Recent Advance in Very Early Onset Inflammatory Bowel Disease

Abstract

Recent studies on pediatric inflammatory bowel disease (IBD) have revealed that early-onset IBD has distinct phenotypic differences compared with adult-onset IBD. In particular, very early-onset IBD (VEO-IBD) differs in many aspects, including the disease type, location of the lesions, disease behavior, and genetically attributable risks. Several genetic defects that disturb intestinal epithelial barrier function or affect immune function have been noted in these patients from the young age groups. In incidence of pediatric IBD in Korea has been increasing since the early 2000s. Neonatal or infantile-onset IBD develops in less than 1% of pediatric patients. Children with “neonatal IBD” or “infantile-onset IBD” have higher rates of affected first-degree relatives, severe disease course, and a high rate of resistance to immunosuppressive treatment. The suspicion of a monogenic cause of VEO-IBD was first confirmed by the discovery of mutations in the genes encoding the interleukin 10 (IL-10) receptors that cause impaired IL-10 signaling. Patients with such mutations typically presented with perianal fistulae, shows a poor response to medical management, and require early surgical interventions in the first year of life. To date, 60 monogenic defects have been identified in children with IBD-like phenotypes. The majority of monogenic defects presents before 6 years of age, and many present before 1 year of age. Next generation sequencing could become an important diagnostic tool in children with suspected genetic defects especially in children with VEO-IBD with severe disease phenotypes. VEO-IBD is a phenotypically and genetically distinct disease entity from adult-onset or older pediatric IBD.

Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn’s disease

“…HLH is a life-threatening condition characterized by hyperinflammation, in which activated T lymphocytes and macrophages accumulate in organs, and produce and induce massive production of proinflammatory cytokines, particularly IFNγ 14 , resulting in tissue damage and multiorgan failure that typically affects the liver and bone marrow 15 . IBD in XIAP-deficient patients usually presents with very early onset 16 ; however, adult onset has also been described 17 , and is characterized by a complicated course, necessity of extensive surgical procedures and unresponsiveness to standard treatment, including biological treatment. These patients have also significantly increased mortality rate, dying within a few years upon manifestation or diagnosis of IBD 18 .…”

Ustekinumab therapy and serum IL-12/IL-23p40 levels for biologic naïve pediatric-onset Crohn disease

“…It is difficult to compare the effects of ustekinumab with those of other biologics because of no direct head-to-head trials [11]. In pediatric cases, the response rates to biologics might be lower than adult ones if monogenic IBD was incorporated into the study population [14]. The major concern is a risk of prolonged biologics therapy for children.…”

Very Early-Onset Inflammatory Bowel Disease: A Challenging Field for Pediatric Gastroenterologists

“…Monogenic or Mendelian disorder-associated IBD (MD-IBD) is a term used to represent IBD caused by genetic mutations [ 11 13 ]. After the first report of IBD caused by the mutations of IL10RA and IL10RB by Glockers et al [ 14 ] in 2009, approximately 60 monogenic IBDs have been reported to date [ 15 16 ]. Evaluating and managing children with VEO-IBD are a challenging field for pediatric gastroenterologists worldwide.…”