Advertisement

Rheumatology International

, Volume 38, Issue 7, pp 1301–1306 | Cite as

Improvement of neurological and ocular symptoms of Behçet’s disease after the introduction of infliximab

  • Marko Barešić
  • Mirna ReihlEmail author
  • Mario Habek
  • Nenad Vukojević
  • Branimir Anić
Cases with a Message

Abstract

Behçet’s disease is a chronic inflammatory condition of unknown origin characterized by multiple organ involvement. The most common symptoms of Behçet’s disease are recurrent oral and/or genital ulcerations in combination with symptoms affecting eyes, skin, central and peripheral nervous system, blood vessels and gastrointestinal tract. We present a 43-year-old female patient with the history of recurrent episodes of genital and oral ulcerations, elevated acute phase reactants and skin lesions. The diagnosis of Behçet’s disease has been delayed (for more than 10 years) and reached only after she developed neurological and ocular symptoms. Treatment with glucocorticoids and azathioprine was partially successful. High doses of glucocorticoids were needed to control the disease and cyclosporine A was nephrotoxic. Remission was reached after the introduction of infliximab (plus methotrexate) and glucocorticoids were stopped. In the recent years, infliximab has been accepted as a standard therapy for refractory cases of Behçet’s disease (neurological, ocular or gastrointestinal). Our patient presented with refractory ocular and neurological symptoms and infliximab was effective for both manifestations. Long-term side-effects of glucocorticoids and other immunosuppressants can be avoided with TNF-α blockade. We emphasize the importance of a timely and accurate diagnosis and significance of excluding more common diseases in a work-up algorithm.

Keywords

Behçet’s disease Neurologic and ocular involvement Glucocorticoids Infliximab 

Notes

Author contributions

Concept: MR, MB; design: MB; supervision: BA; materials: MH, NV; data collection and/or processing: MH, NV; analysis and/or interpretation: BA; literature search: MR; writing manuscript: MR, MB; critical review: BA.

