Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE), an inflammatory atopic disease of the esophagus, causes massive eosinophil infiltration, basal cell hyperplasia, and sub-epithelial fibrosis. To elucidate cellular and molecular factors involved in esophageal tissue damage and remodeling, we examined pinch biopsies from EoE and normal pediatric patients. An inflammation gene array confirmed that eotaxin-3, its receptor CCR3 and interleukins IL-13 and IL-5 were upregulated. An extracellular matrix (ECM) gene array revealed upregulation of CD44 & CD54, and of ECM proteases (ADAMTS1 & MMP14). A cytokine antibody array showed a marked decrease in IL-1α and IL-1 receptor antagonist and an increase in eotaxin-2 and epidermal growth factor. Western analysis indicated reduced expression of intercellular junction proteins, E-cadherin and claudin-1 and increased expression of occludin and vimentin. We have identified a number of novel genes and proteins whose expression is altered in EoE. These findings provide new insights into the molecular mechanisms of the disease.

Disease presentation and clinical course in black and white children with inflammatory bowel disease.

OBJECTIVES: To compare the disease presentation, disease phenotype, and clinical course between black and white children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: A 10-year retrospective review was undertaken of the medical records of 245 pediatric patients with IBD studied at a tertiary care center. RESULTS: In this patient population 24% were black and 76% were white. There were no differences between black and white patients in terms of anatomic distribution of IBD, symptom presentation, and extraintestinal manifestations. A family history of IBD (36.4% vs 17.5%; P = 0.006) was more common in white children. Mean erythrocyte sedimentation rate of black patients with Crohn disease was higher at diagnosis compared with whites (P < 0.001) and a greater proportion of African Americans presented with a body mass index z-score less than -2 (P < 0.009). At 12 months following diagnosis 22.5% of African American children had a hemoglobin level lower than 10 g/dL compared with 4.3% of whites (P = 0.001). African Americans had evidence of more complicating stricturing and penetrating Crohn disease behavior (51.3% vs 27.4%; P = 0.006). African Americans received significantly more corticosteroids and infliximab to treat their IBD compared with whites (P < 0.04). CONCLUSIONS: This study suggests that for pediatric IBD, there may be racial differences in prevalence of family history and in disease phenotype.

Infliximab efficacy in pediatric ulcerative colitis.

BACKGROUND: The effects of infliximab, a tumor necrosis factor-alpha (TNF-alpha) antibody, have been well established in adult patients with inflammatory and fistulizing Crohn's disease. This study evaluates short- and long-term efficacy of infliximab in children with ulcerative colitis. METHODS: All pediatric patients with ulcerative colitis who received infliximab between July 2001 and November 2003 at the Johns Hopkins Children's Center were identified. Short- and long-term outcomes and adverse reactions were evaluated. RESULTS: Twelve pediatric patients with ulcerative colitis received infliximab for treatment of fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid-dependent colitis (5), and steroid-refractory colitis (1). Nine patients had a complete short-term response, and 3 had partial improvement. The mean per patient dose of corticosteroid after the first infliximab infusion decreased from 45 mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day at 8 weeks (P = 0.008). Eight patients were classified as long-term responders with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3 underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long-term nonresponders were steroid-refractory compared with 1 of 8 long-term responders. Patients receiving 6-mercaptopurine had a better response to infliximab. CONCLUSION: Infliximab should be considered in the treatment of children with symptoms of acute moderate to severe ulcerative colitis.