Wegener’s granulomatosis: an update on diagnosis and therapy

References

• Wegener F. Uber generalisierte, septische Gefasser-krankungen. Verh. Dtsch. Ges. Pathol.29, 202–210 (1936).
   Google Scholar
• Wegener F. Uber eine eigenartige rhinogene Granulomatose mit besonderer Beteilgung des Arteriensystems und der Nieren. Beitr Pathol.102, 26–58 (1939).
   Google Scholar
• Godman GC, Churg J. Wegener’s granulomatosis. Pathology and review of the literature. Arch. Pathol.58, 533–553 (1954).
   PubMedGoogle Scholar
• Leavitt RY, Fauci AS, Bloch DA et al. The American Collage of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum.33, 1101–1107 (1990).
   PubMed Web of Science ®Google Scholar
• Matteson EL, Gold KN, Bloch DA, Hunder GG. 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, 129–134 (1996).
   PubMed Web of Science ®Google Scholar
• Hatipoglu U, Rubinstein I. Pulmonary vasculitis: a clinical overview. IMAJ4, 1143–1148 (2002).
   Google Scholar
• Jennette JC, Falk R, Andrassy K et al. Nomenclature of systemic vasculitis. Proposal of an international conference. Arthritis Rheum.37, 187–192 (1994).
   PubMed Web of Science ®Google Scholar
• Watts RA, Lane SE, Scott DG et al. Epidemiology of vasculitis in Europe. Ann. Rheum. Dis.60, 1156–1157 (2001).
   PubMed Web of Science ®Google Scholar
• Guillevin L, Mahr A. Wegener’s granulomatosis. Orphanet Encyclopaedia.January, (2004).
   Google Scholar
• Puéchal X. Antineutrophil cytoplasmic antibody-associated vasculitides. Joint Bone Spine74, 427–435 (2004).
   Google Scholar
• Gonzalez-Gay MA, Garcia-Porrua C, Guerrero J, Rodriguez-Ledo P, Llorca J. The epidemiology of the primary systemic vasculitides in Northwest Spain: implications of the Chapel Hill Consensus Conference definitions. Arthritis Rheum.49, 388–393 (2003).
   PubMed Web of Science ®Google Scholar
• Mahr AD, Neogi T, Merkel PA. Epidemiology of Wegener’s granulomatosis: lessons from descriptive studies and analyses of genetic and environmental risk determinants. Clin. Exp. Rheumatol.24(S41), 82–91(2006).
   Google Scholar
• Jagiello P, Gencik M, Wieczorek S et al. New genomic region for Wegener’s granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes. Hum. Genet.114, 468–477 (2004).
   PubMedGoogle Scholar
• Szyld P, Jagiello P, Csernok E, Gross WL, Epplen JT. On the Wegener granulomatosis associated region on chromosome 6p21.3. BMC Med. Genet.7, 21 (2006).
   Google Scholar
• Jagiello P, Aries P, Arning L et al. The PTPN22 620W allele is a risk factor for Wegener’s granulomatosis. Arthritis Rheum.52, 4039–4043 (2005).
   PubMed Web of Science ®Google Scholar
• Lamprecht P, Gross WL. Current knowledge on cellular interactions in the WG-granuloma. Clin. Exp. Rheum.25, S49–S51 (2007).
   Google Scholar
• Stegeman CA, Cohen Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG. Association of chronic nasal carriage of Staphilococcus aureus and higher relapse rates in Wegener’s granulomatosis. Ann. Intern. Med.120, 12–17 (1994).
   PubMed Web of Science ®Google Scholar
• Boudewyns A, Verbelen J, Koekelkoren E, Van Offel J, Van de Heyning P. Wegener’s granulomatosis triggered by infection? Acta Otorhinolaryngol. Belg.55, 57–63 (2001).
   PubMedGoogle Scholar
• Albert D, Clarkin C, Komoroski J, Brensinger CM, Berlin JA. Wegener’s granulomatosis: possible role of environmental agents in its pathogenesis arthritis and rheumatism. Arthritis Care Res.51(4) 656–664 (2004).
