eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Granulomatosis Diseases

Wegener Granulomatosis: Differential Diagnoses & Workup

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

Differential Diagnoses

Other Problems to Be Considered

Strawberry gums
Gingival hyperplasia induced by drugs (eg, phenytoin anticonvulsants, some calcium channel blockers, cyclosporine, conjugated estrogens)
Sarcoidosis
Tuberculosis
Churg-Strauss
Polyarteritis nodosa
Scurvy (vitamin C deficiency)
Neoplastic processes (squamous cell carcinoma, leukemia, Kaposi sarcoma)
Nasal substance abuse

Workup

Laboratory Studies

  • Diagnosis of WG is made on the basis of clinical features, the presence of raised c-ANCA titers, and histopathologic confirmation. Researchers at the American College of Rheumatology proposed 4 criteria for the diagnosis of WG:
    1. Oral ulcers or nasal discharge
    2. Abnormal chest radiography (nodules, fixed infiltrates, or cavities)
    3. Microhematuria (>5 red blood cells per high power field) or red cell casts in urine sediment3
    4. Granulomatous inflammation on biopsy
  • They associated 2 of 4 positive criteria with a sensitivity of 88.2% and a specificity of 92%.8 Diagnosis may be difficult in early stages when the disease is localized. Early diagnosis is crucial so that effective treatment can intervene before pulmonary and renal involvement takes it toll.
  • Laboratory tests: Nonspecific findings include an elevated erythrocyte sedimentation rate (ESR) and leukocytosis, normocytic normochromic anemia, and thrombocytosis.
  • Renal function tests
  • Urinalysis - Hematuria, RBC casts, proteinuria
  • Elevated creatinine, decreased creatinine clearance
  • Antineutrophil cytoplasm antibodies
    • Serum immunoglobulin G (IgG) autoantibodies are directed against proteinase-3. (See Pathophysiology for a detailed description of the presumed role of c-ANCA in WG.)
    • Techniques include IIF and ELISA.
    • Sensitivity is 90% in generalized WG and 70% in localized WG. Sensitivity can be increased if both IIF and ELISA techniques are obtained.
    • Specificity is 90%.
    • Titers of c-ANCA have been known to correlate with disease activity in more than 85% of WG cases. C-ANCA levels may therefore be used to follow the course of the disease, although it does not always correlate to treatment response.3
  • The best tools for the diagnosis of WG include a high index of suspicion, elevated titers of c-ANCA, and generous biopsy samples of involved sites. Although testing for c-ANCAs remains controversial as a clinical diagnostic tool, it is often the diagnostic feature in patients with nonspecific biopsies.

Imaging Studies

  • Biopsy: Even after the discovery of serologic c-ANCA studies, biopsy remains an essential tool in the diagnosis of WG. In mild cases of WG, ANCA may be negative in up to 40% of individuals. However, although specific, biopsy has been demonstrated to have a significant false-negative rate. A negative predictive value of nearly 75% was demonstrated in one study. To decrease the rate of false negative results, some have suggested that biopsies are both adequate in depth and width, with margins of normal tissue included in the specimen. Although low sensitivity may discourage repeat biopsies, some authors maintain that serial biopsies should be considered based on high levels of clinical suspicion. When considering head and neck involvement, biopsies from the paranasal sinuses have been shown to yield results with the highest sensitivity.1,3

Histologic Findings

WG is typically described by 3 basic histopathologic features: (1) vasculitis of small vessels, (2) granulomatous changes, and (3) focal necrosis. However, diagnosis may be difficult to confirm by the biopsy of head and neck lesions. The small amount of tissue available at most involved otolaryngologic sites often makes it difficult to identify all the histopathologic features of WG.

Additionally, the more classic features are frequently obscured by acute and chronic inflammatory changes, such as pseudoepitheliomatous hyperplasia, multinucleated giant cells, microabscesses, and an inflammatory infiltrate of neutrophils and eosinophils. As a result, biopsies of otolaryngologic lesions may not conclusively confirm the diagnosis and often are only suggestive of WG. The larger the biopsy, the greater the likelihood of obtaining a firm diagnosis. A biopsy of at least 5 mm is recommended.

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

  1. Gubbels SP, Barkhuizen A, Hwang PH. Head and neck manifestations of Wegener's granulomatosis. Otolaryngol Clin North Am. Aug 2003;36(4):685-705. [Medline].

  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].

  7. Gluth MB, Shinners PA, Kasperbauer JL. Subglottic stenosis associated with Wegener's granulomatosis. Laryngoscope. Aug 2003;113(8):1304-7. [Medline].

  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].

  9. Clark WJ, Broumand V, Ruskin JD, et al. Erythematous, granular, soft tissue lesion of the gingiva. J Oral Maxillofac Surg. Aug 1998;56(8):962-7. [Medline].

  10. Dagum P, Roberson JB Jr. Otologic Wegener's granulomatosis with facial nerve palsy. Ann Otol Rhinol Laryngol. Jul 1998;107(7):555-9. [Medline].

  11. Glass EG, Lawton LR, Truelove EL. Oral presentation of Wegener granulomatosis. J Am Dent Assoc. May 1990;120(5):523-5. [Medline].

  12. Hewins P, Tervaert JW, Savage CO, et al. Is Wegener's granulomatosis an autoimmune disease?. Curr Opin Rheumatol. Jan 2000;12(1):3-10. [Medline].

  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].

  14. Langford CA, Talar-Williams C, Barron KS. A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum. Dec 1999;42(12):2666-73. [Medline].

  15. Pathak I, Bryce G. Wegener's granulomatosis masquerading as mastoiditis and lateral-sinus thrombosis. J Otolaryngol. Jun 1997;26(3):207-9. [Medline].

  16. Yumoto E, Saeki K, Kadota Y. Subglottic stenosis in Wegener's granulomatosis limited to the head and neck region. Ear Nose Throat J. Aug 1997;76(8):571-4. [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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