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Epidemiologic and clinical survey of Behcet's disease in Korea: the first multicenter study.

The prevalence of Behcet's disease is the highest in the East Asian and the Mediterranean countries. Behcet's disease is also distributed in the Asian countries, but the nationwide survey has not been performed in Korea yet. The Korean Study Group for Behcet's Disease, founded in 1999, conducted a multicenter, retrospective survey on epidemiologic and clinical features of the patients with Behcet's disease from 20 hospitals around the nation from 1997 to 1999. Of 3,497 patients, 1,527 were classified into complete or incomplete type of Behcet's disease according to the revised Shimizu's classification. The sex ratio was 1:1.75 with the female predominance. Geographical distribution showed the highest frequency in Seoul (38.5%). Clinically, 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions and 50.9% had ocular lesions. As for the minor clinical manifestations, articular symptoms were the most frequent. The pathergy test showed positive in 15.4% of patients and revealed a higher positive rate in males (20.2%) than in females (12.7%). In conclusion, we performed the first multicenter study on Behcet's disease in Korea and revealed the female predominance, higher frequency of ocular lesions, and lower positivity of pathergy test in the patients.


Epidemiologic and Clinical Survey of Behcet's Disease in Korea: the First Multicenter Study
The prevalence of Behcet' s disease is the highest in the East Asian and the Mediterranean countries. Behcet' s disease is also distributed in the Asian countries, but the nationwide survey has not been performed in Korea yet. The Korean Study Group for Behcet' s Disease, founded in 1999, conducted a multicenter, retrospective survey on epidemiologic and clinical features of the patients with Behcet' s disease from 20 hospitals around the nation from 1997 to 1999. Of 3,497 patients, 1,527 were classified into complete or incomplete type of Behcet' s disease according to the revised Shimizu' s classification. The sex ratio was 1:1.75 with the female predominance. Geographical distribution showed the highest frequency in Seoul (38.5%). Clinically, 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions and 50.9% had ocular lesions. As for the minor clinical manifestations, articular symptoms were the most frequent. The pathergy test showed positive in 15.4% of patients and revealed a higher positive rate in males (20.2%) than in females (12.7%). In conclusion, we performed the first multicenter study on Behcet' s disease in Korea and revealed the female predominance, higher frequency of ocular lesions, and lower positivity of pathergy test in the patients.

PATIENTS & METHODS
The multicenter study was performed retrospectively with the current data from January 1997 to December 1999. Twenty-four departments from twenty hospitals in Korea participated to this survey. Typical major features including recurrent oral ulcer, skin lesions, eye lesions, and genital ulcers were evaluated in the patients. The patients with four major features diagnosed as complete type, the patients with three major features, two major plus two minor features or typical ocular symptom plus one major or two minor features diagnosed as incomplete type, and the patients with two major features or one major plus two minor diagnosed as suspected type according to the revised Shimizu' s classification (5).
A total of 3,497 patients who visited the hospitals in the period were included as having Beh et' s disease and were checked by the following inquiry from the hospital records: patient' s name, date of birth, sex, geographic distribution, clinical manifestations, durations of the symptoms, and positivity to pathergy test. Durations of symptoms were determined as the period from the beginning of at least one of the diagnostic symptom criteria to the patient' s first visit. Geographic distribution was based on the location where the symptom first occurred. Of 3,497 patients, 1,527 fulfilled the Diagnostic Criteria of International Study Group for Beh et' s disease (6) and/or the revised Shimizu' s classification (5).
Pathergy test was performed with oblique insertion of 26 gauge needle under sterile condition and read by a physician at 24 hr. Formation of papule or pustule was interpreted as a positive result.
Statistical analysis was performed using SPSS version 9.0 (SPSS Inc. Chicago, U.S.A.). Kolmogorov-Smirnov test was applied to evaluate the normality of the age and sex distribution. Chi-square test was applied for comparing the sex difference of pathergy test. Mann-Whitney test was applied to evaluate the age distributions of onset and diagnosis of the disease between males and females. A value of p<0.05 was regarded as statistically significant.

