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Painful Eruptions in a Patient With Cholangiocarcinoma Treated With Fibroblast Growth Factor Receptor Inhibitor

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 65-year-old woman with locally advanced, unresectable intrahepatic cholangiocarcinoma being treated with pemigatinib, a fibroblast growth factor receptor inhibitor (FGFRi), presented with a painful eruption on the bilateral lower extremities. Pemigatinib treatment was initiated 2 months prior to the skin findings. Laboratory evaluation demonstrated a mildly elevated D-dimer level at 578 ng/mL fibrinogen-equivalent units, prolonged prothrombin time of 12.7 seconds, elevated phosphorus level at 6.8 mg/dL (of note, phosphorus was 3.1 mg/dL 1 month prior), and normal calcium level and kidney function. Other laboratory tests to note include cryoglobulin and cryofibrinogen, which both had negative results. Within weeks, there was rapid progression with skin necrosis despite treatment initiation with rivaroxaban. Physical examination revealed retiform purpura with areas of necrosis involving the bilateral lower extremities (Figure, A and B). A punch biopsy specimen from the right calf was obtained for histopathologic analysis (Figure, C and D).

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A 65-year-old woman with locally advanced, unresectable intrahepatic cholangiocarcinoma being treated with pemigatinib, a fibroblast growth factor receptor inhibitor (FGFRi), presented with a painful eruption on the bilateral lower extremities. Pemigatinib treatment was initiated 2 months prior to the skin findings. Laboratory evaluation demonstrated a mildly elevated D-dimer level at 578 ng/mL fibrinogen-equivalent units, prolonged prothrombin time of 12.7 seconds, elevated phosphorus level at 6.8 mg/dL (of note, phosphorus was 3.1 mg/dL 1 month prior), and normal calcium level and kidney function. Other laboratory tests to note include cryoglobulin and cryofibrinogen, which both had negative results. Within weeks, there was rapid progression with skin necrosis despite treatment initiation with rivaroxaban. Physical examination revealed retiform purpura with areas of necrosis involving the bilateral lower extremities (Figure, A and B). A punch biopsy specimen from the right calf was obtained for histopathologic analysis (Figure, C and D).

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Article Information

Corresponding Author: Natasha S. Wylie, DNP, APRN, Division of Hematology and Medical Oncology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224 (wylie.natasha@mayo.edu).

Published Online: October 28, 2021. doi:10.1001/jamaoncol.2021.5578

Conflict of Interest Disclosures: Dr Starr reported receiving honoraria for consulting from Natera, Pfizer, TerSera Therapeutics, Ipsen, and Advanced Accelerator Applications outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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