Macrophage activation syndrome-associated hemophagocytic lymphohistiocytosis (MAS-HLH) is a rare adult hyperinflammatory syndrome, and its occurrence in myasthenia gravis (MG) is exceptionally uncommon. We describe a 25-year-old woman with acetylcholine receptor antibody-positive MG and antiphospholipid antibody positivity who presented with acute hypoxic respiratory failure, encephalopathy, and polyserositis. Despite antimicrobials and MG-directed therapy, she developed persistent fevers, leukocytosis, and worsening neurologic dysfunction. Laboratory evaluation revealed ferritin >7500 ng/mL, fibrinogen of 151 mg/dL, triglycerides of 339 mg/dL, and soluble interleukin-2 (IL-2) receptor of 5551 pg/mL, yielding an H Score of 238 and a >90% predicted probability of HLH. Bone marrow biopsy demonstrated very rare hemophagocytic histiocytes. Extensive infectious, autoimmune, and paraneoplastic evaluation including cerebrospinal fluid cytology, flow cytometry, multiplex meningoencephalitis polymerase chain reaction, and brain magnetic resonance imaging was unrevealing, supporting a diagnosis of secondary MAS-HLH triggered by MG-associated immune dysregulation. Given progressive hyperinflammation and concern for central nervous system (CNS) involvement, the patient received high-dose corticosteroids followed by etoposide, resulting in rapid clinical improvement, declining ferritin, and normalization of IL-2 receptor. She subsequently completed 4 weekly postdischarge etoposide doses with sustained remission. This case underscores the importance of considering HLH in disorders of autoimmunity and immune dysregulation like MG, in patients who develop disproportionate systemic inflammation or neurologic decline and highlights the critical role of early recognition, multidisciplinary evaluation, and timely cytokine-directed immunosuppression in improving outcomes in adult MAS-HLH.
Samperio et al. (2026) studied this question.