Systemic Sclerosis (SSc)

Systemic sclerosis is a systemic autoimmune disease involving three major processes: vascular injury, abnormal immune activity, and tissue fibrosis.

Skin changes are characteristic, but SSc is not simply a skin disorder. It can also affect the gastrointestinal tract, lungs, heart, kidneys, and musculoskeletal system.

The two major clinical subsets are limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis.

Limited cutaneous disease primarily affects the fingers, hands, forearms, and face, whereas diffuse cutaneous disease may extend to the upper arms, thighs, or trunk and is associated with a higher risk of certain internal organ complications.

The exact cause of systemic sclerosis is unknown.

Current evidence suggests that genetic susceptibility, abnormal immune responses, vascular injury, and environmental factors may all contribute. Immune activation can stimulate fibroblasts and excessive collagen deposition, leading to fibrosis of the skin and internal organs.

SSc has a genetic component, but it is not inherited in a simple pattern. Having a family member with the disease does not mean that other relatives will necessarily develop it.

Symptoms vary widely between patients. Common manifestations include:

• Raynaud phenomenon

• Swollen fingers or hands

• Progressive skin thickening and tightening

• Reduced finger mobility

• Painful fingertip ulcers

• Joint pain or stiffness

• Acid reflux or heartburn

• Difficulty swallowing

• Bloating, diarrhea, or constipation

Some patients also develop telangiectasias or calcium deposits beneath the skin.

Lung involvement may cause persistent dry cough, shortness of breath with activity, or reduced exercise tolerance.

Cardiac involvement may cause chest discomfort, palpitations, shortness of breath, or abnormal heart rhythms.

Scleroderma renal crisis can cause a sudden rise in blood pressure and rapid decline in kidney function and requires urgent treatment.

There is no single diagnostic test for systemic sclerosis. Diagnosis is based on the overall combination of clinical features, autoantibodies, and assessment of internal organs.

Common tests include ANA, anticentromere antibodies, anti-topoisomerase I antibodies, anti-RNA polymerase III antibodies, blood and urine testing, nailfold capillaroscopy, pulmonary function tests, high-resolution chest CT, and echocardiography.

The 2013 ACR/EULAR classification criteria remain widely used. They consider features such as skin thickening, puffy fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, Raynaud phenomenon, interstitial lung disease or pulmonary arterial hypertension, and SSc-related autoantibodies. 

Skin biopsy is not routinely required for diagnosis.

There is no single medication that treats every aspect of systemic sclerosis. Treatment is tailored to the specific involvement of the skin, blood vessels, lungs, gastrointestinal tract, heart, and kidneys.

Current EULAR recommendations organize treatment according to major clinical domains including Raynaud phenomenon, digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis, skin fibrosis, interstitial lung disease, gastrointestinal manifestations, and arthritis.

Raynaud phenomenon and digital ulcers may be managed with cold protection and vasodilator therapies.

For SSc-associated interstitial lung disease, mycophenolate is an important treatment option. Depending on disease severity and progression, cyclophosphamide, rituximab, tocilizumab, or nintedanib may also be considered.

Pulmonary arterial hypertension requires specialist-directed treatment with pulmonary vasodilator therapies, often using combination treatment according to risk.

Gastrointestinal symptoms are managed according to the specific problem, including acid suppression for reflux and targeted treatment for motility disorders or bacterial overgrowth.

Scleroderma renal crisis requires urgent treatment, with ACE inhibitors playing a central role.