Systemic sclerosis (scleroderma, including CREST) !
An autoimmune disease that hardens the skin and can scar the lungs, gut, heart and kidneys. It almost always starts with Raynaud phenomenon.
Updated 2026-11-01
Structures involved
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Why it happens
- Fibrosis in organs: TGF-β and the myofibroblast
- Skin blood flow
- Collagen synthesis
- Connective tissue proper: cells and fibres
What it is
A chronic autoimmune connective-tissue disease marked by small-vessel damage and excess collagen (fibrosis) in the skin and internal organs. It has a limited cutaneous form (CREST) and a diffuse cutaneous form.
Who gets it
Uncommon; it affects women about four times more often than men, usually starting between 30 and 50 years of age. It occurs in Colombia and the rest of Latin America, where it is followed in rheumatology clinics; lung disease is the leading cause of death.
Causes
- Autoimmune; cause unknown
- Genetic predisposition interacting with environmental triggers
- Exposures linked to scleroderma-like disease: silica dust, organic solvents and some drugs
Risk factors
- Female sex
- Age 30 to 50
- Family history of autoimmune disease
- Occupational silica or solvent exposure
Pathophysiology
Three processes interact: injury to small-vessel endothelium (Raynaud phenomenon, digital ulcers, renal and pulmonary vasculopathy), autoimmunity with specific autoantibodies, and fibroblast activation that lays down excess collagen. Fibrosis thickens the skin, stiffens the oesophagus, scars the lung interstitium and the heart muscle, while obliterative vasculopathy can cause pulmonary arterial hypertension and scleroderma renal crisis.
Classification
- Limited cutaneous (CREST: Calcinosis, Raynaud phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia): skin of hands, forearms and face; anti-centromere antibodies; later risk of pulmonary arterial hypertension
- Diffuse cutaneous: skin of trunk and proximal limbs; anti-topoisomerase I (Scl-70) or anti-RNA polymerase III; early lung, heart and kidney disease
- Systemic sclerosis sine scleroderma (organ disease without skin thickening)
- Localised scleroderma (morphoea) is a separate skin-only disease
Symptoms and signs
- Raynaud phenomenon (white, blue then red fingers in the cold), often years before other signs
- Puffy fingers that become tight, shiny and thick (sclerodactyly)
- Digital ulcers and pitting scars of the fingertips
- Heartburn and difficulty swallowing
- Shortness of breath on exertion and dry cough
- Small mouth with tight facial skin, telangiectasias and calcium deposits under the skin
- Joint pain, tendon friction rubs and fatigue
Diagnosis
- Clinical
- Skin thickening of the fingers extending proximal to the knuckles is sufficient for classification (ACR/EULAR criteria); other items are sclerodactyly, fingertip lesions, telangiectasia, Raynaud phenomenon, lung disease and specific antibodies. Nailfold capillaroscopy shows dilated or lost capillaries.
- Tests
- ANA positive in most patients; anti-centromere (limited form), anti-Scl-70 and anti-RNA polymerase III (diffuse form, the latter linked to renal crisis). Creatinine, urinalysis and blood pressure; pulmonary function tests with DLCO; NT-proBNP and ECG.
- Imaging
- High-resolution chest CT for interstitial lung disease; echocardiography to screen for pulmonary hypertension, confirmed by right heart catheterisation; barium swallow or manometry for oesophageal dysmotility.
Differential diagnosis
- Primary Raynaud phenomenon
- Morphoea (localised scleroderma)
- Mixed connective tissue disease and overlap syndromes
- Eosinophilic fasciitis
- Scleromyxoedema and nephrogenic systemic fibrosis
- Diabetic cheiroarthropathy
Goal of treatment
There is no cure; treatment is organ-targeted: control Raynaud phenomenon and heal ulcers, slow skin and lung fibrosis, treat pulmonary hypertension and reflux, and detect renal crisis early to save kidney function and life.
Treatment
- Acute
- Scleroderma renal crisis is an emergency treated with ACE inhibitors, even if creatinine is rising; high-dose corticosteroids are avoided because they can trigger it.
- Medical
- Raynaud phenomenon and digital ulcers: calcium channel blockers (dihydropyridines), phosphodiesterase-5 inhibitors and prostacyclin analogues.
- Medical
- Skin and lung disease: immunosuppressants such as mycophenolate, cyclophosphamide or methotrexate, antifibrotic drugs for progressive lung fibrosis, and selected biologics; autologous stem-cell transplantation in carefully chosen severe cases.
- Medical
- Reflux with proton pump inhibitors and prokinetics; pulmonary arterial hypertension with endothelin receptor antagonists, phosphodiesterase-5 inhibitors and prostacyclin pathway drugs.
- Follow-up
- Regular screening: blood pressure (home monitoring in diffuse disease), kidney function, pulmonary function tests and yearly echocardiography.
- Lifestyle
- Keeping the whole body warm, avoiding smoking and cold exposure, skin care, small frequent meals, head-of-bed elevation, and physiotherapy to preserve hand and mouth movement.
Drugs for this condition
Complications
- Interstitial lung disease, the leading cause of death
- Pulmonary arterial hypertension
- Scleroderma renal crisis with malignant hypertension and acute kidney injury
- Myocardial fibrosis, arrhythmias and heart failure
- Digital ulcers, infection and gangrene
- Oesophageal stricture, Barrett oesophagus, gastric antral vascular ectasia (watermelon stomach) and malabsorption
- Hand contractures and disability
Prognosis
Variable. The limited form progresses slowly but can cause pulmonary hypertension after many years; the diffuse form is more aggressive in the first years. Lung and heart disease drive mortality; with ACE inhibitors, renal crisis is no longer the main cause of death.
Test yourself
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What does CREST stand for?
Calcinosis, Raynaud phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia: the limited cutaneous form of systemic sclerosis.
Which autoantibodies distinguish limited from diffuse systemic sclerosis?
Anti-centromere in limited disease; anti-topoisomerase I (Scl-70) and anti-RNA polymerase III in diffuse disease.
How does scleroderma renal crisis present and how is it treated?
Sudden severe hypertension with acute kidney injury, often in early diffuse disease; treated urgently with ACE inhibitors.
Which drug class can trigger scleroderma renal crisis?
High-dose glucocorticoids.
What is the leading cause of death in systemic sclerosis?
Lung disease: interstitial lung disease and pulmonary arterial hypertension.
Related conditions
- Raynaud phenomenon
- Interstitial lung disease
- Gastro-oesophageal reflux disease (GERD)
- Chronic kidney disease
- Arterial hypertension
- Heart failure
- Sjögren disease
- Inflammatory myopathies (dermatomyositis, polymyositis)
- Systemic lupus erythematosus
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Scleroderma (MedlinePlus (U.S. National Library of Medicine), 2026).
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