Rare but not forgotten, a case of evan's syndrome. Free

A 46-year-old woman with a history of sickle cell trait presented with several weeks of fatigue, nausea, vomiting, and shortness of breath. On examination, she was febrile (100.3°F), tachycardic (118 bpm), and normotensive (BP 125/92 mmHg). Jaundice and cervical and axillary lymphadenopathy were noted on initial examination. Laboratory evaluation revealed severe anemia (hemoglobin 3.4 g/dL), leukocytosis (WBC 9.1 ×10³/μL), and thrombocytopenia (platelet count 19 ×10³/μL). Additional findings included MCV 66 fL, reticulocyte count 2.0%, LDH 574 U/L, total bilirubin 7.3 mg/dL, and haptoglobin <30 mg/dL. Peripheral smear demonstrated microcytic anemia with hemolytic features, but no schistocytes or sickled cells. Ferritin was elevated at 722.6 ng/mL. The direct antiglobulin test was positive for both IgG and C3. These lab tests in addition to her clinical presentation was suggestive of an autoimmune hemolytic anemia. The combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) was suggestive of Evans syndrome. The patient received intravenous methylprednisolone followed by oral prednisone. Hemoglobin and platelet count improved to 7.8 g/dL and 152 ×10³/μL, respectively, within five days. CT imaging revealed small cervical, axillary, and mediastinal lymphadenopathy, along with mild splenomegaly. Lymph node biopsy showed reactive changes without evidence of lymphoproliferative disease, and blood flow cytometry was unremarkable. Other causes of hemolytic anemia were ruled out such as Human Immunodeficiency Virus (HIV), and Epstein Bar Virus (EBV). An incidental thyroid enlargement was noted, with suppressed TSH (<0.01 mIU/mL) and normal T4 and T3 levels. Autoimmune workup revealed positive antinuclear antibodies (ANA >1:80), positive thyroid peroxidase and thyroglobulin antibodies, negative anti-dsDNA and antiphospholipid antibodies, low C4 with normal C3. These autoimmune antibodies being positive favors this patient to have a dysregulatory immune pathway suggestive of Evans Syndrome, and this patient is currently being worked up for an autoimmune thyroiditis in the outpatient setting.

Evans syndrome was first described in 1951 by Dr. Robert Evans, who reported four patients with acquired autoimmune hemolytic anemia, thrombocytopenia, and positive direct antiglobulin tests. The estimated incidence is 1–9 cases per million per year. The current diagnostic definition includes the simultaneous or sequential presence of at least two autoimmune cytopenias: AIHA, ITP, or autoimmune neutropenia. Emerging evidence suggests Evans syndrome reflects a broader immune dysregulation rather than a coincidental clustering of cytopenias. A higher prevalence of positive ANA and antithyroid antibodies has also been observed, supporting this hypothesis. Approximately half of all cases are associated with underlying conditions such as infections, inborn errors of immunity, or systemic autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis. A systematic review of 10 studies reported universal use of corticosteroids as first-line therapy, with rituximab used in 18.4% and splenectomy in 16% of cases. The overall mortality rate was 40%. This case highlights the importance of recognizing Evans syndrome as a potential manifestation of immune dysregulation. Thorough evaluation for underlying autoimmune, infectious, or lymphoproliferative disorders is essential to guide treatment decisions and inform prognosis.