Hemophagocytic Lymphohistiocytosis-Macrophage Activation Syndrome (HLH-MAS) Mimicking Neuropsychiatric Lupus in Systemic Lupus Erythematosus (SLE)

Hemophagocytic lymphohistiocytosis-macrophage activation syndrome (HLH-MAS) is a life-threatening hyperinflammatory syndrome that can complicate systemic lupus erythematosus (SLE) and present with neurologic manifestations that mimic neuropsychiatric SLE (NPSLE). A 28-year-old woman with a four-year history of SLE initially presented to the emergency department of a community hospital with acute altered mental status and mutism. Laboratory evaluation revealed pancytopenia, markedly elevated ferritin (8,670 ng/mL), hypertriglyceridemia, and hypofibrinogenemia with an erythrocyte sedimentation rate (ESR) that declined from 21 to 6 mm/hr despite active inflammation, a recognized clue distinguishing HLH-MAS from NPSLE. Extensive infectious workup was negative. Although bone marrow biopsy and specialized biomarkers were unavailable at the presenting community hospital, an HScore of 271 (>99% probability of reactive hemophagocytic syndrome) strongly supported the diagnosis of HLH-MAS. High-dose IV methylprednisolone resulted in a progressive decline in ferritin and partial improvement in clinical status, following which the patient was transferred to a tertiary care center for further management. Early recognition of HLH-MAS in SLE patients presenting with acute neurologic symptoms is critical, as misdiagnosis can delay appropriate treatment.