Calcinosis Cutis Clinical Presentation
- Author: Julia R Nunley, MD; Chief Editor: Dirk M Elston, MD more...
Most lesions of calcinosis cutis develop gradually and are asymptomatic. However, the history and evolution of the lesions depend on the etiology of the calcification. Patients with dystrophic calcification may provide a history of an underlying disease, a preexisting dermal nodule (which represents a tumor), or an inciting traumatic event. Patients with metastatic calcification most frequently have a history of chronic renal failure. Cases of idiopathic calcinosis cutis usually are not associated with previous trauma or disease. Those who develop iatrogenic calcinosis cutis generally have a history of recent hospitalization.
The clinical presentation of calcinosis cutis can vary according to the diagnosis and underlying process. In general, multiple, firm, whitish dermal papules, plaques, nodules, or subcutaneous nodules are found in a distribution characteristic for the specific disorder. At times, these lesions may be studded with a yellow-white, gritty substance. Not infrequently, the lesions spontaneously ulcerate, extruding a chalky, white material. Most lesions are asymptomatic, though some may be tender, and others may restrict joint mobility. When severe, vascular calcification can cause diminished pulses and cutaneous gangrene.
Note the images below.
Note the following types and manifestations:
Dystrophic calcinosis cutis: Calcification is usually localized to a specific area of tissue damage, though it may be generalized in some disorders.
Metastatic calcinosis cutis: Calcium deposition frequently is widespread. Large deposits are frequently found around large joints, such as knees, elbows, and shoulders, in a symmetrical distribution. Visceral organ deposition of calcium in the lung, kidneys, blood vessels, and stomach actually occurs more frequently than deposition within the skin or muscle.
Idiopathic calcinosis cutis: Calcification most commonly is localized to one general area.
Iatrogenic calcinosis cutis: Calcification generally is located at the site of an invasive procedure, though diffuse deposition may occur.
Disorders of calcinosis cutis may be categorized according to the type of calcification process, ie, dystrophic, metastatic, idiopathic, and iatrogenic.
Dystrophic calcification occurs in the setting of normal serum calcium and phosphate levels. The primary abnormality is damaged, inflamed, neoplastic, or necrotic skin. Tissue damage may be from mechanical, chemical, infectious, or other insults.
Localized tissue damage
Extraosseal calcification can occur in the setting of many local and destructive processes, including burns, arthropod bites, acne lesions, varicose veins, and rhabdomyolysis, among others.
Necrotic tissue produced by an infectious process may subsequently become calcified. Some infectious granulomas produce 1,25-vitamin D. Infections that may result in calcinosis cutis include onchocerciasis, cysticercosis, histoplasmosis, cryptococcosis, and intrauterine herpes simplex.
Benign and malignant tumors may develop calcification. Pilomatrixoma, or calcifying epithelioma of Malherbe, is the most common tumor that becomes calcified. Epithelial cysts and syringomas also have a significant tendency to calcify. Foci of calcification commonly are seen in histologic sections of basal cell carcinomas. In rare cases, melanocytic nevi, malignant melanoma, atypical fibroxanthoma, hemangioma, pyogenic granuloma, seborrheic keratoses, neurilemomas, and trichoepitheliomas show foci of calcification.
Generalized tissue damage
Connective tissue diseases
Examples are dermatomyositis[2, 3] ; lupus erythematosus[4, 5, 6, 7] ; systemic sclerosis; and calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasias (CREST) syndrome.
In dermatomyositis, calcification occurs 3 times more commonly in juvenile dermatomyositis than the adult-onset form and may be seen in 30-40% of patients. In the setting of dermatomyositis, calcinosis cutis is associated with longer disease duration, fingertip ulcers, and NXP-2 autoantibodies. There is a negative association with transcriptional intermediary factor 1-γ antibodies. Typically, calcification is accentuated over joints, sparing the digits. Aggressive corticosteroid therapy decreases the incidence of calcification.
In lupus erythematosus, calcification is rare and usually an insignificant incidental radiologic finding. Calcification occurs most frequently with long-standing systemic disease, and though calcification may develop in lesions of lupus profundus, it usually is not associated with panniculitis. However, an associated myositis may be present. Lesions characteristically are on the extremities.
Regarding scleroderma, systemic scleroderma and CREST syndrome are related diseases frequently associated with the late development of tissue calcification.
Subcutaneous fat necrosis of the newborn typically affects full- or post-term newborns within the first few days to weeks of life. Necrosis of subcutaneous tissues, predominantly on the shoulders and buttocks, results in nodules and plaques that may become calcified. The cause is unknown. Possible inciting events are obstetric trauma, maternal pre-eclampsia or diabetes, or neonatal hypothermia or hypoxia. Pancreatitis or pancreatic malignancy may result in inflammation of the panniculus. The combination of fatty acids released by damaged fat cells and calcium may lead to calcium salt formation.
Examples are Ehlers-Danlos syndrome, Werner syndrome, pseudoxanthoma elasticum, and Rothmund-Thompson syndrome.
Ehlers-Danlos syndrome is a group of inherited disorders of collagen metabolism. Individuals with Ehlers-Danlos type I may develop calcification in healing surgical scars and subcutaneous nodules.
Werner syndrome is an inherited disorder of premature aging. Soft tissue calcification may involve the ligaments, tendons, synovia, vasculature, and/or subcutaneous tissue.
Pseudoxanthoma elasticum is a disorder of abnormal elastic fibers. Calcification occurs in the elastic fibers causing rupture. Late in the disease, collagen fibers may become calcified.
