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Goodpasture Syndrome

by Marvin I. Schwarz, MD

(Anti-GBM Antibody Disease)

Goodpasture syndrome, a subtype of pulmonary-renal syndrome, is an autoimmune syndrome of alveolar hemorrhage and glomerulonephritis (see Pulmonary-Renal Syndrome) caused by circulating anti-glomerular basement membrane (anti-GBM) antibodies. Goodpasture syndrome most often develops in genetically susceptible people who smoke cigarettes, but hydrocarbon exposure and viral respiratory infections are additional possible triggers. Symptoms are dyspnea, cough, fatigue, hemoptysis, and hematuria. Goodpasture syndrome is suspected in patients with hemoptysis or hematuria and is confirmed by the presence of anti-GBM antibodies in the blood or in a renal biopsy specimen. Prognosis is good when treatment is begun before onset of respiratory or renal failure. Treatment includes plasma exchange, corticosteroids, and immunosuppressants, such as cyclophosphamide.

Pathophysiology

Goodpasture syndrome is the combination of glomerulonephritis with alveolar hemorrhage and anti-GBM antibodies. Goodpasture syndrome most often manifests as diffuse alveolar hemorrhage and glomerulonephritis together but can occasionally cause glomerulonephritis (10 to 20%) or pulmonary disease (10%) alone. Men are affected more often than women.

Anti-GBM antibodies are directed against the noncollagenous (NC-1) domain of the α3 chain of type IV collagen, which occurs in highest concentration in the basement membranes of renal and pulmonary capillaries. Environmental exposures—cigarette smoking, viral URI, and hydrocarbon solvent inhalation most commonly and pneumonia less commonly—expose alveolar capillary antigens to circulating antibody in genetically susceptible people, most notably those with HLA-DRw15, -DR4, and -DRB1 alleles. Circulating anti-GBM antibodies bind to basement membranes, fix complement, and trigger a cell-mediated inflammatory response, causing glomerulonephritis, pulmonary capillaritis, or both.

Symptoms and Signs

Hemoptysis is the most prominent symptom; however, hemoptysis may not occur in patients with alveolar hemorrhage, and patients may present with only chest x-ray infiltrates or with infiltrates and respiratory distress, respiratory failure, or both. Dyspnea, cough, fatigue, fever, and weight loss are common. Up to 40% of patients have gross hematuria, although pulmonary hemorrhage may precede renal manifestations by weeks to years.

Signs vary over time and range from clear lungs on auscultation to crackles and rhonchi. Some patients have peripheral edema due to renal failure and pallor due to anemia.

Diagnosis

  • Serum anti-GBM antibody tests

  • Sometimes renal biopsy

Definitive diagnosis of Goodpasture syndrome requires demonstration of serum anti-GBM antibodies by indirect immunofluorescence testing or, when available, direct enzyme-linked immunosorbent assay (ELISA) with recombinant or human NC-1 α3. However, antineutrophil cytoplasmic antibodies (ANCA) testing is positive (in a peripheral pattern) in only 25% of patients with Goodpasture syndrome.

Renal biopsy is indicated in patients with glomerulonephritis (hematuria, proteinuria, red cell casts detected with urinalysis, renal insufficiency, or a combination of these findings). A rapidly progressive focal segmental necrotizing glomerulonephritis with crescent formation is found in biopsy specimens in patients with Goodpasture syndrome and all other causes of pulmonary-renal syndrome (PRS). Immunofluorescence staining of renal or lung tissue classically shows linear IgG deposition along the glomerular or alveolar capillaries. IgG deposition also occurs in the kidneys of patients with diabetes or with fibrillary glomerulonephritis (a rare disorder causing PRS), but GBM binding of antibodies in these disorders is nonspecific and does not occur in linear patterns.

Prognosis

Goodpasture syndrome is often rapidly progressive and can be fatal if prompt recognition and treatment are delayed. Prognosis is good when treatment begins before onset of respiratory or renal failure. Long-term morbidity is related to the degree of renal impairment at diagnosis. Patients requiring dialysis right away and those with > 50% crescents in the biopsy specimen (who often will require dialysis) usually survive for < 2 yr unless kidney transplantation is done. Hemoptysis may be a good prognostic sign because it leads to earlier detection; the minority of patients who are ANCA-positive respond better to treatment. Relapse occurs in a small number and is linked to continued tobacco use and respiratory infection. In patients with end-stage renal disease who receive kidney transplantation, disease can recur in the graft.

Treatment

  • Plasma exchange

  • Corticosteroids and cyclophosphamide

Immediate survival in patients with pulmonary hemorrhage and respiratory failure is linked to airway control; endotracheal intubation see Airway Establishment and Control : Tracheal Intubation and mechanical ventilation are recommended for patients with borderline ABGs and impending respiratory failure. Patients with significant renal impairment may require dialysis or kidney transplantation.

Treatment is daily or every-other-day plasma exchange for 2 to 3 wk using 4-L exchanges to remove anti-GBM antibodies, combined with a corticosteroid (usually methylprednisolone 1 g IV over 20 min once/day or every other day for 3 doses followed by prednisone (1 mg/kg po once/day for 3 wk, then titrated down to 20 mg po once/day for 6 to 12 mo) and cyclophosphamide (2 mg/kg po or IV once/day for 6 to 12 mo) to prevent formation of new antibodies. Therapy can be tapered when pulmonary and renal function stop improving.

Key Points

  • Patients with Goodpasture syndrome may have both pulmonary hemorrhage and glomerulonephritis or either one separately.

  • Pulmonary findings can be mild or nonspecific.

  • Test serum for anti-GBM antibodies.

  • Do a renal biopsy if patients have glomerulonephritis.

  • Diagnose and treat Goodpasture syndrome before organ failure develops whenever possible.

  • Treat using plasma exchange, a corticosteroid, and cyclophosphamide.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • CYTOXAN (LYOPHILIZED)
  • MEDROL
  • RAYOS

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