Funding

This research received no specific Grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Yazici Y, Yurdakul S, Yazici H (2010) Behçet’s syndrome. Curr Rheumatol Rep 12(6):429–435CrossRefPubMedGoogle Scholar
  2. 2.
    Papoutsis NG, Abdel-Naser MB, Altenburg A, Orawa H, Kötter I, Krause L et al (2006) Prevalence of Adamantiades-Behçet’s disease in Germany and the municipality of Berlin: results of a nationwide survey. Clin Exp Rheumatol 24(5 Suppl 42):S125PubMedGoogle Scholar
  3. 3.
    Davatchi F, Shahram F, Chams-Davatchi C, Shams H, Nadji A, Akhlaghi M et al (2010) Behcet’s disease: from East to West. Clin Rheumatol 29(8):823–833CrossRefPubMedGoogle Scholar
  4. 4.
    Mahr A, Belarbi L, Wechsler B, Jeanneret D, Dhote R, Fain O et al (2008) Population-based prevalence study of Behçet’s disease: differences by ethnic origin and low variation by age at immigration. Arthritis Rheum 58(12):3951–3959CrossRefPubMedGoogle Scholar
  5. 5.
    Azizlerli G, Köse AA, Sarica R, Gül A, Tutkun IT, Kulaç M et al (2003) Prevalence of Behçet’s disease in Istanbul, Turkey. Int J Dermatol 42(10):803–806CrossRefPubMedGoogle Scholar
  6. 6.
    Seaman G, Pearce RA (1997) Behcet’s disease manifestation in a population drawn from the UK Behcet’s syndrome society. In: Hamza M (ed). Behcet’s Disease, Pub Adhoua, Tunisia. pp 196–199Google Scholar
  7. 7.
    Davatchi F (2012) Diagnosis/classification criteria for Behcet’s disease. Pathol Res Int.  https://doi.org/10.1155/2012/607921 CrossRefGoogle Scholar
  8. 8.
    International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. Lancet Lond Engl 335(8697):1078–1080Google Scholar
  9. 9.
    Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F et al (2018) 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis.  https://doi.org/10.1136/annrheumdis-2018-213225 PubMedCrossRefGoogle Scholar
  10. 10.
    Mege JL, Dilsen N, Sanguedolce V, Gul A, Bongrand P, Roux H 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(9):1544–1549PubMedGoogle Scholar
  11. 11.
    Misumi M, Hagiwara E, Takeno M, Takeda Y, Inoue Y, Tsuji T et al (2003) Cytokine production profile in patients with Behcet’s disease treated with infliximab. Cytokine 24(5):210–218CrossRefPubMedGoogle Scholar
  12. 12.
    El-Asrar AMA, Struyf S, Kangave D, Al-Obeidan SS, Opdenakker G, Geboes K et al (2011) Cytokine profiles in aqueous humor of patients with different clinical entities of endogenous uveitis. Clin Immunol Orlando Fla 139(2):177–184CrossRefGoogle Scholar
  13. 13.
    Mochizuki M, Akduman L, Nussenblatt R. Behc¸et’s disease. In: Pepose JS, Holland GN, Wilhelmus KR (eds). Ocular infection and immunity. St Louis: Mosby. 1996;663–675Google Scholar
  14. 14.
    Kaburaki T, Araki F, Takamoto M, Okinaga K, Yoshida A, Numaga J et al (2010) Best-corrected visual acuity and frequency of ocular attacks during the initial 10 years in patients with Behçet’s disease. Graefes Arch Clin Exp Ophthalmol 248(5):709–714CrossRefPubMedGoogle Scholar
  15. 15.
    Theodossiadis PG, Markomichelakis NN, Sfikakis PP (2007) Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina Phila Pa 27(4):399–413CrossRefGoogle Scholar
  16. 16.
    Larson T, Nussenblatt RB, Sen HN (2011) Emerging drugs for uveitis. Expert Opin Emerg Drugs 16(2):309–322CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Cantini F, Niccoli L, Nannini C, Kaloudi O, Cassarà E, Susini M, Lenzetti I (2012) Efficacy of infliximab in refractory Behçet’s disease-associated and idiopathic posterior segmentuveitis: a prospective, follow-up study of 50 patients. Biologics 6:5–12PubMedGoogle Scholar
  18. 18.
    Okada AA, Goto H, Ohno S, Mochizuki M, Ocular Behçet’s Disease Research Group Of Japan (2012) Multicenter study of infliximab for refractory uveoretinitis in Behçet disease. Arch Ophthalmol Chic Ill 1960 130(5):592–598CrossRefGoogle Scholar
  19. 19.
    Al Rashidi S, Al Fawaz A, Kangave D, Abu El-Asrar AM (2013) Long-term clinical outcomes in patients with refractory uveitis associated with Behçet disease treated with infliximab. Ocul Immunol Inflamm 21(6):468–474CrossRefPubMedGoogle Scholar
  20. 20.
    Markomichelakis N, Delicha E, Masselos S, Sfikakis PP (2012) Intravitreal infliximab for sight-threatening relapsing uveitis in Behçet disease: a pilot study in 15 patients. Am J Ophthalmol 154(3):534–541.e1CrossRefPubMedGoogle Scholar
  21. 21.
    Akman-Demir G, Serdaroglu P, Tasçi B (1999) Clinical patterns of neurological involvement in Behçet’s disease: evaluation of 200 patients. The Neuro-Behçet Study Group. Brain 122:2171–2182CrossRefPubMedGoogle Scholar