   Google Scholar
• Stageman CA, Tervaert WC, de Jong PE, Kallenberg CGM. Trimethoprim–sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. NEJM16–20 (1996).
   Google Scholar
• Hogan Sl, Satterly KK, Dooley MA, Nackman PH, Jennette JC, Falk RJ. Silica exposure in anti-neutrophil cytoplasmic autoantiody-associated glomerulonephritis and lupus nephritis. J. Am. Soc. Nephrol.12, 134–142 (2001).
   PubMed Web of Science ®Google Scholar
• Lane SE, Watts RA, Bentham G, Innes NJ, Scott DG. Are environmental factors important in primary systemic vasculitis? A case–control study. Arthritis Rheum.48, 814–823 (2003).
   PubMed Web of Science ®Google Scholar
• Harper L, Cockwell P, Savage CO. Case of propylthiouraci-induced ANCA-associated small vessel vasculitis. Nephrol. Dial. Tansplant.13, 455–458 (1998).
   PubMedGoogle Scholar
• Schaffer JV, Davidson DM, McNiff JM, Bolognia JC. Perinuclear antineutrophil cytoplasmic antibody-positive cutaneous polyarteritis nodosa associated with minocycline therapy for acne vulgaris. J. Am. Acad. Dermatol.44, 198–206 (2001).
   PubMed Web of Science ®Google Scholar
• Lionaki S, Hogan SL, Falk RJ et al. Vasculitis and anti-thyroid medication. Nephrol. Dial. Transplant.23(5), 1766–1768 (2008).
   Google Scholar
• Gencik M, Meller S, Borgmann S, Fricke H. Proteinase 3 gene polymorphisms and Wegener’s granulomatosis granules. Kidney Int. (58), 2473–2477 (2000).
   Google Scholar
• Jannette JC, Falk RJ. New insight into the pathogenesis of vasculitis associated with antineutrophil cytoplasmic autoantibodies. Curr. Opin. Rheumatol.20, 55–60 (2008).
   Google Scholar
• Leung N, Ytterberg SR, Blute ML, Lager DJ, Specks U, Fervenza FC. Wegener’s granulomatosis presenting as multiple bilateral renal masses. Nephrol. Dial. Transplant.19, 984–987 (2004).
   PubMed Web of Science ®Google Scholar
• Vanessa R, Hwang E, Hwang PH. Wegener’s granulomatosis: current trends in diagnosis and management. Curr. Opin. Otolaryngol. Head Neck Surg.15, 170–176 (2007).
   Google Scholar
• Harper L, Savage CO. Pathogenesis of ANCA-associated systemic vasculitis. J. Pathol.190,190, 349–359 (2000).
   PubMed Web of Science ®Google Scholar
• Gross WL, Trabandt A, Csernok E. Pathogenesis of Wegener’s granulomatosis. Ann Med Interne (Paris)149(5), 280–286 (1998).
   Google Scholar
• Hoffman GS, Kerr GS, Levitt RY et al. Wegener’s granulomatosis: analysis of 158 patients. Ann. Intern. Med.116, 488–498 (1992).
   PubMed Web of Science ®Google Scholar
• Fauci AS, Wolff SM. Wegener’s granulomatosis: studies in 18 patients and a review of the literature. Medicine (Baltimore)52, 535–561 (1973).
   PubMed Web of Science ®Google Scholar
• McDonald TJ, De Remee RA. Wegener’s granulomatosis. Laryngoscope93, 220–231 (1993).
   Google Scholar
• Luqmani RA, Bacon PA, Moots RJ et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. Q. J. Med.87, 671–678 (1994).
   Google Scholar
• Langford CA. Wegener’s granulomatosis. Am. J. Med. Sci.321, 76–82 (2001).
   PubMed Web of Science ®Google Scholar
• Rasmussen N. Management of the ear, nose, and throat manifestation of Wegener’s granulomatosis: an otorhinolaryngologist’s perspective. Curr. Opin. Rheumatol.13, 3–11 (2001).
   PubMed Web of Science ®Google Scholar
• McDonald TJ, De Remee RA, Kern EB, Harrison EG. Nasal manifestations of Wegener’s granulomatosis. Laryngoscope84, 2101–2112 (1974).
