What is scleroderma?

What is Scleroderma?

Scleroderma (systemic sclerosis) is a rare autoimmune connective tissue disease characterized by widespread fibrosis, vasculopathy, and immune dysregulation that affects skin and multiple internal organs, carrying substantial morbidity and mortality. 1

Disease Definition and Epidemiology

• Systemic sclerosis (SSc) is a rare autoimmune disease with an estimated prevalence of 30-120 cases per million population. 1
• The disease predominantly affects women (approximately 80% of cases), with half presenting before age 40. 2
• The pathological hallmarks are excessive collagen deposition leading to fibrosis, microvascular damage causing vasculopathy, and immune system abnormalities. 1, 3

Clinical Classification and Subtypes

The disease is classified based on the extent and pattern of skin involvement, which has prognostic implications:

Limited Cutaneous SSc (lcSSc)

• Skin fibrosis restricted to areas distal to elbows and/or knees, without truncal involvement (though face and neck may be affected). 1
• Often associated with CREST syndrome features (Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasias). 2

Diffuse Cutaneous SSc (dcSSc)

• Skin involvement extends proximal to knees and/or elbows and includes truncal areas. 1
• Associated with higher risk of internal organ complications and mortality. 1

SSc Sine Scleroderma

• A small subset (1.5-8%) lacking definite skin involvement but developing major internal organ complications. 1
• These patients often follow a clinical trajectory similar to limited cutaneous disease. 1

Prescleroderma

• Patients with isolated Raynaud phenomenon, puffy fingers, SSc-specific antibodies, or characteristic capillaroscopic changes. 1
• Up to half develop defined connective tissue disease (including SSc) during long-term follow-up. 1

Cardinal Clinical Features

Universal and Near-Universal Manifestations

• Nearly all patients (>95%) present with Raynaud phenomenon as an early and hallmark feature. 1, 3
• Skin hardening (scleroderma) and induration are characteristic findings. 3
• Half of patients develop digital ulcers. 1

Gastrointestinal Involvement

• Affects nearly 90% of patients, with the esophagus most commonly involved, followed by small bowel, colon, and anorectum. 1
• Malnutrition is the leading cause of mortality from GI involvement, though mechanical or pseudo-obstruction can be life-threatening. 1, 4
• Only 8% present with severe involvement despite high prevalence of pathological changes. 1

Pulmonary Complications

• Interstitial lung disease (ILD) occurs in 40-75% based on lung function changes, with 15-18% experiencing progressive disease. 1
• Pulmonary arterial hypertension (PAH) represents a major cause of morbidity and mortality. 1

Other Major Organ Involvement

• Scleroderma renal crisis (SRC) - particularly in patients with anti-RNA polymerase III antibodies. 1
• Cardiac involvement including cardiomyopathy. 1
• Inflammatory arthritis, calcinosis, myopathy/myositis, and sicca symptoms. 1

Diagnostic Considerations

Autoantibody Profiles

• Characteristic autoantibodies include antinuclear antibodies (ANA), anticentromere, and anti-Scl-70 (anti-topoisomerase I) antibodies. 2
• Anti-RNA polymerase III antibodies confer high risk for scleroderma renal crisis. 1
• Anti-topoisomerase I antibodies associate with higher frequency of interstitial lung disease. 5

Key Differentiating Features

• The lack of Raynaud phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies suggests alternative diagnoses (scleroderma mimics or pseudosclerodermas). 6

Prognosis and Disease Impact

• Prognosis is determined by the degree of internal organ involvement, not skin extent. 5, 3
• Visceral manifestations drive overall survival, making organ-specific screening essential. 5
• The disease causes significant morbidity and mortality due to fibrosis and vasculopathy affecting multiple organ systems. 1

Critical Clinical Pitfall

The typical presentation is a young or middle-aged woman with a history of Raynaud phenomenon who develops skin induration and internal organ dysfunction. 3 Early recognition is essential because inflammation is potentially reversible if treated early, but transforms into irreversible fibrosis with permanent organ damage if treatment is delayed. 5