The pathogenesis of Crohn's disease

This paper describes a program of research undertaken by the Inflammatory Bowel Disease Study Group at the Royal Free Hospital School of Medicine. The Group has tested the hypothesis that the primary pathological abnormality in Crohn's disease is in the mesenteric blood supply. The first experiments involved microcorrosion resin casting of the arterial supply of specimens of resected intestine affected by Crohn's disease. This revealed severe damage to submucosal blood vessels, even in areas that were not affected macroscopically by Crohn's disease. Resected specimens of bowel were examined after perfusion-fixation: 85% of granulomas were associated with blood vessels, demonstrating that Crohn's disease is a granulomatous vasculitis. Patients with Crohn's disease usually have one or more features of a hypercoagulable state, which may increase the risk of ischemic damage. A model of Crohn's disease was developed in the ferret intestine, by embolizing mesenteric blood vessels using latex particles. Acute embolization results in patchy necrosis of the mucosa, with subsequent recovery. Surgical incision and anastomosis in a previously embolized area results in intense ulceration--suggesting that recurrent Crohn's disease after surgery is due to a second ischemic insult to an already damaged intestine. Finally, electron microscope studies have investigated the mesenteric vascular endothelium associated with granulomata in Crohn's disease. Viral particles have been identified within the vascular endothelium, with the appearance of paramyxoviridae. In situ hybridization and other studies suggest that these particles are measles virus.(ABSTRACT TRUNCATED AT 250 WORDS)