Fulminant Seronegative Systemic Lupus Erythematosus With Class IV/V Lupus Nephritis and Multisystem Involvement

Seronegative systemic lupus erythematosus (SLE) poses a diagnostic challenge, particularly when patients develop organ-threatening disease despite negative traditional serologies. We report a fulminant case in a 24-year-old woman with congenital atrioventricular (AV) block, chronic pancytopenia, chronic kidney disease (CKD), and morbid obesity, who presented with progressive anasarca, dyspnea, dizziness, and cough. Laboratory evaluation revealed severe pancytopenia, nephrotic-range proteinuria 11-13 g/day (reference range: 0-150 mg/24 hours), and acute kidney injury. Renal biopsy demonstrated Class IV proliferative and Class V membranous lupus nephritis, despite negative antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-Smith (anti-Sm) antibodies, anti-Sjögren's-syndrome-related antigen A (SSA) and antigen B (SSB) antibodies, and normal complement levels. Within 24 hours, she developed hypoxia, hemoglobin drop, and a right subcapsular renal hematoma. Echocardiography revealed dilated cardiomyopathy, severe aortic insufficiency with valvular vegetation, and suspected pacing-induced cardiomyopathy, progressing to cardiogenic shock requiring inotropes. She developed necrotizing mucocutaneous lesions, vasculitic purpura, pseudomembranous colitis secondary to Clostridioides difficile (C. difficile), and microangiopathic hemolysis. Despite high-dose steroids and mycophenolate, her condition deteriorated, necessitating transfer for plasmapheresis and rituximab. Seronegative SLE represents up to 5% of cases and is often associated with severe, multisystem involvement. Seronegativity may reflect low antibody titers, immune complex sequestration, or assay variability. This case underscores that negative serologies do not exclude SLE, and early recognition through clinical suspicion and tissue biopsy is critical. Aggressive immunosuppression and multidisciplinary care are essential in managing fulminant seronegative lupus with severe nephritis, vasculopathy, and systemic complications.