Please cite this article in press as: Bousvaros A, et al., Research and clinical challenges in paediatric inflammatory bowel disease, Dig Liver Dis (2007), doi:10.1016/j.dld.2007.07.168 ARTICLE IN PRESS YDLD-1132; No. of Pages 7 Available online at www.sciencedirect.com Digestive and Liver Disease xxx (2007) xxx–xxx Research and clinical challenges in paediatric inflammatory bowel disease A. Bousvaros a,∗,1 , A. Morley-Fletcher b,1 , L. Pensabene c,1 , S. Cucchiara b,1 a Inflammatory Bowel Disease Center, Children’s Hospital Boston, Harvard Medical School, United States b Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, University of Rome, Italy c Department of Pediatrics University “Magna Græcia”, Catanzaro, Italy Received 23 July 2007; accepted 26 July 2007 Abstract Inflammatory bowel disease in childhood has become the subject of intense scientific debate during the last two decades, when there has been a significant rise in its incidence. There is a commonly agreed view that the disorder in children has peculiarities both in terms of underlying mechanisms and clinical management. This review highlights the emerging pathophysiologic concepts and clinical issues in paediatric inflammatory bowel disease and their effects on the management of children with this disorder are discussed. Particular emphasis is given to the link between the improvement of the research in the pathogenetic mechanisms and the development of novel therapeutic strategies able to promote a change in the natural course of the disorder. © 2007 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. Keywords: Biological therapy; Children; Genetics; Immunology; Inflammatory bowel disease; Microbiology 1. Introduction Paediatric inflammatory bowel disease (IBD) has become a topic of major interest over the past 20 years. A detailed document published by the Crohn’s and Colitis Foundation of America in 2006 entitled “Challenges in Pediatric Inflam- matory Bowel Disease” nicely summarized the progress that has been made in the study of this field to date, and many of the high-priority questions that need to be answered in the future [1]. In summary, while our therapy has improved, our understanding of the pathogenesis remains limited. On the positive side, a number of new therapeutic interventions have been developed that have consistently improved the quality of life of children with this serious chronic illness. Specifically, the early introduction of immunomodulator drugs, the proper use of enteral nutrition and the utilization of tumour necrosis ∗ Corresponding author at: Children’s Hospital Boston Inflammatory Bowel Disease Center, 300 Longwood Ave, Boston, MA 02115, United States. Tel.: +1 617 355 2962; fax: +1 617 730 0494. E-mail address: athos.bousvaros@childrens.harvard.edu (A. Bousvaros). 1 These authors contributed equally to this work. factor inhibitors in patients who have failed immunomodu- lators have resulted in improved quality of life and improved growth for children with Crohn’s disease (CD) and ulcerative colitis (UC) [2,3]. Unfortunately, our understanding of the basic biology and pathophysiology of this condition remains suboptimal, and therefore we have no current interventions that prevent the disease. There is a markedly increasing prevalence of IBD throughout the modernized world, with two recent epidemiological paediatric studies from Wiscon- sin and from Sweden indicating an overall incidence rate of 7.05/100.000 and 7.4/100.000, respectively. [4,5]. While some of this reported increase may be due to improved meth- ods of case ascertainment, our technology to diagnose IBD (endoscopy, colonoscopy and radiography) has not changed significantly in the last 15 years. Therefore it is highly likely that the findings of these epidemiological reports represent a true increase in the incidence of paediatric IBD. In order to prevent IBD in the future and to improve the management of the disorder in paediatrics we need to better understand its cause. We now realize that the development of the research over the last decade has led to novel therapeu- tic strategies that target specific immunological pathways in 1590-8658/$30 © 2007 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. doi:10.1016/j.dld.2007.07.168