Review Article

Wegener Granulomatosis: A Case Report and Update

Authors: Eisha Mubashir, MD; M Mubashir Ahmed, MD; Samina Hayat, MD; Shahnila Latif, MD; Maureen Heldmann, MD; Seth Mark Berney, MD

Abstract

Wegener granulomatosis (WG) is a systemic disease of unknown etiology characterized by necrotizing granulomatous inflammation, tissue necrosis, and variable degrees of vasculitis in small and medium-sized blood vessels. The classic clinical pattern is a triad involving the upper airways, lungs and kidneys. Ninety percent of patients present with symptoms involving the upper and/or lower airways, and 80% will eventually develop renal disease. WG should be suspected in any patient with progressive or unresponsive sinus disease, glomerulonephritis, pulmonary hemorrhage, mononeuritis multiplex or unexplained multisystem disease. Before the routine use of glucocorticoids and cyclophosphamide, the one year mortality was 82%. However in 1973, Fauci and Wolf discovered that daily prednisone and cyclophosphamide induced complete remission in 75% of patients. The continued use of prednisone and cyclophosphamide for 1 year past remission leads to marked improvement in more than 90% of patients; however, is also associated with serious toxicities. Depending on the disease severity, current treatments employ induction with short-term cyclophosphamide followed by less toxic agents such as methotrexate to maintain disease remission. Although it is a rare disorder, it is pertinent to internists because it is a multisystem disease that presents in a variety of ways. We describe a 63-year-old white male with WG who presented with progressively worsening headaches, bilateral eye redness, epistaxis, hemoptysis and an unintentional 20 pound weight loss, and review the current treatment recommendations.


Key Points


* Wegener granulomatosis is a vasculitis of the small and medium-sized blood vessels that presents in a variety of ways.


* It should be suspected in any patient with progressive or unresponsive sinus disease, glomerulonephritis, pulmonary hemorrhage, mononeuritis multiplex or unexplained multisystemic disease.


* Biopsy is needed to confirm the diagnosis and begin therapy in the majority of cases.


* Antineutrophil cytoplasmic antibody titers are not reliable indicators of disease activity.


* Current treatment standards employ induction with short-term treatment with daily cyclophosphamide followed by substitution to less toxic agents to maintain disease remission in severe disease categories, and use less toxic agents in limited disease with equal efficacy and much less toxicity.

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References

1. Klinger H. Grenzformen der periarteritis nodosa. Frankfurt Z Pathol 1931;42:455–480.
 
2. Wegener F. über generalisierte, septische Gefasserkrankungen. Verh Dtsch Ges Pathol1936;29:202–210.
 
3. Wegener F. über eine eigenartige rhinogene Granulomatose mit besonderer Beteiligung des Arteriensystems und der Nieren. Beitr Pathol Anat Allg Pathol 1939;36:36–68.
 
4. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992;116:488–498.
 
5. Reinhold-Keller E, Beuge N, Latza U, et al. An interdisciplinary approach to the care of patients with Wegener’s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum 2000;43:1021–1032.
 
6. Fauci AS, Wolff SM. Wegener’s granulomatosis: studies in eighteen patients and a review of the literature. Medicine(Baltimore) 1973;52:535–561.
 
7. Fauci AS, Haynes BF, Katz P, et al. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983;98:76–85.
 
8. Bullen CL, Liesegang TJ, McDonald TJ, et al. Ocular complications of Wegener’s granulomatosis.Ophthalmology 1983; 90:279–290.
 
9. Nishino H, Rubino F, Parisi J. The spectrum of neurologic involvement in Wegener’s granulomatosis.Neurology 1993;43:1334–1337.
 
10. Langford CA. Update on Wegener granulomatosis. Cleve Clin J Med 2005; 72:689–690, 693–697.
 
11. Van der Woude F, Rasmussen N, Lobatto S, et al. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener’s granulomatosis. Lancet1985;1:425–429.
 
12. Gross WL, Schmitt WH, Csernok E. Antineutrophil cytoplasmic autoantibody-associated diseases: a rheumatologist’s perspective. Am J Kidney Dis 1991 Aug 18:175–189.
 
13. Kerr GS, Fleisher TA, Hallahan CW, et al. Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener’s granulomatosis. Arthritis Rheum 1993;36:365–371.
 
14. Boomsma MM, Stegeman CA, van der Leij MJ, et al. Prediction of relapses in Wegener’s granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study.Arthritis Rheum 2000;43:2025–2033.
 
15. Kyndt X, Reumaux D, Bridoux F, et al. Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis. Am J Med 1999;106:527–533.
 
16. Walton EW. Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). Br Med J1958;5091:265–270.
 
17. Hollander D, Manning RT. The use of alkylating agents in the treatment of Wegener’s granulomatosis. Ann Intern Med 1967;67:393–398.
 
18. 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 2003;349:36–44.
 
19. Langford CA, Talar-Williams C, Barron KS, et al. 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 1999;42:2666–2673.
 
20. Langford CA, Talar-Williams C, Barron KS, et al. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener’s granulomatosis: extended follow-up and rate of relapse. Am J Med 2003;114:463–469.
 
21. Reinhold-Keller E, Fink C, Herlyn K, et al. High rate of renal relapse in 71 patients with Wegener’s granulomatosis under maintenance of remission with low-dose methotrexate. Arthritis Care Res2002;47:326–332.
 
22. De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005;52:2461–2469.
 
23. Mahr A, Pagnoux C, Cohen P, et al. Treatment of ANCA-associated vasculitides: corticosteroids and pulse cyclophosphamide followed by maintenance therapy with methotrexate or azathioprine: a prospective multicenter randomized trial (Wegent) [abstract]. Kidney Blood Press Res 2005;28:194.
 
