The ANCA-associated vasculitides, granulomatosis with polyangiitis (GPA, formerly Wegener's), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss), are a group of multisystem autoimmune diseases characterized by necrotizing small- to medium-vessel vasculitis and the presence of anti-neutrophil cytoplasmic antibodies. Current therapeutic strategies consist of glucocorticoids in conjunction with either conventional or biologic agents for both induction of remission and remission maintenance. Treatment goals include reducing toxicity of induction therapy, preventing disease relapse, and limiting overall accrual of both disease-related damage and treatment-related morbidity. Future research directions include investigation of the optimal duration and frequency of maintenance therapy as well as development of targeted therapeutic agents, which is enhanced by emerging insights into disease pathogenesis.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Finkielman JD, Lee AS, Hummel AM. 1.  et al. 2007. ANCA are detectable in nearly all patients with active severe Wegener's granulomatosis. Am. J. Med. 120:79–14 [Google Scholar]
  2. Sablé-Fourtassou R, Cohen P, Mahr A. 2.  et al. 2005. Antineutrophil cytoplasmic antibodies in the Churg-Strauss syndrome. Ann. Intern. Med. 143:9632–38 [Google Scholar]
  3. Flossmann O, Berden A, de Groot K. 3.  et al. 2011. Long-term patient survival in ANCA-associated vasculitis. Ann. Rheum. Dis. 70:3488–94 [Google Scholar]
  4. Hoffman GS, Kerr GS, Leavitt RY. 4.  et al. 1992. Wegener granulomatosis: an analysis of 158 patients. Ann. Intern. Med. 116:6488–98 [Google Scholar]
  5. de Groot K, Rasmussen N, Bacon PA. 5.  et al. 2005. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 52:82461–89 [Google Scholar]
  6. Stone JH, Merkle PA, Spiera R. 6.  et al. 2010. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N. Engl. J. Med. 363:3221–32 [Google Scholar]
  7. Jones RB, Tervaert JW, Hauser T. 7.  et al. 2010. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N. Engl. J. Med. 363:3211–20 [Google Scholar]
  8. Stone JH, Wegener's. 8.  Granulomatosis Etanercept Trial Research Group 2003. Limited versus severe Wegener's granulomatosis: baseline data on patients in the Wegener's granulomatosis etanercept trial. Arthritis Rheum. 48:82299–309 [Google Scholar]
  9. de Groot K, Harper L, Jayne DR. 9.  et al. 2009. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann. Intern. Med. 150:10670–80 [Google Scholar]
  10. Harper L, Morgan MD, Walsh M. 10.  et al. 2012. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann. Rheum. Dis. 71:6955–60 [Google Scholar]
  11. de Groot K, Adu D, Savage CO. 11.  European Vasculitis Study Group (EUVAS) 2001. The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol. Dial. Transplant. 16:102018–27 [Google Scholar]
  12. Mukhtyar C, Guillevin L, Cid MC. 12.  et al. 2009. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann. Rheum. Dis. 68:3310–17 [Google Scholar]
  13. Falagas ME, Manta KG, Betsi GI, Pappas G. 13.  2007. Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review. Clin. Rheumatol. 26:5663–70 [Google Scholar]
  14. Cupps TR, Edgar LC, Fauci AS. 14.  1982. Suppression of human B lymphocyte function by cyclophosphamide. J. Immunol. 128:62453–57 [Google Scholar]
  15. Faurschou M, Westman K, Rasmussen N. 15.  et al. 2012. Brief report: long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 34:103472–77 [Google Scholar]
  16. Hogan SL, Falk RJ, Chin H. 16.  et al. 2005. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann. Intern. Med. 143:9621–31 [Google Scholar]
  17. Walsh M, Flossmann O, Berden A. 17.  et al. 2012. Risk factors for relapse of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 64:2542–48 [Google Scholar]
  18. Pagnoux C, Hogan SL, Chin H. 18.  et al. 2008. Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum. 58:92908–18 [Google Scholar]
  19. Jayne D, Rasmussen N, Andrassy K. 19.  et al. 2003. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N. Engl. J. Med. 349:136–44 [Google Scholar]
  20. Pagnoux C, Mahr A, Hamidou MA. 20.  et al. 2008. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N. Engl. J. Med. 359:262790–803 [Google Scholar]
