Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2017; 23(33): 6137-6146
Published online Sep 7, 2017. doi: 10.3748/wjg.v23.i33.6137
Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases
Morten L Halling, Jens Kjeldsen, Torben Knudsen, Jan Nielsen, Lars Koch Hansen
Morten L Halling, Torben Knudsen, Department of Gastroenterology and Hepatology, Hospital of Southwest Jutland, 6700 Esbjerg, Denmark
Jens Kjeldsen, Lars Koch Hansen, Department of Medical Gastroenterology S, Odense University Hospital, 5000 Odense, Denmark
Jan Nielsen, Center for Clinical Epidemiology, Odense University Hospital, 5000 Odense, Denmark
Author contributions: Halling ML, Kjeldsen J, Knudsen T and Koch Hansen L designed the study; Koch Hansen L performed data collection; Nielsen J performed statistical analyses; Halling ML and Koch Hansen L drafted the manuscript and obtained funding; all authors revised and accepted the final manuscript.
Institutional review board statement: This study was approved by the Danish Data Protection Agency (approval # 2013-41-1596).
Conflict-of-interest statement: The authors report no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Morten L Halling, MD, Department of Gastroenterology and Hepatology, Hospital of Southwest Jutland, Medicinsk Gastroenterologisk Afdeling, Sydvestjysk Sygehus, Finsensgade 35, 6700 Esbjerg, Denmark. mortenhalling@gmail.com
Telephone: +45-79-183141 Fax: +45-79-183147
Received: March 2, 2017
Peer-review started: March 3, 2017
First decision: April 21, 2017
Revised: May 30, 2017
Accepted: July 12, 2017
Article in press: July 12, 2017
Published online: September 7, 2017
Abstract
AIM

To investigate whether immune mediated diseases (IMD) are more frequent in patients with inflammatory bowel disease (IBD).

METHODS

In this population based registry study, a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16, 2013. Controls were randomly selected from the Danish Civil Registration System (CRS) and matched for sex, age, and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis (UC), Crohn’s disease (CD) and Both the latter referring to those registered with both diagnoses. Subsequently, odds-ratios (OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher’s exact test.

RESULTS

There were significantly more women than men in the registry, and a greater percentage of comorbidity in the IBD groups (P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased (P < 0.00125) for primary sclerosing cholangitis (PSC), celiac disease, type 1 diabetes (T1D), sarcoidosis, asthma, iridocyclitis, psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and ankylosing spondylitis. Restricted to UC (P < 0.00125) were autoimmune hepatitis, primary biliary cholangitis, Grave’s disease, polymyalgia rheumatica, temporal arteritis , and atrophic gastritis. Restricted to CD (P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC (P < 0.00125) were atrophic gastritis, rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica. Restricted to women with CD were episcleritis, rheumatoid arthritis, and psoriatic arthritis. The only disease restricted to men (P < 0.00125) was sarcoidosis.

CONCLUSION

Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

Keywords: Immune mediated diseases, Ulcerative colitis, Risk, Prevalence, Registry, Chronic inflammatory diseases, Autoimmune diseases, Inflammatory bowel disease, Crohn’s disease, Extraintestinal manifestations

Core tip: Essential to inflammatory bowel disease (IBD) pathogenesis are environmental factors, altered gut microbiota and genetic susceptibility. The latter causing impairment of barrier function, autophagy, and Th1, 2 and 17 cell responses. Interestingly, these mechanisms are also thought important in other immune mediated diseases, as is the overlap of susceptibility genes. Besides the classic extraintestinal manifestations, we found a variety of immune mediated diseases to be more frequent in individuals with IBD. Physicians should be aware of this when treating these patients. Furthermore, these findings support the hypothesis that immune mediated diseases may have overlapping pathogeneses. Thus, understanding IBD might help us understand other immune mediated diseases and vice versa.