Evaluation of the pediatric crohn disease activity index: a prospective multicenter experience.
ABSTRACT Longitudinal assessment of disease activity is necessary for studies of therapeutic intervention in children with Crohn disease. The Pediatric Crohn Disease Activity Index (PCDAI) was developed a decade ago for such a purpose, but it function has only been examined in a small number of studies with a limited number of patients. The primary objectives of the present study were to develop cut scores reflecting disease activity as determined by physician global assessment (PGA) and to evaluate the responsiveness of the PCDAI to changes in patient condition after therapeutic interventions.
Data were derived from a prospective database of newly diagnosed children with inflammatory bowel disease established in 2002 at 18 pediatric gastroenterology centers in the United States and Canada. At diagnosis, at 30 days and 3 months after diagnosis, and quarterly thereafter, children (<16 years of age) with Crohn disease had disease assessment performed by PGA and PCDAI. Disease management was provided according to the dictates of the attending gastroenterologist and not by predetermined protocol.
181 patients had concomitant PGA and PCDAI performed at diagnosis, and 95 of these had similar assessment at short-term follow up. Mean +/- SD PCDAI scores for mild, moderate, and severe disease by PGA at diagnosis were 19.5 +/- 10.4, 32.2 +/- 12.7, and 47.8 +/- 14.9, respectively (P < 0.001 for all comparisons). Mean +/- SD PCDAI for inactive disease after treatment was 5.2 +/- 5.4. Receiver operating characteristic (ROC) curve analysis suggested that: 1) activity of moderate/severe disease was best reflected by a PCDAI of > or = 30 points, 2) clinical response (moderate/severe disease improving to mild/inactive) was best reflected by a decrease in PCDAI of > or = 12.5 points, and 3) a PCDAI < 10 best reflected inactive disease.
PCDAI scores accurately reflect disease activity as assessed by physician global assessment. A PCDAI score of > or = 30 has acceptable sensitivity and specificity to indicate disease of moderate/severe activity. A PCDAI decrease of 12.5 points or greater following therapeutic intervention accurately reflects a clinically significant response. The PCDAI is an appropriate tool for intervention trials in Crohn disease in children.
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ABSTRACT: Children with inflammatory bowel disease (IBD) manifest low bone mass; the cause remains unclear. We performed transilial bone biopsies in 20 IBD children at diagnosis and found a mild cortical bone deficit and slow bone turnover. It is possible that low mechanical stimulation due to inadequate muscle mass contributes to the bone deficit. Children with newly diagnosed IBD can have low bone mineral density and disturbed bone metabolism, but the tissue level characteristics of the bone involvement in pediatric IBD have not been elucidated. In the present study, we evaluated the skeletal status, including static histomorphometry on transiliac bone samples, in 20 patients (age range 8.4 to 17.7 years, 12 boys) with newly diagnosed IBD and compared results to published normative data. Despite normal height (mean Z-score 0.04, SD 1.2), areal bone mineral density at the lumbar spine was moderately low (mean age- and sex-specific Z-score -0.8, SD 1.1). Total body bone mineral content and lean mass were low for age and sex as well (mean Z-scores -1.2, SD 0.9 and -2.0, SD 0.9, respectively). Biochemical bone markers indicated low bone formation and resorption activity. Bone histomorphometry revealed a slightly low cortical width (mean 23%, SD 25%, below the result expected for age) but a normal amount of trabecular bone. The percentage of trabecular bone surface covered by osteoid or osteoclasts was low, suggesting that both bone formation and bone resorption were suppressed. Our results indicate that young patients manifest a mild cortical bone deficit at the iliac crest and slow trabecular bone turnover even at diagnosis, in the setting of IBD.Osteoporosis International 07/2009; 21(2):331-7. · 4.58 Impact Factor
Article: Cytogenetic damage in blood lymphocytes and exfoliated epithelial cells of children with inflammatory bowel disease.[show abstract] [hide abstract]
ABSTRACT: This longitudinal, prospective study sought to establish whether pediatric Crohn's disease (CD) and ulcerative colitis (UC) are associated with increased levels of cytogenetic damage and whether folate supplementation in combination with other treatments mitigates cytogenetic damage in children with inflammatory bowel disease (IBD). After a 1-mo treatment and folate supplementation, all clinical tests in CD (n = 24) and UC (n = 17) patients improved. Patients with CD were comparable in the cytogenetic response with controls (n = 28) assessed by micronucleus (MN) assay, but both groups differed from the UC group. While the MN frequency in epithelial cells slightly decreased from first to second observations in CD patients (p = 0.05) and controls (p = 0.11), an increase was observed in UC patients (p = 0.001). Similar changes were observed in blood lymphocytes resulting in significantly higher levels of the MNs and chromosome bridges in UC patients. These preliminary findings of a difference in chromosome damage between pediatric UC patients compared with CD patients and healthy controls warrant confirmation and expansion to determine (1) the role of cytogenetic damage in the pathogenesis of these diseases, (2) relative contribution of treatment and folate supplementation, and (3) potential links to the eventual development of cancer in some patients.Pediatric Research 03/2007; 61(2):209-14. · 2.70 Impact Factor
Article: Aberrant responses to TLR agonists in pediatric IBD patients; the possible association with increased production of Th1/Th17 cytokines in response to candida, a luminal antigen.[show abstract] [hide abstract]
ABSTRACT: Toll like receptors (TLR) regulate innate immune responses sensing byproducts of intestinal microbiota. We examined responses to TLR agonists in children with inflammatory bowel disease (IBD). Peripheral blood mononuclear cells (PBMC) obtained from children with IBD [Crohn's disease (CD, n = 10), ulcerative colitis (UC, n = 10)], children with non-IgE-mediated food allergy (NFA, n = 20), and controls (n = 15) were tested for their production of proinflammatory and counter-regulatory cytokines with TLR agonists in comparison with their cytokine production against milk protein and candida. IBD patients were all in the inactive state. IBD PBMC produced more IL-6 with all the TLR agonists tested than controls. CD PBMC produced more counter-regulatory cytokines with TLR agonists, while UC PBMC produced more IL-1ss and IL-10 with TLR 7/8 agonist than controls. Cytokine production by NFA PBMC did not differ from controls. CD but not UC PBMC produced more IFN-gamma and IL-17 with candida. Aberrant responses to TLR agonists may be associated with increase in IFN-gamma/IL-17 production against candida in CD children.Pediatric Allergy and Immunology 08/2009; 21(4 Pt 2):e747-55. · 2.46 Impact Factor