Goodpasture’s Syndrome

Co-existence of acute glomerulonephritis and pulmonary alveolar haemorrhage caused by a type II antigen-antibody reaction involving anti-glomerular basement membrane (anti-GBM) antibodies.

Background

• Rare (incidence 1-2/1000000); accounts for 1-2% of all rapidly progressive glomerulonephritides
• Between 60-80% have both renal and pulmonary involvement; whilst 20-40% just have renal and 10% just have pulmonary

Aetiology/Risk factors

• Association with HLA-DR2/DR15
• Exposure to organic solvents or hydrocarbons
• Smoking
• Infection (influenza A2)
• Cocaine (inhalation)
• Exposure to metal dusts

Pathophysiology

• Autoimmune reaction (type II- cytotoxic) occurs in the glomerulus basement membrane and alveolar basement membrane, which causes glomerulonephritis (crescentic) and pulmonary haemorrhage

Presentation

• Constitutional symptoms
  • Malaise, chills, fever, arthralgia, nausea/vomiting, weight loss
  • Can precede or be concurrent with renal/pulmonary symptoms
• Haemoptysis, cough, dyspnoea, shortness of breath
  • Massive pulmonary haemorrhage may cause respiratory failure
  • Chest pain is uncommon
• Haematuria; oedema; high blood pressure
• Other signs include tachypnoea; inspiratory crackles (po haemorrhage); cyanosis; oedema; pallor

Investigations

• Ideally, renal biopsy for antiGBM fluorescence or anti-GBM ELISA
  • Check other antibodies too e.g. ANCA, dsDNA (in case of SLE as cause)
• Other lab tests
  • FBC (anaemia)
  • U&Es/renal function- be weary of AKI
  • ESR/PV (often normal in GP; but would be raised in vasculitis)
  • Clotting/coagulation study
  • Urinalysis
• CXR
  • Patchy consolidation, often bilateral, symmetrical, perihilar and bibasal
    • Apices/costphrenic angles are often normal
    • CXR can be completely normal in ~20%
• Occasionally, lung biopsy may be required

Management

• IV steroids and usually cyclophosphamide alongside plasmapheresis until anti-GBM undetectable
  • Usually with human albumin solution
  • +/- fresh frozen plasma if there is severe haemorrhage
  • If there is severe AKI, dialysis is required (poor prognosis)
  • Corticosteroids are tapered down over 6-12 months
  • Cyclophosphamide is usually given for 3 months
• In severe kidney failure, transplant may be an option

Complications

• Pulmonary haemorrhage is a significant cause of mortality in these patients (5-year survival is >80%)
• Some patients will require long-term dialysis (20-30%)

Advertisement