Abstract
Due to the variable severity of clinical manifestations of Behcet’s disease (BD), the therapy should be modulated in function of the specific clinical manifestations. New topical therapies such as pimecrolimus and amlexanox are useful for oral and genital ulcers. Old systemic therapies, especially colchicine, azathioprine, and cyclosporine represent the first-line therapy in most cases. In presence of BD serious manifestations, including uveitis, vascular, neurologic, and intestinal involvement, an aggressive therapy with high-dose corticosteroids plus an immunosuppressive drug such as cyclosporine, azathioprine, and cyclophosphamide is required. Recently, the efficacy of interferon alpha and anti-TNF for the treatment of refractory uveitis has been repeatedly reported. These therapies allowed the achievement of complete remission with improvement of visual acuity in 70–90 % of the cases of uveitis. Moreover, anti-TNF has been demonstrated as effective in all other BD manifestations. However, to date, these drugs should be used as second-line therapy in more severe forms of BD unresponsive to old immunosuppressive therapies.
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References
Dalvi SR, Yildirim R, Yazici Y (2012) Behcet’s syndrome. Drugs 72(30):2223–2241
Alpsoy E (2012) New evidence-based treatment approach in Behçet’s disease. Patholog Res Int 2012:871019
Köse O, Dinç A, Simşek I (2009) Randomized trial of pimecrolimus cream plus colchicine tablets versus colchicine tablets in the treatment of genital ulcers in Behçet’s disease. Dermatology 218:140–145
Chams-Davatchi C, Barikbin B, Shahram F et al (2010) Pimecrolimus versus placebo in genital aphthous ulcers of Behcet’s disease: a randomized double-blind controlled trial. Int J Rheum Dis 13:253–258
Meng W, Dong Y, Liu J et al (2009) A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial. Trials 6(10):30
Yurdakul S, Mat C, Tuzun Y et al (2001) A double-blind trial of colchicine in Behçet’s syndrome. Arthritis Rheum 44:2686–2692
Davatchi F, SadeghiAbdollahi B et al (2009) Colchicine versus placebo in Behçet’s disease: randomized, double-blind, controlled crossover trial. Mod Rheumatol 19:542–549
Al-Waiz MM, Sharquie KE, A-Qaissi MH et al (2005) Colchicine and benzathine penicillin in the treatment of Behçet disease: a case comparative study. Dermatol Online J 11:3
Matsuda T, Ohno S, Hirohata S et al (2003) Efficacy of rebamipide as adjunctive therapy in the treatment of recurrent oral aphthous ulcers in patients with Behçet’s disease: a randomised, double-blind, placebo-controlled study. Drugs R.D 4:19–28
Sharquie KE, Najim RA, Abu-Raghif AR (2002) Dapsone in Behçet’s disease: a double-blind, placebo-controlled, cross-over study. J Dermatol 29:267–279
Tiede I, Fritz G, Strand S et al (2003) CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4 + T lymphocytes. J Clin Invest 111:1133–1145
Yazici H, Pazarli H, Barnes CG et al (1990) A controlled trial of azathioprine in Behçet’s syndrome. N Engl J Med 322:281–285
Chaparro M, Ordás I, Cabré E et al (2013) Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis 19:1404–1410
Ozyazgan Y, Yurdakul S, Yazici H et al (1992) Low dose cyclosporin a versus pulsed cyclophosphamide in Behçet’s syndrome: a single masked trial. Br J Ophthalmol 76:241–243
Mudun BA, Ergen A, Ipcioglu SU et al (2001) Short-term chlorambucil for refractory uveitis in Behcet’s disease. Ocul Immunol Inflamm 9:219–29
Aberra FN, Lichtenstein GR (2005) Monitoring of immunomodulators in inflammatory bowel disease. Aliment Pharmacol Ther 21:307–319
Masuda K, Nakajima A, Urayama A et al (1989) Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet’s disease. Lancet 1(8647):1093–1096
Elidan J, Levi H, Cohen E et al (1991) Effect of cyclosporine a on the hearing loss in Behçet’s disease. Ann Otol Rhinol Laryngol 100:464–468
Cantini F, Salvarani C, Niccoli L et al (1999) Treatment of thrombophlebitis of Behçet’s disease with low dose cyclosporin A. Clin Exp Rheumatol 17:391–2
Kötter I, Günaydin I, Batra M et al (2006) CNS involvement occurs more frequently in patients with Behçet’s disease under cyclosporin A (CSA) than under other medications—results of a retrospective analysis of 117 cases. Clin Rheumatol 25:482–486
Kikuchi H, Aramaki K, Hirohata S (2003) Low dose MTX for progressive neuro-Behçet’s disease. A follow-up study for 4 years. Adv Exp Med Biol 528:575–578
Allison AC (2005) Mechanisms of action of mycophenolate mofetil. Lupus 14:S2–S8
Daniel E, Thorne JE, Newcomb CW et al (2010) Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol 149:423–432
Neri P, Mariotti C, Cimino L et al (2009) Long-term control of cystoid macular oedema in non-infectious uveitis with Mycophenolate Mofetil. Int Ophthalmol 29:127–133
Shugaiv E, Tüzün E, Mutlu M et al (2011) Mycophenolate mofetil as a novel immunosuppressant in the treatment of neuro-Behçet’s disease with parenchymal involvement: presentation of four cases. Clin Exp Rheumatol 29(4):S64–S67, Suppl 67
Tompkins WA (1999) Immunomodulation and therapeutic effects of the oral use of interferon-alpha: mechanism of action. J Interferon Cytokine Res 19(8):817–828
