A Case of Diffuse Warts

1
A Case of Diffuse Warts

• Patricia Hutchinson, MD
• Madigan Army Medical Center
• CIS Primary Immunodeficiency School
• September 13, 2008

The views expressed in this presentation are
those of the author and do not reflect the
official policy of the Department of the Army,
Department of Defense, or U.S. Government.
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Initial Presentation

• 16 y/o boy with diffuse flat warts and molluscum
• Infectious history
• Uncomplicated varicella age 5 or 6 years old
• Single episode of herpes labialis as teenager
• Otitis media age 15
• Past medical history
• Premature birth
• Mild intermittent asthma
• Short stature
• Medications
• Tretinoin, Multivitamin
• Family history
• Unremarkable
• Biological father unknown

3
Physical Exam

• Small for age
• Diffuse flat warts on head, neck, upper
  extremities
• Multiple umbilicated papules consistent with
  molluscum, in similar location
• Borderline to enlarged lymph nodes confined to
  upper body
• Question of decreased breath sounds left lung
  base
• No hepatosplenomegaly

4
Laboratory Evaluation

• WBC 5.9 with 23 lymphs, 16 monos
• HGB 11.6 g/dL, HCT 33.7 g/dL
• Phosphorous 6.2 mg/dL
• Total protein 9.5 g/dL
• Creatinine 0.74 mg/dL
• Urine Protein 10 mg/dL
• ESR 27 (subsequently normal)
• Normal CRP, DAT, LDH, ACE
• Negative HIV-1 (PCR), HIV-2, HTLV-1, HTLV-2,
  hepatitis B and C
• Elevated EBV titer (IgG)
• Negative PPD in setting of non-reactive anergy
  panel with tetanus/candida

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Laboratory Evaluation Cont.

• SPEP Faint IgG-? band
• UPEP Negative
• Serum Free Light Chains (?/?) 3.18 (0.26-1.65)
• IgG 4072.8 mg/dL (716-1711)
• IgA 243.8 mg/dL (47-249)
• IgM 135.9 mg/dL (15-188)
• CD4 cells 256 cells/µL (400-2100)
• NK cells 26 cell/µL (adult normal 90-590)
• Normal CD8 and B cell counts
• No aberrant B or T cell population by flow
  cytometry

6
Lymphocyte Function

• Lymphocyte Stimulation Testing
• PHA 121,224 CPM (NL gt 93,000)
• Con A 72,884 CPM (NL gt 76,000)
• Pokeweed 57,603 CPM (NL gt 85,000)
• NK Cell Cytotoxicity Assay
• 0.01 LU20/107 (35.5-153.7)
• Positive tetanus antibody
• Negative hepatitis A antibody 5 months after
  vaccination
• Anergy panel non-reactive to tetanus and candida

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Imaging

• Chest X-ray
• Negative
• Chest/Neck CT
• Conglomerates of lymph nodes
• Right axillary 2.5 x 0.9 cm
• Left submandibular 2.4 x 0.9 cm
• Right submandibular 1.6 x 1.0 cm
• Evidence of retropharyngeal lymphoid hyperplasia

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Lymph Node Biopsy

• Paracortical zone hyperplasia with plasma cell
  proliferation consistent with Castlemans disease
• Focal and localized germinal center hyperplasia
  and increased epithelioid histiocytes, suggestive
  of an infectious process, especially
  toxoplasmosis
• Stains negative for microorganisms, including CMV
• Paracortical zone Negative staining for CD3,
  CD5, CD20. CD43 and BCL-2 reactivity.
• Germinal Center CD20, CD10, and BCL-6
  reactivity
• CD30 and CD15 focally reactive
• No light chain restriction on ? and ? stains
• Cultures negative, including fungal and AFB

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Bone Marrow Biopsy

• Slightly hypercellular marrow (75)
• Trilineal hematopoiesis
• Dysmegakaryopoiesis
• Dyserythropoiesis
• Chromosomal analysis showed 1/22 cells with
  possible deletion of chromosome 9 (p22)

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• Differential Diagnosis
• Chronic Infection (toxo, EBV, TB, CMV, others)
• Lymphoproliferative Disorders (Castlemans
  Disease, ALPS, Lymphoma, Heavy Chain Disease,
  Solitary Plasmacytoma, POEMS Syndrome)
• Immunodeficiency (CD4 Lymphopenia, NK
  Deficiency, WHIM, Ectodermal dysplasia-associated
  immunodeficiencies)
• Miscellaneous (Sarcoidosis)
• Further evaluation
• Serology for Toxoplasmosis, CMV, EBV nuclear
  antigen, HHV6, HHV8
• Flow cytometry to evaluate double-negative
  T-cells and T-regulatory cells
• Antibody titers to pneumovax and hepatitis A
  vaccine (following second dose)

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