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Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715. PubMed PMID: 23045170.
Definition AND EtiologyTop
Anti–glomerular basement membrane (anti-GBM) disease is a vasculitis affecting glomerular capillaries and/or pulmonary capillaries that is uniquely associated with the deposition antibodies to the GBM in the membrane. Pulmonary involvement leads to pulmonary hemorrhage, whereas renal involvement results in glomerulonephritis with necrosis and crescents. Historically, the eponym “Goodpasture syndrome” has referred to the combined pulmonary and renal manifestations of anti-GBM disease.
Clinical Features and Natural HistoryTop
1) General symptoms: Malaise, fever, arthralgia.
2) Symptoms of pulmonary hemorrhage (see Diffuse Alveolar Hemorrhage) can include dyspnea, cough, hemoptysis, fever, respiratory failure, and shock.
3) Symptoms of rapidly progressive glomerulonephritis: Peripheral edema, hypertension. In 30% of patients the time between the onset of renal and pulmonary symptoms is from 1 week to 1 year.
4) Other symptoms: Nausea, vomiting, diarrhea.
The disease is usually rapidly progressive and leads to acute respiratory and renal failure. The main causes of death are pulmonary hemorrhage and respiratory failure. Long-term complications include chronic kidney disease, pulmonary fibrosis, and chronic respiratory failure.
Diagnosis is based on the clinical features, positive circulating antibodies to the GBM, and characteristic histologic features of renal biopsy specimens.
Laboratory findings reveal elevations in the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, normocytic or microcytic hypochromic anemia, leukocytosis (often with eosinophilia), and signs of renal involvement (creatinine, active sediment [cellular casts], proteinuria <3 g/d in urinalysis), antibodies to the GBM (in 80%-90% of patients), myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) (in 10%-40%). Chest radiographs, high-resolution computed tomography (HRCT), and bronchoalveolar lavage reveal abnormalities typical for pulmonary hemorrhage.
1. Other causes of pulmonary-renal syndrome (see Granulomatosis with Polyangiitis).
2. Causes of diffuse alveolar hemorrhage other than vasculitis.
3. Other types of acute glomerulonephritis (see Glomerular Diseases).
4. Renal vein thrombosis with pulmonary embolism.
5. Heart failure with renal failure.
Plasmapheresis (use repeatedly until the complete removal of anti-GBM antibodies) with cyclophosphamide and prednisone is the standard treatment for anti-GBM disease, particularly for improving renal outcomes.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of study but strong clinical effect. Cui Z, Zhao J, Jia XY, et al. Anti-glomerular basement membrane disease: outcomes of different therapeutic regimens in a large single-center Chinese cohort study. Medicine (Baltimore). 2011 Sep;90(5):303-11. doi: 10.1097/MD.0b013e31822f6f68. PubMed PMID: 21862934. Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med. 2001 Jun 5;134(11):1033-42. PubMed PMID: 11388816.
No maintenance therapy of anti-GBM disease is necessary, as relapses are uncommon. Exception to this are patients who are double seropositive for ANCA and anti-GBM antibodies, in which case immunosuppression should be akin to that for ANCA-associated vasculitis (AAV).
In treatment of refractory disease rituximab may be used.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the presence of small case studies, imprecision, indirectness, and risk of bias. Shah Y, Mohiuddin A, Sluman C, et al. Rituximab in anti-glomerular basement membrane disease. QJM. 2012 Feb;105(2):195-7. doi: 10.1093/qjmed/hcr001. Epub 2011 Jan 21. PubMed PMID: 21258056. Arzoo K, Sadeghi S, Liebman HA. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis. 2002 Oct;61(10):922-4. PubMed PMID: 12228164; PubMed Central PMCID: PMC1753910. Kidney transplant should be considered after 6 months of undetectable anti-GBM levels.
In acute disease, assisted ventilation and renal replacement therapy are often necessary. From 60% to 90% of patients receiving appropriate treatment survive the acute phase of the disease.
Treatment is less effective in patients presenting with renal failure. Up to 50% of patients eventually require renal replacement therapy.