Triggering agents and microbiome as environmental factors on Behçet’s syndrome

  • Gonca Mumcu
  • Haner DireskeneliEmail author
Part of the following topical collections:
  1. Behcet disease


Environmental and other triggering factors are suggested to cause the onset and the clinical relapses of Behçet’s syndrome (BS), a multi-systemic inflammatory disorder. In this review, environmental factors are discussed according to their interactions with etiopathogenesis, immune response and disease activity. Stress is a common self-triggering factor for most BS patients. Stimuli such as some foods can activate oral ulcers, and may be linked to the histamine content of the food. Oral/skin trauma and menstruation associated with hormonal factors aggravate, whereas allergy/atopy seem to alleviate the symptoms of BS. Infections are associated with BS, and microbial stimuli can activate inflammation in mucosal surfaces with increased Th1/Th17 responses. Fecal and oral microbiome patterns change in diversity and composition in BS. Better oral hygiene applications and anti-microbial interventions might be helpful to suppress oral ulcers in BS.


Triggering agents Environmental factors Microbiome Behçet’s syndrome 



Behçet’s syndrome


Oral ulcer


Sulfate-reducing bacteria


Butyrate-producing bacteria


Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Statements of human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent



  1. 1.
    Yazici H, Seyahi E, Hatemi G, Yazici Y (2018) Behcet syndrome: a contemporary view. Nat Rev Rheumatol 14(2):107–119. CrossRefPubMedGoogle Scholar
  2. 2.
    McGonagle D, Aydin SZ, Gul A, Mahr A, Direskeneli H (2015) ‘MHC-I-opathy’-unified concept for spondyloarthritis and Behcet disease. Nat Rev Rheumatol 11(12):731–740. CrossRefPubMedGoogle Scholar
  3. 3.
    Direskeneli H (2006) Autoimmunity vs autoinflammation in Behcet’s disease: do we oversimplify a complex disorder? Rheumatology (Oxford) 45(12):1461–1465CrossRefGoogle Scholar
  4. 4.
    Gul A (2015) Pathogenesis of Behcet’s disease: autoinflammatory features and beyond. Semin Immunopathol 37(4):413–418. CrossRefPubMedGoogle Scholar
  5. 5.
    Direskeneli H (2001) Behcet’s disease: infectious aetiology, new autoantigens, and HLA-B51. Ann Rheum Dis 60(11):996–1002CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Anaya JM, Restrepo-Jimenez P, Ramirez-Santana C (2018) The autoimmune ecology: an update. Curr Opin Rheumatol 30(4):350–360. CrossRefPubMedGoogle Scholar
  7. 7.
    Ozen S, Demirkaya E, Amaryan G, Kone-Paut I, Polat A, Woo P, Uziel Y, Modesto C, Finetti M, Quartier P, Papadopoulou-Alataki E, Al-Mayouf SM, Fabio G, Gallizzi R, Cantarini L, Frenkel J, Nielsen S, Hofer M, Insalaco A, Acikel C, Ozdogan H, Martini A, Ruperto N, Gattorno M, Paediatric Rheumatology International Trials O, Eurofever P (2014) Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children. Ann Rheum Dis 73(4):662–667. CrossRefPubMedGoogle Scholar
  8. 8.
    Bergmeier LA (2018) Oral mucosa in health and disease: a concise handbook. Springer, BerlinCrossRefGoogle Scholar
  9. 9.
    Alpsoy E (2016) Behcet’s disease: a comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions. J Dermatol 43(6):620–632. CrossRefPubMedGoogle Scholar
  10. 10.
