Skip to main content

Advertisement

Log in

Combination therapy in autoimmune disease: vasculitis

  • Disease Specific Section
  • Published:
Springer Seminars in Immunopathology Aims and scope Submit manuscript

Conclusion

Therapy is becoming more effective as it is increasingly tailored to both the degree of activity, or disease extent, and the specific syndrome. As acute mortality has decreased, the need to look beyond the immediate flare has supported the use of staged regimes using combinations of drugs which can diminish toxicity. However, the residual mortality, morbidity and high relapse rate suggest there is a continuing need to improve these regimes.

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

  1. Adu D, Pall A, Luqmani RA, Richards NT, Howie AJ, Emery P, Michael J, Savage CO, Bacon PA (1997) Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. QJM 90:401

    Article  PubMed  CAS  Google Scholar 

  2. Allen MB, Caldwell DS, Rice JR (1993) Cyclosporin A therapy for Wegener’s granulomatosis. Adv Exp Med Biol 336:473

    PubMed  CAS  Google Scholar 

  3. Bacon PA, Carruthers DM (1995) Vasculitis associated with connective-tissue disorders. Rheum Dis Clin North Am 21:1077

    PubMed  CAS  Google Scholar 

  4. Ballieux BE, Hiemstra PS, Klar-Mohamad N, Hagen EC, Es LA van, Woude FJ van der, Daha MR (1994) Detachment and cytolysis of human endothelial cells by proteinase 3. Eur J Immunol 24:3211

    Article  PubMed  CAS  Google Scholar 

  5. Breedveld FC, Daha MR (1996) Vasculitis: mechanisms of injury. In: Ansell BM, Bacon PA, Lie JT, Yazici H (eds) The vasculitides: science and practice. Chapman and Hall, London, pp 39–47

    Google Scholar 

  6. Brouwer E, Huitema MG, Mulder AHL, Heeringa P, Vangoor H, Tervaert JWC, Weening JJ, Kallen-berg CGM (1994) Neutrophil activation in-vitro and in-vivo in Wegener’s granulomatosis. Kidney Int 45:1120

    Article  PubMed  CAS  Google Scholar 

  7. Carruthers DM, Bacon PA (2000) Stem cell transplantation in systemic vasculitis. In: Kallenberg CGM, Tervaert JWC (eds) Disease-modifying therapy in the vasculitides. Birkhauser, Basel (in Press)

    Google Scholar 

  8. Carruthers DM, Exley AR, Williams R, Buckley CD, Amft N, Raza K, Rowe I, Bacon PA (1998) Intensive pulse cyclophosphamide for remission induction in systemic necrotising vasculitis. Arthritis Rheum 41:545

    Google Scholar 

  9. Choe YH, Han BK, Koh EM, Kim DK, Do YS, Lee WR (2000) Takayasu’s arteritis: assessment of disease activity with contrast-enhanced MR imaging. Am J Roentgenol 175:505

    CAS  Google Scholar 

  10. Daina E, Schieppati A, Remuzzi G (1999) Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three cases. Ann Intern Med 130:422

    PubMed  CAS  Google Scholar 

  11. De Groot K, Reinhold-Keller E, Tatsis E, Paulsen J, Heller M, Nolle B, Gross WL (1996) Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis — methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum 39:2052

    Article  PubMed  Google Scholar 

  12. Deremee RA, Mcdonald TJ, Harrison EG, Coles DT (1976) Wegener’s granulomatosis. Anatomic correlates, a proposed classification. Mayo Clin Proc 51:777

    PubMed  CAS  Google Scholar 

  13. Dillon MJ, Ansell BM (1995) Vasculitis in children and adolescents. Rheum Dis Clin North 21:1115

    CAS  Google Scholar 

  14. Exley AR, Bacon PA, Luqmani RA, Kitas GD, Carruthers DM, Moots R (1998) Examination of disease severity in systemic vasculitis from the novel perspective of damage using the vasculitis damage index (VDI). Br J Rheumatol 37:57

    Article  PubMed  CAS  Google Scholar 

  15. Exley AR, Carruthers DM, Luqmani RA, Kitas GD, Gordon C, Janssen BA, Savage COS, Bacon PA (1997) Damage occurs early in systemic vasculitis and is an index of outcome. QJM 90:391

