AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Goodpasture syndrome is an eponym used to describe the triad of diffuse pulmonary hemorrhage, glomerulonephritis, and circulating anti–glomerular basement membrane (anti-GBM) antibodies.

Goodpasture first described the disorder in 1919. He reported a case of pulmonary hemorrhage and glomerulonephritis during an influenza epidemic. In 1955, Parkin described 3 cases of lung hemorrhage and nephritis that occurred in the absence of arteritis. In 1958, Stanton and Tang reported a series of young men with pulmonary hemorrhage and glomerulonephritis, similar to Goodpasture's original description. The discovery of anti-GBM antibodies in 1967 led to the understanding of the pathogenesis of Goodpasture syndrome.

Goodpasture disease is a term used to describe glomerulonephritis and the presence of circulating anti-GBM antibodies, without pulmonary hemorrhage. Anti-GBM disease, a better term, should be used to refer to either of the 2 distinct clinical manifestations of this disorder.

Pathophysiology

Anti-GBM disease is an autoimmune disorder. The autoantibodies mediate the tissue injury by binding to their reactive epitopes in the basement membranes. This is a classic type II reaction in the Gell and Coombs classification of antigen-antibody reactions. This binding of antibodies can be visualized as the linear deposition of immunoglobulin along the glomerular basement membrane and, less commonly, the alveolar basement membranes, by direct immunofluorescent techniques.

In the 1950s, Krakower and Greenspun identified GBM as the antigen. Later, Lerner, Glassock, and Dixon subsequently confirmed that the antibodies taken from the diseased kidneys produced nephritis in experimental animals.

The principle component of the basement membrane is type IV collagen, which acts as a support structure and is composed of building blocks that are linked end-to-end. The building blocks are composed of 3 alpha subunits of collagen, which form a triple helix. Type IV collagen can be expressed as 6 different chains, alpha1 to alpha6. The alpha chain itself has 3 structural domains, as follows: (1) 7-S domain at the amino terminus; (2) a triple helix of 3 alpha chains, which ends at the carboxyl terminus; and (3) a noncollagenous domain. The classic triple helix is composed of 2 alpha1 chains and 1 alpha2 chain. The Goodpasture antigen has been localized to the carboxyl terminus of the noncollagenous domain of the alpha3 chain of type IV collagen. The antibodies are directed against a 28-kd monomeric subunit present within the noncollagenous domain.

The anti-GBM antibody can usually be found in serum. In some patients, this antibody also reacts with the pulmonary alveolar basement membrane and causes alveolar hemorrhage. The basement membranes are complex structures that support layers of endothelium and epithelium. The circulating anti-GBM antibodies react with an epitope contained within the basement membranes. Although basement membranes are ubiquitous, only the alveolar and glomerular basement membranes are affected clinically. The preferential binding to the alveolar and glomerular basement membranes appears to be caused by greater accessibility of epitopes and greater expansion of alpha3 collagen units. Furthermore, the alpha3 collagen chains of glomerular and basement membranes are structurally integrated in such a way that they become more accessible to the circulating antibodies.

Under normal conditions, the alveolar endothelium is a barrier to the anti–basement membrane antibodies. However, with increased vascular permeability, antibody binding to the basement membrane occurs in the alveoli. Therefore, for the deposition of antibody, an additional nonspecific lung injury that increases alveolar-capillary permeability is required. These factors include increased capillary hydrostatic pressure, high concentrations of inspired oxygen, bacteremia, endotoxemia, exposure to volatile hydrocarbons, upper respiratory infections, and tobacco smoking.

Strong evidence exists that genetics play an important role. Patients with specific human leukocyte antigen (HLA) types are more susceptible to disease and may have a worse prognosis. Patients with Goodpasture disease have an increased incidence of HLA-DR2 compared to control populations. The association is caused by an excess of the haplotype bearing DR-W 15. In addition, HLA-B7 is found more frequently and is associated with more severe anti-GBM nephritis. The exact role of these genetic findings in the pathogeneses of disease is not clear.

Sophisticated immunologic and molecular techniques have shown that immune response against Goodpasture autoantigen and syntheses of autoantibodies depend not only on the association of antigen with HLA molecules but also on how fragments of the antigen are handled by antigen-processing cells, such as B lymphocytes, monocytes and macrophages, and dendritic cells. Recent reports have shown that presentation of Goodpasture autoantigen to CD4 T lymphocytes, which is strongly associated with HLA-DR 15 alloantigen, is largely dependent on the ability of antigen antigenic epitopes to be processed and is less clearly dependent on the binding affinity to the DR-15 molecule.

