Frequent Occurrence of Perianal Disease and Granuloma Formation in Patients with Crohn's Disease and Coexistent Orofacial Granulomatosis

Abstract

Background: Orofacial granulomatosis (OFG) is an inflammatory disorder of the perioral region and oral cavity. Crohn's disease (CD) in conjunction with OFG (CD-OFG), has been suggested to constitute a phenotype of CD with distinct features at diagnosis.

Aims: The aim of this project was to investigate whether the distinct phenotypic features of CD-OFG persist in the years following the initial diagnosis of CD.

Methods: Clinical data were extracted from medical records covering the first 5 years post-diagnosis for a cohort of patients with CD-OFG, and were compared to those of references with CD without OFG.

Results: The clinical characteristics of our cohort of patients with CD-OFG (N = 25) were evaluated in comparison to references with CD without OFG (ratio 1:2). Five years post-diagnosis, more patients with CD-OFG had a phenotype with perianal disease (cumulative incidence: 16/25, 64% vs 13/50, 26%, P = 0.002) and intestinal granulomas (cumulative incidence: 22/25, 88% vs 24/50, 48%, P = 0.0009) than patients in the CD reference group. The patients with CD-OFG were also more likely to have undergone perianal surgery (12/25, 48% vs 4/50, 8%, P = 0.0002). At the end of the observation period, more of the patients with CD-OFG were receiving combination therapy, i.e., immunomodulators and tumor necrosis factor antagonists, than those in the CD reference group (9/25, 36% vs 5/50, 10%, P = 0.01).

Conclusion: The results support the notion that CD in conjunction with OFG represents a specific phenotype of CD that is characterized by frequent perianal disease, pronounced intestinal granuloma formation and a need for extensive therapy.

Keywords: Crohn’s disease; Granuloma formation; Orofacial granulomatosis; Perianal disease; Phenotype.

Fig. 1

Endoscopic disease extensions in the gastrointestinal tract according to the Paris classification, registered during the 5-year period after diagnosis of Crohn’s disease. Patients with Crohn’s disease and concomitant orofacial granulomatosis (CD-OFG, N = 25) compared with patients with Crohn’s disease only (CD-Ref, N = 50). Paris classification: L1, distal one-third of the ileum with or without limited cecal disease; L2, colonic disease; L3, ileo-colonic disease; and L4, comprising L4a (upper gastrointestinal tract disease above the ligament of Treitz) and L4b (upper gastrointestinal tract disease below the ligament of Treitz and above the distal one-third of the ileum). Due to the low number of patients showing inflammation in the small bowel below the ligament of Treitz and above the distal one-third of the ileum (L4b), we have chosen to report L4a and L4b together as L4

Fig. 2

Prevalence rates of perianal disease in patients with Crohn’s disease with or without concomitant orofacial granulomatosis. Patients with Crohn’s disease and concomitant orofacial granulomatosis (CD-OFG, N = 25; black bar) were compared with patients suffering from Crohn’s disease only (CD-Ref, N = 50; white bar) regarding the prevalence of perianal disease at the time of diagnosis, as well as the cumulative incidence of perianal disease up to 5 years after diagnosis. **P < 0.01 using Fisher’s exact test to compare the matched diagnostic groups

Fig. 3

Frequency of granulomas in intestinal biopsies of patients with Crohn’s disease with or without concomitant orofacial granulomatosis. Patients with Crohn’s disease and concomitant orofacial granulomatosis (CD-OFG, N = 25; black bar) were compared with patients suffering from Crohn’s disease only (CD-Ref, N = 50; white bar) regarding the prevalence of granuloma occurrence at the time of diagnosis, as well as the cumulative incidence of granuloma occurrence up to 5 years from diagnosis. ***P < 0.001 using Fisher’s exact test to compare the matched diagnostic groups