Last updated:
2/20/2026
Years published: 2013, 2026
NORD gratefully acknowledges Harry Durgin, Anna Golian and Sarah Gann Karen, Editorial Interns from the University of Notre Dame and Amanda Bell Grimes, MD, Associate Professor, Baylor College of Medicine, Department of Pediatrics, Texas Children’s Cancer and Hematology Center.
Summary
Evans syndrome is a rare disorder characterized by immune-mediated destruction of certain blood cells. In this condition, the body produces antibodies that destroy red blood cells, platelets, and sometimes certain white blood cells called neutrophils.1,2,3 This leads to abnormally low levels of these blood cells, a condition known as cytopenia.
When red blood cells are destroyed too early, it is called autoimmune hemolytic anemia (AIHA).1,3 When platelets are low due to immune destruction, it is called immune thrombocytopenia (ITP). Low levels of neutrophils caused by the immune system are called autoimmune neutropenia (AIN). Traditionally, Evans syndrome was defined as having both AIHA and ITP, with or without neutropenia, which occurs in about 15% of cases.1,3,4 More recently, some experts define Evans syndrome as the presence of any two of the three immune cytopenias (AIHA, ITP, AIN).5
In some people, these blood problems happen at the same time, but more often they occur one after another.3 Symptoms and severity can vary widely from person to person. Evans syndrome can sometimes lead to serious or life-threatening complications, including severe anemia, infections, and bleeding.5
Evans syndrome may occur on its own, known as primary (or idiopathic) Evans syndrome, or it may develop in association with other autoimmune or lymphoproliferative disorders, in which certain white blood cells proliferate abnormally, often leading to enlarged lymph nodes or spleen1,3 About half of cases are secondary to another underlying condition.6 Distinguishing between primary and secondary Evans syndrome is important because it can affect treatment decisions.3,7
The condition is often severe, with frequent relapses and potentially serious complications during the course of treatment.5 Treatment usually starts with the medication prednisone (first-line therapy). If needed, the medication rituximab may be used as the next option (second-line therapy).8,9
Introduction
Evans syndrome was first described in the medical literature in 1951 by Dr. Robert Evans and associates.1,3 For years, the disorder was considered a coincidental occurrence of AIHA with thrombocytopenia and/or neutropenia. However, researchers now believe that the disorder represents a distinct condition characterized by a chronic, profound immune system dysregulation, more than in ITP or AIHA alone.
The symptoms and severity of Evans syndrome can vary widely from one person to another. The age at onset, overall course, and duration of the disorder may also differ, depending in part on which blood cell lines are affected. ⁹
Most people with Evans syndrome experience a chronic course marked by periods of worsening symptoms (exacerbations) and improvements (remissions), which are often temporary and usually occur in response to treatment. Most symptoms result from low levels of specific blood cells in the body. 1, 2 Red blood cells carry oxygen to tissues and remove carbon dioxide, platelets help the blood clot to prevent bleeding, and white blood cells help fight infection.
Some people first present with accelerated destruction of red blood cells that exceeds the body’s ability to replace them. This results in anemia (low red blood cell levels), which may cause:
Some people may also develop yellowing of the skin (jaundice or icterus) and especially the whites of the eyes (scleral icterus). 1, 2, 9
Other people may initially present with low platelet levels that are immune related, known as immune thrombocytopenia (ITP). Thrombocytopenia may cause:
People with thrombocytopenia bruise easily after minor injury and may experience spontaneous bleeding from mucous membranes, such as the nose or gums. In rare cases, more serious bleeding can occur, including bleeding from the gastrointestinal or genitourinary tract or, very rarely, bleeding in the brain. 1, 2, 10
Low levels of certain white blood cells (neutrophils), known as neutropenia, occur less frequently than anemia or thrombocytopenia in Evans syndrome. 1, 2 People with neutropenia may be more prone to recurrent infections. Symptoms may include:
Additional signs and symptoms in Evans syndrome may include enlargement of the lymph nodes, spleen, and liver. 9 These features may appear during acute episodes and, in some individuals, may improve between flares.
Secondary Evans syndrome is commonly associated with other underlying conditions, including:
Evans syndrome is often difficult to treat. Some individuals do not respond adequately to therapy (refractory Evans syndrome), and the disease may follow a relapsing course.⁷˒¹³ Over time, potentially life-threatening complications may occur, including:
Careful monitoring and long-term management are often necessary due to the risk of relapse and serious complications.⁵
The exact underlying cause of Evans syndrome is unknown. Evans syndrome is an autoimmune disorder.1,2 It occurs when the immune system produces antibodies that mistakenly attack healthy tissue, specifically red blood cells, platelets and sometimes certain white blood cells.
