Clinical Reviews in Allergy & Immunology

, Volume 54, Issue 2, pp 244–260 | Cite as

Unmet Needs in the Pathogenesis and Treatment of Vasculitides

  • Francesco Muratore
  • Giulia Pazzola
  • Alessandra Soriano
  • Nicolò Pipitone
  • Stefania Croci
  • Martina Bonacini
  • Luigi Boiardi
  • Carlo Salvarani
Article

Abstract

Despite the progress in the last years on the field of vasculitides, there are several unmet needs regarding classification, disease activity assessment, predictors of flares and complications, and type of treatment for the different forms. The 1990 American College of Rheumatology (ACR) classification criteria currently used to define giant cell arteritis and Takayasu arteritis were designed to discriminate between different types of vasculitides but not to differentiate vasculitis from other disorders. Recently, efforts have been made to overcome the shortcomings of the ACR criteria. The lack of an accepted definition of disease activity in large-vessel vasculitides presents a major challenge in creating useful and valid outcome tools for the assessment of disease course. Identification of predictors of flares can aid in optimizing therapeutic strategies, minimizing disease flares, and reducing treatment-related side effects. It is furthermore important to recognize and characterize the risk factor that might predict the manifestations associated with poor outcome and prognosis. Two RCTs have evidenced the efficacy of tocilizumab in addition to glucocorticoids (GCs) in the treatment of giant cell arteritis (GCA). However, the role of tocilizumab or other biological agents without GCs needs to be investigated. Recent observational studies have suggested that rituximab is also effective in patients with eosinophilic granulomatosis with polyangiitis and in antineutrophil cytoplasmic antibodies (ANCA)-negative patients with granulomatosis with polyangiitis and microscopic polyangiitis. Rituximab or anti-TNF alfa may represent a possible alternative therapy in case of refractory or difficult to treat polyarteritis nodosa (PAN) patients. The new International Criteria for Behçet’s Disease have shown a better sensitivity and a better accuracy compared to the older International Study Group on Behçet’s Disease criteria. The EULAR recommendations for the management of Behçet’s disease (BD) have been recently updated. However, the treatment of refractory disease is still a real challenge.

Keywords

Vasculitis Treatment Unmet needs Tocilizumab Rituximab Large-vessel vasculitis ANCA-associated vasculitis Behçet’s disease 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

References

  1. 1.
    Hunder GG, Bloch DA, Michel BA et al (1990) The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 33:1122–1128CrossRefPubMedGoogle Scholar
  2. 2.
    Arend WP, Michel BA, Bloch DA et al (1990) The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 33:1129–1134CrossRefPubMedGoogle Scholar
  3. 3.
    Bongartz T, Matteson EL (2006) Large-vessel involvement in giant cell arteritis. Curr Opin Rheumatol 18:10–17CrossRefPubMedGoogle Scholar
  4. 4.
    Muratore F, Kermani TA, Crowson CS, Green AB, Salvarani C, Matteson EL, Warrington KJ (2015) Large-vessel giant cell arteritis: a cohort study. Rheumatology (Oxford) 54:463–470CrossRefGoogle Scholar
  5. 5.
    Pipitone N, Versari A, Salvarani C (2008) Role of imaging studies in the diagnosis and follow-up of large-vessel vasculitis: an update. Rheumatology (Oxford) 47:403–408CrossRefGoogle Scholar
  6. 6.
    Direskeneli H, Aydin SZ, Kermani TA et al (2011) Development of outcome measures for large-vessel vasculitis for use in clinical trials: opportunities, challenges, and research agenda. J Rheumatol 38:1471–1479CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Karahaliou M, Vaiopoulos G, Papaspyrou S, Kanakis MA, Revenas K, Sfikakis PP (2006) Colour duplex sonography of temporal arteries before decision for biopsy: a prospective study in 55 patients with suspected giant cell arteritis. Arthritis Res Ther 8(4):R116CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Craven A, Robson J, Ponte C et al (2013) ACR/EULAR-endorsed study to develop Diagnostic and Classification Criteria for Vasculitis (DCVAS). Clin Exp Nephrol 17:619–621CrossRefPubMedGoogle Scholar
  9. 9.
    Aydin SZ, Direskeneli H, Sreih A et al (2015) Update on outcome measure development for large vessel vasculitis: report from OMERACT 12. J Rheumatol 42:2465–2469CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Aydin SZ, Merkel PA, Direskeneli H (2015) Outcome measures for Takayasu's arteritis. Curr Opin Rheumatol 27:32–37CrossRefPubMedGoogle Scholar
  11. 11.
    Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M, Hoffman GS (1994) Takayasu arteritis. Ann Intern Med 120:919–929CrossRefPubMedGoogle Scholar
  12. 12.
    Pipitone N, Pazzola G, Muratore F, Salvarani C (2013) L30. Assessment of vasculitis extent and severity. Presse Med 42(4 Pt 2):588–589CrossRefPubMedGoogle Scholar
  13. 13.
    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 87:671–678PubMedGoogle Scholar
  14. 14.
    Aydin SZ, Yilmaz N, Akar S et al (2010) Assessment of disease activity and progression in Takayasu's arteritis with Disease Extent Index-Takayasu. Rheumatology (Oxford) 49:1889–1893CrossRefPubMedGoogle Scholar
  15. 15.
    Misra R, Danda D, Rajappa SM et al (2013) Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010). Rheumatology (Oxford) 52:1795–1801CrossRefPubMedGoogle Scholar
  16. 16.
    Alibaz-Oner F, Aydin SZ, Akar S et al (2015) Assessment of patients with Takayasu arteritis in routine practice with Indian Takayasu clinical activity score. J Rheumatol 42:1443–1447CrossRefPubMedGoogle Scholar
  17. 17.
