Scleroderma - Systemic Sclerosis

Scleroderma - Systemic Sclerosis

 

Systemic sclerosis is a chronic multisystem autoimmune disorder characterized by thickening of the skin and accumulation of connective tissue in various organs.

Epidemiology

  • Incidence – 3-20/1,000,000
  • Age – peak onset 20-40 years
  • Gender – F>M
Classification of Scleroderma (Systemic Sclerosis) and Scleroderma-like Disorders
  • Systemic sclerosis
    • Limited cutaneous disease
    • Diffuse cutaneous disease
    • Sine scleroderma
    • Undifferentiated connective tissue disease
    • Overlap syndromes
  • Localized scleroderma
    • Morphea
    • Linear scleroderma
    • En coup de sabre
  • Chemical-induced scleroderma-like disorders
    • Toxic-oil syndrome
    • Vinyl chloride-induced disease
    • Bleomycin-induced fibrosis
    • Pentazocine-induced fibrosis
    • Epoxy- and aromatic hydrocarbons-induced fibrosis
    • Eosinophilia-myalgia syndrome
  • Other scleroderma-like disorders
    • Scleredema adultorum of Buschke
    • Scleromyxedema
    • Chronic graft-vs-host disease
    • Eosinophilic fascitis
    • Digital sclerosis in diabetes
    • Primary amyloidosis and amyloidosis associated with multiple myeloma
(Used with permission from Gilliland, 2005, 1979)

Pathophysiology

  • Pathologic remodeling of connective tissues
  • Typified by 3 cardinal features
    • Excess collagen production
    • Vascular damage
    • Inflammation or autoimmune processes

Clinical Presentation

  • Dermatologic  – thickening of skin
  • Gastrointestinal – Raynaud phenomenon, esophageal dysmotility, reflux, gastroparesis, malabsorption, constipation  
  • Pulmonary – interstitial fibrosis, pulmonary hypertension
  • Musculoskeletal – arthritis, myopathy, weakness
  • Cardiovascular – fibrosis, pericarditis
  • Renal – glomerulonephritis
  • Head and neck – Sicca syndrome, hypothyroidism, Sjögren syndrome
  • Central nervous system – cranial neuropathies, peripheral neuropathies

Diagnosis  

  • Clinical presentation is characteristic of disease
  • Laboratory testing
    • Antibody testing
      • Scl-70 is a specific marker of scleroderma when it is the only autoantibody present
        • Scl-70 seen in only 20-60% of patients with scleroderma
      • Marker not useful in prognostication
Distribution of Antibodies in Connective Tissue Disease Types
  Systemic Lupus Erythematosus (SLE) Sjögren Syndrome Mixed Connective Tissue Disease (MCTD) Progressive Systemic Sclerosis (PSS) Scleroderma
dsDNA abs 50-60% 20-30% 20-25% <5%  
Histone abs Idiopathic 18-53%
Drug-induced 80-95%		   <20% <20% <20%
RNP 20-30%   95-100% 15-25% 5-10%
Scl-70       25% 20-60%
SSA ANA positive patients
30-40%		 70-75%   5-10%  
SSB 15-25% 50-60%   5-10%  
Jo-1 abs Found in polymyositis, dermatomyositis, myositis associated with rheumatic disease

Differential Diagnosis

  • Thyroid disorders
  • Amyloidosis
  • POEMS syndrome
  • Diabetes
  • Porphyria
  • Neoplasm
  • Raynaud phenomenon

Treatment

  • Remittive agents – cyclophosphamide
    • May alter the course of the disease; however as yet no definitive studies

See Also