Systemic sclerosis (SSc)

Eva Niklinska and Raeann Whitney

Background

  • Multisystem autoimmune disease characterized by immune dysregulation causing vascular dysfunction and fibrosis of skin and internal organs
    • Distinguish from localized scleroderma (morphea or linear scleroderma) which is dermal fibrosis without internal organ involvement
  • Categorized into 2 major subtypes:
    • Limited cutaneous (lcSSc): skin thickening limited to the neck, face, or distal to elbows and knees; spares the truck and proximal extremities. Raynaud’s may develop years before other manifestations, which then slowly accumulate over 5-10 years.
      • + anticentromere antibody
      • Renal crisis is rare
      • High risk for developing PAH
    • Diffuse cutaneous: skin thickening extends proximal to the elbows/knees or trunk; rapid development of cutaneous and multiorgan involvement
      • More associated with anti-Scl-70 ab
      • Typically more abrupt onset and rapid progression compared to limited
      • High risk for progressive ILD
      • + RNA polymerase III Ab = high risk of renal crisis, higher risk for malignancy
  • Incidence: onset typically 30-60y, more common in females (~4:1)
  • Etiology: unknown trigger causes microvascular injury and activation of collagen à excess collagen deposition

Presentation

  • CREST: Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia (CREST syndrome is no longer a discrete diagnosis but incorporated into lcSSc)
  • Systemic: fatigue, weight loss
  • Vascular: Raynaud’s +/- digital tip ulcers, telangiectasias, nailfold capillaroscopy with dilated capillary loops
  • Skin: Sclerodactyly, loss of facial wrinkles, decreased oral aperture, calcinosis cutis
  • MSK: arthralgias, myalgias, flexion contractures
  • GI: Esophageal or intestinal dysmotility, GERD, GAVE (watermelon stomach)
  • Pulm: ILD (NSIP, UIP), pulmonary arterial hypertension
  • Cardiac: pericardial effusions, myocarditis, cardiomyopathy, conduction system disease
  • Renal: renal crisis

Evaluation

  • 2013 ACR/EULAR Classification Criteria -> weight-based symptom scoring
  • Laboratory workup: ANA w/ reflex, Scl70, anticentromere, RNA pol III (separate order in Epic, increased risk of scleroderma renal disease)
  • Imaging/Procedures: Baseline PFTs, lung HRCT, TTE, EKG, 6-minute walk test , EGD
  • Skin biopsy: Not often used for dx, may be required to differentiate other rare disorders (eosinophilic fasciitis, linear scleroderma, scleromyxedema)

2013 ACR/EULAR Classification Criteria Items

Sub-items

Weight

Skin thickening of fingers of both hands extending proximal to metacarpophalangeal (MCP) joints9
Skin thickening of fingers (only count the highest score) Puffy fingers
Whole finger, distal to MCP 		2
4
Fingertip lesions (only count the highest score) Digital tip ulcers
Pitting scars 		2
3
Telangiectasia2
Abnormal nailfold capillaries2
Pulmonary arterial hypertension and/or interstitial lung disease2
Raynaud’s phenomenon3
Scleroderma-related antibodies (any of anti-centromere, anti-topoisomerase I [anti-ScL 70], anti-RNA polymerase III)3
Pts with a total score of ≥9 are classified as having definite systemic sclerosis (sensitivity 91%, specificity 92%)

Management

  • Organ-Based Symptomatic Therapy
    • Raynaud’s: CCB (amlodipine, nifedipine), PDE5i, topical nitroglycerin
    • GERD: PPI
    • Renal: Monitor BP and Cr
      • Scleroderma renal crisis: abrupt onset of HTN and renal dysfunction that typically presents early in disease course (can precede skin thickening), usually triggered by steroids
  • Workup: AKI, proteinuria, MAHA, elevated renin
  • Treatment: short-acting ACEi (captopril, enalapril); may require HD
    • ILD: Periodic PFTs (isolated DLCO may suggest PAH); monitor for respiratory symptoms, pulmonology referral
    • Cardiac/PAH: annual TTE, cardiology referral
  • Systemic Immunosuppression (if progressive skin thickening or organ involvement)
    • MTX, MMF, tocilizumab, cyclophosphamide, if refractory rituximab, IVIG
    • Nintedanib may be used in combination with immunosuppression in ILD
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