Pediatric Anti-GBM Disease (Goodpasture Syndrome) Workup

Approximately 20-30% of adults with anti–glomerular basement membrane (anti-GBM) disease (Goodpasture disease) have coexisting antineutrophil cytoplasmic autoantibodies (ANCA) in their circulation. The renal prognosis of these patients was originally thought to be better when both antibodies are present than when anti-GBM is present alone. However, this has been refuted by a report by Rutgers et al, ^[14] which showed a similarly poor renal prognosis in adult patients with either anti-GBM antibodies alone or those who were double-positive for myeloperoxidase (MPO)-ANCA and anti-GBM antibodies. Incidentally, those patients with MPO-ANCA antibodies alone had a significantly better renal prognosis than the groups associated with anti-GBM antibodies.

In a nationwide sample of inpatients, no significant difference was found in in-hospital mortality between hospitalized patients with coexisting ANCA vasculitis and anti-GBM disease and those with anti-GBM disease alone. ^[15]

Azotemia occurs in 55-71% of adults with anti-GBM disease, and proteinuria occurs in 76-100% of adults. Nephrotic syndrome is unusual.

All patients with anti–glomerular basement membrane (anti-GBM) disease (Goodpasture disease) require urinalysis; complete blood cell (CBC) count with differential; and assessments of blood urea nitrogen (BUN), creatinine, and electrolyte levels.

Microscopic hematuria, as defined by the presence of red blood cells (RBCs), occurs in 83-94% of adults with anti-GBM disease, and macroscopic hematuria is present in 10-40% of adults. RBC casts have been reported in 6-100% of adults with anti-GBM disease.

Anemia occurs out of proportion to hemoptysis or renal failure. A hemoglobin level less than 12 mg/dL is observed in 90-100% of adults. In one series involving adults, the mean hemoglobin level was 7.5 g/dL.

Leukocytosis may be present. Approximately 40-50% of adults have a white blood cell (WBC) count of greater than 10,000 cells/µL. A leftward shift is common.

The erythrocyte sedimentation rate (ESR) is usually only mildly elevated, unlike in patients with vasculitis.

It should be noted that very limited pediatric data exists, because very few cases are reported in the literature. As such, details regarding clinical features at presentation are sparse. ^[16] Recently, Williamson et al reported 4 cases over a 25-year period from a single center estimated to have performed 2000 renal biopsies in that period. The most consistent feature is crescentic glomerulonephritis with either circulating anti-GBM antibodies or linear staining of IgG on the immunofluorescence. Clinical features included severe renal dysfunction in all patients and pulmonary hemorrhage in half of them. ^[16]

Assessments of antinuclear antibody (ANA), C3, and C4 levels and of the Westergren sedimentation rate are recommended to eliminate other causes of rapidly progressive glomerulonephritis (RPGN). Test results for ANA and rheumatoid factor are usually negative.

Specific recommended serologic tests include the following:

• Assessments of anti–glomerular basement membrane (anti-GBM) titers and antineutrophil cytoplasmic autoantibodies (ANCA) titers through indirect immunofluorescence testing

• Enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA), to evaluate proteinase 3 and myeloperoxidase

Results from serologic studies such as antistreptolysin O (ASO) titers and complement studies are usually normal.

The presence of anti-GBM antibody formation can be determined in a number of ways. Linear immunoglobulin G (IgG) deposition along the glomerular capillary walls on the immunofluorescence portion of the renal biopsy is highly suggestive of the disease, especially in the setting of crescentic glomerulonephritis (see the following image).

This image of direct immunofluorescence shows smooth linear staining of the basement membrane secondary to immunoglobulin G deposition. This confirms the diagnosis of anti-GBM disease (Goodpasture disease). Image courtesy of K. Orr, MD.

Circulating anti-GBM titers, which are typically of the IgG class, may be elevated in more than 90% of patients. These can be documented through indirect immunofluorescence or RIA techniques. Compared with indirect immunofluorescence, RIA is more sensitive (>90%) and almost as specific (>98%).

IgG can occasionally be eluted from lung or kidney biopsy tissue for analysis and characterization.

ANCA titers are elevated in 20-30% of patients with anti-GBM disease. The ANCA titer is usually perinuclear antineutrophil cytoplasmic autoantibody (p-ANCA) from antimyeloperoxidase antibody.

This section briefly discusses radiologic studies, pulmonary function testing (PFT), pulse oximetry, and bronchoscopy and bronchoalveolar lavage (BAL) in anti–glomerular basement membrane (anti-GBM) disease (Goodpasture disease).

Radiologic evaluation

Chest radiography is the most useful imaging test available to document the presence of pulmonary hemorrhage. The findings depict patchy or diffuse infiltrates with sparing of the upper lung fields. Unlike infection, pulmonary infiltrates from hemorrhage may resolve within a few days. ^[17]

Chest computed tomography (CT) scanning has a more limited role but may be helpful in identifying localized areas of pulmonary hemorrhage.

Pulmonary function testing

Pulmonary function testing can be used to assess pulmonary hemorrhage by demonstrating accelerated diffusion capacity of the lungs for carbon monoxide (DLCO). A progressive decline in vital capacity or total lung capacity suggests developing interstitial fibrosis.

Go to Pulmonary Function Testing for complete information on this topic.

Pulse oximetry

Pulse oximetry is indicated in all patients with suspected anti-GBM disease who may have hypoxemia from their parenchymal lung injury. However, in patients with severe anemia, oximeter readings may become less accurate.

Bronchoscopy and bronchoalveolar lavage

Bronchoscopy with transbronchial forceps biopsy (TBB) has a higher rate of false-negative results, but it is less invasive than collection through open lung biopsy. TBB is technically more difficult in younger children, and the small biopsy forceps used in them results in smaller tissue samples, with lower diagnostic yield.

Bronchoalveolar lavage can be used to detect hemosiderin-laden macrophages.

Renal biopsy is a superior diagnostic test relative to lung biopsy for anti–glomerular basement membrane (anti-GBM) disease (Goodpasture disease).

Renal biopsy in patients with anti-GBM disease (Goodpasture syndrome) can usually be performed without incident, even in a patient in relatively unstable condition. The biopsy allows assessment of the severity of the glomerulonephritis and examination for the characteristic linear immunoglobulin G (IgG) deposition along the GBM.

Renal histologic features include a diffuse glomerulonephritis with focal or complete necrosis of the glomerular tuft and segmental or circumferential cellular crescents surrounding some or all glomeruli. Linear IgG along the GBM can be observed with immunofluorescence testing. Linear C3 along the GBM is present in two thirds of biopsy samples. Other causes of linear staining on direct immunofluorescence analysis include systemic lupus erythematosus (SLE) and diabetes mellitus.

Lung biopsy is rarely indicated, but it may be helpful. Pulmonary histologic features include nonspecific findings of hemorrhage with variable degrees of inflammation and fibrosis. Samples obtained during lung biopsy may show IgG staining of the alveolar septum, which is diagnostic for anti-GBM disease.