   PubMedGoogle Scholar
• Coufani G, Hassid S, Hernebert D. Otological manifestations of Wegener’s granulomatosis. Acta Otorhinolaryngol. Belg.45, 375–379 (1991).
   Google Scholar
• Almadori G, Trivelli M, Scarano E, Cadoni G. Misleading clinical features in Wegener’s granulomatosis. A case report. J. Laryngol. Otol.11, 746–748 (1997).
   Google Scholar
• Macias JD, Wackym PA, McCabe BF. Early diagnosis of otologic Wegener’s granulomatosis using the serologic marker cANCA. Ann. Otol. Rhinol. Laryngol.102, 337–341 (1993).
   PubMedGoogle Scholar
• Cadoni G, Agostino S, Campobasso E, Vulpiani P, Manna R, Galli J. Early diagnosis and stage-adapted treatment of Wegener’s granulomatosis. J. Laryngol. Otol.117, 208–211 (2003).
   PubMedGoogle Scholar
• Ferri E, Armato E, Capuzzo P, Cavaleri S, Ianniello F. Early diagnosis of Wegener’s granulomatosis presenting with bilateral facial paralysis and bilateral serous otitis media. Auris Nasus Larynx34(3), 379–382 (2007).
   PubMed Web of Science ®Google Scholar
• Daderian AD, Chayasirisobhon S. An unusual case of multiple cranial nerve palsies in Wegener’s granulomatosis. J. Natl Med. Assoc.92(9), 455–457 (2000).
   Google Scholar
• Nischino H, Rubino FA, DeRemee RA, Swanson JW, Parisi JE. Neurologic involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann. Neurol.33, 4–9 (1993).
   PubMedGoogle Scholar
• De Groot K, Schmidt DK, Arlt AC, Gross WL, Reinhold-Keller E. Standardized neurologic evaluations of 18 patients with Wegener granulomatosis. Arch. Neurol.58, 1215–1221 (2001).
   PubMedGoogle Scholar
• Laforgia A, Di Venere D, Poli M. Wegener’s sindrome (or granulomatosis). A clinical case. Minerva Stomatol.42, 547–552 (1993).
   PubMedGoogle Scholar
• Lebovics RS, Hoffman GS, Laevitt RY et al. The management of subglottic stenosis in patients with Wegener’s granulomatosis. Laryngoscope102, 1341–1345 (1992).
   PubMed Web of Science ®Google Scholar
• Rottem M, Fauci AS, Hallahan CW et al. Wegener’s granulomatosis in children and adolescents: clinical presentation and outcome. J. Pediatr.112(1), 26–31 (1993).
   Google Scholar
• Gaugna RK, DeSanto LW, McDonald TJ. Use of anticytoplasmic autoantibodies in the diagnosis of Wegener’s granulomatosis with subglottic stenosis. Laryngoscope100, 561–563 (1990).
   Google Scholar
• Matt BH. Wegener’s granulomatosis, acute laryngotracheal obstruction and death in a 17 year old female: case report and review of the literature. Int. J. Pediatr. Otorhinolaryngol.37, 163–172 (1996).
   PubMedGoogle Scholar
• Thickett DR, Richter AG, Nathani N, Perkins GD, Harper L. Pulmonary manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Rheumatology45, 261–268 (2006).
   PubMed Web of Science ®Google Scholar
• Haris M, Koulaouzidis A, Yasir M, Clark S, Kaleem M, Mallya R. Wegener’s granulomatosis. CMAJ178(1), 25–26 (2008).
   Google Scholar
• Seo P. Wegener’s granulomatosis: managing more than inflammation. Curr. Opin. Rheum.20, 10–16 (2008).
   Google Scholar
• Deniz K, Ozseker HS, Balas S, Akpýnar E, Sökmensüer C. Intestinal involvement in Wegener’s granulomatosis. J. Gastrointestin. Liver Dis.16(3), 329–331 (2007).
   PubMed Web of Science ®Google Scholar
• Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrorphil cytoplasmic antibody-associated vasculitis. A systematic review. JAMA298(6), 655–669 (2007).
