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Intestinal histopathology in pediatric PSC-IBD: Characterization of phenotype and assessment of the Nancy Index
Rebecca Little1, Juan Putra2, Binita M Kamath1,3
1Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Pediatric primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD) shows a unique gut histology, differing from standard colitis. The Nancy Index has good reliability but limited clinical correlation in PSC-IBD.
Area of Science:
- Gastroenterology
- Pediatric Pathology
- Inflammatory Bowel Disease Research
Background:
- Pediatric primary sclerosing cholangitis (PSC) frequently co-occurs with inflammatory bowel disease (IBD), termed PSC-IBD.
- The distinct histologic gut phenotype of pediatric PSC-IBD compared to non-PSC colitis is not well-characterized.
- The utility of the Nancy Index (NI) for assessing histologic activity in pediatric PSC-IBD requires evaluation.
Purpose of the Study:
- To characterize the histologic gut phenotype of pediatric PSC-IBD.
- To compare the PSC-IBD histologic phenotype against non-PSC colitis.
- To assess the performance of the Nancy Index in pediatric PSC-IBD.
Main Methods:
- Retrospective cohort study of pediatric patients with PSC-IBD or non-PSC colitis (2000-2018).
- Independent pathologist re-review of intestinal biopsies to assess disease distribution, NI scores, and specific histologic features.
- Evaluation of NI inter-rater reliability and construct validity against endoscopic severity and clinical outcomes.
Main Results:
- PSC-IBD cases (n=50) showed significantly higher rates of pancolitis, right colon-predominant colitis, and backwash ileitis compared to non-PSC colitis controls (n=81).
- Histologic features such as lamina propria neutrophils, eosinophilic infiltration, and villiform change were more frequent in PSC-IBD.
- The NI demonstrated excellent inter-rater reliability and moderate correlation with endoscopic severity, but poor correlation with clinical activity in PSC-IBD.
Conclusions:
- Pediatric PSC-IBD exhibits a distinct histologic gut phenotype, mirroring its endoscopic distribution.
- This phenotype includes features not typically captured by conventional ulcerative colitis histologic activity indices.
- Further research is needed to determine if a PSC-IBD-specific histologic index is warranted.
Objectives:
We aimed to characterize the histologic gut phenotype of pediatric primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) against non-PSC colitis, and to assess Nancy Index (NI) performance in pediatric PSC-IBD.
Methods:
Single-center retrospective cohort study including children diagnosed with PSC-IBD or non-PSC colitis (ulcerative colitis [UC] or IBD-unclassified) from 2000 to 2018, with diagnostic intestinal biopsies. Biopsies were re-reviewed by two independent pathologists who assessed microscopic disease distribution, NI scores, and specific histological features in the right and left colons, overall and stratified by endoscopic severity (moderate-severe vs. no more than mild). We examined NI inter-rater reliability with Fleiss' weighted (quadratic) kappa and NI construct validity against global endoscopic severity (Spearman correlation) and clinical outcomes (logistic regression).
Results:
Fifty children with PSC-IBD and 81 colitis controls were included. Histologically, pancolitis (84% vs. 55%), right colon-predominant colitis (48% vs. 3%), and backwash ileitis (53% vs. 12%) (all p < 0.01) were significantly more common in PSC-IBD; histologic rectal sparing occurred at similar rates (6% vs. 10%, p = 0.54). Lamina propria-predominant neutrophils, prominent eosinophilic infiltration (left colon), and surface villiform change (right colon) were more common in PSC-IBD than colitis controls (p < 0.01). NI showed excellent inter-rater reliability (kappa > 0.9) and correlated moderately with global endoscopic severity but poorly with clinical activity in PSC-IBD.
Conclusions:
Pediatric PSC-IBD has a distinct histologic phenotype that largely mirrors the endoscopic phenotype in distribution and includes a greater frequency of features not included in conventional UC histologic activity indices. Future work should investigate whether a PSC-IBD-specific index incorporating these features is warranted.
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