The spectrum of Evans syndrome: a literature review


  • Hamza Maqsood Department of Medicine, Nishtar Medical University, Multan, Punjab, Pakistan
  • Hassan Abdullah Shakeel Department of Medicine, Nishtar Medical University, Multan, Punjab, Pakistan
  • Azouba Gulraiz Department of Medicine, Nishtar Medical University, Multan, Punjab, Pakistan
  • Muhammad Dilawaer Khan Department of Medicine, Nishtar Medical University, Multan, Punjab, Pakistan



Anemia, Autoimmune, Evans, Reticulocytes, Steroid


Evans syndrome (ES) is an autoimmune disorder characterized by the simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) and/or immune neutropenia in the absence of any underlying cause. Evans syndrome is a rare disorder although the exact frequency is unknown. No sex predilection is known and Evans syndrome has been described in all ethnic groups and at all ages. Classification of ES includes primary, with this being an exclusion diagnosis with no underlying condition, and secondary in the presence of an underlying disease. Clinical features are associated with anemia and thrombocytopenia including pallor, weakness, fatigue, jaundice, petechiae, ecchymosis, gingivorrhagia and epistaxis. First, a detailed history must be taken from the patient to determine the risk factors for developing ES then a family history of immune disorders along with a thorough physical examination. The management of Evans syndrome remains a challenge. Steroids with and without IVIG are recommended as front-line therapy. Red blood cell/platelet transfusion is indicated only in severe symptomatic patients due to the risk of exacerbations. Splenectomy may also be considered a second-line treatment.


Evans RS, Takahashi K, DUANE RT, Payne R, Liu CK. Primary thrombocytopenic purpura and acquired hemolytic anemia: evidence for a common etiology. AMA Archi Int Med. 1951 Jan 1;87(1):48-65.

Evans RS, Duane RT. Acquired hemolytic anemia: I. The relation of erythrocyte antibody production to activity of the disease. II. Significance of thrombocytopenia and leukopenia. Blood. 1949 Nov;4(11):1196-213.

Norton A, Roberts I. Management of Evans syndrome. Br J Haematol. 2006 Jan;132(2):125-37.

Soo‐chin NG. Evans syndrome: a report on 12 patients. Clini Lab Haematol. 1992 Sep;14(3):189-93.

Savaşan S, Warrier I, Ravindranath Y. The spectrum of Evans’ syndrome. Arch Dis Child. 1997 Sep 1;77(3):245-8.

Hansen DL, Möller S, Andersen K, Gaist D, Frederiksen H. Evans syndrome in adults‐incidence, prevalence, and survival in a nationwide cohort. Am J Hematol. 2019 Oct;94(10):1081-90.

Teachey DT, Manno CS, Axsom KM, Andrews T, Choi JK, Greenbaum BH, et al. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). Blood. 2005 Mar 15;105(6):2443-8.

Michel M, Chanet V, Dechartres A, Morin AS, Piette JC, Cirasino L, et al. The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. Blood, J Am Soc Hematol. 2009 Oct 8;114(15):3167-72.

Wright DE, Rosovsky RP, Platt MY. Case 36-2013: A 38-Year-Old Woman with Anemia and Thrombocytopenia. N Engl J Med. 2013 Nov 21;369(21):2032-43.

Seidel MG. Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood. 2014 Oct 9;124(15):2337-44.

Ahmed FE, AlBakrah MS. Neonatal familial Evans syndrome associated with joint hypermobility and mitral valve regurgitation in three siblings in a Saudi Arab family. Ann Saudi Medi. 2009 May;29(3):227-30.

Ahmed FE, Qureshi IM, Wooldridge MA, Pejaver RK. Hereditary spastic paraplegia and Evans's syndrome. Acta Paediatrica. 1996 Jul;85(7):879-81.

McLeod AG, Pai M, Carter RF, Squire J, Barr RD. Familial Evans syndrome: a report of an affected sibship. J Pediatr Hematol/Oncol. 1999;21(3):244-7.

Sarode R. Atypical presentations of thrombotic thrombocytopenic purpura: a review. J Clini Apher: Official J Am Soc Apher. 2009;24(1):47-52.

Zhang C, Chen XH, Zhang X. Quick development and sudden death: Evans syndrome followed by thrombotic thrombocytopenic purpura. Am J Emerg Medi. 2014 Sep 1;32(9):1156-e3.

Dhingra KK, Jain D, Mandal S, Khurana N, Singh T, Gupta N. Evans syndrome: a study of six cases with review of literature. Hematology. 2008 Dec 1;13(6):356-60.

Pui CH, Wilimas J, Wang W. Evans syndrome in childhood. J Pediatr. 1980 Nov 1;97(5):754-8.

