Refractory Autoimmune Hemophagocytic Lymphohistiocytosis in Adults: Multi-therapy Failure and the Limits of Salvage Transplantation

This article presents a case of refractory autoimmune-associated hemophagocytic lymphohistiocytosis (HLH) complicating systemic lupus erythematosus in a young adult. It highlights the diagnostic difficulty created by overlapping features of infection, autoimmune flare, and cytokine-driven hyperinflammation, and details disease progression despite corticosteroids, etoposide, multiple biologic agents, and consideration of hematopoietic stem cell transplantation (HSCT). The discussion broadens to review the epidemiology of autoimmune-triggered HLH in adults, reported response rates to cytokine-directed therapies, the limited role and toxicity of salvage cytotoxic regimens, and contemporary HSCT outcomes, which demonstrate variable survival but remain the only potentially curative strategy in selected patients. Clinicians managing patients with severe or treatment-resistant autoimmune disease should maintain a low threshold for suspecting HLH when cytopenias, hyperferritinemia, or unexplained organ dysfunction emerge. Early calculation of the HScore and prompt initiation of therapy are critical to reducing diagnostic delay. While definitive management requires control of the underlying immune dysregulation, treatment of active hyperinflammation should not be postponed during ongoing evaluation and multidisciplinary planning.