eMedicine Specialties > Nephrology > Glomerular Diseases
Goodpasture Syndrome: Differential Diagnoses & Workup
Updated: Oct 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Glomerulonephritis, mesangial
Nephrotic syndrome with pulmonary emboli
Workup
Laboratory Studies
- CBC count: Anemia may be observed secondary to iron deficiency caused by intrapulmonary bleeding. Leukocytosis is commonly present.
- Electrolytes, BUN, and creatinine: Elevated blood urea nitrogen and creatinine secondary to renal dysfunction may be present.
- Erythrocyte sedimentation rate (ESR): Elevated ESR is commonly observed in patients with vasculitis, but it is uncommon in this disorder.
- Urinalysis: Urinalysis findings are characteristic of acute glomerulonephritis, usually demonstrating low-grade proteinuria, gross or microscopic hematuria, and red blood cell casts.
- Anti-GBM antibodies:
- Serologic assays for antibodies are valuable for confirming the diagnosis and monitoring the adequacy of therapy.
- Radioimmunoassays or enzyme-linked immunosorbent assays (ELISAs) for anti-GBM antibodies are highly sensitive (>95%) and specific (>97%) but are performed only in a few laboratories.
- Although the peak of serum anti-GBM antibody titer does not correlate with the severity of disease, changes in titers over time may be a guide to the efficacy of therapy.
- A study by Yang et al indicated that high levels of circulating anti-GBM antibodies against the epitopes EA and EB may occur in patients whose renal disease is more severe and has a worse prognosis than that in patients with lower levels of these antibodies.3
- Antineutrophilic cytoplasmic antibodies:
- Sometime during the course of illness, as many as one third of patients with Goodpasture syndrome have circulating ANCA in addition to anti-GBM antibody.
- Cytoplasmic ANCA (c-ANCA) and perinuclear ANCA (p-ANCA) are prevalent equally. (See images below and Images 3-4.)
- Since there are different assays available, sensitivity and specificity tests for 4 immunoassay-based anti-GBM antibody kits were performed. All of the assays showed comparably good sensitivity (94.7-100.0%), whereas specificity varied considerably (90.9-100.0%). The recombinant antigen fluorescence immunoassay demonstrated the best sensitivity/specificty.
Cytoplasmic antineutrophilic cytoplasmic antibodies (c-ANCA), which can appear in Goodpasture syndrome, are also commonly observed in Wegener granulomatosis and other vasculitides.
Perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA), which can appear in Goodpasture syndrome, are also observed in Churg-Strauss vasculitis and occasionally in Wegener granulomatosis.
Imaging Studies
- Chest radiograph (see image below and Image 7):
- Patchy parenchymal consolidations are present, which are usually bilateral, symmetric perihilar, and bibasilar. The apices and costophrenic angles are usually spared.
- As many as 18% of patients may have normal findings on chest radiograph.
- The consolidation resolves over 2-3 days, and it gradually progresses to an interstitial pattern as patients experience repeated episodes of hemorrhage.
- Pleural effusions are unusual.
Goodpasture syndrome. A 35-year-old man who previously smoked cigarettes heavily, developed massive hemoptysis. The blood work showed positive anti–glomerular basement membrane antibodies.
Other Tests
- Pulmonary function testing:
- Routine pulmonary function testing is not helpful in the clinical evaluation of the patients with anti-GBM disease.
- Spirometry and lung volume tests may reveal evidence of restriction.
- The diffusing capacity for carbon monoxide (DLCO) is elevated secondary to binding of carbon monoxide to intra-alveolar hemoglobin.
- Recurrent pulmonary hemorrhage may be diagnosed with new opacities observed on chest radiographs and a 30% rise in DLCO.
Procedures
- Diagnostic bronchoscopy: Patients in whom the diagnosis of diffuse alveolar hemorrhage remains uncertain should undergo diagnostic bronchoscopy.
- Kidney biopsy: In patients with evidence of diffuse alveolar hemorrhage and renal involvement, kidney biopsy should be considered to identify the underlying cause and to help direct therapy.
- Percutaneous renal biopsy: Percutaneous kidney biopsy is the preferred invasive procedure to substantiate the diagnosis of anti-GBM disease.
- Lung biopsy: Either transbronchial or open lung biopsy may be performed in cases where renal biopsy cannot be performed.
- Plasmapheresis: Plasmapheresis is employed to remove circulating anti-GBM antibody.
- Hemodialysis: Hemodialysis may be required depending on the severity of the underlying renal disease.
Histologic Findings
In the renal biopsy, light microscopy demonstrates nonspecific features of a proliferative or necrotizing glomerulonephritis with cellular crescents. Over time, the crescents may fibrose, and frank glomerulosclerosis, interstitial fibrosis, and tubular atrophy may be observed. Immunofluorescence stains are confirmatory. These show bright linear deposits of immunoglobulin G (IgG) and complement (C3) along the glomerular basement membranes. Subclass IgG-1 predominates.4 (See images below and Images 5-6.)