    Mumcu G, Sur H, Inanc N, Karacayli U, Cimilli H, Sisman N, Ergun T, Direskeneli H (2009) A composite index for determining the impact of oral ulcer activity in Behcet’s disease and recurrent aphthous stomatitis. J Oral Pathol Med 38(10):785–791. CrossRefPubMedGoogle Scholar
  11. 11.
    Soy M, Erken E, Konca K, Ozbek S (2000) Smoking and Behcet’s disease. Clin Rheumatol 19(6):508–509CrossRefPubMedGoogle Scholar
  12. 12.
    Iris M ÖE, Aksoy A, Alibaz-Öner F, Inanc N, Ergun T, Direskeneli H, Mumcu G (2018) The assessment of contributing factors to oral ulcer presence in Behçet’s disease: Dietary and non-dietary factors. Eur J Rheumatol 5:240–243. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Verschuere S, Bracke KR, Demoor T, Plantinga M, Verbrugghe P, Ferdinande L, Lambrecht BN, Brusselle GG, Cuvelier CA (2011) Cigarette smoking alters epithelial apoptosis and immune composition in murine GALT. Lab Invest 91(7):1056–1067. CrossRefPubMedGoogle Scholar
  14. 14.
    Alibaz-Oner F, Mumcu G, Kubilay Z, Ozen G, Celik G, Karadeniz A, Can M, Oner SY, Inanc N, Atagunduz P, Ergun T, Direskeneli H (2014) Unmet need in Behcet’s disease: most patients in routine follow-up continue to have oral ulcers. Clin Rheumatol 33(12):1773–1776. CrossRefPubMedGoogle Scholar
  15. 15.
    Volle G, Fraison JB, Gobert D, Goulenok T, Dhote R, Fain O, Gonzalez-Chiappe S, Lhote F, Papo T, Thuillier A, Riviere S, Mahr A (2017) Dietary and nondietary triggers of oral ulcer recurrences in Behcet’s disease. Arthritis Care Res (Hoboken) 69(9):1429–1436. CrossRefGoogle Scholar
  16. 16.
    Ilhan B, Can M, Alibaz-Oner F, Yilmaz-Oner S, Polat-Korkmaz O, Ozen G, Mumcu G, Maradit Kremers H, Direskeneli H (2016) Fatigue in patients with Behcet’s syndrome: relationship with quality of life, depression, anxiety, disability and disease activity. Int J Rheum Dis. CrossRefPubMedGoogle Scholar
  17. 17.
    Buyuktas D, Hatemi G, Yuksel-Findikoglu S, Ugurlu S, Yazici H, Yurdakul S (2015) Fatigue is correlated with disease activity but not with the type of organ involvement in Behcet’s syndrome: a comparative clinical survey. Clin Exp Rheumatol 33(6 Suppl 94):S107–S112PubMedGoogle Scholar
  18. 18.
    Grayson PC, Amudala NA, McAlear CA, Leduc RL, Shereff D, Richesson R, Fraenkel L, Merkel PA (2013) Illness perceptions and fatigue in systemic vasculitis. Arthritis Care Res (Hoboken) 65(11):1835–1843. CrossRefGoogle Scholar
  19. 19.
    Melikoglu M, Melikoglu MA (2013) The prevalence of fibromyalgia in patients with Behcet’s disease and its relation with disease activity. Rheumatol Int 33(5):1219–1222. CrossRefPubMedGoogle Scholar
  20. 20.
    Scherrer MAR, Rocha VB, Garcia LC (2017) Behcet’s disease: review with emphasis on dermatological aspects. An Bras Dermatol 92(4):452–464. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Alpsoy E, Akman A (2009) Behcet’s disease: an algorithmic approach to its treatment. Arch Dermatol Res 301(10):693–702. CrossRefPubMedGoogle Scholar
  22. 22.
    Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behcet’s disease. N Engl J Med 341(17):1284–1291. CrossRefPubMedGoogle Scholar
  23. 23.
    Wakabayashi T, Morimura Y, Miyamoto Y, Okada AA (2003) Changing patterns of intraocular inflammatory disease in Japan. Ocul Immunol Inflamm 11(4):277–286CrossRefPubMedGoogle Scholar
  24. 24.
    Yoshida A, Kawashima H, Motoyama Y, Shibui H, Kaburaki T, Shimizu K, Ando K, Hijikata K, Izawa Y, Hayashi K, Numaga J, Fujino Y, Masuda K, Araie M (2004) Comparison of patients with Behcet’s disease in the 1980s and 1990s. Ophthalmology 111(4):810–815. CrossRefPubMedGoogle Scholar
