From the Guidelines
SCL70 (anti-topoisomerase I) positivity in systemic sclerosis is associated with more severe and extensive skin manifestations, including diffuse cutaneous systemic sclerosis (dcSSc), characterized by widespread skin thickening, digital ulcers, calcinosis cutis, telangiectasias, and skin hyperpigmentation or hypopigmentation. The skin manifestations of SCL70 positivity in systemic sclerosis can be broken down into several key features:
- Diffuse cutaneous systemic sclerosis (dcSSc) with widespread skin thickening that extends proximally beyond the elbows and knees, often involving the trunk, face, and neck
- Digital ulcers
- Calcinosis cutis
- Telangiectasias
- Skin hyperpigmentation or hypopigmentation with a salt-and-pepper appearance
- Facial involvement leading to microstomia (small mouth opening) and a characteristic expressionless appearance with thinning of the lips
- Raynaud's phenomenon, which is nearly universal and typically precedes other skin changes 1. These skin manifestations are a result of the anti-topoisomerase I antibodies targeting nuclear enzymes involved in DNA replication, leading to increased fibroblast activity and excessive collagen deposition in the dermis, as noted in studies on the treatment of systemic sclerosis 1. The most recent and highest quality study on the treatment of systemic sclerosis, published in 2025, provides updated recommendations for the treatment of skin fibrosis, including the use of mycophenolate mofetil, nintedanib, rituximab, and tocilizumab 1. The treatment of skin manifestations in SCL70 positive systemic sclerosis should prioritize the use of immunosuppressive therapies, such as mycophenolate mofetil or methotrexate, as first-line treatment, with the option to add rituximab, tocilizumab, or switch to oral or cyclophosphamide for patients who do not respond to initial treatment 1.
From the Research
Skin Manifestations of SCL70 Positivity
The skin manifestations of SCL70 (anti-topoisomerase I) positivity in systemic sclerosis are characterized by:
- Skin thickening, which is a hallmark of the disease 2
- Extent of skin involvement, which correlates with disease severity and prognosis 3, 2
- Presence of digital ulcers, which are a common complication of systemic sclerosis 4
- Increased risk of interstitial lung disease (ILD), myositis, scleroderma renal crisis, and cardiac involvement in SCL70-positive patients 5
Classification of Skin Involvement
Skin involvement in systemic sclerosis can be classified into different subsets, including:
- Limited cutaneous systemic sclerosis (lcSSc), which is characterized by skin involvement confined to the face and extremities 3
- Diffuse cutaneous systemic sclerosis (dcSSc), which is characterized by rapid disease progression and widespread skin involvement 3, 5
- Digital ulcers, which can be classified into different subtypes based on their pathogenetic mechanism and localization 4
Measurement of Skin Thickness
Skin thickness can be measured using various methods, including:
- Modified Rodnan skin score (mRSS), which is a fully validated and feasible method for measuring dermal skin thickness 2
- Ultrasound (US) measurement of the dermis, which is a valid and reproducible method for measuring skin thickness 2
- Durometry, which measures the hardness of skin and has been validated as a method for measuring skin thickness 2
Association with Autoantibodies
SCL70 positivity is associated with a higher risk of major organ involvement, including ILD, myositis, and scleroderma renal crisis 5
- The presence of anti-SCL70 antibodies is correlated with the extent of cutaneous involvement and the presence of antinuclear antibodies 6