Unchecked Immunity to Unleashed Anarchy: A Case of Hemophagocytic Lymphohistiocytosis Following Combination Immune Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors (ICIs) can cause rare but fatal immune-related adverse events such as hemophagocytic lymphohistiocytosis (HLH). We describe a 42-year-old female with metastatic clear cell renal cell carcinoma who developed HLH following treatment with first-line ipilimumab and nivolumab. Initial symptoms mimicked sepsis and recurrent Clostridioides difficile infection, delaying diagnosis. Eventually, laboratory findings met HLH-2004 criteria, and initiation of high-dose corticosteroids led to improvement. This case illustrates the diagnostic complexity of HLH in ICI-treated patients and the importance of early recognition. As ICI use increases, awareness of HLH is critical. Standardized treatment protocols and prospective studies are needed to guide management of this rare but severe complication.