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].

• Splenomegaly

  Physical examination indicated splenomegaly but was otherwise unremarkable with no petechiae or rash. [journalmc.org]

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

  CT abdomen/pelvis: enlarged paraaortic lymph nodes, without splenomegaly. Bone marrow biopsy/aspirate and LN biopsy: negative for evidence of malignancy or infection. Patient was managed with prednisone and topiramate. [authorea.com]

  This veteran having anemia, positive DAT, thrombocytopenia, and splenomegaly got diagnosed with Evans’s syndrome. This syndrome was the initial manifestation of his underlying CLL. [mdedge.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]

• Splenectomy

  However, the cytopenia normalized after a splenectomy. Keywords: Autoimmune hemolytic anemia ; Idiopathic thrombocytopenic purpura ; Liver transplantation ; Splenectomy [dx.doi.org]

  Splenectomy is one of the treatment options for disease refractory to medical therapy. Venous thromboembolism (VTE) following splenectomy for hematological diseases has an incidence of 10%. [thrombosisjournal.biomedcentral.com]

  However both relapsed and subsequently underwent splenectomy at ten and nine months, respectively. [scielo.br]

  However, the cytopenia normalized after a splenectomy. [ekjm.org]

• Fatigue

  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]

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

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

• Pallor

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

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

  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]

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

• Weight Loss

  Protein Only Diet Average Weight Loss Alli Weight Loss Pills Uk Reviews Protein Only Diet Average Weight Loss Selling Best Diet Pills Lilly Weight Loss Medication. [ulysse-transport.fr]

  Sarah E Evans Weight Loss Plan Meal Prep Delivery Services For Weight Loss Sarah E Evans Weight Loss Plan Top 5 Best Best Diet Pills Phd Diet Whey Good For Weight Loss. [slcrb.by]

  The most frequent symptoms on presentation are weight loss, weakness and abdominal pain. Diagnosis of diffuse hepatic angiosarcoma can be challenging. [casesjournal.biomedcentral.com]

  There was also a history of weight loss, hair loss, oral ulcers and polyarthralgia. Clinically, she had severe pallor and petechiae on the upper and lower limbs, icterus, pedal edema and mild splenomegaly. [sjkdt.org]

  […] and insomnia; extreme fatigue; abrupt changes of mood; flawed judgment and thinking; bouts of crying; appetite changes, with resultant weight loss or gain; a variety of symptoms of disturbed health; lethargy; reduced work capacity; hallucinations —feeling [glosbe.com]

• Aspiration

  Bone marrow biopsy/aspirate and LN biopsy: negative for evidence of malignancy or infection. Patient was managed with prednisone and topiramate. [authorea.com]

  Bone marrow aspiration; discreetly decrease megakaryocytes present, morphologically show immature, polysegmentation of neutrophils and cell gigantism. Currently there are no reports of the prevalence of this syndrome in Mexico. [medigraphic.com]

  Coombs test – a blood test that identifies the cause of anemia Reticulocyte count – a blood test that measures how fast new red blood cells called reticulocytes are made by bone marrow and released into the blood Other tests may include bone marrow aspiration [danafarberbostonchildrens.org]

  Fine needle aspiration cytology of axillary lymph node showed reactive hyperplasia. [amhsjournal.org]

  Figures Figure 1: multiple myeloma– cytology: magnification x 100: diffuse infiltration of the bone marrow aspiration by mature plasma cells. [panafrican-med-journal.com]

• Dyspnea

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

  Case Report A 74 years old Veteran presented with complaints of fatigue and worsening dyspnea on exertion. His physical exam was unremarkable except jaundice. [mdedge.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]

  Generalized fatigue and dyspnea are commonly encountered symptoms across medical specialties. Evaluation of these symptoms often may reveal anemia and thrombocytopenia. [consultant360.com]

• Exertional Dyspnea

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

• 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 [slideshare.net]

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

• Ulcer

  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]

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

  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]

