Calciphylaxis

What is calciphylaxis?

Calciphylaxis (kal-si-fuh-lack-sis) is a rare, painful and deadly disease that causes calcium deposits to form in your blood vessels and block blood flow. This leads to areas where skin and tissue just underneath break down and die.

In most cases of calciphylaxis, calcium deposits form in blood vessels that supply your skin and the tissue just underneath it. In rare cases, deposits can form internally in your eyes, lungs, brain, muscles and intestines.

When it affects surface tissue like skin, calciphylaxis is extremely painful. It also causes the affected area to become an open wound, like a bedsore. The skin and tissue around that wound die, and the damage from the dead tissue spreads outward. These calciphylaxis wounds are slow to heal and can lead to major complications.

Infection in a wound can spread through your body and cause an overreaction of your immune system called sepsis. This condition is the most dangerous and deadliest complication of calciphylaxis.

Types of calciphylaxis

Calciphylaxis has two types based on when they happen.

• Uremic (you-reem-ick). This type is the more common of the two, making up the majority of cases. This typically happens in people who are on dialysis because of end-stage kidney disease (ESKD). That means they’re in the later stages of kidney failure and need dialysis to filter waste from their blood.
• Non-uremic. This type is much less common. It happens in people who have earlier stages of kidney disease, who have a recent injury to one or both kidneys or who don’t have kidney problems at all (rarely).

How common is calciphylaxis?

Calciphylaxis is very rare. In people who are on dialysis, it happens to about 35 of every 10,000 people (or about one-third of 1%). In the United States, there are just over 550,000 people on dialysis, so just under 2,000 cases of calciphylaxis happen on average each year. In countries with lower rates of kidney disease, calciphylaxis is much rarer.

Calciphylaxis is more common in females. They’re twice as likely to develop the condition as males.

What are the symptoms?

Symptoms of calciphylaxis may include:

• Pain. Most cases of calciphylaxis are very painful. The sensation of pain may start before lesions or any other visible signs appear. The affected areas can also become hypersensitive to pressure or touch, making the pain more intense.
• Lesions (earlier stages). These are areas of skin that turn red, purple, brown or black. These lesions usually have a netlike appearance. They may also blister, and the affected area of skin may become hardened and leathery.
• Ulcers and wounds (later stages). Lesions usually become wounds that spread outward in starlike shapes. The wounds often have a foul smell. Areas of dead skin and flesh may turn black and take on a scab-like appearance and fall off.
• Vision problems, internal bleeding and muscle damage. Other problems are possible in rare cases where calcium deposits happen internally and not just beneath your skin. Deposits in your eyes can interfere with vision. Deposits in your internal organs can cause bleeding, and muscle damage is also possible.
• Calcification in major blood vessels and the heart. A common complication of end-stage kidney disease is calcium buildup in major blood vessels and heart valves. When calciphylaxis happens, the risk of this happening is even greater.

Types of calciphylaxis lesions

When lesions happen, they most often happen in one of two ways:

• Central distribution: These are lesions that happen mostly on the abdomen and thighs. They’re more common in people who have a higher body mass index (BMI) and in females. At least 70% of lesions in uremic calciphylaxis cases have central distribution, while in non-uremic cases, about 50% of the lesions have central distribution. Cases with more central lesions have a higher risk of death.
• Peripheral distribution: These are lesions near the ends of your arms and legs, especially on your fingers and toes. A provider may need to amputate a finger, toe or limb with advanced peripheral lesions to stop the damage from spreading and causing deadly complications.

What causes calciphylaxis?

The exact cause of calciphylaxis remains unknown, but research suggests it takes more than one factor to cause it. These factors can team up to become calciphylaxis causes.

These factors include:

• Too much parathyroid hormone. When you’re having kidney problems, your parathyroid glands try to keep the calcium levels in your blood stable. In doing this, they produce too much of a hormone your body needs (hyperparathyroidism). This can also happen when you aren’t getting enough vitamin D or calcium.
• Kidney failure. Kidneys that aren’t functioning properly disrupt your body’s chemical balance of handling calcium and phosphorus.
• Too much phosphorus. Your body uses phosphorus in several chemical processes, and your kidneys help control phosphorus levels.
• Certain types of cancer. This is more common with cases of calciphylaxis that have no connection to kidney disease.
• Trauma. This can be due to either injuries or medical procedures like an incision or a needle stick for an intravenous (IV) medication line.

