What is the diagnostic workup and treatment approach for a patient presenting with symptoms suggestive of scleroderma, such as bilateral skin tightness of the feet?

Scleroderma Presentation and Diagnostic Workup

Initial Clinical Assessment

When evaluating a patient with suspected scleroderma (systemic sclerosis), immediately assess for Raynaud phenomenon, skin thickening pattern, and nailfold capillary changes—these three features together strongly suggest the diagnosis and should guide your initial workup. 1, 2

Key Clinical Features to Identify

Vascular manifestations:

• Raynaud phenomenon is present in >95% of systemic sclerosis patients and is typically the earliest manifestation 1
• Digital ulcers affect approximately 50% of patients 1
• Perform nailfold videocapillaroscopy to assess microcirculation—specific capillaroscopic changes are present in the majority of SSc patients and can make a fundamental difference when obvious clinical signs are absent 3

Skin involvement pattern determines disease subtype:

• Limited cutaneous SSc (lcSSc): skin thickening distal to elbows/knees only 1
• Diffuse cutaneous SSc (dcSSc): skin involvement both distal and proximal, including trunk 1
• Use the modified Rodnan skin score (mRSS) to quantify skin thickness at 17 anatomical sites (0-3 scale at each site, total range 0-51) 1
• In dcSSc, skin thickening typically progresses over the first 4 years then may regress 1
• Some patients (1.5-8%) present with SSc sine scleroderma—lacking definite skin involvement but developing major internal organ complications 1

Critical distinguishing features from scleroderma mimics:

• The absence of Raynaud phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies should prompt consideration of alternative diagnoses such as eosinophilic fasciitis, scleromyxedema, nephrogenic systemic fibrosis, or diabetic cheiroarthropathy 4, 2

Essential Laboratory Workup

Autoantibody testing is mandatory for risk stratification and prognosis:

• Anti-topoisomerase 1 (Scl-70): associated with higher frequency of interstitial lung disease 1
• Anti-centromere antibodies: typically seen in lcSSc, associated with primary biliary cholangitis in 8% of cases 1
• Anti-RNA polymerase III: high risk for scleroderma renal crisis and increased malignancy risk 1
• For suspected overlap syndromes, test for extractable nuclear antibodies (RNP, SSA/Ro, SSB/La, Smith, Jo1, PM/Scl-70) 1

Organ-Specific Screening Protocol

Pulmonary assessment (critical for morbidity/mortality):

• Screen all patients with history, physical examination, chest radiography, and pulmonary function testing 1
• Perform high-resolution CT when pulmonary function tests are abnormal or clinical suspicion exists 1
• Interstitial lung disease occurs in 40-75% based on lung function changes, but is progressive in only 15-18% 1
• Screen for pulmonary arterial hypertension, especially in patients with longer disease duration, older age, and/or low diffusing capacity 1

Renal monitoring (especially in early dcSSc):

• Scleroderma renal crisis occurs predominantly in early dcSSc 1
• High-risk features include: anti-RNA polymerase III positivity, male sex, tendon friction rubs, rapidly progressive skin involvement, and glucocorticoid use 1

Gastrointestinal evaluation:

• Nearly 90% of SSc patients have GI involvement, with esophagus most commonly affected 1
• Malnutrition is the leading cause of mortality attributed to GI tract involvement 1

Cardiac screening:

• Evaluate for arrhythmias and heart failure 1
• Patients with skeletal myopathy are 2.5 times more likely to have heart failure or arrhythmias 1

Musculoskeletal examination:

• Inflammatory arthritis occurs in approximately 15% 1
• Myositis or myopathy affects about 15% 1
• Tendon friction rubs indicate more aggressive disease 1

Additional Risk Assessment

Malignancy screening is warranted in specific scenarios:

• Rapidly progressive dcSSc with weight loss, especially in elderly patients 1
• Anti-RNA polymerase III positivity 1
• Presence of interstitial lung disease 1

Comorbidity screening:

• Depression assessment (elevated in SSc patients) 1
• Bone density scanning for osteoporosis risk 1
• Cardiovascular risk factors including hypertension, diabetes, hyperlipidemia, and metabolic syndrome 1
• Erectile dysfunction screening in men 1

Diagnostic Pitfalls to Avoid

The most common error is failing to distinguish systemic sclerosis from scleroderma mimics. If Raynaud phenomenon, nailfold capillary changes, and SSc-specific autoantibodies are all absent, strongly consider alternative diagnoses 2. In such cases, obtain skin biopsy looking for eosinophil infiltration, increased mucin, or amyloid deposition, and check for paraproteins in blood 2.

For localized scleroderma (morphea), MRI of the head is recommended at diagnosis for patients with facial and head involvement due to potential neurological complications 5. Use the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) to assess disease activity and extent 5.