Goodpasture Syndrome - Anti GBM Disease

Goodpasture Syndrome - Anti GBM Disease

 

Goodpasture syndrome is an autoimmune condition that is characterized by rapidly progressive glomerulonephritis, pulmonary hemorrhage and antibodies to the glomerular base membrane.

Epidemiology

  • Incidence – less than 1/1,000,000
  • Age – two age peaks
    • Men in late 20s
    • Women and men >60 years of age
  • Sex – M>F
  • Ethnicity – Caucasians predominate

Inheritance

  • High prevalence of DRB1-1501 and 1502 regions haplotype is consistent with genetic predisposition to autoimmunity

Pathophysiology

  • Antibodies formed are directed against the alpha 3 subunit of collagen type IV (NCI domain)
  • Deposits of antibodies are present in the basement membrane of renal and pulmonary organs
  • Damage to the glomerular and alveolar basement membrane by antibodies
  • Three types of syndromes:
    • ANCA negative
    • ANCA positive (mainly myeloperoxidase antibodies)
    • Post transplantation Alport syndrome (alloantibodies also to alpha 4 and alpha 5 NCI domains)

Clinical Presentation

  • Identification of disease often delayed since Goodpasture syndrome is not the most common cause of hemoptysis or renal failure
  • Pulmonary
    • Pulmonary hemorrhage and hemoptysis (hemoptysis more common in smokers)
    • Pulmonary involvement often precedes nephritis, the main cause of morbidity and mortality
    • Pulmonary opacities on chest radiography
    • Disease course may be dominated by recurrent hemoptysis or life-threatening pulmonary hemorrhage
  • Renal
    • Early presenting signs and symptoms – oliguria, proteinuria, hematuria
    • Renal involvement frequently progresses over a matter of weeks to acute renal failure
    • Immediate treatment required to avoid irreversible kidney damage
    • Acute glomerulonephritis (ususally the rapidly progressive type)
  • Anemia
    • Pulmonary hemorrhage is the main cause of anemia
  • High fatality rate (75-90%) if untreated

Diagnosis

  • Laboratory testing
    • Serum glomerular basement membrane (GBM) antibody assays
      • Faster and more reliable than the less sensitive indirect immunofluorescent test on normal kidney sections
    • ANCA antibody testing
      • Approximately 30% of anti-GBM positive samples are also ANCA positive
      • Rule out other causes of rapidly progressive glomerulonephritis (RPGN)
    • Additional testing
      • CBC, creatinine, blood urea nitrogen and erythrocyte sedimentation rate
  • Renal biopsy
    • Diagnostic confirmation and assessment of renal prognosis

Differential Diagnosis

  • ANCA-associated systemic vasculitis
  • Diabetic nephropathy
  • Lupus nephritis
  • Alport syndrome
  • Poststreptococcal glomerulonephritis
  • Lung cancer

Treatment

  • Cytotoxic drugs and plasma exchange are the cornerstone treatment of anti-GBM disease
    • Plasmapheresis is believed to remove anti-GBM antibodies responsible for initiating damage as well as secondary circulating mediators
  • Remission may follow intensive plasmapheresis combined with corticosteroids and cytotoxic agents

Monitoring

  • Monitoring treatment
    • Anti-GMB titers should decline with effective treatment
    • Serum creatine levels to assess renal function
    • Hemoglobin levels to monitor lung hemorrhage
  • Monitoring side effects of the drugs
    • Surveillance for infections due to immunosuppressive drugs
    • White blood cell count for drug cytotoxicity
    • Platelet count for the effect of plasmapheresis

See Also