Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Relapsing disease in Wegener's granulomatosis and microscopic polyangiitis

INTRODUCTION

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are related systemic vasculitides. Both are associated with antineutrophil cytoplasmic antibodies (ANCA), have similar features on renal histology (eg, a focal necrotizing, pauci-immune glomerulonephritis), and have similar outcomes. There are, however, several differences between these disorders. (See "Clinical manifestations and diagnosis of Wegener's granulomatosis and microscopic polyangiitis", section on 'MPA versus WG'.)

Approximately 85 to 90 percent of patients with WG or MPA attain clinical remission with initial immunosuppressive therapy (typically cyclophosphamide and glucocorticoids). They are then treated with maintenance immunosuppressive therapy with azathioprine or methotrexate, usually for a period of 12 to 18 months. However, relapses are common and some patients have frequent relapses. In addition, among patients who progress to end-stage renal disease, nonrenal relapses can occur in patients treated with maintenance hemodialysis or renal transplantation, and renal manifestations can recur in the transplanted kidney.

Issues related to relapsing disease in patients with WG or MPA will be reviewed here. This includes patients who have progressed to end-stage renal disease and are on chronic renal replacement therapy.

Initial immunosuppressive therapy, the treatment of cyclophosphamide resistant disease, maintenance immunosuppressive therapy, clinical manifestations and diagnosis, and patient and renal outcomes are discussed elsewhere. (See "Initial immunosuppressive therapy in Wegener's granulomatosis and microscopic polyangiitis" and "Treatment of cyclophosphamide-resistant Wegener's granulomatosis and microscopic polyangiitis" and "Maintenance immunosuppressive therapy in Wegener's granulomatosis and microscopic polyangiitis" and "Clinical manifestations and diagnosis of Wegener's granulomatosis and microscopic polyangiitis" and "Patient and renal outcomes in Wegener's granulomatosis and microscopic polyangiitis".)

