Soft tissue and subcutaneous calcification in connective tissue diseases

Calcinosis is a recognized manifestation of many connective-tissue diseases, especially juvenile dermatomyositis (JDM) and systemic sclerosis; however, little is known about the pathogenesis and the treatment of this condition. The purpose of this review is to discuss the most recently published data about calcinosis in connective-tissue diseases with emphasis on the pathogenesis and its treatment.

Calcinosis is more common in patients with sustained disease-activity and longer disease duration. JDM patients with anti-p140 antibodies and tumour necrosis factor (TNF) α-308AA allele are at an increased risk. Low levels of the calcium-regulating proteins, fetuin-A and osteopontin, have been found in the serum of patients with JDM. Macrophages and cytokines interleukin (IL) 6, IL-1β and TNFα isolated from the calcific tissues in JDM have also been implicated in the pathologic process. Raised tissue expression of advanced glycation end products and their receptor has been noted in patients with systemic sclerosis and systemic lupus erythematosus with calcinosis.

Many agents have been used for treatment of calcinosis but none has been accepted as a standard therapy. Case studies have shown that aggressive treatment of the underling inflammatory condition with intravenous immunoglobulin, anti TNF agents, thalidomide and haematopoietic stem cell transplantation has also led to improvement of the calcinosis. Aggressive management of the underlying inflammatory condition should help in treating as well as decreasing the incidence of calcinosis. Some case studies have focused on agents such as warfarin, bisphosphonates, diltiazem and others, which are primarily aimed at treating the process of calcinosis with varying success.