Symptoms Do Not Correlate With Findings From Colonoscopy in Children With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
Background & Aims: Approximately 75% of children with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). IBD in patients with PSC (PSC-IBD) often has a unique phenotype, including a mild clinical course, yet it is associated with an increased risk of colorectal cancer compared with colonic IBD without PSC. We investigated whether subclinical endoscopic and histologic inflammation could account for the increased risk of colorectal cancer in patients with PSC-IBD, and whether these patients have increased fecal levels of calprotectin, a marker of inflammation. Methods: We performed a prospective study of children (age, <18 y) with colonic IBD with and without PSC who underwent colonoscopy from February 1, 2016, through March 31, 2017, at the Hospital for Sick Children in Toronto, Canada. We collected pediatric ulcerative colitis activity index (PUCAI) scores (to measure symptoms) and fecal levels of calprotectin from 37 children with PSC-IBD and 50 children with only IBD (controls; UC or IBD-unclassified). Colonoscopies were scored using the Mayo endoscopic subscore and the UC Endoscopic Index of Severity (UCEIS) scores, and histologic activity was graded. Among patients in clinical remission, endoscopic scores and the odds of active endoscopic disease (based on a UCEIS score ≥1) were compared between patients with and without PSC in univariate and multivariable analyses. Correlations between activity markers were compared between groups. The ability of fecal calprotectin to identify mucosal healing in patients with PSC-IBD was assessed using receiver operating characteristic curve analyses. Analogous analyses were performed for histologic activity. Results: Patients with PSC-IBD in clinical remission had higher endoscopic scores and greater odds of active endoscopic disease than controls (odds ratio, 5.9; 95% CI, 1.6–21.5). There was a higher degree of correlation between PUCAI and UCEIS scores in controls (r = 0.82) than in patients with PSC-IBD (r = 0.51; P = .01). Fecal levels of calprotectin correlated with UCEIS in patients with PSC-IBD (r = 0.84) and controls (r = 0.82; P = .80). Fecal levels of calprotectin identified mucosal healing in patients with PSC-IBD with an area under the receiver operating characteristic curve of 0.94 (optimal cut-point, 93 μg/g; 100% sensitivity and 92% specificity). Histologic activity scores and the odds of active histologic disease were also greater in patients in clinical remission with PSC-IBD than controls. Conclusions: Children with PSC-IBD in clinical remission, based on PUCAI scores, have a significantly higher risk of active endoscopic and histologic disease than children with colitis without PSC. Fecal levels of calprotectin correlate with endoscopic findings in pediatric patients with PSC-IBD; levels below 93 μg/g are associated with mucosal healing.
|Biomarker, Dysplasia, Endoscopy, Histology|
|Clinical Gastroenterology and Hepatology|
|Organisation||Department of Gastroenterology & Hepatology|
Ricciuto, A. (Amanda), Fish, J. (Jennifer), Carman, N. (Nicholas), Walters, T.D. (Thomas D.), Church, P.C. (Peter C.), Hansen, B.E. (Bettina E.), … Griffiths, A.M. (2018). Symptoms Do Not Correlate With Findings From Colonoscopy in Children With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. Clinical Gastroenterology and Hepatology. doi:10.1016/j.cgh.2018.01.020