Pediatric Nephrology

, Volume 25, Issue 8, pp 1397–1407

ANCA-associated vasculitides—lessons from the adult literature

  • Joannis Vamvakopoulos
  • Caroline O. Savage
  • Lorraine Harper


Anti-neutrophil cytoplasmic antigen antibody (ANCA)-associated disease is a rare manifestation of primary systemic vasculitis in paediatric patients but one that carries significant morbidity, potential long-term disability and early mortality. It therefore requires a high index of suspicion, targeted investigation, prompt treatment and long-term follow-up with specialist input at every stage. The well-recognised diversity and overlap in clinical, laboratory and histopathological features of the ANCA-associated systemic vasculitides continue to hamper accurate diagnosis, confounding epidemiological data and necessitating a blanket approach to treatment, which is largely extrapolated from studies in adult patients and carries significant side-effects. Herein we summarise current knowledge of the epidemiology, pathogenesis, principal manifestations, investigation and evidence-based management, extrapolated from adult studies, of these disorders. We also discuss recent efforts towards classification of the childhood vasculitides that emphasise the value of histological diagnosis. Progress in our understanding of the pathophysiology underlying ANCA-associated disease should lead to targeted, safer and more effective therapies for these conditions. Nonetheless, many questions remain outstanding, and academic paediatricians face real challenges in identifying and collating the few cases they encounter into study cohorts. Meeting this challenge will require international collaboration, not only among paediatricians but also with the specialists taking over care of these patients as they reach adulthood.


Microscopic polyangiitis/polyarteritis Paediatric Vasculitis Wegener’s granulomatosis 



