Skip to content

Scleroderma (Systemic Sclerosis)

BASICS

  • Definition: Chronic disease of unknown cause with diffuse fibrosis of skin/viscera and vascular abnormalities.
  • Key Feature: Most manifestations have vascular features (Raynaud phenomenon); frank vasculitis is rare.
  • Spectrum: Ranges from mild skin involvement to severe systemic disease (can be fatal within months).
  • Variants:
  • Diffuse: Proximal/distal extremity and truncal skin thickening.
  • Limited: Confined to fingers, hands, and face; includes CREST syndrome (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia).
  • Systems Affected: Skin, renal, cardiovascular, pulmonary, musculoskeletal, GI.

Special Populations

  • Geriatrics: Uncommon >75 yrs.
  • Pediatrics: Rare.
  • Pregnancy: Higher risk of preterm birth; delay pregnancy until disease stable; diffuse form = greater risk of cardiopulmonary/renal complications.

EPIDEMIOLOGY

  • Incidence (US): 1–5/100,000/year
  • Prevalence (US): 1–25/100,000
  • Onset: Peak 30–50 yrs (most in 3rd–5th decades)
  • Sex: Female > male (4:1)

ETIOLOGY & PATHOPHYSIOLOGY

  • Pathophysiology: Vascular and fibrotic processes; increased TGF-β, PDGF after endothelial activation.
  • Trigger: Unknown (possible immune dysregulation, exposure to silica, vinyl chloride, hydrocarbons, bleomycin, rapeseed oil)
  • Genetics: Rare familial clustering.

RISK FACTORS

  • Unknown (possible environmental/occupational exposures).

DIAGNOSIS

HISTORY

  • Raynaud phenomenon—usually first symptom
  • Skin changes: Thickening, “puffy hands,” pruritus
  • GERD symptoms: Early, often noted

PHYSICAL EXAM

  • Skin: Digital ulcers, pitting, tightness, swelling, hyper-/hypopigmentation, narrowed mouth, calcinosis
  • Vascular: Telangiectasia
  • Musculoskeletal: Flexion contractures, friction rubs, swelling, stiffness, sclerodactyly, proximal weakness
  • GI: Dysphagia, reflux, malabsorption, weight loss, xerostomia
  • Renal: Hypertension, renal crisis (ARF)
  • Pulmonary: Crackles at bases, dyspnea
  • Neuro: Peripheral/trigeminal neuropathy
  • Cardiac: Conduction defects, cardiomyopathy, pericarditis, cor pulmonale

DIFFERENTIAL DIAGNOSIS

  • Mixed connective tissue/overlap syndromes
  • Scleredema
  • Nephrogenic systemic fibrosis
  • Toxic oil syndrome
  • Eosinophilia-myalgia syndrome
  • Diffuse fasciitis with eosinophilia

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests

  • Nailfold capillaroscopy: Drop-out significant
  • Labs: CBC, creatinine, urinalysis, ANA (>90% positive), anti-Scl-70 (diffuse/systemic, risk for ILD), anticentromere (CREST/limited)
  • Imaging: Chest X-ray (reticular pattern, pulmonary fibrosis), hand X-ray (soft tissue atrophy, acroosteolysis, calcinosis)
  • Pulmonary Function: Reduced capacity, diffusion defect
  • Antibodies: Anti-U3-RNP (risk for pulmonary HTN), anti-PM-Scl (myositis), anti-RNA pol III (diffuse/renal crisis)

Further Evaluation

  • ECG: Low voltage, arrhythmia, conduction defects
  • Echo: Pulmonary hypertension/cardiomyopathy
  • Upper GI imaging: Distal esophageal dilatation/dysmotility
  • HRCT Chest: Alveolitis, fibrosis (ground glass or lower lobe changes)
  • Skin biopsy: Thick collagen, arteriolar fibrosis
  • R heart cath: For pulmonary hypertension

TREATMENT

General

  • Supportive, symptomatic.
  • Esophageal dilation for strictures.
  • Lifestyle: Avoid cold, dress warmly, avoid smoking, fingersticks, elevate bed for reflux, use emollients.
  • Renal crisis: May require dialysis.

Medications

First Line

  • ACE inhibitors: For renal crisis
  • Dihydropyridine CCBs: Nifedipine/amlodipine for Raynaud
  • Corticosteroids: Low dose only (for myositis, alveolitis); avoid high doses (renal risk)
  • NSAIDs: Joint/tendon pain (caution with ACEI)
  • Antibiotics: Secondary infection
  • Antacids/PPIs: GERD
  • Metoclopramide: GI dysmotility
  • Hydrophilic ointments: Skin
  • Topical abx/PDE5 inhibitors: For cutaneous ulcers
  • Immunosuppressants: Cyclophosphamide for ILD/life-threatening disease

Additional Options

  • Nitrates, PDE5 antagonists, prostanoids, endothelin-1 antagonists: For Raynaud/pulmonary HTN
  • Immunosuppressants/alkylators: For alveolitis/ILD
  • Physical therapy, heat therapy for joint function

Surgery/Procedures

  • Gastroplasty: GERD correction
  • Sympathectomy: Raynaud (limited role)
  • Lung transplant: Pulmonary HTN/ILD
  • Stem cell transplant: Rapidly progressive SSc

FOLLOW-UP & MONITORING

  • Every 3–6 months: Skin, organ involvement, medication review
  • Yearly: Echo, PFTs

DIET

  • Adequate fluids, adjust diet to GI symptoms

PATIENT EDUCATION

  • Stay active, avoid fatigue, report bruising/nonhealing wounds, smoking cessation, Scleroderma Federation: https://scleroderma.org/

PROGNOSIS

  • Course: Incurable, variable; improvement possible.
  • Poor prognosis: Cardiac, pulmonary, renal involvement early in course.

COMPLICATIONS

  • Renal/respiratory failure, contractures, esophageal dysmotility, reflux, arrhythmia, bowel obstruction, cardiomyopathy, pulmonary hypertension, cancer risk, death.

ICD-10

  • M34.2 Systemic sclerosis induced by drug/chemical
  • M34.9 Systemic sclerosis, unspecified
  • M34.0 Progressive systemic sclerosis

CLINICAL PEARLS

  • Raynaud phenomenon often initial symptom.
  • Skin thickening, puffy hands, and GERD common early findings.
  • Proactive monitoring for pulmonary hypertension or ILD is essential.