Patients often have a history of malaise, arthralgia, and weight loss, but these features are generally far milder than in other causes of focal necrotizing glomerulonephritis, such as antineutrophilic cytoplasmic antibody (ANCA)-associated systemic vasculitis. Anemia is common, and may be symptomatic even in patients with minimal hemoptysis. The principal clinical symptoms relate either to pulmonary hemorrhage or to the development of renal failure. The severity of pulmonary hemorrhage varies and can range from minor hemoptysis to life-threatening hemorrhage with respiratory failure. Typically, hemoptysis is intermittent at the outset and can occur spontaneously or can be precipitated by intercurrent infections or fluid overload. There is a poor correlation between the severity of hemoptysis and the quantity of pulmonary blood loss, with other clinical signs being variable. These include inspiratory crackles and bronchial breathing, with patients often tachypnoeic and cyanosed. Historically hemoptysis has been the most common presenting feature, but its incidence is decreasing with the reduced prevalence of cigarette smoking. It now occurs in about 50% of cases. Even in those with life-threatening pulmonary hemorrhage, the lungs of patients who survive the acute illness recover completely and have no residual pulmonary symptoms of radiologic abnormalities. Histologically they are left with little residual lung pathology or fibrosis.
Renal disease can occur either alone or in association with pulmonary hemorrhage. Mild renal impairment may improve spontaneously, but once significant renal injury has occurred, improvement is rare and deterioration may be extremely rapid. Evolution from normal renal function to established renal failure is less than 12 hours in some patients. Microscopic hematuria is an early sign of renal pathology, and dysmorphic red cells and red cell casts are seen in the urine as the disease progresses. Proteinuria is present, but is usually modest (<3 g/L). Some patients present with macroscopic hematuria and severe loin pain, which are often features of very severe disease. Oliguria is a poor prognostic sign.
Without treatment anti-GBM disease almost always progresses to renal failure, but anti-GBM antibody synthesis is transient, often lasting for less than 2 months. Patients are treated with cytotoxic drugs and plasma exchange. Recurrence of anti-GBM disease is rare, but has been reported, sometimes precipitated by infection or exposure to a toxic agent. The outcome in these cases is generally better than with the original presentation, since the diagnosis is often made more quickly. The disease almost invariably recurs in renal allografts performed when circulating anti-GBM antibodies are still present, but transplantation is safe once they are no longer detectable. Exceptionally, however, renal transplantation can reinitiate anti-GBM antibody production, but this probably occurs in less than 1% of cases. Accordingly, transplantation is normally deferred for at least 6 months after the disappearance of circulating anti-GBM antibodies, and transplanted patients should be monitored closely for changes in urinary sediment or antibody titers.
The diagnosis of Goodpasture's disease is dependent on the detection of anti-GBM antibodies either in the circulation or at renal biopsy. These antibodies are usually detected using an enzyme-linked immunosorbent assay (ELISA), and equivocal results can be confirmed by Western blotting. There is a clear correlation between the titer of anti-GBM antibodies and the severity of renal injury, but the pattern of lung disease is independent of antibody titer.
Other laboratory findings are nonspecific. Anemia is common, and is often microcytic and hypochromic. As in other types of rapidly progressive glomerulonephritis, there may be evidence of microangiopathy on the blood film, but this is mild. Abnormalities of the urinary sediment are an early sign of renal pathology, and are often followed by increases in serum urea nitrogen and creatinine as renal failure develops.
Chest radiographs can be normal or show alveolar shadowing in those with pulmonary hemorrhage. Typically this spares the bases and upper lung fields, but distinguishing pulmonary hemorrhage from infection or edema can be impossible. However, hemorrhage itself is not associated with curly B-lines and is not limited by fissures. Typically the radiologic changes appear and resolve more quickly than is the case for infection (Figure 29–1).
Renal biopsy from a patient with Goodpasture's syndrome showing two glomeruli with segmental necrosis, leakage of blood into Bowman's space, and crescent formation. Renal tubules contain red cell casts and there is periglomerular and interstitial inflammation. Stained with acid fuchsin orange G-stain (AFOG).
There are no specific morphologic abnormalities on any type of renal imaging and the appearance cannot be distinguished from other types of acute renal failure.
A renal biopsy is essential in the diagnosis and management of suspected anti-GBM disease (Figure 29–2). The early histologic changes include very minor mesangial expansion and hypercellularity and are followed by the development of a focal and segmental glomerulonephritis, often with marked neutrophil infiltration. This progresses to a focal necrotizing glomerulonephritis with rupture of glomerular capillaries and leakage of blood into Bowman's space. This initiates the formation of cellular crescents, composed of parietal epithelial cells and macrophages. There is some experimental evidence that crescents may also be comprised of visceral epithelial cells. Are we certain that is not the case in Goodpasture's disease? Characteristically all the crescents are at the same stage of evolution, a feature that reflects the explosive nature of the disease and distinguishes it from other forms of focal necrotizing and crescentic glomerulonephritis. Linear binding of antibody to GBM is found in all patients, regardless of the severity of the renal pathology. The antibody is almost always immunoglobulin (Ig) G, but in one-third of cases IgA or IgM is also detected; exceptionally, reports describe deposition of IgA or IgM alone. Linear C3 is seen in 60–70% of patients, and its presence does not influence the severity of the renal injury.
Glomeruli from a patient with Goodpasture's disease showing linear deposition of IgG along the glomerular basement membrane detected by the immunoperoxidase method.