Updated: 5/15/2019

Wiskott-Aldrich Syndrome

Topic
Review Topic
0
0
Snapshot
  • A 1-year-old boy is brought to the emergency room for bloody diarrhea. He has a history of recurrent ear infections, diarrhea, and atopic dermatitis. He had an older sibling who died of a pulmonary infection at a young age. On physical exam, there is dried blood in his nares bilaterally and bleeding at intravenous puncture sites. Additionally, purpura is noted on his arms. Laboratory results show marked thrombocytopenia requiring platelet transfusions. Immunoglobulin levels show decreased IgG and IgM but increased IgE and IgA.
Introduction
  • Clinical definition
    • primary immunodeficiency disorder of B- and T-cells
    • WATER
      • Wiskott
      • Aldrich
      • Thrombocytopenic purpura
      • Eczema
      • Recurrent infections
  • Pathogenesis
    • loss of cellular and humoral response
  • Genetics
    • X-linked recessive
    • mutation in WAS gene encoding Wiskott-Aldrich Syndrome protein (WASp)
      • T-cells are unable to recognize actin cytoskeleton
      • impaired phagocytosis and chemotaxis
  • Prognosis
    • reduced life expectancy
    • bleeding is the main cause of death
Presentation
  • Symptoms/physical exam
    • ranges from isolated thrombocytopenia to classic Wiskott-Aldrich Syndrome with recurrent infections, eczema, and thrombocytopenia
    • recurrent bacterial, viral, fungal infections
      • frequency increases with age
      • bacterial agents
        • Streptococcus pneumonia, Haemophilus influenza, and Neisseria meningitides
      • viral agents
        • varicella and CMV
      • fungal infections
        • Candida albicans
    • thrombocytopenia
      • recurrent bleeding, especially in first days of life
        • petechiae
        • purpura
        • easy bruising
        • hematemesis
        • epistaxis
        • hematuria
    • chronic eczema
    • hepatosplenomegaly common
Studies
  • Diagnostic testing
    • studies
      • ↓ number of T- and B-cells
      • ↓ to normal IgG and IgM
      • ↑ IgE and IgA
      • thrombocytopenia
  • Diagnostic criteria
    • gene sequence analysis of WAS essential to confirm diagnosis
Differential
  • Severe combined immunodeficiency
    • distinguishing factor
      • similarly presents with recurrent bacterial infections
      • unlike Wiskott-Aldrich syndrome, there is no thrombocytopenia or risk of bleeding
  • Transient hypogammaglobulinemia of infancy
    • distinguishing factor
      • does not extend beyond infancy
Treatment
  • Management approach
    • mainstay of treatment is to treat infections with antibiotics and treat bleeding with platelet transfusions
    • hematopoietic cell transplant is the most effective therapy
  • First-line
    • hematopoietic stem cell transplantation
      • indications
        • all patients as early as possible
    • intravenous immunoglobulin (IVIG)
      • indications
        • all patients
    • platelet transfusions
      • indication
        • bleeding from thrombocytopenia
Complications
  • Increased risk of
    • autoimmune diseases
    • malignancies (lymphomas and leukemias), usually fatal
    • infections
  • Chronic eczema
    • superinfection
 

Please rate topic.

Average 5.0 of 1 Ratings

Thank you for rating! Please vote below and help us build the most advanced adaptive learning platform in medicine

The complexity of this topic is appropriate for?
How important is this topic for board examinations?
How important is this topic for clinical practice?
Topic COMMENTS (0)
Private Note