Case Presentation: A 60-year-old female presented to the emergency department with shortness of breath, worsening edema, and a tender, non-purulent, erythematous rash on her medial thighs bilaterally. Her medical history was significant for atrial fibrillation, heart failure with reduced ejection fraction, and chronic myelomonocytic leukemia. The patient had been recently discharged after an admission for volume overload and atrial fibrillation with rapid ventricular response for which she underwent cardioversion and was switched from warfarin to apixaban.After admission, cardiology and nephrology were consulted and the patient was adequately diuresed. The patient received five days of cephalexin followed by one week of vancomycin for presumed cellulitis. The rash was now hardened, violaceous, and exquisitely tender. Ultrasound and CT showed no acute processes to suggest thrombus. Lactic acid, chest radiographs, urinalysis, and blood cultures were not consistent with infection. Vascular surgery had no concern for arterial insufficiency. Acute care surgery did not recommend surgical intervention. Dermatology took a punch biopsy that revealed vascular congestion with fat necrosis. Extravascular calcification was identified with a Von Kossa stain. Intact parathyroid hormone, calcium, and phosphorus were within respective reference ranges. The patient began 25g IV sodium thiosulfate three times weekly for three months and alendronate once weekly for six weeks. The lesions regressed entirely, and the patient suffered no adverse events following the diagnosis of calciphylaxis.
Discussion: Calciphylaxis is a poorly understood calcification disorder that most frequently presents in patients with end stage renal disease (ESRD). In patients without kidney disease, calciphylaxis is termed “non-uremic”. The most widely accepted pathophysiology is arteriolar calcification and thrombosis causing necrosis of the overlying skin. Presentation involves painful violaceous plaques, purpura, and subcutaneous nodules that often progress to necrotic ulcerations with infection. Risk factors include long-term use of warfarin or glucocorticoids, female gender, hyperparathyroidism, malignancy, and alcoholic liver disease. Diagnosis is made with biopsy showing septal panniculitis, calcification, microthrombosis, and fibrointimal hyperplasia of dermal arterioles. Von Kossa and Alizarin Red stains increase calcium detection. Laboratory evaluation should include a workup for hyperparathyroidism, kidney disease, liver disease, inflammatory disease, and hypercoagulable states. There is currently no approved treatment for calciphylaxis. However, the generally accepted therapy is 12.5-25g intravenous sodium thiosulfate three to four times weekly with dosages tailored to renal function.
Conclusions: Non-uremic calciphylaxis is a rare dermatologic disease with high mortality. However, early diagnosis and treatment can prevent disease progression and significantly reduce morbidity and mortality. Clinical suspicion should remain high in women with normal renal function who are on long term treatment with warfarin or glucocorticoids. Because biopsy is required for definitive diagnosis, there should be a low threshold for dermatology consult.