What is scleroderma?

What is Scleroderma?

Scleroderma is an autoimmune connective tissue disease characterized by excessive collagen deposition leading to fibrosis, but the term "systemic sclerosis" (SSc) is preferred because it encompasses the entire multisystem disease affecting both skin and internal organs, while scleroderma refers specifically to cutaneous manifestations. 1

Disease Classification

Scleroderma divides into two major clinical categories with distinct implications 2, 3:

Systemic Sclerosis (SSc)

• A complex systemic autoimmune disorder defined by three pathogenic factors: vasculopathy, inflammation/autoimmunity, and fibrosis affecting skin and multiple internal organs 4, 1
• Classified into clinical subsets based on skin involvement extent 4, 1:
  • Diffuse cutaneous SSc (dcSSc): distal and proximal skin involvement 4
  • Limited cutaneous SSc (lcSSc): distal skin fibrosis only 4
  • SSc sine scleroderma: absence of skin fibrosis despite SSc-related features 4
• SSc is the rheumatic disease with the highest individual mortality rate, with main causes of death being interstitial lung disease and cardiac involvement 4, 1

Localized Scleroderma (Morphea)

• Confined to skin and/or subcutaneous tissues with collagen deposition and fibrosis, without internal organ involvement 2, 3
• More common in children than systemic forms 5
• Includes five subtypes: circumscribed morphoea, linear scleroderma, generalised morphoea, pansclerotic morphoea, and mixed subtype 4

Key Clinical Features

Systemic Sclerosis Manifestations

• Nearly all patients (>95%) present with Raynaud phenomenon, and approximately 50% develop digital ulcers 1
• Gastrointestinal involvement affects nearly 90% of patients, with esophagus most commonly affected 4, 1
• Interstitial lung disease occurs in 40-75% of patients but is progressive in only 15-18% 1
• Respiratory complications develop in >50% of patients, with persistent or chronic cough as one of the first important symptoms 4
• Increased cough reflex sensitivity occurs in patients with SSc-associated interstitial lung disease 4

Distinguishing Features from Mimics

• The presence of Raynaud's phenomenon, capillaroscopic abnormalities, and scleroderma-specific autoantibodies distinguish true scleroderma from sclerodermoid disorders 3
• Specific autoantibodies help predict disease subtype and organ involvement patterns 1

Pathophysiology

The main defect in scleroderma is abnormal collagen deposition leading to eventual fibrosis in skin and multiple organ systems 5, 6:

• Overproduction of extracellular matrix molecules following induction of gene expression 6
• Close interaction between inflammatory cells and fibroblasts required for initial fibroblast activation 6
• TGF-beta plays an important role, along with other cytokines like PDGF or FGF 6

Clinical Assessment

• The modified Rodnan skin score (mRSS) measures skin thickness on a scale of 0-3 at 17 anatomical sites (score range 0-51) 1
• Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) is recommended to assess disease activity and extent 7
• Comprehensive screening for organ involvement is essential for early detection 1

Treatment Principles

Systemic Sclerosis

• EULAR recommends targeted therapies including mycophenolate mofetil, nintedanib, rituximab, and tocilizumab for key fibrotic manifestations like skin fibrosis and interstitial lung disease 1
• Therapeutics divide into three main subgroups: antifibrotics, anti-inflammatories, and vasodilators 5
• Early treatment before irreversible damage occurs improves both quality of life and survival 8

Localized Scleroderma

• All patients with active, potentially disfiguring or disabling forms should be treated with oral or subcutaneous methotrexate at 15 mg/m²/week 4
• Systemic corticosteroids may be useful in the active inflammatory phase 4
• Local skin-targeted therapy includes topical glucocorticoids, immunomodulatory ointments, and UV irradiation 2, 5

Prognosis

• Despite recent improvements in survival, SSc remains the rheumatic disease with the highest morbidity and mortality 1
• Fatal outcomes often originate from organ complications: lung fibrosis, pulmonary artery hypertension, and scleroderma renal crisis 2
• Localized disease in children can cause major growth defects even if the active disease itself is self-limited 5