eMedicine Specialties > Pediatrics: General Medicine > Pulmonology
Wegener Granulomatosis: Treatment & Medication
Updated: Mar 5, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The mainstay of treatment for Wegener granulomatosis (WG) is a combination of corticosteroids and cytotoxic agents. Because the dosages and the manner of administration can vary according to the stage of treatment, the treatment section is separated into 3 parts: acute supportive treatment, induction therapy, and maintenance therapy.
- Acute supportive treatment
- From an immunosuppressive standpoint, most centers treat patients with either oral prednisone or intravenous methylprednisolone. Pulse methylprednisolone at a dose of 7-15 mg/kg/dose typically is administered in 3 successive doses followed by prednisone at 1-2 mg/kg/d.
- Cyclophosphamide (CYP) is administered in one of two ways. Many centers prefer oral CYP to induce a remission and optimally reduce the incidence of relapses. Others prefer intravenous CYP, which is as efficacious at inducing a remission as the oral preparation. Intravenous CYP can be administered safely with aggressive hydration and 2-mercaptoethane sulfonate sodium (mesna) to minimize the risk of hemorrhagic cystitis. Additionally, the cumulative dose tends to be much lower with the intravenous (IV) preparation, which should result in a reduction in dose-related long-term malignancy risks.
- Other treatments that have been used empirically but have not been well studied include plasma exchange and the use of intravenous immunoglobulin (IVIG). The former treatment brings the theoretical advantage of removing a circulating agent that may be causative, whereas the latter may be immunomodulating.
- Additional supportive treatments, such as oxygen, assisted ventilation, transfusion, extracorporeal membrane oxygenation (ECMO), and dialysis, have been used as life-saving measures.
- Plasma exchange (PE) appears to have a role in patients on dialysis but has not been helpful in patients with significant renal involvement that does not necessitate dialysis therapy. Jayne et al reported improved renal outcomes in adults with Wegener granulomatosis or microscopic polyangiitis (MPA) with severe renal failure (creatinine >5.8 mg/dL) who were treated with PE when compared to IV methylprednisolone.16 The patients in this multicenter European trial were also treated with oral prednisone and oral CYP at the time of enrollment.
- Induction immunosuppressive therapy
- This phase of treatment is defined arbitrarily as the period occurring between 2 weeks and 6 months after diagnosis. Oral corticosteroid therapy is administered typically as prednisone (1-2 mg/kg/d), which is continued for 1-3 months before being tapered down. Some centers taper to alternate day prednisone at a dose of 1-2 mg/kg qod 2 months into treatment. Others slowly reduce the dose of steroids that are continued on a daily basis, which is the authors' preference, especially in patients with generalized disease.
- With regard to the CYP dose, centers administering monthly CYP IV administer an initial dose of 500 mg/m2/dose and a WBC count performed 10-14 days later is used to determine the next dose. Dose increase in increments of 250 mg/m2/dose occurs to a maximum dose of 1000 mg/m2/dose. Oral CYP is administered at a starting dose of 2 mg/kg/d (not to exceed 150 mg). Dosage reductions occur based on the presence of leukopenia/neutropenia on WBC counts monitored weekly during the first 1-2 months.
- Approximately 10% of adult cases are unresponsive to conventional therapy of corticosteroids plus CYP. Rescue therapies may consist of IVIG and plasma exchange.
- Treatment of refractory disease (resistant to corticosteroids and CYP) has also been studied in small single center reports. Infliximab, a chimeric, monoclonal anti–tumor necrosis factor-alpha (TNF-alpha) antibody, was added to the standard therapy of CYP and steroids, and successfully induced a remission in 5 of 6 adult patients with disease previously unresponsive to therapy.
