A Pilot Study of Confocal Laser Endomicroscopy to Predict Barrier Dysfunction and Relapse in Pediatric Inflammatory Bowel Disease

Abstract

Objectives: Probe-based confocal laser endomicroscopy (pCLE) is a novel imaging modality that enables virtual optical biopsy in vivo. Loss of barrier function of the small bowel observed via pCLE as increased density of epithelial gaps (extrusion zones left in the intestinal lining after cells are shed) is predictive of relapse in adult patients with inflammatory bowel disease (IBD). This study aims to determine whether such observations on pCLE are similarly predictive of disease relapse in pediatric patients with IBD.

Methods: Pediatric patients with biopsy-proven IBD underwent pCLE during colonoscopy and subsequent clinical follow-up every 6 months. Relapse was defined as moderate to severe flare with endoscopic evidence of inflammation during the follow-up period. The relations between epithelial gap density, disease relapse, and imaging parameters were determined using Cox models.

Results: Twenty-four patients with IBD (13 with Crohn disease, 11 with ulcerative colitis) with a median age of 14 years (range 10-21) were studied for a median of 13 (4-33) months. The median duration of disease was 2.9 years (range 0-9). Increased epithelial gap density in the terminal ileum on pCLE of normal endoscopic appearing terminal ileum mucosa (N = 19) was predictive of disease relapse when 3 or more areas were imaged (N = 6, log-rank P = 0.02, C-statistic = 0.94).

Conclusions: In pediatric patients with IBD, barrier dysfunction observed on pCLE imaging of the small bowel was predictive of disease relapse.

Trial registration: ClinicalTrials.gov NCT02003859.

Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1

Representative images of villi used for epithelial gap density derivation. A, normal villous with no epithelial gaps seen. Arrows indicate individual intestinal epithelial cells. B, abnormal villous with several epithelial gaps present, arrow heads indicate epithelial gaps.

FIGURE 2

Epithelial gap densities of the terminal ileum based onp-CLE in all study patients. Epithelial gap density is expressed as the number of epithelial gap per 1000 cells counted. pCLE = probe-based confocal laser endomicroscopy.

FIGURE 3

Event-free survival in study patients. A, Kaplan-Meier plot of event-free survival in all study patients with no disease areas imaged, by normal and elevated gap densities based on pCLE of the terminal ileum. B, Kaplan-Meier plot of event-free survival in patients with IBD with normal and elevated gap densities based on pCLE imaging who had ≥3 areas imaged and met other criteria defined in previous studies. pCLE = probe-based confocal laser endomicroscopy; IBD = inflammatory bowel disease.