mercaptopurine and Ileus

Crohn's disease (CD) and ulcerative colitis (UC) are common and heterogeneous chronic inflammatory bowel disorders of childhood that account for up to 25% of all patients with inflammatory bowel disease (IBD). In CD, the familial pattern of disease concordance would suggest that genetics contribute to disease etiology. Children are more likely to have proximal small bowel disease complicated by stricture formation, fistulization and the need for surgical intervention. The predisposition for small bowel disease has been associated with mutations of the nucleotide oligomerization domain 2 (NOD2)/Caspase activation and recruitment domain 15 (CARD15) gene on chromosome 16 in 1/3 of patients with CD. Homozygous patients also show an early age at disease onset and a relatively high relative risk for isolated stricturing distal ileal disease. The potential clinical role for NOD2 testing in either the diagnosis or the therapeutic management of patients with CD has yet to be determined. The precise age of onset of CD and UC can be difficult in children. Subclinical phases of disease can be identified through a decrease in weight and height velocity, and a delay in pubertal development. However, a confident distinction between CD and UC also remains a taxonomic dilemma in 25% of pediatric patients with IBD, despite recent technological advances in diagnostic techniques, including gadolinium enhanced magnetic resonance imaging (MRI) and capsule endoscopy, and serological testing. The early introduction of immunomodulators, including azathioprine and 6-mercaptopurine have proven efficacy in maintaining long-term remission without concurrent corticosteroids. The pharmacogenomic of 6-MP metabolism has been shown to be useful in predicting susceptibility to antimetabolite induced toxicity, and possibly allowing physician's to individualize drug therapy to improve clinical response. Novel treatment strategies, including infliximab are being developed in Pediatrics with the aim at improving overall treatment efficacy and potentially avoid surgery.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites; Child; Colitis, Ulcerative; Environment; Genetic Predisposition to Disease; Humans; Ileus; Immunoglobulin A; Immunoglobulin G; Inflammatory Bowel Diseases; Intracellular Signaling Peptides and Proteins; Mass Screening; Mercaptopurine; Mesalamine; Nod2 Signaling Adaptor Protein; Risk Factors