Clinical Pearls & Morning Reports
Published November 6, 2019
Linear autoantibody deposition along glomerular basement membranes is pathognomonic for antiglomerular basement membrane (anti-GBM) disease. A negative or pauci-immune pattern (without detectible antibody or complement) is associated with the antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis syndromes of granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. Read the Clinical Problem-Solving Article here.
Q: In what ways are anti-GBM disease and ANCA-associated vasculitis similar?
A: Complement factor levels are often normal in ANCA-associated vasculitis or anti-GBM disease, both of which have pulmonary and renal manifestations. Both ANCA-associated vasculitis and anti-GBM disease cause rapidly progressive crescentic glomerulonephritis.
Q: In what ways are anti-GBM disease and ANCA-associated vasculitis different?
A: Malaise, arthralgia, and extended illness are more characteristic of an ANCA-associated vasculitis than of anti-GBM disease, which usually does not cause constitutional symptoms. The pathogenic anti-GBM antibodies affect the alveolar basement membranes and lead to diffuse alveolar hemorrhage; these antibodies would not be expected to cause a focal pneumonitis or pleuritis. ANCA-associated vasculitides such as granulomatosis with polyangiitis or microscopic polyangiitis are more likely to have focal pulmonary and pleural involvement. In contrast to anti-GBM disease, ANCA-associated vasculitis has a propensity to relapse.
A: This disease is caused by autoantibody-mediated injury to the glomerular and alveolar basement membranes. The autoantibody is expressed against the noncollagenous domain 1 of the alpha-3 chain of type IV collagen specific to specialized basement membranes of glomeruli and alveoli. Pulmonary involvement is seen in 30 to 60% of patients at presentation, is more common among smokers than nonsmokers, and is manifested by cough, hemoptysis, dyspnea, and hypoxemia, with extensive alveolar infiltrates on chest imaging. Anti-GBM disease is rare, with an estimated prevalence of less than 1 case per million persons per year, and is typically associated with a rapidly progressive glomerulonephritis without prodromal symptoms. This disease exhibits a bimodal distribution; younger adults (20 to 40 years of age) are more commonly men and typically present with a pulmonary–renal syndrome, whereas older patients (60 years of age or older) tend to be women and often present with isolated renal involvement.
A: Rapidly progressive glomerulonephritis with coexistent ANCAs and anti-GBM antibodies is referred to as double antibody–positive disease. Up to one third of patients with anti-GBM antibodies also have ANCAs (usually myeloperoxidase ANCA). Approximately 5% of patients who are initially positive for ANCAs are found to have anti-GBM antibodies. Patients with double antibody–positive disease have hybrid clinical, prognostic, and pathologic features of anti-GBM disease and ANCA-associated vasculitis. Such patients often have extrarenal disease manifestations of ANCA-associated conditions while also exhibiting more fulminant renal dysfunction similar to that seen in patients with anti-GBM disease. Therapy for double positive–antibody disease mirrors treatment for anti-GBM disease and typically involves high-dose glucocorticoids, cyclophosphamide, and plasmapheresis. Case series suggest that these treatments are unlikely to improve renal function in patients who are initially dependent on dialysis or who have a biopsy that shows a high percentage of glomeruli with crescents, although nonrenal manifestations may abate.