Abstract
A 66-year-old woman with a history of coronary artery disease, atrial fibrillation, and hypertension presented with worsening nonhealing necrotic ulcer over the left calf for the past few weeks. She was applying silver sulfadiazine cream and tea tree oil but did not notice any improvement. She also reported unintentional weight loss of approximately 50 pounds (~23 kg) over several months, and associated loss of appetite. On examination, the posterior aspect of the left leg revealed a 9.0 × 2.0 cm black necrotic ulcer with scant serous drainage and several other smaller ulcers with peri-ulcer induration and tenderness (Panel A). Diff-erential diagnoses included warfarin-induced skin necrosis, calciphylaxis, antiphospholipid antibody syndrome, nephr-ogenic systemic sclerosis, oxalate vasculopathy, heparin-induced thrombocytopenia, pyoderma gangrenosum, and Marjolin’s ulcer.
Initial laboratory assessment included hemoglobin 8.9 g/dL, platelet count 226 k/µL, leukocyte count 4.6 k/µL, serum creatinine 1.2 mg/dL, and blood urea nitrogen 22 mg/dL. Serum calcium, phosphorus, vitamin D, and parathormone levels were normal. Lupus anticoagulant, cardiolipin IgG/IgM/IgA, and β2-glycoprotein IgG/IgM were negative. Additional investigations, including inflammatory markers, extensive vasculitis workup, and human immunodeficiency virus testing were unremarkable. The patient subsequently underwent biopsy of the ulcer that showed prominent fat necrosis, along with basophilic stippling of calcium deposition within the blood vessel walls, and focal areas demonstrating vessel wall necrosis and fibrin thrombi, consistent with calciphylaxis (Panel B). The patient also underwent computed tomography of the abdomen to further investigate her weight loss, which found a left exophytic renal mass with central necrosis (Panel C: black arrow). She was started on sodium thiosulphate for nonuremic calciphylaxis, and underwent a left radical nephrectomy with tissue pathology, confirming renal cell carcinoma. Unfortunately, shortly after the nephrectomy, she died after sustaining cardiac arrest.
Calciphylaxis is a rare complication in patients with end-stage renal disease, characterized by nonhealing skin ulcers caused by arterial calcification and thrombosis. Calciphylaxis in the absence of end-stage kidney disease is called nonuremic calciphylaxis, which is even rarer and the mechanism is unclear. There are a few case reports describing the association of nonuremic calciphylaxis with vitamin D toxicity, primary hyperparathyroidism, malignancy, alcoholic liver disease, bariatric surgery, and connective tissue disease.1–3 Female sex and anticoagulation have been reported as two important risk factors. 4 Warfarin, specifically, has been hypothesized to promote nonuremic calciphylaxis by inhibiting vitamin K-dependent carboxylation of matrix Gla protein, thereby decreasing inhibition of local calcification. 5 Sodium thiosulphate is considered the cornerstone of treatment. 4
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
