Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1002/ibd.20244
Original Clinical Articles: Pediatric Onset Crohn's Colitis: Original Article

Pediatric onset Crohn's colitis is characterized by genotype‐dependent age‐related susceptibility

Levine, Arie MD1*; Kugathasan, Subra MD2; Annese, Vito MD3; Biank, Vincent MD1; Leshinsky‐Silver, Esther PhD4; Davidovich, Ofir MD5; Kimmel, Gad MD, PhD5; Shamir, Ron PhD5; Orazio, Palmieri PhD3; Karban, Amir MD6; Broeckel, Ulrich MD2; Cucchiara, Salvatore MD7

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Background:: Pediatric onset Crohn's disease (CD) is associated with more colitis and less ileitis compared with adult onset CD. Differences in disease site by age may suggest a different genotype, or different host responses such as decreased ileal susceptibility or increased susceptibility of the colon.

Methods:: We evaluated 721 pediatric onset CD patients from 3 cohorts with a high allele frequency of NOD2/CARD15 mutations. Children with isolated upper intestinal disease were excluded. The remaining 678 patients were evaluated for interactions between age of onset, NOD2/CARD15, and disease location.

Results:: We found an age‐related tendency for isolated colitis. Among pediatric onset patients without NOD2/CARD15 mutations, colitis without ileal involvement was significantly more common in first‐decade onset patients (P = 4.57 × 10−5, odds ratio [OR] 2.76, 95% confidence interval [CI] 1.72–4.43). This was not true for colonic disease with ileal involvement (P = 0.35), or for isolated colitis in patients with NOD2/CARD15 mutations (P = 0.61). Analysis of 229 patients with ileal or ileocolonic disease and a NOD2/CARD15 mutation disclosed that ileocolitis was more prevalent through age 10, while isolated ileitis was more prevalent above age 10 (P = 0.016). NOD2/CARD15 mutations were not associated with age of onset.

Conclusions:: In early‐onset pediatric CD, children with NOD2/CARD15 mutations demonstrate more ileocolitis and less isolated ileitis. Young children without NOD2/CARD15 mutations have an isolated colonic disease distribution, suggesting that this phenotype is associated with genes that lead to a specific phenotype of early‐onset disease.

(Inflamm Bowel Dis 2007)

© Crohn's & Colitis Foundation of America, Inc.

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