Mixed Autoimmune Hemolytic Anemia as the Initial Manifestation of Systemic Lupus Erythematosus: A Case Report

Mixed autoimmune hemolytic anemia (mAIHA) is a rare subtype of autoimmune hemolytic anemia (AIHA) characterized by the coexistence of warm (immunoglobulin G (IgG)) and cold (immunoglobulin M (IgM)) autoantibodies. It may occur as a primary disorder or secondary to underlying conditions, including systemic lupus erythematosus (SLE). We report the case of a 16-year-old female who presented with severe hemolytic anemia as the initial manifestation of SLE. On admission, her hemoglobin was 34 g/L with marked reticulocytosis and a positive direct antiglobulin test (DAT) demonstrating both IgG and IgM antibodies, confirming mAIHA. Immunological investigations revealed positive antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, and anti-Smith antibody, supporting a diagnosis of SLE. At the time of the first presentation, she had no other clinical features suggestive of SLE. She was treated with blood transfusions and corticosteroids, resulting in significant improvement, and was discharged on a tapering prednisolone regimen. Shortly after, she was readmitted with a malar rash, arthralgia, joint swelling, nephrotic-range proteinuria, and worsening renal function. She was subsequently diagnosed with SLE complicated by lupus nephritis and recurrent AIHA. Following the rheumatology and nephrology review, she received intravenous methylprednisolone and was transferred to a tertiary care center for renal biopsy and further management. Renal biopsy demonstrated focal segmental glomerulosclerosis (FSGS). Further treatment with prednisolone, mycophenolate mofetil, intravenous belimumab, and hydroxychloroquine resulted in an excellent clinical response, with follow-up confirming remission. This case highlights mAIHA as a rare initial presentation of SLE and underscores the importance of early recognition, close monitoring, and multidisciplinary management, as patients presenting with AIHA may be at increased risk of developing lupus nephritis and other severe SLE-related complications.