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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

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

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)

1Pediatric Gastroenterology Unit, Wolfson Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

2Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin

3Gastroenterology and Molecular Biology Laboratory, “Casa Sollievo della Sofferenza” Hospital, IRCCS, San Giovanni Rotondo, Italy

4Molecular Biology Laboratory, Wolfson Medical Center, Holon, Israel

5School of Computer Science, Tel Aviv University, Tel Aviv, Israel

6Gastroenterology Division, Rambam Medical Center, Haifa, Israel

7Pediatric Gastroenterology Unit, University of Rome La Sapienza, Rome, Italy

*Pediatric Gastroenterology Unit, Wolfson Medical Center, POB 5 Holon, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel


Received 12 February 2007; Accepted 6 July 2007

Published online 30 August 2007 in Wiley InterScience (

Grant sponsor: Tel Aviv University; Grant sponsor: Crohn's & Colitis Foundation of America (CCFA); Grant sponsor: NIH General Clinical Research Center of the Medical College of Wisconsin; Grant sponsor: Children's Hospital Research Institute; Grant sponsor: German-Israeli Fund; Grant Number: 237/2005.

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