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Evan's Syndrome

Evans' Syndrome

Evan's syndrome is a hematological disorder defined by the simultaneous or sequential presence of autoimmune hemolytic anemia and immune-mediated thrombocytopenia. The pathophysiology and etiology remain unclear.


Presentation

Evan's syndrome can present in childhood or adulthood. The thrombocytopenic episodes can precede, appear simultaneously with, or follow the episodes of autoimmune hemolytic anemia (AIHA). The severity of symptoms and the time between AIHA and thrombocytopenia episodes can vary. In adult non-simultaneous cases, this delay can last an average of 4 years.

Immune-mediated thrombocytopenia (ITP) often manifests as petechiae, purpura, ecchymoses, epistaxis and mucocutaneous hemorrhage. In severe thrombocytopenia, cerebro-meningeal or gastrointestinal hemorrhage and hematuria may occur.

AIHA is revealed by pallor, unusual weakness, light-headedness, fatigue, exertional dyspnea, tachycardia, jaundice, splenomegaly, and dark urine.

A U.S. and Canada study identified thrombocytopenia in 76% of Evan's syndrome patients and anemia in 67% of these cases [1]. Additionally, the presence of neutropenia was confirmed in 24% of patients while 14% were found to have pancytopenia.

Since its first description, Evan's syndrome has been considered an idiopathic disease. However, it may be associated with other conditions like lymphoproliferative disorders, primary immunodeficiencies, and systemic lupus erythematosus (SLE) [2] [3] [4] [5].

During childhood, the disease may present with an autoimmune lymphoproliferative syndrome (ALPS) that results from a disruption in lymphocyte homeostasis associated with a mutated Fas apoptotic pathway [6].

The spectrum of Evan's syndrome in children has widened recently as there is growing evidence that suggests the syndrome is the reflection of a profound state of immune dysregulation and not a coincidental presentation of immune cytopenias [7].

Hyperhidrosis
  • […] lesions of the gingiva, and PPK Focal PPK with oral mucosa hyperkeratosis – focal PPK, oral hyperkeratosis, subungual hyperkeratosis (mutation keratin 16) Pachyonychia congenita type I (Jadassohn-Lewandowsky syndrome) – AD, congenital pachyonychia, hyperhidrosis[visualdx.com]

Workup

Evan's syndrome is a diagnosis of exclusion and implies ruling out other conditions including infections, malignancy and autoimmune diseases like thrombotic thrombocytopenic purpura (TTP). To avoid a misdiagnosis, careful analysis of the direct antiglobulin test (DAT) and peripheral blood smear is critical. It is important to distinguish between primary and secondary Evan's syndrome as it can influence the management. The pattern of occurrence of bicytopenia can delay the diagnosis since it may be coincidental, sequential, or separate, and the time frame between episodes can range from months to years [8] [9].

Laboratory tests include CBC, reticulocyte count, lactate dehydrogenase (LDH), direct bilirubin and haptoglobin levels, peripheral blood smear, direct antiglobulin test (Coombs test), and autoantibodies detection.

Th CBC shows anemia (hemoglobin level <12g/dL), thrombocytopenia (platelet count <100,000/microL), neutropenia (neutrophil count <1500/microL), and increased reticulocyte count if anemia is present. It may also reveal combined cytopenias.

Features of hemolysis can be observed as a raised unconjugated bilirubin, decreased haptoglobin levels, elevated lactate dehydrogenase (LDH) and reticulocyte count.

A positive Coombs test confirms that antibodies targeting red blood cell (RBC) antigens are present. Autoantibodies against platelets and neutrophils may be detected.

The identification of thrombocytopenia along with the presence of spherocytes on the blood smear points to an ongoing immune hemolytic anemia, especially when the reticulocyte count is raised. Observing megakaryocytes in the smear suggests an immune origin for the thrombocytopenia. If cytopenia is present, blood smear evaluation can help in ruling out malignancy or proposing its presence.