    Mason JC (2010) Takayasu arteritis—advances in diagnosis and management. Nat Rev Rheumatol 6:406–415CrossRefPubMedGoogle Scholar
  18. 18.
    Salvarani C, Cantini F, Hunder GG (2008) Polymyalgia rheumatica and giant-cell arteritis. Lancet 372:234–245CrossRefPubMedGoogle Scholar
  19. 19.
    Muratore F, Pipitone N, Salvarani C, Schmidt WA (2016) Imaging of vasculitis: state of the art. Best Pract Res Clin Rheumatol 30:688–706CrossRefPubMedGoogle Scholar
  20. 20.
    Muratore F, Pipitone N, Salvarani C (2017) Standard and biological treatment in large vessel vasculitis: guidelines and current approaches. Expert Rev Clin Immunol 13:345–360CrossRefPubMedGoogle Scholar
  21. 21.
    Martinez-Lado L, Calvino-Diaz C, Pineiro A et al (2011) Relapses and recurrences in giant cell arteritis: a population-based study of patients with biopsy-proven disease from northwestern Spain. Medicine (Baltimore) 90:186–193CrossRefGoogle Scholar
  22. 22.
    Alba MA, Garcia-Martinez A, Prieto-Gonzalez S et al (2014) Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients. Medicine (Baltimore) 93:194–201CrossRefGoogle Scholar
  23. 23.
    Liozon E, Roblot P, Paire D et al (2000) Anticardiolipin antibody levels predict flares and relapses in patients with giant-cell (temporal) arteritis. A longitudinal study of 58 biopsy-proven cases. Rheumatology 39:1089–1094CrossRefPubMedGoogle Scholar
  24. 24.
    Proven A, Gabriel SE, Orces C, O'Fallon WM, Hunder GG (2003) Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum 49:703–708CrossRefPubMedGoogle Scholar
  25. 25.
    Labarca C, Koster MJ, Crowson CS, Makol A, Ytterberg SR, Matteson EL, Warrington KJ (2016) Predictors of relapse and treatment outcomes in biopsy-proven giant cell arteritis: a retrospective cohort study. Rheumatology (Oxford) 55:347–356CrossRefGoogle Scholar
  26. 26.
    Kermani TA, Warrington KJ, Cuthbertson D et al (2015) Disease relapses among patients with giant cell arteritis: a prospective longitudinal cohort study. J Rheumatol 42:1213–1217CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Restuccia G, Boiardi L, Cavazza A et al (2016) Flares in biopsy-proven giant cell arteritis in northern Italy: characteristics and predictors in a long-term follow-up study. Medicine (Baltimore) 95:e3524CrossRefGoogle Scholar
  28. 28.
    Comarmond C, Biard L, Lambert M et al (2017) Long-term outcomes and prognostic factors of complications in Takayasu's arteritis: a multicenter study of 318 patients. Circulation.  https://doi.org/10.1161/CIRCULATIONAHA.116.027094
  29. 29.
    Schmidt J, Kermani TA, Bacani AK, Crowson CS, Cooper LT, Matteson EL, Warrington KJ (2013) Diagnostic features, treatment, and outcomes of Takayasu arteritis in a US cohort of 126 patients. Mayo Clin Proc 88:822–830CrossRefPubMedGoogle Scholar
  30. 30.
    Hong S, Bae SH, Ahn SM, Lim DH, Kim YG, Lee CK, Yoo B (2015) Outcome of Takayasu arteritis with inactive disease at diagnosis: the extent of vascular involvement as a predictor of activation. J Rheumatol 42:489–494CrossRefPubMedGoogle Scholar
  31. 31.
    Ohigashi H, Haraguchi G, Konishi M, Tezuka D, Kamiishi T, Ishihara T, Isobe M (2012) Improved prognosis of Takayasu arteritis over the past decade—comprehensive analysis of 106 patients. Circ J 76:1004–1011CrossRefPubMedGoogle Scholar
  32. 32.
    Fukui S, Iwamoto N, Shimizu T et al (2016) Fewer subsequent relapses and lower levels of IL-17 in Takayasu arteritis developed after the age of 40 years. Arthritis Res Ther 18:293CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Westman K, Flossmann O, Gregorini G (2015) The long-term outcomes of systemic vasculitis. Nephrol Dial Transplant 30(Suppl 1):i60–i66PubMedGoogle Scholar
  34. 34.
    Walsh M, Flossmann O, Berden A et al (2012) Risk factors for relapse of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 64:542–548CrossRefPubMedGoogle Scholar
  35. 35.
    Booth AD, Almond MK, Burns A et al (2003) Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis 41:776–784CrossRefPubMedGoogle Scholar
  36. 36.
    Westman KW, Bygren PG, Olsson H et al (1998) Relapse rate, renal survival, and cancer morbidity in patients with Wegener’s granulomatosis or microscopic polyangiitis with renal involvement. J Am Soc Nephrol 9:842–852PubMedGoogle Scholar
  37. 37.
    Pagnoux C, Hogan SL, Chin H et al (2008) Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum 58:2908–2918CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kemna MJ, Damoiseaux J, Austen J, Winkens B, Peters J, van Paassen P, Cohen Tervaert JW (2015) ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol 26:537–542CrossRefPubMedGoogle Scholar
  39. 39.
    Fussner LA, Hummel AM, Schroeder DR et al (2016) Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheum 68:1700–1710CrossRefGoogle Scholar
  40. 40.
    Morgan MD, Szeto M, Walsh M et al (2017) Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse. Arthritis Res Ther 19:129CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Harper L, Morgan MD, Walsh M et al (2012) Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis 71:955–960CrossRefPubMedGoogle Scholar
  42. 42.
    Faurschou M, Westman K, Rasmussen N et al (2012) Long-term outcome of a clinical trial comparing methotrexate to cyclophosphamide for remission induction of early systemic ANCA-associated vasculitis. Arthritis Rheum 64:3472–3477CrossRefPubMedGoogle Scholar
  43. 43.