   PubMed Web of Science ®Google Scholar
• Cadoni G, Prelajade D, Campobasso E et al. Wegener’s granulomatosis: a challenging disease for otorhinolarngologists. Acta Otolaryngol.125, 1105–1110 (2005).
   PubMed Web of Science ®Google Scholar
• Koldingsnes W, Nossent H. Predictors of survival and organ damage in Wegener granulomatosis. Rheumatology41, 572–581 (2002).
   PubMed Web of Science ®Google Scholar
• Hunder GG, Arend WA, Bloch DA et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Introduction. Arthritis Rheum.33, 1065–1067 (1990).
   PubMed Web of Science ®Google Scholar
• Jeanette Jc, Falk RJ, Andrassy K et al. Nomenclature of systemic vasculitides. Proposal of an International Consensus Conference. Arthritis Rheum.37, 187–192 (1994).
   PubMedGoogle Scholar
• Sørensen SF, Slot O, Tvede N, Petersen J. A perspective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature. Ann. Rheum. Dis.59, 478–482 (2000).
   PubMedGoogle Scholar
• Lane SE, Watts RA, Barker TH, Scott DG. Evaluation of the Sørensen diagnostic criteria in the classification of systemic vasculitis. Rheumatology41, 1138–1141 (2002).
   PubMed Web of Science ®Google Scholar
• Jennette JC, Falk RJ. Small-vessel vasculitis. N. Engl. J. Med.337, 1512–1523 (1997).
   PubMed Web of Science ®Google Scholar
• Harris A, Chang G, Vadas M, Gillis D. ELISA is the superior method for detecting antineutrophil cytoplasmic autoantibodies in the diagnosis of systemic necrotising vasculitis. J. Clin. Pathol.2, 670–676 (1999).
   Google Scholar
• Schmitt WH, van der Woude FJ. Clinical applications of antineutrophil cytoplasmic antibody testing. Curr. Opin. Rheumatol.16, 9–17 (2004).
   PubMedGoogle Scholar
• Koldingsnes W, Nossent JC. Increasing incidence of Wegener’s granulomatosis in a stable Caucasian population, during the 15 years period from 1984–1998. Arthritis Rheum.42(Suppl.), 318 (1984).
   Google Scholar
• Savige J, Gillis D, Benson E et al. International Consensus Statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am. J. Clin. Pathol.113, 455–456 (2000).
   PubMedGoogle Scholar
• Lee AS, Finkielman JD, Peikert T et al. Agreement of anti-neutrophil cytoplasmic antibody measurements obtained from serum and plasma. Clin. Exp. Immunol.146, 15–20 (2006).
   Google Scholar
• Damoiseaux J, Vaessen M, Knapen Y et al. Evaluation of the FIDIS vasculitis multiplex immunoassay for diagnosis and follow-up of ANCA-associated vasculitis and Goodpasture’s disease. Ann. NY Acad. Sci.1109, 454–463 (2007).
   PubMedGoogle Scholar
• Carrie S, Hughes KB, Watson MG. Negative ANCA in Wegener’s granulomatosis. J. Laryngol. Otol.108, 420–422 (1994).
   PubMedGoogle Scholar
• Hellmich B, Flossmann O, Gross WL et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann. Rheum. Dis.66, 605–617 (2007).
   PubMed Web of Science ®Google Scholar
• Hoffman GS, Specks U. Antineutrophil cytoplasmic antibodies. Arthritis Rheum.41, 1521–1537 (1998).
   PubMed Web of Science ®Google Scholar
• Finkielman JD, Merkel PA, Schroeder D et al.; WGET Research Group. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann. Intern. Med.147(9), 611–619 (2007).
   PubMed Web of Science ®Google Scholar
• Tervaert JW, Huitema MG, Hené RJ et al. Prevention of relapses in Wegener’s granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet336, 709–711 (1990).
   PubMed Web of Science ®Google Scholar
• Walton E. Giant cell granuloma of the respiratory tract (Wegener’s granulomatosis). Br. Med. J.2, 265–270 (1958).