- Rituximab successfully induced a remission in 10 of 10 adult patients with previously refractory disease.17 In another trial, only 2 of 5 patients with Wegener granulomatosis and renal involvement improved with this regimen.15
- Maintenance immunosuppressive therapy
- This period is arbitrarily defined as the period that follows the first 6 months of treatment. The duration of treatment is quite debatable. Many adult centers now stop corticosteroids 3-4 months into therapy and discontinue all treatment as early as 6 months. Other centers use the 6-month cut off as a time to transition the patient to a less toxic regimen, substituting azathioprine (AZA) for CYP at this point. Rottem et al (1993) chose to treat children with oral CYP for 1 year after remission was achieved before reducing the dosage by 25 mg every 2 months as tolerated.10 Median treatment time with oral CYP was 28 months.
- This author's experience in children with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis and glomerulonephritis (GN) was to transition patients to AZA after a typical 6-month treatment period with CYP IV. A select group of patients who had either a poor response to CYP IV or life-threatening disease at presentation were treated with oral CYP, which was continued for 1 year. Those treated with oral CYP were changed at 1 year to either AZA or methotrexate (MTX) in an effort to provide sufficient immunosuppressive therapy while avoiding long-term use of CYP.
- Newer therapeutic regimens include the use of methotrexate (MTX) as a substitute for CYP during the induction stage of treatment. This has been tried in both children and adults. This agent appears to be reasonably effective (71% remission rate) if selectively used in patients with non–life-threatening forms of WG and when used in conjunction with corticosteroids. Its use may prove to be beneficial to patients with life-threatening WG if used in the maintenance phase of treatment; however, better studies are needed.
- AZA has been proven inferior to CYP during the induction phase of treatment but may have its greatest role in maintaining a remission state, as discussed above. It is far less toxic than CYP and usually is well tolerated.
- Mycophenolate mofetil (MMF), an immunosuppressive medication initially used successfully in renal transplantation, has relatively low toxicity and a lymphocyte selective mode of action. More recent indications include immunologic diseases, such as systemic lupus erythematosus (SLE) and nephrotic syndrome.
- Nowack et al (1999) suggested the use of MMF during the maintenance phase of treatment in 11 adult patients with ANCA-associated systemic vasculitis (9 WG patients, 2 MPA patients).18 Patients were started on a regimen of MMF and low-dose oral corticosteroids after a 14-week induction period with steroids and oral CYP. Outcome was assessed only to 15 months but was very good. Only 1 patient relapsed 14 months into the maintenance treatment phase. MMF was well tolerated at a dose of 2 g/d, with minimal side effects.
- Joy et al evaluated MMF in patients with non–life-threatening recurrent or cyclophosphamide resistant ANCA (+) small-vessel vasculitis.19 A 24-week treatment period in conjunction with corticosteroids resulted in a marked reduction in disease activity as assessed by the Birmingham Vasculitis Activity Scoring system. Thus, MMF may be useful in this setting to avoid recurrent treatment with alkylating agents.
- Trimethoprim-sulfamethoxazole (TMP-SMZ) has become a mainstay of Wegener granulomatosis treatment.
- Prior to its use, Pneumocystis carinii pneumonia occurred in 6% of the population with Wegener granulomatosis studied at the NIH. P carinii pneumonia occurred in patients being treated with both corticosteroids and cytotoxic drugs for either initial therapy or treatment of a relapse. More than one quarter of the patients had not had Wegener granulomatosis involvement of the lungs.
- Reports demonstrate TMP-SMZ use in isolation without other immunosuppressive medications in the induction phase of treatment in patients with very limited disease; however, prospective trials of TMP-SMZ as monotherapy have been disappointing. In adults, TMP-SMZ has been shown to prevent relapses of WG in remission.20 This action of TMP-SMZ may be due to anti-inflammatory action or decrease in infections, particularly respiratory tract infections. Because of the need for P carinii prophylaxis early in therapy and the ability of TMP-SMZ to prevent relapse, institute this therapy early and continue it during corticosteroid and cytotoxic therapy.
