Case Presentation: A 66-year-old female with metastatic small cell lung cancer involving brain, liver, and bones was admitted via ED with generalized weakness, mild confusion, and decreased oral intake for 3 days. She was initiated on immunotherapy with immune checkpoint inhibitors, ipilimumab (human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody) and nivolumab (a programmed death receptor-1 (PD-1) blocking antibody), a week before this presentation. The patient also complained of a skin rash for a day. Physical exam showed diffuse petechial rash most notably on the abdomen and lower extremities. Laboratory results showed a hemoglobin of 9.4 g/dL, white blood cell count of 6.8 k/uL, platelet count of < 5 k/uL, red blood cell distribution width of 15.1%, total bilirubin elevated at 1.9 mg/dL, conjugated bilirubin at 1.2 mg/dL. The patient was transfused multiple units of platelets without a meaningful rise in platelet count. Peripheral smear showed no schistocytes. Further investigations showed a haptoglobin of < 10 mg/dL (40-219), LDH elevated at 883 U/L (116-215), positive direct anti-human globulin (Coombs, DAT) test with both anti-IgG and anti-C3d anti-human globulin (AHG) positive. A formal diagnosis of immune checkpoint inhibitor-related Evans syndrome with immune thrombocytopenia (ITP) and warm antibody autoimmune hemolytic anemia (AIHA) was made and the patient started on oral prednisone 1 mg/kg but shortly thereafter she chose to go home on hospice.
Discussion: Evans syndrome is a rare autoimmune disorder characterized by the simultaneous occurrence of AIHA and ITP with or without the presence of immune neutropenia. Evans syndrome can be idiopathic or primary in about half of the cases and secondary due to an underlying disorder in the rest. Secondary causes include autoimmune diseases, immunodeficiency syndromes, lymphomas, chronic myelomonocytic leukemia, monoclonal gammopathy of unknown significance, Hepatitis C, congenital asplenia, and Idiopathic CD4 lymphocytopenia.Checkpoint inhibitors are immunomodulatory antibodies used to enhance the immune system to treat cancer. The main targets of these antibodies are PD-1 (nivolumab), PD-Ligand 1, and CTLA-4 (ipilimumab). Checkpoint inhibitors have shown promise in treating multiple malignancies but can cause immune-related adverse events (irAEs) due to enhanced immunity. These adverse events can affect all the systems but common are skin manifestations, diarrhea-colitis, hepatotoxicity, endocrinopathies, and pneumonitis. Hematologic manifestations are rare and can include red cell aplasia, neutropenia, thrombocytopenia, acquired hemophilia A, and cryoglobulinemia. We described here a rare case of Evans syndrome in a patient receiving checkpoint inhibitors.
Conclusions: Evans syndrome is one of the irAEs associated with checkpoint inhibitors. Evans syndrome should be considered when patients present with concurrent anemia and thrombocytopenia.