   PubMed Web of Science ®Google Scholar
• Cotch MF, Hoffman GS, Yerg DE, Kaufman GI, Targonski P, Kaslow RA. The epidemiology of Wegener’s granulomatosis. Estimates of the 5 -year period prevalence, annual mortality, and geographic disease distribution fom population-based data sources. Arthritis Rheum.39, 87–92 (1996).
   PubMed Web of Science ®Google Scholar
• Koldingsnes W, Nossent H. Epidemiology of Wegener’s granulomatosis in northern Norway. Arthritis Rheum.43(11), 2481–2487 (2000).
   PubMed Web of Science ®Google Scholar
• Watts RA, Gonzales-Gay M, Garcia-Porrua C et al. ANCA-associated vasculitis in two European regions. Clin. Exp. Immunol.120(Suppl.1), 60 (2000).
   Google Scholar
• Luqmani RA. Assessing disease activity in the systemic vasculitides. Curr. Opin. Rheumatol.14, 23–28 (2002).
   PubMedGoogle Scholar
• Ricciardi V, Valesini G. Terapia della granulomatosi di Wegener. Reumatismo56(2), 69–76 (2004).
   Google Scholar
• 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.98, 76–85 (1983).
   PubMed Web of Science ®Google Scholar
• Guillevin L, Cordier J, 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.40, 2187–2198 (1997).
   PubMed Web of Science ®Google Scholar
• Reinhold-Keller E, Beuge N, Latza U et al. An interdisciplinary approach to the care of patients with Wegener’s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum.43, 1021–1032 (2000).
   PubMed Web of Science ®Google Scholar
• 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.349, 36–44 (2003).
   PubMed Web of Science ®Google Scholar
• de Groot K, Jayne D, Tesar V et al. Randomized controlled trial of daily oral versus pulse cyclophosphamide for induction of remission in ANCA-associated systemic vasculitis. Kidney Blood Press. Res.28, 195 (2005).
   Google Scholar
• Adu D, Pall A, Luqmani RA et al. Controlled trial of pulse versus continous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. Q. J. Med.90, 401–409 (1997).
   Google Scholar
• de Groot K, Adu D, Savage C. The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol. Dial. Transplant.16, 2018–2027 (2001).
   PubMed Web of Science ®Google Scholar
• Gaskin G, Pusey CD. Plasmapheresis in antineutrophil cytoplasmic antibody-associated systemic vasculitis. Ther. Apher.5, 176–181 (2001).
   PubMedGoogle Scholar
• de Groot K, Muhler M, Reinhold-Keller E et al. Induction of remission in Wegener’s granulomatosis with low dose of methotrexate. J. Rheumatol.25, 492–495 (1998).
   Google Scholar
• Sneller MC, Hoffman GS, Talar-Williams C et al. An analysis of forty-two Wegener’s granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum.38, 608–613 (1995).
   PubMed Web of Science ®Google Scholar
• de Groot K, Rasmussen N, Bacon P et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum.52(8), 2461–2469 (2005).
   PubMed Web of Science ®Google Scholar
• Reinhold-Keller E, de Groot K, Rudert H et al. Response to trimethoprim/sulfamethoxazole in Wegener’s granulomatosis depends on the phase of disease. Q. J. Med.89, 15–23 (1996).
   Google Scholar
• Hollander D, Manning R. The use of alcylating agents in the treatment of Wegener’s granulomatosis. Ann. Intern. Med.67, 393–398 (1967).
   PubMed Web of Science ®Google Scholar
• Hoffmann GS. Wegener’s granulomatosis: the path traveled since 1931. Medicine (Baltimora)73(6), 325–329 (1994).
   Google Scholar
• Brandwein S, Esdaile J, Danoff D et al. Wegener’s granulomatosis: clinical features and outcome in 13 patients. Arch. Intern. Med.143(3), 476–479 (1983).
   Google Scholar
• Knight A, Askling J, Granath F et al. Urinary bladder cancer in Wegener’s granulomatosis: risks and relation to cyclophosphamide. Ann. Rheum. Dis.63, 1307–1311 (2004).
   PubMed Web of Science ®Google Scholar
• Fraiser LH, Kanekal S, Kehrer JP. Cyclophosphamide toxicity. Characterising and avoiding the problem. Drugs42, 781–795 (1991).
