What are the clinical features of scleroderma?

Clinical Features of Scleroderma

Scleroderma is characterized by skin fibrosis, vasculopathy, and internal organ involvement affecting the lungs, gastrointestinal tract, heart, and kidneys, with clinical manifestations varying between limited and diffuse cutaneous forms. 1

Cutaneous Manifestations

• Skin fibrosis: One of the dominant clinical features of scleroderma

  • Diffuse cutaneous SSc (dcSSc): Skin thickening proximal to elbows/knees and on trunk
  • Limited cutaneous SSc (lcSSc): Skin thickening limited to areas distal to elbows/knees, may include face and neck
  • SSc sine scleroderma: Internal organ involvement without skin thickening (1.5-8% of cases) 1, 2

• Modified Rodnan skin score (mRSS): Standard measurement tool for skin thickness

  • Scale of 0-3 at 17 anatomical sites (score range 0-51)
  • In dcSSc, skin score typically increases over first 4 years then may regress 1

Vascular Manifestations

• Raynaud's phenomenon: Present in nearly all scleroderma patients

  • Characterized by triphasic color changes in digits (white, blue, red)
  • Triggered by cold, stress, and emotional factors 3

• Digital ulcers: Affect approximately 15% of patients

  • Can lead to complications including gangrene, osteomyelitis, and amputation 1, 3

• Capillaroscopic abnormalities: Diagnostic feature distinguishing primary from secondary Raynaud's phenomenon 3

Pulmonary Manifestations

• Interstitial lung disease (ILD):

  • Present in 40-75% of patients based on lung function changes
  • Progressive in 15-18% of cases
  • More common in patients with anti-topoisomerase 1 (Scl-70) antibodies 1

• Pulmonary arterial hypertension (PAH):

  • Higher risk in patients with longer disease duration, older age, low diffusing capacity
  • Screening includes echocardiography, pulmonary function testing, NT-proBNP, 6-minute walking test 1

Renal Manifestations

• Scleroderma renal crisis (SRC):
  • More common in early dcSSc
  • Risk factors: anti-RNA polymerase III antibodies, male sex, tendon friction rubs, rapidly progressive skin involvement, glucocorticoid use
  • Requires regular blood pressure monitoring 1

Gastrointestinal Manifestations

• GI involvement: Affects nearly 90% of patients

  • Esophagus most commonly affected (40-50% symptomatic, up to 90% have dysfunction on testing)
  • Followed by small bowel, colon, and anorectum 1, 4

• Esophageal dysfunction:

  • Smooth muscle dysfunction causing aperistalsis
  • Reduced lower esophageal sphincter pressure
  • Symptoms include heartburn and dysphagia
  • Complications include peptic stricture and Barrett's esophagus 4

• Severe GI involvement: Occurs in approximately 8% of patients

  • Malnutrition is leading cause of GI-related mortality
  • Mechanical or pseudo-obstruction can be life-threatening 1

Other Manifestations

• Musculoskeletal involvement:

  • Inflammatory arthritis (15% of patients)
  • Myositis/myopathy (15% of patients)
  • Overlap with rheumatoid arthritis in 3% of cases 1

• Sicca symptoms/Sjögren's syndrome: Affects approximately 15% of patients 1

• Cardiac involvement: Can include cardiomyopathy and pericardial effusion 1

• Calcinosis: Calcium deposits in skin and subcutaneous tissues 2

Disease Subsets and Classification

• Diffuse cutaneous SSc: More rapid progression, higher risk of early internal organ involvement
• Limited cutaneous SSc: Slower progression, often with CREST syndrome features
• SSc sine scleroderma: Internal organ involvement without skin changes
• Pre-scleroderma: Isolated Raynaud's, puffy fingers, specific antibodies, or capillaroscopic changes 1

Autoantibody Profiles

• Anti-topoisomerase 1 (Scl-70): Associated with higher frequency of ILD
• Anti-RNA polymerase III: Associated with higher risk of scleroderma renal crisis
• Autoantibodies against antinucleolar antigens: Present in most patients, helpful for classification and prognosis 1, 5

Clinical Course and Prognosis

• SSc remains the rheumatic disease with highest morbidity and mortality despite recent improvements in survival
• Type and severity of organ involvement drive the heterogeneous prognosis 1
• Early diagnosis and screening for organ complications are essential for improving outcomes

Diagnostic Approach

• Clinical history and physical examination: Focus on skin thickening pattern, Raynaud's phenomenon, and internal organ symptoms
• Laboratory tests: Autoantibody testing (ANA, specific autoantibodies)
• Capillaroscopy: Essential for differentiating primary from secondary Raynaud's phenomenon
• Organ-specific screening: Based on symptoms and risk factors 1, 3

Understanding these clinical features is crucial for early diagnosis, appropriate classification, and timely management of organ-specific complications in patients with scleroderma.