Systemic Sclerosis: Types, Organ Involvement and Treatment

What systemic sclerosis is

Three processes drive systemic sclerosis:

1. Blood vessel damage: small arteries narrow and become fragile, causing Raynaud's phenomenon, finger ulcers, high pressure in the lung arteries and kidney crisis.
2. Autoimmunity: the immune system produces specific autoantibodies and inflammatory signals.
3. Fibrosis: fibroblasts lay down excess collagen, thickening the skin and scarring organs.

The cause is unknown. A genetic tendency combined with environmental triggers, such as silica dust and some solvents, appears to play a role. It is not contagious and not usually inherited directly.

Systemic sclerosis differs from localized scleroderma (morphea), which affects only patches of skin and deeper tissue and does not involve internal organs. For an overview of both, see scleroderma.

Limited vs diffuse systemic sclerosis

CREST syndrome is an older name for limited systemic sclerosis, standing for Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasia. Systemic sclerosis sine scleroderma is a rare form with organ involvement but no skin thickening.

Symptoms

Skin, hands and joints

• Raynaud's phenomenon: fingers turning white, then blue, then red in cold or stress. It is present in over 95% of people and usually the first sign
• puffy, swollen fingers early on
• sclerodactyly: tight, shiny skin on the fingers that limits bending
• skin thickening on the hands, face (small mouth, loss of wrinkles) and, in diffuse disease, the trunk
• painful fingertip ulcers and pitting scars
• calcinosis: hard calcium deposits under the skin
• telangiectasias: small red spots of dilated blood vessels on the face, lips and hands
• itching, joint pain, stiffness and tendon friction rubs

Gut

The gut is affected in about 90% of people:

• heartburn and reflux from a weak lower esophageal sphincter
• food sticking on swallowing
• bloating, early fullness, diarrhea or constipation
• bacterial overgrowth and weight loss
• fecal incontinence

Lungs

• Interstitial lung disease: scarring of lung tissue causing a dry cough and breathlessness; the leading cause of death in systemic sclerosis
• Pulmonary arterial hypertension: high pressure in the lung arteries causing breathlessness, fatigue and eventually right heart failure

Heart and kidneys

• heart muscle fibrosis, rhythm problems and fluid around the heart
• scleroderma renal crisis: a sudden rise in blood pressure with rapidly failing kidneys. It is most common in early diffuse disease and with anti-RNA polymerase III antibodies. High-dose steroids increase the risk

Other

Fatigue, dry eyes and mouth, carpal tunnel syndrome, erectile dysfunction, depression and changes in appearance that affect self-esteem.

Diagnosis

The 2013 ACR/EULAR classification criteria give points for features such as skin thickening of the fingers extending above the knuckles (enough on its own), puffy fingers, fingertip ulcers or scars, telangiectasia, abnormal nailfold capillaries, lung involvement, Raynaud's and specific antibodies.

• Blood tests: a positive ANA is found in over 90%. Specific antibodies help predict the pattern: anti-centromere, anti-Scl-70 and anti-RNA polymerase III.
• Nailfold capillaroscopy: a magnified view of the tiny blood vessels at the base of the nails. Characteristic changes separate scleroderma-related Raynaud's from the common, harmless kind.
• Baseline organ testing: - pulmonary function tests with DLCO (gas transfer) - high-resolution chest CT - echocardiogram and ECG - kidney function, urine tests and blood pressure - 6-minute walk test and NT-proBNP

Ongoing screening

Because organ damage can develop silently, people with systemic sclerosis usually have pulmonary function tests every 6 to 12 months in the first years, a yearly echocardiogram and regular blood pressure checks. A right heart catheterization confirms pulmonary arterial hypertension if screening suggests it. Home blood pressure monitoring is advised, especially in diffuse disease.

Treatment

There is no cure yet, but treatment targets each problem:

• Raynaud's and finger ulcers: keep the whole body warm, stop smoking, calcium channel blockers (nifedipine, amlodipine), PDE-5 inhibitors (sildenafil), IV iloprost, and bosentan to prevent new ulcers.
• Skin thickening: methotrexate or mycophenolate in early diffuse disease.
• Interstitial lung disease: mycophenolate, cyclophosphamide, tocilizumab or rituximab, and the antifibrotic nintedanib to slow scarring. Lung transplant in selected cases.
• Pulmonary arterial hypertension: endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin drugs and riociguat, often in combination.
• Gut: proton pump inhibitors, prokinetic drugs, antibiotics for bacterial overgrowth, and nutritional support.
• Scleroderma renal crisis: urgent treatment with an ACE inhibitor such as captopril, increased to control blood pressure, even if kidney function is falling. Dialysis may be needed, sometimes temporarily.
• Severe, rapidly progressive diffuse disease: autologous hematopoietic stem cell transplantation in selected patients at specialist centers can improve survival.
• Supportive care: physical and occupational therapy to maintain hand and mouth movement, skin moisturizers, and dental care.

Steroids are used cautiously and at low doses because of the risk of renal crisis.

Outlook

The course varies widely. Many people with limited disease live for decades with manageable symptoms. Diffuse disease carries more risk in the first few years, when organ complications usually appear, and skin thickening often softens later. Survival has improved substantially, largely because ACE inhibitors turned renal crisis from usually fatal to usually survivable, and because lung and heart complications are now found earlier. Lung disease and pulmonary hypertension are the main causes of death today.

Frequently asked questions

What is the difference between limited and diffuse systemic sclerosis?

Limited systemic sclerosis affects skin of the hands, forearms, feet, lower legs and face, progresses slowly and carries a later risk of pulmonary hypertension. Diffuse systemic sclerosis also involves the upper arms and trunk, progresses faster and has higher early risks of lung, kidney and heart disease.

Is systemic sclerosis the same as scleroderma?

Scleroderma is the umbrella term. It includes localized scleroderma, which affects only skin, and systemic sclerosis, which also affects blood vessels and internal organs. When doctors say scleroderma in adults, they often mean systemic sclerosis.

What is the life expectancy with systemic sclerosis?

It varies with the type and organs involved. Many people, especially with limited disease and no major lung or heart involvement, live a normal or near-normal lifespan. Diffuse disease with significant lung disease or pulmonary hypertension shortens life expectancy, which is why regular screening matters.

What blood tests are used for systemic sclerosis?

ANA is positive in over 90% of people. Specific antibodies include anti-centromere, linked to limited disease and pulmonary hypertension; anti-Scl-70, linked to diffuse disease and lung scarring; and anti-RNA polymerase III, linked to rapid skin changes and renal crisis.

What is scleroderma renal crisis?

It is a sudden, severe rise in blood pressure with rapidly worsening kidney function, most common early in diffuse systemic sclerosis. Symptoms include headache, vision changes and breathlessness. It needs emergency treatment with ACE inhibitors and is much more survivable than it used to be.