Hyperimmunoglobulin E syndromes in pediatrics.

Objective: 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.

Results: 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.

Conclusions: 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.