Goro Inaba

DOUBLE-MASKED TRIAL OF CYCLOSPORIN VERSUS COLCHICINE AND LONG-TERM OPEN STUDY OF CYCLOSPORIN IN BEHÇET'S DISEASE

The efficacy and safety of oral cyclosporin 10 mg/kg per day in Behçets disease were compared in a randomised double-masked study with those of colchicine, 1 mg orally per day, and were also investigated in a long-term open study. The double-masked study showed that cyclosporin was effective in treating not only the ocular manifestations of Behçets disease but also oral aphthous ulcer, dermal lesions, and genital ulceration. Efficacy did not weaken during long-term treatment.

A Clinical Trial of FK506 in Refractory Uveitis

We performed a clinical open trial to evaluate the efficacy and the adverse side effects of a single therapy with FK506 in refractory uveitis as a multicenter study in Japan. Fifty-three patients (41 patients with Bechçets disease, five with Vogt-Koyanagi-Harada disease, four with idiopathic retinal vasculitis, and three with other forms of uveitis) were enrolled in the study. FK506 was given orally for 12 weeks. Treatment with FK506 exhibited therapeutic effects in a dosage-dependent manner: the effectiveness was 38% in patients treated with an initial dosage of 0.05 mg/kg of body weight per day, 60% with 0.10 mg/kg of body weight per day, 83% with 0.15 mg/kg of body weight per day, and 79% with 0.20 mg/kg of body weight per day. Overall efficacy with dosage adjustment when needed was 76.5% at the conclusion of the study at the end of the 12th week. The FK506 therapy induced a variety of adverse side effects, the incidence of which depended on the dosage. The major side effects were renal impairment (28.3%, 15 of 53 patients), neurologic symptoms (20.8%, 11 of 53 patients), gastrointestinal symptoms (18.9%, ten of 53 patients), and hyperglycemia (13.2%, seven of 53 patients). The trough level of FK506 in the whole blood correlated with both the efficacy of the therapy and with the incidence of adverse effects. It is recommended to maintain the trough level between 15 and 25 ng/ml. On the basis of these results, a daily dosage of 0.10 to 0.15 mg/kg of body weight per day was suggested as an appropriate therapeutic dosage for refractory uveitis.

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.

Third complement component in cerebrospinal fluid in neuro-Behçet's syndrome: Conversion patterns by crossed immunoelectrophoresis☆

Thirteen cerebrospinal fluid specimens (CSFs) from 10 patients with neuro-Behçets syndrome (nB) were examined for the presence of conversion products of C3 protein by means of crossed immunoelectrophoresis. C3 conversion products were found in 4 CSFs from nB patients, and the proportions of the split products to the total immunoprecipitate zones were 17, 34, 61 and 63%, respectively. CSFs with C3 conversion patterns showed higher C3 protein (beta 1C/A) levels compared with those with non-conversion, whereas the differences of C4 protein (beta 1E) levels were unremarkable. CSF with C3 conversion patterns also showed apparent inflammatory characteristics indicating blood-CSF barrier involvement which would be deduced from increased alpha 2-macroglobulin and IgA, both being regarded as sensitive internal barrier parameters: but IgA measurement was much higher than usually expected values. It is suggested that the increase in CSF C3 might be initiated by accelerated consumption of complement through the alternative pathway, leading to hypersynthetic or hyperinflux response in CSF.

Specious Behcet's disease.

We reported twelve patients, 11 females and 1 male aged from 33 to 57 years, who had been having a strong attachment for the diagnosis of Behcets disease but had a part of the vexed diagnostic problem because of lacking stringent clinical features of genuine Behcets disease. The chief complaint of the majority of those patients was usually a severe pain somewhere, such as abdominal pain, arthralgia or headache. However, examinations hardly furnished any evidence of inflammatory or organic lesions which could substantiate their complaints, in addition, symptoms were never progressive and no one showed positive skin prick test throughout the clinical course.There may be some other causes for them and the underlying disease condition, although there was a high incidence of HLA-B51 among them, being comparable to that in patients with typical complete type. One must be cautious in making diagnosis of Behcets disease when a patient shows only muco-cutaneous lesions and complaints not confirmed with objective signs.

Advantages and disadvantages in the long-term treatment of Behcet's disease with ciclosporin.

The clinical response to ciclosporin (CYA) in 8 patients with complete Behcets disease was analyzed. The frequency of ocular attacks became fewer after the initiation of CYA treatment (10mg/kg/day), however, it increased again 80-100 weeks later with reduction of CYA dosage. Extra-ocular symptoms (oral aphthous ulcer, skin eruption and genital ulcer) had been in remission throughout the treatment period for 150 weeks. Several adverse events, such as nephrotoxicity, hypertrichosis, gingival hypertrophy or neurologic lesions were noted in the majority of the patients, which necessiated the reduction of the drug dosage. Hence, the initial dosage will be lessened below 8 mg/kg/day and great care must be exercised in close monitoring of the serious side effects of CYA.