Scleroderma

Figure 3.35 A: Morphea (Courtesy of Dr. Paul Getz) B: Morphea (Courtesy of Dr. Sophie M. Worobec) C: Morphea

• Figure 3.36 A: Systemic sclerosis* B: Systemic sclerosis* C: Systemic sclerosis* *Courtesy of Dr. Paul Getz

  Group of autoimmune disorders with initial inflammation and subsequent sclerosis; unknown etiology
• Morphea (localized scleroderma) (Figure 3.35A–C)
  • Localized form of scleroderma with unknown etiology, possibly due to trauma or infection (i.e. Borrelia burgdorferi)
  • Presents initially with expanding erythema → turns into ivory-colored sclerotic plaque → eventually softens; typically becomes inactive within 3–5 years
  • Variants: disseminated morphea, guttate morphea, linear morphea (linear scleroderma), nodular morphea, morphea profunda, progressive hemifacial atrophy (Parry Romberg syndrome)
  • Histology: dense lymphocytic infiltrate around superficial/deep vessels with few eosinophils, inflammation between dermal-subcutaneous fat junction; advanced lesions with dermal sclerosis
  • Labs: ± ANA in disseminated or linear morphea (unlikely to see with plaque-type morphea)
  • Treatment: topical mid to high potency corticosteroid, topical vitamin D analogue, PUVA or UVA1
• Systemic Sclerosis (SSc) (Figure 3.36A–C)
  • Systemic disorder affecting the skin, blood vessels and internal organs; early events in pathogenesis include vascular dysfunction and endothelial injury; fibrosis related to TGF-β, endothelin-1, PDGF, and connective tissue growth factor (CTGF)
  • Onset typically in women (30–50 years/old); African American patients with earlier onset and ↑ risk of diffuse disease
  • Presents with varying symptoms:
    • Cutaneous: pruritus, initial edematous phase (pitting edema of digits) with subsequent sclerosis (shiny, taut appearance) and digital ulcerations, sclerosis may affect arms, face (mask-like) and/or neck; dyspigmentation with leukoderma sparing perifollicular skin (‘salt/ pepper’ sign) or diffuse hyperpigmentation; calcinosis cutis
    • Vascular: Raynaud’s phenomenon (vasospasm of digital arteries secondary to cold stimulus with classic color change: white → blue → red)
    • Other: symmetric synovitis, migratory polyarthritis, pulmonary (interstitial lung disease → pulmonary fibrosis), cardiac, renal, GI (reflux, dysphagia)
  • Labs: ANA (nucleolar/centromeric), anti-Scl-70, anti-fibrillarin, anti-centromere, anti-RNA polymerase
  • Histology: normal to atrophic epidermis, hyalinized dermis with ↑ collagen deposition, ↓ adnexal structures, loss of subcutaneous fat
  • Treatment:
    • Raynaud’s: cold temperature avoidance, calcium channel blockers (nifedipine), low dose aspirin, prostaglandin E1
    • Cutaneous ulcers: oral endothelin receptor antagonist (i.e. bosentan) may prevent new ulcers
    • Systemic: prostaglandins (prostacyclin), immunosuppressants, D-penicillamine, ACEI



Systemic sclerosis: ↑ expression of extracellular matrix (ECM) proteins from dermal fibroblasts and ↑ deposition of collagen type III



• CREST (limited SSc) (Figure 3.37A)
  • Limited form of systemic sclerosis
  • CREST: calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly, telangiectasias
  • Associated with anti-centromere antibodies, rarely progresses to SSc, better prognosis than SSc