    Karras A, Pagnoux C, Haubitz M et al (2017) Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis.  https://doi.org/10.1136/annrheumdis-2017-211123
  44. 44.
    Guillevin L, Pagnoux C, Karras A et al (2014) Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 371:1771–1780CrossRefPubMedGoogle Scholar
  45. 45.
    Walsh M, Merkel PA, Mahr A et al (2010) Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis. Arthritis Care Res 62:1166–1173CrossRefGoogle Scholar
  46. 46.
    Soriano A, Muratore F, Pipitone N, Boiardi L, Cimino L, Salvarani C (2017) Visual loss and other cranial ischaemic complications in giant cell arteritis. Nat Rev Rheumatol 13:476–484CrossRefPubMedGoogle Scholar
  47. 47.
    Evans JM, O'Fallon WM, Hunder GG (1995) Increased incidence of aortic aneurysm and dissection in giant cell (temporal) arteritis. A population-based study. Ann Intern Med 122:502–507CrossRefPubMedGoogle Scholar
  48. 48.
    Robson JC, Kiran A, Maskell J et al (2015) The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK. Ann Rheum Dis 74:129–135CrossRefPubMedGoogle Scholar
  49. 49.
    Kermani TA, Warrington KJ, Crowson CS, Ytterberg SR, Hunder GG, Gabriel SE, Matteson EL (2013) Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence—trends and prognosis. Ann Rheum Dis 72:1989–1994CrossRefPubMedGoogle Scholar
  50. 50.
    Mackie SL, Hensor EM, Morgan AW, Pease CT (2014) Should I send my patient with previous giant cell arteritis for imaging of the thoracic aorta? A systematic literature review and meta-analysis. Ann Rheum Dis 73:143–148CrossRefPubMedGoogle Scholar
  51. 51.
    Hill CL, Black RJ, Nossent JC, Ruediger C, Nguyen L, Ninan JV, Lester S (2017) Risk of mortality in patients with giant cell arteritis: a systematic review and meta-analysis. Semin Arthritis Rheum 46:513–519CrossRefPubMedGoogle Scholar
  52. 52.
    Direskeneli H (2017) Clinical assessment in Takayasu's arteritis: major challenges and controversies. Clin Exp Rheumatol 35(Suppl 103):189–193PubMedGoogle Scholar
  53. 53.
    Grayson PC, Cuthbertson D, Carette S et al (2013) New features of disease after diagnosis in 6 forms of systemic vasculitis. J Rheumatol 40:1905–1912CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Omma A, Erer B, Karadag O et al (2017) Remarkable damage along with poor quality of life in Takayasu arteritis: cross-sectional results of a long-term followed-up multicentre cohort. Clin Exp Rheumatol 35(Suppl 103):77–82PubMedGoogle Scholar
  55. 55.
    Machen L, Clowse ME (2017) Vasculitis and pregnancy. Rheum Dis Clin N Am 43:239–247CrossRefGoogle Scholar
  56. 56.
    Gatto M, Iaccarino L, Canova M, Zen M, Nalotto L, Ramonda R, Punzi L, Doria A (2012) Pregnancy and vasculitis: a systematic review of the literature. Autoimmun Rev 11:A447–A459CrossRefPubMedGoogle Scholar
  57. 57.
    Seyahi E (2017) Takayasu arteritis: an update. Curr Opin Rheumatol 29:51–56CrossRefPubMedGoogle Scholar
  58. 58.
    Ishikawa K, Maetani S (1994) Long-term outcome for 120 Japanese patients with Takayasu's disease. Clinical and statistical analyses of related prognostic factors. Circulation 90:1855–1860CrossRefPubMedGoogle Scholar
  59. 59.
    Park MC, Lee SW, Park YB, Chung NS, Lee SK (2005) Clinical characteristics and outcomes of Takayasu's arteritis: analysis of 108 patients using standardised criteria for diagnosis, activity assessment, and angiographic classification. Scand J Rheumatol 34:284–292CrossRefPubMedGoogle Scholar
  60. 60.
    Li J, Zhu M, Li M, Zheng W, Zhao J, Tian X, Zeng X (2016) Cause of death in Chinese Takayasu arteritis patients. Medicine (Baltimore) 95:e4069CrossRefGoogle Scholar
  61. 61.
    Flossmann O, Berden A, de Groot K et al (2011) Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 70:488–494CrossRefPubMedGoogle Scholar
  62. 62.
    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) 75:17–28CrossRefGoogle Scholar
  63. 63.
    Guillevin L, Pagnoux C, Seror R 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 (Baltimore) 90:19–27CrossRefGoogle Scholar
  64. 64.
    Holle JU, Gross WL, Latza U et al (2011) Improved outcome in 445 patients with Wegener’s granulomatosis in a German vasculitis center over four decades. Arthritis Rheum 63:257–266CrossRefPubMedGoogle Scholar
  65. 65.
    Mohammad AJ, Segelmark M (2014) A population-based study showing better renal prognosis for proteinase 3 antineutrophil cytoplasmic antibody (ANCA)-associated nephritis versus myeloperoxidase ANCA-associated nephritis. J Rheumatol 41:1366–1373CrossRefPubMedGoogle Scholar
  66. 66.
    Jayne DR, Gaskin G, Rasmussen N et al (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
  67. 67.
    de Joode AA, Sanders JS, Stegeman CA (2013) Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin J Am Soc Nephrol 8:1709–1717CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Marco H, Mirapeix E, Arcos E et al (2013) Long-term outcome of antineutrophil cytoplasmic antibody-associated small vessel vasculitis after renal transplantation. Clin Transpl 27:338–347CrossRefGoogle Scholar
  69. 69.
