eMedicine Specialties > Dermatology > Diseases of the Vessels
Wegener Granulomatosis: Treatment & Medication
Updated: Jun 5, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Aggressive medical therapy is usually necessary to control pulmonary and renal involvement.
- Immunosuppressive therapy with cyclophosphamide (CYC) at 2 mg/kg/d up to 200 mg/d and corticosteroids at 0.5-1 mg/kg/d up to 80 mg/d is the treatment of choice for remission induction.
- Glucocorticoids are tapered after 1 month of therapy and discontinued within 6-9 months. CYC is discontinued one full year after remission.3
- After 3-6 months beyond induction of remission, azathioprine, methotrexate (MTX), and leflunomide may be useful as adjuncts for transition to remission-maintenance therapy.6
- Local disease may be controlled with glucocorticoids.
- Trimethoprim and sulfamethoxazole (Bactrim) and potassium iodide (SSKI) have been reported to be useful in a small number of patients.
- Infliximab may be used at dosages of 3-5 mg/kg for adjunctive treatment of WG, with infusions every 4 weeks following induction. Anecdotal evidence indicates a dose-response phenomenon, with higher doses leading to more remissions.
- Remission with rituximab therapy has been shown in a small number of patients with disease refractory to other medications.7
- Predictors of treatment resistance include female sex, black race, and presentation with severe renal disease.
- Predictors of relapse following remission include anti-PR3 seropositivity, upper respiratory tract involvement, and lung involvement.
- In the results of a small study, minimally invasive procedures such as intralesional steroid injections had a more favorable outcome than invasive surgery when treating tracheobronchial WG in specific cases.8
The Medscape CME course Risks of Immunosuppressive Therapies Including Biologic Agents in Patients With Rheumatic Diseases and Co-Existing Chronic Viral Infections may be of interest.
Surgical Care
- Some patients may require myringotomy for chronic otitis media.
- Airway obstruction due to severe subglottic stenosis may necessitate tracheostomy.
- Renal transplantation may be considered in patients with controlled disease. Glomerulonephritis usually does not affect the transplanted kidney.
Consultations
- Internal medicine specialists best coordinate patient care.
- Consult a pulmonologist and a nephrologist to help manage and evaluate the extent of respiratory and renal disease, respectively.
- Consult with an ear, nose, and throat (ENT) specialist to help diagnose and manage upper respiratory tract disease.
- Other consultations may be necessary, depending on the affected systems and extent of disease.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Antineoplastics
CYC is the treatment of choice. Therapy is usually continued for 6-12 months following remission. Many authorities continue immunosuppressive therapy past 12 months because of the high rate of relapse. Corticosteroids (eg, prednisone, prednisolone) are usually combined with CYC at the beginning of treatment, but they are tapered over 3-6 months. MTX may be used as an alternative to CYC in the initial treatment of early disease; however, CYC is superior for remission induction in cases of pulmonary or extensive involvement. Trimethoprim and sulfamethoxazole and potassium iodide have been less frequently reported to be effective in treating WG.
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards. As an alkylating agent, mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
Daily oral dose: 2 mg/kg/d PO qd
IV pulse therapy: 0.5 g/m2 IV every month for 6 mo; adjust subsequent doses to maintain WBC of 3-5 X 103/µL
Pediatric
Administer as in adults
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; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong CYC-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
Caution in leukopenia, thrombocytopenia, previous therapy with other cytotoxic agents or radiation, or impaired renal or hepatic function; associated with numerous potentially serious adverse events, including risk of malignancy, sterility, hemorrhagic cystitis, cardiac toxicity, and serious infection secondary to immune suppression; other common adverse events include nausea, vomiting, and alopecia (anagen effluvium); monitor closely for neutropenia and microscopic hematuria; patients should maintain substantial water intake and void frequently during treatment
Methotrexate (Folex, Rheumatrex)
Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Antimetabolite that inhibits DNA synthesis and cell reproduction in malignant cells; may suppress immune system. Satisfactory response seen 3-6 wk following administration. Adjust dose gradually to attain satisfactory response.
Adult
0.3 mg/kg/wk PO/IM; not to exceed 20 mg
Pediatric
5-15 mg/m2/wk PO/IM single dose or 3 divided doses given 12 h apart
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response to MTX; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; 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; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood cell counts; aspirin, NSAIDs, or low-dose steroids may be concomitantly administered (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)
Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Orasone, Meticorten, Deltasone, Sterapred)
Widely used synthetic glucocorticoid that exerts metabolic effects on multiple organ systems and is commonly used in inflammatory diseases for its potent anti-inflammatory properties. High-dose glucocorticoids may induce more rapid control at the beginning of treatment; however, steroid-sparing drugs (eg, CYC) are needed to control more aggressive cases.
