Calciphylaxis

What is calciphylaxis, and how common is it?

Calciphylaxis (also called calcific uraemic arteriolopathy, or CUA) is a rare but serious condition¹. Calcium builds up in the small blood vessels of the skin and fat, which limits blood flow and causes painful skin ulcers². The wounds can be slow to heal and may become infected³.

It mostly affects people with advanced chronic kidney disease, most commonly stage 4 or 5, and especially people on dialysis⁴. About 1–4% of people on dialysis are reported to be affected⁵. It's reported more often in people on peritoneal dialysis than in people on haemodialysis⁶. It can also occur with normal kidney function⁷. Calciphylaxis is life-threatening⁴.

What causes it, and who gets it?

The exact cause isn't known¹. Calcification and clotting in the small blood vessels are thought to be involved².

Factors commonly linked with a higher risk are diabetes, higher body weight, low blood albumin (a blood protein), abnormal calcium and phosphate levels, use of warfarin-type blood thinners (vitamin K antagonists) and being female¹. Anaemia, inflammation, smoking, high blood pressure and less effective dialysis have also been named, but the links are less consistent¹. These are links, not proven causes.

Warfarin is described as a recognised risk factor⁸, though studies of it have been inconsistent⁹. A painful skin rash in someone taking warfarin can be a sign of calciphylaxis¹⁰. Using warfarin with extreme caution is advised in advanced kidney disease, especially when blood vessel calcification is known¹¹. Evidence on whether stopping it helps is limited, so warfarin shouldn't be stopped or changed without medical advice⁹.

What does it look and feel like, and how is it diagnosed?

Pain is the hallmark, and it can be very hard to control¹². It can come before any skin changes² and be out of proportion to how the skin looks¹³.

Early skin changes are tender, dusky purple-pink lumps or plaques under the skin¹³. The skin may show net-like mottling, purple patches or hard nodules, and it often blisters and breaks down, sometimes with infection⁹. Ulcers commonly have black dead tissue (eschar) on them⁹. They mostly appear on fatty areas such as the abdomen and thighs¹².

Some features mark the condition as becoming more serious: worsening pain, skin breakdown or ulceration, signs of infection (redness, warmth, pus or fever) and new or enlarging nodules⁷. Infected ulcers can progress to sepsis (a dangerous whole-body reaction to infection)². Painful lesions can also turn into dead (necrotic) or gangrenous ulcers, and amputation is sometimes needed⁵.

Early lesions can look like other problems, such as nodules, purpura (purple, bruise-like spots) or cellulitis (a skin infection), so they are easily overlooked⁸. Calciphylaxis is usually suspected in people at high risk who have extensive painful ulcers with a black scab-like covering, once other causes have been ruled out⁸.

There's no standard way to diagnose it. Some authorities say it is mainly a clinical diagnosis, while others rely on a skin biopsy (a small skin sample)¹. A biopsy can help when the picture is unusual or overlaps with other skin conditions¹. It can also cause new or worse lesions, infection, bleeding or tissue death, so its risks are weighed first⁹.

What helps first?

No treatment has been proven to work, and none is approved for calciphylaxis¹⁴. Because the cause is unknown, treatment is difficult and often trial-and-error⁵. Care usually combines decalcification (treatment aimed at reducing the calcium), wound care and pain control¹⁵.

Pain relief needs extra care in kidney disease, because many painkillers are cleared by the kidneys and several different medicines are often needed³. Pain is often severe and under-treated, and some people have been given only basic painkillers such as paracetamol¹⁶.

Protecting the skin is something you can do yourself. That means avoiding knocks, pressure and injury to affected skin, and varying where injections (such as insulin) are given⁹. How much this changes outcomes isn't clear yet⁹.

What helps if that isn't enough?

There's no good evidence that any particular option works when first-line care falls short, and no therapy is approved¹⁴. Lesions can keep developing despite treatment, and management may take many months³.

What is supported is ongoing wound care, careful pain control and protecting lesions from injury¹⁵⁹. Delayed diagnosis, wound care that varies from place to place and a lack of emotional support are also common difficulties¹⁶.

What is the outlook, and can it come back?

The outlook is serious. Reported death rates within a year of diagnosis range widely, from 30% to 80%, and in some reports more than half of people die within the first year². Deaths are largely driven by wound infections and cardiovascular events (heart and blood vessel problems)¹⁷.

How often calciphylaxis comes back after healing isn't clear yet. Ideas for lowering risk that are still being evaluated, and aren't proven, include making dialysis as effective as possible, managing high blood pressure, anaemia and diabetes, cautious weight loss if overweight, stopping smoking, avoiding substances that can harm the liver, using another kind of blood thinner in place of warfarin-type medicines where possible, and keeping calcium and phosphate levels in balance¹.