    Article  PubMed  CAS  Google Scholar 

  16. Fauci AS, Haynes BF, Katz P, Wolff SM (1983) Wegeners granulomatosis — prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98:76

    PubMed  CAS  Google Scholar 

  17. Fauci AS, Katz P, Haynes BF, Wolff SM (1979) Cyclophosphamide therapy of severe systemic necrotising vasculitis. N Engl J Med 301:235

    PubMed  CAS  Google Scholar 

  18. Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis. Ann Rev Immunol 14:397

    Article  CAS  Google Scholar 

  19. Fraga A, Mintz G, Valle L, Flores-Izquierdo G (1972) Takayasu’s arteritis: frequency of systemic manifestations (study of 22 patients) and favorable response to maintenance steroid therapy with adrenocorticosteroids (12 patients). Arthritis Rheum 15:617

    Article  PubMed  CAS  Google Scholar 

  20. Frohnert PP, Sheps SG (1967) Long-term follow-up study of periarteritis nodosa. Am J Med 43:8

    Article  PubMed  CAS  Google Scholar 

  21. Gaskin G, Savage COS, Ryan JJ (1991) Anti-neutrophil cytoplasmic antibodies and disease activity during long-term follow-up of 70 patients with systemic vasculitis. Nephrol Dial Transplant 6:689

    PubMed  CAS  Google Scholar 

  22. Gordon M, Luqmani RA, Adu D, Greaves I, Richards N, Michael J, Emery P, Howie AJ, Bacon PA (1993) Relapses in patients with a systemic vasculitis. QJM 86:779

    PubMed  CAS  Google Scholar 

  23. Gross WL (1999) New concepts in treatment protocols for severe systemic vasculitis. Curr Opin Rheumatol 11:41

    Article  PubMed  CAS  Google Scholar 

  24. Guillevin L, Cevallos R, Durand-Gasselin B, Lhote F, Jarrousse B, Callard P (1997) Treatment of glomerulonephritis in microscopic polyangiitis and Churg- Strauss syndrome. Indications of plasma exchanges, meta-analysis of 2 randomized studies on 140 patients, 32 with glomerulonephritis. Ann Med Interne (Paris) 148:198

    CAS  Google Scholar 

  25. Guillevin L, Cordier JF, Lhote F, Cohen P, Jarrousse B, Royer I, Lesavre P, Jacquot C, Bindi P, Bielefeld P, Desson JF, Detree F, Dubois A, Hachulla E, Hoen B, Jacomy D, Seigneuric C, Lauque D, Stern M, Longy-Boursier M (1997) 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 40:2187

    Article  PubMed  CAS  Google Scholar 

  26. Guillevin L, Lhote F, Cohen P, Sauvaget F, Jarrousse B, Lortholary O, Noel LH, Trepo C (1995) Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients. Medicine (Baltimore) 74:238

    Article  CAS  Google Scholar 

  27. Guillevin L, Lhote F, Gayraud M, Cohen P, Jarrousse B, Lortholary O, Thibult N, Casassus P (1996) Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore) 75:17

    Article  CAS  Google Scholar 

  28. Gutfleisch J, Baumert E, Wolff-Vorbeck G, Schlesier M, Strutz HJ, Peter HH (1993) Increased expression of CD25 and adhesion molecules on peripheral blood lymphocytes of patients with Wegener’s granulomatosis (WG) and ANCA positive vasculitides. Adv Exp Med Biol 336:397

    PubMed  CAS  Google Scholar 

  29. Haubitz M, Koch KM, Brunkhorst R (1998) Cyclosporin for the prevention of disease reactivation in relapsing ANCA-associated vasculitis. Nephrol Dial Transplant 13:2074

    Article  PubMed  CAS  Google Scholar 

  30. Haubitz M, Schellong S, Gobel U, Schurek HJ, Schaumann D, Koch KM, Brunkhorst R (1998) Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study. Arthritis Rheum 41:1835

    Article  PubMed  CAS  Google Scholar 

  31. Healey LA (1991) Relation of giant-cell arteritis to polymyalgia-rheumatica. Baillieres Clin Rheumatol 5:371

    Article  PubMed  CAS  Google Scholar 

  32. Hind CRK, Lockwood CM, Peters DK, Paraskevakou H, Evans DJ, Rees AJ (1983) Prognosis after immunosuppression of patients with crescentric nephritis requiring dialysis. Lancet 1:263

