Evans syndrome

Last updated
Evans syndrome
Specialty Hematology   OOjs UI icon edit-ltr-progressive.svg

Evans syndrome is an autoimmune disease in which an individual's immune system attacks their own red blood cells and platelets, the syndrome can include immune neutropenia. [1] [2] These immune cytopenias may occur simultaneously or sequentially. [1] [3]

Contents

Its overall phenotype resembles a combination of autoimmune hemolytic anemia and immune thrombocytopenic purpura. [1] [4] [5] Autoimmune hemolytic anemia is a condition in which the red blood cells that normally carry oxygen 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 of blood clots in the body to prevent bleeding.

The syndrome was first described in 1951 by R. S. Evans and colleagues. [1]

Signs and symptoms

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/or Petechiae. 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 have autoimmune hemolytic anemia, will also have thrombocytopenia and thus Evans syndrome. The two cytopenias may occur together or sequentially. [1] [3] [9]

Causes

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

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 positive direct 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 against neutrophils and lymphocytes, [14] and "immunopancytopenia" has been suggested as an alternative term for this syndrome. [15]

Treatment

Initial treatment is with glucocorticoid corticosteroids or intravenous immunoglobulin, a treatment that is also used in ITP cases. [5] [16] [17]   In children, it can remain well controlled with a long term immunosuppressant therapy that will occasionally lead to a spontaneous complete resolution of the condition. [18]   Although the majority of cases initially respond well to treatment, relapses are not uncommon [3] [5] and immunosuppressive drugs [3] [5] (e.g. ciclosporin, [19] [20] mycophenolate mofetil, vincristine [21] and danazol [22] ) are subsequently used, [3] or combinations of these. [23]

The off-label use of rituximab (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 hematopoietic stem cell transplantation (SCT). [28] [29]

Prognosis

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 5-year survival of 38%. Among patients with Evans syndrome, the prevailing causes of death were bleeding, infections, and hematological cancer. [4]

It has been observed that there is a risk of developing other autoimmune problems and hypogammaglobulinemia, [30] in one cohort 58% of children with Evans syndrome had CD4-/CD8- T cells which is a strong predictor for having autoimmune lymphoproliferative syndrome. [31]

Epidemiology

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]

See also

Related Research Articles

<span class="mw-page-title-main">Myelodysplastic syndrome</span> Diverse collection of blood-related cancers

A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.

<span class="mw-page-title-main">Immune thrombocytopenic purpura</span> Medical condition with rash and bleeding risk

Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is an autoimmune primary disorder of hemostasis characterized by a low platelet count in the absence of other causes. ITP often results in an increased risk of bleeding from mucosal surfaces or the skin. Depending on which age group is affected, ITP causes two distinct clinical syndromes: an acute form observed in children and a chronic form in adults. Acute ITP often follows a viral infection and is typically self-limited, while the more chronic form does not yet have a specific identified cause. Nevertheless, the pathogenesis of ITP is similar in both syndromes involving antibodies against various platelet surface antigens such as glycoproteins.

<span class="mw-page-title-main">Thrombotic thrombocytopenic purpura</span> Medical condition

Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in blood clots forming in small blood vessels throughout the body. This results in a low platelet count, low red blood cells due to their breakdown, and often kidney, heart, and brain dysfunction. Symptoms may include large bruises, fever, weakness, shortness of breath, confusion, and headache. Repeated episodes may occur.

Microangiopathic hemolytic anemia (MAHA) is a microangiopathic subgroup of hemolytic anemia caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes on microscopy of the blood film.

<span class="mw-page-title-main">Thrombocytopenia</span> Abnormally low levels of platelets in the blood

In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and a third of surgical patients.

<span class="mw-page-title-main">Hemolytic–uremic syndrome</span> Group of blood disorders related to bacterial infection

Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney injury, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure.

<span class="mw-page-title-main">Wiskott–Aldrich syndrome</span> Medical condition

Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia, immune deficiency, and bloody diarrhea. It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present with similar but less severe symptoms and are caused by mutations of the same gene.

<span class="mw-page-title-main">Schistocyte</span> Fragmented portion of a red blood cell

A schistocyte or schizocyte is a fragmented part of a red blood cell. Schistocytes are typically irregularly shaped, jagged, and have two pointed ends.

Cytopenia is a reduction in the number of mature blood cells. It can have many causes, and commonly occurs in people with cancer being treated with radiation therapy or chemotherapy.

<span class="mw-page-title-main">ADAMTS13</span> Metalloprotease enzyme

ADAMTS13 —also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted into the blood and degrades large vWf multimers, decreasing their activity, hence ADAMTS13 acts to reduce thrombus formation.

