Evans syndrome is a rare, chronic autoimmune disorder where the body’s immune system attacks its own blood cells. This condition is characterized by the presence of two or more specific blood cell deficiencies, which can lead to various complications. The body mistakenly produces antibodies that target and destroy its own healthy cells, making it a challenging condition for both patients and healthcare providers.
The Dual Nature of Evans Syndrome
Evans syndrome (ES) is defined by the concurrent or sequential presence of two distinct autoimmune cytopenias: Autoimmune Hemolytic Anemia (AIHA) and Immune Thrombocytopenia (ITP). AIHA is the process where the immune system targets and destroys the body’s red blood cells (RBCs). The destruction of red blood cells in AIHA is typically mediated by immunoglobulin G (IgG) antibodies that react against RBC surface antigens, a process known as warm AIHA. This leads to a low red blood cell count, or anemia.
The second component, ITP, involves the immune system attacking platelets, which are cell fragments necessary for blood clotting. In ITP, auto-antibodies are directed against specific platelet surface proteins, such as GPIIb/IIIa, leading to their premature destruction. The combination of these two destructive processes results in a deficiency of both oxygen-carrying red blood cells and clot-forming platelets. These two conditions may manifest simultaneously in about half of the cases or appear one after the other over a period of time, sometimes years apart.
Recognizing the Symptoms and Confirmation
The clinical presentation of Evans syndrome is a direct result of the low blood cell counts, manifesting as symptoms related to both anemia and thrombocytopenia. Symptoms linked to the destruction of red blood cells (AIHA) include fatigue, paleness of the skin (pallor), and shortness of breath, especially with physical exertion. The rapid breakdown of red blood cells can also cause jaundice, a yellowing of the skin and eyes, and dark urine.
Symptoms arising from low platelet counts (ITP) primarily involve abnormal bleeding and bruising. Patients may experience easy bruising, small red or purple dots on the skin called petechiae, and larger patches of bleeding under the skin known as purpura. More serious manifestations can include nosebleeds, bleeding from the gums, or internal hemorrhage.
Diagnosis requires laboratory confirmation of both conditions and the exclusion of other diseases that might cause similar combined cytopenias. A Complete Blood Count (CBC) is the initial step, revealing low levels of both hemoglobin and platelets. Confirmation of the autoimmune nature of red blood cell destruction relies on the Direct Antiglobulin Test (DAT), also known as the Coombs test. A positive DAT shows that antibodies are attached to the red blood cells, marking them for destruction.
Additional blood tests, such as elevated lactate dehydrogenase (LDH) and decreased haptoglobin, are used as markers to confirm ongoing hemolysis. Because ES is a diagnosis of exclusion in its primary form, extensive testing is often needed to rule out underlying infections, malignancies, or other systemic autoimmune conditions.
Understanding the Underlying Causes
The cause of Evans syndrome is categorized as either primary (idiopathic) or secondary, depending on whether an underlying condition can be identified. In many instances, ES is classified as primary, meaning the exact reason for the immune system’s misdirected attack remains unknown.
Approximately half of all ES cases are considered secondary, occurring alongside another recognized medical condition. These associated disorders include systemic lupus erythematosus (SLE). Other linked conditions are primary immunodeficiency disorders, such as Common Variable Immunodeficiency (CVID) and Autoimmune Lymphoproliferative Syndrome (ALPS). Secondary ES may also be triggered by lymphoproliferative disorders, including Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), or infections like HIV and Hepatitis C. Identifying these underlying causes is important because the cytopenias are often more severe in secondary ES, and treatment must be adjusted to manage the primary disease.
Treatment Strategies and Ongoing Care
The management of Evans syndrome is complex due to the chronic and relapsing nature of the disease, requiring a multi-faceted approach. The initial goal of acute treatment is to rapidly suppress the immune system and increase the circulating blood cell counts. High-dose corticosteroids, such as prednisone, are the most common first-line therapy and are effective in controlling acute episodes.
For patients presenting with severely low platelet counts or acute bleeding, intravenous immunoglobulin (IVIg) is frequently administered. IVIg provides a quick, temporary immune-modulating effect that can help halt the destruction of platelets and red blood cells. While these initial therapies stabilize the patient, the long-term nature of ES means sustained treatment is often required to prevent relapse.
When the condition is refractory (does not respond to first-line agents) or when patients cannot be successfully weaned off steroids, second-line therapies are introduced. The monoclonal antibody rituximab, which targets B cells (the cells that produce the destructive auto-antibodies), is a preferred second-line agent. Other immunosuppressive drugs, such as mycophenolate mofetil and cyclosporine, may also be utilized to control the immune response.
For severe cases unresponsive to medication, a splenectomy may be considered, although it is reserved as a third-line option. Removing the spleen, a major site of blood cell destruction and antibody production, can improve counts but does not guarantee a permanent cure. Regular blood monitoring and ongoing follow-up are necessary to manage the disease effectively and adjust treatment as needed.