Systemic Sclerosis (Scleroderma)
Causes and Risk Factors
Scleroderma is a complex autoimmune condition involving 3 primary pathogenic mechanisms: [Ref]
- Autoimmunity
- Fibrosis
- Vasculopathy
Risk factors: [Ref]
- Females
- African American
- Typically adult-onset
Clinical Features and Complications
Shared clinical features of systemic sclerosis (CREST syndrome): [Ref]
- Calcinosis
- Calcium deposition in subcutaneous tissue
- Appears as hard, raised, white, or yellow nodules +/- chalky white material
- Typically affects the fingertips, hands, elbow and other pressure points
- Raynaud phenomenon
- Esophageal dysmotility
- → Acid reflux, heartburn, dysphagia
- Sclerodactyly
- Tightening and thickening of the skin over the fingers → smooth, shiny, tapered, reduced skin folds and difficult to bend
- Fixed flexion deformities possible
- Telangiectasia
- Multiple visible dilated blood vessels that appear as red spots or fine red patches
- Typically seen on the face, lips, hands and inside the mouth
Other shared features:
- Prior to sclerodactyly, there is often an initial “puffy finger phase” characterised by non-pitting oedema of the hands
- The oedema can cause a mass effect and frequently causes carpal tunnel syndrome
- Facial involvement →
- Tight, smooth facial skin
- Reduced facial expression
- Thinning of the lips
- Microstomia (reduced mouth opening)
- Salt and pepper skin appearance – areas of depigmentation mixed with normally pigmented skin
- ↑ Risk of other autoimmune conditions (e.g. Hashimoto thyroiditis, Graves disease, PBC, and secondary Sjögren syndrome
Additional features / complications that are type-specific: [Ref]
| Limited systemic sclerosis | Diffuse systemic sclerosis | |
|---|---|---|
| Distinguishing features | Raynaud phenomenon tends to manifest years before onset of any visceral involvement
Sclerodactyly is present distal to the elbow and knees (the trunk is spared) |
Raynaud phenomenon tends to manifest simultaneously with, or very shortly after onset of skin changes
Sclerodactyly is present proximal to the elbow and knees; trunk involvement is possible |
| Other associations | Hypothyroidism (seen in up to 15% of patients) | Large joint inflammatory arthritis |
| Complications | Pulmonary arterial hypertension
|
Interstitial lung disease
Scleroderma renal crisis
Cardiac involvement
|
Investigation and Diagnosis
Diagnostic Work-Up
| Investigation | Description |
|---|---|
| Nailfold capillaroscopy | Used to assess the nailfold microcirculation, particularly in patients presenting with Raynaud phenomenon
|
| Serology | ANA is positive in most patients, but is not specific for systemic sclerosis.
Systemic sclerosis-specific antibodies: [Ref1][Ref2]
|
Post-Diagnostic Work-Up
Once diagnosed, all patients should undergo comprehensive screening at baseline to identify any clinically silent organ-based complications.
| General blood panels |
|
| Cardiopulmonary screening | Cardiopulmonary complications are leading causes of mortality in systemic sclerosis; routine screening should be offered to ALL patients:
|
| Malignancy screening | Targeted malignancy screening is recommended for:
Standard malignancy screening involves:
If clinically indicated, consider endoscopy and CT TAP etc. |
| Further symptom-directed organ testing |
|
Management
General approach:
- All patients with diffuse systemic sclerosis should be considered for immunosuppressive treatment
- 1st line: mycophenolate mofetil
- Alternative: methotrexate
- Both diffuse and limited systemic sclerosis require
- Regular organ-screening (see the post-diagnostic workup section above)
- Treatment directed at specific manifestations and complications (see below)
Limited systemic sclerosis is generally managed with complication-directed treatment rather than routine systemic immunosuppression.
However, immunosuppression may still be required if clinically significant inflammatory organ involvement develops.
Complication / Manifestation-Specific Management
| Complication / manifestation | Management |
|---|---|
| Interstitial lung disease |
|
| Pulmonary arterial hypertension |
|
| Cardiac involvement | Immunosuppressive therapy should be considered if there is myocardial inflammation
For the management of heart failure, see the Chronic Heart Failure article |
| Scleroderma renal crisis |
|
| Secondary Raynaud phenomenon |
Also see the Raynaud Phenomenon article |
Ongoing Monitoring / Screening
Long-term monitoring overlaps with the ‘post-diagnosis workup’ section above:
- Annual screening for
- Pulmonary arterial hypertension (lung function test, echocardiogram, NT-proBNP)
- Cardiac involvement (ECG, echocardiogram, troponin, NT-proBNP)
- In those with established interstitial lung disease:
- Lung function tests
- Repeat HRCT
- Individualised long-term malignancy surveillance