Diagnosis change in pediatric inflammatory bowel disease.

OBJECTIVES: This study aims to characterize pediatric inflammatory bowel disease (IBD) patients who change diagnosis and describe the characteristics of that change. METHODS: A retrospective study was conducted on pediatric IBD patients from the ImproveCareNow (ICN) multicenter international cohort from 2007 to January 2019. Primary outcome was change in diagnosis after the first four visits. Other variables included demographics, diagnostics, disease characteristics, and timing. RESULTS: 6.1% of 18,055 patients aged 1-20 years changed diagnosis. Median time between the baseline visit and first diagnosis change was 0.9 years. Change in diagnosis occurred in 257/12,178 (2.1%) patients with Crohn's disease (CD), 347/4758 (7.3%) patients with ulcerative colitis (UC), and 495/1119 (44.2%) patients with IBD-Unclassified (IBD-U). In multivariable analysis, initial diagnosis of IBD-U and longer follow-up times were associated with greater odds of a diagnosis change. CONCLUSION: IBD-U initial diagnosis and longer follow-up were associated with increased diagnosis change risk. The most common change was reclassification to CD. Disease activity, moderate malnutrition, and presence of EIMs were not associated with change in diagnosis.

Free and Bioavailable 25-Hydroxyvitamin D Concentrations are Associated With Disease Activity in Pediatric Patients With Newly Diagnosed Treatment Naïve Ulcerative Colitis.

Background: Vitamin D regulates intestinal epithelial and immune functions, and vitamin D receptor deficiency increases the severity of murine colitis. Bioavailable 25-hydroxyvitamin D (25(OH)D) is available to target tissues and may be a driver of immune function. The aim is to evaluate the relationship of bioavailable 25(OH)D to the clinical expression of treatment naive pediatric ulcerative colitis (UC). Methods: The PROTECT (Predicting Response to Standardized Pediatric Colitis Therapy) study enrolled children ≤17 years newly diagnosed with UC. Free and total 25(OH)D were directly measured and 25(OH)D fractions were compared with disease activity measures. Results: Data were available on 388 subjects, mean age 12.7 years, 49% female, 84% with extensive/pancolitis. The median (IQR) total 25(OH)D concentration was 28.5 (23.9, 34.8) ng/mL, and 57% of subjects demonstrated insufficient vitamin D status (25(OH)D < 30 ng/mL). We found no evidence of association between total 25(OH)D and disease activity. Regression models adjusted for age, sex, race, and ethnicity demonstrated that an increase from 25th to 75th percentile for bioavailable and free 25(OH)D were associated with a mean (95th CI) decrease in the Pediatric Ulcerative Colitis Activity Index (PUCAI) of -8.7 (-13.7, -3.6) and -3.1 (-5.0, -1.2), respectively. No associations were detected between 25(OH)D fractions and fecal calprotectin or Mayo endoscopy score. Conclusions: Vitamin D insufficiency is highly prevalent in children with newly diagnosed UC. We found associations of free and bioavailable, but not total 25(OH)D, with PUCAI. Bioavailable vitamin D may contribute to UC pathophysiology and clinical activity.

Familial Association of Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Inflammatory Bowel Disease.

OBJECTIVES: Elevated granulocyte-macrophage colony-stimulating factor auto-antibodies (GM-CSF Ab) are associated with increased intestinal permeability and stricturing behavior in Crohn disease (CD). We tested for familial association of serum GM-CSF Ab level in CD and ulcerative colitis (UC) families. METHODS: Serum GM-CSF Ab concentration was determined in 230 pediatric CD probands and 404 of their unaffected parents and siblings, and 45 UC probands and 71 of their unaffected parents and siblings. A linear mixed effects model was used to test for familial association. The intra-class correlation coefficient (ICC) was used to determine the degree of association of the serum GM-CSF Ab level within families in comparison with the degree of association among families. RESULTS: The median (IQR) serum GM-CSF Ab concentration was higher in CD probands than in UC probands (1.5 [0.5,5.4] µg/mL vs 0.7 [0.3, 1.6] µg/mL, P = 0.0002). The frequency of elevated serum GM-CSF Ab concentration ≥1.6 µg/mL was increased in unaffected siblings of CD probands with elevated GM-CSF Ab, compared with unaffected siblings of CD probands without elevated GM-CSF Ab (33% vs 13%, respectively, P = 0.04). A similar result was observed within UC families. In families of CD patients, the mean (95th CI) ICC was equal to 0.153 (0.036, 0.275), P = 0.001, whereas in families of UC patients, the mean (95th CI) ICC was equal to 0.27 (0.24, 0.31), P = 0.047. CONCLUSIONS: These data confirmed familial association of serum GM-CSF Ab levels. This could be accounted for by either genetic or environmental factors shared within the family.