eMedicine Specialties > Dermatology > Diseases of the Vessels

Wegener Granulomatosis

Author: Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center
Coauthor(s): David Hensley, MD, Mullanax Dermatology Associates, Arlington Memorial Hospital; Lindsey Ann Dohse, MD, Staff Physician, Department of Dermatology, Geisinger Health System
Contributor Information and Disclosures

Updated: Jun 5, 2008

Introduction

Background

Wegener granulomatosis (WG) is a rare multisystem disease characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tracts and kidneys and by necrotizing vasculitis affecting small- and medium-sized vessels. In 1931, Klinger first classified WG as a variant of polyarteritis nodosa (see Polyarteritis Nodosa). In 1936, Wegener described the disease as a distinct entity with specific clinical and histopathologic criteria.

Pathophysiology

The etiology of WG remains unknown. Current research has focused on the relevant mechanisms of inflammation, particularly the effect of inflammatory mediators and immune effector cells on the endothelium. Evidence suggests that WG is an autoimmune inflammatory process, with antineutrophil cytoplasmic antibodies (c-ANCA) directed at neutrophil proteinase 3 (PR3) involved in the pathophysiology of the disease. Neutrophils and endothelial cells are involved in early lesions as both targets and promotors of inflammation. c-ANCA may be responsible for events that lead to the activation of neutrophils, which, in turn, selectively target the endothelium.1 Endothelial cell damage and activation of neutrophils produce inflammatory mediators, leading to recruitment of monocytes and T cells and increased endothelial damage.

Frequency

United States

WG is a rare disease with an as yet undetermined incidence. The prevalence of WG in the United States of America is estimated to be 3 cases per 100,000 people.2

International

The incidence in the United Kingdom is estimated at 8.5 cases per million persons per year.

Mortality/Morbidity

  • The most common causes of death for persons with WG include renal and respiratory failure, infection, malignancy, and, less often, heart failure and myocardial infarction.3 The 1-year survival rate in persons with untreated disease is estimated at 18%.
  • Most morbidity is currently treatment related.

Race

WG is mostly reported in whites; it rarely occurs in blacks. Black race may be a predictor of treatment resistance in ANCA-positive vasculitides.

Sex

The male-to-female ratio is reportedly 1:1-2:1. A study of 244 patients found a higher male-to-female ratio (2.12:1) for disease affecting the kidneys and at least one other organ system. Females may be more treatment resistant.

Age

Onset may occur at any age; patients typically present at age 35-55 years. Less than 15% of cases occur in children.3

Clinical

History

Necrotizing granulomas may be found in any organ system. The upper respiratory tract (especially the nose and sinuses) is the most commonly affected site. The typical presentation includes upper airway symptoms, such as sinusitis or nasal discharge. The lungs are affected in 85% of patients. Disease severity is usually related to renal involvement, which occurs in 75% of patients.

Cutaneous manifestations occur in 35-50% of patients, and they may be the presenting sign of disease in 13% of patients. Patients exhibiting cutaneous manifestations more commonly have renal and articular disease. Ulcers and vesicles are associated with more severe and extensive disease.

  • Patients may report the following chronic, nonspecific constitutional symptoms: 
    • Fever
    • General malaise
    • Fatigue
    • Arthralgias
    • Weight loss
  • The classic upper respiratory tract manifestations are chronic sinus symptoms that fail to respond to treatment for sinusitis.
  • Chronic otitis, hearing loss, nonhealing ulcerations in the nasal and oral mucosa, and nonspecific ocular disturbances are other symptoms.
  • Various cutaneous eruptions or ulcerations may be the only presenting symptoms.
  • Cough hemoptysis, dyspnea, and chest pain may accompany pulmonary disease.
  • Renal disease may manifest as oliguria and hematuria.

Physical

Physical findings are described below.

