Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy and fibrosis of the skin and other organs.
Epidemiology
- ♀ > ♂ (∼ 5:1)
- Peak incidence: 30–50 years
Etiology
Pathophysiology
Clinical features
CREST syndrome
CREST syndrome refers to a constellation of symptoms traditionally associated with limited SSc (can also be seen in diffuse SSc).
- C: Calcinosis cutis: small white calcium deposits on the pressure points of the extremities (e.g., elbows, knees, fingertips)
- R: Raynaud phenomenon
- E: Esophageal hypomotility (systemic sclerosis): smooth muscle atrophy and fibrosis → esophageal dysmotility and decreased lower esophageal sphincter pressure → dysphagia, gastroesophageal reflux, heartburn → aspiration, Barrett esophagus, stricture
- S: Sclerodactyly
- T: Telangiectasia
Cutaneous
- Thickening and hardening of the skin, which appears smooth, shiny, and puffy
- Sclerodactyly: fibrotic thickening and tightening of the skin on the fingers and hands
- Edema followed by fibrosis that results in a waxy appearance of the skin
- Limited range of motion and possibly flexure contractures and clawing of the digits
- Multiple, painful ischemic digital ulcers with atrophy and necrotic spots
- Digital pitting: hyperkeratotic scarring that most commonly affects the fingertips
- Face changes
- Loss of expression (mask-like facies)
- Smoothing of deep wrinkles
- Microstomia (a disproportionately small mouth) accompanied by characteristic perioral wrinkles
Renal
- Scleroderma renal crisis (SRC)
- Abrupt onset, life threatening
- SRC is caused by immune-mediated injury to small renal vessels that typically spares the glomerular capillaries
- Clinical features of SRC
- Oliguric acute kidney injury, proteinuria, hematuria
- Hypertension with or without symptoms of hypertensive emergency
- Microangiopathic hemolytic anemia (MAHA) and thrombocytopenia
- Treatment: ACE inhibitors
- Chronic kidney disease: reduced kidney function due to abnormal collagen deposition → thickening of renal arteriolar walls → decreased renal blood flow
Pulmonary
- Interstitial lung disease
- Pulmonary artery hypertension
Other extracutaneous
- Gastrointestinal tract
- Esophageal dysmotility → dysphagia and reflux
- Small bowel dysmotility → bloating, gas, constipation, and cramping
- Vascular disease
- Raynaud phenomenon
- Thromboembolism
Diagnostics
Warning
Scleroderma renal crisis is a medical emergency with a high mortality rate. Promptly evaluate serum creatinine and urine protein in individuals with SSc who present with an acute rise in blood pressure and start management of SRC.
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Antinuclear antibodies (ANA): present in ∼ 90% of patients
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SSc-specific autoantibodies
- Anticentromere antibodies: associated with limited SSc, increased risk for vascular complications (e.g., PAH)
- Anti-SCl-70 (anti-topoisomerase I antibody): associated with severe and rapidly progressive diffuse SSc, limited SSc, ILD, digital ulcers
- Anti-RNA polymerase III: associated with diffuse SSc, scleroderma renal crisis