American College of Rheumatology


anti-neutrophil cytoplasmic antigen antibody


ANCA associated systemic vasculitis


cluster designation


Chapel Hill Consensus Conference




C-reactive protein


Churg–Strauss syndrome


computed tomography


chest x-ray


erythrocyte sedimentation rate


European Vasculitis Study Group


Fc receptor gamma chain


human leukocyte antigen


microscopic polyangiitis




proteinase 3


recombination activating gene 2


tumour necrosis factor alpha


Wegener’s granulomatosis


  1. 1.
    Ozen S (2005) Problems in classifying vasculitis in children. Pediatr Nephrol 20:1214–1218CrossRefPubMedGoogle Scholar
  2. 2.
    Jennette J, Falk R (2000) Do vasculitis categorization systems really matter? Curr Rheumatol Rep 2:430–438CrossRefPubMedGoogle Scholar
  3. 3.
    Rao JK, Allen NB, Pincus T (1998) Limitations of the 1990 American College of Rheumatology classification criteria in the diagnosis of vasculitis. Ann Intern Med 129:345–352PubMedGoogle Scholar
  4. 4.
    Fries J, Hunder G, Bloch D, Michel B, Arend W, Calabrese L, Fauci A, Leavitt R, Lie J, Lightfoot RJ, Masi A, McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifler NJ (1990) The American College of Rheumatology 1990 criteria for the classification of vasculitis: summary. Arthritis Rheum 33:1135–1136PubMedCrossRefGoogle Scholar
  5. 5.
    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, van Es LA, Waldherr R, Wiik A (1994) Nomenclature of systemic vasculitides: the proposal of an International Consensus Conference. Arthritis Rheum 37:187–192CrossRefPubMedGoogle Scholar
  6. 6.
    Sørensen S, Slot O, Tvede N, Petersen J (2000) A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature. Ann Rheum Dis 59:478–482CrossRefPubMedGoogle Scholar
  7. 7.
    Murali N, George R, John G, Chandi S, Jacob M, Jeyaseelan L, Thomas P, Jacob C (2002) Problems of classification of Henoch–Schönlein purpura: an Indian perspective. Clin Exp Dermatol 27:260–263CrossRefPubMedGoogle Scholar
  8. 8.
    Bruce I, Bell A (1997) A comparison of two nomenclature systems for primary systemic vasculitis. Br J Rheumatol 36:453–458CrossRefPubMedGoogle Scholar
  9. 9.
    Uppal SS, Hussain MA, Al-Raqum HA, Nampoory MR, Al-Saeid K, Al-Assousi A, Abraham M, Malaviya AN (2006) Henoch-Schonlein’s purpura in adults versus children/adolescents: A comparative study. Clin Exp Rheumatol 24:S26–30PubMedGoogle Scholar
  10. 10.
    Ozen S, Ruperto N, Dillon M, Bagga A, Barron K, Davin J, Kawasaki T, Lindsley C, Petty R, Prieur A, Ravelli A, Woo P (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis 65:936–941CrossRefPubMedGoogle Scholar
  11. 11.
    Matteson E (2000) Notes on the history of eponymic idiopathic vasculitis: the diseases of Henoch and Schönlein, Wegener, Churg and Strauss, Horton, Takayasu, Behçet and Kawasaki. Arthritis Care Res 13:237–245CrossRefPubMedGoogle Scholar
  12. 12.
    Grisaru S, Yuen GW, Miettunen PM, Hamiwka LA (2009) Incidence of Wegener’s granulomatosis in children. J Rheumatol. doi:10.3899/jrheum.090688 PubMedGoogle Scholar
  13. 13.
    Gardner-Medwin J, Dolezalova P, Cummins C, Southwood TR (2002) Incidence of Henoch-Schönlein purpura, Kawasaki disease and rare vasculitides in children of different ethnic origins. Lancet 360:1197–1202CrossRefPubMedGoogle Scholar
  14. 14.
    Watts RA, Al-Taiar A, Scott DG, Macgregor AJ (2009) Prevalence and incidence of Wegener’s granulomatosis in the UK general practice research database. Arthritis Rheum 61:1412–1416CrossRefPubMedGoogle Scholar
  15. 15.
    Mohammad AJ, Jacobsson LT, Westman KW, Sturfelt G, Segelmark M (2009) Incidence and survival rates in Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Rheumatology (Oxford) 48:1560–1565CrossRefGoogle Scholar
  16. 16.
    Zwerina J, Eger G, Englbrecht M, Manger B, Schett G (2008) Churg-Strauss syndrome in childhood: a systematic literature review and clinical comparison with adult patients. Semin Arthritis Rheum 39:108–115CrossRefPubMedGoogle Scholar
  17. 17.
    Knight A, Sandin S, Askling J (2008) Risks and relative risks of Wegener’s granulomatosis among close relatives of patients with the disease. Arthritis Rheum 58:302–307CrossRefPubMedGoogle Scholar
  18. 18.
