New concepts in the pathophysiology of inflammatory bowel disease

Clinical Principles The inflammatory bowel diseases (IBDs), that is, Crohn disease and ulcerative colitis, affect approximately 1 million persons in North America and several million persons worldwide. Approximately 30% of patients present between 10 and 30 years of age. Current therapeutic options are limited and include nonspecific anti-inflammatory and immunosuppresive medications. Surgery is required for 50% to 80% of patients with Crohn disease, while only 20% of patients with ulcerative colitis have surgery. Novel biological therapeutics have greatly improved the quality of life of patients with IBD. Pathophysiologic Principles Both genetic and environmental factors play important roles in disease pathogenesis. New hypotheses implicate the innate immune system and the intestinal epithelium in the pathogenesis of the disease. Lymphocytes, cytokines, and adhesion molecules are dysregulated and have been targeted for therapeutic intervention. Based on a new understanding of the complicated mechanisms that underlie the disease process, combination therapies are currently being pursued. A better understanding of the pathophysiologic mechanisms will aid in prevention and more effective maintenance of remission of IBDs.