nancy, France.
  • 6Dermatology, Humanitas Clinical and Research Center - IRCCS, Milan, Italy.
  • 7Department of Gastroenterology, Humanitas Clinical and Research Center - IRCCS, Milan, Italy.


Background and aims: Extraintestinal manifestations are common in inflammatory bowel disease patients, although there are few data available on their diagnosis, management and follow-up. We systematically reviewed the literature evidence to evaluate tools and investigations used for the diagnosis and for the assessment of the treatment response in inflammatory bowel disease patients with extraintestinal manifestations.

Methods: We searched in PubMed, Embase and Web of Science from January 1999-December 2019 for all interventional and non-interventional studies published in English assessing diagnostic tools and investigations used in inflammatory bowel disease patients with extraintestinal manifestations.

Results: Forty-five studies (16 interventional and 29 non-interventional) were included in our systematic review, enrolling 7994 inflammatory bowel disease patients. The diagnostic assessment of extraintestinal manifestations was performed by dedicated specialists in a percentage of cases ranging from 60-100% depending on the specific condition. The clinical examination was the most frequent diagnostic strategy, accounting for 35 studies (77.8%). In patients with primary sclerosing cholangitis or rheumatological symptoms, biochemical and imaging tests were also performed. Anti-TNF agents were the most used biological drugs for the treatment of extraintestinal manifestations (20 studies, 44.4%), and the treatment response varied from 59.1% in axial spondyloarthritis to 88.9% in ocular manifestations. No benefit was detected in primary sclerosing cholangitis patients after treatment with biologics.

Conclusions: In the clinical management of inflammatory bowel disease patients with extraintestinal manifestations the collaboration of dedicated specialists for diagnostic investigations and follow-up is key to ensure the best of care approach. However, international guidelines are needed to homogenise and standardise the assessment of extraintestinal manifestations.

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