Calcified subcutaneous arterioles with infarcts of the subcutis and skin ("calciphylaxis") in chronic renal failure

Abstract

Patients with chronic renal failure (CRF) are at increased risk for pathological calcifications because of increased serum calcium-phosphorus products. A minority, including those undergoing dialysis, develop a syndrome of deep skin ulcerations in association with calcification of subcutaneous arterioles. The body distribution of the skin lesions may be proximal (central), distal (peripheral), or both. Since 1968, this syndrome has been called "calciphylaxis" in the belief that it is the human analogue of Selye's experimental models of tissue calcification. Our review emphasizes that this syndrome comprises two separate processes not found in calciphylaxis: calcification of subcutaneous arterioles and infarctions of subcutaneous adipose tissue (panniculus adiposus) and skin. The infarctions are acute and clinically dramatic, whereas the calcific arteriolopathy is preexistent, having developed slowly, sometimes over years, and silently. Separating these two processes facilitates analyses of pathogenetic factors, such as those that target subcutaneous arterioles for calcification and those that interfere with blood flow through the calcified arterioles, sufficient in some patients to cause the infarctions, and of why obesity in CRF is a syndrome risk factor. This approach further helps to provide a much needed standardized definition of the syndrome, thereby facilitating comparisons of the results of such treatments as parathyroidectomy, anticoagulants, and phosphate binders. Finally, the separation shows why the application of such terms as calciphylaxis and calcifying panniculitis to this syndrome is inappropriate.