  21. Metzler C, Miehle N, Manger K. 21.  et al. 2007. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis. Rheumatology 46:71087–91 [Google Scholar]
  22. Bremer JP1, Ullrich S, Laudien M. 22.  et al. 2010. Methotrexate plus leflunomide for the treatment of relapsing Wegener's granulomatosis. A retrospective uncontrolled study. Clin. Exp. Rheumatol. 28:1 Suppl. 5767–71 [Google Scholar]
  23. Hiemstra TF, Walsh M, Mahr A. 23.  et al. 2010. Mycophenolate mofetil versus azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 304:212381–88 [Google Scholar]
  24. Silva F, Specks U, Kalra S. 24.  et al. 2010. Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement—a prospective, open-label pilot trial. Clin. J. Am. Soc. Nephrol. 5:3445–53 [Google Scholar]
  25. Han F, Liu G, Zhang X. 25.  et al. 2011. Effects of mycophenolate mofetil combined with corticosteroids for induction therapy of microscopic polyangiitis. Am. J. Nephrol. 33:2185–92 [Google Scholar]
  26. Alba MA, Flores-Suarez LF. 26.  2013. Seven clinical conundrums in the treatment of ANCA-associated vasculitis. Clin. Exp. Rheumatol. 31:Suppl. 7574–83 [Google Scholar]
  27. Tadema H, Heeringa P, Kallenberg CG. 27.  2011. Bacterial infections in Wegener's granulomatosis: mechanisms potentially involved in autoimmune pathogenesis. Curr. Opin. Rheumatol. 23:4366–71 [Google Scholar]
  28. Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG. 28.  1996. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N. Engl. J. Med. 335:116–20 [Google Scholar]
  29. Specks U, Merkle PA, Seo P. 29.  et al. 2013. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N. Engl. J. Med. 369:5417–27 [Google Scholar]
  30. Cartin-Ceba R, Golbin J, Keogh KA. 30.  et al. 2012. Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's): a single-center ten-year experience. Arthritis Rheum. 64:113770–78 [Google Scholar]
  31. Smith RM, Jones RB, Guerry M. 31.  et al. 2012. Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 64:113760–69 [Google Scholar]
  32. Calich AL, Puéchal X, Pugnet G. 32.  et al. 2014. Rituximab for induction and maintenance therapy in granulomatosis with polyangiitis (Wegeners). Results of a single-center cohort study on 66 patients. J. Autoimmun. 50:135–41 [Google Scholar]
  33. 33. Wegener's Granulomatosis Etanercept Research Group 2005. Etanercept plus standard therapy for Wegener's granulomatosis. N. Engl. J. Med. 352:4351–61 [Google Scholar]
  34. Pusey CD, Rees AJ, Evans DJ. 34.  et al. 1991. Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int. 40:4757–63 [Google Scholar]
  35. Jayne DR, Gaskin G, Rasmussen N. 35.  et al. 2007. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J. Am. Soc. Nephrol. 18:72180–88 [Google Scholar]
  36. Klemmer PJ, Chalermskulrat W, Reif MS. 36.  et al. 2003. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am. J. Kidney Dis. 42:61149–52 [Google Scholar]
  37. Walsh M, Merkle PA, Peh CA. 37.  et al. 2013. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials 14:73 [Google Scholar]
  38. Bayry J, Negi VS, Kayeri SV. 38.  2011. Intravenous immunoglobulin therapy in rheumatic diseases. Nat. Rev. Rheumatol. 7:6349–59 [Google Scholar]
  39. Jayne DR, Chapel H, Adu D. 39.  et al. 2000. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 93:7433–39 [Google Scholar]
  40. Martinez V, Cohen P, Pagnoux C. 40.  et al. 2008. Intravenous immunoglobulins for relapses of systemic vasculitides associated with antineutrophil cytoplasmic autoantibodies: results of a multicenter, prospective, open-label study of twenty-two patients. Arthritis Rheum. 58:1308–17 [Google Scholar]
  41. Richter C, Schnabel A, Csernok E. 41.  et al. 1995. Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin. Clin. Exp. Immunol. 101:12–7 [Google Scholar]
  42. Aries PM, Hellmich B, Gross WL. 42.  2005. Intravenous immunoglobulin therapy in vasculitis: speculation or evidence?. Clin. Rev. Allergy Immunol. 29:3237–45 [Google Scholar]
  43. Perenyei M, Jayne DR, Floßmann O. 43.  2014. Gusperimus: immunological mechanism and clinical applications. Rheumatology 531732–41 [Google Scholar]
  44. Flossman O, Baslund B, Bruchfeld A. 44.  et al. 2009. Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. Ann. Rheum. Dis. 68:71125–30 [Google Scholar]
