Characterization of Lymphoid follicles with a red ring sign as first manifestation of early Crohn's disease

Background and Aims: Clinical observations suggest that the initial inflammation in inflammatory bowel disease (IBD), mainly in Crohn's disease (CD), might take place in the lymphoid follicle (LF) especially in those with red ring sign (RRS). Therefore, the aim of this study was to evaluate the role of LFs in patients with IBD compared to healthy controls. The LFs with RRS were additionally analyzed using immunohistochemistry and confocal laser endomicroscopy.

Methods: 146 patients (84 male, 62 female; median age 34.4 years, range 19–55 years) were enrolled in this prospective study when undergoing an ileo-colonoscopy. The standardized pictures from the terminal ileum throughout the colon were taken using video colonoscopes. In each picture LFs were analyzed regarding their number, size and mucosa elevation level in correlation to histological results of biopsy specimens, immunological findings and medical history.

Results: Patients with ulcerative colitis showed a higher numbers of LFs in the terminal ileum and cecum as compared with Crohn's disease and control patients. The numbers of LFs were significantly reduced in both groups of patients under immunosuppressive therapy. Furthermore, our clinical and endoscopical observations together with immunohistochemistry of biopsy specimens, confirmed the hypothesis of early lesions in CD taking place in LF. The appearance of red ring, which was seen almost only in CD patients, might indicate the beginning of development of aphthous ulcers. In contrast to hyperplastic LF's, LFs with RRS showed hypervascularization at the base of LF as well as surrounding it as assessed by immunohistochemistry. In some LFs beginning aphthous ulcers were seen, and also increased inflammatory activity above the LF. CD15 immunostaining demonstrated numerous granulocytes, which weren't seen in the LFs without RRS. Confocal laser endomicroscopy showed abolished normal crypt architecture, crypt distortion, increased cellular infiltrate within the lamina propria, and dilated vessels.

Conclusion: Lymphatic tissue in form of LFs of the lower gastrointestinal tract expands as a consequence of the enhanced immune response under inflammatory conditions; it is reduced in numbers under immunsuppression. LFs surrounded by red ring might represent an early sign of development of aphthous ulcers in CD before first diagnosis according to histologic standard criteria.

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