Interferon alfa-2a in the treatment of Behçet disease: a randomized placebo-controlled and double-blind study

OBJECTIVE: To determine the therapeutic efficacy of interferon alfa-2a in the treatment of Beh?et disease. DESIGN: A randomized placebo-controlled and double-blind study. SETTING: University referral center. PATIENTS: Fifty patients with Beh?et disease were involved in the study. INTERVENTION: The patients were given interferon alfa-2a, 6 x 10(6) IU, subcutaneously 3 times per week or placebo for 3 months, and examined clinically at weekly intervals. MAIN OUTCOME MEASURES: For each mucocutaneous lesion and articular symptom, the mean frequency and duration were evaluated during the 3-month pretreatment, treatment, and follow-up periods. Pain for oral and genital ulcers was scored on a scale of 0 to 3. The ocular inflammatory score, the frequency of attacks, and changes in visual acuities for patients with ocular involvement were assessed before the study, at the end of treatment, and during the follow-up periods. In addition, overall responses at the end of the treatment period were graded as follows: complete remission, disappearance of all clinical signs and symptoms during treatment; partial remission, greater than a 50% decrease in the frequency, duration, and severity of pain for oral and genital ulcers and/or a decrease in the severity and frequency of ocular attacks; stable disease, less than a 50% change in the clinical signs and symptoms; and no effect or deterioration, ineffectiveness or worsening of clinical signs and symptoms. RESULTS: Twenty-three interferon alfa-2a- and 21 placebo-treated patients, ranging in age from 16 to 55 years (mean +/- SD age, 32.38 +/- 7.94 years), were evaluable for efficacy. Interferon alfa-2a treatment significantly decreased the duration (P=.02) and pain (P=.01) of oral ulcers and the frequency of genital ulcers (P=.03) and papulopustular lesions (P=.01). The mean frequency and duration of erythema nodosum-like lesions (P=.77 and.27, respectively), thrombophlebitis (P=.29 and.61, respectively), and articular symptoms (P=.92 and.74, respectively) also decreased. But there were no statistically significant differences. An improvement in the severity and the frequency of ocular attacks occurred in 5 of 6 patients in the interferon alfa-2a-treated group and in 1 of 3 patients in the placebo-treated group. Of the 23 patients in the interferon alfa-2a-treated group, 15 responded to treatment (2 complete and 13 partial responses); and of the 21 patients in the placebo group, 3 responded to treatment (3 partial responses) (P<.005). CONCLUSION: Interferon alfa-2a is an effective alternative treatment for Beh?et disease, particularly for the management of the mucocutaneous lesions of the disease.     

Behçet's disease

A 29-year-old man presented with oral and genital ulcers, erythematous papules and pustules on his back and chest, and deep vein thrombi. A diagnosis of Beh?et disease was made. Beh?et disease is a relapsing disorder that affects the mucocutaneous surfaces. It presents usually as ulcers on the orogenital mucosae, but can also present as an acneiform eruption. The International Study Group on Beh?et disease has established criteria that consist of oral and genital lesions, ocular involvement, skin findings, and a pathergy. Treatment of choice is colchicine or prednisone.     

Acetylator phenotype in Behçet's disease

The purpose of this study was to determine the acetylator status in Behçet's disease (BD) patients and compare it to a matched group of normal individuals. Thirty‐seven healthy volunteers and forty‐one BD patients were included. Detailed history was taken from the patients. HLA‐B51 was determined in the BD patients. In addition, the Clinical Manifestation Index (C.M.I.) was determined for each patient. Pathergy test was also done. After an overnight fast, each control subject and patient received a single oral dose of 100 mg of DDS. A blood sample was collected after 3 hours and the plasma was separated for determination of dapsone/monoacetyldapsone by HPLC. The frequency of slow acetylators in healthy individuals was 70.2%, while the frequency of rapid acetylators was 29.8%. The frequency of slow acetylators in BD patients was 53.7%, while the frequency of non‐acetylators (undetected monoacetyldapsone MADDS in plasma) was 46.3%. There were no rapid acetylators among the BD patients. There was a strong negative association between the acetylator status and the severity of BD. In addition, acetylator status correlated with HLA‐B51, in that BD patients with positive HLA‐B51 were characterized by a very slow or non‐acetylator status. Slow or non‐acetylators had more severe BD. We conclude that BD patients have a unique acetylator status. This finding may have implications for the theories for the pathogenesis of the disease as well as for therapeutic aspects.     

Cardiac complications in Behçet's disease

Summary Behçet's disease (BD) is a multisystem disease of unknown aetiology characterized by chronic relapsing oro‐genital ulcers, uveitis, and systemic involvement including articular, gastrointestinal, cardiopulmonary, neurologic and vascular pathology. Vascular involvement is observed in 30% of cases. Although the pathogenic mechanisms underlying the thrombotic disposition in BD are not well known, prothrombin (PT) gene mutations may be one factor that contributes to the development of vascular involvement in this disorder. We report a case of BD with a PT gene mutation, presenting with cardiovascular involvement.     

Clinical evaluation of Behçet's disease: a five year follow-up study

The frequencies of clinical features of Behçet's disease vary in different studies according to the diagnostic criteria used in the study, the department where the study is done, and the ethnic origin of patients included in the study. In this study, we aimed to evaluate the influence of the length of the follow‐up period of patients on the frequencies of clinical features of Behçet's disease. Out of 231 patients who applied to our dermatology clinic from June of 1991 to October of 1996, only 52 patients that were followed up for at least five years were included in this retrospective study. The baseline characteristics of these 52 patients were almost the same as those of the 179 patients who dropped out. Almost all of the frequencies of clinical features at the end of the follow‐up period of five years were higher than those at the time of presentation. The most prominent increases were observed for erythema nodosum (59.6% to 75.0%), papulopustular lesions (84.6% to 94.2%), and large vessel involvement (23.1% to 30.8%). According to our results, it is most likely that studies mainly including mostly patients with long‐standing disease will report higher figures for the frequencies of these clinical features of Behçet's disease.     

