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Calcinosis cutis
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Calcinosis cutis is a rare disease of aberrant calcium deposition in the skin and subcutaneous tissue. There are five major types:
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Idiopathic: occurs without tissue injury or metabolic defect (e.g., idiopathic scrotal calcinosis)
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Dystrophic: (most common form) secondary to local tissue damage or alterations in collagen, elastin, or subcutaneous fat but normal calcium and phosphate levels (e.g., in autoimmune connective tissue diseases, post trauma or infection)
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Metastatic: abnormal calcium and/or phosphate metabolism leading to precipitation of calcium salts in normal tissue (hyperparathyroidism, sarcoidosis, chronic kidney failure, malignant neoplasms)
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Iatrogenic: secondary to a treatment or procedure (such as extravasation of calcium or phosphate infusions)
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Calciphylaxis: calcific vasculopathy that occurs in the setting of end-stage kidney disease
Other rare variants of calcinosis cutis that have been described include calcinosis cutis circumscripta, calcinosis universalis, tumoral calcinosis, transplant-associated calcinosis cutis, and milia-like idiopathic calcinosis cutis (usually associated with Down syndrome). Firm white or yellow dermal lesions may ulcerate and extrude a gritty material. It most commonly involves the extensor aspect of joints, particularly the fingers, but can also involve large areas of the body. Stiffening of the skin can limit joint mobility and function, and fingertip lesions may be painful.
Management Strategy
The first step in management is to identify any underlying cause, as the subtype influences the approach to treatment. Principles of treatment are to treat an underlying disease, reduce calcium deposits, minimize inflammation, and physical removal of deposits.
Dystrophic calcification occurs in approximately 25% of patients with systemic sclerosis (SSc) and 10%–40% of patients with juvenile dermatomyositis, but is rare in systemic lupus erythematosus. Examination and investigations for connective tissue disease are therefore strongly recommended. Skin biopsy can help to distinguish cutaneous calcification from ossification.
Elevated interleukin-1 levels, along with interleukin-6, interleukin-1β, and tumor necrosis factor-alpha (TNF-α), are found in patients with juvenile dermatomyositis. Mannose-binding lectin levels were significantly increased in SSc patients with calcinosis. It is positively associated with positive anticentromere, anti-PM/Scl, and anticardiolipin antibodies in SSc patients with calcinosis.
A number of malignancies have been implicated in causing metastatic calcification (e.g., leukemia and multiple myeloma). However, successful treatment of the underlying cause does not always have an impact on calcinosis cutis, which frequently requires other treatment modalities. There are no large studies for the treatment of calcinosis cutis, and most therapies are based on case reports or small case series.
Spontaneous extrusion of calcium salts may occur; this may need surgical encouragement. General measures to improve blood flow to extremities, such as avoiding smoking, stress, and cold exposure, are crucial. Diltiazem , colchicine , and minocycline have shown success, mostly in dystrophic calcinosis cutis associated with dermatomyositis. In particular, colchicine and minocycline have been reported to reduce the frequency of ulceration and inflammation associated with cutaneous calcinosis in patients with limited SSc. The mechanism of action may be mainly through inhibition of matrix metalloproteinases and antiinflammatory effects.
Other beneficial therapies for calcinosis cutis associated with connective tissue disease include: intralesional corticosteroids, aluminum hydroxide supplements, bisphosphonates, probenecid, intravenous immunoglobulin, topical sodium thiosulfate, carbon dioxide laser vaporization, and extracorporeal shock wave lithotripsy .
Warfarin has been advocated in both dermatomyositis and SSc-associated calcinosis for small, calcified deposits. Topical sodium metabisulfite, infliximab, and apremilast are recent approaches that have been tried. Surgical removal can be of benefit for idiopathic calcinosis cutis, large lesions, and lesions as a result of calciphylaxis.
Specific Investigations
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First-Line Therapies
Self-healing dystrophic calcinosis following trauma with transepidermal elimination
Pitt AE, Ethington JE, Troy JL. Cutis 1990; 45: 28–32.
A case of dystrophic calcinosis after trauma that resolved over 8 weeks with spontaneous transepidermal elimination.
Calcinosis cutis: part II. Treatment options
Reiter N, El-Shabrawi L, Leinweber B, et al. J Am Acad Dermatol 2011; 65: 15–22.
