What laboratory tests are used to diagnose and manage scleroderma?

Laboratory Tests for Scleroderma Diagnosis and Management

For patients with suspected or confirmed scleroderma, a comprehensive serological panel including antinuclear antibodies, anti-Scl-70/topoisomerase-1, anti-centromere, anti-RNA polymerase III, and other scleroderma-specific antibodies should be performed to confirm diagnosis, determine disease subtype, and assess risk for organ complications. 1

Initial Diagnostic Laboratory Tests

Core Serological Panel

• Antinuclear antibodies (ANA) - Positive in >95% of scleroderma patients, typically with nucleolar or speckled pattern
• Anti-Scl-70/topoisomerase-1 - Associated with diffuse cutaneous scleroderma and higher risk of interstitial lung disease (ILD)
• Anti-centromere antibodies - Associated with limited cutaneous scleroderma and higher risk of pulmonary arterial hypertension (PAH)
• Anti-RNA polymerase III - Associated with diffuse cutaneous scleroderma and higher risk of scleroderma renal crisis

Additional Scleroderma-Specific Antibodies

• Anti-Th/To - Associated with limited cutaneous scleroderma
• Anti-U3-RNP (fibrillarin) - Associated with diffuse cutaneous scleroderma and PAH
• Anti-PM/Scl75 and anti-PM/Scl100 - Associated with overlap syndromes
• Anti-Ku - Associated with overlap syndromes

Inflammatory Markers

• C-reactive protein (CRP)
• Erythrocyte sedimentation rate (ESR)

Organ-Specific Monitoring Tests

Pulmonary Assessment

• Pulmonary function tests - Including forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO)
  • DLCO is particularly important as decreased values (<55% predicted) may predict development of PAH 1
• N-terminal pro-brain natriuretic peptide (NT-proBNP) - Elevated in PAH 1

Renal Assessment

• Serum creatinine and estimated glomerular filtration rate (eGFR)
• Urinalysis - For proteinuria and hematuria
• Urine protein electrophoresis - To detect intermediate molecular weight proteinuria 2
• Urinary albumin excretion rate - Microalbuminuria may indicate early renal involvement 2

Cardiac Assessment

• Cardiac enzymes (troponin) - May be elevated in myocardial involvement 1
• NT-proBNP - For monitoring heart failure and PAH 1

Gastrointestinal Assessment

• Liver function tests - To assess for primary biliary cholangitis, which occurs in 8% of limited cutaneous scleroderma patients 1
• Alkaline phosphatase - Elevated in primary biliary cholangitis 1

Hematological Assessment

• Complete blood count - To detect anemia, leukocytosis, or thrombocytopenia 3
• Peripheral blood smear - To detect microangiopathic hemolytic anemia in scleroderma renal crisis 4

Tests for Overlap Syndromes

• Anti-cyclic citrullinated peptide (anti-CCP) - For overlap with rheumatoid arthritis
• Rheumatoid factor - For overlap with rheumatoid arthritis
• Anti-Jo-1 and other myositis-specific antibodies - For overlap with inflammatory myopathies
• Creatine kinase - For myositis overlap
• Anti-SSA/Ro and anti-SSB/La - For Sjögren's syndrome overlap
• Anti-U1-RNP - For mixed connective tissue disease overlap

Monitoring Algorithm Based on Disease Subtype

For Limited Cutaneous Scleroderma

• Monitor DLCO and echocardiography annually for PAH detection
• Check alkaline phosphatase for primary biliary cholangitis
• Monitor for development of digital ulcers

For Diffuse Cutaneous Scleroderma

• Monitor blood pressure frequently (every 3-6 months) for scleroderma renal crisis, especially in anti-RNA polymerase III positive patients 1
• Perform pulmonary function tests every 3-6 months for ILD detection
• Monitor for cardiac involvement with ECG and cardiac biomarkers

Clinical Pitfalls and Caveats

• Up to 40% of patients with idiopathic pulmonary arterial hypertension have positive ANA, so antibody testing alone is insufficient for diagnosis 1
• Anti-centromere antibodies are considered protective against ILD development 1
• Anti-RNA polymerase III antibodies are associated with increased risk of malignancy and scleroderma renal crisis 1
• Patients with scleroderma renal crisis may have normal blood pressure in 10% of cases, so regular renal function monitoring is essential 4
• Microalbuminuria and intermediate molecular weight proteinuria may indicate early renal involvement and systemic vasculopathy 2

By systematically applying these laboratory tests based on clinical presentation and antibody profile, clinicians can better diagnose scleroderma, determine disease subtype, assess organ involvement, and monitor for complications that significantly impact morbidity and mortality.