Calciphylaxis - Calcific Uremic Arteriolopathy (CUA) Or “Grey Scale”

Introduction:

Calciphylaxis is an uncommon and painful disease that causes calcium deposits to accumulate in the blood vessels supplying the skin and fat tissue. It commonly occurs in patients with end-stage kidney disease, patients on dialysis, and kidney failure. The calcium deposits block blood flow to the skin causing open wounds that can develop dangerous infections or cause the death of the tissues.

What Are the Types of Calciphylaxis?

Calciphylaxis is of two types, namely:

1. Uremic calciphylaxis.

2. Non-uremic calciphylaxis.

• Uremic Calciphylaxis: Uremic calciphylaxis is more common among the two types. It usually affects patients with end-stage kidney disease.

• Non-uremic Calciphylaxis: Non-uremic type is rarer, occurring in people with early-stage kidney disease or those who had a recent injury to one or both the kidneys. It may also occur in people with no kidney disease.

How Common Is Calciphylaxis?

Calciphylaxis is a rare condition occuring mostly in people with end-stage kidney disease (ESKD). Around 35 out of 10,000 people undergoing dialysis are affected by calciphylaxis.

What Are the Causes of Calciphylaxis?

The exact cause of calciphylaxis is not known. However, two factors play an important role in causing calciphylaxis, including hypersensitivity and triggers.

Hypersensitivity:

Hypersensitivity occurs because of certain factors occurring in the body that can cause calciphylaxis. They include:

1. Increase in Parathyroid Hormone: Parathyroid glands are four small pea-sized glands located behind the thyroid gland. They secrete a hormone called parathyroid hormone that helps regulate blood calcium levels. Kidney disease alters the calcium levels in the body, leading to excess secretion of the parathyroid hormone. The hormone increases blood calcium levels.

2. Kidney Failure: The body’s chemical balance is altered when the kidneys fail to function properly. This imbalance can make the body more prone to developing calciphylaxis.

3. Increase in Blood Phosphorus Levels: Calcium and phosphorus together form crystals of calcium phosphate that can get deposited in parts of the body other than the bones.

4. Certain Cancer Types: Calciphylaxis without kidney disease may have a cancer connection.

Triggers:

Triggering factors that can lead to calciphylaxis include the following:

1. Metal-Based Compounds: Metals like lead, aluminum, chromium, iron, or titanium can initiate calciphylaxis.

2. Trauma: Injuries, medical or surgical procedures can trigger the condition.

What Are the Symptoms of Calciphylaxis?

The following are the symptoms of calciphylaxis:

• Pain: Calciphylaxis lesions are very painful. The affected areas become more sensitive to touch and pressure.

• Lesions: Red, purple, brown, or black net-like appearance is noted on the skin, which can develop blisters (blisters are small fluid pockets that form on the skin after injury). The affected part of the skin can turn hard and leathery.

• Ulcers and Sores: Lesions develop into wounds that grow in size, have a foul smell, and spread outwards in star-like shapes. The skin can turn black and fall off.

• Internal Bleeding, Muscle Damage, and Vision Problems: Calciphylaxis can sometimes cause calcium deposits in the internal organs apart from the skin, which can lead to bleeding in the internal organs, muscle damage, and interference with vision.

• Calcifications in the Heart and Blood Vessels: End-stage kidney disease (ESKD) with calciphylaxis pose a high risk of damage to the heart valves and blood vessels.

How Do the Lesions Occur?

Lesions occur in two ways, which include:

1. Central Distribution: Central lesions occur commonly in women and obese persons on the abdomen and thighs. Patients with central lesions are at a greater risk of death.

2. Peripheral Distribution: Peripheral lesions occur in the arms and legs. Advanced peripheral lesions may need amputation (removal of the dead body part) to prevent spreading and causing deadly complications.

What Are the Risk Factors for Calciphylaxis?