Lung biopsy shows extensive hemorrhage with accumulation of hemosiderin-laden macrophages within alveolar spaces. Neutrophilic capillaritis, hyaline membranes, and diffuse alveolar damage may also be found. Medium-vessel or large-vessel vasculitis is not a feature. Immunofluorescence staining may be diagnostic, but performing this on lung tissue is technically difficult.
This is a renal biopsy slide of a patient who presented with hemoptysis and hematuria. The renal biopsy revealed crescentic glomerulonephritis, which may be caused by systemic lupus erythematosus, vasculitis, or Goodpasture syndrome.
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.
More on Goodpasture Syndrome |
| Overview: Goodpasture Syndrome |
 Differential Diagnoses & Workup: Goodpasture Syndrome |
| Treatment & Medication: Goodpasture Syndrome |
| Follow-up: Goodpasture Syndrome |
| Multimedia: Goodpasture Syndrome |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Zhao J, Cui Z, Yang R, et al. Anti-glomerular basement membrane autoantibodies against different target antigens are associated with disease severity. Kidney Int. Sep 9 2009;[Medline].
Yang R, Cui Z, Zhao J, et al. The role of HLA-DRB1 alleles on susceptibility of Chinese patients with anti-GBM disease. Clin Immunol. Aug 3 2009;[Medline].
Yang R, Hellmark T, Zhao J, et al. Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease. Nephrol Dial Transplant. Jun 2009;24(6):1838-44. [Medline].
Zhao J, Yan Y, Cui Z, et al. The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHalpha3(IV)NC1 is associated with disease severity. Hum Immunol. Jun 2009;70(6):425-9. [Medline].
Bolton WK. Goodpasture''s syndrome. Kidney Int. Nov 1996;50(5):1753-66. [Medline].
Bombassei GJ, Kaplan AA. The association between hydrocarbon exposure and anti-glomerular basement membrane antibody-mediated disease (Goodpasture''s syndrome). Am J Ind Med. 1992;21(2):141-53. [Medline].
Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med. Sep 2004;25(3):583-92, vii.
Donaghy M, Rees AJ. Cigarette smoking and lung haemorrhage in glomerulonephritis caused by autoantibodies to glomerular basement membrane. Lancet. Dec 17 1983;2(8364):1390-3. [Medline].
Frankel SK, Cosgrove GP, Fischer A. Update in the diagnosis and management of pulmonary vasculitis. Chest. Feb 2006;129(2):452-65.
Jara LJ, Vera-Lastra O, Calleja MC. Pulmonary-renal vasculitic disorders: differential diagnosis and management. Curr Rheumatol Rep. Apr 2003;5(2):107-15. [Medline].
Jayne DR, Marshall PD, Jones SJ. Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney Int. Mar 1990;37(3):965-70. [Medline].
Kluth DC, Rees AJ. Anti-glomerular basement membrane disease. J Am Soc Nephrol. Nov 1999;10(11):2446-53. [Medline].
Lockwood CM, Rees AJ, Pearson TA. Immunosuppression and plasma-exchange in the treatment of Goodpasture''s syndrome. Lancet. Apr 3 1976;1(7962):711-5. [Medline].
Madore F, Lazarus JM, Brady HR. Therapeutic plasma exchange in renal diseases. J Am Soc Nephrol. Mar 1996;7(3):367-86. [Medline].
Mehler PS, Brunvand MW, Hutt MP. Chronic recurrent Goodpasture''s syndrome. Am J Med. Apr 1987;82(4):833-5. [Medline].
Mokrzycki MH, Kaplan AA. Therapeutic plasma exchange: complications and management. Am J Kidney Dis. Jun 1994;23(6):817-27. [Medline].
Rutgers A, Slot M, van Paassen P. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis. Am J Kidney Dis. Aug 2005;46(2):253-62.
Savage CO, Pusey CD, Bowman C. Antiglomerular basement membrane antibody mediated disease in the British Isles 1980-4. Br Med J (Clin Res Ed). Feb 1 1986;292(6516):301-4. [Medline].
Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture''s syndrome. South Med J. Dec 2002;95(12):1411-8. [Medline].
Sinico RA, Radice A, Corace C. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: a comparison of different assays. Nephrol Dial Transplant. Feb 2006;21(2):397-401.
Sutton DM, Nair RC, Rock G. Complications of plasma exchange. Transfusion. Feb 1989;29(2):124-7. [Medline].
Weber MF, Andrassy K, Pullig O. Antineutrophil-cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture''s syndrome and in Wegener''s granulomatosis. J Am Soc Nephrol. Jan 1992;2(7):1227-34. [Medline].
Further Reading
Clinical trials:
Efficacy of Combined Pentoxifylline and Conventional Immunosuppressive Regimens on Rapidly Progressive Glomerulonephritis
Keywords
Goodpasture syndrome, Goodpasture's syndrome, glomerulonephritis, Goodpasture's disease, type IV collagen, pulmonary hemorrhage, human leukocyte antigen, glomerular basement membrane, , , anti-glomerular basement membrane disease, anti-GBM disease, end-stage renal disease, ESRD, circulating antiglomerular basement membrane antibodies
