Calciphylaxis

What is calciphylaxis?

Calciphylaxis is a rare, painful and deadly disease that is most likely to happen in people with moderate to severe kidney problems. The disease causes calcium deposits to form in your blood vessels and block blood flow, leading to areas where skin and tissue just underneath break down and die.

Are there different types of this condition?

Calciphylaxis has two types based on when they happen.

• Uremic (you-reem-ick). This type is the more common of the two. This typically happens in people who have end-stage kidney disease (ESKD).
• Non-uremic. This type is rarer and 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.

Who does it affect?

Uremic calciphylaxis makes up the majority of cases and 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 calciphylaxis is much less common. It can also happen to people who don't have any kidney disease or problems, but this is extremely rare.

Calciphylaxis is also more common in women, who are twice as likely to develop the condition as men.

How common is this condition?

Calciphylaxis is very rare. In people who are on dialysis, it happens to approximately 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.

How does this condition affect my body?

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

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

Your skin is the most important part of your body’s defense against infection — as long as it’s intact —because it keeps germs out. When a wound gets infected and that infection spreads through your body, it can cause an overreaction of your immune system called sepsis. This condition is the most dangerous and deadliest complication of calciphylaxis.

Symptoms of calciphylaxis:

• 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 become discolored and turn red, purple, brown or black. These lesions usually have a net-like appearance. They may also blister, and the affected area of skin may become hardened and leathery.
• Ulcers and sores (later stages). Lesions usually become wounds that spread outward in star-like 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. These ultimately grow and expand in size.
• Vision problems, internal bleeding and muscle damage. Other problems are possible in rare cases where calcium deposits happen internally and not just beneath the skin. Deposits in the eyes can interfere with vision. Deposits in the 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 build-up on major blood vessels and heart valves. When calciphylaxis happens, the risk of this happening is even greater.

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 are more common in people who have a higher body mass index and in women.

At least 70% of lesions in uremic calciphylaxis cases have central distribution, while in non-uremic cases about half 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. When peripheral lesions become advanced, this can lead to amputation to stop the damage from spreading and causing deadly complications.

What causes the condition?

The exact cause of calciphylaxis remains unknown, but the available research suggests it takes more than one factor to cause it. Researchers found that there were two requirements before calciphylaxis could happen.

Hypersensitivity

In the case of calciphylaxis, hypersensitivity develops because of something that is happening to or around you. Many potential causes of hypersensitivity, known as sensitizers, have connections to each other. Sensitizers are like tinder material. They don’t cause the fire on their own. They just make it more likely to start.

Some of the possible sensitizers include:

• Too much parathyroid hormone. The parathyroid glands, which are at the bottom of each side of your thyroid, produce a hormone your body needs. When you’re having kidney problems, these glands commonly produce too much of the hormone (a condition called hyperparathyroidism) to try and keep the calcium levels in your blood stable. This can also happen when you aren’t getting enough vitamin D or calcium.
• Kidney failure. Your body chemistry relies on your kidneys doing their job. When they aren’t functioning properly, this disrupts your body’s chemical balance. That disruption may make your body more prone to calciphylaxis.
• Too much phosphorus. Your body also 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.

Triggers

Where sensitizers are like flammable tinder, triggers — sometimes called challengers or challenging agents — are the sparks that can start the calciphylaxis process. Possible triggers include:

• Metal compounds. Examples are that contain metals like lead, iron, aluminum, titanium or chromium.
• Organic compounds. An example of this would be egg-based items, such as egg whites and yolks.
• Trauma. This can be due to either injuries or medical procedures (such as an incision or a needle stick for an intravenous (IV) medication line.

Are there any other contributing factors that raise my risk of developing calciphylaxis?

Several conditions and risk factors might have connections to calciphylaxis, but none are proven causes. They include:

• Exposure to any of the sensitizers or triggers mentioned above.
• 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 makes your risk of developing calciphylaxis four times higher.
• Autoimmune diseases. This is especially true for people who aren’t on dialysis or in the later stages of kidney disease. Examples of these conditions include lupus, ulcerative colitis, rheumatoid arthritis and more.
• Liver disease. Alcoholic hepatitis, which is liver inflammation or disease from alcohol abuse, is a possible risk factor.
• Warfarin. The anticoagulant warfarin blocks your body’s use of vitamin K, which is essential in how your blood clots. Vitamin K may also be part of why calciphylaxis happens, though more research is necessary to confirm this.
• Corticosteroids. These medications treat swelling and inflammation. People who develop calciphylaxis have often been on corticosteroids recently. However, corticosteroid use is very common, so just how much of a risk factor these medications might be is unknown.