    Berden AE, Ferrario F, Hagen EC et al (2010) Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol 21:1628–1636CrossRefPubMedGoogle Scholar
  70. 70.
    Goupil R, Brachemi S, Nadeau-Fredette AC, Déziel C, Troyanov Y, Lavergne V, Troyanov S (2013) Lymphopenia and treatment-related infectious complications in ANCA-associated vasculitis. Clin J Am Soc Nephrol 8:416–423CrossRefPubMedGoogle Scholar
  71. 71.
    Hoffman GS, Kerr GS, Leavitt RY et al (1992) Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116:488–498CrossRefPubMedGoogle Scholar
  72. 72.
    Faurschou M, Sorensen IJ, Mellemkjaer L et al (2008) Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 35:100–105PubMedGoogle Scholar
  73. 73.
    Heijl C, Harper L, Flossmann O et al (2011) Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann Rheum Dis 70:1415–1421CrossRefPubMedGoogle Scholar
  74. 74.
    Robson J, Doll H, Suppiah R et al (2015) Damage in the ANCA-associated vasculitides: long-term data from the European Vasculitis Study Group (EUVAS) therapeutic trials. Ann Rheum Dis 74:177–184CrossRefPubMedGoogle Scholar
  75. 75.
    Robson J, Doll H, Suppiah R et al (2014) Glucocorticoid treatment and damage in the anti-neutrophil cytoplasm antibody-associated vasculitides: long-term data from the European Vasculitis Study Group trials. Rheumatology (Oxford) 54:471–481CrossRefGoogle Scholar
  76. 76.
    Nesher G, Sonnenblick M, Friedlander Y (1994) Analysis of steroid related complications and mortality in temporal arteritis: a 15-year survey of 43 patients. J Rheumatol 21:1283–1286PubMedGoogle Scholar
  77. 77.
    Hoes JN, Jacobs JW, Boers M et al (2007) EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 66:1560–1567CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L (2013) Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis 72:1280–1286CrossRefPubMedGoogle Scholar
  79. 79.
    Wagner AD, Wittkop U, Prahst A, Schmidt WA, Gromnica-Ihle E, Vorpahl K, Hudson AP, Zeidler H (2003) Dendritic cells co-localize with activated CD4+ T cells in giant cell arteritis. Clin Exp Rheumatol 21:185–192PubMedGoogle Scholar
  80. 80.
    Andonopoulos AP, Meimaris N, Daoussis D, Bounas A, Giannopoulos G (2003) Experience with infliximab (anti-TNF alpha monoclonal antibody) as monotherapy for giant cell arteritis. Ann Rheum Dis 62:1116CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Uthman I, Kanj N, Atweh S (2006) Infliximab as monotherapy in giant cell arteritis. Clin Rheumatol 25:109–110CrossRefPubMedGoogle Scholar
  82. 82.
    Hoffman GS, Cid MC, Rendt-Zagar KE et al (2007) Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Intern Med 146:621–630CrossRefPubMedGoogle Scholar
  83. 83.
    Roche NE, Fulbright JW, Wagner AD, Hunder GG, Goronzy JJ, Weyand CM (1993) Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum 36:1286–1294CrossRefPubMedGoogle Scholar
  84. 84.
    Noris M, Daina E, Gamba S, Bonazzola S, Remuzzi G (1999) Interleukin-6 and RANTES in Takayasu arteritis: a guide for therapeutic decisions? Circulation 100:55–60CrossRefPubMedGoogle Scholar
  85. 85.
    Stone JH, Tuckwell K, Dimonaco S et al (2017 Jul) Trial of tocilizumab in giant-cell arteritis. N Engl J Med 377:317–328CrossRefPubMedGoogle Scholar
  86. 86.
    Pazzola G, Padovano I, Boiardi L et al (2013) Tocilizumab in glucocorticoid-naïve large-vessel vasculitis. Clin Exp Rheumatol 31(1 Suppl 75):S59–S61PubMedGoogle Scholar
  87. 87.
    Salvarani C, Magnani L, Catanoso M et al (2012) Tocilizumab: a novel therapy for patients with large-vessel vasculitis. Rheumatology (Oxford) 51:151–156CrossRefGoogle Scholar
  88. 88.
    Seitz M, Reichenbach S, Bonel HM, Adler S, Wermelinger F, Villiger PM (2011) Rapid induction of remission in large vessel vasculitis by IL-6 blockade. A case series. Swiss Med Wkly 141:w13156PubMedGoogle Scholar
  89. 89.
    Hernández-Rodríguez J, Segarra M, Vilardell C et al (2003) Elevated production of interleukin-6 is associated with a lower incidence of disease-related ischemic events in patients with giant-cell arteritis: angiogenic activity of interleukin-6 as a potential protective mechanism. Circulation 107:2428–2434CrossRefPubMedGoogle Scholar
  90. 90.
    Reichenbach S, Adler S, Cullmann J et al (2016) Tocilizumab for the treatment of giant cell arteritis—MR-angiography results from the first randomized placebo-controlled trial [abstract]. Arthritis Rheum. http://acrabstracts.org/abstract/tocilizumab-for-the-treatment-of-giant-cell-arteritis-mr-angiography-results-from-the-first-randomized-placebo-controlled-trial/. Accessed 8 Sept 2017
  91. 91.
    Jennette JC, Falk RJ (1995) Clinical and pathological classification of ANCA-associated vasculitis: what are the controversies? Clin Exp Immunol 101(Suppl 1):18–22CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Kubaisi B, Abu Samra K, Foster CS (2016) Granulomatosis with polyangiitis (Wegener's disease): an updated review of ocular disease manifestations. Intractable Rare Dis Res 5:61–69CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Comarmond C, Cacoub P (2014) Granulomatosis with polyangiitis (Wegener): clinical aspects and treatment. Autoimmun Rev 13:1121–1125CrossRefPubMedGoogle Scholar
  94. 94.