RESULTS
Of 3,497 patients, 1,527 were classified as complete or incomplete type of Beh et' s disease. According to the Shimizu' s classification, incomplete type was the most frequent type (32.8%), followed by suspected type (32.3%), possible type (24.0%) and complete type (10.9%), in order of decreas- • ing frequency (Table 1). Table 2 summarizes age and sex distributions of the data. The median age of onset was 33 yr (range 1-75) and the median age of diagnosis was 41 yr (range 5-75). The male to female ratio was 1:1.75, indicating female predominance. The age of onset was most commonly in their thirties, followed by twenties (26.3%), forties (17.6%), and teens (8.1%). The age at diagnosis was most commonly in the forties (41%). There was no differences in the age distributions of onset (p=0.444) and diagnosis (p=0.453) of the disease between males and females.
The results of pathergy test were available in 715 patients with Beh et' s disease and showed positive in 110 patients (15.4%) and revealed higher positive rates in males (20.2%) than in females (12.7%) (p=0.008) ( Table 4).

DISCUSSION
The prevalence of Beh et' s disease is known to be high in Japan, China, Turkey, Tunisia, and the Mediterranean and the Middle Eastern countries. The prevalence of Beh et' s disease in Korea also has been reported as high as the countries mentioned above. However, Beh et' s disease is rarly seen in the Northern Europe or in the United States.
The frequency of Beh et' s disease in this study demonstrated similar results with the previous report in 1997 performed by Bang et al. with the results as follows (2): complete type 16.1%, incomplete type 38.2%, suspected type 25.4%, and possible type 20.3%.
The result of sexual distribution in our studies was 1:1.75 with the female predominance, which is in line with the previous study. However, in contrast to those studies, Zouboulis et al. (7) reported the male predominance in classical Japanese and Turkish patients with Beh et' s disease and yet, there is gradual increase of female patients, which leads to more of 1:1 male-to-female ratio. Saylan et al. (8) also noted the male predominance in almost all middle eastern countries such as Turkey, Iran, Lebanon, Iraq, Jordan, Israel, and Egypt. The countries with the female predominance are Korea, China, the United States and Britain. The difference in sexual distribution among the countries indicates some potential environmental and genetic influences on the pathogenesis of the disease.
The age of onset and the age at diagnosis of Beh et' s disease in the present study were slightly older than those in the previous studies. The proprtion of group with the age of onset under 20 was 8.97%, indicating the rarity of Beh et' s disease in young ages.
The geographical distribution revealed higher proportion in Seoul and Kyonggido. This result may be due to the differences in the accessibility to the hospitals and population density according to the region. The reports in Japan exhibited a higher prevalence in northern area than southern Japan (9). Nonetheless, our study could not determine distributional differences by the north versus south or by east versus west.
As in other studies, the positive rates of major symptoms revealed that the most frequent major symptom was oral ulcers. As for the minor clinical manifestations, articular symptoms were most frequent. Moreover, the positive rate of ocular lesions in the present study was much higher than that in the previous studies in Korea. The increase in frequency of ocular lesions may be due to the increase in routine tests for the eyes since the ocular lesions are considered to be one of the most important prognostic factors. Furthermore, the exclusion of the possible type in this study might have contributed to the higher frequency of ocular and articular symptoms.   The positivity of the pathergy test in the present study (15.4%) was significantly lower than that of Japan (43.8%) and China (62.2%) (4,10). This observation may be attributed to the differences in the method of pathergy test or to the racial differences. The positivity of pathergy test is especially high in the Middle Eastern countries, which made the test as a crucial parameter of diagnosis of Beh et' s disease. In contrast, the low positive rate of pathergy test in the present study suggests a limitation of its use as a diagnostic criteria in Korea. Yazici et al. (11) reported a higher positive rate of pathergy test in males, which was also observed in the present study.
In conclusion, we performed the first multicenter study on Beh et' s disease in Korea and revealed that the female predominance, higher positive rate of ocular lesions and lower positivity of pathergy test were the significant features in Korean patients. Thus, the necessity of close observations on the eyes and further investigation of prevalences through the central registration system should be emphasized.