Ulcerative Colitis Activity Index Score Research Articles

Agreement Between Patient‐ and Physician‐completed Pediatric Ulcerative Colitis Activity Index Scores

Currently validated ulcerative colitis (UC) activity measures are physician based, but incorporate patient reports of symptoms. We aimed to assess whether patient-completed Pediatric UC Activity Index (PUCAI) scores are comparable to those of physician scores. We performed a single-center prospective study to assess agreement between patient- and physician-completed PUCAI scores. Seventy patients with UC (ages 4-29) representative of all of the disease activity categories (inactive, mild, moderate, and severe) in the currently published physician-completed scoring system were recruited. Agreement was analyzed for PUCAI scores both as continuous and categorical measures. To ascertain validity, we compared both patient- and physician-completed PUCAI scores with the physician global assessment and serum inflammatory markers. Patient- and physician-completed PUCAI summary scores were identical 49% of the time, were different but within the minimal clinically important difference (MCID) of 20 points 48% of the time, and were at or beyond the MCID only 3% of the time. In general, patients reported higher mean disease severity on their questionnaires than did their physicians, with a mean difference in PUCAI scores of 3 ± 8 (95% confidence interval 2%-5%). A categorical comparison of the 2 sets of questionnaires using the disease activity groups demonstrated perfect agreement for 60 (86%) pairs (kappa coefficient 0.78; 95% confidence interval 0.65%-0.90%). Both patient- and physician-completed PUCAI scores also correlated well with the physician global assessment and serum inflammatory markers. Our data indicate strong agreement between PUCAI scores obtained directly from patients and those completed by physicians. Hence, a patient-based PUCAI could complement existing instruments in both clinical and research settings.

Profiling Hypoxia Markers in Pediatric Inflammatory Bowel Disease

Background: Inflammation-associated hypoxia has been studied extensively in murinemodels of inflammatory bowel diseases (IBD), and to a lesser extent in human IBD. Results from studies strongly implicate the potential that circulating or tissue markers of hypoxia could serve as important biomarkers of disease. A systematic analysis of hypoxia markers associated with IBD has not been pursued. Aims: To characterize markers of hypoxia in serum and colon biopsies from patients with IBD colitis and controls without colitis, and to correlate hypoxia markers with severity of disease assessed by histology, pro-inflammatory cytokines, questionnaires, and other laboratory data. Methods: Samples of blood and colon biopsies were obtained from 10 pediatric patients (mean age 13.9±2.7) with active IBD colitis and 8 controls (mean age 14.6±2.1), one of which had quiescent IBD. Protein levels of three hypoxia markers were measured in serum: erythropoietin (EPO), vascular endothelial growth factor (VEGF), and insulin-like growth factor binding protein-1 (IGFBP-1); and four proinflammatory cytokines were measured in tissue: IL-1 beta, IL-6, IL-8, and TNF alpha via an electrochemiluminescence-based ELISA platform. Pediatric Ulcerative Colitis Activity Index (PUCAI) and puberty scores were also collected. A single pathologist, blinded to diagnosis, graded biopsy histology based on a standardized scoring system. Differences by study group or PUCAI category were tested with two-sample t-tests or exact chi-square tests, and differences across histology grade by ANOVA. The monotonic relationship between hypoxia markers and pro-inflammatory cytokines and puberty score was tested with Spearman's correlation coefficient. Results: Patient demographics did not significantly differ by gender (p=0.06), race (p=0.7) or age (p=0.6). Children with active colitis had higher levels of EPO than controls (9.4 vs. 3.4, p=0.03). Notably, serum EPO levels did not correlate with hemoglobin. No significant differences were noted in total circulating VEGF (562 vs. 256, p=0.12) or IGFBP-1 (6716 vs. 3812, p=0.45), however all three serum hypoxia markers differed across histology grade (VEGF p=0.002, EPO p<0.0001, IGFBP-1=0.018). Serum VEGF was significantly correlated with tissue IL-6, IL-8, and TNF alpha (0.62, p=0.006; 0.57, p=0.014; 0.60, p=0.008), as was EPO with IL-6, IL-8, and TNF alpha (0.62, p=0.006; 0.63, p=0.005; 0.72, p=0.0008). VEGF and IGFBP-1 did not significantly differ by puberty score or across PUCAI score. Conclusions: These studies identify at least three hypoxia targets which could be pursued as potential biomarkers for disease activity. We conclude that markers of hypoxia strongly correlate with severity of colitis and that peripheral blood hypoxia markers may be useful surrogates to assess tissue inflammation.

