How are Diffuse Systemic Scleroderma (DSSSC) and Limited Systemic Scleroderma (LSSSC) diagnosed?

Diagnosis of Diffuse and Limited Systemic Scleroderma

The diagnosis of Diffuse Systemic Scleroderma (dcSSc) and Limited Systemic Scleroderma (lcSSc) is based on the extent of skin involvement, specific autoantibody profiles, and characteristic organ manifestations, with dcSSc involving skin both proximal and distal to elbows/knees including the trunk, while lcSSc involves only distal areas. 1, 2

Clinical Classification and Skin Assessment

• dcSSc involves skin thickening both distal and proximal to the knees and/or elbows and/or trunk, while lcSSc involves skin distal to the elbows and/or knees without truncal involvement (though face and neck may be affected) 1
• The modified Rodnan skin score (mRSS) is used to measure skin thickness on a scale of 0-3 at 17 anatomical sites (score range 0-51) 1, 2
• In dcSSc, skin thickening typically increases over the first 4 years of disease and may regress somewhat thereafter, though individual patterns vary 1, 2
• A third rare subtype called "SSc sine scleroderma" (1.5-8% of cases) presents with internal organ involvement but lacks definite skin changes 3, 1

Key Diagnostic Features

• Nearly all patients (>95%) present with Raynaud phenomenon, which is often the earliest manifestation 1, 4
• Digital ulcers affect approximately 50% of SSc patients 1, 2
• "Puffy fingers" may be an early sign of disease, particularly in those who may have "prescleroderma" 1, 2
• Tendon friction rubs may indicate more aggressive disease and higher risk for scleroderma renal crisis 2, 1

Autoantibody Testing

• Autoantibody profile is crucial for diagnosis, risk stratification, and prognosis 2, 5
• Key antibodies to test for include:
  • Anti-topoisomerase 1 (Scl-70): associated with dcSSc and higher frequency of ILD 1, 2
  • Anti-centromere: associated with lcSSc and considered protective against ILD development 1, 2
  • Anti-RNA polymerase III (anti-RNAPIII): associated with high risk of scleroderma renal crisis and increased malignancy risk 1, 2
• For suspected overlap syndromes, test for extractable nuclear antibodies (RNP, SSA/Ro, SSB/La, Smith, Jo1, PM/Scl-70) 1, 2

Organ Involvement Assessment

• Interstitial lung disease (ILD) screening should include history, physical examination, chest radiography, pulmonary function testing, and high-resolution CT when appropriate 1
• Pulmonary arterial hypertension (PAH) screening should include echocardiography, pulmonary function testing, electrocardiography, and NT-proBNP measurement 1
• Blood pressure monitoring is essential, especially in early dcSSc and patients positive for anti-RNAPIII, to detect scleroderma renal crisis 1, 2
• Gastrointestinal involvement assessment is important as it affects nearly 90% of patients, with the esophagus most commonly involved 1, 2

Diagnostic Algorithm

1. Initial Assessment:

   • Evaluate for Raynaud phenomenon and puffy fingers 1, 2
   • Assess extent of skin thickening using mRSS to differentiate between dcSSc and lcSSc 1
   • Consider SSc sine scleroderma in patients with internal organ manifestations but minimal skin changes 3, 1

2. Laboratory Testing:

   • Autoantibody panel including anti-topoisomerase 1, anti-centromere, and anti-RNA polymerase III 2, 5
   • For suspected overlap syndromes, test for additional autoantibodies (RNP, SSA/Ro, SSB/La, Smith, Jo1) 1, 2

3. Organ Involvement Screening:

   • Pulmonary: PFTs with DLCO and HRCT for ILD assessment 1
   • Cardiac: Echocardiography for PAH screening 1
   • Renal: Regular blood pressure monitoring, especially in dcSSc 1, 2
   • Gastrointestinal: Assess for dysphagia, reflux, and malabsorption 1, 2

Diagnostic Pitfalls and Caveats

• Early disease may present with only Raynaud phenomenon and subtle skin changes, delaying diagnosis 1, 2
• Pulmonary function tests can be normal in early ILD, so HRCT is essential for accurate assessment 1
• Malignancy should be considered in patients with rapidly progressive dcSSc with weight loss, especially in elderly patients and those with anti-RNAPIII antibodies 1, 2
• Overlap syndromes with other connective tissue diseases (SLE, dermatomyositis, polymyositis, Sjögren syndrome) can complicate the diagnostic picture 1, 2
• Primary biliary cholangitis occurs in 8% of lcSSc cases, usually in anti-centromere antibody positive patients, and should be considered when alkaline phosphatase is elevated 1, 2