Its overall phenotype resembles a combination ofautoimmune hemolytic anemia andimmune thrombocytopenic purpura.[1][4][5]Autoimmune hemolytic anemia is a condition in which the red blood cells that normally carryoxygen are destroyed by an autoimmune process. Immune thrombocytopenic purpura is a condition in which platelets are destroyed by an autoimmune process. Platelets are a component of blood that contribute to the formation ofblood clots in the body to prevent bleeding.
The syndrome was first described in 1951 by R. S. Evans and colleagues.[1]
The symptoms of Evans syndrome vary between patients depending on which blood cells are affected. If red blood cells are attacked, symptoms may include weakness and fatigue, paleness or jaundice, shortness of breath, lightheadedness, and/or a fast heartbeat. If platelets are attacked, symptoms may include increased bruising, prolonged nosebleeds, increased bleeding from minor cuts, and/orPetechiae. In the less common instance that white blood cells are attacked, symptoms may include increased proneness to infection, fevers, and/or mouth sores.[6][7]
It has been variously reported that between 7.8%[4] and 23%[8] of patients who haveautoimmune hemolytic anemia, will also have thrombocytopenia and thus Evans syndrome. The two cytopenias may occur together or sequentially.[1][3][9]
Although Evans syndrome seems to be a disorder of immune regulation, the exact pathophysiology is unknown, but a gradual loss of self-tolerance is postulated.[5] Autoantibodies targeted at different antigenic determinants on red cells and platelets are assumed to cause isolated episodes of hemolytic anemia and thrombocytopenia, respectively.[10]
Diagnosis of Evans syndrome is separated into primary and secondary presentation. There is no single test to confirm a diagnosis of either form of Evans syndrome. It is instead a diagnosis made after a thorough clinical history, documentation of common symptoms, clinical evaluation, and exclusion of all other possible conditions.[1]
The diagnosis of primary Evans syndrome is made upon blood tests to confirm not only hemolytic anemia and immune thrombocytopenic purpura, but also a positivedirect antiglobulin test (DAT) and an absence of any known underlying cause.[3] Additional tests used to eliminate the possibility of other conditions include a computed tomography (CT) scan and a biopsy of bone marrow.[1]
A diagnosis of secondary Evans syndrome is indicative of occurrence after another autoimmune disease is already present.[11] In 27% to 50% of cases there is an associated malignancy or a predisposing autoimmune disease.[4][5][12] Pre-existing autoimmune diseases can include autoimmune lymphoproliferative syndrome (ALPS), combined variable immunodeficiency (CVID), systemic autoimmune disease, or another disorder of immune dysregulation.[13]
Other antibodies may occur directed againstneutrophils andlymphocytes,[14] and "immunopancytopenia" has been suggested as an alternative term for this syndrome.[15]
Theoff-label use ofrituximab (trade name Rituxan) has produced some good results in acute and refractory cases,[3][5][24][25] although further relapse may occur within a year.[3]Splenectomy is effective in some cases,[26] but relapses are not uncommon.[27]
The only prospect for a permanent cure is the high-risk option of an allogeneic hematopoieticstem cell transplantation (SCT).[28][29]
In a nationwide study of Evans syndrome the median survival was 7.2 years (primary Evans syndrome: 10.9 years; secondary Evans syndrome: 1.7 years). Secondary Evans syndrome was associated with higher mortality rate than primary Evans syndrome, with a five-year survival of 38%. Among patients with Evans syndrome, the prevailing causes of death were bleeding, infections, and hematological cancer.[4]
Evans syndrome is considered a very rare autoimmune disease. Only one study has estimated incidence and prevalence adults. In Denmark in 2016 the annual incidence was 1.8 per 1,000,000 person years, and the prevalence was 21.3 per 1,000,000 living persons.[4] In pre-pubertal children the incidence has been estimated to be between 0.7 and 1.2 per 1,000,000 person-years.[32][33]
^Cai JR, Yu QZ, Zhang FQ (1989). "[Autoimmune hemolytic anemia: clinical analysis of 100 cases]".Zhonghua Nei Ke Za Zhi (in Chinese).28 (11):670–3,701–2.PMID2632179.
^Pegels JG, Helmerhorst FM, van Leeuwen EF, van de Plas-van Dalen C, Engelfriet CP, von dem Borne AE (1982). "The Evans syndrome: characterization of the responsible autoantibodies".Br. J. Haematol.51 (3):445–50.doi:10.1111/j.1365-2141.1982.tb02801.x (inactive 12 July 2025).PMID7104228.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
^Mehta JB, Singhal SB, Mehta BC (1992). "Intravenous immunoglobulin therapy of idiopathic thrombocytopenia".The Journal of the Association of Physicians of India.40 (5):340–2.PMID1483999.
^Liu H, Shao Z, Jing L (2001). "[The effectiveness of cyclosporin A in the treatment of autoimmune hemolytic anemia and Evans syndrome]".Zhonghua Xue Ye Xue Za Zhi (in Chinese).22 (11):581–3.PMID11855146.
^Yokoyama K; Kojima M; Komatsumoto S; et al. (1992). "[Thrombotic thrombocytopenic purpura achieving complete remission by slow infusion of vincristine]".Rinsho Ketsueki (in Japanese).33 (8):1084–9.PMID1404865.
^Koike M; Ishiyama T; Saito K; et al. (1993). "[Effective danazol therapy for a patient with Evans syndrome]".Rinsho Ketsueki (in Japanese).34 (2):143–6.PMID8492411.
^Hamidah A, Thambidorai CR, Jamal R (2005). "Prolonged remission after splenectomy for refractory Evans syndrome--a case report and literature review".Southeast Asian J. Trop. Med. Public Health.36 (3):762–4.PMID16124452.
^Martino R, Sureda A, Brunet S (1997). "Peripheral blood stem cell mobilization in refractory autoimmune Evans syndrome: a cautionary case report".Bone Marrow Transplant.20 (6): 521.doi:10.1038/sj.bmt.1700924.PMID9313889.
