Pathogenesis of aphthoid ulcers in Crohn's disease: Correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry

Background-The mechanism of ulceration in Crohn's disease remains unknown. Aims-To clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn's disease. Methods-After identification of colonic lymphoid nodules and aphthoid lesions by magnifying colonoscopy, 76 biopsy specimens were obtained from 10 patients with Crohn's disease and three patients with colonic lymphoid hyperplasia. This study correlated magnifying colonoscopic, electron microscopic, and immunohistochemical findings of biopsy specimens. Results-In Crohn's disease, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy, showed surface erosions 150-200 mu m in size. These lymphoid nodules with red halos had small erosiions either light microscopically or electron microscopically in 18 of 21 specimens (86%). Correlation of scanning and transmission electron microscopy showed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was limited to M cells of FAE in the patients with lymphoid hyperplasia without inflammatory bowel disease. In Crohn's disease patients in remission, however, HLA-DR antigen was strongly expressed over the entire FAE of lymphoid nodules with a red halo endoscopically, while the expression was weak and irregular in the mucosa surrounding the lymphoid nodules. HLA-DR was strongly expressed in the entire inflamed colonic mucosa in the active stage. Conclusion-The red halo appearance surrounding lymphoid follicles seems to precede visible aphthoid ulcers and suggests that ulcerations in Crohn's disease originate from FAE, possibly related to its physiological role as a portal of entry for potentially pathogenic agents.