People with end-stage kidney disease are at a greater risk of developing calciphylaxis. The other possible risk factors include:

1. Obesity.

2. Diabetes.

3. Female sex.

4. The Caucasian race (relates to a group of people having European ancestry).

5. Long-term dialysis or kidney transplant patients.

6. Calcium, phosphorus, and aluminum are imbalanced in the body.

7. Defects in blood-clotting factors (proteins in the blood that stop bleeding).

8. Hyperparathyroidism (a condition where parathyroid glands release excess parathormone, leading to an increase in calcium levels in the blood).

9. Uremia (a toxic condition in which substances normally excreted in the urine are retained in the body).

10. Hypoalbuminemia (a condition in which there is an abnormally low level of a protein called albumin, which is responsible for maintaining osmotic pressure in the blood).

11. Warfarin (an oral anticoagulant that prevents the formation of blood clots). Warfarin skin necrosis (WSN) is a complication of warfarin therapy.

12. Steroid therapy.

What Are the Complications of Calciphylaxis?

Complications of calciphylaxis vary from person to person that may include:

• Severe pain.

• Deep and large ulcers that fail to heal.

• Infections of blood.

• Death occurs due to infection and multi-organ failure.

• Amputation of the fingers and toes (amputation involves removal of necrosed body parts to prevent infection from spreading to different body parts).

How Is Calciphylaxis Diagnosed?

Doctors diagnose calciphylaxis based on medical history, physical examination, and the symptoms. The health care professional may order specific tests that include:

• Blood Tests: Blood tests help assess kidney functioning by measuring the values of different substances like calcium, phosphorus, parathormone, urea nitrogen, creatinine, and albumin, and defects in blood-clotting factors.

• Skin Biopsy: A small part of the affected skin is removed and sent to the laboratory for analysis of calciphylaxis.

• Imaging Tests: X-rays help detect branch-like deposits of calcium in the blood vessels of the skin.

How Is Calciphylaxis Managed?

The following treatment options are considered for managing calciphylaxis, which include:

• Wound Care: The main principles of wound care include wound healing and prevention of infection. Different types of care are:

1. Hyperbaric Oxygen Therapy (HBOT): Oxygen therapy is effective in wound healing. The patient is placed in a 100 percent oxygen atmosphere when compared to a normal 20 percent atmosphere, having a slightly higher pressure.

2. Debridement: Debridement involves the removal of the dead skin that promotes wound healing and the prevention of infection.

3. Skin Grafts: Healthy tissues taken from different parts of the body help in wound repair.

4. Antibiotics: These medications help prevent bacterial infections.

• Management of Pain: As the pain in calciphylaxis is very severe, pain medications help the body to rest and heal better.

• Dialysis: The doctor can change the medicines used or the frequency of dialysis to decrease the number of calcium deposits in the body.

• Treatment of Bone Problems: Maintaining a balance of minerals like calcium and phosphorus in the bloodstream is pivotal. Parathyroid gland dysfunction can cause too low or too high levels of parathormone, which needs to be corrected.

• Management of Diet and Nutrition: It is necessary to monitor the diet in kidney disease patients to prevent any malnourishment.

• Medications: Sodium thiosulphate is given intravenously (IV) three times a week during dialysis, which helps prevent calcium build-up in the blood vessels. Cinacalcet is a medicine that is advised for the management of hyperparathyroidism.

• Surgery: Surgery is recommended to remove overactive parathyroid glands.

Conclusion:

Calciphylaxis is a serious condition that causes calcium deposition in small blood vessels of the skin. The outlook of the condition is not positive as the patients cannot survive more than a year, with sepsis (severe infection in the bloodstream) being the primary cause. Patients with long-term kidney disease have to be under the care of a nephrologist (a doctor who treats diseases of the kidneys) who can monitor and treat conditions that can lead to calciphylaxis. Though calciphylaxis is a complicated condition to manage, new research has led to better care options for these patients.