What is the best treatment approach for a patient with suspected Goodpasture syndrome?

Treatment of Goodpasture Syndrome

Initiate immediate triple therapy with high-dose corticosteroids, cyclophosphamide, and plasmapheresis as soon as Goodpasture syndrome is suspected—do not wait for antibody confirmation or biopsy results. 1, 2

Immediate Treatment Protocol (Start Before Diagnostic Confirmation)

When to Treat Aggressively

• Begin empirical therapy immediately when anti-GBM disease is suspected based on clinical presentation of rapidly progressive glomerulonephritis with or without pulmonary hemorrhage 1, 2
• Treat all patients except those who meet ALL three criteria: dialysis-dependent at presentation AND 100% crescents (or >50% global glomerulosclerosis) on biopsy AND no pulmonary hemorrhage 2, 3
• Always treat patients with pulmonary hemorrhage regardless of renal status or dialysis dependence—this overrides all other considerations due to mortality risk 2, 3

Triple Therapy Components

Plasmapheresis:

• Start daily plasmapheresis immediately 1, 2
• Continue until anti-GBM antibodies are undetectable on 2 consecutive tests (typically 7-10 treatments over 8 weeks) 1, 2
• Use albumin replacement for standard cases 1
• Use fresh frozen plasma replacement if alveolar hemorrhage is present or recent kidney biopsy was performed 1, 3

Corticosteroids:

• Begin with pulse methylprednisolone (500-1000 mg IV daily for 3 days) 1, 2, 3
• Transition to oral prednisone and taper over approximately 6 months 1, 2

Cyclophosphamide:

• Administer oral cyclophosphamide 2-3 mg/kg daily for 2-3 months 1, 2
• Dose-adjust for reduced GFR or older age 1
• Can be started empirically once infection is ruled out, but ideally after disease confirmation 1, 2

Essential Supportive Care

Pneumocystis Prophylaxis:

• Start trimethoprim-sulfamethoxazole and continue until cyclophosphamide is complete AND prednisone dose is <20 mg daily 1, 2

Prognostic Indicators That Guide Treatment Decisions

Favorable indicators for renal recovery:

• Serum creatinine <500 μmol/L (5.7 mg/dL) at presentation predicts 95% renal survival at 1 year 4, 5
• Not requiring dialysis within 72 hours of presentation, even with elevated creatinine 2, 4

Poor prognostic indicators:

• Dialysis-dependent at presentation: 65% patient survival and only 8% renal survival at 1 year, with >90% remaining on dialysis long-term 2, 4
• 100% crescents on biopsy in dialysis-dependent patients: essentially 0% chance of renal recovery 4, 6

Critical exception: Even with poor renal prognosis, always treat if pulmonary hemorrhage is present—pulmonary disease can be successfully controlled with aggressive therapy 2, 3

Maintenance Therapy Decisions

For isolated anti-GBM disease:

• No maintenance immunosuppression is necessary after completing the initial 6-month treatment course 1, 2
• Relapse rate is <5% in treated anti-GBM disease 1, 2

For double-positive patients (anti-GBM + ANCA):

• Require maintenance therapy as for ANCA-associated vasculitis because relapse rates are equivalent to AAV patients, not isolated anti-GBM disease 1, 2
• This is a critical distinction that is frequently missed 2

Refractory Disease

For patients not responding to standard triple therapy:

• Consider rituximab or mycophenolate mofetil 1
• Refer for clinical trials where available 1

Kidney Transplantation Timing

Defer kidney transplantation until anti-GBM antibodies have been undetectable for a minimum of 6 months 1, 2, 3

• Recurrence after transplantation is very low in patients without detectable antibodies 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for biopsy confirmation—begin empirical therapy immediately when suspected based on clinical presentation 1, 2
• Do not withhold treatment from patients with severe renal impairment (creatinine >500 μmol/L) if they are not yet dialysis-dependent—they still have potential for renal recovery 2, 4
• Always treat pulmonary hemorrhage aggressively, regardless of renal involvement severity—this carries significant mortality risk if untreated 2, 3
• Do not forget maintenance therapy in double-positive (anti-GBM + ANCA) patients—they behave like AAV, not isolated anti-GBM disease 1, 2
• Do not use albumin replacement for plasmapheresis if alveolar hemorrhage is present—use fresh frozen plasma instead 1, 3

Monitoring During Treatment

• Follow anti-GBM antibody titers pre- and post-plasmapheresis sessions 1, 2
• Most cases (97%) have undetectable antibodies within 8 weeks of treatment initiation 1
• Monitor for infections given intensive immunosuppression—severe infection accounts for significant mortality (7/16 deaths in one series) 5
• Strongly recommend smoking cessation as hydrocarbon exposure is associated with disease activity 1