HSV-2–related hemophagocytic lymphohistiocytosis in a fingolimod-treated patient with MS

Fingolimod is an oral, disease-modifying therapy used to treat multiple sclerosis (MS). However, severe viral infections, including disseminated varicella-zoster virus infection, herpes simplex encephalitis, varicella-zoster virus encephalitis and vasculopathy, or progressive multifocal leukoencephalopathy, have been reported during fingolimod therapy. Hemophagocytic lymphohistiocytosis (HLH), often triggered by certain viral infections, is a fatal disease characterized by fever, pancytopenia, elevated liver enzymes, hyperferritinemia, hepatosplenomegaly, and hemophagocytosis. A triggering infection causes persistent activation of lymphocytes and histiocytes, resulting in exaggerated immune responses and hemophagocytosis. We describe an autopsied case of disseminated herpes simplex virus type 2 (HSV-2) infection presenting with HLH, following 0.5 mg fingolimod and corticosteroid therapies.