In Rothmund-Thomson syndrome, small, yellow papules of calcification may be numerous on the extremities.
Metastatic calcification arises in the setting of abnormal calcium or phosphate metabolism and is generally associated with hypercalcemia and/or hyperphosphatemia.
Primary or secondary hyperparathyroidism
In primary hyperparathyroidism, the parathyroid glands become hyperplastic and autonomously overproduce parathyroid hormone. Secondary hyperparathyroidism is a functional response to hypocalcemia. The causes of hypocalcemia may be numerous, but the most common cause is chronic renal failure.
Hypercalcemia may occur as part of a malignancy syndrome due to bony metastases or the production of an abnormal hormone that directly affects calcium and bone metabolism.
Destructive bone disease
Malignancy and other conditions, such as Paget disease, may induce enough bone destruction to cause hypercalcemia.
Uncommon today, this syndrome is caused by excessive consumption of sodium bicarbonate and calcium-containing compounds. The result is a metabolic alkalosis with hypercalcemia, hyperphosphatemia, nephrocalcinosis, and renal failure.
Excessive vitamin D
Overconsumption of vitamin D may increase GI calcium absorption, as well as renal calcium reabsorption, giving rise to hypercalcemia. This mechanism is relatively uncommon.
The sarcoidal granuloma may overproduce 1,25-vitamin D, with subsequent hypercalcemia and an elevated calcium-phosphate product.
Chronic renal failure
This is the most common setting in which metastatic calcification occurs. Chronic renal failure affects many factors in calcium metabolism. Hyperphosphatemia due to decreased renal clearance occurs relatively early. Hypocalcemia is the direct result of this hyperphosphatemia and worsened by vitamin D deficiency due to renal failure. As a compensatory measure, excessive parathyroid hormone is produced. This augmentation results in increased calcium and phosphate mobilization; an elevated solubility product; and, subsequently, the formation and precipitation of calcium salts.
This is a poorly understood, highly morbid process that most commonly affects patients with end-stage renal disease. Calcification occurs in the intima of the blood vessels and subcutaneous tissue. Microthrombi formation is a frequent finding. The exact mechanism remains unknown, but the most common unifying disorders are renal failure, hypercalcemia, hyperphosphatemia, and hyperparathyroidism.
Idiopathic calcinosis cutis
Idiopathic calcinosis cutis occurs in the absence of known tissue injury or systemic metabolic defect.
Idiopathic calcinosis of scrotum, penis, or vulva
Calcification may occur after trauma, or it may occur in the absence of known tissue injury. Calcinosis cutis of the penis may also result from calcification of an epidermal cyst.
Milia-like idiopathic calcinosis cutis[9, 10, 11, 12]
Many cases have been associated with Down syndrome and/or syringoma formation. Lesions are usually multiple and occur on the trunk, limbs, and face. The etiology remains controversial, but some evidence of calcium deposition in the sweat glands is present.
Subepidermal calcified nodule
These lesions usually develop in early childhood and are typically solitary, though multiple lesions can also be present. The nodules most commonly occur on the face, though they may occur anywhere. The pathogenesis is unknown, but the lesions may be due to calcification of components of adnexal structures.
This may be caused by an error in renal phosphate metabolism resulting in hyperphosphatemia. General characteristics of the calcified nodules are a large size, a juxta-articular location, progressive enlargement, a tendency to recur after surgical removal, and the ability to encase the adjacent normal structures. The most common locations of calcification are the hip, elbow, scapula, foot, leg, knee, and hand. Tumoral calcinosis is often familial, and the hereditary pattern suggests that it is an autosomal recessive trait. Vitamin D deficiency may also be associated with hyperphosphatemia.
Calcinosis cutis circumscripta and calcinosis universalis
These forms are rare and may be due to altered ground substances. Calcinosis cutis circumscripta generally occurs earlier and tends to involve the extremities, whereas calcinosis universalis occurs later and is usually more widespread. Both have been associated with trauma, foreign body reaction, and (on occasion) scleroderma.
Transplant-associated calcinosis cutis[13, 14, 15]
In addition to calciphylaxis, numerous cases of calcinosis cutis have been described in transplant recipients. Although calcinosis cutis appears to be most common after renal transplantation, it is also described in liver, heart, and lung transplantation. The etiology of this calcification is unknown. Perhaps patients are infused with large numbers of blood products containing citrate and calcium that create an environment that favors calcification. The role of other factors remains to be elucidated.
Iatrogenic calcinosis cutis arises secondary to a treatment or procedure.[16, 17, 18, 19]
Parenteral administration of calcium or phosphate
The intravenous administration of solutions containing calcium or phosphate may cause the precipitation of calcium salts and lead to calcification.
Parental inorganic phosphate
This has been implicated.
Tumor lysis syndrome
Cutaneous calcification associated with tumor lysis syndrome is due to several factors, including chemotherapy-induced tissue damage with resultant hyperphosphatemia, hypocalcemia, hyperuricemia, and the potential for acute renal failure. Hypocalcemia frequently requires parenteral calcium use, increasing the possibility of tissue calcification.
Repeated heel sticks in the newborn
Calcium salt deposition may occur in newborns at sites of repeated heel sticks.
Prolonged use of calcium-containing electrode paste
Prolonged placement of electrode pastes containing calcium on abraded skin in diagnostic procedures such as electroencephalography, electromyography, or brainstem auditory evoked potential testing may result in calcium deposition at the placement site.
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