Introduction

• X-linked primary immunodeficiency disorder characterized by the triad of:
  • Thrombocytopenia with small platelets
  • Eczema
  • Recurrent infections
• Caused by mutations in the WAS gene (Xp11.22-p11.23)
• Incidence: 1-10 cases per million male live births
• Almost exclusively affects males (X-linked recessive)

Clinical Features

1. Hematologic Manifestations:

• Microthrombocytopenia
  • Present from birth
  • Platelet count typically < 50,000/μL
  • Mean platelet volume < 5 fL
• Bleeding manifestations:
  • Petechiae
  • Bruising
  • Bloody diarrhea
  • Risk of intracranial hemorrhage

2. Immunologic Features:

• Recurrent infections
  • Otitis media
  • Pneumonia
  • Sinusitis
  • Meningitis
  • Sepsis
• Common pathogens:
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Pneumocystis jirovecii
  • Herpes simplex virus
• Increased risk of autoimmune disorders
• Higher susceptibility to lymphomas (especially EBV-associated)

3. Dermatologic Manifestations:

• Eczema
  • Variable severity
  • Often presents in early infancy
  • May resemble atopic dermatitis

Diagnosis

Laboratory Studies:

• Complete blood count with peripheral smear
  • Thrombocytopenia
  • Small platelet size
• Immunologic studies:
  • Decreased IgM
  • Elevated IgA and IgE
  • Variable IgG levels
  • Impaired antibody responses to polysaccharide antigens
• Flow cytometry: Absent or decreased WASP protein expression
• Genetic testing: WAS gene sequencing

Differential Diagnosis:

• Immune thrombocytopenia (ITP)
• X-linked thrombocytopenia
• X-linked neutropenia
• Combined immunodeficiencies
• Atopic dermatitis

Management

Definitive Treatment:

• Hematopoietic stem cell transplantation (HSCT)
  • Best outcomes when performed before age 5
  • HLA-matched sibling donor preferred
  • Survival rates >80% with matched donors
• Gene therapy (experimental)
  • Lentiviral vector-based gene transfer
  • Promising results in clinical trials

Supportive Care:

• Platelet transfusions
  • For severe bleeding
  • Before surgical procedures
  • When platelet count < 10,000/μL
• Immunoglobulin replacement therapy
  • IVIG every 3-4 weeks
  • Target trough IgG > 700 mg/dL
• Infection prevention
  • Pneumocystis prophylaxis
  • Appropriate vaccinations
  • Prompt antibiotic therapy
• Skin care
  • Topical steroids
  • Moisturizers
  • Infection prevention

Prognosis

• Without HSCT:
  • Median survival: 20 years
  • Poor quality of life
  • High risk of life-threatening complications
• With successful HSCT:
  • Excellent long-term survival
  • Resolution of clinical manifestations
  • Normal life expectancy possible
• Monitoring required for:
  • Autoimmune complications
  • Malignancy development
  • Post-transplant complications