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PATIENT STORY

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A 55-year-old woman with end-stage renal disease (ESRD), dependent on dialysis for 14 years, presented with multiple highly painful plaques on her abdomen and flank over the last month (Figure 96-1). The lesions ulcerated over that period of time. Her intact parathyroid hormone level was 1514 pg/mL at the time of presentation. This patient underwent parathyroidectomy for tertiary hyperparathyroidism and sodium thiosulfate treatments with dialysis but continued to have chronic pain related to the skin manifestations of calciphylaxis.

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FIGURE 96-1

Proximally located, highly painful ulcerative plaques and eschar characteristically involving the fatty portions of the extremities and lower abdomen. Note the associated livedo racemosa and retiform purpura indicative of ischemia caused by medial arteriolar calcification. (Photograph courtesy of Steven M. Dean, DO.)

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EPIDEMIOLOGY

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  • Calciphylaxis is most likely to occur in ESRD, with reported prevalence of 4.1% in dialysis patients.

  • Primary hyperparathyroidism is the second most commonly associated disorder.1

  • Clinical risk factors in dialysis patients are obesity, female gender, Caucasian race, diabetes mellitus, hyperphosphatemia, malnutrition, and hypercoagulable state (protein S or C deficiency).2

  • Associated medications include warfarin, steroids, calcium-containing phosphate binders, vitamin D analogues, and calcineurin inhibitors.

  • Prospective data for 36 cases demonstrated 33% mortality at 6 months for plaque lesions and 80% mortality at 6 months for ulcerative lesions.3

  • Retrospective data from 64 patients revealed overall 1-year survival of 45.8%.4 Patients who had surgical debridement did better, with 61% 1-year survival. Sepsis from infected ulcers is a common cause of death.

  • There are reports of calciphylaxis associated with acute kidney injury, alcoholic cirrhosis, systemic lupus erythematosus, rheumatoid arthritis, endometrial carcinoma, and Hodgkin lymphoma all in the absence of ESRD.

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ETIOLOGY AND PATHOGENESIS

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  • Pathogenesis is complex and only partially understood.

  • Vascular smooth muscle cells (VSMCs) differentiate into chondrocyte- or osteoblast-like cells.

  • Uremic toxins, hyperphosphatemia, and reactive oxygen species have been implicated in the change in phenotype of the VSMC.

  • Decrease in vascular calcification inhibitory proteins including fetuin-A and matrix Gla protein.

  • Fetuin-A is a glycoprotein made in the liver. It binds calcium and phosphorous in the circulation, and is a systemic inhibitor of vascular calcification. Fetuin-A levels are diminished in dialysis patients, and are also lower in chronic inflammation.

  • Matrix Gla protein is made by VSMC and chondrocytes. It binds calcium and prevents calcification of arteries. Activity is vitamin K dependent, which may explain the association of calciphylaxis with warfarin use.

  • Systemic medial calcification of arterioles is the first step and leads to epidermal ischemia, tissue infarction, and ulceration.4

  • Hyperphosphatemia and elevated parathyroid hormone level have been implicated, but calciphylaxis may occur with normal serum levels of calcium, phosphorous, and parathyroid hormone (PTH).

  • Administration of PTH induces ischemic skin necrosis in animals, and some patients have clinical improvement after parathyroidectomy.

  • Hypercoagulability may play ...

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