PROGRESSIVE SYSTEMIC SCLEROSIS
 
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PROGRESSIVE SYSTEMIC SCLEROSIS

 

DEFINITION:

A multiorgan rheumatologic disease characterized by sclerodermatous skin changes and abnormalities of the visera.

EPIDEMIOLOGY:

  • incidence: 4.5-12/million
  • age of onset:
    • rare in childhood; only 1-10% (<20 years)
  • risk factors:
    • familial (extremely rare)
    • F = M (1:1) <8 years
    • F > M (3:1) >8 years
    • immunogenetic predisposition
      • ? - HLA B8, Bw35, DR1, DR5

PATHOGENESIS:

1. Etiology

  • unknown: principle - factors which increase collagen synthesis or deposition
  • 1. Hypotheses (3)
  • 1. Metabolic - abnormal collagen metabolism
    • excessive collagen deposition (altered glycosylation/ hydroxylation of collagen; decreased collagenase activity)
    • excessive collagen synthesis (serum factors; see below)
  • 2. Vascular - endothelial cell injury
    • injury (via protease-dependent mechanisms or vasoregulatory failure) results in increased vascular permeability -> edema -> activation of fibroblasts -> increased collagen synthesis -> fibrosis
  • 3. Immunogenic - cell-mediated
    • T-cell mediated autoimmunity to a CT antigen stimulates fibroblasts to increase collagen synthesis and induce endothelial cell damage. Against this hypothesis is the observation that there is no clear benefit of corticosteroids or immunosuppressants as PSS appears to be less of an inflammatory disorder and more a disorder characterized by diffuse fibrosis and sclerosis.

CLINICAL FEATURES:

1. Constitutional Symtoms

  • ?

2. Cutaneous Manifestations

1. Sclerosis

  • insidious onset with sequential course (3 phases):
  • 1. Edema
    • digits, hands, arms, face, trunk
    • non-pitting, warm, tender, erythematous
    • persists for weeks to months before next phase
  • 2. Sclerosis
    • acrosclerosis (fingers) -> face -> trunk & limbs
    • waxy, tight, hard
    • persists for months to years
  • 3. Atrophy
    • widespread
    • shiny, variable pigmentation

2. Raynaud's Phenomenon (in 90% of PSS)

  • often initial sympton of PSS preceding the other manifestations by years
  • tricolour: white -> blue -> erythematous

3. Others

  • finger tip pitting and ulceration
  • subcutaneous & periarticular calcifications
  • telangiectasia (periungual)

3. Visceral Manifestations

1. Neurological (Central Nervous System)

  • cerebral arteritis
  • cranial nerve palsies (V-sensory)
  • decreased vibration sense

2. Respiratory

1. Parenchymal Disease

  • dry, hacking cough with shortness of breath of exertion
  • restrictive lung disease with decreased DLCO
  • chest x-ray: bibasilar pulmonary fibrosis

2. Vascular Disease

  • gradual obliteration of the pulmonary vascular bed -> pulmonary hypertension -> cor pulmonale
  • 3 types of lung disease involving the lung parenchyma (P) and vasculature (V): P>V, P=V, P<V

3. Cardiovascular

1. Myocardial Fibrosis

  • rhythm disturbances (heart block, BBB, PAC, PVC, PSVT, VT)
  • thickened left ventricular wall, decreased left ventri- cular compliance, effusions (on 2D Echo)
  • decreased myocardial perfusion and ejection fraction (on scan)

2. Coronary Artery & Microvascular Disease

  • results in coronary artery disease
  • secondary to Raynaud's phenomenon

3. Pericarditis

  • with acute and chronic effusions

4. Gastrointestinal

1. Esophageal Manifestations

  • reflux, esophagitis, stricture, ulceration, dysphagia, regurgitation, aspiration

2. Small Bowel

  • secondary to gut hypotonia
  • abdominal pain & distension, pseudo-obstruction
  • malabsorptive diarrhea & syndrome
  • pneumatosis intestinalis

3. Large Bowel

  • constipation, bloating, diarrhea

4. Sjogren's Syndrome

  • xerostomia, keratoconjunctivitis, parotitis

5. Renal

  • ominous & often present early in disease course
  • 1. Proteinuria
    • most common indicator of renal disease in PSS
  • 2. Systemic Hypertension
    • renovascular Raynaud's phenomenon -> decreased renal plasma flow -> increased renin -> increased BP - ranges from mild to malignant
  • 3. Renal Failure
    • renal or prerenal
    • occurs in about 25% of patients (? children)

6. Musculoskeletal

  • common, occurs at or near onset of disease
  • 1. Arthritis
    • morning stiffness of hands, knees, ankles
    • joint pain - mild & transient in 2/3 rd's of cases
    • joint contractures - insidious, PIP & elbows most often
  • 2. Acroosteolysis
    • distal phalanges - decrease soft tissue, distal tuft resorption
  • 3. Myopathy
    • simple vs complicated

7. CREST Syndrome

  • C - calcinosis - of elbows, MCP jts., knees (periarticular)
  • R - Raynaud's phenomenon - digit ulceration & gangrene
  • E - esophageal dysmotility - reflux, dysphagia, aspiration
  • S - sclerodactyly - sclerotic changes of distal digits only
  • T - telangiectasia - dilation of capillaries on body surface

       

    • lips, tongue, roof of mouth, face
    • very rare in children
    • less sclerodactyly but greater "CRT" than in PSS
    • presence of anticentromere antibody

    • INVESTIGATIONS:

    1. Biologic

    • may be a slight elevation of skeletal muscle enzymes

    2. Pathologic (Biopsy)

    • lungs - fibrosis - diffuse alveolar, interstitial, peribronchial
    • heart - myofibrillar degeneration
    • gastrointestinal - atrophic muscle replaced by fibrous tissue & inflammatory cells
    • kidney - renal vascular intimal thickening
    • muscle - increased deposition of collagen & fat, loss of Type II fibres
    • skin - edema - increased hydrophillic glycosaminoglycan in dermis
      • sclerosis - increased collagin (embryonic) content in dermis
      • atrophic - thinning of epidermis, atrophy of rete pegs,
      • T-cell infiltrates

    3. Others

    1. Radiologic

    • chest x-ray
    • ECG, 2-D Echo, Scan
    • barium swallow, follow-thru, enema
    • renal arteriogram

    2. Serum

    • increased ANA
    • anemia

    MANAGEMENT:

    1. Supportive

    • avoid excess sun exposure, skin care, therapeutic team, physiotherapy, visceral complications

    2. Drugs

    1. Colchicine

    • inhibits fibroproliferative process
    • may soften skin
    • sustained improvement in visceral diseas is inconsistent

    2. Penicillamine

    • most common drug to treat PSS
    • breaks down collagen
    • benefits skin and lung disease

    3. Immunosuppressants

    • no role of corticosteroids or immunosuppressants

    3. Complications

    1. Renal Disease

    • hemodialysis +/- transplantation
    • captopril to decreased blood pressure very effective

    2. Raynaud's Phenomenon

    • avoidance of precipitating factors - cold, trauma
    • nifedipine
    • others: serial plasmaphoresis, biofeedback, sympathectomy,
    • NTG paste

     

     

     

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