Goodpasture Syndrome

Goodpasture syndrome (anti glomerular basement membrane disease) is a small vessel autoimmune disease in which autoantibodies target the alpha 3 chain of type IV collagen, causing rapidly progressive glomerulonephritis with or without diffuse alveolar haemorrhage.

• Incidence about 1 per million per year; bimodal age distribution (young men 20 to 30 with lung involvement, older women 60 to 70 with renal limited disease).
• Associated with HLA DRB1*1501, smoking, hydrocarbon exposure, respiratory infection, cocaine; 10 to 30% are double positive for ANCA.
• Pathology: linear IgG deposition along the glomerular basement membrane, crescentic glomerulonephritis.
• Prognosis depends on serum creatinine at presentation: dialysis dependent with 100% crescents or creatinine over 5.7 mg/dL (500 µmol/L) has poor renal recovery (under 10%); lung haemorrhage can be fatal.

• Haemoptysis, dyspnoea, cough, fever, haematuria (macroscopic or microscopic), oliguria, oedema, hypertension, rapid renal failure, fatigue, anaemia.
• Alveolar haemorrhage may precede renal involvement; pulmonary haemorrhage more common in smokers.
• No extrapulmonary vasculitic features (except ANCA overlap).

• Anti GBM antibodies (ELISA) positive in over 90%; ANCA testing (MPO) also.
• Renal biopsy: crescentic glomerulonephritis with linear IgG (and C3) along the GBM on immunofluorescence (diagnostic).
• Urinalysis: dysmorphic red cells, red cell casts, proteinuria; creatinine, urea; falling haemoglobin, iron deficiency.
• Chest radiograph and CT: bilateral alveolar infiltrates; bronchoalveolar lavage with haemosiderin laden macrophages; DLCO increased during bleeding.
• Exclude other pulmonary renal syndromes (ANCA vasculitis, lupus, IgA vasculitis, cryoglobulinaemia, infection).

Treat urgently, ideally before irreversible renal damage.

• Plasma exchange daily (4 L exchanges, 60 mL/kg, replacement with 5% albumin, using fresh frozen plasma for patients with alveolar haemorrhage or after biopsy) for 14 days or until anti GBM antibodies undetectable.
• Cyclophosphamide 2 mg/kg/day orally (1.5 mg/kg if older; or IV 15 mg/kg), reduced for age and renal function, for 2 to 3 months.
• Corticosteroids: methylprednisolone 500 to 1000 mg IV daily for 3 days, then prednisolone 1 mg/kg/day (maximum 60 to 80 mg) tapered over 6 months.
• Imlifidase (IgG cleaving enzyme) emerging for dialysis dependent disease; rituximab for refractory cases.
• Supportive: pulmonary haemorrhage requires oxygen, ventilation, correction of coagulopathy; dialysis for uraemia, hyperkalaemia, volume overload; blood pressure control; Pneumocystis prophylaxis (co trimoxazole 960 mg three times weekly); gastroprotection; bone protection.
• Stop smoking, avoid hydrocarbons.
• Renal transplantation after antibody negative for at least 6 months; recurrence rare.
• Monitor anti GBM titres, creatinine, relapse (rare, usually smokers).