Goodpasture syndrome requires early and effective treatment if it is not to be fatal. The regimens in use have decreased the mortality rate from the original 96% to less than 20%.
The goals of treatment include:
- To remove anti-GBM autoantibodies from the plasma of the patient
- To suppress antibody production by inhibiting immune cell activity
- To inhibit the autoimmune response
Treatment of Goodpasture syndrome
The treatment objectives are usually met by:
Plasmapheresis
Plasmapheresis is a procedure in which a person’s blood is removed and filtered before the cellular components alone are returned to the circulation. This allows the removal of the autoantibodies from the plasma. To compensate for volume loss, fresh frozen plasma is often added intravenously although fluid or protein infusions are other options in use. Many daily whole volume exchange cycles of plasmapheresis are necessary to reduce the circulating level of antibodies to an insignificantly low level. The process usually takes several weeks.
The use of plasma exchange is crucial because neither steroids nor immunosuppressants affect the level of circulating autoantibodies. They also do not help to restore renal function.
It has been demonstrated that anti-GBM antibodies are not merely biomarkers of active disease but are directly pathogenic to target organs. The therapy is also safe and produces rapid reduction of circulating antibodies. Plasmapheresis improves the renal function in 80% of patients whose serum creatinine is below 600 µmol/L and who do not require dialysis.
Intense immunosuppression
- Immunosuppressives such as cyclophosphamide which target the immune cells may have to be taken for up to a year.
- Corticosteroids, which are powerful inhibitors of the immune response, are started at a high pulsatile intravenous dosage. Usually methylprednisolone is used in the first phase, followed by prednisone continued for months before appropriate tapering until a maintenance dose is finalized.
- Other modes of immunosuppressive treatment include:
- Mycophenolate mofetil: this drug inhibits purine synthesis in the body and thereby prevents proliferation of T and B cells in response to presented antigens. In this way it can prevent the production of both autoantibodies and the cytotoxic T cells which are crucial in the cell-mediated immune component of Goodpasture syndrome.
- Immunoabsorption
- Cyclosporine
- Monoclonal antibodies (experimental)
- Immunomodulation (experimental)
The combination of plasmapheresis and immunosuppression produces good results in the majority of patients. Despite this, it has not succeeded in preventing many early deaths from massive pulmonary hemorrhage, especially when linked to infections.
Supportive management
Antihypertensives are required to restore as much renal function as is possible. Angiotensin-converting enzyme (ACE) inhibitors and angiotensinogen receptor blockers (ARBs) are most often used.
In the presence of acute renal failure, the fluid-electrolyte balance must be maintained, usually by restricting the total fluids taken in and not adding salt to food. Protein-rich foods in the diet may also need to be cut down until renal recovery is complete. If fluid overload sets in, dialysis may be required.
Patient monitoring
Monitoring of the patient is a crucial part of treatment and includes both monitoring of the disease progress, and watching for adverse effects of the powerful drugs used.
Parameters of anti-GBM disease activity
- Serum creatinine (renal function)
- Hemoglobin (falls in pulmonary hemorrhage)
- Anti-GBM antibody levels
- Chest X-rays
- KCO (reduced in pulmonary hemorrhage)
Monitoring adverse effects of the drug regimen
- Total white cell count (cyclophosphamide may induce leukopenia)
- Platelet count (platelets drop because of plasmapheresis-induced consumption)
- New infections due to immunosuppression, especially of the intravenous access lines and urinary catheters
Treatment is continued until a clinical and serological response is obtained. Pulmonary hemorrhage usually stops in a few days, and even with large bleeds, no pulmonary scarring fibrosis is observed. However permanent damage may be sustained to the kidneys which would require dialysis or renal transplantation. The latter is an option only if the levels of anti-GBM antibody become undetectable.
Even after all clinical signs have been controlled, the disease may relapse if:
- Infections set in
- Fluid overload is present
- Rebound increases in the anti-GBM antibody titers occur once plasma exchange has been stopped
References
Further Reading