WiskottAldrich Syndrome: Not a textbook case

1
Wiskott-Aldrich Syndrome Not a textbook case

• Leigh Ann Kerns, M.D.
• Division of Allergy and Immunology
• Childrens Memorial Hospital
• Northwestern University

2
Clinical Presentation

• 5 month old Filipino boy presented with
  fussiness, fever, and right leg swelling and pain
• Past medical history
• Full term, NSVD, birth weight 7 pounds 11 ounces
• Received phototherapy for five days after birth
  due to hyperbilirubinemia
• Uncomplicated circumcision
• Mild eczema, worse with cow milk formula
• No history of prior infection

3
Family History

• Maternal grandmother had two miscarriages
• All four maternal uncles had jaundice and
  reportedly died of blood incompatibility within
  six months of life
• Two male first cousins on the maternal side had
  jaundice and skin asthma and died within the
  first year of life

Patient
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Initial Physical Exam and Labs

• Febrile
• Aphthous ulcer on palate
• Swelling and erythema of right leg
• Mild eczematous patches and hypopigmentation on
  face
• CBC with 37,000 platelets
• Peripheral blood smear with small platelets

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Laboratory Analysis

• WBC 15.8
• 58 Neutrophils
• 28 Lymphocytes
• Hg 11.7
• Platelets 37,000
• ESR 42, CRP 47.9
• Normal PT and PTT
• Normal fibrinogen
• D-dimer 0.5-1 (
• Immunoglobulins
• IgG 1360 (165-781)
• IgE 992 (
• IgA 37.6
• IgM 77.9

• Normal lymphocyte proliferation in response to
  mitogens and Candida
• Protective antibody titers to HiB, tetanus, and
  pneumococcus

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Hospital Course

• Received a 10 day course of clindamycin for
  presumed cellulitis
• Developed transient and migratory edema
• Erythema and edema developed over 24 hours in
  each new location and resolved within 48 hours
• Involved bilateral ears, upper and lower
  extremities
• Often associated with overlying purpuric lesions
• Biopsy of purpuric lesion revealed findings
  consistent with neutrophilic dermatosis
• ANA 1320 speckled

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Further Evaluation

• Bone marrow aspirate and biopsy
• Abundant megakaryocytes with some dysplastic
  features and abundant eosinophils suggestive of
  dysplastic syndrome or extramedullary destruction
• Imaging
• CT of chest/abdomen/pelvis showed enlarged
  anterior mediastinal lymph nodes, bilateral
  axillary, bilateral inguinal, and retroperitoneal
  nodes
• Lymph node biopsy
• Atypical interfollicular proliferation and mild
  follicular hyperplasia consistent with a reactive
  process
• Mixture of T lymphocytes and CD20 PAX5 B
  lymphocytes in interfollicular areas, EBV
  negative

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Complications

• Developed consumptive coagulopathy
• Prolonged PT, low fibrinogen, and elevated
  D-dimer
• Required frequent infusions of FFP and
  cryoprecipitate
• Ultrasound studies with Doppler were negative for
  thrombosis
• Developed new aphthous ulcers and grossly bloody
  stool
• Endoscopy revealed antral nodules
• Colonoscopy showed multiple ulcers throughout
  colon
• Biopsies showed no specific histopathologic
  changes
• CMV negative, EBV negative
• No evidence of malignancy or inflammatory bowel
  disease

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Confirmatory laboratory analysis

• Flow cytometry
• Performed by the University of Washington
• Showed absence of Wiskott-Aldrich protein
• Confirmatory genetic analysis
• Performed by the Childrens Hospital Medical
  Center in Cincinnati
• Revealed a previously unreported frameshift
  mutation in Wiskott-Aldrich sequence
• WAS finding 139_145 del 7 (A47fsX73)

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Management

• IVIG infusions 400 mg/kg every 3 weeks
• Transient and migratory edema resolved shortly
  after initiation of IVIG therapy
• PCP prophylaxis with pentamidine
• Cryoprecipitate infusions as needed for
  persistent consumptive coagulopathy
• Referred for stem cell transplant
• Received reduced intensity conditioning regimen
• Received stem cell transplant from a matched
  unrelated donor on 9/18/07
• Doing well after stem cell transplant