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

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

  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: May 12, 2019 [patientslikeme.com]

• 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]

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.