Midori Nishiyama

A Study of Familial Occurrence of Behcet's Disease With and Without Ocular Lesions

PURPOSE To examine retrospectively the features of Behçets disease patients with familial occurrence and make a comparison between familial Behçets patients with ocular lesions and those without ocular lesions. METHODS We sent questionnaires about Behçets disease patients with familial occurrence to 114 hospitals that reported treating such patients in previous nationwide hospital surveys, and to 341 hospitals selected at random in Japan. RESULTS We obtained reports on 83 Behçets patients with familial occurrence. The positive rate of HLA-B51 was 53.1%. The positive rate of HLA-B51 among patients with ocular lesions was 64.0%, that in patients without ocular lesions was 14.3%, and that in patients with genital ulcers was 40.9%. The mean birth year and onset year of the patients with ocular symptoms was significantly lower than that of the patients without ocular symptoms. Although there was no significant difference between these two groups, parent-child involvement was more common among the patients without ocular lesions than in those with ocular lesions. CONCLUSIONS The findings of this study suggest that the number of familial Behçets disease patients with ocular lesions and high HLA-B51 positivity has been decreasing recently. To elucidate the etiology of familial occurrence, larger scale epidemiological studies and further molecular studies of Behçets disease are needed.

A study of comparison between the nationwide epidemiological survey in 1991 and previous surveys on Behçet's disease in Japan

The 4th nationwide epidemiological survey on Behçet disease (BD), which included all patients with BD at 1,200 hospitals selected at random from 10,081 hospitals in Japan, was carried out by the BD Research Committee of the Ministry of Health and Welfare in 1991 to examine the epidemiological features of BD in Japan by comparing with previous surveys. 3,938 patients from these hospitals were examined by the Japanese diagnostic criteria of BD (JCBD) revised in 1987 and the International criteria for classification of BD (ICBD). Among these 3,938 patients, 622 patients were only suspected of having BD or clinical signs of the disease were unknown, and most of these patients were incompatible with the ICBD. So these patients were excluded from the study of epidemiological features. The average patients age has risen 7–8 years over the last 20 years and the average age of onset in both sexes increased by about 3 years from 1972 to 1991. While a decrease in the sex ratio was seen in the complete-type and the incomplete-type BD without ocular symptoms, a sustained high sex ratio was shown in incomplete-type BD with ocular symptoms. The positive rate of HLA-B51 antigen was 54.9% (men: 56.9%, women: 52.2%) significantly higher than die 15–16% in healthy subjects but it might have been gradually decreasing. Also the clinical course of BD has become too mild for prognosis. According to diese epidemiological features of BD, the clinical manifestation of BD in Japan might have become the Western type of BD.

Microsatellite polymorphisms of the MICA gene among Japanese patients with Behçet's disease

BACKGROUND Behçets disease (BD) is a multisystemic inflammatory disease of unknown origin. Because some researchers have recently suggested a primary association of BD with the A6 allele of the human major histocompatibility complex class I chain-related A (MICA) gene, we investigated microsatellite polymorphisms of the MICA gene in subjects with and without BD. METHODS This was a case-control study of 23 Japanese patients with BD and 23 Japanese volunteers without BD who were compared for MICA microsatellite polymorphisms using the polymerase chain reaction (PCR). We also analysed associations between 5 MICA alleles and the clinical features of patients. RESULTS There was no significant difference between case patients and control subjects in phenotype frequencies. The MICA-A6 allele showed the strongest positive correlation with the human leukocyte antigen allele HLA-B51. Allele A5 showed a strong positive correlation with age at onset and a strong negative correlation with iridocyclitis and HLA-B51. A4 showed a strong negative correlation with ocular lesions and HLA-B51. Patients with the MICA-A6 allele had significantly higher HLA positivity than patients without the allele. INTERPRETATION While the MICA-A6 allele had no significant association with BD, it showed a strong association with HLA-B51. This finding suggests that an association between MICA-A6 and BD may be a secondary phenomenon related to HLA-B51. As several associations with MICA alleles and clinical features have been found, further investigation is expected to elucidate the biological mechanism of action of the MICA protein relative to disease onset.

Clinical Features of Japanese Patients with Behçet's Disease and MICA Polymorphism

1. Tsubota K, Satake Y, Kaido M, et al. Treatment of severe ocularsurface disorders with corneal epithelial stem-cell transplantation. N Engl J Med 1999;340:1697–1703. 2. Strampelli B. Keratoprosthesis with osteodontal tissue. Am J Ophthalmol 1963;89:1029–1039. 3. Falcinelli G, Barogi G, Taloni M. Osteo-odonto-keratoprosthesis: present experience and future prospects. Refract Corneal Surg 1993;9:193–194. 4. Liu C, Sciscio A, Smith G, Pagliarini S, Herold J. Indications and technique of modern osteo-odonto-keratoprosthesis (OOKP) surgery. Eye News 1998;5:17–22. 5. Fukuda M, Liu C, Shimomura Y, Hamada S. Osteo-odontokeratoprosthesis (OOKP) surgery. Ganka Shujutsu (J Jpn Soc Ophthalmic Sur) 2003;16:49–52. Clinical Features of Japanese Patients with Behçet’s Disease and MICA Polymorphism