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

  
  
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  Primary hyperparathyroidism is the second most commonly associated disorder.¹

  
  
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  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

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

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

  
  
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  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.

  
  
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  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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  Pathogenesis is complex and only partially understood.

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

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

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

  
  
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  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.

  
  
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  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.

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

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

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

  
  
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  Hypercoagulability may play a role in the pathogenesis, either due to a thrombotic disorder or procoagulant effects of warfarin.⁵

  
  
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  Wilmer and Magro proposed a two-stage concept in which stage one is development of the vascular lesion, and stage two is development of end-organ ischemia due to expanding calcific vascular lesions, obliterative endovascular thrombosis, and/or vascular thrombosis.²

Clinical Features

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  Painful lesions in adipose areas including abdomen, buttocks, thighs.

  
  
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  Early lesions are painful purpuric plaques, livedo racemosa, and subcutaneous nodules (Figure 96-2).

  
  
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  At later stages the lesions become ischemic and necrotic (Figure 96-3).

  
  
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  Infection of necrotic lesions may lead to bacteremia or sepsis.

  
  
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  A painful proximal myopathy may be present even without skin lesions.

  
  
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  An optic neuropathy related to calciphylaxis has been described.