Systemic sclerosis (Scleroderma)

Systemic sclerosis (SSc) is a chronic disease caused by abnormal growth of connective tissue, which leads to diffuse thickening and hardening of the skin and often the inner organs. SSc is categorized into limited SSc and diffuse SSc. The more common, limited form of SSc begins with sclerosis of the fingers, hands, and face, which then progresses to the center of the body. Limited SSc is often associated with symptoms of CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) and may be followed by internal organ involvement as the disease progresses. Diffuse SSc is less common, but more aggressive, with early organ system involvement that may be life-threatening if damage to the heart, lungs, or kidneys occurs. Treatment is symptomatic and based on the extent of skin and organ system involvement. In the case of diffuse inflammation of the skin and/or organs, immunosuppressive drugs (e.g., methotrexate) should be administered. The prognosis varies depending on which organs are involved, with pulmonary arterial hypertension, interstitial lung disease, and cardiac disease significantly increasing the mortality rate.

• ♀ > ♂ (3:1)
• Higher incidence in African Americans
• Peak incidence: 30–50 years

References:^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Common symptoms

• Cutaneous findings
  • Thickening and hardening of the skin (skin appears smooth and shiny)
  • Depigmentation of the skin with sparing of perifollicular pigmentation (salt-and-pepper appearance)
  • Sclerodactyly
    • Red-blue discoloration of the fingers
    • Edema and fibrosis with waxy appearance of the skin and limited range of motion
    • Atrophy and necrotic spots
    • Lesions on the proximal nail fold
  • Multiple, painful ischemic digital ulcers
  • Face
    • Loss of expression (mask-like facies)
    • Shortened frenulum
    • Microstomia accompanied with characteristic perioral wrinkles
• Vascular disease
  • Raynaud's phenomenon
  • Thromboembolism
• Fatigue, weakness
• Joint stiffness/pain

Limited cutaneous systemic sclerosis

• In 90% of cases, Raynaud's phenomenon precedes the onset of other symptoms.
• Skin manifestations are usually restricted to the hands, fingers, and face.
• Extracutaneous organ involvement may occur.
• Often manifests as CREST syndrome
  • C → Calcinosis cutis (small white calcium deposits on the pressure points of the extremities such as the elbows, knees, and fingertips)
  • R → Raynaud's phenomenon
  • E → Esophageal hypomotility; (esophageal dysmotility, gastroesophageal reflux, heartburn, dysphagia, which is caused by smooth muscle atrophy and fibrosis)
  • S → Sclerodactyly
  • T → Telangiectasia

Diffuse cutaneous systemic sclerosis

• Raynaud's phenomenon often coincides with or follows the onset of other symptoms.
• Skin manifestations typically spread proximally from the trunk to the elbow.
• Extracutaneous organ manifestations are common
  • Arthralgia and myalgia → can result in contractures
  • Gastrointestinal tract
    • Esophageal dysmotility → dysphagia and reflux
    • Small bowel dysmotility → bloating, gas, constipation, and cramping
  • Pulmonary disease: pulmonary hypertension and interstitial lung disease; , increased risk of lung cancer
  • Cardiac disease: fibrosis, myocarditis, pericarditis
  • Renal disease: abnormal collagen deposition → thickening of renal arteriolar walls → decreased renal blood flow → reduced kidney function
    • Scleroderma renal crisis:
      • Occurs in 10–15% of cases of diffuse SSc
      • Life-threatening complication with, e.g.:
        • Oliguric renal failure
        • (Malignant) hypertension
        • Encephalopathy
        • Microangiopathic hemolytic anemia

References:^{[1][4][5][6][7][8][9][10]}

• Auto-antibodies: Antinuclear antibodies (ANA) present in about 90% of cases
  • Limited SSc: anticentromere antibodies (ACA)
  • Diffuse SSc
    • Anti-Scl-70 (anti-topoisomerase I antibody)
    • Anti-RNA polymerase III
  • See Antibody diagnosis of autoimmune diseases
• Serum protein electrophoresis: ↑ γ-globulins
• Complete blood count and differential
• Chest x-ray: detects possible pulmonary involvement
• Other tests may be indicated based on organ-specific symptoms (e.g., signs of renal crisis).

References:^[11][12]