  25. 25.
    Kitamei H, Kitaichi N, Namba K, Kotake S, Goda C, Kitamura M, Miyazaki A, Ohno S (2009) Clinical features of intraocular inflammation in Hokkaido, Japan. Acta Ophthalmol 87(4):424–428. CrossRefPubMedGoogle Scholar
  26. 26.
    Ideguchi H, Suda A, Takeno M, Ueda A, Ohno S, Ishigatsubo Y (2011) Behçet disease: evolution of clinical manifestations. Medicine (Baltimore) 90(2):125–132CrossRefGoogle Scholar
  27. 27.
    Kim DY, Choi MJ, Cho S, Kim DW, Bang D (2014) Changing clinical expression of Behcet disease in Korea during three decades (1983–2012): chronological analysis of 3674 hospital-based patients. Br J Dermatol 170(2):458–461. CrossRefPubMedGoogle Scholar
  28. 28.
    Lee YB, Lee SY, Choi JY, Lee JH, Chae HS, Kim JW, Han KD, Park YG, Yu DS (2018) Incidence, prevalence, and mortality of Adamantiades-Behcet’s disease in Korea: a nationwide, population-based study (2006–2015). J Eur Acad Dermatol Venereol 32(6):999–1003. CrossRefPubMedGoogle Scholar
  29. 29.
    Direskeneli H, Mumcu G (2010) A possible decline in the incidence and severity of Behcet’s disease: implications for an infectious etiology and oral health. Clin Exp Rheumatol 28(4 Suppl 60):S86–S90PubMedGoogle Scholar
  30. 30.
    Horie Y, Kitaichi N, Hijioka K, Sonoda KH, Saishin Y, Kezuka T, Goto H, Takeuchi M, Nakamura S, Kimoto T, Shimakawa M, Kita M, Sugita S, Mochizuki M, Hori J, Iwata M, Shoji J, Fukuda M, Kaburaki T, Numaga J, Kawashima H, Fukushima A, Joko T, Takai N, Ozawa Y, Meguro A, Mizuki N, Namba K, Ishida S, Ohno S (2016) Ocular Behcet’s disease is less complicated with allergic disorders. A nationwide survey in Japan. Clin Exp Rheumatol 34(6 Suppl 102):111–114PubMedGoogle Scholar
  31. 31.
    Karacayli U, Mumcu G, Simsek I, Pay S, Kose O, Erdem H, Direskeneli H, Gunaydin Y, Dinc A (2009) The close association between dental and periodontal treatments and oral ulcer course in behcet’s disease: a prospective clinical study. J Oral Pathol Med 38(5):410–415. CrossRefPubMedGoogle Scholar
  32. 32.
    van de Ree-Pellikaan C, Kiewiet-Kemper RM, Tchetverikov I, Westerweel PE (2016) Oral ulcerations after placement of orthodontic braces and skin pustules after laser hair removal: novel inducers of pathergy reactions in new-onset Behçet’s disease. BMJ Case Rep. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Mizushima Y, Matsuda T, Hoshi K, Ohno S (1988) Induction of Behcet’s disease symptoms after dental treatment and streptococcal antigen skin test. J Rheumatol 15(6):1029–1030PubMedGoogle Scholar
  34. 34.
    Choi S-MCY-J, Kim J-T, Lee S-H, Park M-S, Kim B-C, Kim M-K, Cho K-H, Acikel C (2010) A case of recurrent neuro-Behçet’s disease after tooth extraction. J Korean Med Sci 25:185–187CrossRefPubMedGoogle Scholar
  35. 35.
    Dilsen N, Konice M, Aral O, Ocal L, Inanc M, Gul A (1993) Comparative study of the skin pathergy test with blunt and sharp needles in Behcet’s disease: confirmed specificity but decreased sensitivity with sharp needles. Ann Rheum Dis 52(11):823–825CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Perricone C, Versini M, Ben-Ami D, Gertel S, Watad A, Segel MJ, Ceccarelli F, Conti F, Cantarini L, Bogdanos DP, Antonelli A, Amital H, Valesini G, Shoenfeld Y (2016) Smoke and autoimmunity: the fire behind the disease. Autoimmun Rev 15(4):354–374. CrossRefPubMedGoogle Scholar
