Inflammatory bowel disease and primary immunodeficiency disorders: Clinical presentations and diagnostic work-up
© 2017, Springer Medizin Verlag GmbH. Background: Inflammatory bowel disease (IBD) is a polygenic disorder with two major subtypes Crohn’s disease and ulcerative colitis. Genetic defects that cause primary immunodeficiencies (PID) or intestinal epithelial defects are increasingly recognized as monogenic causes of IBD or IBD-like intestinal inflammation. Objective: This article provides an overview about monogenic IBD, clinical presentations of patients and a diagnostic algorithm for suspected PID-associated IBD (PID-IBD). Material and methods: Review of the literature regarding functional immunological tests and genetic diagnostics of monogenic IBD. Results: More than 60 genes are associated with monogenic IBD presenting with a heterogeneous spectrum of clinical presentations. Monogenic IBD is a rare disease. These disorders are enriched in patients with early onset IBD occurring before the age of six years. Validated functional diagnostic tests are available for many PID disorders, e. g. chronic granulomatous disease, defects in interleukin(IL)-10 signalling, XIAP deficiency, defects in regulatory T cells and disorders of the common variable immunodeficiency (CVID) and severe combined immunodeficiency (SCID) spectrum. Application of parallel sequencing by gene panel sequencing, exome or genome sequencing increases the diagnostic yield. Successful identification of a Mendelian type gene defect in IBD offers personalized therapies (e.g. curative stem cell transplantation or pathway-specific biologicals), allows family counseling and screening for infectious complications or malignancies, and helps to avoid unnecessary surgery including colectomy. Conclusion: A rational diagnostic algorithm helps to diagnose monogenic IBD and offers individualized therapeutic strategies.