Warm antibody autoimmune hemolytic anemia (WAIHA) is the most common form of autoimmune haemolytic anemia. About half of the cases are of unknown cause, with the other half attributable to a predisposing condition or medications being taken. Contrary to cold autoimmune hemolytic anemia which happens in cold temperature (28–31 °C), WAIHA happens at body temperature.

Mean platelet volume (MPV) is a machine-calculated measurement of the average size of platelets found in blood and is typically included in blood tests as part of the CBC. Since the average platelet size is larger when the body is producing increased numbers of platelets, the MPV test results can be used to make inferences about platelet production in bone marrow or platelet destruction problems.

<span class="mw-page-title-main">Thrombotic microangiopathy</span> Medical condition

Thrombotic microangiopathy (TMA) is a pathology that results in thrombosis in capillaries and arterioles, due to an endothelial injury. It may be seen in association with thrombocytopenia, anemia, purpura and kidney failure.

Autoimmune lymphoproliferative syndrome (ALPS) is a form of lymphoproliferative disorder (LPDs). It affects lymphocyte apoptosis.

<span class="mw-page-title-main">Eltrombopag</span> Chemical compound

Eltrombopag, sold under the brand name Promacta among others, is a medication used to treat thrombocytopenia and severe aplastic anemia. Eltrombopag is sold under the brand name Revolade outside the US and is marketed by Novartis. It is a thrombopoietin receptor agonist. It is taken by mouth.

Hematologic diseases are disorders which primarily affect the blood and blood-forming organs. Hematologic diseases include rare genetic disorders, anemia, HIV, sickle cell disease and complications from chemotherapy or transfusions.

Acquired hemolytic anemia can be divided into immune and non-immune mediated forms of hemolytic anemia.

<span class="mw-page-title-main">Fostamatinib</span> Chemical compound

Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP). The drug is administered by mouth.

Atypical hemolytic uremic syndrome (aHUS), also known as complement-mediated hemolytic uremic syndrome, not to be confused with Hemolytic–uremic syndrome is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it can be effectively controlled by interruption of the complement cascade. Particular monoclonal antibodies, discussed later in the article, have proven efficacy in many cases.

<span class="mw-page-title-main">Upshaw–Schulman syndrome</span> Medical condition

Upshaw–Schulman syndrome (USS) is the recessively inherited form of thrombotic thrombocytopenic purpura (TTP), a rare and complex blood coagulation disease. USS is caused by the absence of the ADAMTS13 protease resulting in the persistence of ultra large von Willebrand factor multimers (ULVWF), causing episodes of acute thrombotic microangiopathy with disseminated multiple small vessel obstructions. These obstructions deprive downstream tissues from blood and oxygen, which can result in tissue damage and death. The presentation of an acute USS episode is variable but usually associated with thrombocytopenia, microangiopathic hemolytic anemia (MAHA) with schistocytes on the peripheral blood smear, fever and signs of ischemic organ damage in the brain, kidney and heart.

