Systemic Lupus Erythematosus Presenting With Cold-Antibody Autoimmune Hemolysis and Nephritis: A Case Report

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder that presents with a wide array of clinical features, including autoimmune hemolysis and nephritis. Autoimmune hemolysis in SLE is typically linked to warm antibodies, but the occurrence of cold agglutinin syndrome (CAS), driven by cold-reactive antibodies, is exceptionally rare. Lupus nephritis (LN) is among the most severe complications of SLE, characterized by immune complex-mediated glomerulonephritis, which often leads to considerable morbidity and mortality. Nephritis in SLE is a major indicator of chronic kidney disease, with many patients experiencing progressive renal damage over time. Early diagnosis and individualized treatment approaches are crucial for effectively managing these intertwined conditions. This case report presents a distinct clinical scenario involving a 53-year-old Hispanic female diagnosed with SLE, who concurrently presented with CAS and nephritis. The patient's initial symptoms included chest pain, severe macrocytic anemia, elevated creatinine levels, and evidence of active hemolysis. CAS was diagnosed through a positive direct antiglobulin test for C3d and elevated cold agglutinin titers. Further comprehensive assessments revealed dysgammaglobulinemia, hypocomplementemia, and positive anti-Ro antibodies, with a renal biopsy confirming LN (ISN/RPS Class IV and Class V). The patient exhibited a favorable response to a treatment regimen comprising high-dose steroids and anti-CD20 therapy, resulting in the complete cessation of hemolysis and a >50% decrease in proteinuria after six months. This case underscores the rarity of CAS in the context of SLE, particularly when coupled with nephritis, and highlights the need for tailored treatment strategies. Anti-CD20 therapy, as used in primary CAS management, emerges as a promising option for this unique presentation, offering insights into the complex interplay of autoimmune conditions.