eMedicine Specialties > Pediatrics: General Medicine > Pulmonology
Goodpasture Syndrome: Treatment & Medication
Updated: Mar 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment of anti–glomerular basement membrane (anti-GBM disease), or Goodpasture syndrome (GS), requires a 2-pronged approach consisting of the removal of the pathogenic antibody and the prevention of new antibody production.
- Plasma exchange: For antibody removal, literature about adults recommends plasma exchange every day for 14 days or every third day for a month. Each session consists of an exchange volume of 3-4 L and its replacement with albumin or fresh-frozen plasma.
- Immunosuppression: Therapy with corticosteroids (eg, prednisone) and cyclophosphamide is aimed at eliminating ongoing antibody synthesis. Adult patients who present with a serum creatinine level greater than 8 mg/dL have poor renal outcomes. Therefore, seriously consider whether to use this aggressive treatment regimen in patients presenting with limited pulmonary disease and marked renal impairment (serum creatinine >8 mg dL).
- Isolated reports describe the use of rituximab, an anti-CD20 monoclonal antibody, in autoimmune disorders aimed at targeting B lymphocytes and their antibody production.
- Arzoo reported its use in a 73-year-old woman whose recurrent anti-GBM disease was refractory to treatment with steroids, plasmapheresis, and cyclophosphamide.7 This patient had marked improvement after the second of 6 weekly prescribed doses of rituximab at 375 mg/m2/dose. This coincided with the disappearance of circulating anti-GBM antibodies.
- Pediatric anti-GBM disease: Pediatric patients have also been given plasma exchange in conjunction with corticosteroids and cyclophosphamide. Duration of the immunosuppressive treatment varies but is typically 6 months for steroids and 3 months for cyclophosphamide. Rituximab has been used in pediatric autoimmune disorders, but no reports suggest its use for anti-GBM disease in the pediatric age group. This agent is a potent immunosuppressive and needs to be used with caution, weighing the risks and benefits (see Medication).
- Monitoring the therapeutic response: Closely monitor patients by obtaining regular anti-GBM titers, serum creatinine levels, and chest radiographs to decide on the duration of various therapies.
Consultations
- Patients with anti-GBM disease can present with renal or pulmonary symptoms and are often critically ill. Therefore, pulmonologists, nephrologists, and critical care specialists are commonly involved in the care of these patients.
- Most treatments are aimed at both renal and pulmonary conditions. Effective cooperation and communication with regard to the timing and duration of these therapies is essential.
Diet
- Sodium restriction
- Pediatric patients taking corticosteroids are restricted to a sodium intake of 3 mEq/kg/d. The daily total should not exceed 2 g. On the basis of the molecular weight of sodium, 1 mEq is equal to 23 mg.
- Pediatric patients with severe proteinuria and nephrotic syndrome who are taking corticosteroids are restricted to a sodium intake of 2 mEq/kg/d. The daily total should not exceed 2 g.
- Fluid restriction
- The recommended fluid intake largely depends on the patient's renal function and whether the patient is taking cyclophosphamide.
- Patients with a good urine output and a stable blood pressure do not require fluid restriction. Moreover, if the same patients are taking cyclophosphamide, liberal fluid intake is encouraged to promote urine output and to prevent the risk of hemorrhagic cystitis.
- Conversely, patients with oliguric renal failure who are not likely to be taking cyclophosphamide may require fluid restriction.
Activity
- Once discharged from the hospital, recovering patients can resume their usual activities unless they have undergone renal biopsy. These patients should avoid running and jumping for 2 weeks, and they are restricted from contact sports for 1 month after the date of biopsy.
- If significant anemia is present, the patient's tendency to become fatigued is likely to restrict his or her usual activity level.
Medication
Medications used to treat anti-GBM disease are immunosuppressive agents and prophylactic antibiotics.
Glucocorticoids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.
Methylprednisolone (Solu-Medrol)
Used to treat pulmonary hemorrhage and rapidly progressing glomerulonephritis (RPGN). Decreases anti-GBM antibody production. Decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability.
Adult
1 g IV qd for 3 d
Pediatric
Pulse dose of 10-30 mg/kg IV qd for 3 d; not to exceed 1 g/d
Possible increased clearance with coadministration of barbiturates, phenytoin, and rifampin; salicylates; vaccines; toxoids
Documented hypersensitivity; coadministration of live vaccines; systemic fungal infection
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypothyroidism, cirrhosis, hypertension, congestive heart failure, ulcerative colitis, and thromboembolic disorders
Prednisone (Deltasone, Meticorten, Orasone)
Initially used after pulse methylprednisolone treatment is completed. Decreases anti-GBM antibody production.