References

  1. 1 2 3 4 5 6 7 "Evans Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2022-03-15.
  2. "Evans syndrome". Genetic and Rare Diseases Information Center. Retrieved 2018-04-17.
  3. 1 2 3 4 5 6 7 8 Norton A, Roberts I (2006). "Management of Evans syndrome". Br. J. Haematol. 132 (2): 125–37. doi: 10.1111/j.1365-2141.2005.05809.x . PMID   16398647. S2CID   7633446.
  4. 1 2 3 4 5 Hansen DL; Möller S; Andersen K; Gaist D; Frederiksen H (2019). "Evans syndrome in adults - incidence, prevalence, and survival in a nationwide cohort". Am J Hematol. 94 (10): 1081–1090. doi: 10.1002/ajh.25574 . PMID   31292991. S2CID   195879785.
  5. 1 2 3 4 5 6 7 Michel M; Chanet V; Dechartres A; Morin A-S; Piette J-C; Cirasino L; Emilia G; Zaja F; Ruggeri M; Andrès E; Bierling P; Godeau B; Rodeghiero F (2009). "The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases". Blood. 114 (15): 3167–3172. doi: 10.1182/blood-2009-04-215368 . PMID   19638626.
  6. "Evans syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-11-27.
  7. "Evans Syndrome | Symptoms & Causes | Boston Children's Hospital". www.childrenshospital.org. Retrieved 2020-11-27.
  8. 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. PMID   2632179.
  9. Ng SC (1992). "Evans syndrome: a report on 12 patients". Clinical and Laboratory Haematology. 14 (3): 189–93. doi:10.1111/j.1365-2257.1992.tb00364.x. PMID   1451398.
  10. Adams, Ragini Malika (2024-05-28). "Evans Syndrome: Practice Essentials, Background, Pathophysiology". Medscape Reference. Retrieved 2024-08-06.
  11. Despotovic, Jenny M, ed. (2018). Immune Hematology | SpringerLink (PDF). doi:10.1007/978-3-319-73269-5. ISBN   978-3-319-73268-8. S2CID   46891351.
  12. "Evans syndrome". Genetic and Rare Diseases Information Center. Retrieved 2019-07-28.
  13. Despotovic, Jenny M, ed. (2018). Immune Hematology | SpringerLink (PDF). doi:10.1007/978-3-319-73269-5. ISBN   978-3-319-73268-8. S2CID   46891351.
  14. 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. PMID   7104228.
  15. Pui CH, Wilimas J, Wang W (1980). "Evans syndrome in childhood". J. Pediatr. 97 (5): 754–8. doi:10.1016/S0022-3476(80)80258-7. PMID   7191890.
  16. Nuss R, Wang W (1987). "Intravenous gamma globulin for thrombocytopenia in children with Evans syndrome". The American Journal of Pediatric Hematology/Oncology. 9 (2): 164–7. doi:10.1097/00043426-198722000-00012. PMID   2438958. S2CID   19749102.
  17. 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. PMID   1483999.
  18. "Evan's Syndrome". Boston Children's Hospital. Retrieved 2020-11-23.
  19. Emilia G, Messora C, Longo G, Bertesi M (1996). "Long-term salvage treatment by cyclosporin in refractory autoimmune haematological disorders". Br. J. Haematol. 93 (2): 341–4. doi:10.1046/j.1365-2141.1996.4871026.x. PMID   8639426. S2CID   11724766.
  20. 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. PMID   11855146.
  21. 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. PMID   1404865.
  22. 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. PMID   8492411.
  23. Scaradavou A, Bussel J (1995). "Evans syndrome. Results of a pilot study utilizing a multiagent treatment protocol". J. Pediatr. Hematol. Oncol. 17 (4): 290–5. doi:10.1097/00043426-199511000-00003. PMID   7583383. S2CID   20968070.
  24. Zecca M; Nobili B; Ramenghi U; et al. (15 May 2003). "Rituximab for the treatment of refractory autoimmune hemolytic anemia in children". Blood. 101 (10): 3857–61. doi: 10.1182/blood-2002-11-3547 . PMID   12531800.
  25. Shanafelt TD, Madueme HL, Wolf RC, Tefferi A (November 2003). "Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome" (PDF). Mayo Clin. Proc. 78 (11): 1340–6. doi:10.4065/78.11.1340. PMID   14601692. Archived from the original (PDF) on 2006-03-13. Retrieved 2007-04-18.
  26. 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. PMID   16124452.
  27. Mathew P, Chen G, Wang W (1997). "Evans syndrome: results of a national survey". J. Pediatr. Hematol. Oncol. 19 (5): 433–7. doi:10.1097/00043426-199709000-00005. PMID   9329465. S2CID   24014798.
  28. 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. PMID   9313889.
  29. Oyama Y, Papadopoulos EB, Miranda M, Traynor AE, Burt RK (2001). "Allogeneic stem cell transplantation for Evans syndrome". Bone Marrow Transplant. 28 (9): 903–5. doi: 10.1038/sj.bmt.1703237 . PMID   11781654.
  30. Wang WC (1988). "Evans syndrome in childhood: pathophysiology, clinical course, and treatment". The American Journal of Pediatric Hematology/Oncology. 10 (4): 330–8. doi:10.1097/00043426-198824000-00013. PMID   3071168. S2CID   20125761.
  31. Teachey DT; Manno CS; Axsom KM; et al. (2005). "Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS)". Blood. 105 (6): 2443–8. doi: 10.1182/blood-2004-09-3542 . PMID   15542578.
  32. Mannering N; Hansen DL; Frederiksen H (2020). "Evans syndrome in children below 13 years of age - A nationwide population-based cohort study". PLOS ONE. 15 (4): e0231284. Bibcode:2020PLoSO..1531284M. doi: 10.1371/journal.pone.0231284 . PMC   7145102 . PMID   32271826.
  33. Aladjidi N; Fernandes H; Leblanc T; Vareliette A; Rieux-Laucat F; Bertrand Y; Chambost H; Pasquet M; Mazingue F; Guitton C; Pellier I; Roqueplan-Bellmann F; Armari-Alla C; Thomas C; Marie-Cardine A; Lejars O; Fouyssac F; Bayart S; Lutz P; Piguet C; Jeziorski E; Rohrlich P; Lemoine P; Bodet D; Paillard C; Couillault G; Millot F; Fischer A; Pérel Y; Leverger G (2015). "Evans Syndrome in Children: Long-Term Outcome in a Prospective French National Observational Cohort". Front Pediatr. 3 (79): e0231284. doi: 10.3389/fped.2015.00079 . PMC   7145102 . PMID   32271826.