Frequency

United States

Anti-GBM disease is an uncommon disorder; approximately 1-2% of all cases of rapidly progressive glomerulonephritis are secondary to this disorder.

International

In 1984, the incidence in England was 0.5 cases per million people per year, occurring over a 4-year period. This disorder, compared to Wegener granulomatosis, which has an incidence of approximately 0.5 cases per 100,000 people, is rare.

Mortality/Morbidity

In the past, the disease was almost universally fatal. Currently, the mortality rate is approximately 10%. However, most patients who survive progress to end-stage renal disease (ESRD).

Race

Anti-GBM disease occurs more commonly in white people than in black people, but it also may be more common in certain ethnic groups, such as the Maoris of New Zealand.

Sex

Incidence shows a male predominance, with the male-to-female ratio reported as 2-9:1.

Age

Distribution is bimodal. Young men present with a pulmonary-renal syndrome at ages 20 and 30 years, and elderly women (ie, aged 60-70 y) present primarily with glomerulonephritis.

CLINICAL

Section 3 of 11  

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History

Substantial variation exists in the clinical manifestations of patients with anti-GBM disease. Sixty to 80% of patients have clinically apparent manifestations of pulmonary and renal disease, 20-40% have renal disease alone, and fewer than 10% have disease that is limited to the lungs.

• Hemoptysis is the presenting symptom when the disease affects the lungs. The level of hemoptysis may vary and, in a small percentage of patients, may be absent. Other pulmonary symptoms include cough and dyspnea.
• Chills and fever are present in approximately 25% of patients.
• Nausea and vomiting are present in 41%.
• Approximately 14% of patients report weight loss.
• Chest pain is present in approximately 40% of patients.
• Significant anemia may result from persistent intrapulmonary bleeding.
• Massive pulmonary hemorrhage leading to respiratory failure may also occur.
• Renal manifestations are rapidly progressive glomerulonephritis that may lead to azotemia and volume overload.
• Arthralgias

Physical

• Tachypnea
• Inspiratory crackles over lung bases
• Cyanosis
• Hepatosplenomegaly (may be present)
• Hypertension (present in 20% of cases)
• Skin rash

Causes

Diffuse alveolar hemorrhage represents a medical emergency, and clinicians must have an expedient approach to its identification. There are many causes of diffuse alveolar hemorrhage, including vasculitides, immunologic conditions such as Goodpasture syndrome, collagen vascular disease, and idiopathic conditions. Careful attention to the medical history, physical examination, and targeted laboratory evaluation often suggests the underlying cause.

An initial insult to the pulmonary vasculature is required for exposure of the alveolar capillaries to the anti-GBM antibodies. Certain characteristics may predispose patients to develop this disease, as follows:

• Association with HLA-DR2
• Exposure to organic solvents or hydrocarbons
• Smoking
• Infection (eg, influenza A2)
• Cocaine inhalation
• Exposure to metal dusts

DIFFERENTIALS

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Other Problems to be Considered

Glomerulonephritis, mesangial
Nephrotic syndrome with pulmonary emboli

Wegener granulomatosis should be distinguished from the other systemic diseases listed above and, in particular, from Goodpasture syndrome. Interestingly, some patients with Goodpasture syndrome may present with antineutrophilic cytoplasmic antibodies (ANCA), which are predominantly observed in patients with Wegener granulomatosis.

WORKUP

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Lab 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.
• 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.
  • Both cytoplasmic ANCA (c-ANCA) and perinuclear ANCA (p-ANCA) are prevalent equally.
  • Since there are different assays available, sensitivity and specificity of 4 immunoassay-based anti-GBM antibodies kits were recently performed. All the assays showed a comparable good sensitivity (94.7-100.0%), whereas specificity varied considerably (90.9-100.0%). Sensitivity/specificity was best by using the recombinant antigen fluorescence immunoassay.

Imaging Studies

• Chest radiograph
• • See Media file 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.

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. See Media files 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.

TREATMENT

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Medical Care

In the appropriate clinical setting (ie, alveolar hemorrhage and urinary findings suggestive of an acute glomerulonephritis), the detection of circulating anti-GBM antibodies allows the clinician to make a firm diagnosis of anti-GBM disease. This obviates the need for lung or kidney biopsy. When the diagnosis remains in doubt, renal biopsy is the best method for detecting anti-GBM antibodies in tissues. The biopsy tissue must be processed not only for light microscopy but also for immunofluorescence and electron microscopy. Renal biopsy provides a significantly higher yield compared to lung biopsy.

