Abstract:

Calciphylaxis is a rare condition with high mortality characterized by painful skin necrosis and histologic examination demonstrating calcium deposits in subcutaneous vessels. While it is most commonly associated with end-stage renal disease, non-uremic causes such as primary hyperparathyroidism, malignancy, alcoholic liver disease, diabetes, warfarin use, and obesity have been described in the literature. Herein, we report a case of a 65-year-old female with intrahepatic cholangiocarcinoma treated with pemigatinib who presented with rapidly progressive retiform purpura involving the bilateral lower extremities. Histopathologic examination demonstrated necrotic epidermis and dermis, pseudoxanthoma elasticum-like changes, intravascular fibrin thrombi and calcium deposits in numerous subcutaneous blood vessels. Although calcium levels remained normal, phosphorus levels were elevated peaking at 6.8 mg/dL (normal 2.4-4.7 mg/dL). Appropriate evaluation for occlusive vasculopathy was performed and unremarkable. Unfortunately, her lesions progressed rapidly with areas of impending necrosis necessitating discontinuation of Pemigatinib and initiation of zoledronic acid. Pemigatinib is a fibroblast growth factor receptor (FGFR) inhibitor approved for metastatic cholangiocarcinoma treatment due to the presence of FGFR aberrations in 10-30% of intrahepatic cholangiocarcinomas. FGFRs play a substantial role in calcium and phosphate homeostasis. Therefore, the inhibition of FGFR increases kidney phosphate reabsorption, causing hyperphosphatemia and potentially metastatic calcinosis or calciphylaxis by the binding of elevated serum phosphate with calcium. We present this report to emphasize the importance of recognizing FGFRis as a potential culprit in the development of calciphylaxis. Prompt recognition of this rare complication will allow timely initiation of treatment of this unfortunate medication adverse event.

Financial Disclosure: No current or relevant financial relationships exist.

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Johanny Lopez Dominguez, BS