Calcinosis cutis in dermatomyositis has been successfully treated with diltiazem (2–4 mg/kg/day), with lower doses being ineffective. Surgical excision or curettage is the treatment of choice in idiopathic calcinosis cutis, especially scrotal calcinosis. It is also effective for small, digital calcified skin lesions. A 16-year-old boy with morphea profunda developed small, calcified deposits on both arms, his chest, and left thigh. He was treated with ceftriaxone 2 g/day intravenously for 20 days, and the calcification diminished within weeks.
A case of juvenile dermatomyositis with severe calcinosis and successful treatment with prednisone and diltiazem
Jiang X, Yi Q, Liu D, et al. Int J Dermatol 2011; 50: 74–7.
A 12-year-old boy with calcinosis secondary to juvenile dermatomyositis received diltiazem at a dose of 30 mg/day, resulting in obvious softening and radiologic regression and functional improvement at 4 months.
Calcinosis cutis occurring in association with autoimmune connective tissue disease: the Mayo Clinic experience with 78 patients, 1996 to 2009
Balin SJ, Wetter DA, Andersen LK, et al. Arch Dermatol 2012; 148: 455–62.
Nine of 17 patients with autoimmune connective tissue disorders showed partial response to treatment with diltiazem at the dose of <480 mg/day. This is recommended as first-line treatment. Eight patients were treated with colchicine (<1.2 g/day), resulting in one patient showing complete response and two patients showing partial response. Six patients received minocycline (200 mg/day). Only one patient showed partial response, two patients did not respond, and the response was unknown in three patients. Four patients were treated with warfarin with only one patient partially responding. Out of the 11 patients who received surgical excision alone, all 11 responded, with eight having a complete response. Another 17 patients had surgical and medical treatment with complete response in 14 patients, partial response in two patients, and no response in one patient.
Localized calcinosis in juvenile dermatomyositis: successful treatment with intralesional corticosteroids injection
Al-Mayouf SM, Alsonbul A, Alismail K. Int J Rheum Dis 2010; 13: e26–8.
A 10-year-old boy with juvenile dermatomyositis had calcinosis of his left elbow. It was treated with Depo-Medrol 80 mg and xylocaine 1% under ultrasound guidance with significant improvement.
Severe calcinosis cutis with cutaneous ulceration in juvenile dermatomyositis
Meher BK, Mishra P, Sivaraj P, et al. Indian Pediatr 2014; 51: 925–7.
A 7-year-old girl with severe calcinosis cutis with ulceration improved, with healing of the ulcer and resolution of nodules, after 1 month of oral prednisolone (1 mg/kg/day) and methotrexate (10 mg/week).
Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline
Robertson LP, Marshall RW, Hickling P. Ann Rheum Dis 2003; 62: 267–9.
In an open-label study, eight out of nine patients with limited cutaneous SSc prescribed minocycline 50 mg or 100 mg daily showed definite improvement. The frequency of ulceration and inflammation associated with the calcinosis deposits decreased with treatment. A reduction in calcinosis size was evident but less dramatic, with improvement occurring by 5 months. The mean duration of treatment was 3.5 years.
See also Balin et al. earlier regarding colchicine and minocycline.
Dramatic improvement of subcutaneous calcinosis by intermittent, high-dose etidronate plus cimetidine in a patient with juvenile dermatomyositis
Wakabayashi T, Sasaki N, Chinen N, et al. Case Rep Rheumatol 2015, Article ID 817592, 3 pages, 2015.
A 17-year-old boy with juvenile dermatomyositis and bilateral extensive lower limb calcinosis extending into the subcutaneous tissue and muscle showed marked improvement with intermittent six monthly high-dose etidronate (800 mg/day for 3 months) and cimetidine for over 5 years.
Effectiveness of the treatment with intravenous pamidronate in calcinosis in juvenile dermatomyositis
Marco Puche A, Calvo Penades I, Lopez Montesinos B. Clin Exp Rheumatol 2010; 28: 135–40.
Three children with juvenile dermatomyositis received treatment with intravenous pamidronate at 1 mg/kg/day on 3 consecutive days every 3 months. In all three cases calcinosis significantly decreased and even totally cleared in one of them.
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