What is calciphylaxis?
Calciphylaxis also known as Calcific uremic arteriolopathy (CUA) is characterized by painful, subcutaneous purpuric plaques and nodules.
These nodules may necrose in advanced disease. Although the skin manifestations are dramatic, it is useful to think of it as a systemic disease, and treat aggressively, given its high fatality rate.
When the extremities are involved, the lesions tend to be bilateral and symmetric in distribution and often are described as a mottled or violaceous discoloration with a reticular pattern, similar to livedo reticularis (seen in atheroembolic kidney disease, antiphospholipid syndrome, and cryoglobulinemia).
Of note, those with proximal lesions (trunk, buttocks, and thighs) tend to have a worse prognosis compared with those with more distal lesions (forearms and fingers; calves and toes).
Several known risk factors predispose to CUA—namely, poorly controlled secondary hyperparathyroidism, uncontrolled diabetes mellitus, obesity, female gender, duration of renal replacement therapy, history of skin trauma, and use of warfarin.
The increased expression of osteopontin and bone morphogenic protein 4 suggests the pivotal role that inducers of vascular calcification play in its pathogenesis.
Suspicion is the key to early diagnosis. When identified in its earlier stages (nonulcerative), initiation of therapeutic measures has been shown to improve prognosis.
Prevention is the key to management of CUA. Aggressive control of secondary hyperparathyroidism is pivotal.
Sodium thiosulfate is one of the therapies for established CUA. It is believed to work by two mechanisms of action:
- 1. Chelates calcium from soft tissues
- 2. Antioxidant, inducing endothelial nitric oxide synthesis, thereby improving local blood flow and soft tissue oxygenation.
A commonly used regimen is 5 to 25 g of intravenous (IV) Na thiosulfate administered toward the end of dialysis for several weeks to months.
Bisphosphonates (IV pamidronate and ibandronate and PO etidronate) may be effective in altering ectopic deposition of calcium phosphate and directly inhibiting calcification via the nuclear factor F06BF06BB cascade, although there are limited data.
Hyperbaric oxygen therapy improves oxygen delivery to damaged tissues by increasing the partial pressure of oxygen; it also promotes wound healing by supporting phagocytosis and angiogenesis while decreasing tissue edema.
