Scleroderma Diagnosis and Management

Autoantibody Testing

• A comprehensive autoantibody panel, including anti-nuclear antibody (ANA) testing by indirect immunofluorescence (IIFA) on HEp-2 cells, is essential for diagnosing scleroderma, as recommended by the European League Against Rheumatism and the American College of Rheumatology 1, 2
• Specific scleroderma-associated antibody testing, including anti-Scl-70/topoisomerase-1, anti-centromere, anti-RNA polymerase III, anti-U3-RNP (fibrillarin), anti-PM/Scl-75, anti-PM/Scl-100, and anti-U1-RNP, can help identify different scleroderma subtypes and overlap syndromes, according to the European League Against Rheumatism, American College of Rheumatology, and European Respiratory Society 1, 2, 3

Imaging and Laboratory Tests

• High-resolution CT of lungs, chest radiography, and pulmonary function tests are recommended for evaluating lung involvement in scleroderma patients, as stated by the European League Against Rheumatism 1
• Regular blood pressure monitoring and renal function tests are essential for detecting scleroderma renal crisis, especially in anti-RNA polymerase III positive patients, according to the European League Against Rheumatism 1
• Liver function tests, including alkaline phosphatase, and anti-mitochondrial antibodies (AMA) for primary biliary cholangitis are recommended for patients with limited cutaneous SSc (lcSSc), as reported by the European Association for the Study of the Liver and European League Against Rheumatism 1

Overlap Syndromes

• Rheumatoid factor and anti-CCP are recommended for rheumatoid arthritis overlap, which occurs in 3% of SSc cases, as stated by the European League Against Rheumatism 1
• Anti-SSA/Ro and anti-SSB/La are recommended for Sjögren's syndrome overlap, according to the American College of Rheumatology 1
• Myositis panel is recommended for inflammatory myopathy overlap, as reported by the European Neurological Society 1
• Complement C3, C4, and anti-DNA are recommended for SLE overlap, according to the European League Against Rheumatism 1

Cardiac Involvement

• Patients with scleroderma are at risk for myocardial involvement and arrhythmias, according to the American College of Rheumatology, and may require cardiac MRI or other appropriate cardiac imaging if myocardial involvement is suspected 4
• The American Heart Association recommends checking for signs of instability and obtaining a 12-lead ECG to define the rhythm, and treating the underlying cause of tachycardia rather than the tachycardia itself 5

Primary Biliary Cholangitis (PBC)

• The association between scleroderma and PBC is known as Reynolds syndrome, with PBC occurring in approximately 8% of patients with limited cutaneous systemic sclerosis (lcSSc), and patients may present with symptoms such as pruritus, fatigue, jaundice, and portal hypertension complications 6, 1
• Diagnosis of PBC in scleroderma patients involves liver function tests, antimitochondrial antibodies (AMA), anti-nuclear antibodies (ANA) with centromere pattern, complete autoimmune profile, abdominal ultrasound, transient elastography, and liver biopsy when necessary 6
• The American College of Gastroenterology recommends ursodeoxycholic acid (UDCA) at 15 mg/kg/day as the first-line therapy for PBC, with regular liver function tests and annual abdominal ultrasound for cirrhotic patients 6

Antibody Associations and Risks

7, 8, 1

• The presence of anti-centromere antibodies (ACA) is strongly associated with limited cutaneous systemic sclerosis (lcSSc) and indicates a higher risk for developing pulmonary arterial hypertension (PAH) but lower risk for interstitial lung disease (ILD) compared to other scleroderma-specific antibodies, and regular screening for PAH and monitoring for primary biliary cholangitis with liver function tests is recommended 7, 9, 8, 1