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Yoshiaki Ishigatsubo (editor) - Behçets Disease: From Genetics to Therapies

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Yoshiaki Ishigatsubo (editor) Behçets Disease: From Genetics to Therapies

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This book, besides reviewing basic and clinical aspects of Behets disease, covers the latest findings, including genetic studies and treatment with biologics for the disease.
Although the cause of Behets disease is still unknown, it is well known that genetic factors, such as HLA-B51, are involved in its development. Recently, novel susceptibility loci including IL10, IL23R-IL12RB2, and endoplasmic reticulum aminopeptidase 1 have been identified, providing new insights into the pathogenesis of the disease. In addition to basic research, the beneficial efficacy of anti-TNF-alpha monoclonal antibodies has also been suggested for not only uveitis associated with the disease but also other subtypes of the disease such as entero-, vasculo-, and neuro- Behets disease. Behets Disease: From Genetics to Therapies provides essential information both for basic researchers working in the fields of immunology, inflammation, and genetics, and for clinical physicians who are interested in Behets disease, such as ophthalmologists, rheumatologists, dermatologists, gastroenterologists, neurologists, and vascular surgeons.

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Springer Japan 2015
Yoshiaki Ishigatsubo (ed.) Behet's Disease 10.1007/978-4-431-54487-6_1
1. Overview
Yoshiaki Ishigatsubo 1 and Mitsuhiro Takeno 1
(1)
Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama 236-0004, Japan
Yoshiaki Ishigatsubo
Email:
Abstract
Behets disease is an inflammatory disorder characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions such as erythema nodosum. Although mucocutaneous manifestations are self-limiting, ocular involvement can cause blindness. Involvement of large vessels, gastrointestinal tract, and central nervous system is less frequent but can be life-threatening and leave irreversible damage.
Because of heterogeneity of clinical manifestations, a number of sets of diagnostic or classification criteria have been proposed and are still being discussed. The most common causes of Behets disease related death are the arterial lesions, especially pulmonary arterial aneurysm, followed by chronic progressive neurological involvement. Introduction of anti-TNF mAb has greatly contributed to improvement of visual prognosis. Treatment with biologics, including TNF blockers, is also promising for other serious clinical subtypes.
Although the etiology remains unknown, both genetic and environmental factors are implicated in the development of the disease. In addition to the unique geographic distribution and familial aggregation of BD patients, recent gene-wide association studies and subsequent detail analyses have identified novel susceptible genes which are related to the immune system besides HLA-B51 .
Keywords
Silk Road disease Prevalence Familial clustering Diagnostic criteria Classification criteria ISG criteria ICBD criteria Infliximab Adalimumab
1.1 Introduction
Hulusi Behet, a Turkish dermatologist, reported three patients with a triple symptom complex of aphthae, genital ulcers, and hypopyon uveitis in 1937 []. The name of Behets disease (BD) originated from this report. However, the disease is also called Adamantides-Behets disease in German, because Benediktos Adamantides had reported a patient who presented with various clinical manifestations like BD in 1930. Moreover, Hippocrates of Cos had already described the association of oral ulcers, genital ulcers, ocular lesions, and skin lesions, all of which were compatible with clinical manifestations of BD.
BD is now recognized as an inflammatory disorder characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions such as erythema nodosum [].
The etiology remains unknown, though both genetic and environmental factors are implicated in development of BD. The underlying pathology is vascular damages. In the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides, BD is classified as variable vessel vasculitis [], because the disease can affect vessels of any size and type.
During the last decade, we have had two major progressions in this field. First, advanced molecular technology leads to new insights of genetic predisposition. In 2010, gene-wide association studies (GWAS) identified IL10 and IL12RB-IL23R as susceptible genes besides HLAB51 in two independent patient populations, Japan and Turkey [.
Another progression is the introduction of antitumor necrosis factor (TNF)- mAb for uveitis in BD patients [] which are resistant to conventional treatment.
This overview mainly focuses on clinical issues including epidemiology, classification criteria, clinical course, and prognosis in BD.
1.2 Epidemiology
BD is often called Silk Road disease, because the patients cluster along the ancient Silk Road, which extended from the Mediterranean area and Middle East Asia to Far East Asia [].
Table 1.1
Prevalence of Behets disease in previous epidemiological studies
Author
Year
Country
Study area
Incidence (per 100,000)
Ethnic
Age
Asia
Demirhindi []
1981
Turkey
Istanbul, rural
80.0
Yurdakul []
1988
Turkey
Ordu, rural
370.0
Idil []
2002
Turkey
Ankara, suburban
115.0
>10
Azizlerli []
2003
Turkey
Istanbul, urban
421.0
>12
Cakir []
2004
Turkey
Edirne, rural
20.0
Jaber []
2002
Israel
Taibe, urban
120.0
Arabs
Krause []
2007
Israel
Galilee
15.2
All
>15
46.0
Jewish
49.0
Arabs
146.4
Druze
Davatchi []
1997
Iran
Nationwide
16.7
Davatchi []
2008
Iran
Tehran, urban
80.0
Al-Rawi []
2003
Iraq
Saglawia
17.0
Al-Dalaan []
1997
Saudi Arabia
Al Quassim
19.5
Yamamoto []
1974
Japan
Nationwide
7.08.5
Nakae []
1993
Japan
Nationwide
13.5
2012
Japan
Nationwide
14.6
Mok []
2002
China
Hong Kong
2.6
Chen []
2001
Taiwan
1.0
Europe
Crespo []
1993
Portugal
Coimbra, urban
1.5
Sanchez Burson []
1998
Spain
7.5
Gonzalez-Gay []
2000
Spain
Lugo (19881997)
6.4
Grana []
2001
Spain
Galicia (19781990)
5.6
Mahr []
2008
France
Seine-Saint-Denis
7.2
>15
France
Seine-Saint-Denis
2.4
European
>15
Salvarani []
2007
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