What initial screening tests should be ordered for an adult female (30‑60 years) with newly diagnosed or suspected systemic sclerosis?

Initial Screening Tests for Systemic Sclerosis

For a newly diagnosed or suspected systemic sclerosis patient, order: ANA by immunofluorescence, SSc-specific autoantibody panel (anti-Scl-70, anti-centromere, anti-RNA polymerase III), complete blood count, comprehensive metabolic panel, pulmonary function tests with DLCO, high-resolution chest CT, and nailfold capillaroscopy. 1, 2

Serological Testing (First Priority)

Initial Screening

• Start with ANA testing by indirect immunofluorescence as the initial screening test—this is positive in 90-95% of SSc patients and is recommended by both EULAR and ACR 1, 3, 4
• The immunofluorescence pattern (homogeneous, speckled, nucleolar, centromere) provides crucial clues to specific autoantibody types 2

Disease-Specific Autoantibody Panel

After positive ANA, immediately order the SSc-specific autoantibody panel:

• Anti-topoisomerase I (anti-Scl-70): Present in 26% of SSc patients, strongly predicts diffuse cutaneous disease, interstitial lung disease, digital ulcers, and poor prognosis 2, 5
• Anti-centromere antibodies (ACA): Found in 22% of patients, almost exclusively (96%) in limited cutaneous disease, associated with calcinosis and telangiectasias 5
• Anti-RNA polymerase III: Predicts diffuse disease, rapid skin progression, scleroderma renal crisis, and significantly increased malignancy risk 1, 2

Additional Autoantibodies for Overlap Syndromes

• Anti-U1RNP, anti-U3RNP (fibrillarin), anti-Th/To, anti-PM/Scl, anti-Ku: Test when clinical features suggest overlap with other connective tissue diseases 1, 2
• Anti-SSA/Ro and anti-SSB/La: Order if Sjögren syndrome overlap is suspected 1

Critical caveat: Anti-Scl-70 and anti-centromere antibodies are mutually exclusive—no patient should have both 5

Basic Laboratory Tests

• Complete blood count: Monitor for cytopenias, especially if immunosuppression is planned 2
• Comprehensive metabolic panel: Including glucose, electrolytes, kidney function (creatinine, BUN), and liver enzymes 2
• Inflammatory markers: C-reactive protein and erythrocyte sedimentation rate to assess disease activity 1
• Rheumatoid factor: 3% of SSc cases overlap with rheumatoid arthritis 6, 1
• Alkaline phosphatase: Screen for primary biliary cholangitis, which occurs in 8% of limited cutaneous disease cases, particularly in anti-centromere positive patients 6, 1

Pulmonary Screening (Critical for Mortality)

Baseline Testing for All Patients

• Pulmonary function tests (spirometry and DLCO): Mandatory at baseline since ILD affects 40-75% of patients and is progressive in 15-18% 7, 6, 2
• High-resolution CT of the chest: Essential for detecting interstitial lung disease, especially in high-risk patients (anti-Scl-70 positive, diffuse cutaneous disease) 7, 6, 2

High-risk patients requiring immediate HRCT: Those with anti-Scl-70 antibodies, diffuse cutaneous disease, or abnormal pulmonary function tests 7, 6

Follow-up Pulmonary Monitoring

• Repeat PFTs every 3-6 months in early disease or if ILD is present 2
• Annual HRCT for the first 3-4 years in patients with SSc phenotype or risk factors 7

Cardiovascular Screening

• Electrocardiogram: Screen for arrhythmias 6, 1
• Echocardiography: Assess for pulmonary arterial hypertension, particularly in patients with longer disease duration, older age, or low DLCO 6, 1
• NT-proBNP: Test if arrhythmias or heart failure are present 1, 2
• 6-minute walk test: Evaluate functional capacity and PAH risk 1

Renal Screening

• Urinalysis for proteinuria: Essential at baseline and annually, especially in anti-RNA polymerase III positive patients who are at high risk for scleroderma renal crisis 1, 2
• Blood pressure monitoring: Establish home blood pressure monitoring for early diffuse cutaneous disease patients 1

Critical warning: Anti-RNAP III positivity requires intensive renal monitoring due to high scleroderma renal crisis risk 6, 1, 2

Nailfold Capillaroscopy

• Perform nailfold capillaroscopy with magnification in all suspected SSc patients—this is included in the 2013 EULAR/ACR classification criteria and detects early microvascular changes characteristic of scleroderma spectrum disorders 1

Malignancy Screening

• Age-appropriate cancer screening within 3 years of diagnosis if anti-RNAP III positive, as this antibody significantly increases malignancy risk 6, 2
• Enhanced vigilance for rapidly progressive diffuse disease with weight loss, especially in elderly patients 6

Additional Screening Considerations

• Depression screening: Elevated prevalence in SSc patients 6
• Bone density scanning: Increased osteoporosis risk 6
• Nutritional assessment: If severe gastrointestinal involvement is present, as malnutrition is the leading cause of GI-related mortality 6

Risk Stratification Based on Antibody Profile

The autoantibody result determines subsequent monitoring intensity:

• Anti-Scl-70 positive: Aggressive pulmonary monitoring (PFTs every 3-6 months, annual HRCT for 3-4 years), screen for digital ulcers 7, 2, 5
• Anti-centromere positive: Monitor for PAH with longer disease duration, screen for primary biliary cholangitis 6, 1, 5
• Anti-RNAP III positive: Intensive renal monitoring (home BP checks), malignancy screening, expect rapid skin progression 6, 1, 2

Important pitfall: Up to 40% of patients with idiopathic pulmonary arterial hypertension have elevated ANA, so positive ANA alone is not diagnostic and must be interpreted in clinical context 1