    Slot MC, Sokolowska MG, Savelkouls KG, Janssen RG, Damoiseaux JG, Cohen Tervaert JW (2008) Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis. Clin Immunol 128:39–45CrossRefPubMedGoogle Scholar
  19. 19.
    Segelmark M, Elzouki A, Weislander J, Eriksson S (1995) The PiZ gene of α1-antitrypsin as a determinant of outcome in Pr3-ANCA-positive vasculitis. Kidney Int 48:844–850CrossRefPubMedGoogle Scholar
  20. 20.
    Biezeveld MH, Geissler J, Weverling GJ, Kuipers IM, Lam J, Ottenkamp J, Kuijpers TW (2006) Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease. Arthritis Rheum 54:369–376CrossRefPubMedGoogle Scholar
  21. 21.
    Kamesh L, Heward JM, Williams JM, Gough SC, Savage CO, Harper L (2007) Mannose-binding lectin gene polymorphisms in a cohort study of ANCA-associated small vessel vasculitis. Rheumatology (Oxford) 46:1076–1078CrossRefGoogle Scholar
  22. 22.
    Fujieda M, Hattori M, Kurayama H, Koitabashi Y (2002) Clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment. J Am Soc Nephrol 13:437–445PubMedGoogle Scholar
  23. 23.
    Sato H, Hattori M, Fujieda M, Sugihara S, Inomata H, Hoshi M, Miyamoto S (2000) High prevalence of antineutrophil cytoplasmic antibody positivity in childhood onset Graves’ disease treated with propylthiouracil. J Clin Endocrinol Metab 85:4270–4273CrossRefPubMedGoogle Scholar
  24. 24.
    Stegeman CA, Cohen Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG (1994) Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegner's granulomatosis. Ann Intern Med 120:74–75Google Scholar
  25. 25.
    Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG: Dutch Co-Trimoxazole Wegener Study Group (1996) Trimethoprim-sulfamethoxazole for the prevention of relapses of Wegener’s granulomatosis. N Engl J Med 335:16–20CrossRefGoogle Scholar
  26. 26.
    Kain R, Exner M, Brandes R, Ziebermayr R, Cunningham D, Alderson CA, Davidovits A, Raab I, Jahn R, Ashour O, Spitzauer S, Sunder-Plassmann G, Fukuda M, Klemm P, Rees AJ, Kerjaschki D (2008) Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med 14:1088–1096CrossRefPubMedGoogle Scholar
  27. 27.
    Hagen E, Daha M, Hermans J, Andrassay K, Csernok E, Gaskin G, Lesavre P, Ludemann J, Rasmussen N, Sinico R, Wiik A, van der Woude F (1998) Diagnostic value of standardised assays for antineutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. Kidney Int 53:743–753CrossRefPubMedGoogle Scholar
  28. 28.
    Bansal PJ, Tobin MC (2004) Neonatal microscopic polyangiitis secondary to transfer of maternal myeloperoxidase-antineutrophil cytoplasmic antibody resulting in neonatal pulmonary hemorrhage and renal involvement. Ann Allergy Asthma Immunol 93:398–401CrossRefPubMedGoogle Scholar
  29. 29.
    Silva F, Specks U, Sethi S, Irazabal M, Fervenza FC (2009) Successful pregnancy and delivery of a healthy newborn despite transplacental transfer of antimyeloperoxidase antibodies from a mother with microscopic polyangiitis. Am J Kidney Dis 54:542–545CrossRefPubMedGoogle Scholar
  30. 30.
    Xiao H, Heeringa P, Hu P, Liu Z, Zhao M, Aratani Y, Maeda N, Falk RJ, Jennette JC (2002) Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 110:955–963PubMedGoogle Scholar
  31. 31.
    Xiao H, Heeringa P, Liu Z, Huugen D, Hu P, Maeda N, Falk RJ, Jennette JC (2005) The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies. Am J Pathol 167:39–45PubMedGoogle Scholar
  32. 32.
    Schreiber A, Xiao H, Falk RJ, Jennette JC (2006) Bone marrow-derived cells are sufficient and necessary targets to mediate glomerulonephritis and vasculitis induced by anti-myeloperoxidase antibodies. J Am Soc Nephrol 17:3355–3364CrossRefPubMedGoogle Scholar
  33. 33.
    Harper L, Cockwell P, Adu D, Savage C (2001) Neutrophil priming and apoptosis in ANCA-associated vasculitis. Kidney Int 59:1729–1738CrossRefPubMedGoogle Scholar
  34. 34.
    Muller Kubold A, Mesander G, Stegeman C, Kallenberg C, Cohen Tervaert J (1998) Are circulating neutrophils intravascularly activated in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides? Clin Exp Immunol 114:491–499CrossRefGoogle Scholar
  35. 35.
    Huugen D, Xiao H, van Esch A, Falk RJ, Peutz-Kootstra CJ, Buurman WA, Tervaert JW, Jennette JC, Heeringa P (2005) Aggravation of anti-myeloperoxidase antibody-induced glomerulonephritis by bacterial lipopolysaccharide: role of tumor necrosis factor-alpha. Am J Pathol 167:47–58PubMedGoogle Scholar
