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Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Continuous evolution of clinical phenotype in 578 Japanese patients with Behçet’s disease: a retrospective observational study

Authors: Yohei Kirino, Haruko Ideguchi, Mitsuhiro Takeno, Akiko Suda, Kana Higashitani, Yosuke Kunishita, Kaoru Takase-Minegishi, Maasa Tamura, Toshiyuki Watanabe, Yukiko Asami, Takeaki Uehara, Ryusuke Yoshimi, Tetsu Yamazaki, Akiko Sekiguchi, Atsushi Ihata, Shigeru Ohno, Atsuhisa Ueda, Toshihisa Igarashi, Shohei Nagaoka, Yoshiaki Ishigatsubo, Hideaki Nakajima

Published in: Arthritis Research & Therapy | Issue 1/2016

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Abstract

Background

It has been suggested that the phenotypes of Behçet’s disease (BD) in Japan are changing. To ask whether the evolution of BD holds true in recent-onset cases in Japan, we performed a retrospective study.

Methods

We reviewed the records of 578 patients with BD who met the 1987 revised diagnostic criteria of the Behçet’s disease research committee of Japan. The patients were divided into three groups based on the date of disease onset. We compared the demography, clinical features, and treatments among them with or without adjustment for the observation period. Patients having oral ulcers, genital ulcers, regional skin involvement, and uveitis are categorized as having complete-type BD, and the associated factors were determined by univariate and multivariate logistic regression analyses.

Results

Male patients had a higher propensity for uveitis and central nervous system (CNS) involvement, whereas female patients had higher rates of genital ulcers and arthritis. We found a significant trend in reduction of complete-type, genital ulcer, HLA-B51 carriers, and increment of gastrointestinal BD over time. Multiple regression analysis identified HLA-B51 positivity, earlier date of disease onset, and younger age of onset as independently associated with complete-type BD. Although treatments had been also chronologically changed, the causative relationship between therapeutic agents and phenotypical changes was not determined from the study.

