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A 70-year-old woman on chronic hemodialysis for end-stage renal disease presented with a several week history of a tender eruption on her lower legs. Physical examination revealed bilateral purpuric indurated and atrophic plaques on her lower legs without definitive ulcerations (Figure 1A, 1B). A skin biopsy was taken from one of the indurated plaques.

On low magnification, basophilic alteration of a fibrous septum can be seen (Figure 2). Fibrin thrombi are also present within many of the blood vessels of the subcutaneous adipose tissue (Figure 3). Higher magnification identifies calcium deposition within the fibrous septum, primarily on elastic fibers (Figure 4, Figure 5). Higher magnification of the same area with Verhoeff-van Gieson stain confirms the presence of fragmented elastic fibers (Figure 6). Special stain for calcium (von-Kossa) identifies calcium deposition both within the septum of the fat lobule (Figure 7) and within the walls of blood vessels (Figure 8).

Pertinent laboratory findings included: a calcium level of 9.2mg/dl (8.4-10.2), a phosphate of 9.7mg/dl (2.5-4.5), a BUN of 54mg/dl (10-20), a creatinine of 6.8mg/dl (<1.5) and a parathyroid hormone (PTH) level of 500pg/dl (10-65).

Calciphylaxis is a well-recognized but fortunately rare syndrome usually developing in the setting of chronic renal failure, generally associated with secondary or tertiary hyperparathyroidism. Rarely, it has been recognized in the setting of primary hyperparathyroidism alone and with

hypercalcemia of malignancy and multiple myeloma. Patients usually present with cutaneous ischemic necrosis and vascular calcification of small and medium sized cutaneous blood vessels. Ischemia of visceral organs is not seen, and overall mortality is reported to be over 60%, with most patients succumbing to infection. While the exact pathophysiology of calciphylaxis is not clear, a rise in calcium x phosphate ion product, often associated with elevated levels of parathyroid hormone is found. The histologic findings characteristic of calciphylaxis include: medial calcinosis of vessel walls, vascular thrombosis, epidemal necrosis, and a lobular

panniculitis. A recent study on calciphylaxis identified that calcium deposition with endovascular fibrosis was the most common lesion resulting in the vascular stenosis. The investigators found that initially, there were fine medial calcifications in blood vessel walls without fibrosis, later these changes were associated with endovascular fibrosis, and finally, vessels with calcification and well-developed endovascular fibrosis and stenosis were seen. Interestingly, a giant cell reaction to the calcification may also be seen within the vessel lumen. This characteristic endovascular fibrosis is only seen in 1-2 vessels/per square centimeter of tissue and often is not identified on small punch biopsy specimens.

While calcium deposition was identified in the interstitial areas of the fat lobule, significant calcium deposition within blood vessel walls was not obvious. Only intravascular thrombi were noted, raising other histologic differential diagnoses including platelet abnormalities and other causes of underlying hypercoagulable states. However, fine calcium deposition within blood vessel walls was identified on a von-Kossa stain supporting a diagnosis of calciphylaxis.
Abnormalities in elastic fibers simulating PXE were noted in the deep dermis and septal areas in a patient without other clinical criteria for this disorder. PXE-like alteration of the elastic fibers has been reported in other patients without clinical evidence of PXE and, interestingly, most of these cases have been reported in those with underlying abnormalities in calcium metabolism. PXE-like elastic tissue alterations have been noted in a variety of different clinical settings including: systemic lupus erythematosus with renal failure, exogenous exposure to saltpeter and in idiopathic hypercalcemia with secondary calcinosis cutis. In all these cases it is the excessive calcium deposits on elastic fibers that simulate PXE rather than the calcification of altered elastic fibers.