What is scleroderma?

What is Scleroderma?

Scleroderma, more accurately termed systemic sclerosis (SSc), is a chronic autoimmune connective tissue disease characterized by three pathogenic hallmarks: vasculopathy (small artery damage), inflammation/autoimmunity, and progressive fibrosis affecting both skin and internal organs. 1

Disease Definition and Terminology

• The term "systemic sclerosis" is preferred over "scleroderma" because it encompasses the entire multisystem disease affecting both skin and internal organs, whereas scleroderma refers specifically to cutaneous (skin) manifestations 1
• SSc is a connective tissue disease that affects skin, blood vessels, heart, lungs, kidneys, gastrointestinal tract, and musculoskeletal system 2
• The disease results in significant morbidity and mortality, making it the rheumatic disease with the highest morbidity and mortality despite recent improvements in survival 1

Clinical Classification

SSc is classified into distinct subsets based on skin involvement extent 1:

• Limited cutaneous SSc (lcSSc): Skin fibrosis confined to distal extremities and some areas of face and neck; also known as CREST syndrome 3
• Diffuse cutaneous SSc (dcSSc): Skin abnormalities extending to proximal extremities (above elbow or knee) and trunk 3
• SSc sine scleroderma: Internal organ involvement without significant skin thickening 1
• Localized scleroderma: Patches (morphea) or bandlike (linear scleroderma) areas of skin thickening, more common in children with no internal organ involvement 4, 3

Key Clinical Features

Cardinal Manifestations

• Raynaud phenomenon occurs in >95% of patients and is often the earliest manifestation 1
• Skin thickening and sclerosis is the most obvious and characteristic manifestation 5
• The modified Rodnan skin score (mRSS) measures skin thickness on a scale of 0-3 at 17 anatomical sites (total score range 0-51) 1

Organ Involvement Patterns

• Gastrointestinal involvement affects nearly 90% of patients, with the esophagus most commonly affected 1
• Interstitial lung disease (ILD) occurs in 40-75% of patients but is progressive in only 15-18%; ILD is a leading cause of death 1
• Digital ulcers develop in approximately 50% of patients 1
• Pulmonary arterial hypertension, cardiac involvement, and scleroderma renal crisis are life-threatening complications 2, 6
• Respiratory involvement occurs in up to 85% of patients, including ILD, pulmonary hypertension, and aspiration from esophageal dysfunction 2

Pathophysiology

The disease involves three major pathologic features 7:

1. Vascular damage: Widespread obliterative vasculopathy of small arteries 8
2. Mononuclear cellular infiltrates: Evidence of both humoral and cellular immunity involvement 7
3. Massive deposition of newly synthesized connective tissue: Primarily collagen, leading to progressive fibrosis 7

Diagnostic Clues

• Specific autoantibodies help predict disease subtype and organ involvement patterns, including ANA, anticentromere, and anti-Scl-70 (anti-topoisomerase I) antibodies 1, 3
• Patients with anti-topoisomerase I antibodies require urgent evaluation due to higher ILD frequency 6
• The presence of Raynaud's phenomenon, capillaroscopic abnormalities, and scleroderma-specific autoantibodies help differentiate true scleroderma from mimicking conditions 5

Epidemiology

• Approximately 80% of patients are females, with one-half presenting before age 40 3
• Estimated prevalence is approximately 250 patients per million in the United States 3
• Incidence is approximately 20 new patients per million per year 3
• Some studies suggest higher incidence and severity in black females compared to whites 3

Clinical Heterogeneity

SSc presents unique challenges due to its clinical heterogeneity, with subsets varying in disease expression, organ involvement, and prognosis 8. The disease course spans from mild, subtle findings to aggressive, life-threatening multisystem disease, requiring careful characterization of each patient to understand specific manifestations and disease activity level 8.