What is the treatment for Evan syndrome?

Treatment of Evans Syndrome

First-line treatment for Evans syndrome should consist of corticosteroids (prednisone 1-2 mg/kg/day) with or without intravenous immunoglobulin (IVIG 0.4-1 g/kg/day for 3-5 days) to rapidly address both the autoimmune hemolytic anemia and immune thrombocytopenia components of the disease. 1, 2

Definition and Diagnosis

Evans syndrome is a rare autoimmune disorder characterized by the simultaneous or sequential occurrence of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), with or without autoimmune neutropenia. 1, 3

Diagnostic evaluation should include:

• Complete blood count with differential and reticulocyte count
• Peripheral blood smear
• Direct antiglobulin test (DAT/Coombs test) to confirm AIHA
• LDH, haptoglobin, and bilirubin levels to assess hemolysis
• Bone marrow evaluation to exclude other causes
• Screening for underlying conditions (lymphoproliferative disorders, autoimmune diseases, infections)
• CT scan to evaluate for lymphadenopathy or splenomegaly 2, 4

Treatment Algorithm

First-Line Therapy

• Corticosteroids: Prednisone 1-2 mg/kg/day 1, 2
• IVIG: 0.4-1 g/kg/day for 3-5 days (when rapid response is needed) 1, 2
• Different tapering schedules are recommended for the ITP and AIHA components 4

Second-Line Therapy

• Rituximab: Strongly recommended for:

  • Cold-type AIHA (first-line)
  • Warm-type AIHA (second-line)
  • Patients with antiphospholipid antibodies
  • Previous thrombotic events
  • Associated lymphoproliferative diseases 4

• Thrombopoietin receptor agonists: For chronic ITP component, especially with history of severe infections 4

• Splenectomy: Consider in patients who fail first-line therapy, but avoid in patients with immunodeficiency or severe infections 4, 5

Third-Line and Beyond

• Immunosuppressive agents: Cyclosporine, azathioprine, cyclophosphamide 5
• Fostamatinib: Recommended as third-line or further treatment 4
• Complement inhibitors: Sutimlimab for relapsed cold AIHA 4
• Combination therapy: Rituximab plus bendamustine for Evans syndrome secondary to lymphoproliferative disorders 4

Special Considerations

Supportive Care

• Transfusions: Avoid unnecessary transfusions as they can worsen hemolysis. When required, use extended compatibility matching 2
• Erythropoietin: Consider in AIHA with inadequate reticulocyte counts 2, 4
• Thrombotic prophylaxis: Particularly important in patients with antiphospholipid antibodies 4
• Antibiotic prophylaxis: Consider in patients on significant immunosuppression 4

Monitoring

• Regular assessment of hemoglobin, platelets, reticulocytes, LDH, and haptoglobin to monitor disease activity and treatment response 2

Prognosis

Evans syndrome has a chronic and often relapsing course with significant mortality (24% in one study with 4.8 years follow-up). Only about one-third of patients achieve remission off treatment. 6

Pitfalls and Caveats

• Evans syndrome is often misdiagnosed as isolated ITP or AIHA, delaying appropriate treatment
• Always screen for underlying conditions, as 50% of cases are secondary to other disorders 6
• Treatment response is often transient, with high relapse rates
• Splenectomy has limited long-term efficacy (median response duration of only 1 month) 5
• Cardiovascular complications related to AIHA may pose greater risks than bleeding from ITP, particularly in elderly patients 6
• Infection risk is significant due to multiple immunosuppressive therapies