    Article  PubMed  CAS  Google Scholar 

  33. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS (1992) Wegener granulomatosis — an analysis of 158 patients. Ann Intern Med 116:488

    PubMed  CAS  Google Scholar 

  34. Hoffman GS, Leavitt RY, Fleisher TA, Minor JR, Fauci AS (1990) Treatment of Wegener’s granulomatosis with intermittent high-dose intravenous cyclophosphamide. Am J Med 89:403

    Article  PubMed  CAS  Google Scholar 

  35. Hoffman GS, Leavitt RY, Kerr GS, Fauci AS (1992) The treatment of Wegener’s granulomatosis with glucocorticosteroids and methotrexate. Arthritis Rheum 35:1322

    PubMed  CAS  Google Scholar 

  36. Hoffman GS, Specks U (1998) Antineutrophil cytoplasmic antibodies. Arthritis Rheum 41:1521

    PubMed  CAS  Google Scholar 

  37. Ito S, Ueno M, Arakawa M, Saito T, Aoyagis T, Fujiwara M (1990) Therapeutic effect of 15-deoxy-spergualin on the progression of lupus nephritis in MRL mice. Clin Exp Immunol 81:446

    PubMed  CAS  Google Scholar 

  38. Jayne DRW (1992) Intravenous immunoglobulin in the therapy of systemic vasculitis. Trans Sci 13:317

    Article  Google Scholar 

  39. Jayne DRW (1998) Immunotherapy for ANCA-associated systemic vasculitis. Clin Exp Immunol 112:12

    Google Scholar 

  40. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CGM, Mccluskey RT, Sinico RA, Rees AJ, Vanes LA, Waldherr R, Wiik A (1994) Nomenclature of systemic vasculitides - proposal of an international consensus conference. Arthritis Rheum 37:187

    Article  PubMed  CAS  Google Scholar 

  41. Jordan SC, Toyoda M (1994) Treatment of autoimmune-diseases and systemic vasculitis with pooled human intravenous immune globulin. Clin Exp Immunol 97:31

    PubMed  Google Scholar 

  42. Kallenberg CGM, Tervaert JWC, VanderWoude FJ, Goldschmeding R, Vondemborne AEGK, Weening JJ (1991) Autoimmunity to lysosomal enzymes — new clues to vasculitis and glomerulonephritis. Immunol Today 12:61

    Article  PubMed  CAS  Google Scholar 

  43. Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M, Hoffman GS (1994) Takayasu arteritis. Ann Intern Med 120:919

    PubMed  CAS  Google Scholar 

  44. Kevil CG, Bullard DC (1999) Roles of leucocyte/endothelial cell adhesion molecules in the pathogenesis of vasculitis. Am J Med 106:677

    Article  PubMed  CAS  Google Scholar 

  45. King WJ, Adu D, Daha MR, Brooks CJ, Radford DJ, Pall AA, Savage CO (1995) Endothelial cells and renal epithelial cells do not express the Wegener’s autoantigen, proteinase 3. Clin Exp Immunol 102:98

    Article  PubMed  CAS  Google Scholar 

  46. Kovarsky J (1983) Clinical pharmacology and toxicology of cyclophosphamide — emphasis on use in rheumatic diseases. Semin Arthritis Rheum 12:359

    Article  PubMed  CAS  Google Scholar 

  47. Langford CA, Talar-Williams C, Barron KS, Sneller MC (1999) A staged approach to the treatment of Wegener’s granlomatosis. Arthritis Rheum 42:2666

    Article  PubMed  CAS  Google Scholar 

  48. Liu J (1993) FK506 and cyclosporin, molecular probes for studying intracellular signal transduction. Immunol Today 14:290

    Article  PubMed  CAS  Google Scholar 

  49. Lockwood CM (1979) Reversal of impaired splenic function of patients with nephritis or vasculitis (or both). N Engl J Med 300:524

    PubMed  CAS  Google Scholar 

  50. Lockwood CM, Thiru S, Stewart S, Hale G, Isaacs J, Wraight P, Elliott J, Waldmann H (1996) Treatment of refractory Wegener’s granulomatosis with humanized monoclonal antibodies. QJM 89:903