   Google Scholar
• Cox PJ. Cyclophosphamide cystitis. Identification of acrolein as the causative agent. Biochem. Pharmacol.28, 2045–2049 (1979).
   PubMed Web of Science ®Google Scholar
• Drosos AA, Sakkas LI, Goussia A et al. Pulse cyclophosphamide therapy in Wegener’s granulomatosis: a pilot study. J. Intern. Med.232(3), 279–282 (1992).
   Google Scholar
• Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res.4, 266–273 (2002).
   PubMedGoogle Scholar
• de Groot K, Reinhold-Keller E, Tatsis E et al. Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis: methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum.39, 2052–2061 (1996).
   PubMed Web of Science ®Google Scholar
• de Groot K, Gross WL, Herlyn K et al. Development and validation of a disease extent index for Wegener’s granulomatosis. Clin. Nephrol.55(1), 31–38 (2001).
   PubMed Web of Science ®Google Scholar
• Stone JH, Tun W, Hellman DB. Treatment of non-life-threatening Wegener’s granulomatosis with methotrexate and daily prednisone as the initial therapy of choice. J. Rheumatol.26(5), 1134–1139 (1999).
   PubMedGoogle Scholar
• Semple D, Keogh J, Forni L, Venn R. Clinical review: vasculitis on the intensive care unit – part 2: treatment and prognosis. Crit. Care9(2), 193–197 (2005).
   PubMedGoogle Scholar
• Hellmich B, Lamprecht P, Gross WL. Advances in the therapy of Wegener’s granulomatosis. Curr. Opin. Rheumatol.18(1), 25–32 (2006).
   PubMed Web of Science ®Google Scholar
• Aasarød K, Iversen BM, Hammerstrøm J, Bostad L, Jørstad S. Clinical outcome of patients with Wegener’s granulomatosis treated with plasma exchange. Blood Purif.20(2), 167–173 (2002).
   Google Scholar
• Pagnoux C, Mahr A, Cohen P et al. for the French Vasculitis Study Group (FVSG). Treatment of ANCA-associated systemic vasculitides with pulse cyclophosphamide then azathioprine versus methotrexate to maintain remission: interim analysis of a prospective, randomized, multicenter trial [abstract]. Arthritis Rheum.9, 660 (2003).
   Google Scholar
• Tiede I, Fritz G, Strand S et al. CD-28 dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J. Clin. Invest.111, 1133–1145 (2003).
   PubMed Web of Science ®Google Scholar
• Aries PM, Hellmich B, Reinhold-Keller E et al. High-dose intravenous azathioprine pulse treatment in refractory Wegener’s granulomatosis. Rheumatology (Oxf.)43, 1307–1308 (2004).
   Google Scholar
• 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.24, 251–257 (2005).
   PubMed Web of Science ®Google Scholar
• de Groot K, Reinhold-Keller E, Tatsis E et al. Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis: methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum.39(12), 2052–2061 (1996).
   PubMed Web of Science ®Google Scholar
• Godeau B, Mainardi JL, Roudot-Thoraval F et al. Factors associated with Pneumocystis carinii pneumonia in Wegener’s granulomatosis. Ann. Rheum. Dis.54(12), 991–994 (1995).
   PubMed Web of Science ®Google Scholar
• Gross WL. New concepts in treatment protocols for severe systemic vasculitis. Curr. Opin. Rheumatol.11(1), 41–46 (1999).
   PubMedGoogle Scholar
• Chung JB, Armstrong K, Schwartz JS et al. Cost–effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegener’s granulomatosis undergoing immunosuppressive therapy. Arthritis Rheum.43(8), 1841–1848 (2000).
   PubMed Web of Science ®Google Scholar
• Stegeman CA, Cohen Tervaert JW, de Jong PE et al. Trimethoprim–sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. Dutch Cotrimoxazole Wegener Study Group. N. Engl. J. Med.335(1), 16–20 (1996).
   PubMed Web of Science ®Google Scholar
• 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.64(Suppl. 3), 85 (2005).
