Management of Autosomal Dominant Hyper-IgE Syndrome (AD-HIES)

Introduction to AD-HIES

• The American Academy of Allergy, Asthma, and Immunology recommends that the management of autosomal dominant Hyper-IgE syndrome should focus primarily on aggressive prevention and treatment of infections, with prophylactic antibiotics and antifungals as the cornerstone of therapy, while addressing specific complications like skeletal abnormalities and considering HSCT in selected cases 1, 2

Pathophysiology and Clinical Features

• AD-HIES is primarily caused by heterozygous mutations in STAT3, characterized by elevated IgE levels, recurrent skin and pulmonary infections, and distinctive connective tissue and skeletal abnormalities 3, 4
• Both forms of HIES (autosomal dominant and recessive) are associated with defective development and function of IL-17–producing TH17 cells, which play a critical role in protection against Candida species 5, 6

Infection Management

• The main cause of mortality in AD-HIES is severe infections, with patients experiencing progressive decrease of lung function due to recurrent pneumonias 1, 2
• Aggressive therapeutic and prophylactic antibiotic therapy is indicated as the first-line approach to prevent life-threatening complications 1, 4
• Antifungal prophylaxis should be considered, particularly for patients with recurrent Candida infections 1, 2

Skeletal and Dental Management

• Patients require close monitoring for scoliosis development and fracture risk, as they can experience bone fractures with relatively minor trauma 3, 2

Immunoglobulin Replacement Therapy

• IVIG supplementation should be considered when impaired specific antibody responses are demonstrated, though evidence regarding efficacy is mixed 1, 2

Hematopoietic Stem Cell Transplantation (HSCT)

• HSCT should be considered as a potentially curative option for AD-HIES 1, 2
• The timing of HSCT is critical and should be considered before the development of significant irreversible complications, particularly lung damage 2

Special Considerations

• Intermediate or variant phenotypes of AD-HIES have been described in patients with somatic mosaicism for STAT3 mutations, which may affect treatment decisions 3
• The management approach differs significantly from autosomal recessive HIES (caused by DOCK8 mutations), which requires more focus on viral infections and has different skeletal manifestations 5