Pediatric Inflammatory Bowel Disease (IBD): Phenotypic, Genetic and Therapeutic Differences between Early-Onset and Adult-Onset IBD

Abstract

Inflammatory bowel disease (IBD) develops during childhood or adolescence in approximately 25% of patients with IBD. Recent studies on pediatric IBD have revealed that early-onset IBD has distinct phenotype differences compared to adult onset IBD. Pediatric early-onset IBD differs in many aspects including disease type, location of the lesions, disease behavior, gender preponderance and genetically attributable risks. This review examines the currently published data on the clinical, epidemiological and genetic differences between early-onset and adult-onset IBD. And finally, therapeutic considerations in the management of pediatric-onset IBD are also discussed.

Gut Microbiota in Inflammatory Bowel Disease

“…The most abundant bacteria phyla found in the large intestine of healthy adults are gram-negative Bacteroidetes and gram positive Firmicutes [1]. The intestinal microbiota are considered to act as a "metabolic organ", by deriving energy from nutrients that escape digestion in the upper gut.…”

Biological Therapy for Inflammatory Bowel Disease in Children

“…In the ACT1 and ACT2 studies, for patients with moderate or severe disease unresponsive to corticosteroids and immunomodulators, infliximab showed effects in mucosal healing and remission at 8 and 30 weeks [11], and a recent follow-up study reported a lower risk of bowel resection at 54 weeks [12]. Although research is limited in children and it may not be as effective as it is in Crohn's disease, infliximab is valued as a medication that can be used in patients with severe ulcerative colitis refractory to conventional treatment [1], and is reported to decrease the frequency of bowel resection [13]. In summary, the indications for treatment with infliximab are as follows: refractory Crohn's disease, corticosteroid dependent Crohn's disease, fistulizing Crohn's disease, severe ulcerative colitis, and inflammatory bowel disease with extraintestinal systemic symptom.…”

“…Approximately 10 to 15% of patients diagnosed with inflammatory bowel disease, 25% of Crohn's disease, are diagnosed in childhood [1]. Although the pathogenesis of inflammatory bowel diseases is not very well understood, it is currently thought to be caused by the interaction between genetic factors, environmental factors, immune factors, and intestinal microbes.…”

“…Immunomodulators, such as azathioprine and 6-mercaptopurine, are standard in maintenance therapy for they are effective in maintaining remission in Crohn's disease and show reduction in corticosteroid use. In children with moderate to severe ulcerative colitis, azathioprine is effective for maintenance therapy [1]. However, immunomodulators are inappropriate for induction purposes because of their slow onset of action and are ineffective even with 12 to 16 weeks of treatment [4].…”

Higher Morbidity of Monogenic Inflammatory Bowel Disease Compared to the Adolescent Onset Inflammatory Bowel Disease

“…Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation [ 1 ]. IBD that develops in a child under 6 years of age is called very early onset-IBD (VEO-IBD) [ 2 3 ]. Because VEO-IBD starts earlier in life and has more resistance to immunosuppressive treatment, it is thought to have a strong association with genetic backgrounds.…”