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].

• Fatigue

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

  हैं. en Everything was going smoothly until, as a result of stress and fatigue, he came down with a serious disease. hi कवक परजीवी द्वारा होने वाली महामारी से मक्खियां बहुत मरती हैं. en He who is fatigued in administration of justice will not prosper. [glosbe.com]

  Abstract A 22-year-old man presented to the emergency department with facial swelling, rash, and fatigue. Hehad a past medical history of pericarditis and pericardial effusion. His evaluation showed anemia and thrombocytopenia. [escholarship.org]

  Fatigue/ME referral form - EMIS WEB Chronic Fatigue/ME referral form - Systmone Supporting Information Last updated: 11-10-2022 Home > Referral > Eastern locality > Pain Management > ME/Chronic Fatigue Syndrome Service - Royal Devon University Healthcare [northeast.devonformularyguidance.nhs.uk]

• Pallor

  Signs of anemia include pallor, fatigue, and light-headedness. [de.slideshare.net]

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

  All patients presented an anemic syndrome (pallor = 100%, asthenia = 89%) and 3 had bleeding symptoms. [ejinme.com]

  AIHA manifests as an unusual weakness, pallor, fatigue with tachycardia and exertional dyspnea, and also in some cases jaundice, dark urine and/or splenomegaly. [orpha.net]

• Swelling

  Abstract A 22-year-old man presented to the emergency department with facial swelling, rash, and fatigue. Hehad a past medical history of pericarditis and pericardial effusion. His evaluation showed anemia and thrombocytopenia. [escholarship.org]

  The swelling was predominantly on the right side of his face and upper lip. He had no history of angioedema, had not started any new medications, and was not aware of an environmental exposure that immediately preceded the onset of swelling. [westjem.com]

  Is problem me urine ki quantity badh jati hai, swelling ho jati hai, hypertension ho jata hai. Ye problem mainly bachon me dekhi jati hai. Jo bache ... Metabolic Syndrome Hello Everybody! This is Dr. Muffi from Digestive Health Institute. [lybrate.com]

  • Shortness of breath since 10 days ,insidious onset ,increased on exertion,no orthopnea/ PND,relieved with rest ,not associated with leg swelling. • No h/o of cough ,chest pain,palpitation • No h/o abdominal pain ,vomitings ,loose stools 5. • H/o native [de.slideshare.net]

• Surgical Procedure

  We in the medical profession many times see patients who are suffering and coming for surgical procedures. Unfortunately, most of these people are from the lower and middle income groups. They are made to run from one hospital to another. [loksabhahindi.nic.in]

• Thrombosis

  The risk of thrombosis has been well established in retrospective studies for ITP and AIHA; however, the risk of thrombosis in ES has been limited to case reports and individual case series. [thejh.org]

  These local and systemic factors contribute to all thrombosis, portal/splenic vein thrombosis, deep vein thrombosis, and pulmonary embolus, alike. Local factors and systemic factors that promote thrombosis are centered upon Virchow’s triad. [thrombosisjournal.biomedcentral.com]

  Surgical options like splenectomy would be limited in our patient especially during the COVID-19 pandemic and shunt surgery for correction of the portal vein thrombosis is being considered. [remedypublications.com]

  The main clinical features of primary antiphospholipid syndrome are recurrent foetal loss, arterial or venous thrombosis and thrombocytopaenia. [ncbi.nlm.nih.gov]

  Data including medical history, gynecologic, clinical history of thrombosis, bleeding and anthropometric information will be collected using a questionnaire. [omicsonline.org]

• Oral Ulcers

  She also had a sparse hairline and malar rash with painless oral ulcers. A clinical diagnosis of SLE was made as she met all the American Rheumatology Association criteria for SLE. [sjkdt.org]

  • H/o native medications intake • No h/o joint pains, oral ulcers,no hair loss, no icthing on exposure to sun light • No c/o dryness of mouth ,no redness/grity sensation of eyes, no skin tightness, • No c/o bluish discoloration of hands on exposure [de.slideshare.net]

  There was no erythema, oral ulcer, arthritis, or lymphadenopathy. Laboratory test results are shown in Table 1. [link.springer.com]

• Arthritis

  सन्दर्भ -सामिग्री : (१ )http://rawarrior.com/what-causes-rheumatoid-arthritis-to-trigger/ (२ )https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648 (३ )https://www.webmd.com/rheumatoid-arthritis/ss/slideshow-ra-overview [blogpaksh2015.blogspot.com]

  Evidence for an association between rheumatoid arthritis and autoimmune endocrine disease. Ann. Rheum. Dis. 42 :297, 1983. PubMedCentral PubMed CrossRef Google Scholar 2. Silman A.J., Oilier W.E.R., Bubel M.A. [link.springer.com]

  It has been reported that patients with Evans syndrome have a greater tendency to develop other autoimmune disorders such as lupus and rheumatoid arthritis. Visit Forum [autoimmunesociety.org]

  Rheumatoid arthritis Fibromyalgia Goiter Hashimotos Thyroiditis Lupus (any form) Multiple sclerosis Scleroderma Celiac Disease Graves Disease Psoriasis Sarcoidosis Other (please specify) Question Title * 7. [surveymonkey.com]

  Arthritis Rheum 2003; 48: 1484-92. [ Links ] 12. Reale L, Besa E. Rituximab in autoimmune pancytopenia: a case report and review of literature. Ann Hematol 2007; 86: 913-6. [ Links ] 13. [scielo.conicyt.cl]

