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Chronological Order of Appearance of Extraintestinal Manifestations Relative to the Time of IBD Diagnosis in the Swiss Inflammatory Bowel Disease Cohort

Vavricka, Stephan R. MD1,2; Rogler, Gerhard MD, PhD1; Gantenbein, Claudine BMed1; Spoerri, Muriel BMed1; Prinz Vavricka, Mareike MD3; Navarini, Alexander A. MD4,5; French, Lars E. MD4; Safroneeva, Ekaterina PhD6; Fournier, Nicolas PhD7; Straumann, Alex MD8; Froehlich, Florian MD8; Fried, Michael MD1; Michetti, Pierre MD9,10; Seibold, Frank MD11; Lakatos, Peter L. MD10; Peyrin-Biroulet, Laurent MD12; Schoepfer, Alain M. MD13

doi: 10.1097/MIB.0000000000000429
Original Clinical Articles

Background: Data evaluating the chronological order of appearance of extraintestinal manifestations (EIMs) relative to the time of inflammatory bowel disease (IBD) diagnosis is currently lacking. We aimed to assess the type, frequency, and chronological order of appearance of EIMs in patients with IBD.

Methods: Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed.

Results: The data on 1249 patients were analyzed (49.8% female, median age: 40 [interquartile range, 30–51 yr], 735 [58.8%] with Crohn's disease, 483 [38.7%] with ulcerative colitis, and 31 [2.5%] with indeterminate colitis). A total of 366 patients presented with EIMs (29.3%). Of those, 63.4% presented with 1, 26.5% with 2, 4.9% with 3, 2.5% with 4, and 2.7% with 5 EIMs during their lifetime. Patients presented with the following diseases as first EIMs: peripheral arthritis 70.0%, aphthous stomatitis 21.6%, axial arthropathy/ankylosing spondylitis 16.4%, uveitis 13.7%, erythema nodosum 12.6%, primary sclerosing cholangitis 6.6%, pyoderma gangrenosum 4.9%, and psoriasis 2.7%. In 25.8% of cases, patients presented with their first EIM before IBD was diagnosed (median time 5 mo before IBD diagnosis: range, 0–25 mo), and in 74.2% of cases, the first EIM manifested itself after IBD diagnosis (median: 92 mo; range, 29–183 mo).

Conclusions: In one quarter of patients with IBD, EIMs appeared before the time of IBD diagnosis. Occurrence of EIMs should prompt physicians to look for potential underlying IBD.

Article first published online 27 May 2015Supplemental Digital Content is Available in the Text.

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland;

2Department of Medicine, Division of Gastroenterology and Hepatology, Triemlispital Zurich, Zurich, Switzerland;

3Private Practice for Dermatology, Zurich, Switzerland;

4Department of Dermatology, University Hospital Zurich, Switzerland;

5Division of Genetics and Molecular Medicine, King's College, London, United Kingdom;

6Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland;

7Institute of Social and Preventive Medicine (IUMSP), University of Lausanne, Lausanne, Switzerland;

8Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland;

9Crohn's and Colitis Center, Clinique de La Source, Lausanne, Switzerland;

101st Department of Medicine, Semmelweis University, Budapest, Hungary;

11Department of Medicine, Gastroenterology, Spital Netz Bern Tiefenau, Bern, Switzerland;

12Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy-Brabois, Université Henri Poincaré 1, Vandoeuvre-lès-Nancy, France; and

13Department of Medicine, Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Reprints: Stephan R. Vavricka, MD, Division of Gastroenterology, Department of Internal Medicine, Triemli Hospital, Birmensdorferstrasse 497, CH-8063 Zurich, Switzerland (e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Supported by research Grants from the Swiss National Science Foundation (33CSC0_134274 to Swiss IBD Cohort Study group, 320000-114009/3 and 32473B_135694/1 to S. R. Vavricka, 32003B_135664/1 to A. M. Schoepfer, 310030-120312 to G. Rogler), and the Zurich Center for Integrative Human Physiology of the University of Zurich (to G. Rogler and S. R. Vavricka).

The authors have no conflicts of interest to disclose.

List of members of the SIBDCS study group is available in the Acknowledgments.

Received November 10, 2014

Accepted March 10, 2015

© Crohn's & Colitis Foundation of America, Inc.
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