The immune system normally responds to foreign substances by producing specialized proteins called antibodies. Antibodies work by destroying foreign substances directly or coating them with a substance that marks them for destruction by white blood cells.2 When antibodies target the person’s own healthy tissue they may be referred to as autoantibodies.2 Researchers believe that a triggering event (such as an infection or an underlying disorder) may induce the immune system to produce autoantibodies in Evans syndrome.
Evans syndrome is classified as primary or secondary. Primary Evans syndrome is not associated with other disorders, and it makes up approximately 70% of adult Evans syndrome cases.9 Secondary Evans syndrome can be associated with other disorders including autoimmune lymphoproliferative syndrome (ALPS), lupus, antiphospholipid syndrome, Sjogren’s syndrome, common variable immunodeficiency, IgA deficiency, certain lymphomas, and chronic lymphocytic leukemia.3,4, 7 Furthermore, Evans syndrome can be classified according to the age, as pediatric Evans syndrome (when occurring in a person under the age of 18) and adult Evans syndrome.14
The estimated incidence of Evans syndrome is 1.8 cases per million people per year, with around 30%-50% of ES cases being secondary to an underlying condition. Approximately 7% of AIHA and 2% of ITP is secondary to underlying ES.9 The global incidence and prevalence of Evans syndrome are unknown. The disorder can affect individuals of all ages. The average age at diagnosis of ES among adults is 53 years.9 n US-based studies, white individuals represent the largest reported racial group affected, followed by African American and Hispanic individuals..15
A diagnosis of Evans syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests. Primary Evans syndrome is diagnosed by ruling out other possible diagnoses, while secondary Evans syndrome is diagnosed in addition to another underlying disease.8,18 No specific test is conclusive for Evans syndrome and a diagnosis is made after excluding other possible diagnoses. Specifically, a diagnosis of Evans syndrome may be made when two of three autoimmune cytopenias occur in the same individual even if not at the same time. Autoimmune cytopenias are a group of disorders where the immune system mistakenly attacks and destroys the body’s own blood cells, leading to abnormally low levels. This includes a low platelet count (immune thrombocytopenia (ITP)), white blood cell count (autoimmune neutropenia (AIN)), and/or red blood cell count, with a positive direct Coombs, or direct antiglobulin, test (autoimmune hemolytic anemia (AIHA)).1,3,9 Various antibodies directed against red blood cells (RBCs), white blood cells (WBCs), and platelets are noted in association with Evans syndrome. Antibodies are proteins produced by the immune system that act as tags to identify and help eliminate foreign substances in the body.19 Ruling out differential diagnoses is required, aided by a blood smear to analyze the contents of the blood. Common similar diseases that must be excluded include cold agglutinin disease, thrombotic thrombocytopenic purpura (TTP), HIV, Hepatitis C, and other autoimmune conditions.10
Clinical Testing and Workup
Laboratory studies include a complete blood count (CBC), which can reveal low levels of red blood cells, platelets and white blood cells. Another blood test known as a direct antiglobulin test (DAT) is used to determine whether the number of certain antibodies is higher than normal. Other similar tests may be administered to rule out other conditions. Such tests can include a bone marrow biopsy, additional antibody assays, and computed tomography (CT) scans of the chest, abdomen and pelvis.1,3
Some physicians recommend that children with Evans syndrome be screened for ALPS because of the high prevalence of these two disorders occurring together. Screening involves testing for the presence of double negative T-cells (DNTs) by flow cytometry, the presence of which is indicative of ALPS.4 Additionally, many physicians treating children with Evans syndrome recommend genetic testing to evaluate for the presence of an underlying immunodeficiency or immune dysregulation, given the significant likelihood that pediatric Evans syndrome may be caused by a single genetic change as well.25 Other testing recommended by experts for the purposes of identifying underlying disease (as well as excluding alternative diagnoses) in adults with Evans syndrome includes serum protein electrophoresis, anti-nuclear antibodies, viral serologies, immunoglobulins, and radiographic imaging of the chest and abdomen.24
Treatment
There is no cure for Evans syndrome, and treatment is often challenging.7 Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Hematologists, immunologists, rheumatologists, surgeons, and other healthcare professionals may need to systematically and comprehensively plan an affected individual’s treatment.