  36. 36.
    Falk RJ, Terrell RS, Charles LA, Jennette JC (1990) Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci USA 87:4115–4119CrossRefPubMedGoogle Scholar
  37. 37.
    Williams JM, Kamesh L, Savage CO (2005) Translating basic science into patient therapy for ANCA-associated small vessel vasculitis. Clin Sci (Lond) 108:101–112CrossRefGoogle Scholar
  38. 38.
    Reumaux D, Kuijpers TW, Hordijk PL, Duthilleul P, Roos D (2003) Involvement of Fcgamma receptors and beta2 integrins in neutrophil activation by anti-proteinase-3 or anti-myeloperoxidase antibodies. Clin Exp Immunol 134:344–350CrossRefPubMedGoogle Scholar
  39. 39.
    Nolan SL, Kalia N, Nash GB, Kamel D, Heeringa P, Savage CO (2008) Mechanisms of ANCA-mediated leukocyte-endothelial cell interactions in vivo. J Am Soc Nephrol 19:973–984CrossRefPubMedGoogle Scholar
  40. 40.
    Lamprecht P (2005) Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Clin Exp Immunol 141:201–210CrossRefPubMedGoogle Scholar
  41. 41.
    Giscombe R, Wang XB, Kakoulidou M, Lefvert AK (2006) Characterization of the expanded T-cell populations in patients with Wegener’s granulomatosis. J Intern Med 260:224–230CrossRefPubMedGoogle Scholar
  42. 42.
    Voswinkel J, Mueller A, Kraemer JA, Lamprecht P, Herlyn K, Holl-Ulrich K, Feller AC, Pitann S, Gause A, Gross WL (2006) B lymphocyte maturation in Wegener’s granulomatosis: a comparative analysis of VH genes from endonasal lesions. Ann Rheum Dis 65:859–864CrossRefPubMedGoogle Scholar
  43. 43.
    Hooke D, Gee D, Atkins R (1987) Leukocyte analysis using monoclonal antibodies in glomerulonephritis. Kidney Int 31:964–972CrossRefPubMedGoogle Scholar
  44. 44.
    Popa ER, Stegeman CA, Bos NA, Kallenberg CG, Tervaert JW (1999) Differential B-and T-cell activation in Wegener’s granulomatosis. J Allergy Clin Immunol 103:885–894CrossRefPubMedGoogle Scholar
  45. 45.
    Culton DA, Nicholas MW, Bunch DO, Zhen QL, Kepler TB, Dooley MA, Mohan C, Nachman PH, Clarke SH (2007) Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. J Clin Immunol 27:53–68CrossRefPubMedGoogle Scholar
  46. 46.
    Cabral DA, Uribe AG, Benseler S, O’Neil KM, Hashkes PJ, Higgins G, Zeft AS, Lovell DJ, Kingsbury DJ, Stevens A, McCurdy D, Chira P, Abramson L, Arkachaisri T, Campillo S, Eberhard A, Hersh AO, Huber AM, Kim S, Klein-Gitelman M, Levy DM, Li SC, Mason T, Dewitt EM, Muscal E, Nassi L, Reiff A, Schikler K, Singer NG, Wahezi D, Woodward A (2009) Classification, presentation, and initial treatment of Wegener’s granulomatosis in childhood. Arthritis Rheum 60:3413–3424CrossRefPubMedGoogle Scholar
  47. 47.
    Akikusa JD, Schneider R, Harvey EA, Hebert D, Thorner PS, Laxer RM, Silverman ED (2007) Clinical features and outcome of pediatric Wegener’s granulomatosis. Arthritis Rheum 57:837–844CrossRefPubMedGoogle Scholar
  48. 48.
    Hattori M, Kurayama H, Koitabashi Y (2001) Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in children. J Am Soc Nephrol 12:1493–1500PubMedGoogle Scholar
  49. 49.
    Belostotsky VM, Shah V, Dillon MJ (2002) Clinical features in 17 paediatric patients with Wegener granulomatosis. Pediatr Nephrol 17:754–761CrossRefPubMedGoogle Scholar
  50. 50.
    Lane SE, Watts RA, Shepstone L, Scott DG (2005) Primary systemic vasculitis: clinical features and mortality. Q J Med 98:97–111Google Scholar
  51. 51.
    Rottem M, Fauci A, Hallahan C, Kerr G, Lebovics R, Leavitt R, Hoffman G (1993) Wegener granulomatosis in children and adolescents: clinical presentation and outcome. J Pediatr 122:26–31CrossRefPubMedGoogle Scholar
  52. 52.
    Kallenberg C, Heeringa P, Stegeman C (2006) Mechanisms of disease: pathogenesis and treatment of ANCA-associated vasculitides. Nat Clin Pract Rheumatol 2:661–670CrossRefPubMedGoogle Scholar
  53. 53.
    Stassen PM, Derks RP, Kallenberg CG, Stegeman CA (2008) Venous thromboembolism in ANCA-associated vasculitis—incidence and risk factors. Rheumatology (Oxford) 47:530–534CrossRefGoogle Scholar
  54. 54.
    Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Allen NB, Davis JC Jr, Hoffman GS, McCune WJ, St Clair EW, Specks U, Spiera R, Petri M, Stone JH (2005) Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener’s Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med 142:620–626PubMedGoogle Scholar