Adult
1 mg/kg/d PO
Pediatric
Administer as in adults
Phenytoin, phenobarbital, ephedrine, and rifampin enhance metabolic clearance of corticosteroids; hypokalemia may develop in patients concomitantly treated with potassium-wasting diuretics; corticosteroids may affect anticoagulant effects of coumarin
Documented hypersensitivity; 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
Adrenal insufficiency may develop after prolonged therapy with corticosteroids; symptoms of corticosteroid withdrawal include fever, malaise, myalgia, and arthralgia; corticosteroid therapy should be slowly tapered; corticosteroids may induce or exacerbate psychiatric derangements, ranging from insomnia and euphoria to frank psychosis; impairs wound healing; caution in patients with uncontrolled systemic infections, ocular herpes simplex, renal insufficiency, hypertension, peptic ulcer disease, or myasthenia gravis
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in this clinical setting.
Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Adult
160 mg TMP/800 mg SMZ PO q12h for 10-14 d
Pediatric
<2 months: Do not administer
> 2 months: 15-20 mg/kg/d, based on TMP, PO tid/qid for 14 d
May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of MTX in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase zidovudine levels
Documented hypersensitivity; megaloblastic anemia due to 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
Discontinue at first appearance of rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, persons with long-term alcoholism, elderly persons, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in persons with G-6-PD deficiency; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation
Antithyroids
Most commonly used therapy for this condition is oral potassium iodide.
Potassium iodide (SSKI, Pima)
Works via potassium concentration in granulomas, which releases heparin and inhibits delayed-type hypersensitivity response.
Adult
300-500 mg PO (6-10 gtt) tid
Pediatric
Infants: 150-250 mg (3-6 gtt) PO tid
Children: Administer as in adults
Increases lithium toxicity by producing additive hypothyroid effects
Documented hypersensitivity; pulmonary edema; bronchitis; tuberculosis; hyperkalemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Prolonged use may result in hypothyroidism; caution in renal failure and GI obstruction
Biologics/TNF-alpha inhibitors
TNF-alpha may play a role in ANCA-associated activation of neutrophils and monocytes and/or in neutrophil adherence to endothelial cells. Of note, results of the Wegener's Granulomatosis Etanercept Trial (WGET)9 have shown no effectiveness of etanercept (Enbrel) in the maintenance of disease remission. A high rate of complications was noted in the etanercept group, including a higher rate of solid cancer development.
Infliximab (Remicade)
Infusible chimeric IgG1 monoclonal anti-TNF-alpha antibody approved for the treatment of Crohn disease, rheumatoid arthritis, and psoriatic arthritis. Limited data have shown remission induction in cases refractory to standard CYC and corticosteroid combination therapy with the addition of infliximab. May allow reduction in corticosteroid dosages once remission occurs.
Adult
3-5 mg/kg IV at weeks 0, 2, and 6, with maintenance infusions given q4-6wk after induction; may be increased up to 10 mg/kg
Used at dosages of 3-5 mg/kg for adjunctive treatment of WG, with infusions q4wk following induction; anecdotal evidence indicates dose-response phenomenon, with higher dosages leading to more remissions
Pediatric
Administer as in adults
None reported
Patients with moderate-to-severe heart failure may have worsening of heart failure; relatively contraindicated in uncontrolled infections; tuberculosis or PPD-positive patients should be treated for tuberculosis prior to infliximab initiation
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Black box warning for serious infections, including tuberculosis, histoplasmosis, listeriosis, pneumocystosis, and coccidioidomycosis
Antibody production against infliximab may lead to rare cases of lupuslike syndrome; incidence of lymphoma and other malignancies is 3-5 times higher in rheumatoid arthritis patients treated; rare cases of hepatotoxicity may occur
Azathioprine (Imuran, Azasan)
Has been shown in trials to be an effective substitution for CYC after induction of remission with standard CYC/corticosteroid therapy in systemic vasculitides, including WG. Relapse rates, however, are higher in WG compared with microscopic polyangiitis.
Adult
2 mg/kg/d with corticosteroid therapy
Pediatric
Administer as in adults
Use with TMP-SMZ or ACE inhibitors may induce severe leukopenia
Documented hypersensitivity; low thiopurine methyltransferase activity; relatively contraindicated in patients who have received high-dose CYC therapy due to risk of malignancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause GI hypersensitivity; thioguanine methyltransferase levels should be determined prior to therapy initiation; potential mutagen, with increased risk of neoplasia
Rituximab (Rituxan)
The (rituximab) antibody is a chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.
Adult
375 mg/m2 qwk for 4 wk
Pediatric
Not established
Coadministration with cisplatin 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 vaccination)
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
Severe infusion reactions, tumor lysis syndrome, hepatitis B reactivation with related fulminant hepatitis and other viral infections, and progressive multifocal leukoencephalopathy have been reported with therapy
More on Wegener Granulomatosis |
| Overview: Wegener Granulomatosis |
| Differential Diagnoses & Workup: Wegener Granulomatosis |
 Treatment & Medication: Wegener Granulomatosis |
| Follow-up: Wegener Granulomatosis |
| Multimedia: Wegener Granulomatosis |
| References |
| « Previous Page | Next Page » |
References
Harper L, Savage CO. Pathogenesis of ANCA-associated systemic vasculitis. J Pathol. Feb 2000;190(3):349-59. [Medline].
