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 Diffuse Alveolar Hemorrhage Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage. There are numerous causes, but autoimmune disorders are most common. Most patients present with dyspnea, cough, hemoptysis... read more and glomerulonephritis Overview of Glomerular Disorders The hallmark of glomerular disorders is proteinuria, which is often in the nephrotic range (≥ 3 g/day). Glomerular disorders are classified based on urine changes as those that manifest predominantly... read more 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 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

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.

Patients are tested for serum anti-GBM antibodies by indirect immunofluorescence testing or, when available, 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 Pulmonary-Renal Syndrome Pulmonary-renal syndrome is diffuse alveolar hemorrhage plus glomerulonephritis, often occurring simultaneously. Cause is almost always an autoimmune disorder. Diagnosis is by serologic tests... read more . 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 Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more or with fibrillary glomerulonephritis Fibrillary and Immunotactoid Glomerulopathies Fibrillary and immunotactoid glomerulopathies are rare conditions defined pathologically by organized deposition of nonamyloid microfibrillar or microtubular structures within the renal mesangium... read more (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.

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 Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more 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.

Immediate survival in patients with pulmonary hemorrhage and respiratory failure is linked to airway control; endotracheal intubation Tracheal Intubation Most patients requiring an artificial airway can be managed with tracheal intubation, which can be Orotracheal (tube inserted through the mouth) Nasotracheal (tube inserted through the nose)... read more and mechanical ventilation Overview of Mechanical Ventilation Mechanical ventilation can be Noninvasive, involving various types of face masks Invasive, involving endotracheal intubation Selection and use of appropriate techniques require an understanding... read more are recommended for patients with borderline arterial blood gas measurements (ABGs) and impending respiratory failure. Patients with significant renal impairment may require dialysis Overview of Renal Replacement Therapy Renal replacement therapy (RRT) replaces nonendocrine kidney function in patients with renal failure and is occasionally used for some forms of poisoning. Techniques include continuous hemofiltration... read more or kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more .

Treatment is daily or every-other-day plasma exchange Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more for 2 to 3 weeks using 4-L exchanges to remove anti-GBM antibodies, combined with corticosteroids (usually methylprednisolone 1 g IV over 20 minutes once a day or every other day for 3 doses followed by prednisone (1 mg/kg orally once a day for 3 weeks, then titrated down to 20 mg orally once a day for 6 to 12 months) and cyclophosphamide (2 mg/kg orally or IV once a day for 6 to 12 months) to prevent formation of new antibodies. Therapy can be tapered when pulmonary and renal function stop improving.

Rituximab could be used in some patients who have severe adverse effects due to cyclophosphamide or refuse cyclophosphamide as treatment, but it has not been studied in patients with Goodpasture syndrome.