- Newer treatment strategies include blockade of TNF-alpha. Etanercept is a soluble TNF-alpha receptor blocker, which has been well studied in patients with Wegener granulomatosis. Results of the Wegener's Granulomatosis Etanercept Trial (WGET) Research Group studied of 180 patients with Wegener granulomatosis.21 Etanercept or placebo was added to standard maintenance therapy (steroids plus CYP or MTX). Etanercept had no significant reduction in sustained remission rates or percentage of patients experiencing a severe/life-threatening disease flare relative to controls. Solid cancers also developed in 6 patients in the etanercept group, compared with none in the control group (p=0.01). This agent is ineffective and potentially puts patients at an increased risk for complications; thus, it is not recommended.
- Treatment summary
- Currently, a typical approach to a patient with ANCA (+) vasculitis and GN is to treat with prednisone (1-2 mg/kg/d, not to exceed 80 mg) for 1-2 months before tapering. In patients with severe disease, tapering daily steroids every 2-4 weeks should be considered. In patients with primarily renal disease, consideration of a steroid taper to an alternate day dosing schedule should be considered.
- As for cytotoxic agents, CYP is administered for 6-12 months before changing to AZA. The decision on the duration of CYP is related to the severity of disease at its outset. Patients with non–life-threatening disease typically receive monthly CYP IV for 6 months in conjunction with corticosteroids. If in remission, the patient is changed to AZA at 2 mg/kg/d while steroids continue to be tapered slowly. Those with pulmonary hemorrhage (life-threatening disease) are treated with oral CYP for 1 year in conjunction with corticosteroids. Once again, AZA is substituted for CYP at 1 year if the patient is in remission. Remission is defined as lack of symptoms, stable renal function, benign findings on urinalysis (except for some proteinuria), and a stable erythrocyte sedimentation rate.
- Plasma exchange should be considered in patients with severe renal involvement, especially those that are dialysis dependent.
- Newer adult data raise the question of whether the induction treatment phase can be shortened to 3 months with transition from CYP to AZA. The European Vasculitis Study Group analyzed a group of 144 patients with ANCA-associated vasculitis (Wegener granulomatosis and microscopic polyangiitis) who achieved remission with induction therapy of prednisolone and CYP (2 mg/kg/d) for 3 months. After a 3-month induction phase, patients were randomized to CYP (1.5 mg/kg/d) or AZA (2 mg/kg/d). Remission rates and side effects were similar in both groups. The authors concluded that once remission is achieved with a 3-month course of prednisolone and CYP, patients can be safely switched from CYP to AZA to reduce the exposure to CYP.
- It has been the author's approach to perform a repeat renal biopsy to confirm a histologic remission before transitioning off of CYP. As mentioned above, patients are started on TMP-SMZ at the outset of induction treatment for P carinii prophylaxis and are continued during the maintenance phase of treatment in an effort to reduce disease relapses.
- Agents such as MMF and rituximab warrant further study.22
Surgical Care
The role of surgery in Wegener granulomatosis is adjunctive and only rarely indicated.
- If a sinus biopsy is desired, an otolaryngologist should be consulted. An additional indication for ears, nose, and throat (ENT) surgery would be airway reconstructive surgery for subglottic stenosis failing intratracheal dilatation.
- Urgent surgical decompression of the orbit may be necessary when visual impairment is due to stretching or compression of the optic nerve.
Consultations
- Pediatricians seeing patients with suspected Wegener granulomatosis , ANCA-associated vasculitis, or pulmonary renal syndrome should involve a pediatric medical subspecialist with additional expertise in this area, such as a pediatric nephrologist, pulmonologist, or rheumatologist.
- In addition, a baseline ophthalmologic examination should be considered.
- If a sinus biopsy is desired, an otolaryngologist should be consulted.
Diet
Because of the risks of salt and water retention when on corticosteroids, pediatric patients are usually restricted to 2 mEq/kg/d of sodium (molecular weight 23 mg/mEq). The sodium intake should not exceed 2000 mg/d.
