Low Indeterminate Rates Associated With Use of the QuantiFERON-TB Gold In-Tube Test in Children With Inflammatory Bowel Disease on Long-term Infliximab.

Background: Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term treatment with TNF-α inhibitors. The objective of this study was to assess the proportion of indeterminate results for the QuantiFERON-TB Gold In-Tube in children with inflammatory bowel disease (IBD) on long-term infliximab treatment and to evaluate the range of interferon-γ responses to mitogen. Methods: A single-center prospective study of children 5 to 19 years of age with IBD on long-term infliximab treatment (>3 months). Each child was assessed for tuberculosis exposure risk and had blood drawn for the QuantiFERON-TB Gold In-Tube. Data on the range of interferon-γ responses and final QuantiFERON-TB Gold In-Tube test results were collected. Results: Ninety-three children were included, with a median age of 16 years. The median total duration of infliximab therapy was 34 months (range, 3-119 months). The QuantiFERON-TB Gold In-Tube was indeterminate in 1 patient (1.1%), positive in 2 patients, and negative in 90 patients. The maximum interferon-γ response to mitogen (10 IU/mL) was observed in 82 patients (88%), with only 1 patient having an inadequate response. The proportion of indeterminate results was significantly lower than the prospectively hypothesized rate of 8%, based on prior studies in nonimmunosuppressed patients (P = 0.004). Conclusions: Pediatric patients with IBD on long-term treatment with infliximab had an adequate interferon-γ response to mitogen and a low indeterminate rate when assessed with the QuantiFERON-TB Gold In-Tube test. This study demonstrates a robust interferon gamma response to phytohemagglutinin stimulation in a pediatric population on long-term therapy with infliximab. The QuantiFERON-TB Gold In-Tube test may therefore be useful as a periodic screening tactic for latent TB in children on long-term infliximab therapy.

Impact of abdominal visceral adipose tissue on disease outcome in pediatric Crohn's disease.

BACKGROUND: Increased abdominal visceral adipose tissue (VAT) is associated with systemic inflammation. The influence of VAT on pediatric inflammatory bowel disease (IBD) has not been studied. The objective of this study was to investigate the differences in VAT between pediatric patients with IBD and age-matched controls and identify associations between VAT and Crohn's disease (CD) outcomes. METHODS: Single-center retrospective cohort study of 114 pediatric patients with IBD (101 CD and 13 ulcerative colitis) who had abdominal computed tomography at diagnosis. VAT volumes were measured from computed tomography images. A control group of 78 age-matched patients without IBD who had abdominal computed tomography was selected for comparison. RESULTS: Median VAT was 634 cm (interquartile range, 411-1041) in the IBD group and 659 cm (interquartile range, 394-1015) in the controls. IBD group had 33% higher VAT than controls (95% confidence interval [CI], 11-58) P = 0.002 after adjusting for body mass index and age. In patients with CD, higher VAT was associated with fistulizing or fibrostenotic disease (odds ratio [OR], 1.7; 95% CI, 1.1-2.9; P = 0.03), CD hospitalizations (OR, 1.9; 95% CI, 1.2-3.4; P = 0.01), moderate or severe disease activity scores (OR, 1.8; 95% CI, 1.1-3.1; P = 0.02), and shorter intervals from diagnosis to surgery (hazard ratio, 1.4; 95% CI, 1.0-2.0; P = 0.05) after adjusting for body mass index and age. CONCLUSIONS: At diagnosis, pediatric patients with IBD have higher adjusted VAT volumes than age- and body mass index-matched controls. Higher VAT volumes in pediatric patients with CD predicted more hospitalizations, increased likelihood of complicated disease, shorter interval from diagnosis to surgery, and higher disease activity scores at diagnosis.

The role of growth hormone and insulin-like growth factor-1 in Crohn's disease: implications for therapeutic use of human growth hormone in pediatric patients.

PURPOSE OF REVIEW: This review evaluates the role of the growth hormone (GH) and insulin-like growth factor (IGF) in influencing linear growth in pediatric Crohn's disease. It also examines the current evidence concerning the use of recombinant human growth hormone (rhGH) as a potential therapy in achieving optimal growth and inducing mucosal healing for pediatric Crohn's disease. RECENT FINDINGS: Current treatment strategies for Crohn's disease including antitumor necrosis factor-α (TNF-α) therapy have been demonstrated to improve growth velocity, but linear growth deficits persist despite optimization of therapy. By complex mechanisms, including the reduction of levels of IGF-1 and induction of systemic and hepatic GH resistance, cytokines such as TNF-α and interleukin-6 (IL-6), commonly elevated in active Crohn's disease, are important as mediators of linear growth delay. Recent evidence suggests that rhGH therapy is effective in improving short-term linear growth for a selected group of patients but of limited benefit as a therapy for improving mucosal disease and reducing clinical disease activity. SUMMARY: Crohn's disease interacts with the GH-IGF-1 axis in important ways. Recent studies evaluating rhGH use in pediatric Crohn's disease have demonstrated some efficacy in reversing persistent linear growth delay but limited benefits in terms of improving mucosal disease and clinical disease activity. Larger studies of adequate power are needed to confirm a true benefit in terms of growth, to examine a potential benefit with regard to modification of disease activity, and to evaluate long-term risks.