Silverstein MN, Heck FJ. Acquired hemolytic anemia and associated thrombocytopenic purpura: with special reference to Evans' syndrome. InProceedings of the staff meetings. Mayo Clinic. 1962 Feb;37:122-8.

Aladjidi N, Fernandes H, Leblanc T, Vareliette A, Rieux-Laucat F, Bertrand Y, et al. Evans syndrome in children: long-term outcome in a prospective French national observational cohort. Frontier Pediatr. 2015 Sep 29;3:79.

Mathew P, Chen G, Wang W. Evans syndrome: results of a national survey. J Pediatr Hematol/Oncol. 1997;19(5):433-7.

Wang W, Herrod H, Pui CH, Presbury G, Wilimas J. Immunoregulatory abnormalities in Evans syndrome. Am J Hematol. 1983 Dec;15(4):381-90.

Karakantza M, Mouzaki A, Theodoropoulou M, Bussel JB, Maniatis A. Th1 and Th2 cytokines in a patient with Evans' syndrome and profound lymphopenia. Br J Haematol. 2000 Sep;110(4):968-70.

Schmidt RE, Grimbacher B, Witte T. Autoimmunity and primary immunodeficiency: two sides of the same coin?. Nature Rev Rheumatol. 2018 Jan;14(1):7.

Besnard C, Levy E, Aladjidi N, Stolzenberg MC, Magerus-Chatinet A, Alibeu O, et al. Pediatric-onset Evans syndrome: heterogeneous presentation and high frequency of monogenic disorders including LRBA and CTLA4 mutations. Clini Immunol. 2018 Mar 1;188:52-7.

Stepensky P, Rensing-Ehl A, Gather R, Revel-Vilk S, Fischer U, Nabhani S, et al. Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency. Blood, J Am Soc Hematol. 2015 Jan 29;125(5):753-61.

Colino CG. Avances en el conocimiento y manejo del síndrome linfoproliferativo autoinmune. InAnales de Pediatría 2014 Feb 1;80(2);122-e1.

Seif AE, Manno CS, Sheen C, Grupp SA, Teachey DT. Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study. Blood, J Am Soci Hematol. 2010 Mar 18;115(11):2142-5.

Wang J, Zheng L, Lobito A, Chan FK, Dale J, Sneller M, et al. Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell. 1999 Jul 9;98(1):47-58.

Rieux-Laucat F, Le Deist F, Hivroz CE, Roberts IA, Debatin KM, Fischer A, et al. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science. 1995 Jun 2;268(5215):1347-9.

Thakur N, Chandra J, Dhingra B, Singh V. Pediatric lupus: varied haematological picture and presentation. Indian J Hematol Blood Transfusion. 2015 Mar 1;31(1):68-70.

Lube GE, Ferriani MP, Campos LM, Terreri MT, Bonfá E, Magalhães CS, et al. Evans Syndrome at Childhood‐Onset Systemic Lupus Erythematosus Diagnosis: A Large Multicenter Study. Pediatr Blood & Cancer. 2016 Jul;63(7):1238-43.

Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, et al. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clini Immunol. 2017 Feb 1;13(2):101-15.

Abraham RS, Podjasek JC. Autoimmune cytopenias in common variable immunodeficiency. Frontiers Immunol. 2012 Jul 24;3:189.

Savaşan S, Warrier I, Buck S, Kaplan J, Ravindranath Y. Increased lymphocyte Fas expression and high incidence of common variable immunodeficiency disorder in childhood Evans’ syndrome. Clini Immunol. 2007 Dec 1;125(3):224-9.

O'Reilly A, Murphy J, Rawe S, Garvey M. Chronic lymphocytic leukemia: a review of front-line treatment options, with a focus on elderly CLL patients. Clini Lymphoma Myeloma Leukemia. 2018 Apr 1;18(4):249-56.

Carli G, Visco C, Falisi E, Perbellini O, Novella E, Giaretta I, et al. Evans syndrome secondary to chronic lymphocytic leukaemia: presentation, treatment, and outcome. Ann Hematol. 2016 May 1;95(6):863-70.

Ohkawara H, Furukawa M, Ikeda K, Shichishima-Nakamura A, Fukatsu M, Sano T, et al. Steroid-resistant autoimmune myelofibrosis in a patient with autoimmune hepatitis and Evans syndrome complicated with increased expression of TGF-β in the bone marrow: a case report. Inter J Hematol. 2017 Nov 1;106(5):718-24.

Schneppenheim R, Budde U, Hassenpflug W, Obser T. Severe ADAMTS-13 deficiency in childhood. Seminars Hematol. 2004 Jan 1;41(1):83-9.




How to Cite

Maqsood, H., Shakeel, H. A., Gulraiz, A., & Khan, M. D. (2020). The spectrum of Evans syndrome: a literature review. International Journal of Research in Medical Sciences, 8(5), 1961–1967.



Review Articles