Goodpasture Syndrome

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.

Anti-GBM antibodies are directed against the noncollagenous (NC-1) domain of the alpha3 chain of type IV collagen, which occurs in highest concentration in the basement membranes of renal and pulmonary capillaries.

Environmental exposures—cigarette smoking most commonly, and viral respiratory infection and hydrocarbon solvent inhalation 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.

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.

Other common symptoms include

• Cough

• Dyspnea

• Fatigue

• Fever

• Hematuria

• Weight loss

Alveolar Hemorrhage (Goodpasture Syndrome)

Image

By permission of the publisher. From Cohen A, Glassock R. In Atlas of Diseases of the Kidney: Glomerulonephritis and Vasculitis. Edited by R Schrier (series editor), RJ Glassock, and AH Cohen. Philadelphia, Current Medicine, 1999.

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.

• Serum anti-GBM antibody tests

• Sometimes renal biopsy

Patients are tested for serum anti-GBM antibodies by indirect immunofluorescence testing or direct enzyme-linked immunosorbent assay (ELISA) with recombinant or human NC-1 alpha3. Presence of these antibodies confirms the diagnosis.

Antineutrophil cytoplasmic antibodies (ANCA) testing is positive (in a peripheral pattern) in only 25% of patients with Goodpasture syndrome.

If anti-GBM antibodies are absent and patients have evidence of glomerulonephritis (hematuria, proteinuria, red cell casts detected with urinalysis, renal insufficiency, or a combination of these findings), renal biopsy is indicated to confirm the diagnosis. 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.

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 the pulmonary-renal syndrome), but glomerular basement membrane binding of antibodies in these disorders is nonspecific and does not occur in linear patterns.

• Plasma exchange

Immediate survival in patients with pulmonary hemorrhage and respiratory failure is linked to airway control; endotracheal intubation and mechanical ventilation are recommended for patients with borderline arterial blood gas measurements (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

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 urgent dialysis and those with > 50% crescents in the biopsy specimen (who often will require dialysis) usually survive for < 2 years 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 of patients 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.