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Goodpasture Syndrome Workup

  • Author: Pranay Kathuria, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Aug 25, 2016
 

Approach Considerations

Diffuse alveolar hemorrhage represents a medical emergency, and clinicians must have an expedient approach to its identification.[18] In the appropriate clinical setting (ie, alveolar hemorrhage and urinary findings suggestive of an acute glomerulonephritis), the detection of circulating anti–glomerular basement membrane (anti-GBM) antibodies allows the clinician to make a firm diagnosis of anti-GBM disease. This obviates lung or kidney biopsy.

When the diagnosis remains in doubt, renal biopsy is the best method for detecting anti-GBM antibodies in tissues. Patients in whom the diagnosis of diffuse alveolar hemorrhage remains uncertain should undergo diagnostic bronchoscopy.

Urinalysis and blood studies

Urinalysis findings are characteristic of acute glomerulonephritis, usually demonstrating low-grade proteinuria, gross or microscopic hematuria, and red blood cell casts.

On the complete blood cell count, anemia may be observed secondary to iron deficiency caused by intrapulmonary bleeding. Leukocytosis is commonly present.

Elevated blood urea nitrogen (BUN) and serum creatinine levels secondary to renal dysfunction may be present.

Elevation of the erythrocyte sedimentation rate (ESR) is commonly observed in patients with vasculitis, but it is uncommon in anti-GBM disease.

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Anti–GBM Antibody Testing

Serologic assays for anti-GBM 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 in only a few laboratories. Positive results should be confirmed by Western blotting on collagenase-solubilized human GBM, especially if a kidney biopsy is not being performed.

In a comparison study of 4 immunoassay-based anti-GBM antibody kits, all 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/specificity.[19]

Healthy individuals may have circulating antibodies against GBM belonging to IgG2 and IgG4 subclasses. With onset of clinical disease, IgG1 and IgG3 subclasses increase and levels may correlate with disease severity.[5]

A study by Yang et al indicated that higher levels of circulating anti-GBM antibodies against the epitopes EA and EB occurred in patients whose renal disease was more severe and that these patients had a worse prognosis. Correlation was noted between the levels of anti-GBM antibodies and the serum creatinine at diagnosis and the presence of oliguria. Correlation existed between the percentage of crescents on biopsy and levels of antibodies, but it was significant only for anti-EA antibodies (P < .05).[20]

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Antineutrophilic Cytoplasmic Antibody Testing

At some time during the course of illness, as many as one third of patients with Goodpasture syndrome have circulating antineutrophilic cytoplasmic antibodies (ANCAs) in addition to anti-GBM antibody.[17] In most cases, the ANCA antibodies precede the development of anti-GBM antibodies by months to years.[21] It is postulated that the renal involvement in ANCA vasculitis leads to the exposure of antigens from the basement membrane and the formation of antibodies. These patients are referred to as double-positive.

Cytoplasmic ANCA (c-ANCA) and perinuclear ANCA (p-ANCA) are seen in the images below.

Cytoplasmic antineutrophilic cytoplasmic antibodieCytoplasmic antineutrophilic cytoplasmic antibodies (c-ANCA), which can appear in Goodpasture syndrome, are also commonly observed in Wegener granulomatosis and other vasculitides.
Perinuclear antineutrophilic cytoplasmic antibodiePerinuclear antineutrophilic cytoplasmic antibodies (p-ANCA), which can appear in Goodpasture syndrome, are also observed in Churg-Strauss vasculitis and occasionally in Wegener granulomatosis.

In the majority of double-positive patients, the ANCAs have specificity for myeloperoxidase (MPO-ANCA).[22, 23] In patients with both anti-GBM antibodies and MPO-ANCAs, histological findings differ from those of patients with anti-GBM antibodies only. The renal survival in these patients is similar to anti-GBM–positive patients and is worse compared with patients with MPO-ANCAs only.