    De Groot K, Rasmussen N, Bacon PA et al (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
  95. 95.
    Flossmann O, Jones RB, Jayne DR, Luqmani RA (2006) Should rituximab be used to treat antineutrophil cytoplasmic antibody associated vasculitis? Ann Rheum Dis 65:841–844CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Jones RB, Tervaert JW, Hauser T et al (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363:211–220CrossRefPubMedGoogle Scholar
  97. 97.
    Stone JH, Merkel PA, Spiera R et al (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363:221–232CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Seo P, Specks U, Keogh KA (2008) Efficacy of rituximab in limited Wegener's granulomatosis with refractory granulomatous manifestations. J Rheumatol 35:2017–2023PubMedGoogle Scholar
  99. 99.
    Aries PM, Hellmich B, Voswinkel J et al (2006) Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations. Ann Rheum Dis 65:853–858CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Holle JU, Dubrau C, Herlyn K et al (2012) Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. Ann Rheum Dis 71:327–333CrossRefPubMedGoogle Scholar
  101. 101.
    Khan A, Lawson CA, Quinn MA et al (2010) Successful treatment of ANCA-negative Wegener's granulomatosis with rituximab. Int J Rheumatol 2010:846063CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Martinez Del Pero M, Chaudhry A, Jones RB et al (2009) B cell depletion with rituximab for refractory head and neck Wegener's granulomatosis: a cohort studies. Clin Otolaryngol 34:328–335CrossRefPubMedGoogle Scholar
  103. 103.
    Ooka S, Maeda A, Ito H et al (2009) Treatment of refractory retrobulbar granuloma with rituximab in a patient with ANCA-negative Wegener's granulomatosis: a case report. Mod Rheumatol 19:80–83CrossRefPubMedGoogle Scholar
  104. 104.
    Shah S, Hruskova Z, Segelmark M et al (2015) Treatment of severe renal disease in ANCA positive and negative small vessel vasculitis with rituximab. Am J Nephrol 41(4–5):296–301CrossRefPubMedGoogle Scholar
  105. 105.
    Charles P, Néel A, Tieulié N et al (2014) Rituximab for induction and maintenance treatment of ANCA-associated vasculitides: a multicentre retrospective study on 80 patients. Rheumatology (Oxford) 53:532–539CrossRefGoogle Scholar
  106. 106.
    Mukhtyar C, Guillevin L, Cid MC et al (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 68:310–317CrossRefPubMedGoogle Scholar
  107. 107.
    Samson M, Puéchal X, Devilliers H et al (2013) Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials. J Autoimmun 43:60–69CrossRefPubMedGoogle Scholar
  108. 108.
    Healy B, Bibby S, Steele R et al (2013) Antineutrophil cytoplasmic autoantibodies and myeloperoxidase autoantibodies in clinical expression of Churg-Strauss syndrome. J Allergy Clin Immunol 131:571–576CrossRefPubMedGoogle Scholar
  109. 109.
    Vaglio A, Strehl JD, Manger B et al (2012) IgG4 immune response in Churg-Strauss syndrome. Ann Rheum Dis 71:390–393CrossRefPubMedGoogle Scholar
  110. 110.
    Vaglio A, Moosig F, Zwerina J (2012) Churg-Strauss syndrome: update on pathophysiology and treatment. Curr Opin Rheumatol 24:24–30CrossRefPubMedGoogle Scholar
  111. 111.
    Mohammad AJ, Hot A, Arndt F et al (2016) Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Ann Rheum Dis 75:396–401CrossRefPubMedGoogle Scholar
  112. 112.
    Novikov P, Moiseev S, Smitienko I, Zagvozdkina E (2016) Rituximab as induction therapy in relapsing eosinophilic granulomatosis with polyangiitis: a report of 6 cases. Joint Bone Spine 83:81–84CrossRefPubMedGoogle Scholar
  113. 113.
    Thiel J, Hässler F, Salzer U et al (2013) Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Arthritis Res Ther 24(15):R133CrossRefGoogle Scholar
  114. 114.
    Cartin-Ceba R, Keogh KA, Specks U et al (2011) Rituximab for the treatment of Churg–Strauss syndrome with renal involvement. Nephrol Dial Transplant 26:2865–2871CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Donvik KK, Omdal R (2011) Churg–Strauss syndrome successfully treated with rituximab. Rheumatol Int 31:89–91CrossRefPubMedGoogle Scholar
  116. 116.
    Pepper RJ, Fabre MA, Pavesio C et al (2008) Rituximab is effective in the treatment of refractory Churg–Strauss syndrome and is associated with diminished T-cell interleukin-5 production. Rheumatology (Oxford) 47:1104–1105CrossRefGoogle Scholar
  117. 117.
    Roccatello D, Sciascia S, Rossi D et al (2011) Long-term effects of rituximab added to cyclophosphamide in refractory patients with vasculitis. Am J Nephrol 34:175–180CrossRefPubMedGoogle Scholar
  118. 118.
    Koukoulaki M, Smith HG, Jayne DR (2006) Rituximab in Churg–Strauss syndrome. Ann Rheum Dis 65:557–559CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Fanouriakis A, Kougkas N, Vassilopoulos D et al (2015) Rituximab for eosinophilic granulomatosis with polyangiitis with severe vasculitic neuropathy: case report and review of current clinical evidence. Semin Arthritis Rheum 45:60–66CrossRefPubMedGoogle Scholar
  120. 120.
    Martinez-Villaescusa M, Lopez-Montes A, Lopez-Rubio E et al (2013) Treatment-resistant Churg–Strauss syndrome: progression after five years using rituximab. Nefrologia 33:737–739PubMedGoogle Scholar
  121. 121.