Conclusion

The present study revealed that phenotypical evolution was characterized by decreased incidence of the complete type and increment of gastrointestinal involvement in Japanese patients with BD during the last 30 years.
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Literature
2.
go back to reference Isogai E, Ohno S, Kotake S, Isogai H, Tsurumizu T, Fujii N, Yokota K, Syuto B, Yamaguchi M, Matsuda H, et al. Chemiluminescence of neutrophils from patients with Behcet's disease and its correlation with an increased proportion of uncommon serotypes of Streptococcus sanguis in the oral flora. Arch Oral Biol. 1990;35(1):43–8.PubMedCrossRef Isogai E, Ohno S, Kotake S, Isogai H, Tsurumizu T, Fujii N, Yokota K, Syuto B, Yamaguchi M, Matsuda H, et al. Chemiluminescence of neutrophils from patients with Behcet's disease and its correlation with an increased proportion of uncommon serotypes of Streptococcus sanguis in the oral flora. Arch Oral Biol. 1990;35(1):43–8.PubMedCrossRef
3.
go back to reference Sohn S, Lee ES, Bang D, Lee S. Behcet's disease-like symptoms induced by the Herpes simplex virus in ICR mice. Eur J Dermatol. 1998;8(1):21–3.PubMed Sohn S, Lee ES, Bang D, Lee S. Behcet's disease-like symptoms induced by the Herpes simplex virus in ICR mice. Eur J Dermatol. 1998;8(1):21–3.PubMed
4.
go back to reference Kirino Y, Zhou Q, Ishigatsubo Y, Mizuki N, Tugal-Tutkun I, Seyahi E, Ozyazgan Y, Ugurlu S, Erer B, Abaci N, et al. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behcet disease. Proc Natl Acad Sci U S A. 2013;110(20):8134–9.PubMedPubMedCentralCrossRef Kirino Y, Zhou Q, Ishigatsubo Y, Mizuki N, Tugal-Tutkun I, Seyahi E, Ozyazgan Y, Ugurlu S, Erer B, Abaci N, et al. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behcet disease. Proc Natl Acad Sci U S A. 2013;110(20):8134–9.PubMedPubMedCentralCrossRef
6.
go back to reference Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, et al. Behcet's syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015;14(4):269–76.PubMedCrossRef Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, et al. Behcet's syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015;14(4):269–76.PubMedCrossRef
7.
go back to reference Wakabayashi T, Morimura Y, Miyamoto Y, Okada AA. Changing patterns of intraocular inflammatory disease in Japan. Ocul Immunol Inflamm. 2003;11(4):277–86.PubMedCrossRef Wakabayashi T, Morimura Y, Miyamoto Y, Okada AA. Changing patterns of intraocular inflammatory disease in Japan. Ocul Immunol Inflamm. 2003;11(4):277–86.PubMedCrossRef
8.
go back to reference Ideguchi H, Suda A, Takeno M, Ueda A, Ohno S, Ishigatsubo Y. Behcet disease: evolution of clinical manifestations. Medicine (Baltimore). 2011;90(2):125-132. Ideguchi H, Suda A, Takeno M, Ueda A, Ohno S, Ishigatsubo Y. Behcet disease: evolution of clinical manifestations. Medicine (Baltimore). 2011;90(2):125-132.
9.
go back to reference Kim DY, Choi MJ, Cho S, Kim DW, Bang D. Changing clinical expression of Behcet disease in Korea during three decades (1983-2012): chronological analysis of 3674 hospital-based patients. Br J Dermatol. 2014;170(2):458–61.PubMedCrossRef Kim DY, Choi MJ, Cho S, Kim DW, Bang D. Changing clinical expression of Behcet disease in Korea during three decades (1983-2012): chronological analysis of 3674 hospital-based patients. Br J Dermatol. 2014;170(2):458–61.PubMedCrossRef
10.
go back to reference Mizushima Y, Inaba G, Mimura Y. Guide for the diagnosis of Behçet’s disease. Japan: Report of Behçet’s Disease Research; 1987. p. 8–17. Mizushima Y, Inaba G, Mimura Y. Guide for the diagnosis of Behçet’s disease. Japan: Report of Behçet’s Disease Research; 1987. p. 8–17.