  • General: Patients may be febrile and appear ill.
  • Neurologic: Patients may have mononeuritis multiplex, neuropathy, stroke, seizure, cerebritis, or meningitis.2
  • Head, ears, eyes, nose, and throat  
    • Ocular findings include conjunctivitis, keratitis, and scleritis.
    • Proptosis may signal retrobulbar granuloma.
    • Xanthelasma has been reported.
    • Nearly 75% of patients present with ear, nose, and throat findings.
    • Subglottic stenosis and tracheal stenosis may prove fatal if not treated.2
    • Sinusitis and disease in the nasal mucosa are the most common findings.
    • Purulent or sanguinous nasal discharge may be seen.
    • Otitis media may be present; deformation or destruction of the pinnae or nose (saddle nose) is rare.
    • Oral involvement is rare; however, a classic presentation includes "strawberry gingival hyperplasia."2
  • Integument  
    • Cutaneous findings are variable and usually nonspecific.
    • Palpable purpura, papules, subcutaneous nodules, and ulcerations are the most common findings.
    • Ulcerations may resemble pyoderma gangrenosum (see Pyoderma Gangrenosum).
    • Petechiae, vesicles, pustules, hemorrhagic bullae, livedo reticularis, digital necrosis, subungual splinter hemorrhages, and genital ulcers resembling squamous cell carcinoma have been reported.
    • The lower extremities are most commonly affected.

The Medscape CME course Examining the Ears, Nose, and Oral Cavity in the Older Patient may be of interest.

Causes

The etiology is unknown. Studies suggest that c-ANCA may be directly related to the pathogenesis. Other studies favor a delayed-type hypersensitivity reaction to unknown antigens.

  • Despite little evidence of an infectious etiology, WG has been successfully treated with trimethoprim and sulfamethoxazole.
  • In some studies, relapse rates have been associated with chronic nasal carriage of Staphylococcus aureus.4
  • Large studies have failed to show a genetic predisposition for the disease.

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

  1. Harper L, Savage CO. Pathogenesis of ANCA-associated systemic vasculitis. J Pathol. Feb 2000;190(3):349-59. [Medline].

  2. 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].

  3. 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].

  4. 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].

  5. 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].

  6. Wung PK, Stone JH. Therapeutics of Wegener's granulomatosis. Nat Clin Pract Rheumatol. Apr 2006;2(4):192-200. [Medline].

  7. Antoniu SA. Treatment options for refractory Wegener's granulomatosis: a role for rituximab?. Curr Opin Investig Drugs. Nov 2007;8(11):927-32. [Medline].

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. [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].

  13. Duna GF, Galperin C, Hoffman GS. Wegener's granulomatosis. Rheum Dis Clin North Am. Nov 1995;21(4):949-86. [Medline].

  14. 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.

  15. 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].

  16. 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].

  17. 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].

  18. Hellmich B, Lamprecht P, Gross WL. Advances in the therapy of Wegener's granulomatosis. Curr Opin Rheumatol. Jan 2006;18(1):25-32. [Medline].

  19. 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].

  20. 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].

  21. Hu CH, O'Loughlin S, Winkelmann RK. Cutaneous manifestations of Wegener granulomatosis. Arch Dermatol. Feb 1977;113(2):175-82. [Medline].

  22. 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].

  23. 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].

  24. Jennette JC, Falk RJ. Antineutrophil cytoplasmic autoantibodies and associated diseases: a review. Am J Kidney Dis. Jun 1990;15(6):517-29. [Medline].

  25. 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].

  26. Jennette JC, Woosley JT, Falk RJ. Microscopic polyarteritis, Wegener's granulomatosis, and Churg-Strauss syndrome. J Cutan Med Surg. 1996;522-7.

  27. 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].

  28. Mangold MC, Callen JP. Cutaneous leukocytoclastic vasculitis associated with active Wegener's granulomatosis. J Am Acad Dermatol. Apr 1992;26(4):579-84. [Medline].

  29. 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].

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Further Reading

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Keywords

Wegener's granulomatosis, WG

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Contributor Information and Disclosures

Author

Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center
Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

David Hensley, MD, Mullanax Dermatology Associates, Arlington Memorial Hospital
David Hensley, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Pennsylvania Medical Society, Southern Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Lindsey Ann Dohse, MD, Staff Physician, Department of Dermatology, Geisinger Health System
Lindsey Ann Dohse, MD is a member of the following medical societies: Alpha Omega Alpha
Disclosure: Nothing to disclose.

Medical Editor

Abby S Van Voorhees, MD, Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania
Abby S Van Voorhees, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, National Psoriasis Foundation, Phi Beta Kappa, Sigma Xi, and Women's Dermatologic Society
Disclosure: Amgen Honoraria Consulting; Astellas Grant/research funds Other; Abbott Honoraria Consulting; Genentech Honoraria Consulting; Incyte Grant/research funds Other; Centocor Honoraria Consulting; Warner Chilcott  Consulting; Merck Salary Review panel membership

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology
Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Honoraria Consulting; Centocor Honoraria Consulting

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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