Severe Treatment-Refractory Macrophage Activation Syndrome-Hemophagocytic Lymphohistiocytosis Presenting With Neurologic Crisis in Systemic Lupus Erythematosus

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by uncontrolled activation of macrophages and cytotoxic lymphocytes, resulting in multi-organ dysfunction and high mortality if not promptly recognized. HLH can arise from genetic immune dysregulation or secondary to autoimmune disease, infection, or malignancy. When associated with autoimmune disease, it is referred to as macrophage activation syndrome (MAS). We describe a 21-year-old woman with severe, complicated systemic lupus erythematosus (SLE) who presented with a month of progressive lethargy and episodic confusion that culminated in new-onset status epilepticus and severe neurologic involvement at admission. Laboratory studies and bone marrow biopsy confirmed MAS-HLH. The trigger was thought to be multifactorial, possibly related to recent initiation of cyclophosphamide, underlying severe autoimmune disease, and a preceding gastrointestinal illness. Treatment of MAS-HLH with neurologic involvement is not standardized dure to the rarity of the disease. Current approaches include high-dose intravenous glucocorticoids, anakinra, intravenous immunoglobulin (IVIG), and plasma exchange, with variable responses. For refractory disease, the HLH-94 and HLH-2004 protocols, which are based on etoposide and dexamethasone, with or without cyclosporine, have been used. Our patient was initially managed with high-dose steroids and five days of plasma exchange, with inadequate clinical response. She was trialed on anakinra but ultimately required escalation to HLH-94/2004 protocol for disease control. This case underscores the importance of maintaining high suspicion for MAS-HLH in patients with autoimmune disease and acute neurologic decline. Early recognition and timely escalation of therapy are critical to improving outcomes. Our patient highlights both the diagnostic challenges and therapeutic considerations in managing a rare and refractory case of MAS-HLH.