11.
go back to reference Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet. 1990;335(8697):1078–80. Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet. 1990;335(8697):1078–80.
12.
go back to reference Saadoun D, Wechsler B, Desseaux K, Le Thi HD, Amoura Z, Resche-Rigon M, Cacoub P. Mortality in Behcet's disease. Arthritis Rheum. 2010;62(9):2806–12.PubMedCrossRef Saadoun D, Wechsler B, Desseaux K, Le Thi HD, Amoura Z, Resche-Rigon M, Cacoub P. Mortality in Behcet's disease. Arthritis Rheum. 2010;62(9):2806–12.PubMedCrossRef
13.
go back to reference Bonitsis NG, Luong Nguyen LB, LaValley MP, Papoutsis N, Altenburg A, Kotter I, Micheli C, Maldini C, Mahr A, Zouboulis CC. Gender-specific differences in Adamantiades-Behcet's disease manifestations: an analysis of the German registry and meta-analysis of data from the literature. Rheumatology (Oxford). 2015;54(1):121–33.CrossRef Bonitsis NG, Luong Nguyen LB, LaValley MP, Papoutsis N, Altenburg A, Kotter I, Micheli C, Maldini C, Mahr A, Zouboulis CC. Gender-specific differences in Adamantiades-Behcet's disease manifestations: an analysis of the German registry and meta-analysis of data from the literature. Rheumatology (Oxford). 2015;54(1):121–33.CrossRef
14.
go back to reference Maldini C, Lavalley MP, Cheminant M, de Menthon M, Mahr A. Relationships of HLA-B51 or B5 genotype with Behcet's disease clinical characteristics: systematic review and meta-analyses of observational studies. Rheumatology (Oxford). 2012;51(5):887–900.CrossRef Maldini C, Lavalley MP, Cheminant M, de Menthon M, Mahr A. Relationships of HLA-B51 or B5 genotype with Behcet's disease clinical characteristics: systematic review and meta-analyses of observational studies. Rheumatology (Oxford). 2012;51(5):887–900.CrossRef
15.
go back to reference Ishigatsubo Y, Takeno M. Overview. In: Ishigatsubo Y, editor. Behçet's Disease: From Genetics to Therapies. Tokyo: Springer Japan; 2015. p. 1–20. Ishigatsubo Y, Takeno M. Overview. In: Ishigatsubo Y, editor. Behçet's Disease: From Genetics to Therapies. Tokyo: Springer Japan; 2015. p. 1–20.
16.
go back to reference Ideguchi H, Suda A, Takeno M, Miyagi R, Ueda A, Ohno S, Ishigatsubo Y. Gastrointestinal manifestations of Behcet's disease in Japan: a study of 43 patients. Rheumatol Int. 2014;34(6):851–6.PubMedCrossRef Ideguchi H, Suda A, Takeno M, Miyagi R, Ueda A, Ohno S, Ishigatsubo Y. Gastrointestinal manifestations of Behcet's disease in Japan: a study of 43 patients. Rheumatol Int. 2014;34(6):851–6.PubMedCrossRef
17.
go back to reference Hamuryudan V, Ozyazgan Y, Hizli N, Mat C, Yurdakul S, Tuzun Y, Senocak M, Yazici H. Azathioprine in Behcet's syndrome: effects on long-term prognosis. Arthritis Rheum. 1997;40(4):769–74.PubMedCrossRef Hamuryudan V, Ozyazgan Y, Hizli N, Mat C, Yurdakul S, Tuzun Y, Senocak M, Yazici H. Azathioprine in Behcet's syndrome: effects on long-term prognosis. Arthritis Rheum. 1997;40(4):769–74.PubMedCrossRef
18.
go back to reference Kitamei H, Kitaichi N, Namba K, Kotake S, Goda C, Kitamura M, Miyazaki A, Ohno S. Clinical features of intraocular inflammation in Hokkaido, Japan. Acta Ophthalmol. 2009;87(4):424–8.PubMedCrossRef Kitamei H, Kitaichi N, Namba K, Kotake S, Goda C, Kitamura M, Miyazaki A, Ohno S. Clinical features of intraocular inflammation in Hokkaido, Japan. Acta Ophthalmol. 2009;87(4):424–8.PubMedCrossRef
19.