  45. Schmitt WH, Birck R, Heinzel PA. 45.  et al. 2005. Prolonged treatment of refractory Wegener's granulomatosis with 15-deoxyspergualin: an open study in seven patients. Nephrol. Dial. Transplant. 20:61083–92 [Google Scholar]
  46. Holle J, Dubrau C, Herlyn K. 46.  et al. 2012. Rituximab for refractory granulomatosis with polyangiitis: comparison of efficacy in granulomatous versus vasculitic manifestation. Ann. Rheum. Dis. 71:3327–33 [Google Scholar]
  47. Aries PM, Hellmich B, Voswinkel J. 47.  et al. 2006. Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations. Ann. Rheum. Dis. 65:7853–85 [Google Scholar]
  48. Seo P, Specks U, Keogh KA. 48.  2008. Efficacy of rituximab in limited Wegener's with refractory granulomatous manifestations. J. Rheum. 35:102017–23 [Google Scholar]
  49. Martinez DP, Chaudhry A, Jones RB. 49.  et al. 2009. B-cell depletion with rituximab for refractory head and neck Wegener's granulomatosis: a cohort study. Clin. Otolaryngol. 34:4328–35 [Google Scholar]
  50. Lally L, Lebovic R, Huang WT, Spiera R. 50.  2014. Effectiveness of rituximab for the otolaryngologic manifestations of granulomatosis with polyangiitis. Arthritis Care Res. 66:1403–9 [Google Scholar]
  51. Xiao H, Schreiber A, Heeringa P. 51.  et al. 2007. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am. J. Pathol. 170:152–64 [Google Scholar]
  52. Schreiber A, Xiao H, Jeannette JC. 52.  et al. 2009. C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J. Am. Soc. Nephrol. 20:289–98 [Google Scholar]
  53. Yuan J, Gou SJ, Huang J. 53.  2012. C5a and its receptors in human anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Arthritis Res. Ther. 14:3R140–52 [Google Scholar]
  54. Xiao H, Dairaghi DJ, Powers JP. 54.  et al. 2014. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J. Am. Soc. Nephrol. 25:2225–31 [Google Scholar]
  55. Berden AE, Jones RB, Erasmus DD. 55.  et al. 2012. Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody associated glomerulonephritis after rituximab therapy. J. Am. Soc. Nephrol. 23:2313–21 [Google Scholar]
  56. Wilde B, Thewissen M, Deamoiseaux J. 56.  et al. 2010. T cells in ANCA-associated vasculitis: What can we learn from lesional versus circulating T cells?. Arthritis Res. Ther. 12:1204–13 [Google Scholar]
  57. McKinney EF, Lyons PA, Carr EJ. 57.  2010. A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nat. Med. 16:5586–91 [Google Scholar]
  58. Langford CA, Monarch PA, Specks U. 58.  et al. 2013. An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener's). Ann. Rheum. Dis. 73:71376–9 [Google Scholar]
  59. Walsh M, Chaudhry A, Jayne D. 59.  2008. Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-IH). Ann. Rheum. Dis. 67:91322–27 [Google Scholar]
  60. Comarmond C, Pagnoux C, Khellaf M. 60.  et al. 2013. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 65:1270–81 [Google Scholar]
  61. Sinico RA, Di Toma L, Maggiore U. 61.  et al. 2005. Renal involvement in Churg-Strauss syndrome. Am. J. Kidney Dis. 47:5770–79 [Google Scholar]
  62. Guillevin L, Lhote F, Gayraud M. 62.  et al. 1996. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine 75:117–28 [Google Scholar]
  63. Guillevin L, Pagnoux C, Seror R. 63.  et al. 2011. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine 90:119–27 [Google Scholar]
  64. Ribi C, Cohen P, Pagnoux C. 64.  et al. 2008. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum. 58:2586–94 [Google Scholar]
  65. Gayraud M, Guillevin L, le Toumelin P. 65.  et al. 2001. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis Rheum. 44:3666–75 [Google Scholar]
  66. Thiel J, Hässler F, Salzer U. 66.  et al. 2013. Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Arthritis Res. Ther. 15:5R133–42 [Google Scholar]
  67. Jakiela B, Szczeklik W, Plutecka H. 67.  et al. 2012. Increased production of IL-5 and dominant Th2-type response in airways of Churg-Strauss syndrome patients. Rheumatology 51:101887–93 [Google Scholar]
  68. Kim S, Marigowda G, Oren E. 68.  et al. 2010. Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome. J. Allergy Clin. Immunol. 125:61336–43 [Google Scholar]
  69. Moosig F, Gross WL, Hermann K. 69.  et al. 2011. Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome. Ann. Intern. Med. 155:5341–34 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error