Calcific Uremic Arteriolopathy (Calciphylaxis)

Abstract

A 61-year-old man who had had diabetes mellitus for 25 years and renal failure requiring peritoneal dialysis for 7 years initially presented with a gangrenous left foot and underwent a partial amputation. During that admission, the patient received low-dose warfarin prophylaxis. Four months later, he presented with a presumed penile infection. The infection did not resolve with antibiotic treatment, and the tip of his penis formed an eschar. He returned 1 month later with complaints of tenderness and a violet rash on the lateral aspect of both thighs. Skin biopsy findings were consistent with a diagnosis of calcific uremic arteriolopathy (CUA). Histopathologic studies showed thrombi within arterioles (white arrows) and intimal calcification (black arrow). Retrospective evaluation of specimens obtained from the original foot surgery also revealed evidence of CUA. The penile lesion was not biopsied but was likely related to the same disease process. Acral (fingers, toes, tongue, penis) distribution of lesions has been described in patients with CUA. Dermatologic findings may resemble vasculitis and atherosclerotic peripheral vascular disease. The defining feature of CUA is calcification of the medial layer of small vessels. Although calcification is usually chronic, unknown triggers lead to acute thrombogenic microangiopathy and infarction of subcutaneous adipose tissue. Lesions begin as localized tender, broad violaceous nodular plaques. Necrosis and eschar formation may develop within days. Risk factors for CUA include elevated phosphorus levels, increased body mass index, and hypoalbuminemia. Warfarin therapy has also been implicated as a cause of CUA, and animal studies have helped to define the pathophysiology. Matrix Gla protein (MGP) has been shown to inhibit vascular calcification. In mice, disruption of MGP leads to diffuse calcification of vessels and rapid death. Warfain-induced γ-carboxylation inhibits activation of MGP and predisposes patients to vascular calcification. Therapy consists of lowering serum phosphorus, calcium, and parathyroid hormone levels. Local wound management including debridement and antibiotics may be necessary. In some cases, hyperbaric oxygen therapy helps heal wounds.