go back to reference Mahr A, Belarbi L, Wechsler B, Jeanneret D, Dhote R, Fain O, Lhote F, Ramanoelina J, Coste J, Guillevin L. Population-based prevalence study of Behcet's disease: differences by ethnic origin and low variation by age at immigration. Arthritis Rheum. 2008;58(12):3951–9.PubMedCrossRef Mahr A, Belarbi L, Wechsler B, Jeanneret D, Dhote R, Fain O, Lhote F, Ramanoelina J, Coste J, Guillevin L. Population-based prevalence study of Behcet's disease: differences by ethnic origin and low variation by age at immigration. Arthritis Rheum. 2008;58(12):3951–9.PubMedCrossRef
20.
go back to reference Hirohata T, Kuratsune M, Nomura A, Jimi S. Prevalence of Behcet's syndrome in Hawaii with particular reference to the comparison of the Japanese in Hawaii and Japan. Hawaii Med J. 1975;34(7):244–6.PubMed Hirohata T, Kuratsune M, Nomura A, Jimi S. Prevalence of Behcet's syndrome in Hawaii with particular reference to the comparison of the Japanese in Hawaii and Japan. Hawaii Med J. 1975;34(7):244–6.PubMed
21.
go back to reference Zouboulis CC, Kotter I, Djawari D, Kirch W, Kohl PK, Ochsendorf FR, Keitel W, Stadler R, Wollina U, Proksch E, et al. Epidemiological features of Adamantiades-Behcet's disease in Germany and in Europe. Yonsei Med J. 1997;38(6):411–22.PubMedCrossRef Zouboulis CC, Kotter I, Djawari D, Kirch W, Kohl PK, Ochsendorf FR, Keitel W, Stadler R, Wollina U, Proksch E, et al. Epidemiological features of Adamantiades-Behcet's disease in Germany and in Europe. Yonsei Med J. 1997;38(6):411–22.PubMedCrossRef
22.
go back to reference Lewis KA, Graham EM, Stanford MR. Systematic review of ethnic variation in the phenotype of Behcet's disease. Scand J Rheumatol. 2007;36(1):1–6.PubMedCrossRef Lewis KA, Graham EM, Stanford MR. Systematic review of ethnic variation in the phenotype of Behcet's disease. Scand J Rheumatol. 2007;36(1):1–6.PubMedCrossRef
23.
go back to reference Mumcu G, Inanc N, Yavuz S, Direskeneli H. The role of infectious agents in the pathogenesis, clinical manifestations and treatment strategies in Behcet's disease. Clin Exp Rheumatol. 2007;25(4 Suppl 45):S27–33.PubMed Mumcu G, Inanc N, Yavuz S, Direskeneli H. The role of infectious agents in the pathogenesis, clinical manifestations and treatment strategies in Behcet's disease. Clin Exp Rheumatol. 2007;25(4 Suppl 45):S27–33.PubMed
24.
go back to reference Behcet H, Matteson EL. On relapsing, aphthous ulcers of the mouth, eye and genitalia caused by a virus. Clin Exp Rheumatol. 2010;28(4 Suppl 60):S2–5.PubMed Behcet H, Matteson EL. On relapsing, aphthous ulcers of the mouth, eye and genitalia caused by a virus. Clin Exp Rheumatol. 2010;28(4 Suppl 60):S2–5.PubMed
25.
go back to reference Lehner T, Lavery E, Smith R, van der Zee R, Mizushima Y, Shinnick T. Association between the 65-kilodalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behcet's syndrome. Infect Immun. 1991;59(4):1434–41.PubMedPubMedCentral Lehner T, Lavery E, Smith R, van der Zee R, Mizushima Y, Shinnick T. Association between the 65-kilodalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behcet's syndrome. Infect Immun. 1991;59(4):1434–41.PubMedPubMedCentral
26.
go back to reference Rizvi SW, McGrath Jr H. The therapeutic effect of cigarette smoking on oral/genital aphthosis and other manifestations of Behcet's disease. Clin Exp Rheumatol. 2001;19(5 Suppl 24):S77–8.PubMed Rizvi SW, McGrath Jr H. The therapeutic effect of cigarette smoking on oral/genital aphthosis and other manifestations of Behcet's disease. Clin Exp Rheumatol. 2001;19(5 Suppl 24):S77–8.PubMed
27.
go back to reference Catrina AI, Joshua V, Klareskog L, Malmstrom V. Mechanisms involved in triggering rheumatoid arthritis. Immunol Rev. 2016;269(1):162–74.PubMedCrossRef Catrina AI, Joshua V, Klareskog L, Malmstrom V. Mechanisms involved in triggering rheumatoid arthritis. Immunol Rev. 2016;269(1):162–74.PubMedCrossRef
28.