  37. 37.
    Tuzun B, Wolf R, Tuzun Y, Serdaroglu S (2000) Recurrent aphthous stomatitis and smoking. Int J Dermatol 39(5):358–360CrossRefPubMedGoogle Scholar
  38. 38.
    Malek Mahdavi A, Khabbazi A, Yaaghoobian B, Ghojazadeh M, Agamohammadi R, Kheyrollahiyan A, Rashtchizadeh N (2018) Cigarette smoking and risk of Behcet’s disease: a propensity score matching analysis. Mod Rheumatol. CrossRefPubMedGoogle Scholar
  39. 39.
    Kalayciyan A, Orawa H, Fimmel S, Perschel FH, Gonzalez JB, Fitzner RG, Orfanos CE, Zouboulis CC (2007) Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behcet’s disease. J Invest Dermatol 127(1):81–89. CrossRefPubMedGoogle Scholar
  40. 40.
    Ciancio G, Colina M, La Corte R, Lo Monaco A, De Leonardis F, Trotta F, Govoni M (2010) Nicotine-patch therapy on mucocutaneous lesions of Behcet’s disease: a case series. Rheumatology (Oxford) 49(3):501–504. CrossRefGoogle Scholar
  41. 41.
    Hill SC, Stavrakoglou A, Coutts IR (2010) Nicotine replacement therapy as a treatment for complex aphthosis. J Dermatol Treat 21(5):317–318. CrossRefGoogle Scholar
  42. 42.
    Ozer HT, Gunesacar R, Dinkci S, Ozbalkan Z, Yildiz F, Erken E (2012) The impact of smoking on clinical features of Behcet’s disease patients with glutathione S-transferase polymorphisms. Clin Exp Rheumatol 30(3 Suppl 72):S14–S17PubMedGoogle Scholar
  43. 43.
    Pandey A, Garg J, Krishnamoorthy P, Palaniswamy C, Doshi J, Lanier G, Ahmad H (2014) Predictors of coronary artery disease in patients with Behcet’s disease. Cardiology 129(4):203–206. CrossRefPubMedGoogle Scholar
  44. 44.
    Chang HK, Lee SS, Kim JW, Jee YK, Kim JU, Lee YW, Yoon BY (2003) The prevalence of atopy and atopic diseases in Behcet’s disease. Clin Exp Rheumatol 21(4 Suppl 30):S31–S34PubMedGoogle Scholar
  45. 45.
    Yazici A, Orge Gonullu E, Kardes B, Cefle A (2013) The prevalence of atopy in patients with familial Mediterranean fever and Behcet’s disease. Clin Exp Rheumatol 31(3 Suppl 77):68–70PubMedGoogle Scholar
  46. 46.
    Dhuban KB, d’Hennezel E, Ben-Shoshan M, McCusker C, Clarke A, Fiset P, Mazer B, Piccirillo CA (2013) Altered T helper 17 responses in children with food allergy. Int Arch Allergy Immunol 162(4):318–322. CrossRefPubMedGoogle Scholar
  47. 47.
    Fattahi F, Brandsma CA, Lodewijk M, Reinders-Luinge M, Postma DS, Timens W, Hylkema MN, Ten Hacken NH (2016) Atopy and inhaled corticosteroid use associate with fewer IL-17 + cells in asthmatic airways. PLoS One 11(8):e0161433. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Yavuz S, Ozilhan G, Elbir Y, Tolunay A, Eksioglu-Demiralp E, Direskeneli H (2007) Activation of neutrophils by testosterone in Behcet’s disease. Clin Exp Rheumatol 25(4 Suppl 45):S46–S51PubMedGoogle Scholar
  49. 49.
    Yavuz S, Akdeniz T, Hancer V, Bicakcigil M, Can M, Yanikkaya-Demirel G (2016) Dual effects of testosterone in Behcet’s disease: implications for a role in disease pathogenesis. Genes Immun 17(6):335–341. CrossRefPubMedGoogle Scholar
  50. 50.
    Nowak J, Borkowska B, Pawlowski B (2016) Leukocyte changes across menstruation, ovulation, and mid-luteal phase and association with sex hormone variation. Am J Hum Biol 28(5):721–728. CrossRefPubMedGoogle Scholar
  51. 51.
