Childhood-onset IBD seems to be a more aggressive and rapidly progressive disease compared to adult-onset IBD [6,7]. CD is more prevalent than UC in children. The ratio of boys to girls is as high as 1.8:1. The most common type of disease distribution is pan-enteric or pan-colic. These cases were more often treated with systemic steroids and azathioprine and had a higher frequency of steroid dependence. The patients showed a more severe disease course compared to that in adults with IBD. These patients were more likely to have upper GI involvement, extraintestinal manifestations, and stricturing and penetrating disease. Among pediatric IBD patients, 44% required surgery at some point, with a 34% risk within the first 5 years after diagnosis [7-10]. In CD, no differences were found when comparing corticosteroid responsiveness between pediatric and adult patients; however, the inflammatory phenotype is more common than the stricturing or penetrating phenotype in childhood [11,12].

Among patients with IBD onset at a young age, 29% have 1 or more family members with IBD. The subgroup of children younger than 3 years of age with UC had the highest prevalence of first-degree relatives with IBD (44%) [13]. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype [14]. Monogenic defects, especially those affecting the interleukin-10 (IL-10) signaling pathway, result in severe or intractable disease [15]. Patients with IL-10 pathway defects often show initial presentation before 1 year of age. Intractable perianal fistula is a cardinal manifestation and diarrhea with bloody stools is also common with this defect [16,17]. There is no specific treatment for IL-10 pathway defects, except for hematopoietic stem cell transplantation [18,19].

Very-early-onset IBD (VEOIBD) is usually defined when IBD occurs in children less than 6 years of age. A child less than 2 years of age can be classified as having infantile IBD [20]. However, in the Paris classification, which is a modified pediatric version of the Montreal classification and is frequently cited in textbooks, pediatric onset IBD is only classified as A1a and A1b, which occur at less than 10 years of age or between age 10 and 17 years, respectively (Table 1) [21]. Recent advances in translational research and next generation sequencing or whole exome sequencing have made it possible to change the diagnosis and treatment in VEOIBD. A gene panel or gene chip showed promising results in the diagnosis of VEOIBD [14]. The clinical course of monogenic IBD, which is a subgroup of VEOIBD, is more severe than adolescent onset disease. The initial Pediatric Crohn’s Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) scores, the annual incidence of surgery, and the number of hospitalization per year were higher in the monogenic IBD group than that in other IBD groups [22]. There is no specific treatment for VEOIBD; however, a few reports showed that hematopoietic stem cell transplantation showed effectiveness in IL-10 receptor deficiency and XIAP mutations. VEOIBD could be useful in identifying the pathophysiology of IBD, because pediatric cases have a relatively stronger genetic background and less exposure to environmental and behavioral influences than adults [23,24]. As recent advances in VEOIBD make this category important in pediatric IBD, the Paris classification alone is unable to categorize all patient groups.

The traditional treatment strategy based on clinical symptom improvement does not improve long-term outcomes in CD and patients cannot avoid bowel damage. Therefore, the “treat to target” concept was introduced to incorporate use of biological markers and mucosal healing into IBD treatment [25]. This new method was adopted from the experience with rheumatic diseases, and can be tentatively regarded as an active approach to the severe disease group [26]. However, there are insufficient data with regard to optimal indications, biomarkers, and treatment strategies, especially in children. Early introduction of biologics in patients with poor prognostic factors, such as deep colonic ulcerations, extensive disease, marked growth retardation, severe osteoporosis, B2 and/or B3 behavior, and severe perianal disease, can be recommended to reduce bowel damage [27].

Endoscopic evaluation is the gold standard for diagnosis of CD in children. However, esophagogastroduodenoscopy and colonoscopy are more difficult and dangerous in children. To overcome the gap between the need to frequently evaluate disease severity and the difficulty of performing endoscopy in children, the PCDAI and PUCAI have been developed [28,29]. The PCDAI includes growth in children as an important parameter. These scoring systems are often used to determine treatment parameters in many clinical settings and investigational trials, as well as for insurance reimbursement (Tables 2 and 3).