    Saech J, Owczarczyk K, Rosgen S et al (2009) Successful use of rituximab in a patient with Churg–Strauss syndrome and refractory central nervous system involvement. Ann Rheum Dis 69:1254–1255PubMedGoogle Scholar
  122. 122.
    Rees F, Yazdani R, Lanyon P (2011) Long-term follow-up of different refractory systemic vasculitides treated with rituximab. Clin Rheumatol 30:1241–1245CrossRefPubMedGoogle Scholar
  123. 123.
    Lovric S, Erdbruegger U, Kumpers P et al (2009) Rituximab as rescue therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-centre experience with 15 patients. Nephrol Dial Transplant 24:179–185CrossRefPubMedGoogle Scholar
  124. 124.
    Najem CE, Yadav R, Carlson E (2015) Successful use of rituximab in a patient with recalcitrant multisystemic eosinophilic granulomatosis with polyangiitis. BMJ Case Rep 15:2015Google Scholar
  125. 125.
    Diamanti L, Berzero G, Bini P et al (2014) Spinal hemorrhage in eosinophilic granulomatosis with polyangiitis (Churg–Strauss). J Neurol 261:438–440CrossRefPubMedGoogle Scholar
  126. 126.
    Chao MP, Hong J, Kunder C et al (2015) Refractory warm IgM-mediated autoimmune hemolytic anemia associated with Churg–Strauss syndrome responsive to eculizumab and rituximab. Am J Hematol 90:78–81CrossRefPubMedGoogle Scholar
  127. 127.
    Grigoriou A, Endean A, Sangle SR, DP D′C (2014) B cell depletion therapy and eosinophilic granulomatosis with polyangiitis with hepatic involvement. Rheumatology (Oxford) 53:1741CrossRefGoogle Scholar
  128. 128.
    Umezawa N, Kohsaka H, Nanki T et al (2014) Successful treatment of eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg–Strauss syndrome) with rituximab in a case refractory to glucocorticoids, cyclophosphamide, and IVIG. Mod Rheumatol 24:685–687CrossRefPubMedGoogle Scholar
  129. 129.
    Smith KG, Jones RB, Burns SM, Jayne DR (2006) Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse, and re-treatment. Arthritis Rheum 54:2970–2982CrossRefPubMedGoogle Scholar
  130. 130.
    Kaushik VV, Reddy HV, Bucknall RC (2006) Successful use of rituximab in a patient with recalcitrant Churg–Strauss syndrome. Ann Rheum Dis 65:1116–1117CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Baikunje S, Vankalakunti M, Upadhyaya VS, Hosmane GB (2016) Eosinophilic granulomatosis with polyangiitis with severe pulmonary hemorrhage treated with rituximab. Indian J Nephrol 26:142–144CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Groh M, Pagnoux C, Baldini C et al (2015) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. Eur J Intern Med 26:545–553CrossRefPubMedGoogle Scholar
  133. 133.
    Jennette J, Falk R, Bacon P et al (2013) 2012 revised International Chapel Hill Consensus Conference Nomenclature of vasculitides. Arthritis Rheum 65:1–11CrossRefPubMedGoogle Scholar
  134. 134.
    Ribi C, Cohen P, Pagnoux C et al (2010) Treatment of polyarteritis nodosa and microscopic polyangiitis without poor-prognosis factors: a prospective randomized study of one hundred twenty-four patients. Arthritis Rheum 62:1186–1197CrossRefPubMedGoogle Scholar
  135. 135.
    Gayraud M, Guillevin L, le Toumelin P et al (2001) Long-term follow-up of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis Rheum 44:666–675CrossRefPubMedGoogle Scholar
  136. 136.
    Pagnoux C, Seror R, Henegar C et al (2010) Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum 62:616–626CrossRefPubMedGoogle Scholar
  137. 137.
    Da Silva LS, De Campos KV, de Melo AK et al (2015) Rituximab as an alternative for patients with severe systemic vasculitis refractory to conventional therapy: report of seven cases and literature review. Rev Bras Reumatol 55:531–535CrossRefPubMedGoogle Scholar
  138. 138.
    Seri Y, Shoda H, Hanata N et al (2015) A case of refractory polyarteritis nodosa successfully treated with rituximab. Mod Rheumatol 12:1–3Google Scholar
  139. 139.
    Krishnan S, Bhakuni DS, Kartik S (2012) Rituximab in refractory cutaneous polyarteritis. Int J Rheum Dis 15:e127CrossRefPubMedGoogle Scholar
  140. 140.
    Néel A, Masseau A, Hervier B et al (2011) Life-threatening hepatitis C virus-associated polyarteritis nodosa successfully treated by rituximab. J Clin Rheumatol 17:439–441CrossRefPubMedGoogle Scholar
  141. 141.
    Bansal NK, Houghton KM (2010) Cutaneous polyarteritis nodosa in childhood: a case report and review of the literature. Arthritis 2010:687547CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Ribeiro E, Cressend T, Duffau P et al (2009) Rituximab efficacy during a refractory polyarteritis nodosa flare. Case Rep Med 2009:738293CrossRefPubMedGoogle Scholar
  143. 143.
    Eleftheriou D, Melo M, Marks SD et al (2009) Biologic therapy in primary systemic vasculitis of the young. Rheumatology (Oxford) 48:978–986CrossRefGoogle Scholar
  144. 144.
    Zoshima T, Matsumura M, Suzuki Y et al (2013) A case of refractory cutaneous polyarteritis nodosa in a patient with hepatitis B carrier status successfully treated with tumor necrosis factor alpha blockade. Mod Rheumatol 23:1029–1033CrossRefPubMedGoogle Scholar
  145. 145.
    Feinstein J, Arroyo R (2005) Successful treatment of childhood onset refractory polyarteritis nodosa with tumor necrosis factor alpha blockade. J Clin Rheumatol 11:219–222CrossRefPubMedGoogle Scholar
  146. 146.
