Very Early Onset Inflammatory Bowel Disease: A Clinical Approach With a Focus on the Role of Genetics and Underlying Immune Deficiencies

Abstract

Very early onset inflammatory bowel disease (VEO-IBD) is defined as IBD presenting before 6 years of age. When compared with IBD diagnosed in older children, VEO-IBD has some distinct characteristics such as a higher likelihood of an underlying monogenic etiology or primary immune deficiency. In addition, patients with VEO-IBD have a higher incidence of inflammatory bowel disease unclassified (IBD-U) as compared with older-onset IBD. In some populations, VEO-IBD represents the age group with the fastest growing incidence of IBD. There are contradicting reports on whether VEO-IBD is more resistant to conventional medical interventions. There is a strong need for ongoing research in the field of VEO-IBD to provide optimized management of these complex patients. Here, we provide an approach to diagnosis and management of patients with VEO-IBD. These recommendations are based on expert opinion from members of the VEO-IBD Consortium (www.VEOIBD.org). We highlight the importance of monogenic etiologies, underlying immune deficiencies, and provide a comprehensive description of monogenic etiologies identified to date that are responsible for VEO-IBD.

Risk of Prevalent Asthma among Children Affected by Inflammatory Bowel Disease: A Population-Based Birth Cohort Study

“…It has been hypothesized, in fact, that VEO-IBD may represent a phenotypically different type of IBD, as opposed to later onset IBD [8]. Children with VEO-IBD have been receiving increasing attention by the scientific community for specific genetic characteristics and different health trajectories that characterize the clinical progression of this disease [8,9,46].…”

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

“…To date, approximately 60 causative genes for MD-IBD have been identified, generally classified as follows: 1) epithelial barrier function defects; 2) immune dysregulation; 3) T-cell, B-cell, and complex function defects; 4) phagocyte and NADPH oxidase complex defects; 5) hyperinflammatory and autoinflammatory defects; and 6) others. The representative disorders and genes are summarized in Table 1 [ 15 16 22 23 24 ].…”

“…After Uhlig et al [ 11 ] introduced the first comprehensive approach for differentiating MD-IBD from VEO-IBD, several reviews and position papers have been published [ 15 16 25 ]. Although the diagnostic algorithms are practical and useful in some areas or countries, owing to the different levels of available resources, not all countries or hospitals could apply them.…”

“…However, prolonged EEN could interfere with the proper development of chewing and swallowing, and could lead to an increased risk of developing eating disorders. In this particular age group, the amino acid-based elemental formula is generally used as the first-line treatment for VEO-IBD [ 16 ]. It is safe, and physicians could retain the time to differentiate PID, which could expose the child to the risk of severe infection from the use of immunosuppressive medications.…”

“…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.…”