    Guzelant G, Ozguler Y, Esatoglu SN, Karatemiz G, Ozdogan H, Yurdakul S, Yazici H, Seyahi E (2017) Exacerbation of Behcet’s syndrome and familial Mediterranean fever with menstruation. Clin Exp Rheumatol 35(Suppl 108 6):95–99PubMedGoogle Scholar
  52. 52.
    Coit P, Mumcu G, Ture-Ozdemir F, Unal AU, Alpar U, Bostanci N, Ergun T, Direskeneli H, Sawalha AH (2016) Sequencing of 16S rRNA reveals a distinct salivary microbiome signature in Behcet’s disease. Clin Immunol 169:28–35. CrossRefPubMedGoogle Scholar
  53. 53.
    Mumcu G, Inanc N, Yavuz S, Direskeneli H (2007) The role of infectious agents in the pathogenesis, clinical manifestations and treatment strategies in Behcet’s disease. Clin Exp Rheumatol 25(4 Suppl 45):S27–S33PubMedGoogle Scholar
  54. 54.
    Mumcu G, Ergun T, Inanc N, Fresko I, Atalay T, Hayran O, Direskeneli H (2004) Oral health is impaired in Behcet’s disease and is associated with disease severity. Rheumatology (Oxford) 43(8):1028–1033CrossRefGoogle Scholar
  55. 55.
    Mumcu G (2008) Behcet’s disease: a dentist’s overview. Clin Exp Rheumatol 26(4 Suppl 50):S121–S124PubMedGoogle Scholar
  56. 56.
    Mumcu G, Inanc N, Aydin SZ, Ergun T, Direskeneli H (2009) Association of salivary S. mutans colonisation and mannose-binding lectin deficiency with gender in Behcet’s disease. Clin Exp Rheumatol 27(2 Suppl 53):S32–S36PubMedGoogle Scholar
  57. 57.
    Mumcu G, Ergun T, Elbir Y, Eksioglu-Demiralp E, Yavuz S, Atalay T, Direskeneli H (2005) Clinical and immunological effects of azithromycin in Behcet’s disease. J Oral Pathol Med 34(1):13–16CrossRefPubMedGoogle Scholar
  58. 58.
    Akman A, Kacaroglu H, Donmez L, Bacanli A, Alpsoy E (2007) Relationship between periodontal findings and Behcet’s disease: a controlled study. J Clin Periodontol 34(6):485–491. CrossRefPubMedGoogle Scholar
  59. 59.
    Mumcu G, Cimilli H, Karacayli U, Inanc N, Ture-Ozdemir F, Eksioglu-Demiralp E, Ergun T, Direskeneli H (2013) Salivary levels of HNP 1-3 are related to oral ulcer activity in Behcet’s disease. Int J Dermatol 52(10):1198–1201. CrossRefPubMedGoogle Scholar
  60. 60.
    Mumcu G, Cimilli H, Karacayli U, Inanc N, Ture-Ozdemir F, Eksioglu-Demiralp E, Ergun T, Direskeneli H (2012) Salivary levels of antimicrobial peptides Hnp 1-3, Ll-37 and S100 in Behcet’s disease. Arch Oral Biol 57(6):642–646. CrossRefPubMedGoogle Scholar
  61. 61.
    Hatemi G, Yazici H (2011) Behcet’s syndrome and micro-organisms. Best Pract Res Clin Rheumatol 25(3):389–406. CrossRefPubMedGoogle Scholar
  62. 62.
    Marta M, Santos E, Coutinho E, Silva AM, Correia J, Vasconcelos C, Giovannoni G (2015) The role of infections in Behcet disease and neuro-Behcet syndrome. Autoimmun Rev 14(7):609–615. CrossRefPubMedGoogle Scholar
  63. 63.
    The Behçet’s Disease Research Committee of Japan (1989) Skin hypersensitivity to streptococcal antigens and the induction of systemic symptoms by the antigens in Behçet’s disease–a multicenter study. J Rheumatol 16(4):506–511Google Scholar
  64. 64.
    Tojo M, Zheng X, Yanagihori H, Oyama N, Takahashi K, Nakamura K, Kaneko F (2003) Detection of herpes virus genomes in skin lesions from patients with Behcet’s disease and other related inflammatory diseases. Acta Derm Venereol 83(2):124–127CrossRefPubMedGoogle Scholar
  65. 65.