The Course of Life and Health-Related Quality of Life of Adolescents With Inflammatory Bowel Disease

Background: Inflammation-associated hypoxia has been studied extensively in murinemodels of inflammatory bowel diseases (IBD), and to a lesser extent in human IBD. Results from studies strongly implicate the potential that circulating or tissue markers of hypoxia could serve as important biomarkers of disease. A systematic analysis of hypoxia markers associated with IBD has not been pursued. Aims: To characterize markers of hypoxia in serum and colon biopsies from patients with IBD colitis and controls without colitis, and to correlate hypoxia markers with severity of disease assessed by histology, pro-inflammatory cytokines, questionnaires, and other laboratory data. Methods: Samples of blood and colon biopsies were obtained from 10 pediatric patients (mean age 13.9±2.7) with active IBD colitis and 8 controls (mean age 14.6±2.1), one of which had quiescent IBD. Protein levels of three hypoxia markers were measured in serum: erythropoietin (EPO), vascular endothelial growth factor (VEGF), and insulin-like growth factor binding protein-1 (IGFBP-1); and four proinflammatory cytokines were measured in tissue: IL-1 beta, IL-6, IL-8, and TNF alpha via an electrochemiluminescence-based ELISA platform. Pediatric Ulcerative Colitis Activity Index (PUCAI) and puberty scores were also collected. A single pathologist, blinded to diagnosis, graded biopsy histology based on a standardized scoring system. Differences by study group or PUCAI category were tested with two-sample t-tests or exact chi-square tests, and differences across histology grade by ANOVA. The monotonic relationship between hypoxia markers and pro-inflammatory cytokines and puberty score was tested with Spearman's correlation coefficient. Results: Patient demographics did not significantly differ by gender (p=0.06), race (p=0.7) or age (p=0.6). Children with active colitis had higher levels of EPO than controls (9.4 vs. 3.4, p=0.03). Notably, serum EPO levels did not correlate with hemoglobin. No significant differences were noted in total circulating VEGF (562 vs. 256, p=0.12) or IGFBP-1 (6716 vs. 3812, p=0.45), however all three serum hypoxia markers differed across histology grade (VEGF p=0.002, EPO p<0.0001, IGFBP-1=0.018). Serum VEGF was significantly correlated with tissue IL-6, IL-8, and TNF alpha (0.62, p=0.006; 0.57, p=0.014; 0.60, p=0.008), as was EPO with IL-6, IL-8, and TNF alpha (0.62, p=0.006; 0.63, p=0.005; 0.72, p=0.0008). VEGF and IGFBP-1 did not significantly differ by puberty score or across PUCAI score. Conclusions: These studies identify at least three hypoxia targets which could be pursued as potential biomarkers for disease activity. We conclude that markers of hypoxia strongly correlate with severity of colitis and that peripheral blood hypoxia markers may be useful surrogates to assess tissue inflammation.

What is the optimal management approach for pediatric patients with severe ulcerative colitis?

The treatment of severe ulcerative colitis in pediatric patients presents a unique challenge to clinicians. In this Practice Point commentary we discuss the findings and limitations of a retrospective, longitudinal cohort study by Turner and colleagues, which provides valuable information on response to and predictors of outcome from corticosteroid therapy for pediatric patients with severe ulcerative colitis. The results suggest that daily monitoring of response to therapy and the Pediatric Ulcerative Colitis Activity Index score can accurately predict failure to respond to therapy. Second-line medical therapy (e.g. infliximab, ciclosporine and tacrolimus) should be considered, particularly for cases of new-onset severe pediatric ulcerative colitis, before colectomy to allow for better timing of surgery and to exclude the possibility of Crohn's disease colitis.