Hyperimmunoglobulin E syndromes in pediatrics

The hyper-IgE syndromes (HIES) are primary immunodeficiencies characterized by eczema, sinopulmonary infections, and elevated serum IgE. This review discusses the clinical similarities and differences between the autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES) forms, as well as their causative genetic and pathophysiological mechanisms.

Over the past 4 years, three genetic defects have been identified in HIES. Mutations in STAT3 are associated with AD-HIES, whereas mutations in DOCK8, or rarely TYK2, are associated with AR-HIES. Recent work has confirmed that measuring T helper 17 cell numbers can help predict STAT3 mutations. In AR-HIES, loss of DOCK8 expression was found to impair T cell expansion and durable-specific antibody production by B cells. These factors probably contribute to the viral skin and other infectious susceptibilities, severe allergies, and high risk of malignancies that define this disorder.

Establishing the molecular diagnosis of HIES is important for optimal patient management. Infections in AD-HIES are usually well controlled by antibiotics. By contrast, the viral infections in AR-HIES are difficult to manage. Their higher mortality and progressive course emphasizes the need to identify AR-HIES patients early, for consideration of potentially curative hematopoietic cell transplantation.