Management of Progressive Skin Involvement in Diffuse Scleroderma

Skin thickening of early diffuse cutaneous systemic sclerosis (dcSSc) is in itself a major source of pain, disability, and disfigurement. Skin involvement progresses and then tends to plateau, usually within the first 3–5 years and then usually decreases. Predictors of progressive skin disease must be identified, such as short disease duration and joint synovitis, new tendon friction rubs, and positive anti-RNA polymerase III antibody. The modified Rodnan skin score (mRSS) is used clinically and in research practice to assess the degree of skin involvement and is a validated outcome measure. Management of skin involvement must be as early as possible to reduce pain and disability and reduce risk of progression. Adequate analgesia is an important aspect of management. The use of low-dose corticosteroids is controversial and is based more on the presence of arthralgia or arthritis and myalgia or myositis rather than on skin involvement, with the possible exception of pruritus or recent oedematous SSc forms. All patients should be assessed by an occupational therapist. A Bayesian study has shown that oral methotrexate at a dose of 15 mg/week is associated with a high probability of beneficial effect on the mRSS. It is difficult to recommend the use of cyclophosphamide (rather than methotrexate or mycophenolate [MMF]) for the treatment of skin progression in early dcSSc based on current published data. If cyclophosphamide is chosen as a first-line treatment, the duration of treatment should not exceed 12 months, followed by an alternative immunosuppressive drug. The preferred choice of many rheumatologists for first-line treatment of progressive skin involvement in early dcSSc is now MMF. Its use is of course more relevant in cases of associated interstitial lung disease (ILD). There is little evidence to specify whether there is an indication for the use of rituximab in early progressive dcSSc. Tocilizumab failed to reach primary endpoint on mRSS in early dcSSc in a Phase 3 RCT, but showed a significant benefit on forced vital capacity (FVC) in ILD patients. There are some encouraging preliminary results with romilkimab (a bispecific humanized monoclonal antibody which binds and neutralizes IL-4 and IL-13). Autologous hematopoietic stem-cell transplantation (HSCT) can be used for the treatment of severe and rapidly progressive dcSSc. However, none of the RCTs were designed to evaluate the benefit of HSCT on skin involvement as a primary endpoint, but a benefit was observed on mRSS. In conclusion, identifying safe and effective therapies for the skin disease of early dcSSc remains a major unmet need.