| Sumario: | Simple Summary: Pemigatinib, an FGFR2 inhibitor, is used to treat FGFR2-altered cholangiocarcinoma but may lead to rare, serious side effects. We report a 43-year-old woman with metastatic intrahepatic cholangiocarcinoma who developed calciphylaxis—a rare, life-threatening condition involving vascular calcification—after seven months of pemigatinib. Despite stopping the drug and initiating antibiotics and supportive care, her condition worsened, and she died from sepsis and disease progression. Skin biopsy confirmed calciphylaxis. This case highlights the importance of recognizing skin changes in patients treated with FGFR inhibitors at an early stage. Stopping therapy and managing complications promptly may improve outcomes. Fibroblast growth factor receptor 2 (FGFR2) inhibitors such as pemigatinib are targeted therapies for cholangiocarcinoma with FGFR2 alterations. While generally well tolerated, they are associated with unique adverse events. Calciphylaxis, a potentially fatal vascular calcification disorder, is a rare complication. We present a 43-year-old woman with metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 fusion who developed calciphylaxis after seven months of pemigatinib therapy. Despite drug discontinuation, antibiotics, and multidisciplinary supportive care, she deteriorated rapidly and died from sepsis and advanced disease. Histopathological analysis confirmed dermal and vascular calcifications consistent with calciphylaxis. This case highlights the importance of early recognition of cutaneous lesions in patients on FGFR inhibitors. Prompt cessation of therapy, management of metabolic derangements, and consideration of sodium thiosulfate may be lifesaving.
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