Abstract Body: Calciphylaxis is a catastrophic dermal arteriolar calcification disorder with microvascular
thrombosis resulting in painful cutaneous necrosis. There are no approved therapies, and the
prognosis remains grim. Recent mechanistic work demonstrated that calciphylaxis serum triggers
a feed-forward cytokine–coagulation cascade in the dermal microenvironment, characterized by
IL-6 and tissue factor (TF) procoagulant activity. This IL-6–TF signaling axis establishes a
permissive niche for thrombotic vasculopathy and lesion progression. Based on this molecular
framework, we report a 62-year-old woman with a failed kidney transplant and biopsy-proven
calciphylaxis refractory to metabolic correction and sodium thiosulfate. Skin biopsy showed
strong IL-6 and TF staining in thrombosed dermal microvessels. Tocilizumab, an FDA-approved IL-6R inhibitor, produced
immediate pain relief and improvement in bilateral thigh lesions after two doses. Serum profiling
revealed markedly elevated baseline IL-6 levels that rose following tocilizumab, while serum-
induced TF activity in endothelial cells decreased concurrently with clinical improvement. The
lesion recurred immediately upon treatment discontinuation. This case provides first-in-human
evidence that IL-6 blockade may modify the biology of calciphylaxis. Moreover, dynamic IL-6
and TF activity measurements in endothelial cells in response to serum may serve as
mechanistically grounded disease activity and therapeutic response biomarkers, supporting
further exploration of IL-6- targeted interventions for this devastating condition.