Hyper-IgE syndrome

Background

• Rare primary immunodeficiency

Pathophysiology

• Defect in STAT3 causes the autosomal dominant form
• Defect in DOCK8 or TYK2 causes autosomal recessive form

Clinical Manifestations

• Elevated IgE, eczema, and recurrent infections

Autosomal Dominant (STAT3)

• Infections include:
  • Non-inflammatory staphylococcal abscesses
  • Pneumonias that leave pneumatoceles
  • Chronic mucocutaneous candidiasis
• Pneumatoceles can also get infected by Pseudomonas aeruginosa, non-tuberculous mycobacteria, or Aspergillus species
• Also have coarse facial features, persistence of deciduous teeth, recurrent bone fractures, scoliosis, osteoporosis, joint hyperextensibility, and coronary artery dilatation or aneurym

Autosomal Recessive (DOCK8 or TYK2)

• Same infections as above, as well as HSV-1, HPV, molluscum contagiosum, and varicella
• Also have atopic disease, autoimmunity with hemolytic anemia or vasculitis, and increased risk for squamous cell carcinoma and lymphoma

Investigations

• Elevated IgE, eosinophilia, and antibody deficiency

Diagnosis

• Genetic testing for STAT3 (or DOCK8 or TYK2) mutations

Management

• Treat intercurrent infections
• Prophylactic antibotics
• Increased hygiene, including bleach baths