Autoimmune Disease: Scleroderma Overview

Scleroderma is an autoimmune disease that is typically characterized by progressive fibrosis and inflammation. However, it is a complex disorder that affects multiple systems in the body, and the clinical presentation of this condition can vary widely between individual patients.¹

Scleroderma is broadly divided into two types: localized scleroderma and systemic scleroderma (also called systemic sclerosis or SSc).² The localized form affects the skin and subcutaneous tissue. While the skin is affected in people with the systemic form of the disorder as well, this type can also damage blood vessels and internal organs. Cases of systemic scleroderma can be further classified as limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, or systemic sclerosis sine scleroderma, depending on what parts of the body are involved.^{3 , 4}

The age of onset for scleroderma can vary depending on the type. Systemic scleroderma generally appears between the ages of 30 and 50 years; juvenile onset for this type of scleroderma is rare.^{3 , 5} Scleroderma occurs at earlier ages in women than in men, and it is more common overall among women.³ For example, the incidence of systemic sclerosis is between four and five times higher in women than in men.⁶ The reasons for these disparities are not entirely clear, but genetic factors appear to play a role in the development of this condition, especially pathways that involve the X chromosome.⁷ Exposure to certain environmental factors (e.g., silica dust) and viruses (e.g., Epstein-Barr virus) have been associated with cases of systemic scleroderma.^{3 , 8}

Diagnosing scleroderma typically involves a clinical evaluation (which may include a skin biopsy) and a series of autoantibody tests.^{3 , 9} While there are no definitive treatments for scleroderma, some of the signs and symptoms can be managed with medications. Immunosuppressants, such as azathioprine, cyclophosphamide, or methotrexate, are often beneficial for people with systemic scleroderma.³ However, treatment plans will vary depending on the type of scleroderma and the stage of the disease. More research is needed to develop effective treatments for systemic scleroderma, especially treatments that can inhibit fibrosis in a variety of different organs.^{10 , 11} Recent research has identified some potential targets for disrupting fibrosis, including B cells and the transforming growth factor β (TGF- β) pathway.^{11 , 12} Tocilizumab, nintedanib, and rituximab may be helpful in treating systemic sclerosis-associated interstitial lung disease, a common cause of death among people with systemic scleroderma.¹³

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports researchers who are investigating the causes of scleroderma and potential treatments for the symptoms of this condition. Areas of ongoing research include identifying the genetic factors that are linked to scleroderma and scleroderma-associated lung fibrosis, understanding the role of cytokines in the development of scleroderma, and locating targets for new therapies.¹⁴ One NIAMS-supported observational study is looking at people who have a common complication of systemic scleroderma called calcinosis cutis, in which painful calcium deposits form in the skin. Currently, there are no treatment guidelines for this condition, in part because it is difficult to quantitatively measure the effectiveness of potential treatments. This study aims to test the performance of two novel quantitative outcomes for calcinosis, which could be used in future Phase 3 trials of treatments for this condition.¹⁵