Definition
• An autoimmune syndrome characterized by glomerulonephritis and pulmonary hemorrhage occurring predominantly in males
Pathogenesis
• Immune-mediated disease due to antibodies against α3 subunit of type IV collagen
Clinical features
Epidemiology
• Incidence: 1 to 2 per 1,000,000
• Accounts for 10% to 20% of patients who present with acute renal failure due to rapidly progressive glomerulonephritis
• Usually occurs in males between 25 and 29 years (more common in females than males if >60 years)
• Ethnicity: predominantly seen in whites
Presentation
• Pulmonary:
• Pulmonary involvement often precedes nephritis
• Pulmonary hemorrhage and hemoptysis
• Pulmonary opacities on chest radiography
• Renal:
• Oliguria, proteinuria, hematuria
• Acute glomerulonephritis (usually rapidly progressive crescentic glomerulonephritis)
• Renal involvement frequently progresses to acute renal failure
• Anemia:
• Pulmonary hemorrhage is the main cause of anemia
Prognosis and treatment
• Plasmapheresis is believed to remove serum anti-GBM antibodies
• Remission may follow intensive plasmapheresis combined with corticosteroids and cytotoxic agents
• Patient survival at 1 year (with treatment [but no dialysis] and creatinine <6 mg/dL) is 83%
• If dialysis is needed, patient survival at 1 year decreases to 65%
Pathology
Histology
• Recent and old (hemosiderin-laden macrophages) hemorrhages; diffuse and bilateral
• In early phase of disease, capillaritis may be present
• Lung tissue is usually not sampled because the diagnosis is made on detection of serum anti-GBM antibodies and confirmed by renal biopsy
Immunopathology/special stains
• Linear IgG deposits along the GBM are pathognomonic
• The same antibodies can be detected in the lung but much less frequently than in the kidney
Main differential diagnoses
• Pulmonary hemorrhage:
• Antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (Churg-Strauss syndrome)
• Infections
– Pneumocystis jiroveci infection
– Tuberculosis
• Löffler syndrome
• Lung cancer
• Cryptogenic organizing pneumonia
• Combined renal and pulmonary disease:
• ANCA-associated systemic vasculitis (Wegener granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome)
Fig 1 Goodpasture syndrome. Low power shows extensive hemorrhage in this lung biopsy.
(Courtesy of Dr. Jerome B. Taxy, University of Chicago.)
Fig 2 Goodpasture syndrome. High power of the lung biopsy shows recent intraalveolar hemorrhage intermixed with macrophages. This feature helps differentiate it from intraoperative hemorrhage.
Fig 3 Goodpasture syndrome. Focal interstitial fibrosis is present in addition to recent and old hemorrhage.
Fig 4 Goodpasture syndrome. Direct immunofluorescence with anti-IgG antibody on lung biopsy shows linear staining along the alveolar basement membranes.
Fig 5 Goodpasture syndrome. Direct immunofluorescence with anti-IgG antibody is strongly positive in this kidney biopsy.