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Lymphoid follicles (LFs) have been suggested to play a role at the early stage of Crohn's disease (CD) lesions. In the small bowel, LFs are grouped, forming Peyer's patches, which develop early in fetal life, grow in size and number until puberty, and undergo involution. In contrast, colonic LFs are isolated and undergo little change during life. As a result, if LFs play a role in the occurrence of CD lesions, the distribution of ileal and colonic lesions is expected to be altered in small children.Medical records of 2 independent French (n = 136) and Swedish (n = 55) cohorts of consecutive pediatric CD were reviewed. Disease sites and age of onset were recorded, and the age-dependent probability to develop ileal lesions was computed. The CARD15/NOD2 genotype was also analyzed when available (n = 99).The curves of disease occurrence were significantly different in case of CD with or without ileal lesions (P < 0.0001). At the age of 8 years, the probability (95% confidence interval) of small bowel involvement was 0.19 (0.07-0.39). It increased until 16 years of age to 0.61 (0.54-0.68). It was slightly higher in patients carrying 1 or more CARD15/NOD2 mutations [0.75 (0.55-0.89)] than in wild-type patients [0.46 (0.34-0.58)]. CARD15 mutations also influenced the age of onset of ileal disease (P < 0.02).In children, ileal CD lesions are delayed compared with colonic lesions. This observation is in agreement with the previously proposed hypothesis of a pathophysiological role of Peyer's patches in ileal CD. The rarity of small bowel lesions should be a warning to be cautious when classifying chronic colitis in small children.