   Google Scholar
• Metzler C, Fink C, Lamprecht P et al. Maintenance of remission with leflunomide in Wegener’s granulomatosis. Rheumatology63, 339–340 (2004).
   Google Scholar
• Metzler C, Miehle N, Manger K et al.; German Network of Rheumatic Diseases. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener’s granulomatosis. Rheumatology (Oxf.)46(7), 1087–1091 (2007).
   PubMed Web of Science ®Google Scholar
• Nowack R, Gobel 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.10(9), 1965–1971 (1999).
   PubMed Web of Science ®Google Scholar
• Langford CA, Talar-Williams C, Sneller MC. Mycophenolate mofetil for remission maintenance in the treatment of Wegener’s granulomatosis. Arthritis Rheum.51(2), 278–283 (2004).
   PubMed Web of Science ®Google Scholar
• Koukoulaki M, Jayne DR. Mycophenolate mofetil in anti-neutrophil cytoplasm antibodies-associated systemic vasculitis. Nephron. Clin. Pract.102(3–4), c100–c107 (2006).
   PubMedGoogle Scholar
• Joy MS, Hogan SL, Jennette JC, Falk RJ, Nachman PH. A pilot study using mycophenolate mofetil in relapsing or resistant ANCA small vessel vasculitis. Nephrol. Dial. Transplant.20(12), 2725–2732 (2005).
   PubMed Web of Science ®Google Scholar
• Jayne D. Update on the European Vasculitis Study Group (EUVAS). Curr. Opin. Rheumatol.13, 48–55 (2001).
   PubMed Web of Science ®Google Scholar
• Ludviksson BR, Sneller MC, Chua KS et al. 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, 3602–3609 (1998).
   PubMed Web of Science ®Google Scholar
• Csernok E, Trabandt A, Müller A et al. Cytokine profiles in Wegener’ s granulomatosis: predominance of type 1 (Th1) in the granulomatous inflammation. Arthritis Rheum.42, 742–750 (1999).
   PubMed Web of Science ®Google Scholar
• Kindler V, Sappino AP, Grau GE et al. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell56, 731–740 (1989).
   PubMed Web of Science ®Google Scholar
• Huugen D, Willem J, Tervaert C, Heeringa P. TNF-α bioactivity-inhibiting therapy in ANCA-associated vasculitis: clinical and experimental considerations. Clin. J. Am. Soc. Nephrol.1, 1100–1107 (2006).
   PubMed Web of Science ®Google Scholar
• Nassonov E, Samsonov M, Tilz GP et al. Serum concentrations of neopterin, solubile interleukin 2 receptor and solubile tumor necrosis factor receptor in Wegener’s granulomatosis. J. Rheumatol.24, 666–670 (1997).
   PubMed Web of Science ®Google Scholar
• Falk RJ, Terrell RS, Charles LA et al. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro.Proc. Natl Acad. Sci. USA87, 4115–4119 (1990).
   PubMed Web of Science ®Google Scholar
• Lamprecht P, Voswinkel J, Lilienthal T et al. Effectiveness of TNF-α blockade with infliximab in refractory Wegener’s granulomatosis. Rheumatology (Oxf.)41, 1303–1307 (2002).
   PubMed Web of Science ®Google Scholar
• Booth AD, Bacon PA, Griffith ME et al. Infliximab in ANCA-associated vasculitis: the ‘ACTIVE’ trial. Kidney Blood Press. Res.26, 292–293 (2003).
   Google Scholar
• Stone JH, Uhfelder ML, Hellmann DB et al. Etanercept combined with conventional treatment in Wegener’s granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum.44, 1149–1154 (2001).
   PubMed Web of Science ®Google Scholar
• The Wegener’s Granulomatosis Etanercept (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N. Engl. J. Med.352, 351–361 (2005).
   PubMed Web of Science ®Google Scholar
• Stone JH, Holbrook JT, Marriott MA et al.; Wegener’s Granulomatosis Etanercept Trial Research Group. Solid malignancies among patients in the Wegener’s Granulomatosis Etanercept Trial. Arthritis Rheum.54(5), 1608–1618 (2006).
