Abstract: FR-PO0902
Targeting Interferon-γ in Autoimmune Hemophagocytic Lymphohistiocytosis (HLH): A Case of Lupus-Associated HLH Responding to Emapalumab
Session Information
- Glomerular Case Reports: Lupus, FSGS, Complement, and More
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Alnemer, Faisal Khalid, King Abdulaziz Medical City in Riyadh, Riyadh, Riyadh Province, Saudi Arabia
- Alsadhan, Abdulmajeed Abdullah, King Abdulaziz Medical City in Riyadh, Riyadh, Riyadh Province, Saudi Arabia
- Tawhari, Mohammed Hadi, King Abdulaziz Medical City in Riyadh, Riyadh, Riyadh Province, Saudi Arabia
- Alzahrani, Nora Mohsin M, King Abdulaziz Medical City in Riyadh, Riyadh, Riyadh Province, Saudi Arabia
Introduction
Emapalumab is a monoclonal antibody that targets interferon-gamma (IFN-γ), FDA-approved for primary (familial) HLH, particularly in refractory, recurrent, or progressive cases or when patients are intolerant to conventional therapy. Its use in secondary HLH (sHLH) triggered by infections, malignancies, or autoimmune diseases is less defined. Though not part of formal sHLH guidelines, expert consensus suggests it may be considered in refractory cases with suspected IFN-γ hyperactivity when standard treatments fail.
Case Description
A 31-year-old female with longstanding systemic lupus erythematosus (SLE) presented with refractory disease activity characterized by persistent hypocomplementemia, elevated anti-dsDNA titers, and worsening proteinuria. Kidney biopsy confirmed class IV-A lupus nephritis. Despite induction with intravenous methylprednisolone and subsequent escalation to cyclophosphamide, belimumab, and rituximab, her kidney function deteriorated and was admitted to initiate dialysis. During hospitalization she developed refractory shock associated with pancytopenia, transaminitis, and high-grade fevers. Work up revealed hyperferritinemia and hypertriglyceridemia; bone marrow biopsy confirmed HLH. Her HLH gene panel was negative, favouring sHLH due to SLE. She failed initial treatment with etoposide, dexamethasone and intravenous immunoglobulin. Due to refractory HLH, she was started on emapalumab, resulting in significant clinical and laboratory response. Emapalumab was then tapered over 14 months.
Discussion
Secondary HLH is a rare but life-threatening complication of autoimmune disease like SLE. The diagnosis is particularly challenging due to overlapping features with lupus flares, including cytopenias, fever, organomegaly, and elevated ferritin levels. Our patient met HLH criteria and failed standard therapy. Emapalumab led to marked clinical improvement. Although approved for primary HLH, this case supports its off-label use in refractory autoimmune-associated HLH and demonstrates its safety in long-term use.