Journal of Pediatric Gastroenterology & Nutrition:
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
Address correspondence and reprint requests to Subra Kugathasan, MD, Pediatrics and Human Genetics, Division of Pediatric Gastroenterology, Emory Children's Center, 2015 Uppergate Dr NE, Atlanta, GA 30322 (e-mail: email@example.com).
Received 19 May, 2011
Accepted 23 May, 2011
The authors report no conflicts of interest.
See “Epidemiology of Inflammatory Bowel Disease: Is There a Shift Towards Onset at a Younger Age?” by Braegger et al on page 141.
Inflammatory bowel diseases (IBD) are ranked among the 5 most prevalent gastrointestinal diseases in the United States (1) and together they represent the most common chronic gastrointestinal disorder in children. About 25% of patients with IBD are diagnosed during childhood. The estimated annual disease-attributable direct cost of IBD is $6.3 billion, and the cost is significantly higher for children with IBD compared with adults (2). Recent epidemiological studies indicate a rising incidence of IBD in children, especially in those younger than 10 years old (3,4); these reports are of major concern.
The Braegger et al (5) report in this issue addresses the important question of whether higher IBD prevalence in young children is a consequence of rising incidence or of a shift toward onset at a younger age. In this retrospective study, 1688 patients were enrolled from a Swiss IBD cohort and analyzed using a regression model. The study concludes that rising incidence of IBD in children was not because the age of onset has decreased. The authors further speculate that the increased prevalence of IBD in children is the result of a true rise in the incidence of childhood-onset IBD.
Childhood-onset IBD has been proposed as a distinct disease form within a larger disease category because of the phenotypic variation and the differences in the natural history of IBD in young patients (6). There is no doubt that IBD is heritable: up to 30% of patients with IBD have a positive family history, and twin studies revealed >50% concordance rate among identical twins. With the advent of newer techniques such as genome-wide association studies, which uses high-density single-nucleotide polymorphism array technology, more than 50 disease-predisposing loci in IBD have been identified, confirming the richness of the heritability of IBD. These gene discoveries cannot explain the rising incidence of IBD in children, however, because the gene pool does not change rapidly in a few generations. This rapid rise in the incidence, if true, can only be attributed to either environmental factors such as infectious triggers and diet, or host factors such as immune inflammatory cells, intestinal epithelia, and microbial flora. In addition, gene–environment interactions may be important determinants of disease development, phenotype, and progression.
Descriptive epidemiological studies such as the Braegger et al (5) study are limited in scope, but they do reveal some intriguing observations. We can only hope that many ongoing prospective epidemiological studies augmented with concurrent collections of genetic, serological, and microbiota data will yield much more needed information regarding disease pathogenesis, disease evolution, and risk stratification. There is a real optimism that the recent success in gene discovery efforts coupled with the ongoing follow-up studies on gene expression, functional studies of the genes, and gene–gene or gene–environment interactions will uncover new pathways and translate into improved clinical management. Perhaps the most intriguing piece that emerges from these genetic epidemiology investigations may be the ability to predict disease development in at-risk population, disease evolution, treatment responses, and finally disease-risk stratifications.
1. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology 2002; 122:1500–1511.
2. Kappelman MD, Rifas-Shiman SL, Porter CQ, et al. Direct health care costs of Crohn's disease and ulcerative colitis in US children and adults. Gastroenterology 2008; 135:1907–1913.
3. Benchimol EI, Guttmann A, Griffiths AM, et al. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut 2009; 58:1490–1497.
4. Cucchiara S, Stronati L. Incidence in pediatric IBD is rising: help from health administrative data. Inflamm Bowel Dis 2011; 17:1048–1049.
5. Braegger CP, Ballabeni P, Rogler D, et al. Epidemiology of inflammatory bowel disease: is there a shift towards onset at a younger age? J Pediatr Gatroenterol Nutr 2011;53:141–4.
6. Ruemmele FM. Pediatric inflammatory bowel diseases: coming of age. Curr Opin Gastroenterol 2010; 26:332–336.