Systemic Sclerosis

Overview

Systemic sclerosis (SSc) is a multisystem autoimmune disease leading to increased fibroblast activity causing abnormal growth of connective tissue. This can cause vascular damage and fibrosis. Fibrosis takes place in the skin, gastrointestinal tract, heart, lungs, and other internal organs.

There are three main patterns of SSc:

• Limited cutaneous SSc (lcSSc)
• Diffuse cutaneous SSc (dcSSc)
• Scleroderma

Epidemiology

• Women more affected than men
• People of African origin affected more than men
• Peak onset of age 40-50 years, but can happen in any age
• Rare in children

Presentation

Limited cutaneous systemic sclerosis (lcSSc)

Also known as limited systemic scleroderma:

• Most common type
• Areas of skin affected are generally the face and distal limbs
• A subtype of lcSSc is known as CREST syndrome:
  • Calcinosis
  • Raynaud’s disease
  • (O)Esophageal dysmotility and gastro-oesophageal reflux (GORD)
  • Sclerodactyly
  • Telangiectasia
• Symptoms are usually relatively unnoticed until internal complications happen e.g. renal failure

Diffuse cutaneous systemic sclerosis (dcSSC)

Also known as diffuse scleroderma:

• Less common
• Areas of skin affected are the trunk and proximal limbs
• Usually more rapid onset with skin thickening and Raynaud’s phenomenon happening together or with a short interval
• Internal organ involvement more common such as interstitial lung disease

General features

• Skin:
  • Raynaud’s phenomenon is common in around 90% of cases
  • Calcinosis
  • Symmetrical swelling of fingers and toes
  • Sclerodactyly – hard and thickened skin
  • Prayer sign – swelling and sclerosis cause patients to be unable to make a fist or place the palmar surfaces together
  • Digital ulcers
  • Tightening of skin around the face and mouth
  • Telangiectasia
  • “Salt and pepper” appearance of skin due to areas of hypopigmentation and hyperpigmentation
• Musculoskeletal symptoms:
  • Joint pain and swelling
  • Myalgia
  • Restriction of joint movement
• Gastrointestinal features:
  • GORD
  • Dysphagia
• Pulmonary features:
  • Interstitial lung disease
  • Pulmonary hypertension
    • Leading cause of death in SSc
• Cardiovascular features:
  • Microvascular coronary artery disease and subsequent MI
  • Pericarditis
  • Arrhythmias
  • Left ventricular dysfunction
• Renal features:
  • Antineutrophil cytoplasmic antibodies (ANCA) – are associated with glomerulonephritis
  • Scleroderma renal crisis:
    • Presents with accelerated hypertension with:
      • Oliguria
      • Headache
      • Fatigue
      • Oedema
      • Rapidly rising serum creatinine
      • Proteinuria
      • Microscopic haematuria
• Genitourinary features:
  • Erectile dysfunction in 80-90% of men due to vascular changes
  • Women may have dyspareunia

Investigations

• Autoantibodies:
  • Antinuclear antibodies (ANA):
    • In 90% of patients
  • Anti-centromere antibodies:
    • Associated with limited cutaneous systemic sclerosis
  • Anti-scl-70 antibodies:
    • Associated with diffuse cutaneous systemic sclerosis

Other investigations include:

• Full blood count (FBC):
  • May show microcytic anaemia with a chronic gastrointestinal bleed
• Urea and electrolytes (U&Es):
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP):
  • May be normal or elevated
• ECG:
  • Considered if patients have cardiorespiratory symptoms such as shortness of breath, decreased exercise tolerance, or cough
  • May show arrhythmia 
• Echocardiogram:
  • Considered if patients have cardiorespiratory symptoms such as shortness of breath, decreased exercise tolerance, or cough
  • May show pulmonary hypertension or left ventricular dysfunction
• Pulmonary function tests:
  • May show restrictive lung disease

Management

Renal crisis

• 1^st line: Angiotensin-converting enzyme (ACE) inhibitors + IV 0.9% saline
  • This is to control hypertension in renal crises due to systemic sclerosis

Overall management

• 1^st line: smoking cessation, exercise, and physiotherapy
• Immunosuppression is considered in patients with lung involvement, myositis, or inflammatory arthritis:
  • Inflammatory arthritis/myositis present: methotrexate
  • Interstitial lung disease present: mycophenolate, cyclophosphamide, azathioprine, rituximab

Other manifestations of the disease are managed accordingly

Patient Advice

• Patients should stop smoking as this can worsen digital ulcers and Raynaud’s phenomenon

Complications

• Interstitial lung disease, pulmonary fibrosis, pulmonary hypertension – leading causes of death
• Malignancy – associated with lung, breast, and haematological malignancies 
• Small bowel bacterial overgrowth syndrome
• Inflammatory arthritis
• Carpal tunnel syndrome
• Sjögren’s syndrome
• Scleroderma renal crisis
• Cardiomyopathy
• Myopathy and myositis

Prognosis

• Leading causes of death are pulmonary fibrosis and pulmonary hypertension