Objective: To identify and describe endoscopic and histological features of children with non-monogenic very early-onset inflammatory bowel diseases (VEO-IBD) compared to endoscopic and histological features of children with later-onset (LO-IBD).

Methods: A multicenter retrospective observational study in two Italian Pediatric IBD referral centers was done. Patients with VEO-IBD were matched with LO-IBD controls with a similar disease phenotype, with a 1:1 ratio for ulcerative colitis (UC) and 1:2 for Crohn's disease (CD). Clinical, endoscopic, and histological data were retrospectively collected.

Results: Fifty-three children with VEO-IBD, 42 UC, 11 CD, and 68 with LO-IBD (44 UC and 24 CD) were identified. Patients with VEO-CD had more frequently isolated colonic disease compared to those with LO-CD (p = 0.002), whereas patients with VEO-UC had more frequent pancolonic involvement (p = 0.05). As regards histologic findings, basal plasmacytosis intermingled with eosinophils, goblet cells depletion, active inflammation, and crypt architectural distortion were significantly more frequent in patients with LO-UC compared to VEO-UC (83.7% vs. 61.9%, p = 0.021, 100.0% vs. 73.8%, p < 0.001, 86.4% vs. 66.7%, p = 0.028), while in CD, skip lesions were more frequent in LO-CD than in VEO-CD (83.3% vs. 45.5%, p = 0.031).

Conclusions: VEO-IBD and LO-IBD exhibit different phenotypes with regard to disease localization and histological features. Younger children with UC exhibit a lower histological burden than those with LO-UC, whereas typical characteristics of CD are rarely observed in VEO-CD.