- Patients on oral CYP are asked to drink approximately 2000 mL/m2/d and attempt to void every 4 hours to maintain high urine output and reduce the risk of hemorrhagic cystitis.
- Similarly, oral CYP should be taken as a one-time dose upon awakening in the morning to avoid high bladder concentrations in the middle of the night when fluid intake diminishes.
Activity
- Contact sports are to be avoided for 1 month following a kidney biopsy. Otherwise, activities are as tolerated.
- Because patients are immunosuppressed, patients should attempt to minimize exposure to ill contacts.
Medication
Medications for the treatment of Wegener granulomatosis (WG) include immunosuppressive medications (ie, corticosteroids, cytotoxic agents) and TMP-SMZ (ie, methylprednisolone or prednisone, cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil, and TMP-SMZ).
Systemic corticosteroids
Immunosuppressant and anti-inflammatory action used to reduce activity of systemic vasculitis. High-dose methylprednisolone is used to halt pulmonary hemorrhage and reverse crescentic glomerulonephritis (GN). Decreases inflammation by suppression of migration of polymorphonuclear neutrophils (PMNs) and reversal of increased capillary permeability.
Methylprednisolone (Solu-Medrol)
Used to treat pulmonary hemorrhage and/or rapidly progressive glomerulonephritis (RPGN). Patients with >50% crescents on renal biopsy who do not necessarily have a rising serum creatinine are good candidates for pulse methylprednisolone therapy.
Adult
Up to 1 g/d IV for 3-5 consecutive d; follow pulse IV dose regimen with PO prednisone
Pediatric
Pulse dose: 10-30 mg/kg IV qd for 3-5 consecutive d; not to exceed 1 g/d; follow pulse dose regimen with PO prednisone
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity; coadministration of live-virus vaccines; systemic fungal infections
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 caution in patients with hypothyroidism, cirrhosis, hypertension, CHF, ulcerative colitis, and thromboembolic disorders; hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use
Prednisone (Deltasone, Meticorten, Orasone, Sterapred)
Initially instituted after pulse methylprednisolone treatment is completed. Taper is based on clinical response and adverse effects.
Adult
80 mg PO qd or divided bid
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 administered once every am for 1 additional mo before tapering (Taper can vary from reduction of daily dose to changing to qod regimen [see above])
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin 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; varicella; serious infections; systemic fungal infections
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 hypothyroidism, cirrhosis, hypertension, CHF, ulcerative colitis, and thromboembolic disorders; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Alkylating agents (cytotoxic agents)
Interfere with inflammatory response by decreasing bone marrow response through the interference of DNA cross-linking.
Cyclophosphamide (Cytoxan, Neosar)
Potent immunosuppressant that markedly improved the outcome of patients with WG when first used in the 1970s. Ideal for induction of remission. Can be administered IV or PO. Both methods are similar in inducing remission, but PO is associated with fewer relapses. Because the adverse effects are often dose related, PO administration, which is needed in higher cumulative doses, has more adverse effects. Duration of therapy varies from 3 mo to at least 1 y. Used in addition to corticosteroids.
Adult
PO: 150 mg PO qd
IV: Up to 1 g/m2/dose
IV every mo; titrate dose to maintain WBC count
Pediatric
Initial dose: 500 mg/m2/dose IV every mo; subsequent increase to 750 mg/m2/mo based on WBC count measured 10-14 d after dose; not to exceed 1 g/m2/mo
PO: 2 mg/kg/d PO; not to exceed 150 mg/dose
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects of cyclophosphamide; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life of cyclophosphamide while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; 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
Use with caution in setting of bone marrow suppression, renal impairment, or hepatic dysfunction; dosage reduction required for renal impairment and bone marrow suppression
Immunosuppressive agents
Patients with immune dysregulation and autoimmunity often benefit from immunosuppression. Adjunctive immunosuppressants may be used in place of cyclophosphamide. Administered in addition to corticosteroids.
