eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Granulomatosis Diseases

Wegener Granulomatosis: Treatment & Medication

Author: Neil Tanna, MD, MBA, Staff Physician, Division of Otolaryngology-Head and Neck Surgery, The George Washington University
Coauthor(s): Charles A Elmaraghy, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Ohio State University Medical Center; Douglas R Sidell, MD, Resident Physician, Department of Otolaryngology-Head and Neck Surgery, University of California at Los Angeles Medical Center; John Boone, MD, Consulting Staff, Department of Otolaryngology, Naval Hospital Oak Harbor
Contributor Information and Disclosures

Updated: Mar 24, 2008

Treatment

Medical Care

Immunosuppression using a combination of glucocorticoids and cyclophosphamide is the mainstay for treatment of generalized WG. Complete remission or a marked improvement is seen in more than 90% of cases. However, patients receiving such therapy experience relatively high incidences of relapse (50%) and drug-related toxicity (40%).

The substitution of methotrexate in place of cyclophosphamide after the former has induced remission has gained favor because of methotrexate's lower toxicity profile. In combination with glucocorticoids, methotrexate may also play a role in the initial treatment of limited disease. Trimethoprim-sulfamethoxazole (TMP-SMZ) may be of benefit to reduce relapses and may be useful as a sole agent in patients with extremely limited disease. As a prophylactic measure to reduce Pneumocystis carinii infections, recommendations for TMP-SMZ also include all patients who are taking cyclophosphamide or methotrexate and prednisone. The use of cotrimoxazole during remission periods as a means to control infection and improve quality of life in both localized and generalized WG patients has also been reported with good results.2,4

Intravenous immunoglobulin (IVIG): Some positive results have been demonstrated using IVIG in patients with cases of WG that are refractory to immunosuppressive treatment.4

Plasmapheresis: Plasma exchange has been used with WG patients who are dialysis dependent and those who have rapidly progressive glomerulonephritis (RPGN).2,4

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Glucocorticoids

These are used in combination with cytotoxic agents. Glucocorticoids are ineffective when used alone in generalized WG. Palliation of limited disease may be achieved by using glucocorticoids alone, but relapses and progression are common.


Prednisone (Deltasone, Meticorten, Orasone)

Used as an immunosuppressant in the treatment of autoimmune disorders and vasculitis. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.
Tapering of glucocorticoids precedes that of the cytotoxic agent.

Adult

1 mg/kg/d PO

Pediatric

Not established

Coadministration with estrogens may decrease 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; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; and fungal or tubercular skin infections; GI disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

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

Cytotoxic agents

These agents treat by inhibiting key factors responsible for deregulated cell proliferation.


Cyclophosphamide (Cytoxan, Neosar)

Used in combination with glucocorticoids in treatment of generalized WG.

Adult

2 mg/kg/d PO

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; coadministration with 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

X - Contraindicated; benefit does not outweigh risk

Precautions

Life-threatening conditions, such as renal failure and pulmonary hemorrhage, may occur; initiate at 3-5 mg/kg/d PO, then taper to usual dose; use leukocyte count to titer subsequent doses; continue for 1 y following clinical remission; toxicities include dose-related bone marrow suppression, hemorrhagic cystitis, bladder fibrosis, transitional cell carcinoma of the bladder, increased incidence of lymphoma


Methotrexate (Folex PFS, Rheumatrex)

Used as substitute for cyclophosphamide after initial remission of the disease to reduce toxicity and relapse. May also have a role in combination with GC in initial treatment of patients with limited disease.

Adult

1 double-strength tab PO bid

Pediatric

Not established

PO aminoglycosides may decrease absorption and blood levels of concurrent PO methotrexate (MTX); activated charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity of MTX; 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 MTX plasma levels; may decrease phenytoin serum levels
Probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; 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); renal insufficiency

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Monitor CBCs monthly and liver and renal function q1-3mo during therapy (monitor more frequently in initial dosing, dose adjustments, or risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems
Discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, eg, salicylates, not yet tested)

Antibiotics

Therapy must cover all likely pathogens in the context of this clinical setting.


Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Presumed to act by reducing microorganisms, serving as an antigenic primer in the pathogenesis of WG. May be beneficial for reducing relapses in patients with limited upper respiratory tract disease. Therapeutic role, if any, to be determined. Used in prophylaxis of Pneumocystis carinii.

Adult

Septra DS: 1 tab PO bid

Pediatric

Not established

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 methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency

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

Patients taking methotrexate can safely receive TMP-SMZ 3 times weekly for prophylaxis of P carinii, but they should not receive TMP-SMZ twice daily because this combination has been associated with severe pancytopenia; discontinue at first appearance of rash or sign of adverse reaction; obtain CBCs 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, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholism, elderly age, current anticonvulsant therapy, malabsorption syndrome); hemolysis may occur in 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

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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  2. Cadoni G, Prelajade D, Campobasso E. Wegener's granulomatosis: a challenging disease for otorhinolaryngologists. Acta Otolaryngol. Oct 2005;125(10):1105-10. [Medline].

  3. Klippel JH. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation; 2001:392-394, 643.

  4. Cummings CW, Haughey BH, Thomas JR, et al. Otolaryngology - Head and Neck Surgery. 4th ed. St. Louis, MO: Mosby, Inc; 2005:934-936; 1493-1508.

  5. Langford CA, Hoffman GS. Rare diseases.3: Wegener's granulomatosis. Thorax. Jul 1999;54(7):629-37. [Medline].

  6. Finley JC, Bloom DC, Thiringer JK. Wegener granulomatosis presenting as an infiltrative retropharyngeal mass with syncope and hypoglossal paresis. Arch Otolaryngol Head Neck Surg. Mar 2004;130(3):361-5. [Medline].

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  8. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. Aug 1990;33(8):1101-7. [Medline].

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  13. Illei GG, Austin HA, Crane M. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. Aug 21 2001;135(4):248-57. [Medline].

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Further Reading

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Keywords

Wegener granulomatosis, WG, Wegener's granulomatos, granuloma, respiratory tracts, disseminated vasculitis, glomerulonephritis

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Contributor Information and Disclosures

Author

Neil Tanna, MD, MBA, Staff Physician, Division of Otolaryngology-Head and Neck Surgery, The George Washington University
Neil Tanna, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Medical Association, and Medical Society of the District of Columbia
Disclosure: Nothing to disclose.

Coauthor(s)

Charles A Elmaraghy, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Ohio State University Medical Center
Charles A Elmaraghy, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Medical Association, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Douglas R Sidell, MD, Resident Physician, Department of Otolaryngology-Head and Neck Surgery, University of California at Los Angeles Medical Center
Disclosure: Nothing to disclose.

John Boone, MD, Consulting Staff, Department of Otolaryngology, Naval Hospital Oak Harbor
John Boone, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery
Disclosure: Nothing to disclose.

Medical Editor

David J Terris, MD, FACS, Porubsky Professor and Chairman, Department of Otolaryngology, Medical College of Georgia
David J Terris, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American Association for the Advancement of Science, American Bronchoesophagological Association, American College of Surgeons, American Head and Neck Society, Federation of American Societies for Experimental Biology, International Association of Endocrine Surgeons, Phi Beta Kappa, Radiation Research Society, Society of University Otolaryngologists-Head and Neck Surgeons, and Triological Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Peter S Roland, MD, Professor, Department of Neurological Surgery, Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, Director of Clinical Center for Auditory, Vestibular and Facial Nerve Disorders, Chief of Pediatric Otology, University of Texas Southwestern Medical Center; Adjunct Professor of Communicative Disorders, School of Human Development.
Peter S Roland, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American Auditory Society, American Laryngological Rhinological and Otological Society, American Neurotology Society, American Otological Society, North American Skull Base Society, and Society of University Otolaryngologists-Head and Neck Surgeons
Disclosure: Alcon labs Honoraria Speaking and teaching; GSK Honoraria Speaking and teaching; Advanced Bionics Honoraria Board membership; Cochlear corp Honoraria Board membership; Med El corp travel grants Speaking and teaching; Insight vision Consulting fee Consulting

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: Advanced Headache Intervention Consulting fee Consulting; Covidien Corp Consulting fee Consulting

 
 
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