Systemic Sclerosis or Scleroderma

Systemic Sclerosis (Scleroderma)

• A generalized disorder of connective tissue characterized by thickening and fibrosis of the skin (scleroderma) and distinctive forms of involvement of internal organs, notably the heart, lungs, kidneys, and gastrointestinal tract.

Definition

• A multisystemic, autoimmune disease affecting small arteries, microvessels, and fibroblasts, resulting in vascular obliteration, collagen accumulation, and scarring (fibrosis) of skin and internal organs.
• Serologic specificity of the disease is the presence of ANA, directed against cellular nuclear enzymes, like DNA topoisomerase-1 (anti-Topo 1) and RNA polymerase, as well as centromeric proteins (anticentromere Ab).

Epidemiology

• Scleroderma affects all races, but it is more destructive in blacks than in Caucasians.
• The incidence is higher among people in their 40's, and females are affected more than males.

Etiology

• Environmental factors that trigger or accelerate the development of SSc include:
  • Silica exposure
  • Vinyl chloride
  • Trichloroethylene
  • Epoxy resins
  • Benzene
  • CCl4
  • Radiation exposure/radiotherapy
  • Infection - CMV, HHV 5, PBV B19
  • Drugs - bleomycin, pentazocine, l-tryptophan
  • Common in coal and gold miners

Pathology

• Pathogenic mechanisms always present:
  • Endothelial cell injury
  • Fibroblast activation
  • Cellular and humoral immunologic derangement
  • Activation of the immune system is an outstanding disease feature

Types of Scleroderma

• 1. Localized (majority of Paediatric cases):
  • A. Morphea:
    • Single patch
    • Multiple patches
  • B. Linear:
    • Face, forehead, and scalp (en coup de sabre)
    • Limb (en bande)
  • C. Generalized morphoea
• 2. Diffuse (systemic sclerosis)
• 3. Limited scleroderma (CREST syndrome)
• 4. Sine Scleroderma (visceral involvement without skin involvement)
• 5. Overlap Syndromes

Linear Morphoea

• Linear morphoea is usually solitary and unilateral in distribution.
• Affects the underlying skeletal muscle and even bone, giving rise to contractures and deformities.

Localized Scleroderma/Morphea

• Morphea involves isolated patches of hardened skin - there is generally no internal organ involvement.
• Aetiology: ?Autoimmune, higher frequencies of anti-histone and anti-topoisomerase IIa antibodies.

Clinical Features

• Focal thickening and hardening of the skin and subcutaneous tissues from excessive collagen deposition.

Treatment

• Topical, intra-lesional, and systemic corticosteroids
• Antimalarials (hydroxychloroquine or chloroquine)
• Methotrexate
• Topical tacrolimus
• Penicillamine
• Phototherapy

Diagnostic Criteria

• The American College of Rheumatology (ACR) criteria for the classification of systemic sclerosis:
  • One major criterion, two or more minor criteria for diagnosis.
  • Major criterion: Proximal scleroderma - characterized by symmetrical thickening, tightening, and induration of the skin of the fingers and the skin proximal to the MCP /MTP joints.
  • Minor criteria:
    • 1. Sclerodactyly - thickening, induration, tightening of the skin limited only to fingers.
    • 2. Digital pitting scars or loss of substance from the finger pads - due to ischemia.
    • 3. Bibasilar pulmonary fibrosis - b/l reticular pattern of linear or lineonodular densities in basilar portions of the lung on CXR.