Azathioprine (Imuran)
Antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. May interfere with mitosis and cellular metabolism. Used as second-line agent in relation to cyclophosphamide. Typically is substituted for cyclophosphamide in patients during remission who have received 6-12 mo of cyclophosphamide. Is used in conjunction with corticosteroids.
Adult
2 mg/kg/d PO/IV qd; may increase up to 3 mg/kg/d; IV dose may be administered qd or divided q12h
Pediatric
Administer as in adults
Toxicity increases with allopurinol (decrease azathioprine dose by 25-33%); concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level before therapy and monitor liver, renal, and hematologic function; pancreatitis rarely associated
Methotrexate (Folex PFS, Rheumatrex)
An antimetabolite that binds dihydrofolate reductase, leading to a reduction of tetrahydrofolic acid and resulting in decreased DNA and purine synthesis. Used as a cyclophosphamide-sparing agent during maintenance therapy. Used for induction therapy in place of cyclophosphamide in patients with limited disease.
Adult
Initial test dose: 0.3 mg/kg/wk PO; not to exceed 15 mg/wk; dosage may be divided into 2 or 3 doses if GI symptoms occur; if GI symptoms persist, dose is administered IM qwk; titrate q1-2wk; not to exceed 25 mg/wk
Pediatric
Initial dose: 0.3 mg/kg/wk PO/IM; not to exceed 15 mg; dose is taken as a single dose once per wk PO and is increased up to 0.6 mg/kg/wk; not to exceed 25 mg/wk
PO aminoglycosides may decrease absorption and blood levels; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; 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
Use with caution in peptic ulcer disease, ulcerative colitis, preexisting bone marrow suppression, renal impairment, or hepatic impairment; 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 exists [eg, dehydration]); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood cell counts occurs; aspirin, NSAIDs, or low-dose corticosteroids may be administered concomitantly (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)
Mycophenolate mofetil (CellCept)
Inhibits T-cell and B-cell proliferation, resulting in reduced cytotoxic T cells and antibody production. Recent adult WG studies suggest a role during the maintenance phase of therapy as a substitute for cyclophosphamide. No published reports exist of its use for WG in children. Pediatric safety experience best studied in pediatric renal transplantation.
Adult
1 g PO bid
Pediatric
Not established for WG
Transplant dose: 600 mg/m2/dose PO bid; not to exceed 2 g/d
May elevate levels of acyclovir and ganciclovir; antacids and cholestyramine decreases absorption, reducing levels (do not administer together); probenecid may increase levels of mycophenolate; salicylates may increase toxicity of mycophenolate
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Use with caution in patients with active GI disease because of high incidence of gastritis; modify dose in patients with neutropenia, increases risk for infection; increases toxicity in patients with renal impairment
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)
A chimeric (murine/human) monoclonal IgG directed against CD20 antigen. Antibody is an IgG1 kappa immunoglobulin containing murine light-chain and heavy-chain variable region sequences and human constant region sequences. This CD20 antigen is expressed on pre-B and mature B lymphocytes. B-cell lysis occurs and results in depletion with reduction of IgM and IgG. The rationale for its use in WG is reduced ANCA production. Reduced number of B cells also results in interference with antigen presentation-another B-cell function. B cells remain depleted for 6-9 months.
Adult
375 mg/m2/dose given IV qwk for 4 doses
Pediatric
Not established
Data limited; coadministration with cisplatin causes severe renal toxicity including acute renal failure; does not appear to interact with cyclophosphamide or methotrexate when used concomitantly in rheumatoid arthritis; may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity; IgE-mediated reaction to murine proteins; relative contraindications include active or subclinical 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
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; severe reactions can occur with the first infusion (administer slowly and monitor, do not administer IV push or bolus); anaphylaxis kit with glucocorticoids, epinephrine, bronchodilators, and oxygen should be at the bedside; discontinue treatment if life-threatening cardiac arrhythmias occur; may cause renal failure
Antibiotics
Indicated to prevent infections and possibly disease relapses.
