Scleroderma (Systemic Sclerosis)

What happens in scleroderma

"Scleroderma" means "hard skin". Three processes drive it:

1. Autoimmunity: the immune system makes autoantibodies and triggers inflammation.
2. Blood vessel damage: small arteries narrow and become fragile, causing Raynaud's, finger ulcers and, in some people, high pressure in the lung arteries or kidney crisis.
3. Fibrosis: fibroblasts produce excess collagen, which stiffens the skin and can scar the lungs, gut and heart.

The cause is unknown. It is not contagious and not usually inherited directly, although a family history of autoimmune disease raises the risk slightly. Exposure to silica dust and some solvents has been linked to systemic sclerosis.

Types of scleroderma

CREST stands for calcinosis, Raynaud's, esophageal problems, sclerodactyly (tight finger skin) and telangiectasias (small red spots). Detailed information on the systemic form is on the systemic sclerosis page.

Early signs of scleroderma

• Raynaud's phenomenon: fingers or toes turn white, then blue, then red in the cold or with stress. Present in more than 95% of people with systemic sclerosis, often years before other signs
• Puffy fingers: swollen, sausage-like fingers, often worse in the morning
• Skin tightening: shiny, tight skin on the fingers, making it hard to make a fist, spreading to the hands and face
• Heartburn and difficulty swallowing
• Itching in early diffuse disease
• Tiredness and joint pain

Symptoms by body system

• Skin: thickening, loss of wrinkles, a small mouth opening, beak-like nose, darkening or loss of pigment, small red spots (telangiectasias) and calcium deposits (calcinosis).
• Fingers: ulcers on fingertips, pitted scars, and shortening of the fingertip bones.
• Gut: reflux and difficulty swallowing affect up to 90%. Also bloating, constipation, diarrhea and poor absorption from slow bowel movement and bacterial overgrowth.
• Lungs: interstitial lung disease causes breathlessness and dry cough. Pulmonary arterial hypertension causes breathlessness, fatigue and fainting.
• Heart: scarring can cause rhythm problems and heart failure.
• Kidneys: scleroderma renal crisis, a sudden rise in blood pressure with kidney failure, mostly in early diffuse disease.
• Muscles and joints: stiffness, pain, tendon friction rubs and contractures.
• Mouth and eyes: dryness from overlap with Sjogren's syndrome.

Diagnosis

A rheumatologist uses the history and examination, often applying the ACR/EULAR classification criteria. Tests include:

1. Antinuclear antibody (ANA): positive in more than 90% of people with systemic sclerosis.
2. Specific antibodies: anti-centromere (limited disease), anti-Scl-70 or anti-topoisomerase I (diffuse disease and lung fibrosis), anti-RNA polymerase III (rapid skin spread and kidney crisis).
3. Nailfold capillaroscopy: magnifies the tiny vessels at the nail base. Enlarged or missing loops point to scleroderma rather than simple Raynaud's.
4. Skin biopsy for localized scleroderma when the diagnosis is unclear.
5. Organ screening at diagnosis and regularly: lung function tests with DLCO, high-resolution chest CT, echocardiogram, ECG, blood pressure, kidney function and urine tests.

Treatment

There is no single cure. Treatment targets the parts of the body affected.

• Skin: methotrexate or mycophenolate for skin thickening. Moisturizers, and topical steroids or phototherapy for morphea.
• Raynaud's and finger ulcers: keeping warm, stopping smoking, calcium channel blockers (nifedipine, amlodipine), PDE5 inhibitors (sildenafil), IV iloprost for severe cases, and bosentan to prevent new ulcers.
• Gut: proton pump inhibitors for reflux, prokinetic drugs for slow movement, antibiotic courses for bacterial overgrowth, and nutritional support.
• Lungs: mycophenolate, cyclophosphamide, tocilizumab or rituximab for interstitial lung disease, and the antifibrotic nintedanib. Pulmonary arterial hypertension is treated with targeted vasodilators.
• Kidneys: ACE inhibitors are lifesaving in renal crisis. Home blood pressure monitoring helps catch it early. High-dose steroids are avoided because they can trigger renal crisis.
• Severe early diffuse disease: autologous stem cell transplantation in carefully selected people at specialist centers.
• Physical and occupational therapy: stretching to preserve hand and mouth movement.

Outlook

Localized scleroderma does not affect internal organs and often softens over 3 to 5 years, although it can leave discoloration or limb differences. Systemic sclerosis varies widely. Limited disease often progresses slowly over decades. Diffuse disease is most active in the first 3 to 5 years, then skin often softens. Lung involvement is now the leading cause of death, which is why regular screening matters. Survival has improved considerably with ACE inhibitors for kidney crisis and better lung and heart treatments.

Living with scleroderma

• Keep the whole body warm, not just the hands. Wear gloves, layers and use hand warmers.
• Do not smoke, and avoid cold-triggering medicines such as decongestants where possible.
• Eat small, frequent meals, sit upright after eating and raise the head of the bed for reflux.
• Moisturize daily and protect fingertips from injury.
• Do daily hand and face stretching exercises.
• Keep appointments for lung function tests, echocardiograms and blood pressure checks.

Frequently asked questions

What are the first signs of scleroderma?

The earliest sign is usually Raynaud's phenomenon, in which fingers turn white or blue in the cold. Many people then notice puffy, swollen fingers, followed by tight, shiny skin on the fingers and hands, heartburn or difficulty swallowing. Localized scleroderma starts instead with a firm, discolored patch of skin.

What is the difference between limited and diffuse scleroderma?

In limited cutaneous systemic sclerosis, skin thickening stays on the fingers, hands, forearms and face, and organ problems usually develop slowly. In diffuse disease, thickening spreads to the upper arms, thighs and trunk, often quickly, and lungs, kidneys and heart are more likely to be affected early.

Is scleroderma life-threatening?

Localized scleroderma is not. Systemic sclerosis can be serious when it affects the lungs, heart or kidneys, but many people, especially with limited disease, live for decades. Early diagnosis, regular organ screening and modern treatments have improved survival considerably.

What is CREST syndrome?

CREST is the old name for limited cutaneous systemic sclerosis. The letters stand for calcinosis, Raynaud's phenomenon, esophageal problems, sclerodactyly (tight finger skin) and telangiectasias (small dilated blood vessels on the skin). It often goes with anti-centromere antibodies.

Is scleroderma hereditary?

Not directly. Most people with scleroderma have no affected relatives, and the risk to a child or sibling is only slightly higher than average. Families with one autoimmune disease do have a somewhat increased rate of other autoimmune conditions.