Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study.

INTRODUCTION: Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. METHODS: All patientswith a diagnosis ofCDbefore the age of17years between1988and2011within the populationbased registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Coxmodel was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. RESULTS: Amongthe1,005 includedpatients (females, 450[44.8%]; medianage at diagnosis 14.4years [interquartile range 12.0-16.1]), 257(25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4%(95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P 5 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P5 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P5 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. DISCUSSION: Anal ulceration is frequent in pediatric-onsetCD, with nearly half of patients presenting with at least1episode after 10 years of evolution. Fistulizing pCDis twice as frequent in patients with present or past anal ulceration.