Calcinosis

Summary of the talk presented to the London and South East Group December ‘06 by Geraldine Brough

Calcinosis is a significant source of pain and disability in patients with scleroderma. As yet there is no known cure. The literature reveals a paucity of studies of its treatment. There are no pharmacological treatments to prevent or eliminate calcinosis. Reported rates of calcinosis in scleroderma patients vary between 20 and 40 percent. Yet Xrays confirm an additional 20 percent making the prevalence probably much higher.

Scleroderma is not the only connective tissue disease associated with calcinosis. Reports indicate about 17 percent of patients with systemic lupus erythematosus and between 30 and 70 percent of patients with dermatomyositis are affected by this condition.

So, what do we know about the causes of calcinosis? It is known to occur in damaged tissue for whatever reason and also in low vascularised tissue. So does hypoxia, or low oxygenation, play a role? We know that there seems to be a relationship between calcinosis and severe Raynaud's.

Calcium and phosphate in normal tissues are close to their saturation. Abnormal levels of calcium and phosphorus will lead to calcification in normal tissues. Such conditions arise in hyperparathyroidism and in some cases of malignant cancer where there is an associated rise in serum calcium. Calcification is then found as firm nodules located just below the skin around the large joints.

In renal failure, where there is again alteration of concentration of calcium and phosphorus, calcification occurs in the blood vessel walls leading to thrombosis and death of tissues which are supplied by those vessels.

In connective tissue diseases such as systemic sclerosis the calcium/ phosphorus levels in the blood are normal and calcinosis usually occurs around pressure sites such as finger tips, forearms, elbows, ears, buttocks, hips, knees and feet where it usually arises as nodules, plaques or large masses. Many of these sites are in the periphery and therefore subject to poorer circulation and reduced temperatures. These factors are all thought to contribute to calcinosis formation.

So what treatments have been tried and do we have any evidence of their effectiveness or even of their mechanism of action?

There are anecdotal reports for the use of Warfarin, colchicine and probenecid (drugs used in acute gout), bisphosphonates (normally used for the treatment of osteoporosis), anti-TNF agents (used in rheumatoid arthrtitis) and diltiazem (a calcium channel blocker used extensively in the treatment of hypertension and for effective relief of Raynaud's phenomenon).

Surgical treatment (occasionally with the use of a dental drill) is effective for temporarily debulking larger troublesome lesions, while smaller superficial lesions may respond to carbon dioxide laser.

Recent studies (Shetty S et al), using a small number of patients, have looked at driving a small current into the skin and replacing the calcium carbonate with acetate to form a more soluble compound. Ultrasound was then applied. Results showed only a small reduction of calcium on Xray and further studies are ongoing.

Minocycline is known to have antibiotic, anti-inflammatory and calcium binding activities as well as inhibiting some of the enzymes associated with laying down excess collagen. We have tried this in a number of patients in our unit with reduction in inflammation and possible progression of calcinotic lesions in a few who could tolerate this treatment. However the effects are small and we still do not have either an effective treatment or adequate mechanisms to prevent calcinosis occurring.

We do know however that if and when these lesions become infected, they should be treated early with the most appropriate antibiotic for an adequate period of time in order to affect the best outcome for the patient in terms of pain relief and restoration of function.

References:

Calcinosis in Rheumatic Diseases N.Boulman et al. Seminars in Arthritis and Rheumatism 2005

Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline. L.P Robertson et al Annals of Rheumatic Diseases 2003; 62:267-269

A pilot study of acetic acid iontophoresis and ultrasound in the treatment of systemic sclerosis-related calcinosis. Rheumatology(Oxford) 2005 April;44(4)536-538. Epub 2005 Jan.11