What are the steps to diagnose scleroderma?

Diagnosing Scleroderma: A Comprehensive Approach

The diagnosis of scleroderma requires a combination of clinical evaluation, serological testing, and specialized studies including nailfold capillaroscopy and skin biopsy to confirm the diagnosis and classify the disease as either limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc). 1

Initial Diagnostic Evaluation

Clinical Assessment

• Skin examination: Document cutaneous architectural changes
  • Look for skin thickening/hardening (particularly fingers and hands)
  • Assess for Raynaud's phenomenon (often the earliest manifestation)
  • Evaluate for digital ulcers or pitting scars
  • Check for telangiectasias (dilated blood vessels visible on skin)
  • Note facial changes (microstomia, radial furrowing around lips)

Laboratory Testing

• Autoantibody panel (critical for diagnosis and classification):
  • Anti-centromere antibodies (associated with lcSSc)
  • Anti-topoisomerase I (Scl-70) antibodies (associated with dcSSc and higher risk of ILD)
  • Anti-RNA polymerase III antibodies (associated with dcSSc and higher risk of scleroderma renal crisis)
  • Anti-nucleolar antibodies (U3-RNP, B23, Th/To)

Specialized Studies

• Nailfold capillaroscopy: Evaluates microvasculature changes characteristic of scleroderma
  • Look for dilated capillaries, capillary dropout, and distorted capillary architecture
• Skin biopsy: Confirms diagnosis in uncertain cases
  • Shows increased collagen deposition in dermis
  • Thinning of epidermis
  • Reduction in skin appendages

Classification and Disease Subtyping

Differentiate Between Major Types:

1. Limited Cutaneous Systemic Sclerosis (lcSSc):

   • Skin involvement limited to hands, face, feet, and forearms
   • Often has long history of Raynaud's phenomenon before other symptoms
   • Associated with anti-centromere antibodies
   • Higher risk of pulmonary arterial hypertension

2. Diffuse Cutaneous Systemic Sclerosis (dcSSc):

   • Widespread skin thickening extending to trunk and proximal extremities
   • More acute onset with constitutional symptoms
   • Associated with anti-topoisomerase I or anti-RNA polymerase III antibodies
   • Higher risk of early internal organ involvement

3. Localized Scleroderma (Morphea):

   • Limited to skin without systemic involvement
   • Subtypes include plaque, linear, generalized, and pansclerotic forms
   • Lacks Raynaud's phenomenon and scleroderma-specific antibodies 2

Organ Involvement Assessment

Pulmonary Evaluation

• Pulmonary function tests: Assess for restrictive pattern and reduced diffusing capacity
• High-resolution CT of chest: Evaluate for interstitial lung disease
• Echocardiography: Screen for pulmonary arterial hypertension
  • Patients with anti-topoisomerase I antibodies have higher frequency of ILD
  • Patients with markedly reduced DLCO (< 55% predicted) are at higher risk for developing PAH 3

Cardiac Assessment

• ECG and echocardiography: Screen for arrhythmias, heart failure, and pericardial effusion
• Further cardiac testing if symptoms suggest cardiac involvement

Gastrointestinal Evaluation

• Upper GI studies: Assess for esophageal dysmotility
• Gastric emptying studies: Evaluate for gastroparesis
• Small bowel follow-through: Check for intestinal dysmotility

Renal Assessment

• Regular blood pressure monitoring: Especially important in early dcSSc
• Urinalysis and renal function tests: Screen for proteinuria and declining renal function
• Home blood pressure monitoring: Recommended for patients with early dcSSc and positive anti-RNA polymerase III antibodies 3

Special Considerations

Screening for Overlap Syndromes

• Test for overlap with other connective tissue diseases:
  • Rheumatoid factor and anti-CCP for rheumatoid arthritis overlap (occurs in ~3% of SSc cases)
  • Extractable nuclear antibodies for overlap with SLE, dermatomyositis, polymyositis
  • Complement levels (C3, C4) and anti-DNA for SLE overlap 3

Malignancy Screening

• Consider age-appropriate cancer screening, particularly in patients with:
  • Rapidly progressive dcSSc
  • Weight loss
  • Older age at onset
  • Anti-RNA polymerase III antibodies (associated with increased malignancy risk) 3

Common Pitfalls to Avoid

1. Missing early diagnosis: Raynaud's phenomenon may precede other manifestations by years, especially in lcSSc
2. Confusing with scleroderma-like disorders: Conditions such as scleromyxedema, scleredema, and eosinophilic fasciitis can mimic scleroderma 2
3. Overlooking internal organ involvement: Systematic screening for organ involvement is essential even in asymptomatic patients
4. Incomplete antibody testing: A comprehensive autoantibody panel is crucial for classification and prognosis
5. Inadequate follow-up: Regular monitoring is needed to detect progressive organ involvement

By following this systematic approach to diagnosis, clinicians can accurately identify scleroderma, classify its subtype, and assess for organ involvement to guide appropriate management and improve patient outcomes.