Skip to main content

Advertisement

Log in

Small-vessel vasculitis: Therapeutic management

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Small-vessel vasculitis is defined by the presence of blood vessel inflammation involving the arterioles, venules, or capillaries. This can be seen in a broad spectrum of settings, but it is most commonly associated with Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Although prednisone combined with cyclophosphamide induces remission and prolongs survival in these diseases, this regimen is toxic and does not prevent relapse. Current therapeutic approaches seek to minimize cyclophosphamide exposure through the use of staged induction-maintenance regimens or cyclophosphamide alternatives for induction of nonsevere disease. Emerging trials with biologic agents are exploring new treatment options.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Fauci A, Haynes B, 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.

    PubMed  CAS  Google Scholar 

  2. Hoffman GS, Kerr GS, Leavitt RY, et al.: Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992, 116:488–498.

    PubMed  CAS  Google Scholar 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. de Groot K, Adu D, Savage CO, et al.: The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant 2001, 16:2018–2027.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. Benenson E, Fries JW, Heilig B, et al.: High-dose azathioprine pulse therapy as a new treatment option in patients with active Wegener’s granulomatosis and lupus nephritis refractory or intolerant to cyclophosphamide. Clin Rheumatol 2005, 24:251–257.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. 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, 47:326–332.

    Article  PubMed  CAS  Google Scholar 

  11. Sneller M, Hoffman G, Talar-Williams C, et al.: Analysis of 42 Wegener’s granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum 1995, 38:608–613.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. Hoffman GS, Langford CA: Are there different forms of life in the antineutrophil cytoplasmic antibody universe? Ann Intern Med 2005, 143:683–685.

    PubMed  Google Scholar 

  14. Nowack R, Göbel 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.

    PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. Koukoulaki M, Jayne DR: Mycophenolate mofetil in anti-neutrophil cytoplasm antibodies-associated systemic vasculitis. Nephron Clin Pract 2006, 102:c100–107.

    Article  PubMed  CAS  Google Scholar 

  17. Joy MS, Hogan SL, Jennette JC, et al.: A pilot study using mycophenolate mofetil in relapsing or resistant ANCA small vessel vasculitis. Nephrol Dial Transplant 2005, 20:2725–2732.

    Article  PubMed  CAS  Google Scholar 

  18. 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, 66:798–802.

    Article  PubMed  CAS  Google Scholar 

  19. Metzler C, Fink C, Lamprecht P, et al.: Maintenance of remission with leflunomide in Wegener’s granulomatosis. Rheumatology (Oxford) 2004, 43:315–320.

    Article  CAS  Google Scholar 

  20. Metzler C, Wagner-Bastmeyer R, Gross W, et al.: Leflunomide versus methotrexate for maintenance of remission in Wegener’s granulomatosis-unexpected high relapse rate under oral methotrexate. Ann Rheum Dis 2005, 64(Suppl 3):262.

    Google Scholar 

  21. Jayne DR, Chapel H, Adu D, et al.: Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 2000, 93:433–439.

    Article  PubMed  CAS  Google Scholar 

  22. Clements PJ, Davis J: Cytotoxic drugs: their clinical application to the rheumatic diseases. Sem Arth Rheum 1986, 15:231–254.

    Article  CAS  Google Scholar 

  23. Allen NB, Caldwell DS, Rice JR, et al.: Cyclosporin A therapy for Wegener’s granulomatosis. Adv Exp Med Biol 1993, 336:473–476.

    PubMed  CAS  Google Scholar 

  24. Schmitt WH, Hagen EC, Neumann I, et al.: Treatment of refractory Wegener’s granulomatosis with antithymocyte globulin (ATG): an open study in 15 patients. Kidney Int 2004, 65:1440–1448.

    Article  PubMed  CAS  Google Scholar 

  25. Birck R, Newman M, Braun C, et al.: 15-Deoxyspergualin and cyclophosphamide, but not mycophenolatemofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis. Nephrol Dial Transplant 2006, 21:58–63.

    Article  PubMed  CAS  Google Scholar 

  26. DeRemee RA, McDonald TJ, Weiland LH: Wegener’s granulomatosis: observations on treatment with antimicrobial agents. Mayo Clin Proc 1985, 60:27–32.

    PubMed  CAS  Google Scholar 

  27. Stegeman CA, Cohen Tervaert JW, de Jong PE, et al.: Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. N Engl J Med 1996, 335:16–20.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  Google Scholar 

  29. Langford CA, Sneller MC, Hallahan CW, et al.: Clinical features and therapeutic management of subglottic stenosis in patients with Wegener’s granulomatosis. Arthritis Rheum 1996, 39:1754–1760.

