Advanced searchCitation search
Skip main navigation
Close Drawer MenuOpen Drawer Menu
Review15 March 1992

Wegener Granulomatosis: An Analysis of 158 Patients

    Author, Article, and Disclosure Information
    https://doi.org/10.7326/0003-4819-116-6-488

    Abstract

    ▪ Objective: To prospectively study the clinical features, pathophysiology, treatment, and prognosis of Wegener granulomatosis.

    ▪ Design: Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years).

    ▪ Measurements: Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system.

    ▪ Setting: The Warren Magnuson Clinical Center of the National Institutes of Health.

    ▪ Main Results: Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low-dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for > 5 years, 44% had remissions of > 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%).

    ▪ Conclusions: The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our longterm follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens. Annals of Internal Medicine. 1992;116:488-498.

    References

    • 1. Klinger H. Grenzformen der periarteritis nodosa. Frankf Z Pathol. 1931;42:455-80. Google Scholar
    • 2. Wegener F. Über generalisierte, septische efäberkrankungen. Verh Dtsch Pathol Ges. 1936;29:202-10. Google Scholar
    • 3. Wegener F. Über eine eigenartige rhinogene granulomatose mit besonderer beteiligung des arterien systems und der nieren. Beitr Pathol Anat Allg Pathol. 1939;36-68. Google Scholar
    • 4. Pinching A, Lockwood C, Pussell B, Rees A, Sweny P, and Evans D. Wegener's granulomatosis: observations on 18 patients with severe renal disease. Q J Med. 1983;208:435-60. Google Scholar
    • 5. Fauci A and Wolff S. Wegener's granulomatosis: studies in eighteen patients and a review of the literature. Medicine. 1973;52:535-61. CrossrefMedlineGoogle Scholar
    • 6. Fauci A, Haynes B, Katz P, and Wolff S. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983;98:76-85. LinkGoogle Scholar
    • 7. Walton E. Giant cell granuloma of the respiratory tract (Wegener's granulomatosis). Br Med J. 1958;2:265-70. CrossrefMedlineGoogle Scholar
    • 8. Hollander D and Manning R. The use of alkylating agents in the treatment of Wegener's granulomatosis. Ann Intern Med. 1967;67:393-8. LinkGoogle Scholar
    • 9. Reza M, Dornfeld L, Goldberg L, Bluestone R, and Pearson C. Wegener's granulomatosis. Long-term followup of patients treated with cyclophosphamide. Arthritis Rheum. 1975;18:501-6. CrossrefMedlineGoogle Scholar
    • 10. Van Der Woude F, Lobatto S, Permin H, van der Giessen M, Rasmussen N, and Wiik A. Autoantibodies against neutrophils and monocytes: Tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet. 1985;1:425-9. CrossrefMedlineGoogle Scholar
    • 11. Specks U, Wheatley C, McDonald T, Rohrbach M, and DeRemee R. Anticytoplasmic autoantibodies in the diagnosis and follow-up of Wegener's granulomatosis. Mayo Clin Proc. 1989;64:28-36. CrossrefMedlineGoogle Scholar
    • 12. NÖlle B, Specks U, LÜdemann J, Rohrback M, DeRemee R, and Gross W. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener's granulomatosis. Ann Intern Med. 1989;111:28-40. LinkGoogle Scholar
    • 13. LÜdemann J, Csernok E, Ulmer M, Lemke H, Utecht B, and Rautmann A. Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis: immunodiagnostic value, monoclonal antibodies and characterization of the target antigen. Neth J Med. 1990;36:157-62. MedlineGoogle Scholar
    • 14. Cohen Tervaert J, Huitem M, Hene R, and Sluiter W. Prevention of relapses in Wegener's granulomatosis by treatment based on anti-neutrophil cytoplasmic antibody titer. Lancet. 1990;336:709-11. CrossrefMedlineGoogle Scholar
    • 15. Devaney K, Travis W, Hoffman G, Leavitt R, Lebovics R, and Fauci A. Interpretation of head and neck biopsies in Wegener's granulomatosis. A pathologic study of 126 biopsies in 70 patients. Am J Surg Pathol. 1990;14:555-64. CrossrefMedlineGoogle Scholar
    • 16. Travis W, Hoffman G, Leavitt R, Pass H, and Fauci A. Surgical pathology of the lung in Wegener's granulomatosis. Review of 87 open lung biopsies from 67 patients. Am J Surg Pathol. 1991;15:315-33. CrossrefMedlineGoogle Scholar
    • 17. Travis W, Colby T, Lombard C, and Carpenter H. A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation. Am J Surg Pathol. 1990;14:112-25. CrossrefGoogle Scholar
    • 18. Antonovych T, Sabnis S, Tuur S, Sesterhenn I, and Balow J. Morphologic differences between polyarteritis and Wegener's granulomatosis using light, electron and immunohistochemical techniques. Mod Pathol. 1989;2:349-59. MedlineGoogle Scholar
    • 19. Watanabe T, Yoshikawa Y, and Toyoshima H. Morphological and clinical features of the kidney in Wegener's granulomatosis. A survey of 28 autopies in Japan. Jap J Nephrol. 1981;23:921-30. Google Scholar
    • 20. Weiss M and Crissman J. Renal biopsy findings in Wegener's granulomatosis: Segmental necrotizing glomerulonephritis with glomerular thrombosis. Hum Pathol. 1984;15:943-56. CrossrefMedlineGoogle Scholar
