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Evolution of Pediatric Inflammatory Bowel Disease Unclassified (IBD-U): Incorporated With Serological and Gene Expression Profiles. Inflamm Bowel Dis 2018 Sep 15;24(10):2285-2290

Date

06/04/2018

Pubmed ID

29860529

DOI

10.1093/ibd/izy136

Scopus ID

2-s2.0-85056878759 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

BACKGROUND: Inflammatory bowel disease (IBD) mainly consists of Crohn's disease (CD) and ulcerative colitis (UC). About 10%-15% of patients with IBD cannot be firmly diagnosed with CD or UC; hence, they are initially diagnosed as inflammatory bowel disease unclassified (IBD-U). Having a firm diagnosis is clearly preferred to guide treatment choices, and better understanding of the nature of IBD-U is required.

METHODS: We performed an analysis of a subset of pediatric subjects from an inception IBD cohort of patients initially enrolled in a prospective multicenter study (the RISK study). Initial diagnosis and 2-year follow-up data from the subjects diagnosed with IBD-U were analyzed. An expert panel verified final diagnosis using predefined criteria as a guide. Serological and disease-relevant ileal and rectal tissue gene expression profiles were investigated. The use and the time to initiate anti-TNFα treatment was analyzed among the outcome groups.

RESULTS: A total of 1411 subjects were enrolled with initial diagnosis of IBD, and among them, 136 subjects were initially diagnosed as IBD-U at enrollment. And 26% were reclassified as UC and 14% as CD within 2 years of diagnosis, while 60% remained as IBD-U. Of those who were reclassified, there was a 2:1 ratio, UC (n = 35) to CD (n = 19). The molecular and serological features of IBD-U at the end of follow-up were very similar to UC and very different from CD. There was less likelihood of receiving anti-TNFα agents if the diagnosis was IBD-U compared with CD (P < 0.0001).

CONCLUSIONS: In our cohort, 60% of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U. 10.1093/ibd/izy136_video1Video 1.Video 1. Watch now at https://academic.oup.com/ibd/article-lookup/doi/10.1093/ibd/izy136izy136.video15791389938001.

Author List

Chandradevan R, Hofmekler T, Mondal K, Harun N, Venkateswaran S, Somineni HK, Ballengee CR, Kim MO, Griffiths A, Noe JD, Crandall WV, Snapper S, Rabizadeh S, Rosh JR, Walters TD, Bertha M, Dubinsky MC, Denson LA, Sauer CG, Markowitz JF, LeLeiko NS, Hyams JS, Kugathasan S

Author

Joshua D. Noe MD Associate Dean, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Biomarkers
Child
Child, Preschool
Female
Follow-Up Studies
Humans
Immunosuppressive Agents
Infant
Infant, Newborn
Inflammatory Bowel Diseases
Male
Prognosis
Prospective Studies
Transcriptome