Very early-onset inflammatory bowel disease: an integrated approach

Abstract

Purpose of review: Immune dysregulation disorders are among the most rapidly growing set of inborn errors of immunity. One particular subset is the category where early-onset inflammatory bowel disease (IBD) is the most common manifestation. These disorders are being increasingly appreciated although there has been minimal effort to articulate a unified approach to their diagnosis and management. This review will cover current thinking and strategies related to diagnosis and management of very early-onset IBD.

Recent findings: There is an expanding set of monogenic causes of early-onset IBD. In many cases, the precise genetic cause dictates management. Lessons learned from the management of these monogenic conditions can sometimes be extrapolated to other refractory cases of IBD.

Summary: An integrated approach to diagnosis, risk analysis, and management can include diagnostic approaches not often utilized for traditional IBD such as whole exome sequencing. Management can also include nontraditional approaches such as targeted biologics or hematopoietic cell transplantation.

Figure 1.. The genetic basis of VEO IBD.

A schematic diagram illustrating the contributions to the development of IBD. Environmental effects are most pronounced in polygenic disease where the effect size of any individual gene is low and collectively, the genetic contribution to disease is less than what is seen for single gene causality. Environment and microbiome are nearly always a contribution, in the monogenic cases of VEO IBD, their relative contribution is less than what is seen in polygenic disease. Age of onset somewhat tracks with single gene causality but increasingly adults are being recognized with significant inborn errors of immunity causing IBD.