Calciphylaxis

Calciphylaxis is a condition characterised by necrosis (cellular death) of the skin and fatty tissue. It is seen mainly in patients with end stage kidney disease. It is also sometimes called calcific uraemic arteriolopathy.

In 1981, approximately 50 cases of calciphlaxis were reported in the world literature. Today, the incidence is estimated at 1 percent per year in patients undergoing dialysis. The mortality is extremely high, up to 80%, often within several months of onset. The primary cause of death is from secondary infection of the ulcers, and sepsis.

How does it occur?

The cause of calciphylaxis is not properly understood. Calcification affects small blood vessels resulting in spreading skin necrosis (tissue death).

It is associated with a condition known as secondary hyperparathyroidism. The damaged kidneys don’t excrete phosphate properly, which results in a build up of phosphate in the blood, which combines with calcium. Vitamin-D levels are reduced because of the kidney failure and reduced absorption through the gut. The bones become resistant to parathyroid hormone. The parathyroid glands therefore increase in size and produce more hormone increasing the amount of calcium circulating in the blood.

Calciphylaxis can occur in those with high or normal levels of serum calcium and phosphate, with or without vitamin D replacement, in dialysed patients and less often in those who have not yet commenced dialysis or in those who have received a renal transplant. It is more common in women than in men, in obese patients compared to those of normal weight , and in patients who have been taking corticosteroids or other immunosuppressive medicines.

Small blood vessels become blocked with blood clots, which leads to the black painful necrotic areas. It is thought that the clots occur because of calfication within the walls of the blood vessels.

Clinical Features

Calciphylaxis begins as surface purple-coloured mottling of the skin then bleeding occurs within the affected area. There may be blood-filled blisters. The skin goes black in the centre of star-shaped purple lesions. The skin cells die because of lack of blood supply (dry gangrene). This causes deep and often extensive ulcers.

Calciphylaxis

Patients usually experience unbearable pain, burning and sometimes itching at the lesion sites.

Calciphylaxis most often occurs on the lower limb especially in fatty areas. Lesions on the trunk, abdomen, buttocks or thighs, appear to be more dangerous than lesions on the lower legs and feet.

Risk factors

Certain conditions in addition to renal failure are associated with accelerated calcium deposition in soft tissues:

• Obesity
• Diabetes
• Caucasian race
• Female gender
• Hypoalbuminemia

How is the diagnosis made?

A skin biopsy may be necessary to diagnose calciphylaxis as a similar appearance can be seen in other conditions such as necrotising fasciitis, cryoglobulinaemia, antiphosopholipid syndrome, coumarin necrosis and vasculitis. The pathologist finds calcium within scarred and blocked blood vessels in the skin. There may also be inflammation of the fat (panniculitis).

Xrays of the affected limb may demonstrate vascular calcification within the skin; however this may also be seen in healthy patients with renal disease who are not affected by calciphylaxis.

Management

The best treatment for calciphylaxis is not yet clear.

The most important initial step is to normalise the calcium and phosphate product levels, and control the hyperphosphatemia associated with renal failure. A calcium and phosphate restricted diet and dialysis with a lower diasylate calcium concentration is important initial management in the calciphylaxis associated with renal failure.

In patients with significantly elevated parathyroid hormone that cannot be medically controlled, surgical removal of the parathyroid glands (parathyroidectomy) has been shown to reduce pain and promote wound healing, especially in early wound development. Parathyroidectomy should not be performed in calciphylaxis in the absence of hyperparathyroidism, as it can result in low levels of calcium in the blood and bone disease.

Some patients may also be treated with anticoagulants to reduce the tendency to form blood clots, but these are not always suitable or helpful.

Wound management is important.

• Keep wounds clean
• Surgically remove the necrotic tissue (particularly if moist) – sometimes this means a limb must be amputated
• Systemic antibiotics

Etidronate, a biphosphonate, has been reported of benefit, but biphosphonates may not be suitable for patients on haemodialysis. Intravenous infusions of sodium thiosulfate, and antioxidant and chelator, has also been used successfully.