Prevalence of Behçet's disease in Istanbul, Turkey

Background The prevalence of Behçet's disease (BD) is much higher in countries along the ancient Silk Route, extending from Japan to Mediterranean countries including Turkey, than in northern Europe and the USA. Three previous epidemiologic surveys have been carried out in different regions of Turkey. Patients and methods This study investigated the cross‐sectional prevalence of BD in individuals aged > 12 years in Istanbul, Turkey, in two stages. The first stage aimed to identify individuals with recurrent oral ulcers (ROUs) by visiting them in their homes, and the second stage aimed to further examine those with ROUs for the presence of other BD‐related manifestations under hospital conditions. The sample size was determined to be 24,000 with an expected BD prevalence rate of 1/1000 and a sampling error of 4/10,000, with a 95% confidence interval (CI) of 6–14/10,000. The number of individuals to be screened in each district was determined in proportion to the population of all districts in Istanbul. Results The standard questionnaire was applied to a total of 23,986 individuals at their homes. A history of ROU was recorded in 2289 individuals (9.5%), and a previous diagnosis of BD was recorded in 47. The diagnosis of ROU was confirmed in 700, and the diagnosis of BD was established in 101 according to the International Study Group criteria. The prevalence rate of BD was estimated as 42/10,000 (95% CI, 34–51/10,000) in Istanbul, Turkey. Conclusions This survey conducted in Istanbul, the largest cosmopolitan city in Turkey with immigrants from all over the country, has a larger sample size than other previous studies, and therefore the reported prevalence rate of BD has a more acceptable confidence interval. This study aids in the estimation of the prevalence of BD in Turkey, and supports previous findings that Turkey has the highest prevalence rate of the disease in the world.     

Possible isotretinoin-induced keloids in a patient with Behçet's disease

Isotretinoin‐induced keloid formation has occasionally been reported in patients who have undergone dermabrasion or laser treatment. This report describes a man with Behçet's disease (BD) who was prescribed isotretinoin for nodulocystic acne. After approximately 8 weeks of this treatment, the patient developed extensive keloids. There are no previous reports of possible isotretinoin‐induced keloid formation in the setting of BD. This article discusses possible connections between BD, keloid formation and isotretinoin, which may be manifested in this case.     

Neutrophilic eccrine hidradenitis in a patient with Behçet's disease

Patients with Beh?et's disease may develop multiple mucocutaneous manifestations, several of which are mediated by neutrophils. These include aphthous ulcers, pseudofolliculitis, acneform lesions, and pathergy. We report another neutrophil-mediated disorder, neutrophilic eccrine hidradenitis (NEH), in a patient with Beh?et's disease. NEH should be added to the list of mucocutaneous lesions that may be seen in patients with Beh?et's disease.     

Clinical features and natural course of Behçet's disease in 661 cases: a multicentre study

Background Behçet’s disease (BD) is a systemic inflammatory disease with unpredictable exacerbations and remissions. The natural course of BD is not fully known. Objectives We aimed retrospectively to determine the occurrence of the symptoms in chronological order. We also evaluated the influence of the treatment and follow‐up on the clinical severity and tried to identify the factors determining severe organ involvement. Methods Six hundred and sixty‐one patients were involved in this multicentre study. The symptoms of the disease were recorded retrospectively in the time order of the manifestations in each patient. Results Oral ulcers were the most common manifestation (100%), followed by genital ulcers (85·3%), papulopustular lesions (55·4%), erythema nodosum (44·2%), skin pathergy reaction (37·8%), and articular (33·4%) and ocular involvement (29·2%). Oral ulcers were the most common onset manifestation (88·7%). The mean ± SD duration between the onset symptom and the fulfilment of diagnostic criteria was calculated to be 4·3 ± 5·7 years. The clinical severity score was significantly increased in the noncompliant treatment group compared with the compliant group with the passage of time (P < 0·001). The frequency of ocular involvement and genital ulcers was significantly higher in patients whose disease onset was at < 40 years. Genital ulcers, ocular involvement, papulopustular lesions, thrombophlebitis and skin pathergy reaction were found to be significantly more frequent in males. Conclusions Mucocutaneous lesions are the hallmarks of the disease, and especially oral ulcers precede other manifestations. The increase in clinical severity score is more pronounced in patients without regular treatment and follow‐up. Male sex and a younger age at onset are associated with more severe disease.     

Clinical features of Behçet's disease in children

Background Behçet's disease (BD) is a systemic inflammatory vasculitis of young adults with unknown etiology. Objective The aim of this study was to determine the clinical features and outcome of BD in childhood. Patients and methods Seventeen patients with BD within a pediatric age group were studied since 1997. Results Boys : girls ratio was 12:5. Familial cases were very frequent (45%). Oral aphthous ulcers were present in all patients (100%), genital aphthous ulcers were present in 16 (94%), ocular lesions in 4 (24%), erythema nodosum in 3 (18%), papulopustules in 8 (47%), joint symptoms in 13 (76%), mild gastrointestinal symptoms in 2 (12%), neurological involvement in 2 (12%), positive pathergy reactions in 13 (76%), and thrombophlebitis in 1 (6%). We used colchicine, systemic corticosteroids, cyclosporine, nonsteroidal anti‐inflammatory drugs, sulfasalazine, and topical agents for the treatment of children with BD. Conclusion The findings of BD in children are similar as in adults, but the frequency of familial cases is significantly higher.