Treatment of Goodpasture Syndrome
Initiate immediate triple therapy with cyclophosphamide, high-dose corticosteroids, and plasmapheresis as soon as Goodpasture syndrome is confirmed—or even when highly suspected while awaiting confirmation—unless the patient is dialysis-dependent with 100% crescents or >50% global glomerulosclerosis on biopsy and no pulmonary hemorrhage. 1
Immediate Treatment Protocol
First-Line Therapy Components
Plasmapheresis is the cornerstone of acute management and should be started without delay 1. The standard protocol involves daily or alternate-day sessions, with most patients requiring a median of 13 sessions (range 9-17) 2. The number of plasmapheresis sessions directly correlates with overall survival 2.
Cyclophosphamide should be administered, with oral formulation showing near-significant superiority over intravenous administration in terms of mortality outcomes 2. This finding from a large French cohort of 122 patients suggests oral cyclophosphamide may be the preferred route 2.
High-dose corticosteroids (typically intravenous methylprednisolone) complete the triple therapy regimen 3, 4. Treatment should begin immediately upon diagnosis confirmation, or even earlier if clinical suspicion is high 1.
When to Withhold Aggressive Treatment
Do not initiate the full triple therapy regimen in patients who meet all three of the following criteria 1:
- Dialysis-dependent at presentation
- 100% crescents or >50% global glomerulosclerosis on kidney biopsy
- No active pulmonary hemorrhage
This exception exists because renal recovery is extremely unlikely in this specific scenario, though pulmonary hemorrhage remains an indication for treatment regardless of renal status 1.
Diagnostic Confirmation
Laboratory Testing
Anti-GBM antibodies are positive in approximately 90% of cases 1, 5. A critical pitfall: approximately 10% of patients may be seronegative for anti-GBM antibodies 1, 3. In these cases, kidney biopsy becomes essential for diagnosis 3.
Kidney Biopsy Findings
The pathognomonic finding is linear IgG staining on the glomerular basement membrane by immunofluorescence 1, 3. Histology typically shows necrotizing and crescentic glomerulonephritis 1, 4.
Specialized Care Requirements
Transfer patients to centers with immediate plasmapheresis capability and experience managing rapidly progressive glomerulonephritis 1. This is non-negotiable given the time-sensitive nature of the disease and the technical requirements of plasmapheresis 1.
A designated coordinator (typically a specialized nurse) should manage the complex treatment schedule involving multiple plasmapheresis sessions, immunosuppression administration, and monitoring 1.
Prognostic Factors
Overall Survival Predictors
One-year survival in treated patients is approximately 87% 2. Key predictors of survival include 2:
- Age <60 years (better prognosis)
- Higher number of plasmapheresis sessions (better prognosis)
- Avoiding alternative immunosuppressive drugs (their use correlates with mortality, likely reflecting refractory disease)
Severe infection is the leading cause of death, accounting for 7 of 16 deaths in one large cohort 2.
Renal Recovery Predictors
Serum creatinine <500 μmol/L (approximately 5.7 mg/dL) at presentation is the only independent predictor of renal survival in patients who survive to one year 2. This underscores the critical importance of early diagnosis and treatment 3, 5.
Special Considerations
Double-Positive Patients
Some patients have both anti-GBM antibodies and ANCA positivity, requiring careful treatment consideration 1. These patients may have different disease trajectories and treatment responses.
Pulmonary Hemorrhage Management
Smoking is strongly associated with pulmonary hemorrhage in Goodpasture syndrome 5. Patients presenting with severe ARDS from pulmonary hemorrhage may require ECMO support 6. In refractory cases with life-threatening pulmonary hemorrhage despite standard therapy, eculizumab (complement C5 inhibitor) has shown promise as rescue therapy 6.
Kidney Transplantation
Defer kidney transplantation until anti-GBM antibodies have been undetectable for a minimum of 6 months 1. This waiting period is essential to prevent disease recurrence in the transplanted kidney.
Monitoring and Follow-Up
Relapses are rare but have been reported, necessitating ongoing monitoring for at least the first 2 years 1. Patients requiring dialysis at presentation have poor renal recovery rates, with many remaining dialysis-dependent long-term 4.