Adult
1-2 mg/kg/d for 8-12 wk; alternatively, taper weekly to 20 mg/d with slower taper over 1-2 y
Pediatric
2 mg/kg/d PO in divided doses for 1 mo; not to exceed 80 mg/d; after 1 mo, 60-80 mg/d typically given every am for 1 additional mo; then, change to alternate-day regimen
Barbiturates, phenytoin, rifampin, salicylates, vaccines, toxoids
Documented hypersensitivity; serious infections; systemic fungal infections; varicella infection
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypothyroidism, cirrhosis, hypertension, congestive heart failure, ulcerative colitis, and thromboembolic disorders
Alkylating agent (cytotoxic agent)
Cyclophosphamide interferes with inflammatory response by decreasing bone marrow response through the interference of DNA cross-linking. Decreases anti–glomerular basement membrane (anti-GBM) antibody production.
Cyclophosphamide (Cytoxan)
Potent immunosuppressant used as an adjunct to corticosteroids and plasma exchange. Used to prevent further antibody production in anti-GBM disease.
Adult
2-3 mg/kg/d PO for 8-12 wk; adjust dose in renal insufficiency or WBC count <3500
Pediatric
2 mg/kg/d PO for 8-12 wk; not to exceed 150 mg/dose
Increased myelotoxicity with allopurinol; possible increased conversion of cyclophosphamide to active metabolites with coadministration of phenobarbital, phenytoin, or chloral hydrate; possible increased bone marrow suppression with allopurinol, chloramphenicol, phenothiazines, or imipramine; possible prolonged neuromuscular blocking activity of succinylcholine with coadministration
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in bone marrow suppression, renal impairment, or hepatic dysfunction; dose reduction required for renal impairment and bone marrow suppression
Monoclonal antibodies
Rituximab (anti-CD-20) monoclonal antibody binds to pre-B cells and mature B cells. It results in lymphocytotoxic effects to B cells, which should result in reduced autoantibody production.
Rituximab (Rituxan)
Antibody genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on surface of normal and malignant B lymphocytes. Antibody is an IgG1 kappa immunoglobulin containing murine light-chain and heavy-chain variable region sequences and human constant region sequences. Isolated reports of its use for Goodpasture syndrome in adults with disease refractory to corticosteroids, alkylating agents, and plasmapheresis.
Adult
Not established; limited data suggest 375 mg/m2/dose slow IV infusion (over 4 h) qwk for 6 doses
Pediatric
Not established, limited data suggest 375 mg/m2/dose slow IV infusion (over 4 h) qwk 4-6 doses; has been used in pediatric patients for SLE and other autoimmune disorders
Coadministration with cisplatin is known to cause severe renal toxicity including acute renal failure; may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine); no reported interactions with concomitant use of cyclophosphamide
Documented hypersensitivity; IgE-mediated reaction to murine proteins
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use with caution in patients with dormant infections such as hepatitis B, hepatitis C, or CMV due to risk of reactivation; hypotension, bronchospasm, and angioedema may occur, premedication with acetaminophen and diphenhydramine may decrease incidence; discontinue treatment if life-threatening cardiac arrhythmias occur; must administer by slow IV infusion, do not administer IV push or bolus; may cause renal failure
Antibiotics
These agents are used to prevent opportunistic infection with Pneumocystis carinii.
Trimethoprim and sulfamethoxazole (Bactrim, Septra)
Prevents or reduces incidence of P carinii pneumonia in immunosuppressed patients.
Adult
P carinii prophylaxis: 1 DS tab (ie, 160 mg trimethoprim and 800 mg sulfamethoxazole) PO qd or 3 times/wk
Pediatric
P carinii prophylaxis: 5 mg/kg/d PO divided bid (dose based on trimethoprim component); not to exceed 320 mg/d; dose may need to be reduced if leukopenia significant
Decreased clearance of warfarin with coadministration; methotrexate displaced from protein-binding sites; increased effect of sulfonylureas, phenytoin, and thiopental with coadministration; decreased cyclosporine concentrations
Documented hypersensitivity; porphyria; megaloblastic anemia from folate deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with G-6-PD deficiency, renal impairment, or hepatic impairment
More on Goodpasture Syndrome |
| Overview: Goodpasture Syndrome |
| Differential Diagnoses & Workup: Goodpasture Syndrome |
 Treatment & Medication: Goodpasture Syndrome |
| Follow-up: Goodpasture Syndrome |
| Multimedia: Goodpasture Syndrome |
| References |
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Further Reading
Keywords
Goodpasture syndrome, GS, anti–glomerular basement membrane disease, anti-GBM disease, Goodpasture disease, Goodpasture's disease, pulmonary renal syndrome, Goodpasture's syndrome, Wegener granulomatosis, Wegener's granulomatosis, glomerulonephritis, pulmonary hemorrhage, anti-GBM antibody formation, pulmonary renal syndrome of alveolar hemorrhage, small vessel vasculitis, glomerulonephritis, cigarette smoking, end-stage renal disease, ESRD, systemic lupus erythematosus, SLE, Henoch-Schönlein purpura, HSP, respiratory failure, proteinuria, nephrotic syndrome
