Wiscott-Aldritch, Acrodermatitis enteropathica, ataxia telangiectasia, atopic dermatitis, Langerhans cell histiocytosis (LCH)

Wiscott-Aldritch

• Problem: results from mutations in WASP (intracellular signaling molecule involved in T cell receptor signaling)
• X-linked recessive disorder (X chrom p11.22-23)
• triad
  • recurrent infections
    • defects in humoral and cell-mediated immunity, esp IgM deficiency
    • causing recurrent sinopulmonary infections (PNA, OM) with encapsulated organisms (S. pneumoniae, H. influenzae), in the first year of life
    • opportunistic infections with P. jiroveci, recurrent HSV (later)
    • sepsis or meningitis due to encapsulated orgs, or opportunistic orgs.
  • bleeding (due to thrombocytopenia)
    • platelet counts in the range of 15 to 30 x 10^3/ mm3
    • small platelets (think of Scott, a small asian, vs a big St. bernard (bernard soulier - large platelets)
    • prolonged bleeding from circumcision site, or bloody diarrhea during infancy (usual presenting symptoms)
    • at times, may be life-threatening (eg, intracranial hemorrhage).
  • eczema - often seen before 6 mos of age; cutaneous findings are typical of atopic dermatitis, although petechiae may be observed.
• Long term px (death by 6-11 years)
  • Infections common cause of death
  • Hemorrhage is a common cause of death
  • Autoimmune cytopenias
  • Vasculitis
  • Increased risk of lymphoma and leukemia
  • #1 cause of death= EBV-induced lymphoma
• Labs: Decreased T cell numbers (CD3+, CD4+, CD8+) and function; low IgM
• Prenatal Dx: chorionicvillous sampling, amniocentesis
• Treatment: IVIG, BMT

Discussion:

• also see Acrodermatitis enteropathica

Ataxia Telangiectasia

Patients who have Ataxia telangiectasia (an autosomal recessive disorder) may be distinguished from those who have WAS by the presence of severe cerebellar ataxia and telangiectasias involving the conjunctivae and skin. Other cutaneous manifestations include vitiligo, café au lait spots, and premature graying of the hair.

Although the lesions of atopic dermatitis are analogous to those seen in WAS, patients who have the latter disorder often exhibit petechiae and the associated abnormalities discussed previously.

Langerhans cell histiocytosis (LCH, see Histiocytosis) is the term applied to a group of disorders characterized by the accumulation of histiocytes in the skin or other organs. Unlike the lesions of WAS, those of LCH are erythematous, orange or yellow-brown papules or nodules. Individual lesions may exhibit scale or petechiae or may become purpuric. Affected individuals may present with skin disease alone or systemic complications (eg, bone pain or swelling, diabetes insipidus).

References:
Hong R. Combined immunodeficiency diseases. In: McMillan JA,
DeAngelis CD, Feigin RD, Warshaw JB, eds. Oski’s Pediatrics:
Principles and Practice. 3rd ed. Philadelphia, Pa: Lippincott
Williams & Wilkins; 1999:2092-2099
Weston WL, Lane AT, Morelli JG. Color Textbook of Pediatric
Dermatology. 2nd ed. St Louis, Mo: Mosby, Inc; 1996:200-202, 313-314