• Erythema

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

  Batten disease バッテン病 Frederick Eustace Batten（1865-1918） English neurologist and pediatrician Battle バトル Battle's sign バトル徴候 William HenryBattle （1856-1936） English surgeon Bauhin バウヒン Bauhin's valve バウヒン弁 Bayes ベイズ Bayes theorem ベイズの定理 Bazin バザン Bazin's erythema [jams.med.or.jp]

• Skin Rash

  A 34-year-old lady presented with complaints of breathlessness on exertion and skin rash of two weeks' duration and decreased urine output of two days. Further history revealed that she had an abortion five months ago. [sjkdt.org]

• Eruptions

  Annual Conference Orlando, FL Unilateral Impaction of a Primary Canine: A Case Report, Stern R, Stinton NM, Uston KA Pulpal Revascularization: Comparison of Techniques in Prevention of Coronal Staining, Guzzardi JR, Uston KA, Stern R, Stinton NM Pre-eruptive [geisinger.edu]

• Malar Rash

  A petechial rash was observed on his upper chest, bilateral shoulders, tongue, and soft palate (Image 2). A malar rash was also noted (Image 3). The remainder of his examination was normal. [westjem.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]

  Concurrent or sequential thrombocytopenia and/or neutropenia could represent Evans syndrome Lymphadenopathy could indicate the presence of chronic lymphocytic leukemia or other lymphoproliferative disorder A malar rash and/or arthritis might suggest systemic [cancertherapyadvisor.com]

• Hematuria

  A 64-year-old male with past medical history significant for hypertension, hyperlipidemia, diabetes mellitus and coronary artery disease, presented to the emergency room complaining of a 2-week history of chest pain, shortness of breath and hematuria. [journalmc.org]

  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. [symptoma.com]

  In case of severe thrombocytopenia, hematuria, gastrointestinal and/or cerebromeningeal hemorrhage may be observed in rare cases. [orpha.net]

• Renal Injury

  Interest in the role of free hemoglobin in renal injury is well-documented in experimental and clinical studies dating over the past 50 or more years [10–13]. [hindawi.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.

• Cytopenia

  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. [symptoma.com]

  The cytopenia improved transiently after the second dose of rituximab, but soon worsened again. However, the cytopenia normalized after a splenectomy. [dx.doi.org]

  Though rare, physicians should maintain high suspicion for this syndrome in patients with multi-lineage cytopenia which are usually not even responding well to the common treatment for cytopenia. [mdedge.com]

  Median age at onset of cytopenias was 9 years (range 2–15 years) and median follow-up time was 4 years (range 1–17 years). At presentation multiple cytopenias were found in five children (42%). [frontiersin.org]

  Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. [hemonc.theclinics.com]

• Leukocytes Decreased

  After the methylprednisolone doses, hydrocortisone (9 mg/kg/day) was continued and a progressive increase in hemoglobin levels was observed, with normal red blood cell indices, leukocyte decrease with conserved differential cell lines and normal platelet [elsevier.es]

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]

Jesse says the treatment with bortezomib has worked exceptionally well. “After years of treatment for Cole, I see a big difference with this medical treatment. Cole has not really had side effects from it and his relapses are significantly shorter. [childrensdmc.org]

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

Other treatment options include immunosuppressive drugs.[1] Most affected individuals respond to these treatments; however, relapse is frequent.[6] In people who do not respond to standard treatments, therapy with rituximab may be considered. [rarediseases.info.nih.gov]

[…] 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]

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]

Animals suffering from this disease have a poorer prognosis than those with either disease alone. [en.wikivet.net]

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]

Given that both primary and secondary Evans syndrome confer a poor prognosis, “suspicion of Evans syndrome should prompt vigilant clinical follow-up.” Reference 1. Hansen DL, Möller S, Andersen K, Gaist D, Frederiksen H. [hematologyadvisor.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]

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

[…] 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]

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]

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]

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]

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]

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]

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

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

| 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]

Early intervention and management can prevent mortality and morbidity. [journalmc.org]

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]

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