    • 21. Hoffman G, Sechler J, Gallin J, Shelhamer J, Suffredini A, and Ognibene F. Bronchoalveolar lavage analysis in Wegener's granulomatosis. Am Rev Respir Dis. 1991;143:401-7. CrossrefMedlineGoogle Scholar
    • 22. Baltaro R, Hoffman G, Sechler J, Suffredini A, Shelhamer J, and Fauci A. Immunoglobulin G antineutrophil cytoplasmic antibodies are produced in the respiratory tract of patients with Wegener's granulomatosis. Am Rev Respir Dis. 1991;143:275-8. CrossrefMedlineGoogle Scholar
    • 23. Hoffman G, Leavitt R, Fleisher T, Minor J, and Fauci A. Treatment of Wegener's granulomatosis with intermittent high-dose intravenous cyclophosphamide. Am J Med. 1990;89:403-10. CrossrefMedlineGoogle Scholar
    • 24. Balow J, Austin H, Muenz L, Joyce K, Antonovych T, and Klippel J. Effect of treatment on the evolution of renal abnormalities in lupus nephritis. N Engl J Med. 1984;311:491-5. CrossrefMedlineGoogle Scholar
    • 25. Balow J, Austin H, Tsokos G, Antonovych T, Steinberg A, and Klippel J. Lupus nephritis. Ann Intern Med. 1987;106:79-94. LinkGoogle Scholar
    • 26. Austin H, Klippel J, Balow J, LeRiche N, Steinberg A, and Plotz P. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986;314:614-9. CrossrefMedlineGoogle Scholar
    • 27. Sessoms S and Kovarsky J. Monthly intravenous cyclophosphamide in the treatment of severe systemic lupus erythematosus. Clin Exp Rheumatol. 1984;2:247-51. MedlineGoogle Scholar
    • 28. Steppat D and Gross W. Stage adapted treatment of Wegener's granulomatosis. Klin Wochenschr. 1989;67:666-71. CrossrefMedlineGoogle Scholar
    • 29. De Remee R, McDonald T, and Weiland L. Wegener's granulomatosis: observations on treatment with antimicrobial agents. Mayo Clin Proc. 1985;60:27-32. CrossrefMedlineGoogle Scholar
    • 30. West B, Todd J, and King J. Wegener's granulomatosis and tri-methoprim-sulfamethoxazole: complete remission after a twenty-year course. Ann Intern Med. 1987;106:840-2. LinkGoogle Scholar
    • 31. Yuasa K, Tokitsu M, Goto H, Kato H, and Shimada K. Wegener's granulomatosis: diagnosis by transbronchial lung biopsy, evaluation by gallium scintigraphy and treatment with sulfamethoxazole/trimethoprim. Am J Med. 1988;84:371-2. CrossrefMedlineGoogle Scholar
    • 32. De Remee R. The treatment of Wegener's granulomatosis with trimethoprim/sulfamethoxazole: illusion or vision? Arthritis Rheum. 1988;31:1068-72. CrossrefMedlineGoogle Scholar
    • 33. Israel H. Sulfamethoxazole-trimethoprim therapy for Wegener's granulomatosis. Arch Intern Med. 1988;148:2293-5. CrossrefMedlineGoogle Scholar
    • 34. Leavitt R, Hoffman G, and Fauci A. Response: the role of trimethoprim/sulfamethoxazole in the treatment of Wegener's granulomatosis. Arthritis Rheum. 1988;31:1073-4. CrossrefMedlineGoogle Scholar
    • 35. Anderson P, West S, O'Dell J, Via C, Claypool R, and Kotzin B. Weekly pulse methotrexate in rheumatoid arthritis. Ann Intern Med. 1985;103:489-96. LinkGoogle Scholar
    • 36. Weinstein A, Marlowe S, Korn J, and Farouhar F. Low dose methotrexate treatment of rheumatoid arthritis. Am J Med. 1985;79:331-7. CrossrefMedlineGoogle Scholar
    • 37. Kremer J and Lee J. The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum. 1986;29:822-31. CrossrefMedlineGoogle Scholar
    • 38. Williams H, Wilkens R, Samuelson C, Alarcon G, and Guttadauria M. Comparison of low dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. Arthritis Rheum. 1985;28:721-30. CrossrefMedlineGoogle Scholar
    • 39. Hamdy H, McKendry R, Mierins E, and Liver J. Low dose methotrexate compared to azathioprine in the treatment of rheumatoid arthritis. Arthritis Rheum. 1987;30:361-8. CrossrefMedlineGoogle Scholar
    • 40. Tugwell P, Bennett K, and Gent M. Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy and safety. Ann Intern Med. 1987;107:358-66. LinkGoogle Scholar
    • 41. Weinblatt M, Kaplan H, Germain B, Merriman R, Solomon S, and Wall B. Low dose methotrexate compared with auranofin in adult rheumatoid arthritis. A thirty-six week, double blind trial. Arthritis Rheum. 1990;33:330-8. CrossrefMedlineGoogle Scholar
    • 42. Espinoza L, Espinoza C, Vasey F, and Germain B. Oral methotrexate for chronic rheumatoid arthritis ulcerations. J Am Acad Dermatol. 1986;15:508-12. CrossrefMedlineGoogle Scholar
    • 43. Falk R, Terrell R, Charles L, and Jennette J. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci USA. 1990;87:4115-9. CrossrefMedlineGoogle Scholar
    • 44. Van der Woude F, Van Es L, and Daha M. The role of the C-ANCA antigen in the pathogenesis of Wegener's granulomatosis. A hypothesis based on both humoral and cellular mechanisms. Neth J Med. 1990;36:169-71. MedlineGoogle Scholar
    • 45. Kallenberg C. Antineutrophil cytoplasmic antibodies (ANCA) and vasculitis. Clin Rheumatol 9. (suppl) 1990;132-5. CrossrefMedlineGoogle Scholar

    This content is PDF only. To continue reading please click on the PDF icon.

    Previous
    Next

    Submit a Comment

    Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
    *All comments submitted after October 1, 2021 and selected for publication will be published online only.
    Cancel