Discussion

Adamantiades-Behget's disease is a rather rare disorder in ethnic Germans, however, there is a continuous increase in diagnosed cases. The prevalence of the disease evaluated in Berlin citizens of German origin was similar to that reported from other northern European countries and the U.S.A.2 In contrast, the prevalence of the disease in residents of Turkish origin in Germany is high, although it is 5-fold lower than the prevalence determined in the European part of Turkey and 18-fold lower than in Anatolia2. This markedly different prevalence of the disease in Turks dependent on the geographic area of residence in association with similar data reported from Japan and Hawaii for individuals of Japanese origin leads to the suggestion of an unknown environmental factor possibly influencing the development or onset of the disease5.

A median age of onset in the third decade of life as well as cases with early and late onset of the disease were also reported from other European countries6. The rate of German patients with juvenile disease reported in this study (7%) is similar to those reported from Turkey (6%), Iran (3%), Morocco (3%), Tunis (2%), and Japan (2%)2. These observations are important regarding the better prognosis reported for German patients than for those from endemic areas6 and also the better prognosis detected in juvenile than in adult patients7. The delay of diagnosis in ethnic Germans compared to those of Turkish origin may be due to the supposition that Adamantiades-Behget's disease is an eastern Mediterranean disorder which is still wide-spread in western Europe.

In contrast to the classical Japanese and Turkish reports of an androtropism, more recent epidemiological studies registered an approx. 1:1 male-to-female ratio in Japan, Korea, China, Iran, Turkey, Brazil, and Europe2. An androtropism is still observed in some countries around the eastern Mediterranean area (Saudi Arabia, Israel, Egypt, Morocco, Greece, and Italy)6 whereas gynaecotropism is evident in northern European countries.

The familial occurrence in patients of German origin was as low as in other European countries, namely Greece (0%), Italy (1-3%), Great Britain (4%), Spain (5%), and Portugal (3%). Familial occurrence was as high in patients of Turkish origin in Germany as in patients from endemic geographic areas (12-13% in Israel, Korea and Tunisia)2.

The high frequencies of oral aphthous ulcers, genital ulcers, skin and ocular lesions in European patients and their almost exclusive occurrence as onset signs confirmed the importance of these clinical features for diagnosis. Higher rates of ocular lesions could be detected in south-eastern European patients (Italian and Greek) compared to south-western as well as northern European patients, while all further manifestations were overall similar6. Highly recurrent oral aphthosis, the most frequent onset sign, is a warning signal for Adamantiades Behget's disease. In Korea, fifty-two percent of 67 prospectively evaluated patients with recurrent oral aphthosis (averagely 10 recurrences per year) developed Adamantiades Behget's disease 8 years after onset of oral aphthous ulcers . The high prevalence of oral aphthous ulcers as onset sign in German patients was compatible with reports on several groups of native European patients6.

The potentially severe prognosis of the disease (10-year mortality9 in 5%) was confirmed in our study. Retinal vasculitis leading to blindness, central nervous system and vascular involvement are the most disabling and/or life-threatening features. The disease led to a lethal outcome in German patients probably due to delayed diagnosis and treatment.

The close association of HLA-B51 with the disease is well established. The confirmation of this association in several ethnic groups2,6 led to the assumption that HLA-B51 may be directly involved in the development of the disease. However, more recent data indicate that the pathogenic gene(s) responsible for the disease is not HLA-B51 itself but other gene(s) around the HLA-B locus10. Our data support the alternative suggestion that HLA-

B51 is a marker of severe prognosis11, being especially associated with an earlier development of the complete clinical picture, ocular lesions, vascular involvement, and cutaneous lesions. However, HLA-B51-positive individuals of German origin as well as patients from other northern European countries presented a lower odds ratio regarding the development of the disease compared to HLA-B51-positive southern Europeans, especially patients from south-eastern European countries6. On the other hand, the present study confirms our previous data concerning the association of moderately increased cardiolipin autoantibodies with

cutaneous vasculitis .

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