Cutaneous Calcification

Cutaneous calcification occurs when calcium salts build up in the skin and tissue beneath it, forming hard deposits that can range from harmless bumps to painful, disabling lesions that significantly affect daily life.

Calcinosis cutis

L94.2

Table of contents

• What is cutaneous calcification?
• Types of cutaneous calcification
• What causes cutaneous calcification?
• Signs and symptoms
• How is it diagnosed?
• Treatment options

What is cutaneous calcification?

Cutaneous calcification is a condition in which calcium salts are deposited in the skin and subcutaneous tissue (the innermost layer of skin that contains fat). These calcium deposits consist primarily of hydroxyapatite crystals or amorphous calcium phosphate.^[1] The deposits form hard bumps that don’t dissolve on their own.

The condition was first described by Virchow in 1855.^[4] While calcium is essential for healthy bones and teeth, sometimes it accumulates in places where it shouldn’t. The calcium and phosphate in your blood are normally in a relatively stable balance. When this balance is disrupted, or when tissue becomes damaged, solid calcium deposits can form in the skin.^[8]

This is a rare condition that has many different causes, ranging from infection and injury to chronic diseases like kidney failure.^[14]

Types of cutaneous calcification

Cutaneous calcification is classified into five main types based on what causes the calcium to deposit:^[1]

Dystrophic calcification is the most common type. It occurs when calcium deposits form in areas where the skin or tissue has been damaged, inflamed, or diseased. People with this type have normal calcium and phosphorus levels in their blood. The tissue damage creates a starting point for calcium to collect.^[1]

Metastatic calcification happens when calcium and phosphorus levels in the blood become abnormally high. Deposits occur when the calcium-phosphate product exceeds a certain value (typically 70 mg²/dL²). This elevated level in the blood causes calcium to precipitate in normal, undamaged tissues.^[1]

Idiopathic calcification occurs without any known cause. People with this type have normal calcium and phosphorus levels, no tissue damage, and no underlying disease. It includes specific conditions such as tumoral calcinosis, subepidermal calcified nodules, and scrotal calcinosis. This type often appears in teenagers and children, and some children are born with these bumps on their scalp and face.^[1]

Iatrogenic calcification results from medical treatments or procedures. It is caused by the administration of calcium or phosphate-containing medications that trigger the precipitation of calcium salts. Examples include calcium deposits on newborns’ heels from repeated blood draws.^[1]

Calciphylaxis is a rare and serious type that involves calcification of small and medium-sized blood vessels. It is associated with chronic kidney failure and dialysis. The blood vessels in the skin or fat layer become hardened by calcium deposits.^[1]

Cutaneous calcification can also be classified by extent. Calcinosis circumscripta refers to calcium deposits limited to an extremity or joint. Calcinosis universalis occurs when there is widespread involvement of subcutaneous tissue and fibrous structures of muscles and tendons.^[1]

What causes cutaneous calcification?

The causes of cutaneous calcification vary depending on the type. The pathogenesis is not completely understood, but metabolic and physical factors play important roles in most cases.^[4]

Dystrophic calcification occurs in damaged, inflamed, or diseased tissue. Tissue damage may result from mechanical injury, chemical exposure, infections, or other factors. Conditions that can cause dystrophic calcification include:^[2]

• Trauma, acne, varicose veins, or burns
• Infections
• Tumors such as pilomatrixoma, cysts, or basal cell carcinomas
• Connective tissue diseases including dermatomyositis, systemic sclerosis, cutaneous lupus erythematosus, and mixed connective tissue disease
• Panniculitis
• Inherited diseases of connective tissue such as Ehlers-Danlos syndrome, Werner syndrome, Pseudoxanthoma elasticum, and Rothmund-Thomson syndrome

Dystrophic calcification is frequently associated with systemic autoimmune rheumatic diseases. The most common are systemic sclerosis and dermatomyositis, followed by mixed connective tissue disease, and rarely, systemic lupus erythematosus.^[3] In systemic sclerosis, the calcium deposits are characterized by hydroxyapatite and amorphous calcium phosphate crystal deposition in the extracellular matrix of the dermis and subcutaneous tissue.^[3]

Metastatic calcification occurs when calcium and phosphate metabolism is abnormal, often with high blood levels of calcium and/or phosphate. Conditions that can cause metastatic calcification include:^[2]

• Primary or secondary hyperparathyroidism
• Paraneoplastic hypercalcemia
• Destructive bone diseases such as Paget disease
• Milk-alkali syndrome
• Excessive vitamin D intake
• Sarcoidosis
• Chronic kidney disease or chronic renal failure

Iatrogenic calcification arises from medical procedures, such as parenteral administration of calcium or phosphate, contact with calcium chloride paste used in electrode tests, organ transplant, or calcium deposition in newborns from repeated heel sticks.^[2]

Infections can also lead to calcification. Necrotic tissue produced by an infectious process may subsequently become calcified. Some infectious granulomas produce a form of vitamin D that promotes calcium deposition. Infections that may result in cutaneous calcification include onchocerciasis, cysticercosis, histoplasmosis, cryptococcosis, and intrauterine herpes simplex.^[4]

Signs and symptoms

The signs and symptoms of cutaneous calcification vary according to the underlying cause and location. In many cases, the lesions develop gradually and are often without symptoms initially.^[2]