• The 3 principles of therapy are (1) to rapidly remove circulating antibody, primarily by plasmapheresis; (2) to stop further production of antibodies using immunosuppression with medications; and (3) to remove offending agents that may have initiated the antibody production.
• Before the availability of current therapy, the mortality rate exceeded 90%, with a mean survival time of less than 4 months. Currently, with the combination of plasmapheresis, corticosteroids, and cyclophosphamide, the mortality rate has been reduced to less than 20%.
• Based on published case series and one randomized trial, plasmapheresis has been shown to be beneficial in the treatment of Goodpasture syndrome by removal of anti-GBM antibodies. Plasmapheresis is generally instituted after the diagnosis of Goodpasture syndrome is established either by renal biopsy or by detection of anti-GBM antibodies. However, when a patient presents in a life-threatening situation secondary to pulmonary hemorrhage, plasmapheresis may be initiated if the diagnosis appears very likely, even though the confirmation is not available immediately. The extent and duration of plasmapheresis is not known, but 4 plasma exchanges (1 L each) daily or every other day are performed. The plasmapheresis is continued for 2-3 weeks or until the patient's clinical course has improved and serum anti-GBM antibodies are not detected.
• Immunosuppressive therapy
• • Immunosuppressive therapy is required to inhibit antibody production and rebound hypersynthesis, which may occur following discontinuation of plasma exchange.
  • Cyclophosphamide at 2 mg/kg orally, adjusted to maintain a white blood cell count of approximately 5000, is instituted and continued for 6 months.
  • Corticosteroids (eg, prednisone at 1-1.5 mg/kg) are also initiated and gradually tapered over 6 months following clinical remission.
  • Treatment of acute life-threatening alveolar hemorrhage in patients with Goodpasture syndrome is with pulse methylprednisolone at 1 g/d for 3 days, followed by a gradual corticosteroid taper. Intravenous cyclophosphamide is begun concomitantly at 1 g/m² and repeated 3-4 weeks later, depending on the recovery of bone marrow.
  • The duration of immunosuppressive therapy is not well established. Treatment is continued for 3-6 months, provided a sustained remission has been achieved and anti-GBM antibodies have disappeared.
• Relapse
  • The circulating antibodies clear within 8 weeks, but an early relapse (ie, within first 2 mo) may occur when circulating antibodies are still present. This typically manifests as alveolar hemorrhage.
  • The risk factors for relapse include infection, volume overload, and cigarette smoking.
  • Late relapse has been documented only rarely.

Surgical Care

Renal transplantation has been used for ESRD secondary to Goodpasture syndrome. The incidence of linear deposits of IgG along glomeruli of the renal allograft is high, but this development does not cause histologic or functional damage to the transplanted kidney. Most transplant centers prefer to wait 6-12 months after serologic evidence indicates that anti-GBM antibodies have cleared.

Consultations

• Renal consultation: Consult a nephrologist for evaluation of the patient in regard to the differential diagnosis of the renal disease, indication for renal biopsy, requirement for hemodialysis or plasmapheresis, and therapeutic input.
• Pulmonary consultation: Consult a pulmonologist for patients with significant hemoptysis or respiratory compromise because these patients may deteriorate very rapidly and require bronchoscopy and/or intubation.
• Vascular surgery: A consultation with a vascular surgeon may be required for placement of vascular access for hemodialysis or plasmapheresis.

Diet

Renal diet is instituted.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Immunosuppressive agents

The treatment of choice is a combination of plasmapheresis to remove the circulating anti-GBM antibodies and immunosuppression with glucocorticoids and cytotoxic agents to inhibit further autoantibody formation. For induction therapy, prednisone and cyclophosphamide are initiated. Prednisone is tapered over 2-3 months, and cyclophosphamide is continued for as long 6 months (depending on the status of anti-GBM antibodies). Azathioprine may be used for patients who do not tolerate cyclophosphamide therapy.

Drug Name	Methylprednisolone (Solu-Medrol)
Description	DOC for severe disease. Should be started concomitantly with plasmapheresis. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult Dose	500 mg to 1 g IV for 3 d qd or bid/qid followed by gradual reduction to lowest level that maintains clinical response
Pediatric Dose	0.5-1.7 mg/kg/d or 5-25 mg/m2/d PO/IV/IM divided q6-12h
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking diuretics concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use; caution in patients with hypertension, congestive heart failure, ulcerative colitis, or thromboembolic disease

