What is Systemic Sclerosis (SSc)?

From the Guidelines

Treatment of systemic sclerosis should be organ-based or aimed at disease modification, with autologous haematopoietic stem cell transplantation considered for patients with early diffuse cutaneous SSc who are at high risk of mortality, as evidenced by the most recent study in 2023 1. The management of scleroderma involves a multidisciplinary approach, focusing on symptom control and prevention of complications. Key considerations include:

• Organ-based treatment, such as mycophenolate mofetil for interstitial lung disease (ILD) and calcium channel blockers for Raynaud's phenomenon 1
• Disease modification, with immunosuppressives and biologic agents like rituximab and tocilizumab, as recommended in the 2023 EULAR update 1
• Autologous haematopoietic stem cell transplantation for patients with early diffuse cutaneous SSc and high-risk features, such as very high skin scores or worsening ILD 1
• Novel therapies, including nintedanib for fibrotic ILD and anti-fibrotic agents for skin fibrosis, as suggested in the 2023 EULAR update 1
• Regular monitoring by a rheumatologist to detect and manage organ involvement early, improving outcomes in patients with systemic sclerosis 1

From the Research

Definition and Clinical Subsets of Scleroderma

• Scleroderma is a complex systemic autoimmune disorder characterized by inflammation, vasculopathy, and excessive fibrosis of the skin and multiple internal organs 2.
• There are two major clinical subsets of scleroderma: systemic sclerosis (SSc) and localized scleroderma (LoS) 2.
• SSc is a rare but significant disease associated with morbidity and mortality, often resulting from organ complications such as lung fibrosis, pulmonary artery hypertension (PAH), and scleroderma renal crisis (SRC) 2.
• LoS, also known as morphea, is confined to the skin and/or subcutaneous tissues, resulting in collagen deposition and subsequent fibrosis 2.

Treatment Options for Scleroderma

• Current treatment modalities in SSc focus on targeting vascular damage, fibrosis, and regulation of inflammation as well as autoimmune responses 2.
• Some canonical medications, including glucocorticoids, immunosuppressants, and vasodilators, have had some success in treating various manifestations in SSc patients 2.
• Biologic agents targeting collagen, cytokines, and cell surface molecules may have promising therapeutic effects in SSc 2.
• Hematopoietic stem cell transplantation (HSCT) has made great progress as a promising treatment option in severe and refractory SSc 2.
• Local skin-targeted therapy, including topical application of glucocorticoids or other immunomodulatory ointments and ultraviolet (UV) irradiation, is generally used for LoS 2.
• Systemic immunosuppressants are also utilized in several forms of LoS 2.

Immunotherapy and Immunosuppression in Scleroderma

• Nonselective immunosuppression, particularly cyclophosphamide, remains the main treatment for progressing skin involvement and active interstitial lung disease in SSc 3.
• Mycophenolate mofetil is a promising alternative to cyclophosphamide 3.
• Newer T-cell and B-cell targeted therapies have provided some encouraging results in small pilot studies 3.
• Immunosuppressive therapy is associated with male gender, interstitial lung disease, anti-Scl70 positivity, ACA negativity, and inflammatory joint disease in limited cutaneous systemic sclerosis 4.
• Methotrexate is being more frequently used, and mycophenolate mofetil has gained favor over cyclophosphamide in the treatment of SSc 4.

Specific Treatments for Scleroderma-Associated Interstitial Lung Disease

• Mycophenolate mofetil (MMF) has been used to treat scleroderma-associated interstitial lung disease, with stable pulmonary function observed in most patients after 12 months of treatment 5.
• Methotrexate has been used to treat patients with scleroderma and mixed connective tissue disease, with available data concerning its efficacy discussed in the literature 6.