24. Hoffman GS, Leavitt RY, Fleisher TA, et al. Treatment of Wegener’s granulomatosis with intermittent high-dose intravenous cyclophosphamide. Am J Med 1990;89:403–410.
 
25. Reinhold-Keller E, Kekow J, Schnabel A, et al. Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with Wegener’s granulomatosis. Arthritis Rheum 1994;37:919–924.
 
26. Guillevin L, Cordier JF, Lhote F, et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener’s granulomatosis. Arthritis Rheum 1997;40:2187–2198.
 
27. De Groot K, Adu D, Savage CO. The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant 2001;16:2018–2027.
 
28. Booth AD, Pusey CD, Jayne DR. Renal vasculitis–an update in 2004. Nephrol Dial Transplant2004;19:1964.
 
29. De Groot K, Jayne D, Tesar V, et al. Randomized controlled trial of daily oral versus pulse cyclophosphamide for induction of remission in ANCA-associated systemic vasculitis [abstract]. Kidney Blood Press Res 2005;28:195.
 
30. Metzler C, Fink C, Lamprecht P, et al. Maintenance of remission with leflunomide in Wegener’s granulomatosis. Rheumatology (Oxford) 2004;43:315–320.
 
31. Metzler C, Wagner-Bastmeyer R, Gross W, et al. Leflunomide versus methotrexate for maintenance of remission in Wegner’s granulomatosis: unexpected high relapse rate under oral methotrexate. Ann Rheum Dis 2005;64 (Suppl. 3):85.
 
32. Nowack R, Gobel U, Klooker P, et al. 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 1999;10:1965–1971.
 
33. Langford CA, Talar-Williams C, Sneller MC. Mycophenolate mofetil for remission maintenance in the treatment of Wegener’s granulomatosis. Arthritis Rheum 2004;51:278–283.
 
34. Sneller MC, Hoffman GS, Talar-Williams C, et al. An analysis of forty-two Wegener’s granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum 1995;38:608–613.
 
35. Stone JH, Tun W, Hellman DB. Treatment of non-life threatening Wegener’s granulomatosis with methotrexate and daily prednisone as the initial therapy of choice. J Rheumatol 1999;26:1134–1139.
 
36. Stegeman CA, Tervaert JW, de Jong PE, et al. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis.Dutch Co-Trimoxazole Wegener Study Group.N Engl J Med 1996;335:16–20.
 
37. Buhaescu I, Covic A, Levy J. Systemic vasculitis: still a challenging disease. Am J Kidney Dis2005;46:173–185.
 
38. Gallagher H, Kwan JT, Jayne DR. Pulmonary renal syndrome: a 4-year, single-center experience.Am J Kidney Dis 2002;39:42–47.
 
39. Klemmer PJ, Chalermskulrat W, Reif MS, et al. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am J Kidney Dis 2003;42:1149–1153.
 
40. Birck R, Warnatz K, Lorenz HM, et al. 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol 2003;14:440–447.
 
41. Bartolucci P, Ramanoelina J, Cohen P, et al. Efficacy of the anti-TNF-alpha antibody infliximab against refractory systemic vasculitides: an open pilot study on 10 patients. Rheumatology (Oxford)2002;41:1126–1132.
 
42. Lamprecht P, Voswinkel J, Lilienthal T, et al. Effectiveness of TNF-alpha blockade with infliximab in refractory Wegener’s granulomatosis. Rheumatology (Oxford) 2002;41:1303–1307.
 
43. Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med 2005;352:351–361.
 
44. Specks U, Fervenza FC, McDonald TJ, et al. Response of Wegener’s granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthritis Rheum 2001;44:2836–2840.
 
45. Keogh KA, Wylam ME, Stone JH, et al. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum2005;52:262–268.
 
46. Hogan SL, Falk RJ, Chin H, et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med 2005;143:621–631.
 
47. Andrassy K, Erb A, Koderisch J, et al. Wegener’s granulomatosis with renal involvement: patient survival and correlations between initial renal function, renal histology, therapy and renal outcome. Clin Nephrol 1991;35:139–147.
 
48. Talbot SF, Main DM, Levinson AI. Wegener’s granulomatosis: first report of a case with onset during pregnancy. Arthritis Rheum 1984;27:109–112.
 
49. Luisiri P, Lance NJ, Curran JJ. Wegener’s granulomatosis in pregnancy. Arthritis Rheum1997;40:1354–1360.
 
50. Dayoan ES, Dimen LL, Boylen C. Successful treatment of Wegener’s granulomatosis during pregnancy: a case report and review of the medical literature. Chest 1998;113:836–838.
 
51. Palit J, Clague RB. Wegener’s granulomatosis presenting during first trimester of pregnancy. of Br J Rheumatol 1990;29:389–90.
 
52. Habib A, MacKay K, Abrons HL. Wegener’s granulomatosis complicating pregnancy: presentation of two patients and review of the literature. Clin Nephrol 1996;46:332–336.
 
53. Milford CA, Bellini M. Wegener’s granulomatosis arising in pregnancy. J Laryngol Otol1986;100:475–476.
 
54. Masterson R, Pellicano R, Bleasel K, et al. Wegener’s granulomatosis in pregnancy: a novel approach to management. Am J Kidney Dis 2004;44:e68–72.
 
55. Talar-Williams C, Hijazi YM, Walther MM, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 1996;124:477–484.
 
56. De Groot K, Gross WL, Herlyn K, et al. Development and validation of a disease extent index for Wegener’s granulomatosis. Clin Nephrol 2001;55:31–38.