Sulfamethoxazole and trimethoprim (Bactrim, Septra, Cotrim)
Used to prevent or reduce the incidence of P carinii pneumonia in immunosuppressed patients. This may prevent systemic disease relapses by reducing respiratory relapses through antibiotic or unknown immunosuppressive mechanism.
Adult
160 mg TMP/800 mg SMZ PO q12h
Pediatric
<2 months: Contraindicated
>2 months: 5 mg/kg/d PO divided bid, based on TMP component; not to exceed 320 mg/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 people; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Documented hypersensitivity; megaloblastic anemia due to folate deficiency; age <2 mo
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
Do not use in pregnancy near term (risk of kernicterus); 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; caution in folate deficiency (eg, chronic alcoholism, elderly patients, those receiving anticonvulsant therapy, malabsorption syndrome); hemolysis may occur in G-6-PD deficiency; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation
More on Wegener Granulomatosis |
| Overview: Wegener Granulomatosis |
| Differential Diagnoses & Workup: Wegener Granulomatosis |
 Treatment & Medication: Wegener Granulomatosis |
| Follow-up: Wegener Granulomatosis |
| Multimedia: Wegener Granulomatosis |
| References |
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References
Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. Feb 1994;37(2):187-92. [Medline].
Breda L, Nozzi M, De Sanctis S, Chiarelli F. Laboratory Tests in the Diagnosis and Follow-Up of Pediatric Rheumatic Diseases: An Update. Semin Arthritis Rheum. Feb 24 2009;[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].
Hogan SL, Satterly KK, Dooley MA, Nachman PH, Jennette JC, Falk RJ. Silica exposure in anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and lupus nephritis. J Am Soc Nephrol. Jan 2001;12(1):134-42. [Medline].
Schlieben DJ, Korbet SM, Kimura RE, Schwartz MM, Lewis EJ. Pulmonary-renal syndrome in a newborn with placental transmission of ANCAs. Am J Kidney Dis. Apr 2005;45(4):758-61. [Medline].
Cotch MF, Hoffman GS, Yerg DE, Kaufman GI, Targonski P, Kaslow RA. The epidemiology of Wegener's granulomatosis. Estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources. Arthritis Rheum. Jan 1996;39(1):87-92. [Medline].
US Renal Data System. Annual Data Report. In: Atlas of End-Stage Renal Disease in the United States. Vol 2. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2008.
North American Pediatric Renal Trials and Collaborative Studies 2007. Annual Report. Dialysis Access Data. NAPRTCS. Available at https://web.emmes.com/study/ped/. Accessed February 12, 2009.
Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. Mar 15 1992;116(6):488-98. [Medline].
Rottem M, Fauci AS, Hallahan CW, et al. Wegener granulomatosis in children and adolescents: clinical presentation and outcome. J Pediatr. Jan 1993;122(1):26-31. [Medline].
Ellis EN, Wood EG, Berry P. Spectrum of disease associated with anti-neutrophil cytoplasmic autoantibodies in pediatric patients. J Pediatr. Jan 1995;126(1):40-3. [Medline].
Valentini RP, Smoyer WE, Sedman AB, Kershaw DB, Gregory MJ, Bunchman TE. Outcome of antineutrophil cytoplasmic autoantibodies-positive glomerulonephritis and vasculitis in children: a single-center experience. J Pediatr. Feb 1998;132(2):325-8. [Medline].
Hattori M, Kurayama H, Koitabashi Y. Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in children. J Am Soc Nephrol. Jul 2001;12(7):1493-500. [Medline].
Luqmani RA, Bacon PA, Moots RJ, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. Nov 1994;87(11):671-8. [Medline].
Sneller MC. Rituximab and Wegener's granulomatosis: are B cells a target in vasculitis treatment?. Arthritis Rheum. Jan 2005;52(1):1-5. [Medline].
[Best Evidence] Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. Jul 2007;18(7):2180-8. [Medline].