go back to reference Mizushima Y, Matsuda T, Hoshi K, Ohno S. Induction of Behcet's disease symptoms after dental treatment and streptococcal antigen skin test. J Rheumatol. 1988;15(6):1029–30.PubMed Mizushima Y, Matsuda T, Hoshi K, Ohno S. Induction of Behcet's disease symptoms after dental treatment and streptococcal antigen skin test. J Rheumatol. 1988;15(6):1029–30.PubMed
29.
go back to reference Choi SM, Choi YJ, Kim JT, Lee SH, Park MS, Kim BC, Kim MK, Cho KH. A case of recurrent neuro-Behcet's disease after tooth extraction. J Korean Med Sci. 2010;25(1):185–7.PubMedCrossRef Choi SM, Choi YJ, Kim JT, Lee SH, Park MS, Kim BC, Kim MK, Cho KH. A case of recurrent neuro-Behcet's disease after tooth extraction. J Korean Med Sci. 2010;25(1):185–7.PubMedCrossRef
30.
go back to reference Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, Le JM, Yang B, Korman BD, Cakiris A, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease. Nat Genet. 2010;42(8):698–702.PubMedPubMedCentralCrossRef Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, Le JM, Yang B, Korman BD, Cakiris A, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease. Nat Genet. 2010;42(8):698–702.PubMedPubMedCentralCrossRef
31.
go back to reference Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci. Nat Genet. 2010;42(8):703–6.PubMedCrossRef Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci. Nat Genet. 2010;42(8):703–6.PubMedCrossRef
32.
go back to reference Cheon JH, Kim ES, Shin SJ, Kim TI, Lee KM, Kim SW, Kim JS, Kim YS, Choi CH, Ye BD, et al. Development and validation of novel diagnostic criteria for intestinal Behcet's disease in Korean patients with ileocolonic ulcers. Am J Gastroenterol. 2009;104(10):2492–9.PubMedCrossRef Cheon JH, Kim ES, Shin SJ, Kim TI, Lee KM, Kim SW, Kim JS, Kim YS, Choi CH, Ye BD, et al. Development and validation of novel diagnostic criteria for intestinal Behcet's disease in Korean patients with ileocolonic ulcers. Am J Gastroenterol. 2009;104(10):2492–9.PubMedCrossRef
33.
go back to reference Shoda R, Matsueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr. 1996;63(5):741–5.PubMed Shoda R, Matsueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr. 1996;63(5):741–5.PubMed
34.
go back to reference Asakura K, Nishiwaki Y, Inoue N, Hibi T, Watanabe M, Takebayashi T. Prevalence of ulcerative colitis and Crohn's disease in Japan. J Gastroenterol. 2009;44(7):659–65.PubMedCrossRef Asakura K, Nishiwaki Y, Inoue N, Hibi T, Watanabe M, Takebayashi T. Prevalence of ulcerative colitis and Crohn's disease in Japan. J Gastroenterol. 2009;44(7):659–65.PubMedCrossRef
35.
go back to reference Magro-Checa C, Salvatierra J, Rosales-Alexander JL, Orgaz-Molina J, Raya-Alvarez E. Life-threatening vasculo-Behcet following discontinuation of infliximab after three years of complete remission. Clin Exp Rheumatol. 2013;31(3 Suppl 77):96–8.PubMed Magro-Checa C, Salvatierra J, Rosales-Alexander JL, Orgaz-Molina J, Raya-Alvarez E. Life-threatening vasculo-Behcet following discontinuation of infliximab after three years of complete remission. Clin Exp Rheumatol. 2013;31(3 Suppl 77):96–8.PubMed
Metadata
Title
Continuous evolution of clinical phenotype in 578 Japanese patients with Behçet’s disease: a retrospective observational study
Authors
Yohei Kirino
Haruko Ideguchi
Mitsuhiro Takeno
Akiko Suda
Kana Higashitani
Yosuke Kunishita
Kaoru Takase-Minegishi
Maasa Tamura
Toshiyuki Watanabe
Yukiko Asami
Takeaki Uehara
Ryusuke Yoshimi
Tetsu Yamazaki
Akiko Sekiguchi
Atsushi Ihata
Shigeru Ohno
Atsuhisa Ueda
Toshihisa Igarashi
Shohei Nagaoka
Yoshiaki Ishigatsubo
Hideaki Nakajima
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1115-x

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