Chapter 19 - The Many Faces of the Hyper-IgE Syndrome

Abstract

The classic form of hyper-IgE syndrome (HIES), first published as Job syndrome in 1966, describes patients with recurrent “cold” staphylococcal boils, pneumonias and elevated levels of serum IgE. Autosomal dominant (AD) inheritance and multisystem involvement was soon recognized; in addition to recurrent staphylococcal and fungal skin and lung infections, patients suffer from eczema, pneumatoceles, scoliosis, hyperflexible joints, fractures after trivial trauma and retained primary teeth. Dominant-negative mutations in STAT3 were discovered in 2007 as the genetic cause of AD-HIES. Reduced Th17 cell numbers were detected in 2008, explaining localized bacterial and fungal infections in AD-HIES. Autosomal recessive (AR) HIES was described in 2004 as a distinct entity, characterized by persistent viral infections but absence of non-immune features. In 2009, homozygous loss-of-function mutations in DOCK8 were found in the majority of AR-HIES patients. In recent years, bone marrow transplantation emerged as a curative therapy for DOCK8-deficient patients, and perhaps also for individuals with Job syndrome.