What is the management of Evan's syndrome?

Management of Evans Syndrome

The management of Evans syndrome should begin with corticosteroids as first-line therapy, with or without intravenous immunoglobulin (IVIg), followed by rituximab as second-line treatment for refractory cases. 1

Definition and Diagnosis

Evans syndrome is a rare autoimmune disorder characterized by the simultaneous or sequential development of:

• Autoimmune hemolytic anemia (AIHA) with positive direct antiglobulin test (DAT)
• Immune thrombocytopenia (ITP)
• Sometimes autoimmune neutropenia

Diagnostic workup should include:

• Complete blood count with peripheral smear
• Direct antiglobulin test (DAT)
• Bone marrow evaluation
• CT scan to rule out underlying conditions 1

Treatment Algorithm

First-Line Therapy

• Corticosteroids: Prednisone (1-2 mg/kg/day)
  • Different treatment durations for ITP (shorter) vs AIHA (longer with gradual tapering) 1
• IVIg (1 g/kg): Can be used alone if corticosteroids are contraindicated or in combination with corticosteroids when rapid platelet count increase is needed 2

Second-Line Therapy

• Rituximab: Strongly recommended for:

  • Cold-type AIHA (first-line)
  • Warm-type AIHA (second-line)
  • Patients with ITP and antiphospholipid antibodies
  • Previous thrombotic events
  • Associated lymphoproliferative diseases 1
  • Caution: Avoid in patients with immunodeficiency or severe infections

• Thrombopoietin receptor agonists: Recommended for:

  • Chronic ITP component
  • Patients with previous grade 4 infection
  • Patients at risk of bleeding who relapse after splenectomy or have contraindication to splenectomy 2

• Splenectomy: Consider for patients who have failed corticosteroid therapy 2

  • Less effective in Evans syndrome than in uncomplicated ITP 3
  • Both laparoscopic and open approaches offer similar efficacy 2

Third-Line and Beyond

• Fostamatinib: Recommended as third-line or further treatment

  • Consider as second-line for patients with previous thrombotic events 1

• Immunosuppressive agents:

  • Cyclosporine
  • Mycophenolate mofetil
  • Azathioprine
  • Cyclophosphamide 3

• For refractory cases:

  • Combination therapy (rituximab plus bendamustine) for Evans syndrome secondary to lymphoproliferative disorders 1
  • Stem cell transplantation for very severe and refractory cases 3

Supportive Care

• Recombinant erythropoietin: For AIHA with inadequate reticulocyte counts 1
• Complement inhibitor sutimlimab: For relapsed cold AIHA 1
• Thrombotic prophylaxis: Particularly important in patients with antiphospholipid antibodies 1
• Antibiotic prophylaxis: Consider in immunosuppressed patients 1

Special Considerations

• Pregnancy: Pregnant patients requiring treatment should receive either corticosteroids or IVIg 2
• Secondary Evans syndrome: Treat underlying causes when identified:
  • HIV: Antiviral therapy should be considered before other treatment options 2
  • H. pylori: Eradication therapy if infection is detected 2
  • HCV: Consider antiviral therapy in the absence of contraindications 2

Monitoring and Follow-up

• Monitor for relapse as Evans syndrome typically runs a chronic course with frequent exacerbations and remissions 3
• No further treatment needed in asymptomatic patients after splenectomy who maintain platelet counts >30 × 10⁹/L 2

Common Pitfalls

• Failure to exclude underlying conditions (lymphoproliferative disorders, autoimmune diseases, infections)
• Inadequate duration of corticosteroid therapy, especially for AIHA component
• Premature splenectomy before adequate trial of medical therapy
• Overlooking the need for different treatment approaches for the ITP and AIHA components