Disease behavior in children with Crohn's disease: the effect of disease duration, ethnicity, genotype, and phenotype.
BACKGROUND
Disease behavior in Crohn's disease (CD) may be modified by disease location and genotype. Disease behavior may change over time, and thus analysis requires follow-up. To date, there have been few pediatric studies that have evaluated the association between disease behavior and genotype with prolonged follow-up. The aim of our study was to evaluate the effect of genotype, phenotype, and ethnicity on disease behavior in pediatric CD.


METHODS
Evaluation of 128 pediatric CD was followed by analysis of 232 pediatric and adult-onset CD patients. Inclusion required at least 2 years of follow-up. Phenotype, ethnicity, and disease duration were recorded. Patients were genotyped for polymorphisms in the NOD2/CARD15 gene.


RESULTS
Colonic involvement was more frequent in younger patients. Pediatric disease at end of follow-up was classified as inflammatory (78%), penetrating (7%), and stricturing (17%). Duration of follow-up (mean 4.9 pediatric and 6.4 years mixed) was associated with more stricturing and penetrating disease. There was no association between mean age of onset and NOD2/CARD15, or either of these with disease behavior. These observations were replicated in the mixed cohort. Sephardic Jewish origin was inversely correlated with inflammatory behavior (P = 0.006), independent of NOD2/CARD15 genotype.


CONCLUSIONS
Duration of disease and ethnicity, irrespective of NOD2/CARD15 genotype and age of onset, were the only predictors for penetrating or stricturing disease.
Shaoul
Ron
R
Pediatric Day Care Unit, Department of Pediatrics, Bnai Zion Medical Center, 47 Golomb St., POB 4940, Haifa, 31048, Israel. shaoul_r@012.net.il
Karban
Amir
A
Reif
Shimon
S
Weiss
Batia
B
Shamir
Raanan
R
Tamir
Ada
A
Davidovich
Ofir
O
Halevi
Jonathan
J
Silver
Esther Leshinsky
EL
Levine
Arie
A
D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D003251:Constriction, Pathologic / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007082:Ileum / Q000503:physiopathology; D007249:Inflammation / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D007557:Israel; D008297:Male; D009154:Mutation / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D013997:Time Factors
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein