Real lymphonodular hyperplasia is not associated with NOD2/CARD15 mutations

Introduction: Lymphonodular hyperplasia (LNH) is a mass of lymphoid tissue that has been described in the terminal ileum, colon and duodenum mainly in children. Controversy exists regarding the benign nature of LNH. The combination of chronic abdominal pain and hematochezia leads many of these patients to undergo investigations for inflammatory bowel diseases. NOD2/CARD15 on chromosome 16 has been identified as a susceptibility gene for Crohn disease (CD). No study has yet examined the possible association of NOD2/CARD15 mutations with patients with LNH. The purpose of this study was to investigate the presence of NOD2/CARD15 mutations in patients with clinically proven LNH. Methods: Children and young adults with gastrointestinal symptoms diagnosed as having terminal ileum LNH were eligible for the study. Results: The study group consisted of 32 patients (15 males and 17 females), age range 3-23 years, mean 13.1 +/- 5 years. Twentyseven (84%) had abdominal pain, 3 (9%) had rectal bleeding. The duration of symptoms ranged from 1-60 months (17.9 +/- 14.5). Only 2 patients (6.2%) were found to be heterozygote for the NOD2/CARD15 mutation (1007 fs), whereas all of the others did not carry any of the 3 common mutant alleles. This number is significantly lower (P < 0.001) than the mutation prevalence demonstrated in both pediatric and adult Israeli CD patients. Conclusions: NOD2/CARD15 mutations are not associated with LNH. This may strengthen the lack of association between CD and LNH that has been previously reported. We suggest that genotyping NOD2/CARD15 may help to distinguish LNH from inflammatory bowel diseases in selected patients.