Systemic Sclerosis (SSc)

Background

Multisystem autoimmune disease characterized by immune dysregulation causing vascular dysfunction and fibrosis of skin and internal organs. Nearly all patients have sclerodactyly, Raynaud’s, and a positive ANA.
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.

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.

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) joints		9
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
Telangiectasia		2
Abnormal nailfold capillaries		2
Pulmonary arterial hypertension and/or interstitial lung disease		2
Raynaud’s phenomenon		3
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%)

Organ-Based 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.