   PubMed Web of Science ®Google Scholar
• Hellmann DB, Imboden JB. Update in rheumatology. Ann. Intern. Med.145(11), 834–838 (2006).
   Google Scholar
• Akobeng AK, Zachos M. Tumor necrosis factor-α antibody for induction of remission in Crohn’s disease. Cochrane Database Syst. Rev.1, CD003574 (2004).
   Google Scholar
• Bartolucci P, Ramanoelina J, Cohen P et al. Efficacy of the anti-TNF-α antibody infliximab against refractory systemic vasculitides: an open pilot study on 10 patients. Rheumatology (Oxf.)41(10), 1126–1132 (2002).
   PubMed Web of Science ®Google Scholar
• Booth A, Harper L, Hammad T et al. Prospective study of TNFα blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J. Am. Soc. Neophrol.15(3), 717–721 (2004).
   PubMed Web of Science ®Google Scholar
• Booth AD, Jefferson HJ, Ayliffe W et al. Safety and efficacy of TNFℵ blockade in relapsing vasculitis. Ann. Rheum. Dis.61(6), 559 (2002).
   PubMedGoogle Scholar
• Sneller MC. Rituximab and Wegener’s granulomatosis: are B cells a target in vasculitis treatment? Arthritis Rheum.52, 1–5 (2005).
   PubMed Web of Science ®Google Scholar
• Keogh KA, Ytterberg SR, Fervenza FC et al. Rituximab for refractory Wegener’s granulomatosis: report of prospective, open-label pilot trial. Am. J. Respir. Crit. Care Med.173(2), 180–187 (2006).
   PubMed Web of Science ®Google Scholar
• Omdal R, Wildhagen K, Hansen T et al. Anti-CD20 therapy of treatment-resistant Wegener’s granulomatosis: favourable but temporary response. Scand. J. Rheumatol.34, 229–232 (2005).
   PubMed Web of Science ®Google Scholar
• Aries PM, Hellmich B, Voswinkel J et al. Lack of efficacy of rituximab in Wegener’s granulomatosis with refractory granulomatous manifestations. Ann. Rheum. Dis.65, 853–858 (2006).
   PubMed Web of Science ®Google Scholar
• Keogh KA, Wylam ME, Stone JH, Specks U. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum.52, 262–268 (2005).
   PubMed Web of Science ®Google Scholar
• Rose BD, Appel GB, Stone JH. Alternative agents in the treatment of Wegener’s granulomatosis and microscopic poliangioitis. Uptodate online, version 14.3.
   Google Scholar
• Birck R, Warnatz K, Lorenz HM et al. 15-deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J. Am. Soc. Nephrol.14, 440–447 (2003).
   PubMed Web of Science ®Google Scholar
• Schmitt WH, Birck R, Heinzel PA et al. Prolonged treatment of refractory Wegener’s granulomatosis with 15-deoxyspergualin: an open study in seven patients. Nephrol. Dial. Transplant.20, 1083–1092 (2005).
   PubMed Web of Science ®Google Scholar
• Diegel M, Nadler SG, Kiener PA. In vivo administration of 15-deoxyspergulin inhibits antigen-presenting cell stimulation of T cells and NF-κB activation. Int. Immunopharmacol.2, 1451–1464 (2002).
   PubMed Web of Science ®Google Scholar
• Kälsch AI, Schmitt WH, Breedijk A et al.In vivo effects of cyclic adminitration of 15-deoxyspergulin on leucocyte function in patients with Wegener’s granulomatosis. Clin. Exp. Immunol.146, 455–462 (2006).
   PubMed Web of Science ®Google Scholar
• Jayne DR, Chapel H, Adu D et al. Intravenous immunoglobulin for ANCA associated systemic vasculitis with persistent disease activity. QJM93, 433–439 (2000).
   PubMed Web of Science ®Google Scholar
• Linsley PS, Greene JL, Tan P et al. Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J. Exp. Med.176(6), 1595–1604 (1992).
   PubMed Web of Science ®Google Scholar
• Davidson A, Diamond B, Wofsy D, Daikh D. Block and tackle: CTLA4Ig takes on lupus. Lupus14(3), 197–203 (2005).
   PubMed Web of Science ®Google Scholar