• Ulcer

  Therefore, ulcerative PG was favored in our patient. [mdpi.com]

  We have described a case of herpes genitalis in a patient with Evans's syndrome who had violaceous macules leading to deep ulcerations. [ncbi.nlm.nih.gov]

  It is more common with ulcerative colitis than Crohn’s disease, and it is associated with greater disease severity and the presence of concurrent extraintestinal manifestations.17–20 In the two case reports found regarding AIHA and Crohn’s disease; both [casereports.bmj.com]

  She also had a sparse hairline and malar rash with painless oral ulcers. A clinical diagnosis of SLE was made as she met all the American Rheumatology Association criteria for SLE. [sjkdt.org]

  A case of Evans’ syndrome in a patient with ulcerative colitis. Dig Liver Dis 2003; 6: 439-41. Knecht H, Baumberger M, Tobon A, Steck A. Sustained remission of CIDP associated with Evans' syndrome. Neurology 2004; 4: 730-2. [medigraphic.com]

• Seizure

  The symptomatology was: seizures (n=4), cranial nerve palsy (n=2), Brown-Sequard syndrome (n=2) and / or sensory neuronopathy (n=1). No infectious pathogens were identified. [learningcenter.ehaweb.org]

  Image source, Dravet Syndrome UK Image caption, Paige Slocombe with her family from Okehampton, Devon Sam Slocombe said: "Paige stops breathing with her seizures, and wherever she goes, her medical bag goes with her. [bbc.co.uk]

  On top of that, Devan also suffers from seizures, currently having one seizure every day. There is no cure for Aicardi Syndrome, but Devan beat the odds from birth. The odds of having a child born with Aicardi Syndrome are 1 in 500,000. [tapinto.net]

  It is classified as complicated if the impairment present in uncomplicated HSP is accompanied by other systemic or neurologic abnormalities such as ataxia, seizures, cognitive impairment, dementia, amyotrophy, extrapyramidal disturbance, or peripheral [cags.org.ae]

  Because of sudden, unexplained seizures that left her paralyzed and with a permanent tracheotomy, by 1978, Evans could no longer work at a nursing home, instead, she lived in one. [medical-dictionary.thefreedictionary.com]

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.

• Oxygen Saturation Decreased

  Her shortness of breath exacerbated, and her oxygen saturation decreased rapidly. She received endotracheal intubation and mechanical ventilation. Later on, her acid-fast bacilli sputum smear results indicated a grade of 3+. [bmcinfectdis.biomedcentral.com]

Hers is one of few reported cases in which Evans syndrome was treated with rituximab, an alternative to standard treatment regimens, prior to treatment failure or relapse. [consultant360.com]

Corticosteroids and IVIG are the first-line treatment options for Evans syndrome. Rituximab is the preferred second-line treatment. Other treatment options include splenectomy, danazol, and immunosuppressants. [statpearls.com]

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]

[…] syndrome Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Evans syndrome from other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications and Prognosis [wikidoc.org]

Here we assess both frequency and prognosis in Danish children below 13 years of age with ES, and compare their prognosis both with children from the general population and with children who have either isolated AIHA or ITP. [journals.plos.org]

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]

Determining this is important because it can affect treatment and prognosis. No one specific test is used to diagnose Evans syndrome. Instead, a doctor may conduct various tests to rule out other conditions. [healthline.com]

Cytogenetics showed trisomy-12 which is associated with intermediate prognosis for CLL. PET scan done subsequently revealed only a reactive marrow and an enlarged 15.8cm non-hypermetabolic spleen. [mdedge.com]

The etiology and pathogenesis of the syndrome are not fully clarified [10]. [panafrican-med-journal.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]

Etiology: ▪ The exact cause of Evans syndrome is not known. ▪ Disorders of the immune system like Evans syndrome occur when the immune system produces antibodies that mistakenly attack healthy tissue, specifically red blood cells, platelets, and white [slideshare.net]

={Journal of Pediatric Hematology/Oncology}, year={1988}, volume={10}, pages={330–338} } Evans syndrome is defined as the simultaneous or sequential occurrence of Coombs' positive hemolytic anemia and immune thrombocytopenia without known underlying etiology [semanticscholar.org]

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

For patient information click here Evans syndrome Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Evans syndrome from other Diseases Epidemiology and Demographics Risk Factors [wikidoc.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]

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

For patient information click here Evans syndrome Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Evans syndrome from other Diseases Epidemiology and Demographics Risk Factors [wikidoc.org]

@article{Wang1988EvansSI, title={Evans Syndrome in Childhood: Pathophysiology, Clinical Course, and Treatment}, author={Winfred C. [semanticscholar.org]

Discussion Evans syndrome is a rare autoimmune regulation disorder whose exact pathophysiology is unknown. [scielo.br]

The pathophysiology and etiology remain unclear. 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). [symptoma.com]

| Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies Case Studies Case #1 Template:Hematology Template:WikiDoc Sources [wikidoc.org]

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]

Our Blood Disorders Center provides comprehensive diagnostic, treatment, and preventive services for a wide range of non-malignant blood disorders, including Evans syndrome. [childrenshospital.org]

Vaccines are expected to prevent further spread and aggravation of COVID-19. [link.springer.com]

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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.
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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.