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].

• Palpable Spleen

  – Liver not palpable – Spleen-not palpable • Percussion: – No evidence of ascites • Auscultation : – No abnormality detected – No hepatic bruit and renal bruit – Bowel sounds are heard 12. • Respiratory system: –Normal vesicular breath sounds are heard [slideshare.net]

• Generalized Lymphadenopathy

  • General physical examination: – Pt Is Conscious,coherent, –pallor ,icterus – ,no cyanosis/clubbing/pedal edema – No generalized lymphadenopathy – No purpura ,petechiae – No markers of tuberculosis – No markers of connective tissue disorders 9. • Vital [slideshare.net]

• Fatigue

  Signs and symptoms may include purpura, paleness, fatigue, and light-headedness. The exact cause of this condition is unknown. [aarda.org]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019 [patientslikeme.com]

  The condition can cause serious complications including fatigue, yellowing of the skin, increased heart rate and enlargement of the liver and spleen. [childrensdmc.org]

• Wheelchair Bound

  He was wheelchair-bound, although with physiotherapy, he was able to walk again at the age of 8-years. His 9-year old brother was also diagnosed with congenital spastic diplegia at the age of 14-months. [cags.org.ae]

• Plethora

  Doctors will test for a plethora of illnesses before diagnosing a patient with Evans Syndrome. Doctors will do a CBC which will tell them your complete blood count and a Coombs test which identifies the cause of anemia. [evanssyndromefoundation.org]

• Hepatic Bruit

  – Liver not palpable – Spleen-not palpable • Percussion: – No evidence of ascites • Auscultation : – No abnormality detected – No hepatic bruit and renal bruit – Bowel sounds are heard 12. • Respiratory system: –Normal vesicular breath sounds are heard [slideshare.net]

• Distractibility

  Essentially, the IVIG distracts your immune system temporarily so that the platelets are not destroyed as rapidly. IVIG is not as effective in AIHA or AIN. [verywellhealth.com]

• Focal Neurological Deficit

  • Respiratory system: –Normal vesicular breath sounds are heard • Cardiovascular system: –S1 S2 ,systolic murmer present • Nervous system :No focal neurological deficit 13. • LAB REPORTS: • CBP: Hb -3.6 gm/dl mcv-98 f/l wbc-10,000 PLT-60,000 Dengue [slideshare.net]

• Lower Extremity Spasticity

  Hereditary spastic paraplegia (HSP) is a group of clinically and genetically diverse disorders characterized by lower extremity spasticity and weakness. [cags.org.ae]

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.

• Reticulocyte Count Decreased

  On day 25 platelet count was 169,000/cmm and Reticulocyte count decreased to 2.5%. He was discharged and followed in the out patient clinic. Five months later, his hemoglobin was 11.2 gms/dl, platelet count 250.000/cmmm, and reticulocyte count 1.5%. [jpma.org.pk]

Table 3 - Clinical presentation, treatment, and relapse of six patients diagnosed with Evans syndrome. # Clinical presentation Treatment Response time after first-line treatment (days) PLT (109/L) Hb (g/dL) Relapse C.P. of relapse Treatment after relapse [scielo.br]

Management and treatment Immunosuppressive therapy combined or not with intravenous immunoglobulin for ITP constitutes the first-line treatment. [orpha.net]

Treatment & Care The first-line treatments for Evan’s syndrome are corticosteroid, such as prednisone, and intravenous immunoglobulin, which help to control acute episodes. Most children respond to this treatment, but relapses frequently occur. [danafarberbostonchildrens.org]

Treatment There is a long list of possible treatments. [verywellhealth.com]

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]

In conclusion, we found that both primary and secondary Evans syndrome conferred a poor prognosis. Lethal complications probably derive primarily from manifestations of underlying autoimmune hemolytic anemia and immune thrombocytopenia. [onlinelibrary.wiley.com]

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]

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]

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]

[…] 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]

This fact suggested an infectious etiology of ES as it was associated with elevated IgG antibody titers for cytomegalovirus. [elsevier.es]

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]

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]

Southern Denmark, Grant/Award Number: 16/13496; University of Southern Denmark, Grant/Award Number: SDUSF‐2015‐202‐(459) Abstract Patients with Evans syndrome have both immune thrombocytopenia and autoimmune hemolytic anemia, but little is known about the epidemiology [onlinelibrary.wiley.com]

EPIDEMIOLOGY • Evans syndrome is uncommon but not rare; its exact frequency is unknown. [slideshare.net]

We also describe current treatment options in pregnancy and briefly discuss the pathophysiology of Evan's syndrome and perinatal outcome. [ncbi.nlm.nih.gov]

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]

Pathophysiology The exact pathophysiology of Evans syndrome is unknown, although the mechanism generally seems to be related to the one associated with autoimmune hemolytic anemia and immune thrombocytopenia. [emedicine.medscape.com]

Although Evans syndrome seems to be a disorder of immune regulation, the exact pathophysiology is unknown. [myriverside.sd43.bc.ca]

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]

Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. [thrombosisjournal.biomedcentral.com]

There is no treatment to prevent or reverse nerve degeneration in HSP. Saudi Arabia Ahmed et al. (1996) reported two Saudi brothers with hereditary spastic paraplegia and Evans syndrome. They were born to a first cousin parents. [cags.org.ae]

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]

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]

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.