Drug Name	Cyclophosphamide (Cytoxan)
Description	Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Has anti-inflammatory effect. Treat for 6-12 mo (the time usually required for cessation of anti-GBM antibody formation).
Adult Dose	2 mg/kg IV initially; not to exceed 200 mg/d; goal is to reduce and maintain WBC count at 4000-7000/mm3
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severely depressed bone marrow function
Interactions	Allopurinol may increase the risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration of barbiturates, phenytoin, or chloral hydrate may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy	D - Unsafe in pregnancy
Precautions	Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; caution in impaired renal or hepatic function, leukopenia, or thrombocytopenia

Drug Name	Azathioprine (Imuran)
Description	Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity. Treat for 6-12 mo (the time usually required for cessation of anti-GBM antibody formation).
Adult Dose	2 mg/kg/d PO as single dose; not to exceed 200 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Pregnancy	D - Unsafe in pregnancy
Precautions	GI disturbances (eg, nausea, vomiting, diarrhea, abdominal pain, pancreatitis) may occur; adverse effects include leukopenia, anemia, thrombocytopenia, hepatotoxicity, and increased risk of neoplasm; caution with liver disease and renal impairment

Drug Category: Antibiotics

Patients receiving immunosuppressive therapy should also receive prophylaxis against Pneumocystis pneumonia.

FOLLOW-UP

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Further Inpatient Care

• Patients who develop massive hemoptysis or acute respiratory failure should be cared for in an ICU.
• Patients who develop renal failure are placed immediately into dialytic therapy. If renal failure does not recover, dialysis is continued indefinitely and the patient should be referred for renal transplantation.

Further Outpatient Care

• Patients require long-term regular visits for monitoring of renal function and immunosuppressive therapy.

Transfer

• Patients may require transfer to a hospital where plasmapheresis and/or hemodialysis is available.

Complications

• Acute respiratory failure and acute or chronic renal failure are the usual complications.

Prognosis

• In the past, Goodpasture syndrome was usually fatal. Aggressive therapy with plasmapheresis, corticosteroids, and immunosuppressive agents has dramatically improved prognosis. With this approach, the 5-year survival rate exceeds 80% and fewer than 30% of patients require long-term dialysis.
• In a literature review of all published cases, most patients were treated with immunosuppression and plasma exchange and were alive at follow-up.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Goodpasture syndrome (ie, anti-GBM disease) is an uncommon disorder of complex pathogeneses. Early recognition and treatment of this syndrome are critical because the prognosis for recovery of renal function depends on the initial extent of injury. Patients presenting with initial serum creatinine levels greater than 4 mg/dL, oliguria, and more than 50% crescents on renal biopsy rarely recover and usually progress to end-stage renal failure that requires long-term dialysis. The rapid institution of appropriate therapy depends on distinguishing anti-GBM disease from other pulmonary renal syndromes with similar presentations. Beginning therapy despite a pending or preliminary negative test result for serum anti-GBM antibodies may be necessary; a delay in this setting can be associated with adverse clinical outcomes.
• Patients receiving renal transplants must be informed that anti-GBM disease can recur in the transplanted kidney, although graft loss due to this is very rare.

Special Concerns

• Pneumocystis carinii pneumonia has an annual incidence of 1% but is a potentially deadly complication of immunosuppressive therapy in patients with Goodpasture syndrome. Prophylaxis with trimethoprim-sulfamethoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole 3 times per wk) may be a cost-effective method of prolonging life in these patients.
• In a substantial proportion of patients with crescentic glomerulonephritis (CGN), both anti-GBM antibodies and antineutrophil cytoplasmic antibodies (ANCAs) with specificity for myeloperoxidase (MPO-ANCA) are detected. 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.

MULTIMEDIA

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Media file 1:  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.
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Media type:  Photo

Media file 2:  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.
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Media type:  Photo

Media file 3:  Goodpasture syndrome. Cytoplasmic antineutrophilic cytoplasmic antibodies (c-ANCA) are commonly observed in Wegener granulomatosis and other vasculitides.
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Media type:  Photo

Media file 4:  Goodpasture syndrome. Perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA) are observed in Churg-Strauss vasculitis and occasionally in Wegener granulomatosis.
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Media type:  Photo

Media file 5:  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.
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Media type:  Photo

Media file 6:  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.
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Media type:  Photo

Media file 7:  Goodpasture syndrome. A 35-year-old man who previously smoked cigarettes heavily developed massive hemoptysis. The blood work showed positive antiglomerular basement membrane antibodies.
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Media type:  X-RAY

REFERENCES

Section 11 of 11

• Authors and Editors
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• Bolton WK. Goodpasture''s syndrome. Kidney Int. Nov 1996;50(5):1753-66. [Medline].
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• 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].
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• 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].
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• 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].

Article Last Updated: Jan 30, 2007