Evans Syndrome

Evans syndrome is an autoimmune disorder that is defined as a co-occurrence of two or more cytopenias, or low levels of blood cell counts (i.e., red blood cells, white blood cells, or platelets) in the blood. Evans syndrome can cause the destruction of red blood cells (i.e., anemia), which are primarily responsible for the transportation of oxygen; neutrophils (i.e., neutropenia), which are a type of white blood cell that help to fight infection; and platelets (i.e., thrombocytopenia), which assist with blood clotting. Evans syndrome is a chronic condition with periods of remission and exacerbations, and it primarily affects children. 

Evans syndrome can be primary or idiopathic in nature, meaning the exact cause is unknown; or secondary, meaning that it’s associated with an underlying condition. Common secondary conditions in younger individuals include common variable immunodeficiency (CVID), autoimmune lymphoproliferative syndrome (ALPS), and systemic lupus erythematosus (SLE). In those older than 50 years old, it can occur alongside chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. 

Evans syndrome is an autoimmune disorder, meaning the body’s own immune system attacks itself. Specifically, Evans syndrome causes the autoimmune destruction of red blood cells, neutrophils, and/or platelets. If red blood cells are primarily affected, the patients with Evans syndrome will likely develop autoimmune hemolytic anemia (AIHA); if neutrophils are affected, then neutropenia will arise; and lastly, if platelets are affected, immune thrombocytopenia (ITP) can develop. Most commonly, Evans syndrome is caused by the combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). 

Signs and symptoms of Evans syndrome vary and depend on which blood cell is primarily affected. Children with Evans syndrome where AIHA is present can present with jaundice, fatigue, shortness of breath, pale skin (i.e., pallor), dark brown urine, and decreased activity intolerance. Patients with Evans syndrome who have neutropenia can present with mouth sores, fevers, and recurrent bacterial and fungal infections. Lastly, if an individual has ITP, then symptoms may include petechiae (i.e., red, purple, or brown pinpoint lesions on the skin); excessive bruising; and increased bleeding, such as heavy menses in those who menstruate or frequent epistaxis. Those with ITP can also present with a life-threatening hemorrhage when platelet counts drop, most commonly with platelet counts less than 10000-20000 platelets per microliter. 

Evans syndrome is a diagnosis of exclusion, meaning other possible conditions must be ruled out before the diagnosis can be made. Evans syndrome may be suspected based on a history and physical examination. Blood tests are typically indicated and can include a complete blood count (CBC) with differential, including a reticulocyte count, which calculates the amount of immature red blood cells that are circulating; a Coombs test, which detects the presence of antibodies against circulating red blood cells; and a peripheral smear. 

In addition to blood tests, a bone marrow biopsy can be performed to evaluate different types of blood cells, including their quantity, color, shape, and size. 

Treatment of Evans syndrome can be challenging and generally depends on the severity of the condition, an individual's signs and symptoms, and the presence of comorbid conditions. Even with proper treatment, relapses are common. In general, treatment usually begins with the administration of a corticosteroid, like prednisone, or intravenous immunoglobulin (IVIG), an intravenous form of functional antibodies which can be used to modify the activity of the immune system of an individual with Evans syndrome. Patients with Evans syndrome who don’t respond to the first-line treatment or who are steroid-dependent can be given rituximab (i.e., monoclonal antibody) due to its increased response when used in combination with corticosteroids. In those with thrombocytopenia that is nonresponsive, a splenectomy can be considered; however, this treatment has fallen out of favor in the medical community due to the increased risk of infection and lowered response rates. 

Immunosuppressive medications like cyclosporine can also be given to those who are nonresponsive to first- and second-line treatments. A hematopoietic stem cell transplantation can also be done; however, its use is rare and is considered a last resort treatment reserved for those who are nonresponsive to previous treatments. 

Evans syndrome is an autoimmune disorder that is defined as a co-occurrence of two or more cytopenias, or low levels of blood cell counts in the blood. This is most often autoimmune hemolytic anemia (AIHA) plus immune thrombocytopenia (ITP), and less commonly, autoimmune neutropenia. Signs and symptoms of Evans syndrome vary and depend on which blood cell is primarily affected. Diagnosis is one of exclusion and can be suspected based on a history and physical exam as well as a variety of blood tests, which can include a complete blood count (CBC) with differential, Coombs test, and a reticulocyte count. In general, treatment usually begins with the administration of a corticosteroid, like prednisone, or intravenous immunoglobulin (IVIG). Patients with Evans syndrome who don’t respond to the first-line treatment or who are steroid-dependent can be given rituximab due to its increased response when used in combination with corticosteroids.