CALCIPHYLAXIS

By Gary M. White, MD

Calciphylaxis


Calciphylaxis (calcific uremic arteriolopathy) is a small vessel vasculopathy associated with soft tissue calcification that leads to ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscle. It occurs predominantly in individuals with renal failure on dialysis. The syndrome causes significant morbidity in the form of infection, organ failure, and pain. Mortality is high. In individuals with renal failure, risk factors for the development of calciphylaxis include female sex, Caucasian race, obesity, and diabetes mellitus. The term vascular calcification-cutaneous necrosis syndrome has been recommended for this syndrome in which certain triggers induce soft tissue calcification.   

Clinical           

Painful mottling of the skin resembling livedo racemosa in a patient with CRF on dialysis is characteristic of the initial lesion. Later, these areas become indurated, ecchymotic plaques which enlarge and develop central necrosis and ulceration. Distal gangrene and autoamputation of multiple digits is common. Extensive calcification of blood vessels may be seen histologically and on X-rays. The calcium-phosphorus product is usually greater than 6.5 mmol x mmol/LxL. The typical patient has elevated phosphate and parathyroid hormone. The calcium level may be normal.

Differential

In metastatic calcification, the calcium x phosphate product is usually markedly higher than 6.5 mmol2/L2 and frequently, the GIT, lungs, kidneys and cardiovascular system are involved.

Rarely patients with primary hyperoxaluria may go undiagnosed into adulthood, develop renal failure, go on hemodialysis and develop necrotic skin lesions similar to calciphylaxis.

Radiologic imaging might enable more rapid diagnosis of calciphylaxis when skin biopsy specimen is pending or not available [JAAD 2017;77;241].

Warfarin-associated nonuremic calciphylaxis

Warfarin-associated nonuremic calciphylaxis (WANC) is a distinct subset. In one series, after switching off coumadin, 83% achieved full recovery [JAMADerm 2017;153;309]. 83% were female. Lesions most commonly occurred below the knees. The calcium-phosphate product is not elevated.

Treatment

The lesions can be very painful. Counseling, emotional support and pain medications are in order. Efforts must be made to normalize the plasma calcium and phosphorus concentrations, the calcium and phosphorus product and the serum parathyroid hormone level. Parathyroidectomy is often needed. Unfortunately, some patients disease cannot be controlled and they may die from complications such as sepsis.

Wound Debridement

Surgical debridement to remove necrotic tissue and promote healing is widely used, but controversial as it may cause local progression of the disease. Enzymatic debridement, specialized dressings and negative pressure wound therapy may be beneficial. A wound care specialist is valuable here.

Apixaban

A single retrospective study of 16 patients with calciphylaxis at the Mayo clinic using an oral anticoagulant, the most common being apixaban, showed great promise in the treatment of calciphylaxis. At a follow up of 418 days, 9 of 16 were still alive and 5 of those 9 had complete resolution of their symptoms (study by Brian J. King, MD presented at the European Academy of Dermatology and Venereology as reported by Dermatology News, December, p. 8). Coumadin cannot be recommended as it may predispose to calciphylaxis.

Sodium Thiosulfate

Sodium thiosulfate is thought to act as an antioxidant, vasodilator and calcium chelator. Four patients completely cleared with remission of disease with IL sodium thiosulfate 250 mg/ml [JAMA Derm Aug 2013]. It is proposed that the agent dissolves the insoluble calcium salts embedded in tissue. Intravenous therapy is given as well. For that, the doses vary from 5 g to 25 g given intravenously over 1 h after high-flux hemodialysis three times a week for months.

Additional Pictures

Calciphylaxis Calciphylaxis

References

Calciphylaxis of the penis Dermatology Online Journal 21;6

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