How is this condition diagnosed?

A medical professional, usually a doctor, can often begin to suspect calciphylaxis based on your condition, symptoms and a physical exam of your body. This includes looking and feeling for any changes to the skin or just underneath it. A healthcare provider will also ask questions about your medical history, personal circumstances and more as they try to make a diagnosis. Once a provider suspects calciphylaxis, the next step is confirming that suspicion with medical tests.

What tests will be done to diagnose this condition?

Because available research on calciphylaxis is limited,

The following tests are possible or likely:

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 positively. The sample is usually taken 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.

In cases where a person already has a diagnosis of end-stage kidney disease and has more advanced wounds with black scabbing, a biopsy may be unnecessary.

Lab testing

Blood and urine tests are often useful in helping with the diagnosis, assessing the severity of the case and how best to treat it. The tests used 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 filtered by your liver 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. They 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

Diagnostic imaging tests like X-rays or bone density scans may be done, but they aren’t as common. Using these tests is more likely when other tests are inconclusive.

How is calciphylaxis treated?

Because there isn’t a great deal of research on calciphylaxis available, there’s also limited guidance on the best ways to treat it. Currently, the disease isn’t curable, but it can go into remission if treatment is successful.

In general, healthcare providers will focus on the following:

Wound care

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

• 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 on the body may help with wound repair and healing.
• Antibiotics. These medications can help stop infections from bacteria.

Pain management

Calciphylaxis is an extremely painful condition, making it harder for you to rest and let your body heal. Opioid pain medications tend to be the most recommended because morphine can cause low blood pressure, which is not ideal.

Sodium thiosulfate

This medication, given in 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 both of the parathyroid glands.

Dialysis

This therapy removes waste products from your blood when your kidneys aren’t working as they should. Managing this type of care also takes into account any concerns possible with calciphylaxis.

Dietary and nutrition management

It's important to avoid malnourishment or dietary 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 are suspected sensitizers or triggers.

What are the possible complications of calciphylaxis or side effects from treatment?

Your healthcare provider can best explain to you the possible complications and side effects that may happen. Because calciphylaxis isn't well-understood, 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.
• Amputation (especially with lesions on your hands or feet). This is sometimes necessary when limbs — especially fingers and toes — are damaged beyond repair or recovery.
• Side effects from sodium thiosulfate. These include nausea, vomiting, fluid balance issues, low blood pressure and blood acidity problems. In many cases, adjusting the dose of this medication or treating the side effect symptoms was effective.

How to take care of myself/manage symptoms?

Following your healthcare provider’s instructions as closely as possible is very important with calciphylaxis. You should make sure to 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 your diet, medication or any new supplements or home remedies you want to take.

How can I prevent this?

Because the causes of calciphylaxis are not fully understood, it is harder to prevent it from happening. For that reason, healthcare providers often recommend minimizing use or exposure to sensitizers or triggers as much as possible. This includes things in your diet, personal care or hygiene items, medications, etc.

What is the long-term outlook for this condition?

Unfortunately, the outlook for calciphylaxis tends to be negative because the disease isn’t well-understood. About half of all patients with this condition do not 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 as follows:

• 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 was a little over 61%, compared to about 27% in people who did not have wound debridement.

How long does this condition last?

Calciphylaxis is a chronic, life-long condition because it isn’t currently curable. However, it’s possible in some cases for the disease to go into remission after treatment. How long it’s possible to keep it in remission isn’t yet known.

When should I see my healthcare provider or go to the hospital?

If you think you might be or know you’re at risk for calciphylaxis, or if you already have a diagnosis of this condition, it’s a good idea to talk to your healthcare provider. They are the best source of information on your risk factors, what symptoms you should watch for, and when you should seek medical attention.

In general, you should pay attention to your body. For example, if you notice new spots that are painful, changes in the color of your skin, or if your skin or the tissue underneath feels different, you should call your provider. This can help them catch calciphylaxis early, which can be helpful in your treatment.

If you have calciphylaxis, your healthcare provider can also guide you 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.
• If the area around the wound is hot to the touch.
• If the wound oozes any fluid and/or has a foul smell.
• If a black scab or covering forms on the wound.

A note from Cleveland Clinic

Calciphylaxis is a rare condition, and understanding it can be difficult because there’s limited available research and information. Talking to your healthcare provider or your loved one can help you better understand and know what to expect. While calciphylaxis may be a complicated and difficult-to-treat condition, some of the new research that’s now available may offer care options that can help.