Calcinosis in Rheumatic Diseases

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Background

Calcinosis, or dystrophic soft-tissue calcification, occurs in damaged or devitalized tissues in the presence of normal calcium/phosphorus metabolism. It is often noted in the subcutaneous tissues of connective tissues diseases—primarily systemic lupus erythematosus, scleroderma, or dermatomyositis—and may involve a relatively localized area or be widespread. The calcinotic accumulations may lead secondarily to muscle atrophy, joint contractures, and skin ulceration complicated by recurrent episodes of local inflammation and infection.

Objectives

To review the classification, pathogenesis, clinical features, and treatment of calcinosis in rheumatic diseases.

Method

A MEDLINE search of articles from 1972 to 2004 was conducted utilizing the index word “calcinosis” with the coindexing terms “scleroderma,” “lupus,” “dermatomyositis,” and “dystrophic calcification.”

Results

Calcinosis may be the source of both pain and disability in connective tissue disease patients. Illustrative cases of patients with severe calcinosis are described. The literature available was critically reviewed. While warfarin, colchicine, probenecid, bisphosphonates, diltiazem, minocycline, aluminum hydroxide, salicylate, surgical extirpation, and carbon dioxide laser therapies have been used, no treatment has convincingly prevented or reduced calcinosis.

Conclusions

Calcinosis is common in the conditions reviewed and a number of agents have been used for treatment. However, the approach to calcinosis management is disorganized, beginning with the lack of a generally accepted classification and continuing with a lack of systematic study and clinical therapeutic trials.

Section snippets

Case 1

An 80-year-old woman, who had been diagnosed with the CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) variant of scleroderma (SSc), hypertension, recurrent gastric bleeding due to “watermelon stomach,” and mild dementia, was hospitalized with prolonged fever and deterioration in general function. Physical examination was notable for hard cutaneous plaques overlying both hips, shoulders, elbows, wrists, and fingers, with small areas of skin

Case 2

A 20-year-old woman with a history of systemic lupus erythematosus (SLE) since age 18 presented with increased oral ulcers, arthralgias, fatigue, “butterfly” facial rash, and erythematous plaques on her skin. Her physical examination revealed, additionally, finger cyanosis of Raynaud’s phenomenon, arthritis of the wrists, and sclerotic erythematous cutaneous plaques resulting in disfigurement of the upper arms and contractures of the elbows. Skin biopsy demonstrated lobular and septal

Methods

A MEDLINE search of articles from 1972 to 2004 was conducted utilizing the index word “calcinosis” with the coindexing terms “scleroderma,” “lupus,” “dermatomyositis,” and “dystrophic calcification.” References noted in relevant articles also were accessed. The articles reviewed herein are not exhaustive, with preference given, where possible, to series over individual case reports.

Pathogenesis (Fig. 3)

Although normal physiologic tissue concentrations of calcium (Ca) and phosphate (P) are close to their saturation, tissue calcification is unusual due to the presence of endogenous inhibitors of calcification (9). Dystrophic calcification occurs in tissues that have been altered in some way to promote calcification, but with normal serum levels of Ca and P. Pathophysiologic changes that promote calcification may include tissue structural damage, hypovascularity and hypoxia, age-related tissue

General Features

Calcinosis may be limited, involving a relatively localized area, with small deposits in the skin and subcutaneous tissues, especially over the extensor aspects of the joints and fingertips. Or it may be widespread, not only in the skin and subcutaneous tissues, but also deeper in periarticular regions and areas of repeated trauma (18, 19, 20). The accumulation of calcinotic material may form small- or medium-sized hard nodules that, secondarily, induce muscle atrophy and contractures (19). In

Treatment of Calcinosis

No pharmacological treatment is generally accepted as standard treatment to prevent or reduce calcinosis. Calcinosis treatment suffers from a notable lack of controlled clinical trials. Warfarin, colchicine, probenecid, bisphosphonates, and diltiazem have been tried with variable success (36). Surgical extirpation can be of benefit for larger lesions (36) and smaller superficial lesions may be effectively treated with carbon dioxide (CO2) laser therapy (37). Minocycline (21), aluminum hydroxide

Discussion

Calcinosis, soft-tissue calcification which occurs in the presence of normal metabolism in damaged or devitalized tissues, is widespread in connective tissue diseases with a prevalence of 17% in SLE, about 25% in scleroderma, and 30 to 70% in DM, including JDM. Although calcinosis is the source of significant pain and disability in these patients, the literature reveals a paucity of studies of its treatment, many reports being extended case descriptions. The lack of a unified classification of

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    Fellow in Rheumatology, Clinical Instuctor

    Senior Physician, Internal Medicine A, Clinical Instructor

    Assistant Director of Rheumatology, Senior Clinical Lecturer

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    Director of Rheumatology, Senior Clinical Lecturer

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