Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy, immune activation, and fibrosis affecting skin and internal organs. Cutaneous involvement defines two main subsets: limited cutaneous SSc (lcSSc; distal to elbows/knees, face) and diffuse cutaneous SSc (dcSSc; proximal limbs and trunk). Early recognition of Raynaud’s phenomenon, puffy fingers, and nailfold capillary changes enables earlier diagnosis and organ surveillance. Management is organ- and symptom-directed, with immunomodulation for inflammatory skin disease and targeted therapies for vasculopathy (Raynaud’s/digital ulcers) and interstitial lung disease (ILD).
Epidemiology and Subsets
- Female predominance; peak onset 30–60 years.
- Subsets:
- lcSSc: anti-centromere antibodies common; pulmonary arterial hypertension (PAH) risk.
- dcSSc: anti–topoisomerase I (Scl-70) or RNA polymerase III; higher risk of ILD, renal crisis, and rapid skin progression.
Pathogenesis
- Endothelial injury → dysregulated vasculature (Raynaud’s, digital ulcers), immune activation with autoantibodies, and fibroblast activation → collagen deposition and fibrosis.
Clinical Cutaneous Features
- Raynaud’s phenomenon (often first sign); digital color changes with cold/stress.
- Puffy fingers → sclerodactyly (tight, thick skin), digital pitting scars, calcinosis cutis, telangiectasias (face, hands), microstomia with perioral radial furrowing.
- Skin thickening distribution by subset (mRSS used to quantify).
- Pruritus, dyspigmentation, anhidrosis; mat telangiectasias correlate with PAH risk.
- Nailfold capillaroscopy: dilated/giant capillary loops, dropout, hemorrhages (scleroderma pattern).
Systemic Associations (brief)
- ILD (dcSSc>lcSSc), PAH (lcSSc), scleroderma renal crisis (RNA Pol III), GI dysmotility (esophageal reflux, pseudo-obstruction), cardiac fibrosis/arrhythmias, myopathy.
Differential Diagnosis
- Morphea, nephrogenic systemic fibrosis, eosinophilic fasciitis, scleredema, scleromyxedema, chronic graft-versus-host disease, diabetic cheiroarthropathy.
Diagnosis and Workup
- 2013 ACR/EULAR criteria; key items: skin thickening of fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, Raynaud’s, SSc-specific autoantibodies.
- Serologies: ANA, anti-centromere, anti–Scl-70, anti–RNA polymerase III, anti–U3 RNP, anti–PM-Scl, anti–Th/To.
- Baseline organ assessment: PFTs with DLCO, HRCT chest (especially dcSSc), echocardiogram (PAH screen), creatinine/urinalysis (renal crisis risk), GI assessment as indicated.
Management of Cutaneous and Vascular Manifestations
- Raynaud’s phenomenon/digital ischemia
- First-line: lifestyle (thermal protection, smoking cessation), dihydropyridine CCBs (nifedipine/amlodipine).
- Add-ons for refractory: PDE-5 inhibitors (sildenafil/tadalafil), topical nitroglycerin, losartan; IV prostacyclin infusions (iloprost) for severe ischemia; botulinum toxin peri-digital injections as adjunct in specialized centers.
- Digital ulcer prevention: PDE-5 inhibitors, bosentan (reduces new ulcers).
- Inflammatory skin thickening
- Immunomodulators:
- Mycophenolate mofetil (common first-line, also treats ILD).
- Methotrexate for skin disease and arthropathy.
- Cyclophosphamide for severe progressive skin/ILD (consider toxicity).
- Tocilizumab may slow skin/ILD progression in early inflammatory dcSSc.
- Rituximab shows benefit in skin and lung in studies; increasingly used.
- Phototherapy (UVA1) for localized symptomatic skin tightness/pruritus in select cases.
- Calcinosis cutis
- Difficult to treat; options include diltiazem, minocycline, colchicine; procedural removal or laser for focal symptomatic deposits.
- Pruritus and symptomatic care
- Emollients, antihistamines, gabapentinoids, mirtazapine; occupational therapy for hand function; oral stretching devices and dental care for microstomia.
- Organ-specific considerations (brief pointers)
- ILD: mycophenolate, cyclophosphamide; nintedanib antifibrotic approved for SSc-ILD; rituximab/tocilizumab emerging.
- PAH: right heart catheterization confirmation; endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin pathway agents per PH guidelines.
- Renal crisis: avoid high-dose steroids; prompt ACE inhibitor (captopril) initiation is lifesaving.
Monitoring
- Serial mRSS scoring; annual PFTs and echocardiograms (more frequent early in dcSSc); skin and vascular complication surveillance; digital ulcer documentation.
Prognosis
- Variable; worse with dcSSc, early rapid skin thickening, ILD/PAH, renal crisis, and RNA Pol III positivity. Cutaneous severity often parallels systemic risk early.
References (recent guidelines and key reviews)
- EULAR recommendations for SSc management, 2023–2024.
- Evidence for mycophenolate, tocilizumab, rituximab, and nintedanib in SSc, 2021–2024.
- Raynaud’s/digital ulcer management consensus, 2022–2024.