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Increased Prevalence of Luminal Narrowing and Stricturing Identified by Enterography in Pediatric Crohns Disease Patients With Elevated GranulocyteMacrophage Colony Stimulating Factor Autoantibodies

Dykes, Dana M. H. MD*; Towbin, Alexander J. MD; Bonkowski, Erin*; Chalk, Claudia; Bezold, Ramona RN, BSN*; Lake, Kathleen MSW*; Kim, Mi-Ok PhD§,‖; Heubi, James E. MD*; Trapnell, Bruce C. MD; Podberesky, Daniel J. MD; Denson, Lee A. MD*

doi: 10.1097/MIB.0b013e31829706e0
Original Clinical Articles

Background: Crohn’s disease (CD) patients with elevated granulocyte–macrophage colony-stimulating factor autoantibodies (GM-CSF Ab) are more likely to develop stricturing behavior requiring surgery. Computed tomography or magnetic resonance enterography (CTE or MRE) may detect luminal narrowing (LN) before stricture development. The objective of this study was to determine whether CD patients with elevated GM-CSF Ab (≥1.6 μg/mL) have a higher prevalence of LN and stricturing on CTE or MRE.

Methods: A single-center, cross-sectional study of 153 pediatric patients with CD and control subjects undergoing diagnostic CTE or MRE. Examinations were evaluated for disease activity using a novel scoring system and for the presence of LN, stricture, intra-abdominal abscess, or fistulae. Dichotomous outcomes were compared with respect to antibody status (high or low) using Fisher’s exact test and logistic regression, whereas continuous outcomes were evaluated using unpaired t test.

Results: GM-CSF Ab were elevated in CD patients (n = 114) with a median (interquartile range) GM-CSF Ab level of 2.3 μg/mL (0.5–6.6 μg/mL) compared with 0.6 μg/mL (0.3–1.3 μg/mL) in healthy and disease control subjects (n = 39) (P = 0.001). Ileal disease location was more common in CD patients with high GM-CSF Ab (P < 0.001). LN increased from 39% in CD patients with low GM-CSF Ab to 71% in those with high levels (P = 0.004) and remained significantly associated with high GM-CSF Ab in a multivariate logistic model, which included age, gender, small bowel location, and duration of disease. Stricturing prevalence on CTE or MRE examination increased from 4% in CD patients with low GM-CSF Ab to 19% in those with high GM-CSF Ab (P = 0.03).

Conclusions: Pediatric CD patients with high GM-CSF Ab levels have a higher prevalence of LN on CTE or MRE. Further study will be needed to determine whether medical therapy will reduce progression to stricturing behavior in these patients.

Article first published online 25 July 2013

*Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;

Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH;

Division of Pulmonary Biology and

§Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.

Reprints: Dana M. H. Dykes MD, MLC 2010, 3333 Burnet Avenue, Cincinnati, OH 45229 (e-mail: Dana.Dykes@cchmc.org).

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 (www.ibdjournal.org).

The authors have no conflicts of interest to disclose.

Supported by the National Institutes of Health grants (R01 DK078683) (L.A.D.) and T32 DK007727 (D.M.H.D.). This investigation was supported by Public Health Service research grant UL1-RR025764 and CO6-RR11234 from the National Center for Research Resources.

Received February 01, 2013

Accepted April 14, 2013

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