A variety of antibodies targeting RBCs, white blood tests (WBCs) and platelets have been associated with Evan's syndrome.

The differential diagnoses of Evan's syndrome consists of drug-induced hemolytic anemia, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and chronic cold agglutinin disease.

Anisocytosis
  • Peripheral blood smear examination showed a marked anisocytosis comprising of macrocytes, polychromatic cells, and microspherocytes. A high percentage of nucleated RBC and thrombocytopenia were also seen [Figure 1] .[ijem.in]
Bone Marrow with Hyperplasia
  • Evidence of hemolysis included hyperbilirubinemia (3.8 mg/dl), an increased LDH (424 U/l), decreased haptoglobin (7 mg/dl), reticulocytosis (corrected reticulocyte count 5.5%), bone marrow erythroid hyperplasia, and a direct Coombs test (DAT) positive[nature.com]

Treatment

  • We also describe current treatment options in pregnancy and briefly discuss the pathophysiology of Evan's syndrome and perinatal outcome.[ncbi.nlm.nih.gov]
  • The patient was treated successfully with clarithromycin, vancomycin, ciprofloxacin and imipenen which appear to be effective in combination for this unusual condition in which the treatment regimen has been controversial.[ncbi.nlm.nih.gov]
  • Each treatment of IViG costs around 6,500 and she just finished up treatment number 8. She will continue to receive these treatments every 2-3 weeks.[gofundme.com]
  • The patient required 4 months of steroid treatment before his platelet levels finally stabilised and he could be put back on his regular medicine regime.[ncbi.nlm.nih.gov]
  • Management and treatment Immunosuppressive therapy combined or not with intravenous immunoglobulin for ITP constitutes the first-line treatment.[orpha.net]

Prognosis

  • Animals suffering from this disease have a poorer prognosis than those with either disease alone.[en.wikivet.net]
  • The prognosis with Evans syndrome is guarded. Some patients have episodes of major blood cell destruction followed by long remissions, while others have chronic problems with no remissions.[autoimmunesociety.org]
  • Evans Syndrome and depression What is Evans Syndrome Evans Syndrome synonyms Evans Syndrome prognosis Which advice would you give to someone who has just been diagnosed with Evans Syndrome? 1 answer[diseasemaps.org]
  • A series of blood tests are performed to confirm this autoimmune disease Prognosis Evan's Syndrome is very serious and has a mortality rate of 7% Full transcript[prezi.com]
  • Prognosis Evans syndrome is a chronic disease with alternating periods of remission and relapse of AIHA and/or ITP despite treatment, which can be associated with significant morbidity and mortality due to severe hemorrhage and infections in case of severe[orpha.net]

Etiology

  • […] thrombocytopenia (a blood disorder characterized by too few platelets which help blood clot) and Coombs' positive hemolytic anemia (an abnormality of the immune system that causes red blood cells to be destroyed prematurely) and have no other known underlying etiology[igliving.com]
  • Definition : A rare, chronic and relapsing autoimmune disorder of unknown etiology, characterized by the presence of immune thrombocytopenia and autoimmune hemolytic anemia.[sideeffects.embl.de]
  • […] sindrom Evans adalah adanya simultan atau sekuensial langsung Coombs positif autoimun anemia hemolitik (AIHA) dalam hubungannya dengan trombositopenia imun yang dimediasi, tanpa etiologi yang mendasari dikenal.[autoimun.weebly.com]
  • The possible etiologies include ABO mismatch, viral infection, post-transplantation lymphoproliferative disease, graft-versus-host disease, and the use of certain immunosuppressive drugs (e.g., calcineurin inhibitors).[dx.doi.org]
  • Conclusion Evans' Syndrome although a rare disorder should definitely be considered in cases presenting with AIHA or AITP occurring simultaneously or in follow up after excluding the causes of known etiology.[amhsjournal.org]

