Etiology of inflammatory bowel disease

New and recycled hypotheses on the etiology of ulcerative colitis and Crohn's disease-the key role of the ″starved″ colonic epithelium in ulcerative colitis, the involvement of vasculitis and ischemia in Crohn's disease, and the old ″toothpaste″ hypothesis of Crohn's disease-have all provoked interest. Further evidence that ulcerative colitis and Crohn's disease are separate diseases has derived from divergent patterns of pathogenic mechanisms and of epidemiologic features, notably the effect of smoking. Divergent histopathologic patterns have also been noted for extensive compared with distal ulcerative colitis. Specific studies in the etiology of ulcerative colitis now focus on the colonic epithelium since new morphologic and biochemical evidence has been presented supporting the occurrence of some epithelial abnormalities independently of the presence of mucosal inflammation. Autoimmune injury to colonic epithelium remains a poorly substantiated hypothesis. A microbial cause of Crohn's disease has been pursued, and there has been negative systemic immunologic evidence for mycobacterial involvement but positive though circumstantial serologic evidence for involvement of chlamydiae and of some dietary yeasts. Further evidence that abnormal intestinal permeability may be a predisposing factor for the development of Crohn's disease has been advanced but many problems remain with this hypothesis. In conclusion, progress has been made but the answers remain elusive.