A Rare Case of Early-Onset Steroid-Refractory Fulminant Hepatitis Following Dual Checkpoint Inhibition in Melanoma...

Hemorrhagic central nervous system (CNS) metastases are well recognized in melanoma yet seldom represent the initial manifestation, and fulminant, steroid-refractory hepatitis from immune checkpoint inhibitors (ICIs) remains exceedingly rare. Here, we present a 54-year-old man with no prior medical history who was brought to the emergency department with acute confusion and aphasia and was found to have a large right frontal hemorrhagic mass with midline shift. Urgent craniotomy and hematoma evacuation revealed high-grade melanoma, BRAF V600-negative. Imaging identified stage IV disease with pulmonary and hepatic metastases. He was started on ipilimumab and nivolumab combination therapy outpatient; however, treatment was held after 2 cycles due to marked transaminitis, and prednisone was initiated for presumed ICI-related hepatitis. Despite corticosteroids, liver function progressively worsened over the following weeks, which required a second hospitalization and culminated in fulminant liver failure and encephalopathy. High-dose methylprednisolone offered minimal improvement. Although second-line immunosuppressants were considered, rapid deterioration prompted initiation of tocilizumab. His hospitalization was complicated by multiorgan failure and radiographic progression of CNS metastases, and he ultimately transitioned to comfort care and died on hospital day 7. This case demonstrates hemorrhagic CNS disease at diagnosis alongside early, fulminant, steroid-refractory ICI hepatitis and highlights the need for heightened hepatic surveillance and early escalation of immunosuppression during dual checkpoint blockade.