Immunology · Year 2 · from Immunology
Case 2: Wiskott-Aldrich Syndrome
Patient Demographics
- Age: 3 years old
- Sex: Male
- Ethnicity: Caucasian
Chief Complaint
Recurrent infections, bloody diarrhea, and extensive eczema
History of Present Illness
A 3-year-old boy is referred for evaluation of recurrent infections and unusual bleeding. Since infancy, he has had severe eczema unresponsive to topical treatments. He has experienced multiple ear infections, two episodes of pneumonia, and recurrent skin abscesses. His mother reports he bruises easily and has had several episodes of bloody diarrhea. Neonatal records reveal thrombocytopenia noted on day 2 of life.
Past Medical History
- Thrombocytopenia since birth
- Severe eczema since 1 month of age
- Recurrent otitis media (10+ episodes)
- Two hospitalizations for pneumonia
- Multiple skin abscesses
- Bloody diarrhea (presumed colitis)
Family History
- Maternal uncle died at age 5 from "bleeding and infection"
- Mother's brother's son (maternal cousin) also died young
Physical Examination
- General: Small, irritable child with diffuse rash
- Vital Signs: T 37.5C, HR 110, RR 24
- Growth: Weight 5th percentile, Height 10th percentile
- Skin: Diffuse eczematous dermatitis on face, trunk, and extremities; multiple petechiae and ecchymoses
- HEENT: Bilateral TM scarring
- Abdomen: Mild hepatosplenomegaly
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 8,500/uL | 6,000-17,500/uL |
| Hemoglobin | 9.5 g/dL | 10-14 g/dL |
| Platelet count | 35,000/uL | 150,000-400,000/uL |
| Mean platelet volume (MPV) | 5.5 fL | 7.5-11.5 fL |
| IgG | 450 mg/dL (low-normal) | 345-1236 mg/dL |
| IgA | 350 mg/dL (elevated) | 14-159 mg/dL |
| IgM | 25 mg/dL (low) | 43-207 mg/dL |
| IgE | 1800 IU/mL | <100 IU/mL |
| Isohemagglutinins | Absent | Present |
| CD4+ T cells | Moderately reduced | -- |
| WASP protein | Absent (by flow cytometry) | Present |
| WAS gene | Hemizygous mutation | Wild type |
Clinical Image
Image showing severe eczematous rash similar to that seen in Wiskott-Aldrich syndrome. Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Allergischer_Hautausschlag_Arm.jpg). Licensed under CC BY-SA 3.0.
Diagnosis
Wiskott-Aldrich Syndrome (WAS) due to WAS gene mutation.
Discussion
WAS is an X-linked combined immunodeficiency caused by mutations in the WAS gene, encoding WASP (Wiskott-Aldrich Syndrome Protein):
WASP function:
- Regulates actin cytoskeleton reorganization in hematopoietic cells
- Required for proper immune cell function and platelet production/function
Classic triad:
- Thrombocytopenia with SMALL platelets (pathognomonic finding)
- Eczema (severe, refractory)
- Immunodeficiency (progressive, combined)
Why are platelets small?
- Unlike ITP (large platelets), WAS platelets are small due to intrinsic defect
- Low MPV (<7 fL) is highly characteristic and helps distinguish from ITP
Immunological abnormalities:
- Low IgM, normal/low IgG, elevated IgA and IgE (characteristic pattern)
- Poor antibody responses to polysaccharide antigens
- Absent isohemagglutinins (which are anti-polysaccharide antibodies)
- Progressive T cell lymphopenia and dysfunction
Complications:
- Autoimmunity (30%): AIHA, ITP, vasculitis, inflammatory bowel disease
- Malignancy: Markedly increased lymphoma risk
- Life-threatening bleeding
- Severe infections (bacterial, viral, opportunistic)
Treatment
- HSCT: Curative and recommended for classic WAS; best outcomes with early transplant
- Gene therapy: Emerging option with promising results
- Supportive care:
- IVIG for antibody replacement
- Prophylactic antibiotics
- Aggressive eczema management
- Platelet transfusion for severe bleeding (avoid if possible due to alloimmunization)
- Splenectomy: Can improve platelet count but increases infection risk; controversial
- Avoid live vaccines and aspirin/NSAIDs