Alpsoy E, Durusoy C, Yilmaz E et al (2002) Interferon alfa-2a in the treatment of Behçet disease: a randomized placebo-controlled and double-blind study. Arch Dermatol 138:467–471
Kötter I, Zierhut M, Eckstein AK et al (2003) Human recombinant interferon alpha-2a for the treatment of Behçet’s disease with sight threatening posterior or panuveitis. Br J Ophthalmol 87:423–431
Tugal-Tutkun I, Guney-Tefekli E, Urgancioglu M (2006) Results of interferon-alfa therapy in patients with Behçet uveitis. Graefe’s Arch Clin Exp Ophthalmol 244:1692–1695
Onal S, Kazokoglu H, Koc A et al (2011) Long-term efficacy and safety of low-dose and dose-escalating interferon alfa-2a therapy in refractory Behçet uveitis. Arch Ophthalmol 129:288–294
De Vos AF, van Haren MAC, Verhagen C et al (1994) Kinetics of intraocular tumor necrosis factor and interleukin 6 in endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 35:1100–1106
Mege JL, Dilsen N, Sanguedolce V et al (1993) Overproduction of monocyte derived tumor necrosis factor alpha, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet’s disease. A comparative study with familial Mediterranean fever and healthy subjects. J Rheumatol 20:1944–1949
Ohno S, Nakamnura S, Hori S et al (2004) Efficacy, safety, and pharmacokinetics of multiple administration of Infliximab in Behçet’disease with refractory uveitis. J Rheumatol 31:1362–1368
Sfikakis PP, Theodossiadis PG, Katsiari CG et al (2001) Effect of infliximab on sight-threatening panuveitis of Behçet’s disease. Lancet 358:295–296
Munoz-Fernandez S, Hidalgo V, Fernandez-Melon J et al (2001) Effect of infliximab on threatening panuveitis in Behçet’s disease. Lancet 358:1644
Triolo G, Vadalà M, Accardo-Palumbo A et al (2002) Anti-tumor necrosis factor monoclonal antibody treatment for ocular Behçet’s disease. Ann Rheum Dis 61:560–561
Niccoli L, Nannini C, Benucci M et al (2007) Long-term efficacy of infliximab in refractory posterior uveitis of Behcet’s disease: a 24-month follow-up study. Rheumatol (Oxford) 46:1161–1164
Cantini F, Niccoli L, Nannini C et al (2012) Efficacy of infliximab in refractory Behçet’s disease-associated and idiopathic posterior segment uveitis: a prospective, follow-up study of 50 patients. Biologics 6:5–12
Okada AA, Goto H, Ohno S et al (2012) Multicenter study of infliximab for refractory uveoretinitis in Behçet disease. Arch Ophthalmol 130:592–598
Iwata S, Saito K, Yamaoka K et al (2009) Effects of anti-TNF-alpha antibody infliximab in refractory entero-Behcet’s disease. Rheumatol (Oxford) 48:1012–1013
Giardina A, Ferrante A, Ciccia F et al (2011) One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behçet’s disease refractory to standard immunosuppressive drugs. Rheumatol Int 31:33–37
Perra D, Alba MA, Callejas JL et al (2012) Adalimumab for the treatment of Behçet’s disease: experience in 19 patients. Rheumatol (Oxford) 51:1825–1831
Melikoglu M, Fresko I, Mat C et al (2005) Short-term trial of etanercept in Behçet’s disease: a double blind, placebo controlled study. J Rheumatol 32:98–105
van der Horst-Bruinsma IE, Nurmohamed MT (2012) Management and evaluation of extra-articular manifestations in spondyloarthritis. Ther Adv Musculoskelet Dis 4:413–422
Davatchi F, Shams H, Rezaipoor M et al (2010) Rituximab in intractable ocular lesions of Behcet’s disease; randomized single-blind control study (pilot study). Int J Rheum Dis 13:246–252
Schoels MM, van der Heijde D, Breedveld FC et al (2013) Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement. Ann Rheum Dis 72:583–589
Hirohata S, Kikuchi H, Sawada T et al (2012) Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis. Mod Rheumatol 22:405–413
Hirano T, Ohguro N, Hohki S et al (2012) A case of Behçet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab. Mod Rheumatol 22:298–302
Shapiro LS, Farrell J, Haghighi AB (2012) Tocilizumab treatment for neuro-Behcet’s disease, the first report. Clin Neurol Neurosurg 114:297–298
Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behçet treated by tocilizumab: a case report. Clin Exp Rheumatol 30(3):S73–S75, Suppl 72)
Gül A, Tugal-Tutkun I, Dinarello CA et al (2012) Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet’s disease: an open-label pilot study. Ann Rheum Dis 71:563–566
Hatemi G, Silman A, Bang D et al (2008) EULAR recommendations for the management of Behçet’s disease: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 67:1656–1662
Tayer-Shifman OE, Seyahi E, Nowatzky J et al (2012) Major vessel thrombosis in Behçet’s disease: the dilemma of anticoagulant therapy—the approach of rheumatologists from different countries. Clin Exp Rheumatol 30:735–740
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Cantini, F., Di Scala, G. (2014). Old and New Treatment for Behçet’s Disease. In: Emmi, L. (eds) Behçet's Syndrome. Rare Diseases of the Immune System. Springer, Milano. https://doi.org/10.1007/978-88-470-5477-6_19
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DOI: https://doi.org/10.1007/978-88-470-5477-6_19
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