eMedicine Specialties > Pediatrics: General Medicine > Pulmonology
Goodpasture Syndrome: Differential Diagnoses & Workup
Updated: Mar 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
| Behcet Syndrome | Systemic Lupus Erythematosus |
| Hemosiderosis | Wegener Granulomatosis |
| Henoch-Schoenlein Purpura | |
| Legionella Infection | |
| Mixed Connective Tissue Disease |
Other Problems to Be Considered
Essential mixed cryoglobulinemia
Workup
Laboratory Studies
- All patients with Goodpasture syndrome (GS) require urinalysis; CBC count with differential; and assessments of BUN, creatinine, and electrolyte levels.
- The erythrocyte sedimentation rate is usually only mildly elevated, unlike in patients with vasculitis.
- Specific serologic tests include assessments of anti–glomerular basement membrane (anti-GBM) titers and antineutrophil cytoplasmic autoantibodies (ANCA) titers through indirect immunofluorescence testing, as well as enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA), to evaluate proteinase 3 and myeloperoxidase.
- Results from serologic studies such as antistreptolysin O (ASO) titers and complement studies are usually normal.
- Circulating anti-GBM titers may be elevated in more than 90% of patients.
- ANCA titers are elevated in 20-30% of patients with anti-GBM disease. The ANCA titer is usually perinuclear antineutrophil cytoplasmic autoantibody (p-ANCA) from antimyeloperoxidase antibody.
- Assessments of antinuclear antibody (ANA), C3, and C4 levels and of the Westergren sedimentation rate are recommended. Test results for ANA and rheumatoid factor are usually negative.
- Tests for anti-GBM antibodies may be helpful.
- The presence of anti-GBM antibody formation can be determined in a number of ways.
- Linear immunoglobulin G (IgG) deposition along the glomerular capillary walls on the immunofluorescence portion of the renal biopsy is highly suggestive of the disease, especially in the setting of crescentic glomerulonephritis.
This image of direct immunofluorescence shows smooth linear staining of the basement membrane secondary to immunoglobulin G deposition. This confirms the diagnosis of Goodpasture syndrome. Image courtesy of K. Orr, MD.
- Circulating anti-GBM antibodies, which are typically of the IgG class, can be documented through indirect immunofluorescence or RIA techniques. Compared with indirect immunofluorescence, RIA is more sensitive (>90%) and almost as specific (>98%).
- IgG can occasionally be eluted from lung or kidney biopsy tissue for analysis and characterization.
- Anemia occurs out of proportion to hemoptysis or renal failure.
- A hemoglobin level less than 12 mg/dL is observed in 90-100% of adults.
- In one series involving adults, the mean hemoglobin level was 7.5 g/dL.
- Leukocytosis may be present. Approximately 40-50% of adults have a WBC count of greater than 10,000/mcL. A leftward shift is common.
- Azotemia occurs in 55-71% of adults with anti-GBM disease.
- Hematuria may be present.
- Microscopic hematuria, as defined by the presence of RBCs, occurs in 83-94% of adults with anti-GBM disease.
- Macroscopic hematuria is present in 10-40% of adults. RBC casts have been reported in 6-100% of adults with anti-GBM disease.
- Proteinuria occurs in 76-100% of adults. Nephrotic syndrome is unusual.
Imaging Studies
- Chest radiography is the most useful imaging test available to document the presence of pulmonary hemorrhage.
- Chest radiographic findings depict patchy or diffuse infiltrates with sparing of the upper lung fields.
- Unlike infection, pulmonary infiltrates from hemorrhage may resolve within a few days.6
- Chest CT scanning has a more limited role but may be helpful in identifying localized areas of hemoptysis.
Other Tests
- Pulmonary function testing can be used to assess pulmonary hemorrhage by demonstrating accelerated diffusing capacity of lung for carbon monoxide (DLCO). A progressive decline in vital capacity or total lung capacity suggests developing interstitial fibrosis
- Pulse oximetry is indicated in all patients with suspected anti-GBM disease who may have hypoxemia from their parenchymal lung injury. However, in patients with severe anemia, oximeter readings may become less accurate.
Procedures
- Renal biopsy can usually be performed without incident, even in a patient in relatively unstable condition.
- Biopsy allows assessment of the severity of the glomerulonephritis and examination for the characteristic linear IgG deposition along the GBM.
- Compared with lung biopsy, renal biopsy is a superior diagnostic test.
- Lung biopsy is rarely indicated, but it may be helpful.
- In comparison, bronchoscopy with transbronchial forceps biopsy (TBB) has a higher rate of false-negative results, but it is less invasive than collection through open lung biopsy. TBB is technically more difficult in younger children, and the small biopsy forceps used in them results in smaller tissue samples, with lower diagnostic yield.
- Bronchoalveolar lavage can be used to detect hemosiderin-laden macrophages.
Histologic Findings
- Renal biopsy: Renal biopsy shows a diffuse glomerulonephritis with focal or complete necrosis of the glomerular tuft and segmental or circumferential cellular crescents surrounding some or all glomeruli. Linear IgG along the GBM can be observed with immunofluorescence testing. Linear C3 along the GBM is present in two thirds of biopsy samples. Other causes of linear staining on direct immunofluorescence analysis include systemic lupus erythematosus (SLE) and diabetes mellitus.
- Lung biopsy: Lung biopsy usually shows nonspecific findings of hemorrhage with variable degrees of inflammation and fibrosis. Samples obtained during lung biopsy may show IgG staining of the alveolar septum, which is diagnostic for anti-GBM disease.
More on Goodpasture Syndrome |
| Overview: Goodpasture Syndrome |
 Differential Diagnoses & Workup: Goodpasture Syndrome |
| Treatment & Medication: Goodpasture Syndrome |
| Follow-up: Goodpasture Syndrome |
| Multimedia: Goodpasture Syndrome |
| References |
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References
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Further Reading
Keywords
Goodpasture syndrome, GS, anti–glomerular basement membrane disease, anti-GBM disease, Goodpasture disease, Goodpasture's disease, pulmonary renal syndrome, Goodpasture's syndrome, Wegener granulomatosis, Wegener's granulomatosis, glomerulonephritis, pulmonary hemorrhage, anti-GBM antibody formation, pulmonary renal syndrome of alveolar hemorrhage, small vessel vasculitis, glomerulonephritis, cigarette smoking, end-stage renal disease, ESRD, systemic lupus erythematosus, SLE, Henoch-Schönlein purpura, HSP, respiratory failure, proteinuria, nephrotic syndrome