  22. 22.
    Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A et al (2008) EULAR recommendations for the management of Behçet disease. Ann Rheum Dis 67(12):1656–1662CrossRefPubMedGoogle Scholar
  23. 23.
    Desbois AC, Addimanda O, Bertrand A, Deroux A, Pérard L, Depaz R et al (2016) Efficacy of anti-TNFα in severe and refractory neuro-Behcet Disease. Medicine (Baltimore).  https://doi.org/10.1097/MD.0000000000003550 CrossRefGoogle Scholar
  24. 24.
    Arida A, Fragiadaki K, Giavri E, Sfikakis PP (2011) Anti-TNF agents for Behçet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum 41(1):61–70CrossRefPubMedGoogle Scholar
  25. 25.
    Neves FS, Ferreira RM, Pereira IA, Zimmermann AF, Lin K (2013) Neuro-Behçet’s disease, its mimickers and anti-TNF therapy: a case-based review. Clin Exp Rheumatol. 31:133–140PubMedGoogle Scholar
  26. 26.
    Fromont A, De Seze J, Fleury MC, Maillefert JF, Moreau T (2009) Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine 45(2):55–57CrossRefPubMedGoogle Scholar
  27. 27.
    Costa MF, Said NR, Zimmermann B (2008) Drug-induced lupus due to anti-tumor necrosis factor alpha agents. Semin Arthritis Rheum 37(6):381–387CrossRefPubMedGoogle Scholar
  28. 28.
    Wallis RS (2009) Infectious complications of tumor necrosis factor blockade. Curr Opin Infect Dis 22(4):403–409CrossRefPubMedGoogle Scholar
  29. 29.
    Abalos-Medina GM, Sánchez-Cano D, Ruiz-Villaverde G, Ruiz-Villaverde R, Quirosa Flores S, Raya Alvarez E (2009) Successful use of infliximab in a patient with neuro-Behçet’s disease. Int J Rheum Dis 12(3):264–266CrossRefPubMedGoogle Scholar
  30. 30.
    Borhani Haghighi A, Safari A, Nazarinia MA, Habibagahi Z, Shenavandeh S (2011) Infliximab for patients with neuro-Behcet’s disease: case series and literature review. Clin Rheumatol 30(7):1007–1012CrossRefPubMedGoogle Scholar
  31. 31.
    Studer U, Ruehe B, Waldegg G, Vajtai I, Escher R, Aeberli D (2012) Atypical presentation of Behçet’s disease with central nervous system involvement successfully treated with infliximab. Rheumatol Int 32(5):1431–1435CrossRefPubMedGoogle Scholar
  32. 32.
    Kanemaru H, Makino T, Jinnin M, Yonemitsu A, Makino K, Ihn H (2013) Case of neuro-Behçet’s disease successfully maintained a remission using infliximab for 2 years. J Dermatol 40(8):632–634CrossRefPubMedGoogle Scholar
  33. 33.
    Filippo MD, Gregorio MD, Nannini C, Gaetani L, Gallina C, Floridi P et al (2014) Infliximab monotherapy for neuro-Behçet’s disease: a case report. J Neurol Sci 347(1):389–390CrossRefPubMedGoogle Scholar
  34. 34.
    Hibi T, Hirohata S, Kikuchi H, Tateishi U, Sato N, Ozaki K et al (2016) Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study. Medicine (Baltimore) 95(24):e3863CrossRefGoogle Scholar
  35. 35.
    Zeydan B, Uygunoglu U, Saip S, Demirci ON, Seyahi E, Ugurlu S et al (2016) Infliximab is a plausible alternative for neurologic complications of Behçet disease. Neurol Neuroimmunol Neuroinflammation 3(5):e258CrossRefGoogle Scholar
  36. 36.
    Kikuchi H, Aramaki K, Hirohata S (2008) Effect of infliximab in progressive neuro-Behçet’s syndrome. J Neurol Sci 272(1–2):99–105CrossRefPubMedGoogle Scholar
  37. 37.
    Jalili A, Kinaciyan T, Barisani T, Peck-Radosavljevic M, Stingl G, Geusau A et al (2009) Successful treatment of refractory Behçet’s disease with the TNF-alpha blocker infliximab. Iran J Immunol IJI 6(1):55–58PubMedGoogle Scholar
  38. 38.
    Donghi D, Mainetti C (2010) Infliximab for the treatment of refractory Adamantiades-Behçet disease with articular, intestinal, cerebral and ocular involvement. Dermatol Basel Switz 220(3):282–286CrossRefGoogle Scholar
  39. 39.
    Karube H, Kamoi K, Ohno-Matsui K (2016) Anti-TNF therapy in the management of ocular attacks in an elderly patient with long-standing Behçet’s disease. Int Med Case Rep J 9:301–304CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, University of ZagrebUniversity Hospital Center ZagrebZagrebCroatia
  2. 2.Division of Physical Medicine, Rehabilitation and RheumatologyVukovar General HospitalVukovarCroatia
  3. 3.Department of Neurology, Referral Center for Autonomic Nervous System Disorders, School of Medicine, University of ZagrebUniversity Hospital Center ZagrebZagrebCroatia
  4. 4.Department of Ophthalmology, School of Medicine, University of ZagrebUniversity Hospital Centre ZagrebZagrebCroatia

Personalised recommendations