The lesions usually appear as firm, whitish or yellowish bumps (papules), flat raised areas (plaques), or larger lumps (nodules) on the surface of the skin. A single lesion may develop, although multiple lesions are more common. They can be skin-colored or white, and hard or soft. The shape and size vary.^[2]

Lesions may become tender and ulcerate, discharging a chalk-like creamy material consisting mainly of calcium phosphate with a small amount of calcium carbonate. Some might leak a white fluid and be very painful.^[2]

Depending on the type of cutaneous calcification, lesions can appear in different places on the body. Common locations include:^[6]

• Elbows, fingers, knees, and forearms
• Buttocks
• Around joints
• Face, scalp, and eyelids
• Under lupus sores (in people with lupus)

Fingertip lesions may be particularly painful, while lesions at other sites may restrict joint mobility and limit movement due to stiffening of the skin. In severe cases, complications can include trouble walking or moving, disability, skin ulcers, muscle or tendon rigidity, joint deformity, loss of movement, and in rare cases, cutaneous gangrene (tissue death).^[2]

In systemic sclerosis and dermatomyositis, calcinosis appears more frequently in juvenile dermatomyositis, where as many as 70% of patients may be affected. In adults with myositis, about 20% of patients report this complication.^[18] Calcinosis usually appears within the first three years after diagnosis, however, it is sometimes the first symptom to appear. Other times, it doesn’t occur until many years after diagnosis.^[18]

How is it diagnosed?

Diagnosis of cutaneous calcification involves several approaches to determine the type, extent, and underlying cause of the condition.

Laboratory tests are performed to determine any metabolic abnormalities that may give rise to elevated calcium and phosphate levels. These tests measure serum calcium and phosphorus to distinguish between dystrophic calcification (normal levels) and metastatic calcification (abnormal levels).^[2]

Radiological examinations are useful in demonstrating the extent of tissue calcification. These include plain film X-ray, CT scanning (computed tomography), and bone scintigraphy (a type of nuclear imaging).^[2] On imaging, calcium deposits appear as bright white spots or areas.

Biopsy of cutaneous lesions is used to confirm the diagnosis. During a biopsy, a small sample of affected skin is removed and examined under a microscope. On histology (microscopic examination) of cutaneous calcification, granules and deposits of calcium are seen in the dermis (the layer of skin beneath the outer surface), often with a surrounding foreign-body giant cell reaction. Calcium deposits may also be found in subcutaneous tissue.^[2]

The underlying cause of cutaneous calcification should be identified. This may require additional testing to look for associated conditions such as connective tissue diseases, kidney disease, or metabolic disorders.^[2]

Treatment options

Treatment for cutaneous calcification can be challenging, and the effectiveness varies from person to person. Medical therapy is generally of limited and variable benefit. The underlying cause should be identified and treated accordingly.^[2]

Early and aggressive treatment of underlying diseases such as dermatomyositis with immunosuppression (medication that reduces immune system activity) is strongly recommended, as inadequate initial treatment may play a role in the development of calcium lesions.^[18]

Medical treatments that may be tried include:^[2]

• Corticosteroids (anti-inflammatory medications)
• Bisphosphonates (medications that may reduce bone turnover and inhibit growth of calcium crystals)
• Probenecid and colchicine
• Diltiazem (a calcium-channel blocker)
• Magnesium and aluminum antacids (which may act as phosphate binders)
• Topical or intralesional sodium thiosulfate
• Warfarin (a blood thinner)
• Minocycline (an antibiotic)

Sodium thiosulfate has shown promise in various forms. Topical sodium thiosulfate can be self-applied but requires patient adherence, with treatment typically lasting several months (mean 4.9 months, range 2-24 months). Intralesional sodium thiosulfate injections have been reported to decrease pain associated with calcification. Intravenous sodium thiosulfate has been used in some cases, particularly for calciphylaxis.^[19]

In a study of minocycline for cutaneous calcification associated with limited systemic sclerosis, improvement was noted in eight of nine patients within 1-7 months. Although lesion size was only moderately improved, ulceration and inflammation were markedly reduced.^[11]

Surgical or minimally invasive treatments may be indicated when lesions:^[2]

• Become very painful
• Ulcerate and cause recurrent infections
• Cause functional impairment

Options include surgical excision, carbon dioxide laser removal, or extracorporeal shock-wave lithotripsy (ESWL). Laser therapy has enabled complete remission of small calcium deposits (microcalcifications) after a single procedure in some cases. However, because surgical trauma may stimulate further calcification, it may be best to excise a small site before proceeding with a large excision.^[2]

A systematic review of local, non-systemic, and minimally invasive therapies found that partial or complete remission after single treatment approaches was observed in 64% to 81% of cases. The most common adverse event was scarring and hyperkeratosis (thickening of the outer layer of skin), observed after CO2 laser treatment. Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up period were rare (2%).^[19]

Lifestyle measures may also be helpful. Increasing blood flow to the extremities through smoking cessation, stress reduction, and limiting exposure to cold may be beneficial. Appropriate sun protection is always important in dermatomyositis and may also help prevent calcification, since sun exposure can stimulate the immune system.^[18]

The good news is that cutaneous calcification occasionally clears on its own with no intervention.^[18] However, treatment remains challenging, and patients should work closely with their healthcare providers to find the most effective approach for their individual situation.