Clinical significance of granulomas in Crohn's disease: A systematic review and meta-analysis

Background and aim: Epithelioid granuloma is one hallmark used to histologically diagnose Crohn's disease (CD). However, the clinical significance of granulomas in CD is unclear. Therefore, we performed a meta-analysis to compare the clinical features with CD according to the presence of granulomas.

Methods: A literature search in PubMed, EMBASE, and Cochrane databases was performed on manuscripts published until October 2018. We included studies that met the following inclusion criteria: (i) patient: patients with CD; (ii) exposure: granulomas on the pathology; (iii) comparator: no granulomas; and (iv) outcomes: disease location, disease behavior, perianal disease, disease activity, use of biologics, and CD-associated hospitalization, surgery.

Results: Nineteen studies met our inclusion criteria. Granulomas in CD patients were associated with a higher proportion of ileocolonic disease (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.21-1.83), a higher proportion of upper gastrointestinal disease (OR: 2.25, 95% CI: 1.28-3.95), a higher proportion of penetrating behavior (OR: 1.48, 95% CI: 1.09-2.01), a higher prevalence of perianal disease (OR: 2.15, 95% CI: 1.48-3.11), and a higher severity index at presentation (standardized mean difference: 0.20, 95% CI: 0.09-0.32). In addition, the use of biologics was significantly higher in CD patients with granulomas compared with without granulomas (OR: 1.66, 95% CI: 1.07-2.59). The presence of granulomas was significantly associated with CD-associated hospitalization (OR: 3.88, 95% CI: 1.44-10.49), but not with CD-associated surgery.

Conclusions: Clinical features in CD patients were significantly different according to the presence of granulomas. It may indicate a more aggressive phenotype of CD.