Epidemiology

  • Summary Epidemiology The prevalence in Europe is estimated at 1/1,000,000 but there are no robust epidemiological data available. Clinical description The syndrome can manifest both in childhood or adulthood.[orpha.net]
  • EPIDEMIOLOGY • Evans syndrome is uncommon but not rare; its exact frequency is unknown.[de.slideshare.net]
  • […] developing other autoimmune problems and hypogammaglobulinemia , [23] with recent research finding that 58% of children with Evans syndrome have CD4-/CD8- T cells which is a strong predictor for having autoimmune lymphoproliferative syndrome . [24] Epidemiology[en.wikipedia.org]
Sex distribution
Age distribution

Pathophysiology

  • We also describe current treatment options in pregnancy and briefly discuss the pathophysiology of Evan's syndrome and perinatal outcome.[ncbi.nlm.nih.gov]
  • Pathophysiology The exact pathophysiology of Evans syndrome is unknown. Non-cross-reacting autoantibodies are directed against antigens specific to RBCs, platelets, or neutrophils.[emedicine.medscape.com]
  • Although Evans syndrome seems to be a disorder of immune regulation, the exact pathophysiology is unknown.[myriverside.sd43.bc.ca]
  • Etiology Evans syndrome is an autoimmune disorder in which non-cross-reacting autoantibodies are targeted towards different antigenic determinants on red cells, platelets, sometimes neutrophils; however, the exact pathophysiologic mechanism is unknown[orpha.net]

Prevention

  • This followed shortly after he had started taking orlistat to prevent weight gain from a course of steroids, and once the orlistat was stopped, his platelets began to rise.[ncbi.nlm.nih.gov]
  • Some preventions for Evan's syndrome are to not smoke or drink at an early age. Another prevention is to not loose to much blood. The End Full transcript[prezi.com]
  • The spleen is the place in the body where red blood cells and platelets are broken down, so removing it helps prevent this. Intravenous immune globulin or IVIG may be used.[cafamily.org.uk]
  • There is no treatment to prevent or reverse nerve degeneration in HSP. The molecular basis of spastic paraplegia and Evans syndrome is unknown. Ahmed et al. (1996) reported two Saudi brothers with hereditary spastic paraplegia and Evans syndrome.[cags.org.ae]
  • Because of this, a person without a spleen is wise to take extra precautions to prevent infection or exposure to illness throughout the rest of their life.[evanssyndrome.blogspot.com]

References

Article

  1. Mathew P, Chen G, Wang W. Evans syndrome: results of a national survey. J Pediatr Hematol Oncol. 1997 Sep-Oct.; 19(5):433-7.
  2. Delezé M, Oria CV. Alarcon-Segovia D. Occurrence of both hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) in systemic lupus erythematosus. Relationship to antiphospholipid antibodies. J Rheumatol 1988;15(4):611-615.
  3. García-Muñoz R, Rodriguez-Otero P, Pegenaute C, et al. Splenic marginal zone lymphoma with Evans' syndrome, autoimmunity, and peripheral gamma/delta T cells. Ann Hematol 2009;88(2):177-178.
  4. Hauswirth AW, Skrabs C, Schützinger C, et al. Autoimmune thrombocytopenia in non-Hodgkin's lymphomas. Haematologica 2008;93(3):447-450.
  5. Michel M, Chanet V, Galicier L, et al. Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of literature. Medicine 2004;83(4):254-263.
  6. Teachy DT, Manno CS, Axsom KM, et al. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). Blood 2005;105(6):2443-2448.
  7. Wang W, Herrod H, Pui CH, Presbury G, Wilimas J. Immunoregulatory abnormalities in Evans syndrome. Am J Hematol 1983;15(4):381-390.
  8. Norton A., Roberts I. Management of Evans syndrome. Br J Haematol. 2006;132(2):125–137.
  9. Kohler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256(5517):495–497.

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Last updated: 2018-06-22 10:55