DEFINITION

Relapse is defined as the recurrence of signs or symptoms of active vasculitis in any organ system [1,2]. Relapse can be manifested by one or more of the following features:
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2010 UpToDate, Inc.
References Top
  1. 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.
  2. Nachman, PH, Hogan, SL, Jennette, JC, Falk, RJ. Treatment response and relapse in antineutrophil cytoplasmic antibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996; 7:33.
  3. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005; 352:351.
  4. Savage, CO, Winearls, CG, Evans, DJ, et al. Microscopic polyarteritis: presentation, pathology and prognosis. Q J Med 1985; 56:467.
  5. Reinhold-Keller, E, Fink, CO, 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 Rheum 2002; 47:326.
  6. Chen, M, Yu, F, Zhao, MH. Relapses in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: likely to begin with the same organ as initial onset. J Rheumatol 2008; 35:448.
  7. Geffriaud-Ricouard, C, Noël, LH, Chauveau, D, et al. Clinical spectrum associated with antineutrophil cytoplasmic antibodies of defined antigen specificities in 98 selected patients. Clin Nephrol 1993; 39:125.
  8. Jayne, DR, Gaskin, G, Pusey, CD, Lockwood, CM. ANCA and predicting relapse in systemic vasculitis. QJM 1995; 88:127.
  9. Seo, P, Min, YI, Holbrook, JT, et al. Damage caused by Wegener's granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET). Arthritis Rheum 2005; 52:2168.
  10. Jayne, D, Rasmussen, N, Andrassy, K, Bacon, P. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003; 349:36.
  11. Bacon, PA. The spectrum of Wegener's granulomatosis and disease relapse. N Engl J Med 2005; 352:330.
  12. Gayraud, M, Guillevin, L, le Toumelin, P, et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. French Vasculitis Study Group. Arthritis Rheum 2001; 44:666.
  13. Rarok, AA, Stegeman, CA, Limburg, PC, Kallenberg, CG. Neutrophil membrane expression of proteinase 3 (PR3) is related to relapse in PR3-ANCA-associated vasculitis. J Am Soc Nephrol 2002;13:2232.
  14. 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.
  15. Goek, ON, Stone, JH. Randomized controlled trials in vasculitis associated with anti-neutrophil cytoplasmic antibodies. Curr Opin Rheumatol 2005; 17:257.
  16. Stegeman, CA, Cohen Tervaert, JW, Sluiter, WJ, et al. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med 1994; 120:12.
  17. 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.
  18. Popa, ER, Tervaert, JW. The relation between Staphylococcus aureus and Wegener's granulomatosis: current knowledge and future directions. Intern Med 2003; 42:771.
  19. Popa, ER, Stegeman, CA, Abdulahad, WH, et al. Staphylococcal toxic-shock-syndrome-toxin-1 as a risk factor for disease relapse in Wegener's granulomatosis. Rheumatology (Oxford) 2007; 46:1029.
  20. Andrassy, K, Waldherr, R, Erb, A, Ritz, E. De novo glomerulonephritis in patients during remission from Wegener's granulomatosis. Clin Nephrol 1992; 38:295.
  21. Pettersson, E, Heigl, Z. Antineutrophil cytoplasmic antibody (cANCA and pANCA) titers in relation to disease activity in patients with necrotizing vasculitis. A longitudinal study. Clin Nephrol 1992; 37:219.
  22. Finkielman, JD, Merkel, PA, Schroeder, D, et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med 2007; 147:611.
  23. 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.
  24. 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.
  25. Gaskin, G, Savage, CO, Ryan, JJ, et al. Anti-neutrophil cytoplasmic antibodies and disease activity during long-term follow-up of 70 patients with systemic vasculitis. Nephrol Dial Transplant 1991; 6:689.
  26. Cohen Tervaert, JW, Huitema, MG, Hene, RJ, et al. Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet 1990; 336:709.
  27. Russell, KA, Fass, DN, Specks, U. Antineutrophil cytoplasmic antibodies reacting with the pro form of proteinase 3 and disease activity in patients with Wegener's granulomatosis and microscopic polyangiitis. Arthritis Rheum 2001; 44:463.
  28. Jindal, KK. Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: Evidence-based recommendations. Kidney Int Suppl 1999; 70:S33.
  29. Seo, P, Stone, JH. The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med 2004; 117:39.
  30. Stassen, PM, Cohen Tervaert, JW, Stegeman, CA. Induction of remission in active anti-neutrophil cytoplasmic antibody-associated vasculitis with mycophenolate mofetil in patients who cannot be treated with cyclophosphamide. Ann Rheum Dis 2007; 66:798.
  31. Eriksson, P. Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab. J Intern Med 2005; 257:540.
  32. Stegeman, CA, Cohen Tervaert, JW, de Jong, PE, Kallenberg, CG. 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.
  33. Lionaki, S, Hogan, SL, Jennette, CE, et al. The clinical course of ANCA small-vessel vasculitis on chronic dialysis. Kidney Int 2009; 76:644.
  34. Falk, RJ, Nachman, PH, Hogan, SL, Jennette, JC. ANCA glomerulonephritis and vasculitis: a Chapel Hill perspective. Semin Nephrol 2000; 20:233.
  35. Allen, A, Pusey, C, Gaskin, G. Outcome of renal replacement therapy in antineutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol 1998; 9:1258.
  36. Weidanz, F, Day, CJ, Hewins, P, et al. Recurrences and infections during continuous immunosuppressive therapy after beginning dialysis in ANCA-associated vasculitis. Am J Kidney Dis 2007; 50:36.
  37. Haubitz, M, Koch, KM, Brunkhorst, R. Survival and vasculitis activity in patients with end-stage renal disease due to Wegener's granulomatosis. Nephrol Dial Transplant 1998; 13:1713.
  38. Haubitz, M, de Groot, K. Tolerance of mycophenolate mofetil in end-stage renal disease patients with ANCA-associated vasculitis. Clin Nephrol 2002; 57:421.
  39. Nachman, PH, Segelmark, M, Westman, K, et al. Recurrent ANCA-associated small vessel vasculitis after transplantation: A pooled analysis. Kidney Int 1999; 56:1544.
  40. Gera, M, Griffin, MD, Specks, U, et al. Recurrence of ANCA-associated vasculitis following renal transplantation in the modern era of immunosupression. Kidney Int 2007; 71:1296.
  41. Moroni, G, Torri, A, Gallelli, B, et al. The long-term prognosis of renal transplant in patients with systemic vasculitis. Am J Transplant 2007; 7:2133.
  42. Elmedhem, A, Adu, D, Savage, CO. Relapse rate and outcome of ANCA-associated small vessel vasculitis after transplantation. Nephrol Dial Transplant 2003; 18:1001.
  43. Steinman, TI, Jaffe, BF, Monaco, AP, et al. Recurrence of Wegener's granulomatosis after kidney transplantation. Am J Med 1980; 68:458.
  44. Clarke, AE, Bitton, A, Eappen, R, et al. Treatment of Wegener's granulomatosis after renal transplantation: is cyclosporine the preferred treatment?. Transplantation 1990; 50:1047.
  45. Rostaing, L, Modesto, A, Oksman, F, et al. Outcome of patients with antineutrophil cytoplasmic autoantibody-associated vasculitis following cadaveric kidney transplantation. Am J Kidney Dis 1997; 29:96.
  46. Haubitz, M, Kliem, V, Koch, KM, et al. Renal transplantation for patients with autoimmune diseases: Single-center experience with 42 patients. Transplantation 1997; 63:1251.
  47. Rich, LM, Piering, WF. Ureteral stenosis due to recurrent Wegener's granulomatosis after kidney transplantation. J Am Soc Nephrol 1994; 4:1516.
white circle LOG IN
white circle DEMO