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Calciphylaxis - Submitted on: Tuesday October, 10, 2006
Contributed by:Shaofeng Yan, MD, PhD, N/A
Calciphylaxis is a poorly understood disease of vascular calcification and skin necrosis.

Definition:
Calciphylaxis is a poorly understood disease of vascular calcification and skin necrosis1. The pathogenesis of calciphylaxis remains obscure. It is associated with chronic renal failure, hypercalcemia, hyperphosphatemia, an elevated calcium-phosphate product, and secondary hyperparathyroidism. Most patients with calciphylaxis have a long-standing history of chronic renal failure associated with abnormal calcium metabolism and results in a spectrum of end-organ damage due to ischemia.

Clinical Features:
Calciphylaxis often presents as violaceous plaques and nodules associated with ulceration and ischemic necrosis. Lesions of calciphylaxis typically develop suddenly and progress rapidly. The mortality rate of calciphylaxis is reported to be as high as 60-80%. The mortality is higher in patients with truncal lesions, whereas those with peripheral lesions, as on the legs, have a lesser mortality sometimes as low as 40%. The leading cause of death is sepsis from infected, necrotic skin lesions, although death due to internal organ failure has been reported. The patients almost invariably have an underlying coagulopathy such as a protein C or S deficiency.

Histology:
Figures
(Click on an image for a larger view)
Figure 1. Calcium deposition within a small artery in the septum of subcutaneous fat (Hematoxylin and Eosin, 40x).
Figure 2. Basophilic calcium deposition within a small artery in the lobule of subcutaneous fat (Hematoxylin and Eosin, 40x)
Figure 3. Von Kossa stain (40x).
Figure 4. Microthrombi within a small artery (Hematoxylin and Eosin, 40x).
Calciphylaxis commonly affects vessels, especially arteries of small size ranging from 40 to 600 m, with the average size being approximately 100 m 1. It is a small vessel vasculopathy characteristic of mural calcification with intimal proliferation and microthrombosis. Early changes may show a venule with prominent thrombosis and calcium deposited in the thrombus. There is usually deeply basophilic amorphous calcium deposition within the small arteries in septa (Fig 1) and lobules (Fig 2) of the subcutaneous fat.   Calcium deposition within the tissue can be highlighted as fine black granules by Von Kossa stain (fig 3). Microthrombi within the small vessels are easily identifiable (Fig 4). Extensive calcification of dermal and subcutaneous blood vessels may result in ulceration and extensive cutaneous and fat necrosis secondary to vascular compromise and ischemia.

The pathologic differential diagnosis of calciphylaxis includes dystrophic calcification, calcinosis cutis and Monckeberg's sclerosis. In calciphylaxis, calcium deposition can occur in areas without abundant inflammatory cell infiltrate 2, which differentiates it from dystrophic calcification of necrotic tissue. Dystrophic calcification involves calcification of injured tissue in the setting of a normal serum calcium and phosphate while calcinosis cutis is characteristic of calcification in skin tissue but not in vessels. Monckeberg's sclerosis can be differentiated by the presence of calcium in large vessels in the media.


Treatment:
Treatment of calciphylaxis is mainly supportive with elimination of the trigger factors and aggravating conditions, maintaining serum calcium and phosphate concentrations to low-normal levels. The use of milk alkali is sometimes helpful and is a first line of therapeutic strategies. Marked improvement of calciphylaxis has been reported with the use of intravenous sodium thiosulfate, early systemic glucocorticoids, unless ulcerated lesions are present. Improvement in some cases by parathyroidectomy has been documented. Conditions of hypercoagulability should be sought and addressed.

Bibliography:
  • 1. Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial. 2002 May-Jun;15(3):172-86.
  • 2. Moe SM, Chen NX., Calciphylaxis and vascular calcification: a continuum of extra-skeletal osteogenesis. Pediatr Nephrol. 2003 Oct;18(10):969-75.
     

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