eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases
Wegener Granulomatosis: Treatment & Medication
Updated: Nov 25, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Various medication regimens involving immunosuppressants are administered in patients with Wegener's granulomatosis (ie, combinations of steroids and cyclophosphamide, azathioprine, or methotrexate primarily). The authors suggest that most patients with Wegener's granulomatosis have their condition stabilized initially by administering pulse steroids along with cyclophosphamide, 600-800 mg/m2/mo for 6-12 months, followed by methotrexate at 7.5-15 mg/wk for 12-24 months as tolerated. In patients unable to tolerate cyclophosphamide, azathioprine 1.5-2.5 mg/kg/d may be substituted (see Medication).
Medication
Initially, Wegener's granulomatosis was uniformly fatal within a few months of diagnosis; the prognosis was improved minimally after institution of steroid therapy. Cyclophosphamide has since been used very effectively and now is the usual drug of choice for induction of remission. The well-recognized toxicity of oral cyclophosphamide has led to institution of pulse therapy as the present standard of care. Azathioprine may be used as maintenance therapy or as initial therapy in patients unable to tolerate cyclophosphamide. Less frequently used therapies include methotrexate.
Excellent remission is achieved in about 70% of patients, but unfortunately relapses are common. Aggressive treatment of pulmonary and renal involvement at the time of disease onset seems to lessen the probability of later neurologic involvement.
Various dosing regimens for steroids have been suggested, ranging from high-dose pulse IV to continuous oral therapy, generally in addition to immunosuppressants. The adverse effects of steroids are well known and are beyond the scope of this review. Cyclophosphamide is an alkylating agent with significant potential toxicity to bone marrow, liver, and bladder, and it should be used only by experienced clinicians. Pulse IV therapy regimens (eg, 600-800 mg/m2/mo) and oral regimens (eg, 1-2.5 mg/kg/d) require careful monitoring of pertinent laboratory tests. Azathioprine and methotrexate (both antimetabolites) have similar toxic effects and also require careful monitoring. None of the immunosuppressant therapies are considered safe during pregnancy.
Antimetabolites
These agents inhibit cell growth and proliferation. They also have immunosuppressant properties.
Cyclophosphamide (Neosar, Cytoxan)
Alkylating agent with significant potential toxicity to bone marrow, liver, and bladder. Should be used only by experienced clinicians. Well-recognized toxicity of oral cyclophosphamide has led to institution of pulse therapy as present standard of care.
Adult
Pulse IV therapy regimens (eg, 600-800 mg/m2/mo) and PO regimens (eg, 1-2.5 mg/kg/d) require careful monitoring of pertinent laboratory tests
Pediatric
Not established
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult
Startup dosage and dosage regimen to steady state are variable; treatment with this drug should be attempted only by clinicians experienced in its use and in monitoring for its adverse effects
Pediatric
Not established
Allopurinol increases toxicity; ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity; breastfeeding
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution in patients with liver disease or renal impairment; hematologic toxic effects may occur; routine monitoring of CBC count necessary to watch for development of leukopenia, thrombocytopenia, or macrocytic anemia; rarely causes hepatotoxicity, but 2- 3-fold elevation of hepatic enzymes common; may increase risk of serious infections and neoplasia; 20-30% of patients will have severe flu-like reaction and cannot tolerate medication
Methotrexate (Folex-PFS)
Antimetabolite that inhibits DNA synthesis and cell reproduction in malignant cells; may suppress immune system. Satisfactory response seen in 3-6 wk following administration.
Adjust dose gradually to attain satisfactory response.
Adult
Startup dosage and dosage regimen to steady state are variable; treatment with this drug should be attempted only by clinicians experienced in its use and in monitoring for its adverse effects
Pediatric
Not established
Coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels
Oral aminoglycosides may decrease absorption and blood levels; charcoal lowers levels; etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines
Documented hypersensitivity; inadequate renal function (patients must have CrCl of 100 mL/min); inability to achieve hydration (as might occur with markedly raised intracranial pressure); concurrent immunosuppressive therapy; prior cranial irradiation; pregnancy or lactation; significant ascites or pleural effusions (third space accumulation may delay clearance); diabetes insipidus (complicates fluid management)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Major adverse effects include myelosuppression, mucositis, and renal toxicity; acute myelotoxicity occurs with nadir for anemia at 6-13 d, for leukopenia at 4-7 d, and for thrombocytopenia at 5-12 d; rapidly reversible liver dysfunction also occurs; leucovorin "rescue" allows minimization of systemic toxicity, markedly reducing bone marrow and mucosal toxicity, but cannot reverse renal toxicity; levels must be monitored daily after administration, and leucovorin continued until levels fall below 1 X 107 M
Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Meticorten, Orasone)
May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult
Startup dosage and dosage regimen to steady state are variable; treatment with this drug should be attempted only by clinicians experienced in its use and in monitoring for its adverse effects
Pediatric
Not established
Estrogens may decrease clearance; may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
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
Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur
More on Wegener Granulomatosis |
| Overview: Wegener Granulomatosis |
| Differential Diagnoses & Workup: Wegener Granulomatosis |
 Treatment & Medication: Wegener Granulomatosis |
| Follow-up: Wegener Granulomatosis |
| References |
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References
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Kerr GS, Fleisher TA, Hallahan CW, Leavitt RY, Fauci AS, Hoffman GS. Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener's granulomatosis. Arthritis Rheum. Mar 1993;36(3):365-71. [Medline].
Moore PM. Immune-mediated vasculopathies of the central nervous system. In: Gilchrist J, ed. Prognosis in Neurology. Boston, Mass: Butterworth-Heinemann; 1998.
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Spranger M, Schwab S, Meinck HM, Tischendorf M, Sis J, Breitbart A, et al. Meningeal involvement in Wegener's granulomatosis confirmed and monitored by positive circulating antineutrophil cytoplasm in cerebrospinal fluid. Neurology. Jan 1997;48(1):263-5. [Medline].
Tervaert JW, Huitema MG, Hené RJ, Sluiter WJ, The TH, van der Hem GK, et al. Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet. Sep 22 1990;336(8717):709-11. [Medline].
Travis WD, Hoffman GS, Leavitt RY, Pass HI, Fauci AS. Surgical pathology of the lung in Wegener's granulomatosis. Review of 87 open lung biopsies from 67 patients. Am J Surg Pathol. Apr 1991;15(4):315-33. [Medline].
Wegener F. [Uber eine eigenartige rhinogene Granulomatose mit besonderer Beteilgung des Arteriensytems und der Nieren]. Beitrage der Pathologischen Anatomie. 1939;102:30-68.
Further Reading
Keywords
Wegener's granulomatosis, granuloma, lymphomatoid granulomatosis, necrotizing inflammation, autoimmune disease, autoantibodies, neutrophil cytoplasmic antibodies, ANCA, c-ANCA, vasculitis, vasculitides, arteritis
