What scleroderma serologies need to be sent?

Scleroderma Serological Testing

All patients with suspected scleroderma should undergo antinuclear antibody (ANA) testing by immunofluorescence as the initial screening test, followed by a comprehensive panel of scleroderma-specific autoantibodies including anti-Scl-70/topoisomerase-I, anti-centromere, and anti-RNA polymerase III. 1, 2

Initial Screening Test

• ANA by indirect immunofluorescence is the mandatory first-line screening test, as circulating antinuclear antibodies are present in approximately 95% of systemic sclerosis patients 1, 3
• The immunofluorescence pattern (homogeneous, speckled, nucleolar, centromere) provides initial clues to specific autoantibody types and guides subsequent testing 2
• Up to 40% of patients with idiopathic pulmonary arterial hypertension have elevated ANA, so positive results must be interpreted in clinical context with other features 1

Essential Scleroderma-Specific Autoantibody Panel

The following autoantibodies must be tested as they predict specific disease manifestations and prognosis:

High-Priority Antibodies

• Anti-topoisomerase I (anti-Scl-70): Strongly associated with diffuse cutaneous systemic sclerosis, interstitial lung disease, digital ulcers, and poor prognosis 2, 4
• Anti-centromere antibodies: Associated with limited cutaneous systemic sclerosis, pulmonary arterial hypertension risk, and primary biliary cholangitis (occurs in 8% of limited cutaneous cases) 5, 1, 4
• Anti-RNA polymerase III (anti-RNAP III): Associated with diffuse cutaneous disease, rapid skin progression, scleroderma renal crisis, and significantly increased malignancy risk requiring enhanced cancer screening 5, 1, 2

Additional Important Antibodies

• Anti-U3RNP (anti-fibrillarin): Associated with diffuse scleroderma and pulmonary arterial hypertension 5, 4
• Anti-Th/To: Associated with limited skin disease but high risk for severe internal organ involvement including pulmonary arterial hypertension 4, 6
• Anti-PM/Scl (PM-Scl 75 and/or 100): Associated with scleroderma-myositis overlap syndromes and interstitial lung disease 4, 7

Overlap Syndrome Evaluation

When clinical features suggest overlap with other connective tissue diseases, test for:

• Anti-U1RNP: Suggests mixed connective tissue disease or systemic sclerosis overlap syndrome 2, 4
• Anti-SSA/Ro and anti-SSB/La: For Sjögren syndrome overlap (sicca symptoms occur in approximately 15% of systemic sclerosis patients) 5, 2
• Rheumatoid factor and anti-citrullinated peptide antibody: If inflammatory arthritis is present, as 3% of systemic sclerosis cases overlap with rheumatoid arthritis 5, 1

Supporting Laboratory Tests

• Complete blood count, glucose, electrolytes, kidney function, and liver enzymes should be obtained in all patients 2
• Inflammatory markers (CRP and ESR) to assess disease activity 1
• Alkaline phosphatase to screen for primary biliary cholangitis, particularly in anti-centromere positive patients 5

Critical Clinical Caveats

• Anti-RNA polymerase III positivity mandates age-appropriate malignancy screening within 3 years of diagnosis due to increased cancer risk 1, 2
• Scleroderma-specific antibodies are typically mutually exclusive: patients rarely have both anti-Scl-70 and anti-centromere antibodies simultaneously 7
• Negative ANA does not exclude scleroderma but makes the diagnosis less likely, as approximately 5% of patients are ANA-negative 3
• Obtain detailed medication and environmental exposure history to exclude drug-induced or toxic causes of scleroderma-like syndromes 1