    PubMed  CAS  Google Scholar 

  51. Ludviksson BR, Sneller MC, Chua KS, TalarWilliams C, Langford CA, Ehrhardt RO, Fauci AS, Strober W (1998) Active Wegener’s granulomatosis is associated with HLA-DR+ CD4(+) T cells exhibiting an unbalanced Th1-type T cell cytokine pattern: reversal with IL-10. J Immunol 160: 3602

    PubMed  CAS  Google Scholar 

  52. Luqmani R, Jayne D (1999) A multi-centre randomised trial of cyclophosphamide versus azathioprine during remission in ANCA-associated systemic vasculitis (cycazarem). Arthritis Rheum 42:928

    Google Scholar 

  53. Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P, Savage C, Adu D (1994) Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 87:671

    PubMed  CAS  Google Scholar 

  54. Martin-Suarez I, D’Cruz D, Mansoor M, Fernandes AP, Khamashta MA, Hughes GR (1997) Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide. Ann Rheum Dis 56:481

    Article  PubMed  CAS  Google Scholar 

  55. Matteson EL, Gold KN, Bloch DA, Hunder GG (1996) Long-term survival of patients with Wegener’s granulomatosis from the American College of Rheumatology Wegener’s granulomatosis classification criteria cohort. Am J Med 101:129

    Article  PubMed  CAS  Google Scholar 

  56. Mayet WJ, Csernok E, Szymkowiak C, Gross WL, Meyer zum Buschenfelde KH (1993) Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener’s granulomatosis. Blood 82:1221

    PubMed  CAS  Google Scholar 

  57. McCarthy SA, Kuzu I, Gatter KC, Bicknell R (1991) Heterogeneity of the endothelial cell and its role in tumour metastasis. Trends Pharmacol Sci 12:462

    Article  PubMed  CAS  Google Scholar 

  58. Metzler C, Reinholdkeller E, Schmitt W, Gross WL (1997) Maintenance of remission with leflunomide in 11 patients with Wegeners granulomatosis. Arthritis Rheum 40:808

    Google Scholar 

  59. Mulder AH, Heeringa P, Brouwer E, Limburg PC, Kallenberg CG (1994) Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA): a Fc gamma RH-dependent process. Clin Exp Immunol 98:270

    PubMed  CAS  Google Scholar 

  60. Mulder AH, Stegeman CA, Kallenberg CG (1995) Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener’s granulomatosis: a predominant role for the IgG3 subclass of ANCA. Clin Exp Immunol 101:227

    PubMed  CAS  Google Scholar 

  61. Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, Glode MP, Mason WH, Reddy V, Sanders SP, Shulman ST, Wigins JW, Hicks RV, Fulton DR, Lewis AB, Leung DYM, Colton T, Rosen FS, Melish ME (1986) The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 315:341

    PubMed  CAS  Google Scholar 

  62. Nowack R, Gobel U, Klooker P, Andrassy K, VanderWoude FJ (1997) Mycophenolate mofetil is effective for maintenance therapy of systemic vasculitis. J Am Soc Nephrol 8:A0453

    Google Scholar 

  63. Pusey CD, Rees AJ, Evans DJ, Peters DK, Lockwood CM (1991) Plasma exchange in focal necrotising glomerulonephritis without anti-GBM antibodies. Kidney Int 40:757

    Article  PubMed  CAS  Google Scholar 

  64. Raza K, Exley AR, Carruthers DM, Buckley C, Hammond LA, Bacon PA (1999) Localized bowel vasculitis — postoperative cyclophosphamide or not? Arthritis Rheum 42:182

    Article  PubMed  CAS  Google Scholar 

  65. Reinhold-Keller E, De Groot K, Rudert H, Nolle B, Heller M, Gross WL (1996) Response to trimethoprim sulfamethoxazole in Wegener’s granulomatosis depends on the phase of disease. QJM 89:15

    PubMed  CAS  Google Scholar 

  66. Reinhold-Keller E, Kekow J, Schnabel A (1993) Effectiveness of cyclophosphamide pulse-treatment in Wegener’s granulomatosis. Adv Exp Med Biol 336:483

    PubMed  CAS  Google Scholar 

  67. Reinhold-Kelfer E, Kekow J, Schnabel A, Schmitt WH, Heller M, Beigel A, Duncker G, Gross WL (1994) Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with Wegeners granulomatosis. Arthritis Rheum 37:919