In an analysis of the diagnostic performance of two rapid ANCA and anti-GBM test methods in 260 patients with suspected ANCA-associated small vessel vasculitis, de Joode and colleagues found that both the Dotblot and Phadia ELiA on anti-GBM, anti-PR3(s) and anti-MPO(s) performed well. Results with these tests were almost identical to those achieved with routine ELISA.[24]

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Chest Radiograph

Characteristically, the chest film shows patchy parenchymal consolidations, which are usually bilateral, symmetric perihilar, and bibasilar. The apices and costophrenic angles are usually spared (see the image below). However, as many as 18% of patients may have normal findings on chest radiographs.

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 previoGoodpasture syndrome. A 35-year-old man who previously smoked cigarettes heavily, developed massive hemoptysis. The blood work showed positive anti–glomerular basement membrane antibodies.
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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.

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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 kidney biopsy is the preferred invasive procedure to substantiate the diagnosis of anti-GBM disease. Renal biopsy provides a significantly higher yield than lung biopsy, but transbronchial or open lung biopsy may be performed in cases where renal biopsy cannot be performed.

The biopsy tissue must be processed for light microscopy, immunofluorescence, and electron microscopy. Light microscopy demonstrates nonspecific features of a proliferative or necrotizing glomerulonephritis with cellular crescents (as seen in the image below). Over time, the crescents become fibrotic, and frank glomerulosclerosis, interstitial fibrosis, and tubular atrophy may be observed.

This is a renal biopsy slide of a patient who presThis 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.

Immunofluorescence stains are confirmatory. These show bright linear deposits of immunoglobulin G (IgG), as seen in the image below, and complement (C3) along the glomerular basement membranes. Subclass IgG-1 predominates.[25]

Immunofluorescence staining for immunoglobulin (IgImmunofluorescence staining for immunoglobulin (IgG) reveals diffuse, high-intensity, linear staining of the glomerular basement membrane in a patient with anti–glomerular basement membrane (GBM) disease. Courtesy of Glen Markowitz, MD, Department of Pathology, Columbia University.

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.[26] Immunofluorescence staining may be diagnostic, but performing this study on lung tissue is technically difficult.

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Contributor Information and Disclosures
Author

Pranay Kathuria, MD FACP, FASN, FNKF, Professor of Medicine, Director, Division of Nephrology and Hypertension, University of Oklahoma School of Community Medicine

Pranay Kathuria, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Heart Association, American Society of Hypertension, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, World Medical Association

Disclosure: Nothing to disclose.

Frazier T Stevenson, MD Associate Professor of Clinical Medicine and Director of Education Development, University of California Davis School of Medicine

Disclosure: Nothing to disclose.

Prateek Sanghera, MD Parkland Memorial Hospital

Prateek Sanghera, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research

Disclosure: Genzyme Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mauro Verrelli, MD, FRCP(C), FACP Assistant Professor, Department of Medicine, Section of Nephrology, University of Manitoba, Canada

Mauro Verrelli, MD, FRCP(C), FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, Canadian Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

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Goodpasture syndrome. A 45-year-old man was admitted to the intensive care unit with respiratory failure secondary to massive hemoptysis and acute renal failure. The antiglomerular basement membrane antibodies were strongly positive. The autopsy showed consolidated lung from extensive bleeding, which led to asphyxiation.
Goodpasture syndrome. Close-up view of gross pathology in a 45-year-old man admitted to the intensive care unit with respiratory failure secondary to massive hemoptysis and acute renal failure. The antiglomerular basement membrane antibodies were strongly positive. The autopsy showed consolidated lung from extensive bleeding, which led to asphyxiation.
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.
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.
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.
Immunofluorescence staining for immunoglobulin (IgG) reveals diffuse, high-intensity, linear staining of the glomerular basement membrane in a patient with anti–glomerular basement membrane (GBM) disease. Courtesy of Glen Markowitz, MD, Department of Pathology, Columbia University.
 
 
 
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