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In Israel, Behçet’s researchers try to uncover clues to disease etiology
Investigators seek to explain different disease findings in Arabs, Jews.
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The etiology of Behçet’s disease remains largely misunderstood, despite the fact that it is a leading cause of blindness in some areas of the world.
Since the prevalence of the disease has strong regional variations, the diverse ethnic makeup of a country like Israel, where Jews from around the world mix with a large Arab population, provides a backdrop against which researchers can study these questions.
“The etiology of the disease … is still obscured but probably includes genetic, metabolic, environmental and autoimmune factors,” said Behçet’s researcher Ilan Krause, MD. “It is well known, however, that Behçet’s disease has diverse clinical expression in various geographical areas, not only regarding the ocular disease, but for other systemic manifestations of the disease as well.”
Behçet’s disease (BD) is a multisystem autoimmune disorder categorized by oral aphthous ulcers, skin lesions and genital ulcers. Ocular inflammation is one of its most severe complications, making the disease one of the leading causes of blindness along what was once the Silk Road, a historic trade route between Asia and the Mediterranean Sea.
Global incidence
In Turkey, which may have the highest incidence of Behçet’s disease in the world, the disorder affects 42 of every 100,000 people, according to a study last year in the International Journal of Dermatology. In contrast, the prevalence of the disease is less than 1 in 100,000 people in European and North American countries.
Dr. Krause noted that the prevalence in Israel has not been formally studied. The Web site of the Behçet Israel Group, run by a family of Behçet’s patients, estimates that there are between 500 and 1,000 cases there, citing several sources.
The different manifestations of the disease among ethnic groups are better understood, according to Dr. Krause, who with colleagues has studied disease expression among Arab and Jewish Israelis.
“In our study, we found that although the overall rate of eye manifestations was similar in Arab and Jewish patients, Arabic patients had more severe ocular disease, manifested by a significantly higher rate of posterior uveitis,” Dr. Krause told Ocular Surgery News in an e-mail from Tel Aviv. “Our study was not designed to evaluate the causes for differences in disease expression, and we have no information about it.”
Jewish variations
Investigators also found that the disease was more severe among Jewish patients originating from North Africa than among Jewish patients from Iran, Iraq or Turkey. In general, however, Jewish patients were more likely to have anterior uveitis, as opposed to the more devastating posterior uveitis typically seen among Arab patients.
The incidence of the disease in Jews is believed to mirror regional variations, with the fewest cases reported among Ashkenazi Jews or Jews from Eastern and Western Europe.
North African Jews also tended to have more severe manifestations of other symptoms of the disease, including arthritis, vasculitis and deep vein thrombosis, but this trend did not reach statistical significance, according to Dr. Krause’s study.
Genetic marker
In other studies, investigators have sought to explain regional differences in disease etiology through the presence or absence of the HLA-B5 genetic marker, which was first reported by Ohno in 1973.
“In our studies in Israeli BD patients, we found an HLA-B5 prevalence of about 70%,” Dr. Krause said. “The significance of this genetic marker in BD is not clear, and it is definitely not a criterion of diagnosis.”
A 1999 study that he and colleagues conducted found a greater incidence of thrombophlebitis and a lower rate of erythema nodosum among HLA-B5-positive Israelis. Yet Dr. Krause is careful to add that such studies do not tell the whole story.
Uncertain significance
“Some studies reported an increased incidence of certain disease manifestations, such as uveitis, erythema nodosum, genital ulceration or vascular thrombosis in HLA-B5-positive BD patients, while others found no difference in the expression of BD among HLA-B5-positive and -negative patients,” he said.
And researchers have made little headway in determining the pathogenesis of the disease. “Unfortunately, I can’t point to a major breakthrough in that area,” he said.
Where researchers have focused their efforts – and with good success – is on new treatments. One therapy in particular that has shown progress is the use of anti-tumor necrosis factor antibodies to target cytokines believed to play a role in Behçet’s pathogenesis, according to Dr. Krause.
For Your Information:References:
- Ilan Krause, MD, can be reached at Department of Medicine E, Rabin Medical Center, Beilinson Campus, Petah-Tiqva, Israel; +972-3-937-7377; fax: +972-3-937-6512; e-mail: ikrause@post.tau.ac.il. The Behçet’s Israel Group can be reached on the Web at www.behcet.org.il.
- Azizlerli G, Kose AA, et al. Prevalence of Behçet’s disease in Istanbul, Turkey. Int J Dermatol. 2003; 42:803-806.
- Krause I, Mader M. Behçet’s disease in Israel: the influence of ethnic origin on disease expression and severity. J Rheumatol. 2001;28:1033-1036.
- Krause I, Molad Y, Weinberger A. Association of HLA-B5 with clinical expression and expression and severity of Behçet’s disease in Israel. J Clin Rheumatology. 1999;137-140.