    Article  Google Scholar 

  68. Richter C, Schnabel A, Csernok E, De Groot K, Reinholdkeller E, Gross WL (1995) Treatment of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin. Clin Exp Immunol 101:2

    PubMed  CAS  Google Scholar 

  69. Rose GA, Spencer H (1957) Polyarteritis nodosa. QJM 26:43

    PubMed  CAS  Google Scholar 

  70. Savage COS, Winearls CG, Evans DG, Rees AJ, Lockwood CM (1985) Microscopic polyarteritis: presentation, pathology and prognosis. QJM 56:467

    PubMed  CAS  Google Scholar 

  71. Schaufelberger C, Andersson R, Nordborg E, (1998) No additive effect of cyclosporin A compared with glucocorticoid treatment alone in giant cell arteritis: results of an open, controlled, randomized study. Br J Rheumatol 37:464

    Article  PubMed  CAS  Google Scholar 

  72. Segal R, Yaron M, Tartakovsky B (1990) Methotrexate: mechanism of action in rheumatoid arthritis. Semin Arthritis Rheum 20:190

    Article  PubMed  CAS  Google Scholar 

  73. Shinohara M, Sone K, Tomomasa T, Morikawa A (1999) Corticosteroids in the treatment of the acute phase of Kawasaki disease. J Pediatr 135:465

    Article  PubMed  CAS  Google Scholar 

  74. Slavin S (1993) Treatment of life-threatening autoimmune-diseases with myeloablative doses of immunosuppressive agents — experimental background and rationale for ABMT. Bone Marrow Transplant 12:85

    PubMed  CAS  Google Scholar 

  75. Sneller MC, Hoffman GS, Talar-Williams C, Kerr GS, Hallahan CW, Fauci AS (1995) An analysis of forty-two Wegener’s granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum 38:608

    Article  PubMed  CAS  Google Scholar 

  76. Stegeman CA, Cohen Tervaert JW, Jong PE de, Kallenberg CG (1996) Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Eng J Med 335:16

    CAS  Google Scholar 

  77. Stegeman CA, Tervaert JW, Huitema MG, Jong PE de, Kallenberg CG (1994) Serum levels of soluble adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin in patients with Wegener’s granulomatosis. Relationship to disease activity and relevance during follow-up. Arthritis Rheum 37:1228

    Article  PubMed  CAS  Google Scholar 

  78. Stegeman CA, Tervaert JWC, Sluiter WJ, Manson WL, Jong PE de, Kallenberg CGM (1994) Association of chronic nasal carriage of staphylococcus-aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med 120:12

    PubMed  CAS  Google Scholar 

  79. Sundy JS, Haynes BF (1995) Pathogenic mechanisms of vessel damage in vasculitis syndromes. Rheum Dis Clin North Am 21:861

    PubMed  CAS  Google Scholar 

  80. Talar-Williams C, Hijazi YM, Walther MM, Linehan WM, Hallahan CW, Lubensky I, Kerr GS, Hoffman GS, Fauci AS, Sneller MC (1996) Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 124:477

    PubMed  CAS  Google Scholar 

  81. Tizard EJ, Suzuki A, Levin M, Dillon MJ (1991) Clinical aspects of 100 patients with kawasaki disease. Arch Dis Childhood 66:185

    Article  CAS  Google Scholar 

  82. Walton EW (1957) Giant cell granuloma of the respiratory tract (Wegener’s Granulomatosis). BMJ 2:265

    Article  Google Scholar 

  83. Weyand CM, Goronzy JJ (1995) Giant-cell arteritis as an antigen-driven disease. Rheum Dis Clin North Am 21:1027

    PubMed  CAS  Google Scholar 

  84. Wilke WS, Hoffman GS (1995) Treatment of corticosteroid-resistant giant cell arteritis. Rheum Dis Clin North Am 21:59

    PubMed  CAS  Google Scholar 

  85. Williams RC, Staud R, Malone CC, Payabyab J, Byres L, Underwood D (1994) Epitopes on proteinase recognized by antibodies from patients with Wegener’s granulomatosis. J Immunol 152:4722

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David M. Carruthers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carruthers, D.M., Bacon, P. Combination therapy in autoimmune disease: vasculitis. Springer Semin Immunopathol 23, 91–108 (2001). https://doi.org/10.1007/s002810100057

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002810100057

Keywords

Navigation