Fibroblast Growth Factor Receptor Inhibitors and Nonuremic Calciphylaxis

Abstract

Discussion | These findings show that the burden of nail complications in SJS/TEN survivors may be significantly higher, affecting up to 70% of patients compared with prior studies with reported incidence of 10% to 50%. 2,3 These range from mild changes such as Beau lines to cosmetically disabling sequelae of onychomadesis and anonychia. We believe that the spectrum of nail complications is a representation of the varying extents and patterns of nail matrix damage that occurs during the acute phase of SJS/TEN. Beau lines arise from a partial arrest of the nail matrix 4 ; onychomadesis arises from complete arrest 4 ; erythronychia arises from focal loss of matrix function 5 ; and onychoschizia and onychorrhexis arise from defective nail plate production with impairment of intercellular adhesions owing to nail matrix dysfunction. 6 A novel observation was the presence of distal yellow dyschromia, which occurred in 18% of patients. We postulate that this distal dyschromia arises owing to the retardation of nail growth during the acute phase of the disease, analogous to yellow nail syndrome. We also observed that periungual bullae during the acute phase may predict for severe nail changes, such as onychomadesis and anonychia. There are limitations of the study-notably, the small sample size and the potential for referral bias.In conclusion, our study adds to the growing literature on the burden of SJS/TEN and demonstrates the spectrum of its nail complications. This highlights the urgency to identify interventions to prevent such complications and/or treat them when they occur.

Calciphylaxis Cutis Associated With Fibroblast Growth Factor Receptor (FGFR) Inhibitor Therapy: A New Challenge

“…Calciphylaxis is characterized by calcium deposition into the microvessels, leading to vascular compromise and necrosis of subcutaneous tissues [8]. Although usually identified in the setting of hyperphosphatemia and end-stage renal disease (ESRD), our patient had preserved renal function, similar to other cases of FGFR inhibitor-associated calciphylaxis [5][6][7].…”

“…Non-uremic calciphylaxis cutis is a very rare, potentially adverse, event with only a few cases reported in association with FGFR inhibitor therapy to date [5][6][7]. Calciphylaxis is characterized by calcium deposition into the microvessels, leading to vascular compromise and necrosis of subcutaneous tissues [8].…”

Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

“…[156][157][158] Altered calcium-phosphate homeostasis resulting in hyperphosphatemia is a frequent adverse event from FGFR inhibitors and hyperphosphatemia occurs in 45% to 100% of patients treated with pan-FGFR and FGFR1-3 inhibitors. 158,159 Calcinosis cutis and calciphylaxis are infrequent dermatologic toxicities from FGFR inhibitors, [160][161][162] however, awareness of this type of adverse skin reaction and monitoring of phosphate levels are critical in these patients.…”

Calciphylaxis and its co‐occurrence with connective tissue diseases

“…However, calciphylaxis can also occur in patients without kidney involvement or disorders of calcium and phosphorus metabolism (ie, non‐uremic calciphylaxis). Some pathological states and diseases including obesity, 11 rapid weight loss, 12 hypoalbuminemia, 13 hypercoagulability, 14 hyperparathyroidism, pneumonia, 15 autoimmune diseases, 16 diabetes, 17 liver diseases 18 and tumours, 5 or specific drug use 19 , 20 may contribute to the development of calciphylaxis.…”