Wiskott-Aldrich disease

The Wiskott-Aldrich syndrome (WAS) is a X-linked hematologic disorder characterized by recurrent pyogenic infection, thrombocytopenia, eczema, and immunodeficiency of variable severity. WAS is characterized by a combined immune defect.

Images

 microthrombocytopenia

• https://twitter.com/KyleBradleyMD/status/738330158218805250

Synopsis

 upper respiratory tract infections

• sinusitis
• otitis media

 lower respiratory tract infections

• pneumonia

 gastrointestinal anomalies
 diarrhea
 inflammatory bowel disease

 splenic anomalies (9989845)

• significant depletion of the splenic white pulp
• significant depletion of B cell zone
• significant decrease of marginal zone (MZ) thickness

 nephropathy
 eczema
 microthrombocytopenia
 hemorrhages

• epistaxis
• oral bleeding
• hematemesis
• melena
• petechiae
• Purpura

 meningitis
 small and large vessel vasculitis

 autoimmunity (40%) (12728121, 9514127)

• vasculitides
• autoimmune hemolytic anemia
• inflammatory bowel disease (9%) (ulcerative colitis) (12244510)
• neutropenia (25%), arthritis
• cerebral vasculitis (7%), inflammatory bowel disease
• glomerulonephritis (3%)
• hemolytic anemia
• arthritis (29%)
• leukocytoclastic vasculitis (skin vasculitis) (22%)
• Kawasaki disease (12627860)
• aortic dilatation, aneurysm formation (11808912, 10560364, 7677502)
• Henoch-Schonlein purpura with immunoglobulin A nephropathy (9016903)
• Takayasu arteritis (1356386)

 tumoral predisposition

• atypical lymphoproliferative disorder (ALPD) (16118678)
• Epstein-Barr virus (EBV) related lymphoproliferative disorders (LPDs)
  • lymphomatoid granulomatosis (angiocentric and angiodestructive form of EBV associated B cell LPD) (12835306)

• B-cell lymphoma
  • diffuse large cell lymphoma from follicular lymphoma
  • Epstein-Barr virus-associated hodgkin lymphoma

• T-cell lymphoma
  • cutaneous T cell lymphoma (3877477)

• Kaposi sarcoma

Biology

 thrombocytopenia
 small platelets size
 hemolytic anemia
  iron deficiency anemia
 CD43 (sialophorin) defectively expressed on surface of blood cells
 Moderately depressed antibody response to polysaccharide antigens
 Lymphopenia
 Abnormal delayed hypersensitivity skin test
 Absent microvilli on the surface of peripheral blood lymphocytes
 Prolonged bleeding time
 Normal IgG levels
 Increased IgA levels
 Increased IgE levels
 Reduced IgM levels
 Raised ESR
 Raised CRP

Etiology

 mutations in the WASP gene

• anomalies of ilopodia formation

Associations

 cilial immotility (11092120)

References

 Calle Y, Chou HC, Thrasher AJ, Jones GE. Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells. J Pathol. 2004 Nov;204(4):460-9. PMID: 15495215

 Burns S, Cory GO, Vainchenker W, Thrasher AJ. Mechanisms of WASp-mediated hematologic and immunologic disease. Blood. 2004 Dec 1;104(12):3454-62. PMID: 15308573

 Snapper SB, Rosen FS: The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. Annu Rev Immunol 17:905, 1999.

 Vermi W, Blanzuoli L, Kraus MD, Grigolato P, Donato F, Loffredo G, Marino CE, Alberti D, Notarangelo LD, Facchetti F. The spleen in the Wiskott-Aldrich syndrome: histopathologic abnormalities of the white pulp correlate with the clinical phenotype of the disease. Am J Surg Pathol. 1999 Feb;23(2):182-91. PMID: 9989845

 White JG. Inherited abnormalities of the platelet membrane and secretory granules. Hum Pathol. 1987 Feb;18(2):123-39. PMID: 3542800

 Snover DC, Frizzera G, Spector BD, Perry GS 3rd, Kersey JH. Wiskott-Aldrich syndrome: histopathologic findings in the lymph nodes and spleens of 15 patients. Hum Pathol. 1981 Sep;12(9):821-31. PMID: 6975749