Mixed autoimmune hemolytic anemia as a rare initial presentation of systemic lupus erythematosus Free

Introduction: Autoimmune hemolytic anemia (AIHA) is a rare disorder in which autoantibodies produced by the immune system attach to red blood cells, leading to their premature destruction. It is primarily divided into warm IgG antibodies (65% prevalence), cold C3 antibodies (15-20% prevalence), and mixed IgG and C3 antibodies (10% prevalence) based on antibody agglutination temperature. Mixed autoimmune hemolytic anemia (MAIHA) is an exceedingly rare disorder that usually presents as severe anemia with a median hemoglobin of 6. We report a rare case of a patient who presented with MAIHA as an initial presentation of SLE.

Case Description:A 22-year-old Hispanic female, with no past medical history, presented to the emergency department with complaints of RUQ abdominal pain, fatigue, and dark discoloration of urine for 2 weeks. Initial labs showed a hemoglobin of 5.3 g/dL, an RBC count of 1.28 million/mcL, MCV of 126 fL, an elevated total bilirubin of 2.7 mg/dL (with an indirect bilirubin of 2.1 mg/dL), a high LDH of 278 U/L, and a significantly low haptoglobin of less than 30 mg/dL. The Direct Coombs Test (DAT) was positive with both polyspecific and C3 reagents, and the Antibody Screen was positive on both the Immediate Spin and Prewarm Indirect Coombs tests. Furthermore, a positive antibody screen was noted, and both warm and cold autoantibodies were identified. Iron studies, folate, and B-12 levels were within normal limits.

The patient was started on immunosuppressive therapy for mixed autoimmune hemolytic anemia with prednisone 1 mg per kilogram divided into twice daily dosing and IVIG 1g/kg for two doses. She did not receive any blood transfusion because of no overt signs of bleeding and lack of availability of cross-matched blood. Her hemoglobin improved to 5.8 after the first dose of steroids and IVIG.

On further testing, infectious workup was negative for influenza virus, RSV, SARS-CoV-2, HIV, hepatitis panel, EBV, and CMV. C4 levels were low at 9, and C3 levels were normal. Her ANA screen was positive, and the double-stranded DNA antibody level was 18 UL/ml. The patient met SLICC criteria for SLE, manifested with positive ANA by IFA 1:1280, positive dsDNA, low complement level, and hemolytic anemia.

The patient continued to improve on prednisone. She was discharged on the eighth day of her hospitalization on oral prednisone at 45 mg twice daily. Her hemoglobin on the day of discharge was 7.6 g/dL, hematocrit 21.7%, and the RDW was 24.5%

Discussion: MAIHA is associated with autoimmune diseases, lymphoproliferative disorders, and infections. SLE is the most common autoimmune disorder associated with mixed AIHA. Autoimmune hemolysis occurs in about 10% of patients with SLE; however, MAIHA is rarely the presenting feature.

The primary treatment of MAIHA is corticosteroid therapy and avoiding exposure to cold. Our patient achieved remission with steroids and IVIG. We preferred IVIG as it is faster acting than rituximab and has fewer side effects. IVIG inhibits extravascular hemolysis by saturating the reticuloendothelial system. Most patients require more than one therapeutic intervention for AIHA.Conclusion: This case highlights that although rare, SLE can present with MAIHA. SLE should be considered as one of the causes of MAIHA, and clinicians should have a high clinical suspicion for it.