    Tous-Romero F, Rodríguez-Almaraz E, Rodríguez-Peralto JL, Postigo-Llorente C (2017) Polyarteritis nodosa with a systemic inflammatory response pattern: effectiveness of anti-TNF. Actas DermosifiliogrGoogle Scholar
  147. 147.
    Valor L, Monteagudo I, de la Torre I et al (2014) Young male patient diagnosed with cutaneous polyarteritis nodosa successfully treated with etanercept. Mod Rheumatol 24:(4)688–689CrossRefPubMedGoogle Scholar
  148. 148.
    Capuozzo M, Ottaiano A, Nava E et al (2014) Etanercept induces remission of polyarteritis nodosa: a case report. Front Pharmacol 5:122CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Matsuo S, Hayashi K, Morimoto E et al (2017) The successful treatment of refractory polyarteritis nodosa using infliximab. Intern Med 56:1435–1438CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Garcia-Porrua C, Gonzalez-Gay MA (2003) Successful response to infliximab in a patient with undifferentiated spondyloarthropathy coexisting with polyarteritis nodosa-like cutaneous vasculitis. Clin Exp Rheumatol 21(6 Suppl 32):S138PubMedGoogle Scholar
  151. 151.
    Wu K, Throssell D (2006) A new treatment for polyarteritis nodosa. Nephrol Dial Transplant 21:1710–1712CrossRefPubMedGoogle Scholar
  152. 152.
    Al-Bishri J, le Riche N, Pope JE (2005) Refractory polyarteritis nodosa successfully treated with infliximab. J Rheumatol 32:1371–1373PubMedGoogle Scholar
  153. 153.
    Keystone EC (2004) The utility of tumour necrosis factor blockade in orphan diseases. Ann Rheum Dis 63(Suppl 2):ii79–ii83PubMedPubMedCentralGoogle Scholar
  154. 154.
    Vega Gutierrez J, Rodriguez Prieto MA, Garcia Ruiz JM (2007) Successful treatment of childhood cutaneous polyarteritis nodosa with infliximab. J Eur Acad Dermatol Venereol 21:570–571PubMedGoogle Scholar
  155. 155.
    Campanilho-Marques R, Ramos F, Canhão H, Fonseca JE (2014) Remission induced by infliximab in a childhood polyarteritis nodosa refractory to conventional immunosuppression and rituximab. Joint Bone Spine 81:277–278CrossRefPubMedGoogle Scholar
  156. 156.
    Wahezi DM, Gomes WA, Ilowite NT (2010) Cranial nerve involvement with juvenile polyarteritis nodosa: clinical manifestations and treatment. Pediatrics 126:e719–e722CrossRefPubMedGoogle Scholar
  157. 157.
    Braun-Moscovici Y, Markovits D, Rozin A et al (2008) Anti-tumor necrosis factor therapy: 6 year experience of a single center in northern Israel and possible impact of health policy on results. Isr Med Assoc J 10:277–281PubMedGoogle Scholar
  158. 158.
    Soriano A, Pipitone N, Salvarani C Cardiac involvement in Behçet disease. In: The heart in rheumatic, autoimmune and inflammatory diseases. Elsevier Ed. ISBN: 978-0-12-803267-1 | Feb 28, 2017Google Scholar
  159. 159.
    Ombrello MJ, Kirino Y, de Bakker PI, Kastner DL, Remmers EF (2014) Behcet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated toxicity. Proc Natl Acad Sci U S A 111(24):8867–8872CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Dilsen N, Konice M, Aral O et al (1988) Behcet's disease associated with amyloidosis in Turkey and in the world. Ann Rheum Dis 47:157–163CrossRefPubMedPubMedCentralGoogle Scholar
  161. 161.
    Mahr A, Belarbi L, Wechsler B et al (2008) Population-based prevalence study of Behcet's disease: differences by ethnic origin and low variation by age at immigration. Arthritis Rheum 58:3951–3959CrossRefPubMedGoogle Scholar
  162. 162.
    Salvarani C, Pipitone N, Catanoso MG et al (2007) Epidemiology and clinical course of Behcet's disease in the Reggio Emilia area of Northern Italy: a seventeen-year population-based study. Arthritis Rheum 57:171–178CrossRefPubMedGoogle Scholar
  163. 163.
    Calamia KT, Wilson FC, Icen M, Crowson CS, Gabriel SE, Kremers HM (2009) Epidemiology and clinical characteristics of Behcet's disease in the US: a population-based study. Arthritis Rheum 61:600–604CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    Zouboulis CC (1999) Epidemiology of Adamantiades-Behcet's disease. Ann Med Interne (Paris) 150:488–498Google Scholar
  165. 165.
    Savey L, Resche-Rigon M, Wechsler B et al (2014) Ethnicity and association with disease manifestations and mortality in Behcet's disease. Orphanet J Rare Dis 9:42CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Behcet H (1937) Über rezidivierende, aphthöse, durch ein virus verursachte Geschwüre am Mund, am Auge und an den Genitalien. Dermatol Wochenschr 105:1152–1157Google Scholar
  167. 167.
    Davatchi F, Sadeghi AB, Chams-Davatchi C et al (2015) The saga of diagnostic/classification criteria in Behcet's disease. Int J Rheum Dis 18:594–605CrossRefPubMedGoogle Scholar
  168. 168.
    Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet 1990; 335:1078–80Google Scholar
  169. 169.
    O'Neill TW, Rigby AS, Silman AJ, Barnes C (1994) Validation of the International Study Group criteria for Behcet's disease. Br J Rheumatol 33:115–117CrossRefPubMedGoogle Scholar
  170. 170.
