What is the appropriate workup and treatment for a patient with suspected scleroderma?

Scleroderma Workup

Initial Diagnostic Evaluation

Begin with antinuclear antibody (ANA) testing by immunofluorescence as the initial screening test, followed by scleroderma-specific autoantibodies including anti-Scl-70/topoisomerase-I, anti-centromere, and anti-RNA polymerase III to establish diagnosis and predict organ involvement. 1

Essential Serological Testing

• ANA by immunofluorescence is the first-line screening test, as circulating antinuclear antibodies are present in most patients with systemic scleroderma 1
• Scleroderma-specific autoantibodies are critical for both diagnosis and predicting disease manifestations:
  • Anti-Scl-70/topoisomerase-I: associated with diffuse cutaneous disease and interstitial lung disease 1
  • Anti-centromere: associated with limited cutaneous disease and increased risk of primary biliary cholangitis 1
  • Anti-RNA polymerase III: significantly increases risk of scleroderma renal crisis and malignancy 1
• Additional autoantibodies including anti-U3RNP (fibrillarin) should be tested when evaluating for overlaps, particularly with pulmonary arterial hypertension 1

Supporting Laboratory Tests

• Inflammatory markers (CRP and ESR) to assess disease activity 1
• Rheumatoid factor as 3% of systemic sclerosis cases overlap with rheumatoid arthritis 1
• Connective tissue disease antibodies (anti-SSA/Ro, anti-SSB/La) when clinical features suggest overlap syndromes 1

Nailfold Capillaroscopy

• Perform nailfold capillaroscopy with magnification in all patients with suspected scleroderma to detect early microvascular changes, as this is included in the 2013 EULAR/ACR classification criteria 1

Mandatory Organ-Based Screening

All patients require comprehensive screening for life-threatening organ involvement, as early detection and intervention can modify the natural history of these complications. 2

Pulmonary Screening

Interstitial Lung Disease (ILD):

• High-resolution CT (HRCT) of the chest is the primary diagnostic tool 3
• Pulmonary function tests (PFTs) with DLCO to detect subclinical ILD, which is present in many patients at diagnosis 3
• Repeat PFTs every 3-6 months to track forced vital capacity (FVC) 3
• Higher risk in patients positive for anti-topoisomerase 1 (Scl-70) antibodies and those with diffuse cutaneous disease 2

Pulmonary Arterial Hypertension (PAH):

• Enrich high-risk groups: those with longer disease duration, older age, and/or low diffusing capacity 2
• Screening algorithms include echocardiography, pulmonary function testing, electrocardiography, NT-proBNP, and 6-minute walking distance 2

Renal Screening for Scleroderma Renal Crisis

• Any patient positive for anti-RNA polymerase III is at high risk and requires intensive monitoring 2
• All patients with early diffuse cutaneous disease should have regular blood pressure checks 2
• Home blood pressure monitoring should be encouraged 2
• Additional risk factors include active early disease with other organ involvement (pericardial effusion, ILD, cardiac involvement), male sex, tendon friction rubs, rapidly progressive skin involvement, and glucocorticoid use 2

Other Organ Screening

The "15% Rule": 1 in 6 patients with systemic sclerosis have prevalent digital ulcers, complicated digital ulcers, inflammatory arthritis, myositis/myopathy, sicca symptoms, or Sjögren syndrome 2

• Cardiac screening if arrhythmias and/or heart failure are present 2
• Liver function tests (alkaline phosphatase) as primary biliary cholangitis occurs in 8% of limited cutaneous disease cases, usually in those positive for anti-centromere antibodies 2
• Nutritional screening if malabsorption is present or suspected due to severe gastrointestinal involvement 2
• Depression screening as it is elevated in patients with chronic diseases 2

Disease Classification

Classify patients by extent of skin involvement as this determines prognosis and treatment approach 2:

• Diffuse cutaneous SSc (dcSSc): skin involvement both distal and proximal to knees/elbows and/or truncal 2
• Limited cutaneous SSc (lcSSc): fibrosis distal to elbows/knees without truncal involvement (face and neck may be involved) 2
• SSc sine scleroderma: major internal organ complications without definite skin involvement (1.5-8% of cases), often follows trajectory similar to limited cutaneous disease 2

Skin Assessment

• Modified Rodnan skin score (mRSS) measures skin thickness on a scale of 0-3 at 17 anatomical sites (range 0-51) 2
• Minimal clinically important difference is 3.5-5.3 points 2, 3
• In diffuse cutaneous disease, mRSS generally increases over the first 4 years then regresses somewhat thereafter 2

Critical Pitfalls to Avoid

• Do not rely on positive ANA alone for diagnosis, as up to 40% of patients with idiopathic pulmonary arterial hypertension have elevated ANA; interpretation requires clinical context 1
• Obtain detailed medication and environmental exposure history to exclude other causes of interstitial lung disease that may mimic scleroderma 1
• Recognize that anti-RNA polymerase III positivity requires enhanced monitoring for both scleroderma renal crisis and malignancy 1
• Patients should be referred to a specialized center due to disease heterogeneity, complexity of diagnostic evaluation, and wide array of treatment options 4