Keogh KA, Ytterberg SR, Fervenza FC, Carlson KA, Schroeder DR, Specks U. Rituximab for refractory Wegener's granulomatosis: report of a prospective, open-label pilot trial. Am J Respir Crit Care Med. Jan 15 2006;173(2):180-7. [Medline].
Nowack R, Gobel U, Klooker P, Hergesell O, Andrassy K, van der Woude FJ. Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement. J Am Soc Nephrol. Sep 1999;10(9):1965-71. [Medline].
Joy MS, Hogan SL, Jennette JC, Falk RJ, Nachman PH. A pilot study using mycophenolate mofetil in relapsing or resistant ANCA small vessel vasculitis. Nephrol Dial Transplant. Dec 2005;20(12):2725-32. [Medline].
Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Engl J Med. Jul 4 1996;335(1):16-20. [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].
Patel AM, Lehman TJ. Rituximab for severe refractory pediatric Wegener granulomatosis. J Clin Rheumatol. Oct 2008;14(5):278-80. [Medline].
Gottlieb BS, Miller LC, Ilowite NT. Methotrexate treatment of Wegener granulomatosis in children. J Pediatr. Oct 1996;129(4):604-7. [Medline].
Hoffman GS, Leavitt RY, Kerr GS, Fauci AS. The treatment of Wegener's granulomatosis with glucocorticoids and methotrexate. Arthritis Rheum. Nov 1992;35(11):1322-9. [Medline].
Hogan SL, Nachman PH, Wilkman AS, Jennette JC, Falk RJ. Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol. Jan 1996;7(1):23-32. [Medline].
Jagiello P, Aries P, Arning L, et al. The PTPN22 620W allele is a risk factor for Wegener's granulomatosis. Arthritis Rheum. Dec 2005;52(12):4039-43. [Medline].
Jayne D, Rasmussen N, Andrassy K, 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].
Kist-van Holthe JE, Ho PL, Stablein D, Harmon WE, Baum MA. Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant. Jun 2005;9(3):305-10. [Medline].
Lamprecht P, Voswinkel J, Lilienthal T, et al. Effectiveness of TNF-alpha blockade with infliximab in refractory Wegener's granulomatosis. Rheumatology (Oxford). Nov 2002;41(11):1303-7. [Medline].
Lynch JP 3rd, Hoffman GS. Wegener's granulomatosis: controversies and current concepts. Compr Ther. Sep 1998;24(9):421-40. [Medline].
Pediatric end-stage renal disease. USRDS. United States Renal Data System. Am J Kidney Dis. Aug 1997;30(2 Suppl 1):S128-44. [Medline].
Sneller MC, Fauci AS. Pathogenesis of vasculitis syndromes. Med Clin North Am. Jan 1997;81(1):221-42. [Medline].
Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook. 4th ed. Hudson, Ohio: Lexi-comp Inc; 1997.
Further Reading
Keywords
Wegener granulomatosis, WG, Wegener's granulomatosis, ANCA disease, antineutrophil cytoplasmic autoantibodies disease, ANCA-associated vasculitis, ANCA-associated glomerulonephritis, ANCA-associated GN, antineutrophil cytoplasmic autoantibodies–associated vasculitis, antineutrophil cytoplasmic autoantibodies–associated glomerulonephritis, antineutrophil cytoplasmic autoantibodies–associated GN, pulmonary renal syndrome, necrotizing granulomatous lesions of the upper or lower respiratory tract, generalized necrotizing vasculitis involving both arteries and veins, focal necrotizing glomerulonephritis, microscopic polyangiitis, Churg-Strauss syndrome, microscopic polyangiitis, MPA, end-stage renal disease, ESRD, sinusitis, otitis media, subglottic stenosis, pulmonary infiltrates, pulmonary nodules, hemoptysis, hematuria, proteinuria, arthralgia, arthritis, rhinorrhea, epistaxis, pharyngitis, congestive heart failure, CHF