    Yazici H, Yazici Y (2014) Criteria for Behçet’s disease with reflections on all disease criteria. J Autoimmun 48-49:104–107CrossRefPubMedGoogle Scholar
  171. 171.
    The International Criteria for Behcet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014; 28:338–47Google Scholar
  172. 172.
    Ozguler Y, Leccese P, Christensen R et al (2016) A systematic literature review on the treatment of major organ involvement of Behçet’s syndrome informing the EULAR recommendations for the management of Behçet’s syndrome. Clin Exp Rheumatol 34(Suppl. 102):S175Google Scholar
  173. 173.
    Guzelant G, Ucar D, Hatemi G et al (2016) Earlier use of infliximab for the uveitis of Behçet’s syndrome appears to be associated with better outcome. Clin Exp Rheumatol 34(Suppl. 102):S143Google Scholar
  174. 174.
    Esatoglu SN, Hatemi G, Leccese P (2016) Olivieri I. Highlights of the 17th International Conference on Behçet’s syndrome. Matera, Italy, 15-17 September 2016. Clin Exp Rheumatol 34(Suppl 012):S3–S9Google Scholar
  175. 175.
    Lopalco G, Emmi G, Gentileschi S et al (2016) Certolizumab pegol treatment in Behçet’s disease: a multicenter retrospective observational study. Clin Exp Rheumatol 34(Suppl. 102):S187Google Scholar
  176. 176.
    Tsianakas A, Brunner PM, Ghoreschi K et al (2016) The single-chain anti-TNF antibody DLX105 induces clinical and biomarkers responses upon local administration in patients with chronic plaque-type psoriasis. Exp Dermatol 25:428–433CrossRefPubMedGoogle Scholar
  177. 177.
    Xenitidis T, Berger C, Jung T, Henes J, Koetter I (2016) Effective and rapid treatment of flares in patients with Behçet’s disease by the single chain anti-TNF antibody DLX105. Clin Exp Rheumatol 34(Suppl. 102):S188Google Scholar
  178. 178.
    Hatemi G, Melikoglu M, Tunc R et al (2015) Apremilast for Behçet’s syndrome—a phase 2, placebo-controlled study. N Engl J Med 372:1510–1518CrossRefPubMedGoogle Scholar
  179. 179.
    Touzot M, Cacoub P, Bodaghi B, Soumelis V, Saadoun D (2015) IFN-a induces IL-10 production and tilt the balance between Th1 and Th17 in Behçet disease. Autoimmun Rev 14:370e375CrossRefGoogle Scholar
  180. 180.
    Habibagahi Z, Habibagahi M, Heidari M (2010) Raised concentration of soluble form of vascular endothelial cadherin and IL-23 in sera of patients with Behçet's disease. Mod Rheumatol 20:154e159CrossRefGoogle Scholar
  181. 181.
    Mirouse A, Barete S, Monfort JB et al (2017) Ustekinumab for Behçet’s disease. J Autoimmun 82:41–46CrossRefPubMedGoogle Scholar
  182. 182.
    Cantarini L, Vitale A, Scalini P, Dinarello CA, Rigante D, Franceschini R, Simonini G et al (2015) Anakinra treatment in drug-resistant Behcet’s disease: a case series. Clin Rheumatol 34:1293–1301CrossRefPubMedGoogle Scholar
  183. 183.
    Botsios C, Sfriso P, Furlan A, Punzi L, Dinarello CA (2008) Resistant Behçet disease responsive to anakinra. Ann Intern Med 149:284–286CrossRefPubMedGoogle Scholar
  184. 184.
    Vitale A, Rigante D, Caso F et al (2014) Inhibition of interleukin-1 by canakinumab as a successful mono-drug strategy for the treatment of refractory Behçet’s disease: a case series. Dermatology 228:211–214CrossRefPubMedGoogle Scholar
  185. 185.
    Capittini C, De Silvestri C, De Silvestri A, Scotti V, Scudelleri L, Tinelli C (2016) Systematic review of the literature for the use of intravenous immunoglobulins in Behçet disease. Clin Exp Rheumatol 34(Suppl. 102):S182Google Scholar
  186. 186.
    Capittini C, De Amici M, De Silvestri A (2016) Plasma cytokines as biomarkers for clinical response during nine months of intravenous immunoglobulins therapy in a Behçet disease patient unsuitable for immunosuppression. Clin Exp Rheumatol 34(Suppl. 102):S182Google Scholar
  187. 187.
    Shapiro LS, Farrell J, Borhani HA (2012) Tocilizumab treatment for neuro-Behcet’s disease, the first report. Clin Neurol Neurosurg 114:297–298CrossRefPubMedGoogle Scholar
  188. 188.
    Addimanda O, Pipitone N, Pazzola G, Salvarani C (2015) Tocilizumab for severe refractory neuro-Behçet: three cases IL-6 blockade in neuro-Behçet. Semin Arthritis Rheum 44:472–475CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Francesco Muratore
    • 1
    • 2
  • Giulia Pazzola
    • 1
    • 2
  • Alessandra Soriano
    • 1
    • 3
  • Nicolò Pipitone
    • 1
  • Stefania Croci
    • 4
  • Martina Bonacini
    • 4
  • Luigi Boiardi
    • 1
  • Carlo Salvarani
    • 1
    • 2
  1. 1.Division of Rheumatology, Department of MedicineArcispedale Santa Maria Nuova Istituto di Ricovero e Cura a Carattere ScientificoReggio EmiliaItaly
  2. 2.University of Modena and Reggio EmiliaModenaItaly
  3. 3.Campus Bio-MedicoUniversity of RomeRomeItaly
  4. 4.Unit of Clinical Immunology, Allergy and Advanced BiotechnologiesArcispedale Santa Maria Nuova Istituto di Ricovero e Cura a Carattere ScientificoReggio EmiliaItaly

Personalised recommendations