What is the treatment approach for a patient diagnosed with Goodpasture syndrome, a rare autoimmune disease characterized by the presence of anti-glomerular basement membrane (anti-GBM) antibodies?

Treatment of Goodpasture Syndrome

Immediately initiate triple therapy with cyclophosphamide, high-dose corticosteroids, and plasmapheresis without delay when Goodpasture syndrome is suspected—even before antibody confirmation—unless the patient is dialysis-dependent with 100% crescents on biopsy and no pulmonary hemorrhage. 1, 2

Immediate Treatment Protocol

Start empirical therapy the moment Goodpasture syndrome is suspected:

• Begin pulse methylprednisolone and plasmapheresis immediately while awaiting anti-GBM antibody confirmation 1, 2
• Add cyclophosphamide once infection is ruled out, ideally after disease confirmation but do not delay if clinical suspicion is high 2
• Use fresh frozen plasma for plasmapheresis replacement if alveolar hemorrhage is present or recent kidney biopsy was performed; otherwise albumin replacement is sufficient 2

The rationale for this aggressive approach is clear: untreated Goodpasture syndrome has a mortality rate up to 96%, and kidney failure is inevitable without treatment 1. Early intervention is the single most important determinant of outcome.

Complete Treatment Regimen

Plasmapheresis:

• Continue daily plasmapheresis until anti-GBM antibodies are undetectable on 2 consecutive tests 2
• Median number of sessions is typically 13 (range 9-17) 3

Cyclophosphamide:

• Oral cyclophosphamide 2-3 mg/kg daily for 2-3 months 2
• Dose-adjust for reduced GFR or older age 2
• Oral cyclophosphamide may be superior to intravenous administration 3

Corticosteroids:

• Start with pulse methylprednisolone, then transition to oral prednisone 2
• Taper over approximately 6 months with complete glucocorticoid therapy by 6 months 2

Prophylaxis:

• Use trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis until cyclophosphamide is complete AND prednisone dose is <20 mg daily 2

Critical Exception: When NOT to Treat

Withhold immunosuppression only if ALL three criteria are met: 1, 2

1. Patient is dialysis-dependent at presentation
2. Kidney biopsy shows 100% crescents (or >50% global glomerulosclerosis)
3. No pulmonary hemorrhage is present

This exception exists because patients presenting on dialysis have a 35% mortality rate and >90% remain on dialysis at 1 year 1, 2. However, always treat if pulmonary hemorrhage is present, regardless of renal status 2.

Prognostic Indicators for Treatment Response

Favorable indicators:

• Not requiring dialysis within 72 hours of presentation, even with creatinine >500 μmol/L (5.7 mg/dL) 1, 2
• Serum creatinine <500 μmol/L at presentation predicts renal survival 3
• Alveolar hemorrhage and/or AKI not requiring dialysis 1
• Acute presentation that is nonoliguric 1
• Biopsy features of acuity: acute tubular injury, <50% glomerulosclerosis, <100% crescents 1

Poor prognostic indicators:

• Dialysis-dependent at presentation 1, 2
• Age >60 years correlates with worse overall survival 3
• Fewer plasma exchange sessions correlate with worse survival 3

Diagnosis Considerations

Diagnostic workup must be rapid but should not delay treatment:

• Send serologies for anti-GBM, ANA, and ANCA immediately 1
• Anti-GBM antibodies can be falsely negative in approximately 10% of cases 1, 4
• Kidney biopsy is crucial when safe and feasible, showing linear IgG staining on GBM by immunofluorescence, which is pathognomonic 1, 4, 5
• The disease targets the noncollagenous (NC1) domain of the α3 chain of type IV collagen in glomerular and alveolar basement membranes 1, 6

Maintenance and Long-Term Management

No maintenance immunosuppression is required for isolated anti-GBM disease because the relapse rate is <5% 2

Critical exception: Patients who are both anti-GBM and ANCA-positive (double-positive) require maintenance therapy as for ANCA-associated vasculitis, because their relapse rates are equivalent to AAV patients 2

Kidney Transplantation

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

Emerging Therapies

A phase 2 study of imlifidase (an IgG-degrading enzyme from Streptococcus pyogenes) combined with plasma exchange and corticosteroids showed rapid antibody decline within 6 hours and 67% dialysis-free survival at 6 months 1, 2. This represents a promising future option for severe cases.

In one case report, eculizumab (complement C5 inhibitor) combined with ECMO rescued a patient with severe ARDS from Goodpasture syndrome when conventional therapy was failing 7. This suggests complement blockade may be beneficial in life-threatening pulmonary hemorrhage.

Common Pitfalls to Avoid

• Do not delay treatment waiting for biopsy or antibody confirmation—begin empirical therapy immediately when suspected 1, 4, 2
• Do not withhold treatment from patients with severe renal impairment (creatinine >500 μmol/L) if they are not yet dialysis-dependent 2
• Do not assume ANCA positivity excludes anti-GBM disease—double-positive patients exist and require specific management 4, 2
• Do not exclude anti-GBM disease based on absence of pulmonary symptoms—isolated renal-limited disease occurs frequently 4
• Do not forget maintenance therapy in double-positive (anti-GBM + ANCA) patients—they behave like AAV, not isolated anti-GBM disease 2
• Do not underestimate infection risk—severe infection accounts for 7 of 16 deaths in one large cohort 3