What are the risk factors for calciphylaxis?

Several conditions and risk factors might have connections to calciphylaxis. They include:

• Kidney problems. The vast majority of people who develop calciphylaxis are in the final stages of kidney failure and are on dialysis.
• Obesity. This condition increases your risk of developing calciphylaxis.
• Diabetes. Getting insulin injections every day may traumatize your skin at the injection site(s).
• Autoimmune diseases. Examples of these conditions include lupus, ulcerative colitis, rheumatoid arthritis and more.
• Liver disease. Alcohol-induced hepatitis, which is liver inflammation or disease from alcohol misuse, is a possible risk factor.
• Warfarin. This anticoagulant blocks your body’s use of vitamin K, which is essential in how your blood clots. Vitamin K also activates a protein that keeps calcification in check. Many people with end-stage kidney disease don’t have enough vitamin K. This allows calcium deposits to form more easily.
• Corticosteroids. These medications treat swelling and inflammation. People who develop calciphylaxis have often taken corticosteroids recently.

What are the complications of calciphylaxis?

Complications of calciphylaxis may include:

• Insomnia.
• Loss of appetite.
• Depression.
• Severe ulcers.
• Infections.
• Amputation.
• Sepsis.

How is calciphylaxis diagnosed?

A healthcare provider may suspect calciphylaxis based on your condition, symptoms and a physical exam of your body. This exam includes looking and feeling for any changes to your skin or the area just underneath it. They’ll also ask questions about your medical history as they try to make a calciphylaxis diagnosis. Once a provider suspects calciphylaxis, they’ll order medical tests to learn more.

What tests will be done to diagnose calciphylaxis?

A healthcare provider may order the following tests:

Skin biopsy

Taking a sample of skin and tissue just underneath (usually about 4 or 5 millimeters deep) is the most reliable way to identify calciphylaxis. A provider usually takes a sample at the edge of a lesion or wound. Analyzing the sample involves looking at it under a microscope and using certain substances to cause color or chemical changes that can help confirm the diagnosis.

You might not need a biopsy if you already have a diagnosis of end-stage kidney disease and more advanced wounds with black scabbing.

Lab testing

Blood and urine (pee) tests can help with making a diagnosis, assessing the severity of the case and deciding how best to treat it. The tests providers use most often include:

• Kidney function tests. These tests analyze urine to check how well your kidneys are working.
• Mineral bone parameters: An analysis of calcium, phosphorus, parathyroid hormone and vitamin D can help determine the severity of a case.
• Liver function tests: When you can’t take medications that your kidneys filter out, medications your liver filters are often the next option. Checking your liver function helps healthcare providers make sure it’s safe to give you liver-dependent medications.
• Immune system markers: This test looks for signs that your body is fighting an infection. It can also help check for autoimmune diseases.
• Blood coagulation markers: Analyzing how well your blood clots (or doesn’t clot) is helpful because it can reveal the potential for internal bleeding or other problems.

Imaging

A provider may order diagnostic imaging tests like X-rays or bone density scans, but it’s not as common. You’re more likely to have imaging when other tests don’t provide answers that help with a diagnosis.

How is calciphylaxis treated?

Because researchers don’t fully understand calciphylaxis, there’s limited guidance on the best calciphylaxis treatment. Currently, the disease isn’t curable, but your symptoms can go away if treatment is successful.

In general, healthcare providers will focus on the following:

Wound care

Preventing infection and helping wounds heal are both top priorities. This can include several advanced types of care, like:

• Hyperbaric oxygen therapy. This involves placing you in an airtight chamber with a 100% oxygen atmosphere (instead of the normal oxygen concentration of about 20%). The pressure in the chamber will also be slightly higher than normal. This can be very effective at encouraging wounds to heal.
• Debridement. This is the removal of dead or dying tissue from a wound, helping prevent infection and encouraging the wound to heal. In more severe cases, this may involve surgery.
• Skin and tissue grafting. In cases with greater tissue loss, grafts from elsewhere in your body may help with wound repair and healing.
• Antibiotics. These medications can help stop bacterial infections.

Pain management

Calciphylaxis is an extremely painful condition, making it harder for you to rest and let your body heal. Providers tend to prescribe opioid pain medications for calciphylaxis.

Sodium thiosulfate

This medication, which you get through an IV, may help remove calcium built up in blood vessels or other tissues.