    Article  PubMed  CAS  Google Scholar 

  30. Hoffman GS, Thomas-Golbanov CK, Chan J, et al.: Treatment of subglottic stenosis, due to Wegener’s granulomatosis, with intralesional corticosteroids and dilation. J Rheumatol 2003, 30:1017–1021.

    PubMed  Google Scholar 

  31. Wegener’s Granulomatosis Etanercept Trial Research Group: Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med 2005, 352:351–361.

    Article  Google Scholar 

  32. Stone JH, Holbrook JT, Marriott MA, et al.: Solid malignancies among patients in the Wegener’s Granulomatosis Etanercept Trial. Arthritis Rheum 2006, 54:1608–1618.

    Article  PubMed  CAS  Google Scholar 

  33. Mukhtyar C, Luqmani R: Current state of tumour necrosis factor alpha blockade in Wegener’s granulomatosis. Ann Rheum Dis 2005, 64(Suppl 4):iv31–36.

    Article  PubMed  CAS  Google Scholar 

  34. Aries PM, Lamprecht P, Gross WL: Biological therapies: new treatment options for ANCA-associated vasculitis? Expert Opin Biol Ther 2007, 7:521–533.

    Article  PubMed  CAS  Google Scholar 

  35. Booth A, Harper L, Hammad T, et al.: Prospective study of TNFalpha blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol 2004, 15:717–721.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    Article  PubMed  CAS  Google Scholar 

  37. 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 Rheum 2005, 52:262–268.

    Article  PubMed  Google Scholar 

  38. Keogh KA, Ytterberg SR, Fervenza FC, et al.: Rituximab for refractory Wegener’s granulomatosis: report of a prospective, open-label pilot trial. Am J Respir Crit Care Med 2006, 173:180–187.

    Article  PubMed  CAS  Google Scholar 

  39. Eriksson P: Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab. J Intern Med 2005, 257:540–548.

    Article  PubMed  CAS  Google Scholar 

  40. Stasi R, Stipa E, Del Poeta G, et al.: Long-term observation of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis treated with rituximab. Rheumatology (Oxford) 2006, 45:1432–1436.

    Article  CAS  Google Scholar 

  41. Omdal R, Wildhagen K, Hansen T, et al.: Anti-CD20 therapy of treatment-resistant Wegener’s granulomatosis: favourable but temporary response. Scand J Rheumatol 2005, 34:229–232.

    Article  PubMed  CAS  Google Scholar 

  42. Aries PM, Hellmich B, Voswinkel J, et al.: Lack of efficacy of rituximab in Wegener’s granulomatosis with refractory granulomatous manifestations. Ann Rheum Dis 2006, 65:853–858.

    Article  PubMed  CAS  Google Scholar 

  43. Sneller MC: Rituximab and Wegener’s granulomatosis: are B cells a target in vasculitis treatment? Arthritis Rheum 2005, 52:1–5.

    Article  PubMed  Google Scholar 

  44. Guillevin L, Cohen P, Gayraud M, et al.: Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999, 78:26–37.

    Article  CAS  Google Scholar 

  45. 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. Arthritis Rheum 2001, 44:666–675.

    Article  PubMed  CAS  Google Scholar 

  46. Pagnoux C, Guilpain P, Guillevin L: Churg-Strauss syndrome. Curr Opin Rheumatol 2007, 19:25–32.

    Article  PubMed  Google Scholar 

  47. Metzler C, Hellmich B, Gause A, et al.: Churg Strauss syndrome—successful induction of remission with methotrexate and unexpected high cardiac and pulmonary relapse ratio during maintenance treatment. Clin Exp Rheumatol 2004, 22(6 Suppl 36):S52–S61.

    PubMed  CAS  Google Scholar 

  48. Tatsis E, Schnabel A, Gross WL: Interferon-alpha treatment of four patients with the Churg-Strauss syndrome. Ann Intern Med 1998, 129:370–374.

    PubMed  CAS  Google Scholar 

  49. Metzler C, Lamprecht P, Hellmich B, et al.: Leucoencephalopathy after treatment of Churg-Strauss syndrome with interferon alpha. Ann Rheum Dis 2005, 64:1242–1243.

    Article  PubMed  CAS  Google Scholar 

  50. Kaushik VV, Reddy HV, Bucknall RC: Successful use of rituximab in a patient with recalcitrant Churg-Strauss syndrome. Ann Rheum Dis 2006, 65:1116–1117.

    Article  PubMed  CAS  Google Scholar 

  51. Koukoulaki M, Smith KG, Jayne DR: Rituximab in Churg-Strauss syndrome. Ann Rheum Dis 2006, 65:557–559.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carol A. Langford MD, MHS.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Langford, C.A. Small-vessel vasculitis: Therapeutic management. Curr Rheumatol Rep 9, 328–335 (2007). https://doi.org/10.1007/s11926-007-0052-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-007-0052-8

Keywords

Navigation