Diagnosis of Goodpasture Syndrome
The diagnosis of Goodpasture syndrome requires demonstration of anti-glomerular basement membrane (anti-GBM) antibodies along with evidence of kidney and/or lung involvement, with renal biopsy showing linear IgG deposition on the glomerular basement membrane as the gold standard diagnostic test.
Diagnostic Criteria
Clinical Presentation
- Pulmonary-renal syndrome: Combination of pulmonary hemorrhage and rapidly progressive glomerulonephritis
- Renal manifestations:
- Rapidly progressive glomerulonephritis
- Hematuria with dysmorphic red blood cells and red cell casts
- Proteinuria (typically moderate 1-3 g/day, but can be nephrotic-range)
- Rapidly declining glomerular filtration rate (GFR)
- Pulmonary manifestations:
- Hemoptysis
- Alveolar hemorrhage
- Dyspnea
Laboratory Testing
Serological testing
- Anti-GBM antibody testing (ELISA or immunofluorescence)
- Note: A small percentage of patients may be seronegative despite having the disease 1, 2
- ANCA testing (positive in 10-30% of Goodpasture cases - "double positive" cases)
- Complete blood count (anemia may be present due to pulmonary hemorrhage)
- Renal function tests (elevated creatinine, BUN)
- Urinalysis (hematuria, proteinuria, red cell casts)
Kidney biopsy (gold standard)
- Linear IgG deposition along the glomerular basement membrane on immunofluorescence
- Necrotizing and crescentic glomerulonephritis on light microscopy 3
- Focal global glomerulosclerosis may be present
Pulmonary evaluation
- Chest imaging (infiltrates consistent with pulmonary hemorrhage)
- Bronchoscopy with bronchoalveolar lavage (hemosiderin-laden macrophages)
Diagnostic Algorithm
Initial evaluation for patients with suspected pulmonary-renal syndrome:
- Obtain anti-GBM antibodies, ANCA, anti-nuclear antibodies
- Assess renal function (creatinine, BUN)
- Urinalysis with microscopy
- Chest imaging (X-ray or CT)
If anti-GBM antibodies are positive:
- Proceed with kidney biopsy to confirm diagnosis unless contraindicated
- Evaluate for pulmonary hemorrhage even if asymptomatic
If anti-GBM antibodies are negative but clinical suspicion remains high:
Definitive diagnosis requires:
- Linear IgG deposition on the glomerular basement membrane on kidney biopsy
- Pattern of injury: necrotizing and crescentic glomerulonephritis 3
Important Considerations
Differential Diagnosis
- ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis)
- Lupus nephritis
- Cryoglobulinemic vasculitis
- Post-infectious glomerulonephritis
- Drug-induced vasculitis
Potential Triggers
- Cigarette smoking
- Hydrocarbon solvent exposure
- Infections
- Cocaine use 4
Pitfalls to Avoid
- Relying solely on serology: Up to 10% of Goodpasture syndrome cases may have negative standard anti-GBM antibody tests 2
- Delaying diagnosis: Early diagnosis is critical as treatment outcomes are significantly better when initiated before severe kidney damage occurs
- Missing ANCA co-positivity: Up to 30% of patients may have both anti-GBM and ANCA antibodies, which can affect prognosis and treatment decisions 4
- Overlooking atypical presentations: Some patients may present with nephrotic-range proteinuria rather than the classic rapidly progressive glomerulonephritis 1
Treatment Approach
While not the focus of the diagnostic question, it's important to note that early treatment is critical:
Immediate therapy upon strong clinical suspicion:
- Plasma exchange to remove circulating antibodies
- High-dose corticosteroids
- Cyclophosphamide for immunosuppression
Factors affecting prognosis:
Early diagnosis and aggressive treatment are essential, as untreated Goodpasture syndrome has a mortality rate approaching 100%, while current treatment protocols have reduced mortality to approximately 10-15% 5.