Inflamm Bowel Dis. 2020 May 12;26(6):820-842. doi: 10.1093/ibd/izz259.

Jodie Ouahed ¹, Elizabeth Spencer ², Daniel Kotlarz ³, Dror S Shouval ⁴, Matthew Kowalik ¹, Kaiyue Peng ^1 5, Michael Field ¹, Leslie Grushkin-Lerner ¹, Sung-Yun Pai ⁶, Athos Bousvaros ¹, Judy Cho ⁷, Carmen Argmann ⁸, Eric Schadt ^8 9, Dermot P B Mcgovern ¹⁰, Michal Mokry ¹¹, Edward Nieuwenhuis ¹¹, Hans Clevers ¹², Fiona Powrie ¹³, Holm Uhlig ¹⁴, Christoph Klein ⁴, Aleixo Muise ¹⁵, Marla Dubinsky ², Scott B Snapper ¹

Author information

• ¹Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
• ²Division of Gastroenterology, Hepatology and Nutrition, Mount Sinai Hospital, New York City, NY, USA.
• ³Department of Pediatrics, Dr. Von Haunder Children's Hospital, University Hospital, Ludwig-Maximillians-University Munich, Munich, Germany.
• ⁴Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
• ⁵Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China.
• ⁶Division of Hematology-Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA USA.
• ⁷Icahn School of Medicine at Mount Sinai, Dr. Henry D. Janowitz Division of Gastroenterology, New York, NY, USA.
• ⁸Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
• ⁹Sema4, Stamford, CT, USA.
• ¹⁰F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
• ¹¹Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
• ¹²Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences, Utrecht, the Netherlands.
• ¹³University of Oxford, Kennedy Institute of Rheumatology, Oxford, UK.
• ¹⁴Translational Gastroenterology Unit, University of Oxford, Oxford, UK; Department of Pediatrics, University of Oxford, Oxford, UK.
• ¹⁵SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada. Department of Pediatrics and Biochemistry, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada.

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.