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      New Insights in the Clinical Understanding of Behçet's Disease

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          Abstract

          Behçet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behçet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behçet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness.

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          Behçet's disease.

          T Sakane, M Takeno, N. Suzuki … (1999)
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            Behçet's disease, the Silk Road and HLA-B51: historical and geographical perspectives.

            D H Verity, J Marr, S. Ohno … (1999)
            Behçet's disease (BD), also known as the Silk Road disease, is a blinding inflammatory disorder of young adults found predominantly between the Mediterranean basin and the Orient, and is strongly associated with the major histocompatibility complex (MHC) antigen HLA-B51. In this article we review the history of Behçet's disease since its first description by Hippocrates, the development of the trading routes collectively known as the Silk Road and the effect of population movement on the distribution of HLA-B51. The global distribution of this antigen among healthy control populations bears a striking similarity both to the ancient trading routes and the distribution of Behçet's disease, suggesting a genetic risk that migrated in parallel with population movement between the Mediterranean and Asia. However, certain indigenous Amerindian peoples have a high prevalence of HLA-B51 but no reported cases of BD. Furthermore, a clear genealogical relationship exists between eastern, but not central, Siberian populations with the Amerindians. Since a high level of recombination within the MHC is known to have occurred in these eastern populations before their migration into Beringia, we suggest that disruption of genetic loci in linkage disequilibria with HLA-B51 may be one reason for the absence of disease in these high HLA-B51-bearing populations. However, a contributory influence of environmental factors is not excluded by this data, and the wide variation that exists in relative risk of HLA-B51 even within Europe would support other non-genetic risk factors on the Silk Road which may be absent, or non-contributory to disease, in the Americas.
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              Current concepts in the etiology and treatment of Behçet disease.

              Cem Evereklioglu (2015)
              Behçet disease is an idiopathic, multisystem, chronic, and recurrent disease characterized by exacerbations alternating with phases of quiescence, episodic panuveitis, and aggressive non-granulomatous occlusive vasculitis of the arteries and veins of any size with explosive ocular inflammatory attacks that primarily affect the retinal and anterior segment vasculature of the eye. The disease is characterized by endothelial dysfunction and may produce a wide variety of symptoms. In mild cases, orogenital ulcers and skin lesions are the only findings during the entire clinical course, whereas ocular lesions that occur in more than half of the cases, frequently bilateral, can eventually lead to blindness. Pulmonary, gastrointestinal, and central nervous system involvements may sometimes be life-threatening. This review examines the epidemiology, frequency, immunology, and immunohistopathology of Behçet disease with recent theories of several agents, including phosphoantigens, superantigens, heat-shock proteins, and adenosine deaminase. Perspectives on the possible roles of new etiopathological molecules, such as nitric oxide, endothelin, and homocysteine, are presented. Ocular and systemic clinical features, diagnostic criteria, classifications, laboratory, fundus fluorescein angiography, and radiologic imaging are discussed. Differential diagnosis, disease in pregnancy and childhood, and prognosis with regard to Behçet-induced systemic and ocular complications are also evaluated. Traditional and current treatments with topical, paraocular and systemic corticosteroids, colchicine, dapsone, cyclosporine, azathioprine, methotrexate, cyclophosphamide and chlorambucil are summarized and recent insights into the pharmacology and effects of thalidomide, tacrolimus (FK-506), interferon-alpha, anti-TNF-alpha blocking monoclonal autoantibody (infliximab) and soluble TNF receptor (etanercept) are reviewed. Key clinical investigations with the status of ongoing clinical trials aimed at addressing the drug's efficacy, surgical care, and studies that have raised the possibility of new therapeutic uses are also presented. The challenges posed by the drug's teratogenicity and adverse effects are also considered, if present.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Yonsei Med J
                Journal ID (publisher-id): YMJ
                Title: Yonsei Medical Journal
                Publisher: Yonsei University College of Medicine
                ISSN (Print): 0513-5796
                ISSN (Electronic): 1976-2437
                Publication date (Print): 01 January 2012
                Publication date (Electronic): 30 November 2011
                Volume: 53
                Issue: 1
                Pages: 35-42
                Affiliations
                Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
                Author notes
                Corresponding author: Dr. Dongsik Bang, Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: 82-2-2228-2086 Fax: 82-2-393-9157, dbang@ 123456yuhs.ac
                Article
                DOI: 10.3349/ymj.2012.53.1.35
                PMC ID: 3250322
                PubMed ID: 22187230
                SO-VID: fc14d6cd-3c1a-42cf-9e73-b42e1ba61cf0
                Copyright © © Copyright: Yonsei University College of Medicine 2012
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 04 October 2011
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Medicine
                Keywords: animal model,diagnosis,behçet's disease,etiopathogenesis,epidemiology,new biologics
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: animal model, diagnosis, behçet's disease, etiopathogenesis, epidemiology, new biologics

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