  55. 55.
    Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P, Adu D (1994) Birmingham Vasculitis Activity Score (BVAS) in systemic necrotising vasculitis. Q J Med 87:671–678Google Scholar
  56. 56.
    Birck R, Schmitt WH, Kaelsch IA, van der Woude FJ (2006) Serial ANCA determinations for monitoring disease activity in patients with ANCA-associated vasculitis: systematic review. Am J Kidney Dis 47:15–23CrossRefPubMedGoogle Scholar
  57. 57.
    Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, Hauser T, Hellmich B, Jayne D, Kallenberg CG, Merkel PA, Raspe H, Salvarani C, Scott DG, Stegeman C, Watts R, Westman K, Witter J, Yazici H, Luqmani R (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 68:310–317CrossRefPubMedGoogle Scholar
  58. 58.
    Mukhtyar C, Flossmann O, Hellmich B, Bacon P, Cid M, Cohen-Tervaert JW, Gross WL, Guillevin L, Jayne D, Mahr A, Merkel PA, Raspe H, Scott D, Witter J, Yazici H, Luqmani RA (2008) Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism Systemic Vasculitis Task Force. Ann Rheum Dis 67:1004–1010CrossRefPubMedGoogle Scholar
  59. 59.
    de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO, EUVAS (European Vasculitis Study Group) (2009) Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis. A randomized trial. Ann Intern Med 150:670–680PubMedGoogle Scholar
  60. 60.
    Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C (2003) A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 349:36–44CrossRefPubMedGoogle Scholar
  61. 61.
    Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RA, Pusey CD (2007) Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 18:2180–2188CrossRefPubMedGoogle Scholar
  62. 62.
    Tizard E, Dillon M (1991) Plasmapheresis in childhood. Care Critically Ill 7:51–56Google Scholar
  63. 63.
    DM WE, Tullus K (2007) Childhood vasculitis and plasma exchange. Eur J Pediatr 166:145–151Google Scholar
  64. 64.
    de Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, Gross WL, Luqmani R, Jayne DR (2005) Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 52:2461–2469CrossRefPubMedGoogle Scholar
  65. 65.
    Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, Kyndt X, Lifermann F, Papo T, Lambert M, Le Noach J, Khellaf M, Merrien D, Puechal X, Vinzio S, Cohen P, Mouthon L, Cordier JF, Guillevin L (2008) Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 359:2790–2803CrossRefPubMedGoogle Scholar
  66. 66.
    Hiemstra T, Walsh M, De Groot K, Hauser T, Mahr A, Pagnoux C, Harper L, Savage C, Tesar V, Neumann I, Wissing K, Schmitt W, Jayne D (2009) Randomized trial of mycophenolate mofetil versus azathioprine for maintenance therapy in ANCA-associated vasculitis. APMIS 117[Suppl 127]:177Google Scholar
  67. 67.
    Brunner J, Freund M, Prelog M, Binder E, Sailer-Hoeck M, Jungraithmayr T, Huemer C, Sergi C, Zimmerhackl LB (2009) Successful treatment of severe juvenile microscopic polyangiitis with rituximab. Clin Rheumatol 28:997–999CrossRefPubMedGoogle Scholar
  68. 68.
    Patel AM, Lehman TJ (2008) Rituximab for severe refractory pediatric Wegener granulomatosis. J Clin Rheumatol 14:278–280CrossRefPubMedGoogle Scholar
  69. 69.
    Jones RB, Ferraro AJ, Chaudhry AN, Brogan P, Salama AD, Smith KG, Savage CO, Jayne DR (2009) A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 60:2156–2168CrossRefPubMedGoogle Scholar
  70. 70.
    Eleftheriou D, Melo M, Marks SD, Tullus K, Sills J, Cleary G, Dolezalova P, Ozen S, Pilkington C, Woo P, Klein N, Dillon MJ, Brogan PA (2009) Biologic therapy in primary systemic vasculitis of the young. Rheumatology (Oxford) 48:978–986CrossRefGoogle Scholar
  71. 71.
    Walsh M, Jayne D (2007) Rituximab in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis and systemic lupus erythematosus: past, present and future. Kidney Int 72:676–682CrossRefPubMedGoogle Scholar
  72. 72.
    Ferraro AJ, Drayson MT, Savage CO, MacLennan IC (2008) Levels of autoantibodies, unlike antibodies to all extrinsic antigen groups, fall following B cell depletion with rituximab. Eur J Immunol 38:292–298CrossRefPubMedGoogle Scholar
  73. 73.