Treatment of bone and mineral problems

Ensuring the right levels and balance of minerals in your blood is important to help avoid complications and problems. This also includes making sure your parathyroid hormone levels don’t go too low or too high. In some cases, it may involve surgery to remove one or more of your parathyroid glands.

Dialysis

This therapy removes waste products from your blood when your kidneys aren’t working as they should.

Nutrition management

It’s important to avoid malnourishment or nutrient deficiencies that can happen with kidney problems and related conditions.

Medication management

A review of all medications you’re taking is important to avoid possible side effects and problems. This is especially true if you take warfarin or certain other medications that may raise your risk of calciphylaxis.

Complications/side effects of the treatment

Your healthcare provider can best explain to you the possible complications and side effects that may happen. Because calciphylaxis isn’t a well-understood condition, complications and side effects can be unpredictable and may be very different from person to person.

Some of the possible side effects and complications include:

• Infection. This refers to infections that might happen in connection with medical procedures, dialysis or surgeries rather than infections from calciphylaxis-caused wounds.
• Side effects from sodium thiosulfate. These include nausea, vomiting, fluid balance issues, low blood pressure and blood acidity problems. Providers need to consider these issues, particularly in people with heart failure. In many cases, adjusting the dose of this medication or treating the side effect symptoms is effective.

Can calciphylaxis be prevented?

Because researchers don’t fully understand the causes of calciphylaxis, it’s harder to prevent this condition. But healthcare providers often recommend minimizing risk factors as much as possible, like keeping calcium and phosphate at normal levels.

What can I expect if I have calciphylaxis?

Unfortunately, the outlook for calciphylaxis tends to be negative because of a lack of understanding of the disease. Most people with calciphylaxis lose their mobility to the condition, spending much of their time in a wheelchair or bed.

About half of all people with calciphylaxis don’t survive more than a year, with sepsis being the most common cause of death.

Depending on the circumstances of the condition, the one-year survival odds may be higher or lower. Those circumstances and odds are:

• Non-uremic calciphylaxis (not connected to end-stage kidney disease): People who have calciphylaxis without end-stage kidney disease are less likely to die within a year. The risk of death within a year in non-uremic calciphylaxis cases is between 25% and 45%. With uremic calciphylaxis, the risk of death is between 45% and 80%.
• Ulcers and wounds: Lesions become ulcers and wounds in the late stages of calciphylaxis. The later a diagnosis happens, the worse the prognosis tends to be. About 20% of people survive more than six months if they’ve developed wounds or ulcers.
• Debridement of wounds (removing dead or dying tissue): There’s evidence that this kind of wound care improves survival. One-year survival rates for people who had wound debridement were a little over 61%, compared to about 27% in people who didn’t have wound debridement.

How long calciphylaxis lasts

Calciphylaxis is a chronic, lifelong condition because it currently isn’t curable. But it’s possible, in some cases, for the disease to go into remission after treatment. Researchers don’t know how long it’s possible to keep it in remission.

How do I take care of myself?

Following your healthcare provider’s instructions as closely as possible is very important with calciphylaxis. You should be especially careful when it comes to wound care, keeping any sores or ulcers clean and protected from infection. You should also consult with your healthcare provider about any changes to the foods you eat, medication you take or any new supplements or home remedies you want to try.

When should I see my healthcare provider?

Talk to your healthcare provider if:

• You think you might be or know you’re at risk for calciphylaxis.
• You already have a diagnosis of this condition.
• You notice new spots that are painful.
• You see changes in the color of your skin.
• Your skin or the tissue underneath feels different.

Your provider is the best source of information on your risk factors, what symptoms you should watch for and when you should seek medical attention. They can catch calciphylaxis early, which can be helpful in your treatment.

When should I go to the ER?

If you have calciphylaxis, your healthcare provider can guide you on when to call their office or seek immediate medical care in connection with care for lesions or wounds. Among the biggest things to watch for are signs of infection or problems in and around a wound. These include:

• Swelling or redness around the wound.
• An area around the wound that’s hot to the touch.
• Fluid and/or a foul smell coming from a wound.
• A black scab or covering forming on the wound.

What questions should I ask my doctor?

Questions to consider asking your healthcare provider may include:

• What type of calciphylaxis do I have?
• What are the best treatments for me?
• Can you help me connect to resources that can help me during my illness?
• What’s the prognosis for someone in my situation?