Case Presentation: A 27 year old previous healthy male presented to the Emergency Department with 4 days of progressive fatigue and scleral icterus. These symptoms were preceded by 2 days of a nonproductive cough. Upon presentation, the patient’s labs were notable for an indirect hyperbilirubinemia of 5.9 mg/dL. Complete blood count revealed a macrocytic anemia with a hemoglobin of 5.3 g/dL and a pronounced thrombocytopenia of 10×103/µL. The white blood cell count and differential remained within normal limits. Thrombotic thrombocytopenic purpura was unlikely given absence of schistocytes and presence of spherocytes on peripheral smear review. Given the aggregate findings of acute anemia, thrombocytopenia, and indirect hyperbilirubinemia, further workup for acute hemolysis was obtained, revealing an elevated lactate dehydrogenase, and undetectable haptoglobin levels. The patient was admitted to the medical ward and started on daily oral dexamethasone and IVIG given suspected concurrent AIHA and ITP. A comprehensive secondary workup for precipitating causes was negative except for a positive polymerase chain reaction test for SARS-CoV-2. A direct antiglobulin test (DAT) resulted positive for IgG, confirming warm autoimmune hemolytic anemia (WAHA). Upon further review of medical history, the patient endorsed a prior history of Evan’s Syndrome when he was 7 years old. Without evidence of alternative inciting factors, the etiology for the patient’s relapsed Evan’s Syndrome was attributed to COVID-19 infection. To reduce mortality and improve sustained remission, the patient received rituximab in addition to oral prednisone at 2 mg/kg daily. The patient’s cytopenias improved by hospital day 10 with a hemoglobin of 9.2 g/dL and platelet count of 173×103/µL. He was discharged in stable condition and completed four weekly ritxumab infusions with a continued steroid taper.
Discussion: Evan’s syndrome is a rare condition consisting of an autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) or, unusually, autoimmune neutropenia. Epidemiologically, Evan’s syndrome is estimated to comprise 0.8 – 3% of patients diagnosed with an AIHA or ITP. Primary Evan’s syndrome is most frequently diagnosed in the pediatric population. Secondary Evan’s is triggered by various malignancies, viral infections, and other autoimmune conditions. Medical knowledge of the novel SARS-CoV-2 virus is rapidly expanding. Cytopenia and coagulopathy are well known complications of infection, with relapses in various autoimmune diseases now being described. Our case presents a patient with a history of Evan’s syndrome during childhood without prior relapse, admitted for AIHA and ITP following SARS-CoV-2 infection.
Conclusions: Our case illustrates a relapse of Evan’s syndrome in the setting of severe COVID-19 pneumonia. Upon literature review, scant evidence exists specifically regarding the onset of relapsed Evan’s syndrome secondary to COVID-19 infection. Angileri et al. have proposed a plausible mechanism associating COVID-19 and AIHA via similar immunogenic epitope peptide sequences on the RBC cell membrane and SARS-CoV-2 spike protein. To date no pathophysiologic mechanisms have been proposed to elucidate the association between SARS-CoV-2 and ITP. This case serves to underscore relative diagnostic uncertainty while awaiting a comprehensive laboratory workup and to inform the medical community that severe autoimmune hematologic complications may develop in patients with acute SARS-CoV-2 infection.