What is the treatment for Evans syndrome?

Treatment for Evans Syndrome

First-line treatment for Evans syndrome should begin with prednisone 1-2 mg/kg/day orally, with the addition of intravenous immunoglobulin (IVIg) at 1 g/kg when a more rapid increase in platelet count is required. 1

Definition and Diagnosis

Evans syndrome is defined as the simultaneous or sequential occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), with or without autoimmune neutropenia 2, 3. It represents approximately 5-10% of all warm AIHA and 2-5% of all ITP cases in adults 4.

Diagnostic workup should include:

• Complete blood count with differential, peripheral smear, and reticulocyte count 1
• Direct antiglobulin test (DAT) to confirm the autoimmune hemolytic anemia component 1
• Testing for underlying conditions including HIV, hepatitis C virus, hepatitis B virus, CMV, and Helicobacter pylori 1, 5
• Evaluation for lymphoproliferative disorders and autoimmune conditions such as systemic lupus erythematosus and antiphospholipid syndrome 1
• Bone marrow evaluation if abnormalities in blood tests require further investigation 6

Treatment Algorithm

First-Line Treatment

• Corticosteroids: Prednisone 1-2 mg/kg/day orally until platelet count increases to 30-50 × 10^9/L 1

  • Continue for 2-4 weeks, then taper over 4-6 weeks to the lowest effective dose 6
  • Alternative regimen: High-dose dexamethasone (40 mg/day for 4 days) 1

• Intravenous Immunoglobulin (IVIg):

  • Add to corticosteroids when a more rapid increase in platelet count is required 1
  • Initial dose: 1 g/kg as a one-time dose, which may be repeated if necessary 6

Second-Line Treatment Options

• Rituximab is strongly recommended as second-line treatment, particularly in:

  • Cold-type AIHA (first-line) 2
  • Warm-type AIHA 2
  • Patients with antiphospholipid antibodies or previous thrombotic events 2
  • Patients with associated lymphoproliferative diseases 2
  • Not recommended for patients with immunodeficiency or severe infections 2

• Thrombopoietin receptor agonists (eltrombopag, romiplostim):

  • Recommended for chronic immune thrombocytopenia component 7
  • Particularly useful in cases with previous severe infections 7
  • Response rates: 70-81% for eltrombopag and 79-88% for romiplostim 7

Third-Line and Beyond Options

• Immunosuppressive agents:

  • Horse ATG plus cyclosporine 6
  • If no response, consider rabbit ATG plus cyclosporine or cyclophosphamide 6

• For refractory cases:

  • Eltrombopag plus supportive care 6
  • Combination chemotherapy with cyclophosphamide, prednisone, vincristine, plus either azathioprine or etoposide 7
  • Plasma exchange in severe cases not responding to other therapies 7
  • Hematopoietic stem cell transplantation in cases unresponsive to all immunosuppressive agents 7
  • Alemtuzumab (Campath-1H) for severe, refractory cases (requires prolonged antimicrobial prophylaxis) 7

Special Considerations

Secondary Evans Syndrome

• If associated with HIV: Treat HIV infection with antiretroviral therapy before other treatments unless significant bleeding is present 6, 5
• If associated with HCV: Consider antiviral therapy, though monitor platelet counts closely due to potential worsening with interferon-based regimens 6, 5
• If associated with H. pylori: Administer eradication therapy 6
• If associated with lymphoproliferative disorders: Consider rituximab plus bendamustine 2

Supportive Care

• Recombinant erythropoietin in AIHA cases with inadequate reticulocyte counts 2
• Complement inhibitor sutimlimab for relapsed cold AIHA 2
• Consider thrombotic and antibiotic prophylaxis in high-risk patients 2

Monitoring and Response Assessment

• Evaluate response based on platelet count improvement (goal >30 × 10^9/L and at least 2-fold increase from baseline) 1
• Monitor for resolution of hemolysis (improved hemoglobin, decreased reticulocyte count, normalized bilirubin) 1
• Regular follow-up to assess for relapse, as Evans syndrome is often characterized by recurrent episodes of thrombocytopenia and hemolytic anemia 8

Prognosis

Despite advances in management, Evans syndrome has a higher mortality rate compared to isolated autoimmune cytopenias 3. The disease course is typically chronic and recurrent, often requiring multiple treatment modalities 8.