Its All Good: A Case of Thymoma with Immune Dysfunction

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Its All GoodA Case of Thymoma with Immune
Dysfunction

• David Stukus, MD
• Assistant Professor of Pediatrics
• Division of Pulmonary Medicine, Allergy
  Immunology
• Childrens Hospital of Pittsburgh
• September 12, 2008

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Initial Presentation

• D.H. is a 63 year old previously healthy female
• Developed extreme dyspnea and palpitations in
  April, 2003
• Chest CT scan 7 x 10 cm anterior mediastinal
  mass
• Dramatic increase in size from initial
  incidental finding on chest x-ray 6 years prior
  
• Successful excision in May, 2003
• Stage I benign mixed epithelial/lymphocyte
  thymoma without capsular invasion
• Immediate post-op course
• Sinus node dysfunction and bradycardia
• Mild macrocytic anemia

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Subsequent Course During the Following Year

• New onset intermittent solid food dysphagia
• Resolved after dilation of Schiatzki ring
• Extreme fatigue and weakness
• Unremarkable evaluation for myasthenia gravis
• Routine evaluation by oncologist in August, 2004
• Macrocytic anemia
• Profound hypogammaglobulinemia
• I believe there may be an association between
  thymoma and immune deficiency

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Initial Allergy/Immunology Consultation

• No increased frequency of sinopulmonary or
  invasive infections
• Episode of chronic bronchitis in 1997
• Required several courses of antibiotics
• Prior hospitalization in 2000
• Left sided pneumonia with effusion that required
  chest tube insertion
• Chronic tongue and buccal mucosal ulcerations
• Painful, erythematous ulcers that last for 3-4
  weeks with intermittent asymptomatic periods
• Also reports chronic cold sores

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Additional History

• Past Medical History
• Sinus node dysfunction, mitral valve
  regurgitation, depression, hyperlipidemia
• Family History
• Unremarkable for atopy, immunodeficiency,
  malignancy, autoimmune disease
• Medications
• Paxil, Tricor, Valtrex as needed
• Initial physical exam
• Several shallow ulcerations on lateral tongue and
  bilateral buccal mucosa
• Remainder of exam within normal limits

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Laboratory Evaluation

• Immunoglobulins
• IgG 93 mg/dL
• IgM lt 6.2 mg/dL
• IgA lt 5 mg/dL
• IgE lt 2 mg/dL

• Antibody Titers
• Diphtheria 0.243 IU/mL
• Tetanus lt 0.01 IU/mL
• Strep pneumo lt 0.01 mg/mL

Vaccination with tetanus and 23 valent
pneumococcal vaccines resulted in no significant
change in titers when measured 4 weeks later
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Laboratory Evaluation

• T Lymphocyte Subsets
• CD3 1659 c/mL
• CD3 CD4 1058 c/mL
• CD3 CD8 572 c/mL
• CD19 lt1 c/mL
• CD56 246 c/mL
• CD4/CD8 ratio 1.85

• Mitogen Proliferation (CPM)
• Mitogen Control 484 (gt50)
• Phytohemagglutinin 45102 (normal gt188800)
• Concanavalin A 47172 (normal gt81283)
• Pokeweed Mitogen 35231 (normal gt68549)
• Staph A Cowen Strain 0 (normal gt3412)

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Additional Evaluation

• Sinus CT scan
• Mild mucosal thickening of ethmoid and left
  maxillary sinus
• Chest CT scan
• Unremarkable no bronchiectasis
• Culture of oral ulcerations
• Positive for candida

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Treatment

• IVIG (400 mg/kg) every 4 weeks
• Gammagard due to low serum IgA levels
• First infusion
• Acute onset bradycardia, hypotension,
  unresponsiveness
• Symptoms lasted lt 5 minutes and vitals returned
  to normal with suspension of infusion and NS
  bolus
• Anti-IgA IgG levels normal no IgE available
• Biweekly infusions (200 mg/kg) resumed after
  cardiac evaluation without adverse effect

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Subsequent Course

• Worsening fatigue and dyspnea
• Emergent hospitalization x 2 due to acute decline
  in Hb to 6 g/dL
• Extensive evaluation with 2 bone marrow biopsies
• Ultimate diagnosis ? pure red cell aplasia
• Remained transfusion dependant for several months
• Improved after cyclosporine treatment
• Baseline Hb remains 11 g/dL

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Subsequent Course

• Persistent painful oral ulcerations
• Biopsy in January, 2005
• Changes consistent with lichen planus
• Symptoms well controlled with topical decadron
  and tacrolimus
• Recurrence after starting cyclosporine
• Repeat biopsy revealed active herpes simplex
• Improved promptly with antiviral therapy

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Subsequent Course

• Despite addition of cyclosporine, D.H. remained
  free of significant or recurrent infections
• Able to tolerate monthly IVIG
• Antibiotics twice/year for sinusitis
• IVIG adjusted to every 3 weeks after trough IgG
  decreased to 680 mg/dL

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Discussion
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Thank You