Characterization of lymphoid follicles with red ring signs as first manifestation of early Crohn's disease by conventional histopathology and confocal laser endomicroscopy

Int J Clin Exp Pathol. 2012;5(5):411-21. Epub 2012 May 23.


Background and aims: Clinical observations suggest that the lymphoid follicles (LFs) may play a crucial role in the pathogenesis of inflammatory bowel disease (IBD), especially in Crohn's disease (CD) as the site of initial mucosal inflammation. The aim of this study was to compare the morphology of LFs in CD, ulcerative colitis (UC) and control patients using confocal laser endomicroscopy (CLE) in correlation to histological and immunohistochemical findings of biopsies.

Methods: 79 patients with IBD (46 with CD, 32 with UC and 1 patient with indeterminate colitis) and 67 controls patients were enrolled prospectively in this study. Median age was 32.5 years (range 19-65) and 37.4 years (range 20-65 years) respectively. To analyze the LFs, standardized images from the terminal ileum and the colon were taken using white-light video endoscopes. Additionally, CLE was performed to analyze subsurface structure of LFs. Targeted biopsies of LFs were analyzed using haematoxylin and eosin stain and immunohistochemistry.

Results: LFs were seen in all parts of the lower GI tract, but mostly in the terminal ileum and cecum. Endoscopy in 15 out of 17 patients with the first manifestation of CD showed LFs surrounded by red ring (so-called red ring sign, RRS). Histologically, LFs with RRS showed hypervascularization at the base of the LFs associated with numerous CD15-positive granulocytes. Similar features were not seen in LFs without RRS and in the control group. In some LFs with RRS early aphthous ulcers were seen. Using CLE, RRS showed abolished normal crypt architecture, crypt distortion, increased cellular infiltrate within the lamina propria, and dilated vessels.

Conclusion: LFs with RRS probably represent an early sign of aphthous ulcers in early CD and, thus, may be considered as early markers of first manifestation and flares in CD.

Keywords: CLE; Crohn`s disease; Endomicroscopy; inflammatory bowel disease; lymphoid follicle; lymphoid hyperplasia; pathology; red ring sign; ulcerative colitis.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Capsule Endoscopy
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / pathology*
  • Colon / metabolism
  • Colon / pathology
  • Crohn Disease / complications
  • Crohn Disease / diagnosis*
  • Crohn Disease / metabolism
  • Early Diagnosis
  • Endoscopy, Gastrointestinal
  • Fucosyltransferases / metabolism
  • Granulocytes / metabolism
  • Granulocytes / pathology
  • Humans
  • Ileum / metabolism
  • Ileum / pathology
  • Lewis X Antigen / metabolism
  • Lymph Nodes / blood supply
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Microscopy, Confocal / methods*
  • Middle Aged
  • Prospective Studies
  • Stomatitis, Aphthous / etiology
  • Stomatitis, Aphthous / metabolism
  • Stomatitis, Aphthous / pathology
  • Young Adult


  • Biomarkers
  • Lewis X Antigen
  • FUT4 protein, human
  • Fucosyltransferases