Most affected individuals require treatment, although, in rare cases, spontaneous remission has been reported. A variety of different therapies have been used to treat individuals with Evans syndrome and their effectiveness among affected individuals has been highly variable. Some individuals have long remissions of the disorder; others experience chronic problems with no remission.
Consequently, specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease severity; blood cell count levels; the presence or absence of certain symptoms; an individual’s age and general health; presence of additional underlying diagnosis (secondary Evans syndrome); and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the individual, based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; affected individual preference; and other appropriate factors.
First-line therapy for Evans syndrome often consists of corticosteroids such as prednisolone.7 Corticosteroids help to suppress the immune system and decrease the production of autoantibodies. Initial results are often effective, with response rates between 80% and 100%. However, approximately 75% will additionally require second-line treatments.4,5
Intravenous immunoglobulin (IVIg) therapy has also been used to treat individuals with Evans syndrome when steroids are inefficient or potentially harmful.7,11,19 IVIg therapy modifies the activity of the immune system. IVIg is a solution containing antibodies donated from healthy individuals and delivered directly into a vein.
Surgical removal of the spleen (splenectomy) has been used to treat some individuals with Evans syndrome. The overall initial response rate of splenectomies is approximately 80%, but the effectiveness of the procedure is difficult to determine because of the simultaneous (concomitant) use of other therapies.9 Splenectomy is generally reserved for individuals who do not respond to other therapeutic options (refractory Evans syndrome). In children, splenectomy rarely produces long term remission of symptoms. In adults, the effectiveness varies and symptoms usually return at some point.7,13 Therefore, this intervention is usually delayed as long as possible, and every effort is made not to perform it. For those with secondary Evans syndrome, splenectomies are avoided due to the risk of infections and venous thromboembolism (VTE).9
During an acute episode, blood and/or platelet transfusions may be necessary to address symptoms. However, the use of blood or platelet transfusions should be avoided as much as possible.7
New therapies are being explored for Evans syndrome. Rituximab appears to be a highly effective treatment for individuals with Evans syndrome, when the Evans syndrome does not respond to, or becomes dependent upon, corticosteroids. Initial response rate to rituximab is approximately 80%, with better results in those with chronic ITP and SLE. Rituximab is classified as a monoclonal antibody or biologic therapy, medications that act like antibodies but are artificially created in a lab. Initial studies have shown that the drug is generally safe and effective. it may avoid some of the broader toxicities associated with long-term conventional immunosuppressants.20,21,22 The disadvantage is that in cases of Evans syndrome in which underlying ALPS or CVID is the cause it appears likely that hypogammaglobulinemia will develop and may persist in rituximab-treated individuals.4,17 Hypogammaglobulinemia is a condition in which the body’s immune system does not produce sufficient antibodies, potentially leaving affected individuals susceptible to bacterial infections and to a lesser extent certain viral infections.
Additional medications have been studied in small case series of individuals with Evans syndrome. Immunosuppressants–such as mycophenolate mofetil and sirolimus–have been used for individuals who did not respond to corticosteroids, rituximab, or splenectomy. However, these have shown variable effectiveness.11,23 Immunosuppressants prevent the immune system from being overactive and attacking healthy cells and tissues. Fostamatinib has been suggested as a novel third-line therapy for individuals with two or more thrombocytopenia relapses, particularly regarding previous thrombotic events.
Additionally, thrombopoietin receptor agonists (TPO-RAs) have been used as a second-line therapy to stimulate the production of platelets.24 These drugs may be used alone or in combination, as second-line or third-line therapies for individuals with Evans syndrome who do not respond to corticosteroids or IVIg therapy; particularly in the setting of significant prior infection. More research is necessary to determine the long-term safety and effectiveness of these potential therapies for individuals with Evans syndrome.
Some individuals with Evans syndrome have been treated with allogeneic or autologous stem cell transplantation. Stem cells are special cells found in the bone marrow that manufacture different types of blood cells (i.e. red blood cells, white blood cells and platelets). In autologous stem cell transplantation, an affected individual’s stem cells are removed after prior treatment, usually with drugs. These healthy stem cells are later re-infused into the bone marrow after the disorder has progressed. In allogeneic stem cell transplantation, stem cells are donated from another person, usually from a closely matched family member. These procedures have generally been used as a last resort for individuals who have failed to respond to other forms of treatment. They have produced mixed results and more experience is necessary to determine their potential effectiveness as a treatment for Evans syndrome.7,13
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ . All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
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