Pediatric Crohn's disease: epidemiology and emerging treatment options

Abstract

Pediatric Crohn's disease: epidemiology and emerging treatment options Shivani Kansal,1–3 Anthony G Catto-Smith1,2 1Department of Paediatrics, University of Melbourne, 2Department of Gastroenterology, The Royal Children's Hospital Melbourne, 3Murdoch Children's Research Institute, Melbourne, VIC, Australia Abstract: There has been a dramatic increase in the incidence of Crohn's disease over the last two to three decades worldwide, which has affected both the developed world and increasingly also the developing world. Crohn's disease is a disease of youth and can have a profound effect on the growing child, both in terms of growth and skeletal health as well psychosocial maturation. Environmental risk factors appear to be crucially important, but it is not clear at present whether improved hygiene, especially in childhood, influences immunological conditioning, or whether there is a direct impact on the gut from a disturbed gut microbiota. Genetic variation appears to relate to how the host interacts with its microbiota, determining susceptibility rather than causation. The outcome is a sustained immune response, clinically presenting as a relapsing/remitting disease process. There is no current cure for Crohn's disease; treatments are designed to reduce symptoms and control inflammation, initially by inducing a remission, then trying to maintain it. Historical therapies have included 5-aminosalicylic acid-based drugs, corticosteroids, and immunomodulators. Two approaches which are gaining increasing interest are the use of exclusive enteral nutrition and biologicals. Enteral nutrition is a remarkably effective approach, though there is a limited understanding of its mechanism and difficulties in acceptance among the medical community. Biologicals are a class of drugs which specifically target molecules and pathways central to the inflammatory process; they are also very effective, but patients can develop a secondary loss of response as a result of antibodies to the biological agent. Infection and the development of secondary malignancies have provided concerns with these very potent agents and with combination therapies, but inadequately controlled disease appears to pose a bigger threat for many patients than the side effects of medications. A wide range of alternative therapies are also being explored, such as the manipulation of gut flora and pathways which might influence immune responsiveness. The marked recent increase in Crohn's disease, especially in children, has prompted a large research effort which to date has led to a better knowledge of the biology of the disease and more effective treatments. These therapies need to be used judiciously to optimize benefit and minimize side effects. Keywords: inflammatory bowel disease, ulcerative colitis, tumor necrosis factor, biologicals, microbiota, enteral nutrition