Hematology Oncology · Year 2 · from Hematology Oncology
Case 3: Chronic Eosinophilia with Hypereosinophilic Syndrome
Patient Presentation
Demographics: 48-year-old male
Chief Complaint: Progressive fatigue, shortness of breath, and skin rash for 3 months
History of Present Illness: The patient reports gradually worsening fatigue and exertional dyspnea over 3 months. He has developed pruritic skin lesions on his trunk and extremities. He reports occasional palpitations. He has no history of asthma, allergies, or atopic conditions. He has not traveled internationally and has no pets. He takes no medications and has no occupational exposures.
Physical Examination:
- Vital signs: BP 128/78, HR 96 (irregular), RR 18, Temp 37.0C, SpO2 95% on room air
- General: Fatigued-appearing male
- Cardiac: Irregularly irregular rhythm, III/VI systolic murmur at apex
- Lungs: Bibasilar crackles
- Abdomen: Hepatomegaly, splenomegaly (4 cm below costal margin)
- Skin: Scattered erythematous papules and nodules
- Neuro: Mild peripheral sensory loss in stocking distribution
Workup and Results
Complete Blood Count:
- WBC: 28,400/uL
- Differential:
- Eosinophils: 58% (absolute 16,470/uL - marked eosinophilia)
- Neutrophils: 32%
- Lymphocytes: 8%
- Hemoglobin: 11.2 g/dL
- Platelets: 185,000/uL
Additional Labs:
- Troponin I: 0.45 ng/mL (elevated)
- BNP: 890 pg/mL (elevated)
- IgE: 350 IU/mL (mildly elevated)
- B12: Normal
- Tryptase: Normal
Cardiac Workup:
- ECG: Atrial fibrillation with RVR
- Echocardiogram: Restrictive pattern, apical thrombus, EF 40%
- Cardiac MRI: Endomyocardial fibrosis pattern
Bone Marrow Biopsy:
- Hypercellular with 45% eosinophils
- No blasts or dysplasia
- FISH: FIP1L1-PDGFRA fusion POSITIVE
Other Studies:
- Stool O&P: Negative x 3
- Strongyloides serology: Negative
- Chest CT: Patchy ground-glass opacities
Clinical Image
Peripheral blood smear demonstrating marked eosinophilia with numerous eosinophils characterized by bilobed nuclei and prominent orange-red cytoplasmic granules.
Diagnosis
Hypereosinophilic Syndrome - FIP1L1-PDGFRA-Positive (Myeloproliferative Variant)
Diagnostic criteria met:
- Absolute eosinophil count >1,500/uL for >6 months
- Eosinophil-mediated organ damage (cardiac, pulmonary, skin, neurologic)
- FIP1L1-PDGFRA fusion gene positive
- Secondary causes excluded (parasites, allergies, drugs)
Treatment Plan
- First-line therapy:
- Imatinib 100 mg daily (dramatic response expected in FIP1L1-PDGFRA+ cases)
- Check cardiac troponin before starting (risk of myocardial necrosis with rapid eosinophil death)
- Consider concurrent prednisone 1 mg/kg for first 1-2 weeks
- Cardiac management:
- Anticoagulation for atrial fibrillation and LV thrombus
- Heart failure management (diuretics, ACE inhibitor)
- Rate control for atrial fibrillation
- Monitoring:
- CBC weekly initially, then monthly
- Target AEC <500/uL
- Repeat echocardiogram at 3 months
- Prognosis:
- FIP1L1-PDGFRA+ HES has excellent response to imatinib
- Near-complete hematologic remission expected
- Cardiac damage may be partially reversible if treated early
Teaching Points
- Eosinophilia causes: NAACP - Neoplasm, Allergic/Atopic, Adrenal insufficiency, Connective tissue disease, Parasites
- Hypereosinophilic syndrome requires persistent eosinophilia with organ damage
- The FIP1L1-PDGFRA fusion creates a constitutively active tyrosine kinase responsive to imatinib
- Eosinophilic heart disease (Loeffler endocarditis) causes restrictive cardiomyopathy and mural thrombi
- Major basic protein and other eosinophil granule contents cause direct tissue damage
- Always exclude parasitic infection before immunosuppressive therapy for eosinophilia
- FIP1L1-PDGFRA+ cases are male-predominant and exquisitely sensitive to low-dose imatinib