Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The treatment of choice is a combination of plasmapheresis to remove the circulating anti–glomerular basement membrane (anti-GBM) antibodies and immunosuppression with glucocorticoids and cytotoxic agents to inhibit further autoantibody formation. In addition, antibiotic prophylaxis is indicated to reduce the risk of opportunistic infection secondary to immunosuppressive therapy.
Immunosuppressive agents
Class Summary
For induction therapy, prednisone and cyclophosphamide are initiated. For severe or rapidly progressing disease, methylprednisolone at a dose of 250 mg every 6 hours should be administered. Once the patient is stabilized, continue oral therapy with prednisone.
Azathioprine may be used for patients who do not tolerate cyclophosphamide.
Prednisone (Deltasone, Rayos)
Prednisone is used as an immunosuppressant in the treatment of autoimmune disorders. This agent may reduce inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity.
Methylprednisolone (Solu-Medrol, Medrol, Depo-Medrol)
Methylprednisolone is the drug of choice for severe disease. It should be started concomitantly with plasmapheresis. This agent decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Azathioprine (Imuran, Azasan)
Azathioprine antagonizes purine metabolism and inhibits the synthesis of DNA, RNA, and proteins. It may decrease the proliferation of immune cells, which results in lower autoimmune activity.
Alkylating Agents (Cytotoxic Agents)
Class Summary
Alkylating agents bind with DNA and interfere with cell growth and differentiation.
Cyclophosphamide
Cyclophosphamide is chemically related to nitrogen mustards. It is a potent immunosuppressant used as an adjunct to corticosteroids and plasma exchange. This agent interferes with the inflammatory response by decreasing bone marrow response through the interference of DNA cross-linking and decreases anti–glomerular basement membrane (anti-GBM) antibody production.
Antibiotics
Class Summary
Patients receiving immunosuppressive therapy should also receive prophylaxis against Pneumocystisjiroveci pneumonia.
Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS)
This combination inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, thus inhibiting folic acid synthesis. It results in inhibition of bacterial growth. The antibacterial activity of trimethoprim-sulfamethoxazole (TMP-SMZ) includes common urinary tract pathogens, except Pseudomonas aeruginosa. Each double strength (DS) tablet contains 160 mg of TMP and 800 mg SMZ.
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Goodpasture syndrome. A 45-year-old man was admitted to the intensive care unit with respiratory failure secondary to massive hemoptysis and acute renal failure. The antiglomerular basement membrane antibodies were strongly positive. The autopsy showed consolidated lung from extensive bleeding, which led to asphyxiation.
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Goodpasture syndrome. Close-up view of gross pathology in a 45-year-old man admitted to the intensive care unit with respiratory failure secondary to massive hemoptysis and acute renal failure. The antiglomerular basement membrane antibodies were strongly positive. The autopsy showed consolidated lung from extensive bleeding, which led to asphyxiation.
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Cytoplasmic antineutrophilic cytoplasmic antibodies (c-ANCA), which can appear in Goodpasture syndrome, are also commonly observed in Wegener granulomatosis and other vasculitides.
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Perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA), which can appear in Goodpasture syndrome, are also observed in Churg-Strauss vasculitis and occasionally in Wegener granulomatosis.
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This is a renal biopsy slide of a patient who presented with hemoptysis and hematuria. The renal biopsy revealed crescentic glomerulonephritis, which may be caused by systemic lupus erythematosus, vasculitis, or Goodpasture syndrome.
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Goodpasture syndrome. A 35-year-old man who previously smoked cigarettes heavily, developed massive hemoptysis. The blood work showed positive anti–glomerular basement membrane antibodies.
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Immunofluorescence staining for immunoglobulin (IgG) reveals diffuse, high-intensity, linear staining of the glomerular basement membrane in a patient with anti–glomerular basement membrane (GBM) disease. Courtesy of Glen Markowitz, MD, Department of Pathology, Columbia University.
