Evans syndrome

Overview

Evans syndrome is a rare and chronic autoimmune disorder in which the body's immune system mistakenly attacks its own red blood cells, white blood cells, and/or platelets. It is characterized by the simultaneous or sequential occurrence of two or more autoimmune cytopenias—most commonly autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), and sometimes autoimmune neutropenia. Evans syndrome can occur on its own (primary) or in association with other immune system disorders (secondary), such as systemic lupus erythematosus or immunodeficiencies.

Causes

The exact cause of Evans syndrome is unknown, but it involves a dysfunction of the immune system, which leads to the production of autoantibodies that destroy the body's own blood cells. Causes can be classified as:

• Primary (idiopathic): No identifiable underlying condition; immune dysregulation appears to arise spontaneously.

• Secondary: Occurs in association with other diseases, including:

  • Systemic lupus erythematosus (SLE)

  • Common variable immunodeficiency (CVID)

  • Autoimmune lymphoproliferative syndrome (ALPS)

  • Hematologic malignancies (e.g., lymphomas)

  • Post-viral immune activation

Genetic and environmental factors may contribute to the development of immune system dysregulation in affected individuals.

Symptoms

Symptoms of Evans syndrome reflect the destruction of various blood cells and may vary based on which type is primarily affected. Common clinical features include:

From autoimmune hemolytic anemia (AIHA):

• Fatigue

• Pallor (pale skin)

• Shortness of breath

• Jaundice (yellowing of the skin and eyes)

• Dark urine

From immune thrombocytopenia (ITP):

• Easy bruising

• Prolonged bleeding from cuts

• Petechiae (small red or purple spots on the skin)

• Nosebleeds or bleeding gums

From autoimmune neutropenia:

• Increased susceptibility to infections

• Fever

• Mouth ulcers

Symptoms can appear gradually or acutely and may fluctuate with periods of remission and relapse.

Diagnosis

Diagnosis of Evans syndrome is based on laboratory findings that show evidence of multiple autoimmune cytopenias. The diagnostic process typically includes:

• Complete blood count (CBC): Shows low levels of red cells, platelets, and/or neutrophils

• Peripheral blood smear: To assess for hemolysis and platelet abnormalities

• Direct antiglobulin test (Coombs test): Positive in autoimmune hemolytic anemia

• Bone marrow biopsy: May be done to exclude leukemia or other bone marrow disorders

• Immunological testing: To evaluate for associated autoimmune diseases or immunodeficiencies

• Infectious disease screening: To rule out underlying viral infections (e.g., HIV, EBV)

Treatment

There is no standard treatment for Evans syndrome, and therapy is tailored based on symptom severity, type of cytopenia, and patient response. Management typically includes:

• Corticosteroids: First-line treatment to suppress the immune system and reduce autoantibody production

• Intravenous immunoglobulin (IVIG): Especially useful in immune thrombocytopenia

• Immunosuppressive agents: Such as rituximab, azathioprine, or cyclosporine for steroid-refractory or relapsing cases

• Splenectomy: Sometimes considered in patients who do not respond to medical treatment

• Supportive care: Blood transfusions, antibiotics for infections, and monitoring for bleeding complications

• Treatment of underlying conditions: In secondary cases associated with autoimmune or immunodeficiency syndromes

Prognosis

Evans syndrome is a chronic condition with a variable course. Some patients experience periods of remission, while others may have frequent relapses and complications. Long-term outcomes depend on the severity of cytopenias, response to treatment, and presence of underlying disorders. With appropriate and timely care, many individuals can manage the disease successfully, though close monitoring is often necessary due to the risk of recurrence, infections, or treatment-related side effects.