    Hatemi G, Bahar H, Uysal S, Mat C, Gogus F, Masatlioglu S, Altas K, Yazici H (2004) The pustular skin lesions in Behcet’s syndrome are not sterile. Ann Rheum Dis 63(11):1450–1452. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Fresko I, Yazici H, Bayramicli M, Yurdakul S, Mat C (1993) Effect of surgical cleaning of the skin on the pathergy phenomenon in Behcet’s syndrome. Ann Rheum Dis 52(8):619–620CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Forbes JD, Van Domselaar G, Bernstein CN (2016) The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol 7:1081. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Meta HITC, Bork P, Ehrlich SD, Wang J (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59–65. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, Centanni M, Cianchi F, Gotti R, Emmi L, Brigidi P, Bizzaro N, De Bellis G, Prisco D, Candela M, D’Elios MM (2015) Behcet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev 14(4):269–276. CrossRefPubMedGoogle Scholar
  70. 70.
    Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N (2016) Bifidobacteria abundance-featured gut microbiota compositional change in patients with Behcet’s disease. PLoS One 11(4):e0153746. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Bik EM, Long CD, Armitage GC, Loomer P, Emerson J, Mongodin EF, Nelson KE, Gill SR, Fraser-Liggett CM, Relman DA (2010) Bacterial diversity in the oral cavity of 10 healthy individuals. ISME J 4(8):962–974. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Cameron SJ, Huws SA, Hegarty MJ, Smith DP, Mur LA (2015) The human salivary microbiome exhibits temporal stability in bacterial diversity. FEMS Microbiol Ecol 91(9):fiv091. CrossRefPubMedGoogle Scholar
  73. 73.
    Seoudi N, Bergmeier LA, Drobniewski F, Paster B, Fortune F (2015) The oral mucosal and salivary microbial community of Behcet’s syndrome and recurrent aphthous stomatitis. J Oral Microbiol 7:27150. CrossRefPubMedGoogle Scholar
  74. 74.
    Ye Z, Zhang N, Wu C, Zhang X, Wang Q, Huang X, Du L, Cao Q, Tang J, Zhou C, Hou S, He Y, Xu Q, Xiong X, Kijlstra A, Qin N, Yang P (2018) A metagenomic study of the gut microbiome in Behcet’s disease. Microbiome 6(1):135. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Calguneri M, Ertenli I, Kiraz S, Erman M, Celik I (1996) Effect of prophylactic benzathine penicillin on mucocutaneous symptoms of Behcet’s disease. Dermatology 192(2):125–128. CrossRefPubMedGoogle Scholar
  76. 76.
    Kaneko F, Oyama N, Nishibu A (1997) Streptococcal infection in the pathogenesis of Behcet’s disease and clinical effects of minocycline on the disease symptoms. Yonsei Med J 38(6):444–454. CrossRefPubMedGoogle Scholar
  77. 77.
    Mumcu G, Inanc N, Ozdemir FT, Tulunay A, Eksioglu-Demiralp E, Ergun T, Direskeneli H (2013) Effects of azithromycin on intracellular cytokine responses and mucocutaneous manifestations in Behcet’s disease. Int J Dermatol 52:1561–1566. CrossRefPubMedGoogle Scholar
  78. 78.
    Wagner EH, Austin BT, Davis C, Hindmarsh M, Schaefer J, Bonomi A (2001) Improving chronic illness care: translating evidence into action. Health Aff (Millwood) 20(6):64–78. CrossRefGoogle Scholar

Copyright information

© Società Italiana di Medicina Interna (SIMI) 2018

Authors and Affiliations

  1. 1.Department of Health Management, Faculty of Health SciencesMarmara UniversityIstanbulTurkey
  2. 2.Department of Internal Medicine, Division of Rheumatology, School of MedicineMarmara UniversityIstanbulTurkey

Personalised recommendations