Erickson VR, Hwang PH. Wegener's granulomatosis: current trends in diagnosis and management. Curr Opin Otolaryngol Head Neck Surg. Jun 2007;15(3):170-6. [Medline].
Mubashir E, Ahmed MM, Hayat S, Latif S, Heldmann M, Berney SM. Wegener granulomatosis: a case report and update. South Med J. Sep 2006;99(9):977-88. [Medline].
Stegeman CA, Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med. Jan 1 1994;120(1):12-7. [Medline].
Savige J, Gillis D, Benson E, Davies D, Esnault V, Falk RJ, et al. International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA). Am J Clin Pathol. Apr 1999;111(4):507-13. [Medline].
Wung PK, Stone JH. Therapeutics of Wegener's granulomatosis. Nat Clin Pract Rheumatol. Apr 2006;2(4):192-200. [Medline].
Antoniu SA. Treatment options for refractory Wegener's granulomatosis: a role for rituximab?. Curr Opin Investig Drugs. Nov 2007;8(11):927-32. [Medline].
Nouraei SA, Obholzer R, Ind PW, Salama AD, Pusey CD, Porter F, et al. Results of endoscopic surgery and intralesional steroid therapy for airway compromise due to tracheobronchial Wegener's granulomatosis. Thorax. Jan 2008;63(1):49-52. [Medline].
Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. Jan 27 2005;352(4):351-61. [Medline].
Barksdale SK, Hallahan CW, Kerr GS, Fauci AS, Stern JB, Travis WD. Cutaneous pathology in Wegener's granulomatosis. A clinicopathologic study of 75 biopsies in 46 patients. Am J Surg Pathol. Feb 1995;19(2):161-72. [Medline].
Daoud MS, Gibson LE, DeRemee RA, Specks U, el-Azhary RA, Su WP. Cutaneous Wegener's granulomatosis: clinical, histopathologic, and immunopathologic features of thirty patients. J Am Acad Dermatol. Oct 1994;31(4):605-12. [Medline].
[Best Evidence] De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. Aug 2005;52(8):2461-9. [Medline].
Duna GF, Galperin C, Hoffman GS. Wegener's granulomatosis. Rheum Dis Clin North Am. Nov 1995;21(4):949-86. [Medline].
Fauci AS. Wegener's granulomatosis. In: Fauci AS, Braunwald E, Isselbacher, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:1914-7.
Fauci AS, Gallo RC, Koenig S, Salk J, Purcell RH. NIH conference. Development and evaluation of a vaccine for human immunodeficiency virus (HIV) infection. Ann Intern Med. Mar 1 1989;110(5):373-85. [Medline].
Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. Jan 1983;98(1):76-85. [Medline].
Francès C, Du LT, Piette JC, Saada V, Boisnic S, Wechsler B, et al. Wegener's granulomatosis. Dermatological manifestations in 75 cases with clinicopathologic correlation. Arch Dermatol. Jul 1994;130(7):861-7. [Medline].
Hellmich B, Lamprecht P, Gross WL. Advances in the therapy of Wegener's granulomatosis. Curr Opin Rheumatol. Jan 2006;18(1):25-32. [Medline].
Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. Mar 15 1992;116(6):488-98. [Medline].
Hogan SL, Falk RJ, Chin H, Cai J, Jennette CE, Jennette JC, et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med. Nov 1 2005;143(9):621-31. [Medline].
Hu CH, O'Loughlin S, Winkelmann RK. Cutaneous manifestations of Wegener granulomatosis. Arch Dermatol. Feb 1977;113(2):175-82. [Medline].
Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniené J, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. Jul 3 2003;349(1):36-44. [Medline].
Jennette JC, Ewert BH, Falk RJ. Do antineutrophil cytoplasmic autoantibodies cause Wegener's granulomatosis and other forms of necrotizing vasculitis?. Rheum Dis Clin North Am. Feb 1993;19(1):1-14. [Medline].
Jennette JC, Falk RJ. Antineutrophil cytoplasmic autoantibodies and associated diseases: a review. Am J Kidney Dis. Jun 1990;15(6):517-29. [Medline].
Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. Feb 1994;37(2):187-92. [Medline].
Jennette JC, Woosley JT, Falk RJ. Microscopic polyarteritis, Wegener's granulomatosis, and Churg-Strauss syndrome. J Cutan Med Surg. 1996;522-7.
Lamprecht P, Voswinkel J, Lilienthal T, Nolle B, Heller M, Gross WL, et al. Effectiveness of TNF-alpha blockade with infliximab in refractory Wegener's granulomatosis. Rheumatology (Oxford). Nov 2002;41(11):1303-7. [Medline].
Mangold MC, Callen JP. Cutaneous leukocytoclastic vasculitis associated with active Wegener's granulomatosis. J Am Acad Dermatol. Apr 1992;26(4):579-84. [Medline].
Patten SF, Tomecki KJ. Wegener's granulomatosis: cutaneous and oral mucosal disease. J Am Acad Dermatol. May 1993;28(5 Pt 1):710-8. [Medline].
Further Reading
Keywords
Wegener's granulomatosis, WG
