What is the diagnosis and treatment approach for a young adult with suspected Goodpasture syndrome, presenting with recent respiratory infection and potential exposure to certain chemicals?

Goodpasture Syndrome Diagnosis

Goodpasture syndrome is definitively diagnosed by detecting anti-glomerular basement membrane (anti-GBM) antibodies in serum combined with kidney biopsy showing linear IgG staining along the glomerular basement membrane, and treatment must begin immediately with plasmapheresis, cyclophosphamide, and high-dose corticosteroids to prevent irreversible renal failure and death. 1

Diagnostic Criteria

Serologic Testing

• Measure serum anti-GBM antibodies immediately in any young adult presenting with pulmonary-renal syndrome, particularly following respiratory infection or chemical exposure 1, 2
• Approximately 10% of cases may have falsely negative anti-GBM antibodies, so proceed with kidney biopsy if clinical suspicion remains high 1
• Some patients (up to one-third) may be "double-positive" with both anti-GBM antibodies and ANCA, requiring careful treatment consideration 1, 2

Kidney Biopsy Findings

• Linear immunofluorescent staining for IgG on the glomerular basement membrane is pathognomonic and distinguishes Goodpasture syndrome from other pulmonary-renal syndromes 1
• Necrotizing and crescentic glomerulonephritis is typically present on histology 1
• The percentage of crescents and degree of glomerulosclerosis predict renal prognosis: >50% global glomerulosclerosis or 100% crescents indicates poor renal recovery 1, 2

Clinical Presentation Clues

• Cough, hemoptysis, and dyspnea with fatigue are the most common presenting features, though some patients present without hemoptysis despite life-threatening pulmonary hemorrhage 2, 3
• Recent respiratory infection or chemical exposure (hydrocarbon solvents, cocaine) may trigger disease in genetically susceptible individuals 2, 4
• Serum creatinine >500 μmol/L (approximately 5.7 mg/dL) at presentation predicts need for long-term dialysis 5, 2

Immediate Treatment Protocol

Triple Therapy Initiation

Begin treatment immediately upon diagnosis confirmation, or even while awaiting confirmation if clinical suspicion is high 1

• Plasmapheresis: Median 13 sessions (range 9-17), targeting removal of circulating anti-GBM antibodies 5
• Cyclophosphamide: Oral cyclophosphamide appears superior to intravenous formulation based on survival data 5
• High-dose corticosteroids: Systemic corticosteroids should be started immediately 1, 2

Critical Exception to Treatment

Do not initiate aggressive immunosuppression in patients who are dialysis-dependent at presentation with 100% crescents or >50% global glomerulosclerosis on biopsy AND no pulmonary hemorrhage, as renal recovery is futile 1

Management Setting Requirements

• Transfer immediately to a center with experience in rapidly progressive glomerulonephritis and immediate plasmapheresis capability 1
• Dedicated nephrology service beds are essential for managing the complex treatment schedule 1
• A specialized nurse coordinator should manage plasmapheresis sessions, immunosuppression administration, and monitoring 1

Prognostic Factors

Survival Predictors

• One-year survival is 86.9% with aggressive treatment 5
• Age <60 years and higher number of plasmapheresis sessions correlate with better overall survival 5
• Severe infection accounts for 7 of 16 deaths, making infection prevention critical 5

Renal Recovery Predictors

• Serum creatinine <500 μmol/L at presentation is the only independent predictor of renal survival in patients alive at one year 5
• Need for hemodialysis at initial presentation portends necessity of long-term dialysis 2

Long-Term Monitoring

• Monitor for relapses for at least the first 2 years, though relapses are rare 1
• Defer kidney transplantation until anti-GBM antibodies have been undetectable for a minimum of 6 months 1
• 90% of patients survive the acute presentation with early intensive treatment 2

Key Pitfalls to Avoid

• Do not delay treatment waiting for biopsy results if anti-GBM antibodies are positive and clinical presentation is consistent 1
• Do not confuse with hypersensitivity pneumonitis despite chemical exposure history; HP presents with lymphocytic BAL and granulomas, not linear IgG staining 6
• Do not use alternative immunosuppressive drugs initially, as their use correlates with increased one-year mortality 5
• Renal biopsy carries hemorrhage risk but remains necessary for definitive diagnosis; be prepared for potential complications requiring renal artery embolization 3