    Ferraro AJ, Smith SW, Neil D, Savage CO (2008) Relapsed Wegener’s granulomatosis after rituximab therapy—B cells are present in new pathological lesions despite persistent ‘depletion’ of peripheral blood. Nephrol Dial Transplant 23:3030–3032CrossRefPubMedGoogle Scholar
  74. 74.
    Jones RB, Walsh M, Jayne D, EUVAS (2008) Randomised trial of rituximab versus cyclophosphamide for ANCA-associated vasculitis. J Am Soc Nephrol 19:61AGoogle Scholar
  75. 75.
    Wilkinson NM, Erendzhinova E, Zeft A, Cabral DA (2006) Infliximab as rescue therapy in three cases of paediatric Wegener’s granulomatosis. Rheumatology (Oxford) 45:1047–1048CrossRefGoogle Scholar
  76. 76.
    WGET Research Group (2005) Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med 352:351–361CrossRefGoogle Scholar
  77. 77.
    Martinez V, Cohen P, Pagnoux C, Vinzio S, Mahr A, Mouthon L, Sailler L, Delaunay C, Sadoun A, Guillevin L (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 58:308–317CrossRefPubMedGoogle Scholar
  78. 78.
    Flossmann O, Baslund B, Bruchfeld A, Cohen Tervaert JW, Hall C, Heinzel P, Hellmich B, Luqmani RA, Nemoto K, Tesar V, Jayne DR (2009) Deoxyspergualin in relapsing and refractory Wegener’s granulomatosis. Ann Rheum Dis 68:1125–1130CrossRefPubMedGoogle Scholar
  79. 79.
    Walsh M, Chaudhry A, Jayne DR (2008) Long-term follow-up of relapsing/refractory ANCA associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H). Ann Rheum Dis 67:1322–1327CrossRefPubMedGoogle Scholar
  80. 80.
    Schmitt WH, Hagen EC, Neumann I, Nowack R, Flores-Suarez LF, van der Woude FJ (2004) Treatment of refractory Wegener’s granulomatosis with antithymocyte globulin (ATG): an open study in 15 patients. Kidney Int 65:1440–1448CrossRefPubMedGoogle Scholar
  81. 81.
    Turnbull A, Harper L (2009) Adverse effects of therapy for ANCA-associated vasculitis. Best Pract Res Clin Rheumatol 23:391–401CrossRefGoogle Scholar
  82. 82.
    Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C, Jayne DR, Harper L (2009) Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis. doi:10.1136/ard.2009.109389 PubMedGoogle Scholar
  83. 83.
    Charlier C, Henegar C, Launay O, Pagnoux C, Berezne A, Bienvenu B, Cohen P, Mouthon L, Guillevin L (2009) Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients. Ann Rheum Dis 68:658–663CrossRefPubMedGoogle Scholar
  84. 84.
    Harper L, Savage CO (2005) ANCA-associated renal vasculitis at the end of the twentieth century—a disease of older patients. Rheumatology (Oxford) 44:495–501CrossRefGoogle Scholar
  85. 85.
    Chung JB, Armstrong K, Schwartz JS, Albert D (2000) Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner’s granulomatosis undergoing immunosuppressive therapy. Arthritis Rheum 43:1841–1848CrossRefPubMedGoogle Scholar
  86. 86.
    Hellmich B, Schnabel A, Gross W (1999) G-CSF treatment for cyclophosphamide-induced severe neutropenia in Wegener’s granulomatosis. Arthritis Rheum 42:1752–1756CrossRefPubMedGoogle Scholar
  87. 87.
    Stassen PM, Sanders JS, Kallenberg CG, Stegeman CA (2008) Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis. Nephrol Dial Transplant 23:654–658CrossRefPubMedGoogle Scholar
  88. 88.
    Holvast A, Stegeman C, Benne C, Huckriede A, Wilschut J, Palache A, Kallenberg C, Bijl M (2009) Wegener’s granulomatosis patients show an adequate antibody response to influenza vaccination. Ann Rheum Dis 68:873–878CrossRefPubMedGoogle Scholar
  89. 89.
    Flossmann O, Berden A, de Groot K, Harper L, Heijl C, Hoglund P, Jayne D, Luqmani R, Mahr A, Mukhtyar C, Pusey C, Rasmussen N, Westmann K (2009) Longterm survival of ANCA-associated vasculitis. APMIS 117[Suppl s127]:139Google Scholar
  90. 90.
    Ozen S, Anton J, Arisoy N, Bakkaloglu A, Besbas N, Brogan P, Garcia-Consuegra J, Dolezalova P, Dressler F, Duzova A, Ferriani VP, Hilario MO, Ibanez-Rubio M, Kasapcopur O, Kuis W, Lehman TJ, Nemcova D, Nielsen S, Oliveira SK, Schikler K, Sztajnbok F, Terreri MT, Zulian F, Woo P (2004) Juvenile polyarteritis: results of a multicenter survey of 110 children. J Pediatr 145:517–522CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2010

Authors and Affiliations

  • Joannis Vamvakopoulos
    • 1
  • Caroline O. Savage
    • 1
  • Lorraine Harper
    • 1
  1. 1.School of Immunity and Infection, College of Medical and Dental SciencesUniversity of BirminghamBirminghamUK

Personalised recommendations