Avaliação não-invasiva das propriedades da parede arterial em pacientes com doença de Behçet / Non-invasive evaluation of arterial wall properties in patients with Behçets disease

INTRODUÇÃO: O envolvimento vascular tem sido reconhecido como uma importante causa de morbidade e mortalidade na Doença de Behçet (DB), mas a importância de métodos não-invasivos em identificar lesões vasculares precoces ainda não foi bem estabelecida. OBJETIVO: Avaliar as propriedades estruturais e funcionais dos vasos na DB utilizando a medida da velocidade de onda de pulso (VOP) carótido-femoral e a avaliação de carótida pelo echo-tracking system. MÉTODOS: Pacientes com DB sem fatores de risco cardiovasculares tradicionais (hipertensão, diabetes, tabagismo e obesidade) foram selecionados consecutivamente. Todos os pacientes com DB realizaram aferição de VOP e ultrasom de carótida. Pacientes com DB foram divididos de acordo com a presença ou não de envolvimento sistêmico (vascular e/ou ocular e/ou sistema nervoso central) e vascular. Controles saudáveis, pareados para sexo e idade, com os mesmos critérios de exclusão foram selecionados. RESULTADOS: Os vinte e três pacientes com DB (11 homens, média de idade de 35,0±7,6 anos), tiveram níveis significativamente maiores de VOP, comparados ao grupo controle (8,4±1,1 vs. 7,5±1,4 m/s, p=0,017). A espessura íntima-média (594,8±138,6 vs. 561,0±134,2 m, p=0,371), o diâmetro diastólico (6383,7±960,4 vs. 6447,6±1159,7 m, p=0,840), a distensão (401,9±117,7 vs. 337,9±175,3 m, p=0,225) e a distensão relativa (6,2±2,8 vs. 5,4±2,4 m, p=0,293) da artéria carótida foram semelhantes entre os grupos. O grupo com doença sistêmica teve níveis significativamente maiores de VOP (8,7±1,2 vs. 7,8±0,7 m/s, p=0,036) comparado àqueles com manifestação exclusivamente mucocutânea. Pacientes com DB e acometimento vascular tiveram os parâmetros de VOP e echotracking similares aos pacientes sem acometimento vascular, mas apresentaram níveis maiores de colesterol total e LDL (p=0,019 e p=0,012, respectivamente). Uma análise de regressão linear multivariada identificou o nível de triglicerídeos...

INTRODUCTION: Vascular involvement has been recognized as an important cause of morbidity and mortality in Behçets disease (BD) but the role of noninvasive methods in identify early vascular lesions is not established. OBJECTIVE: To evaluate structural and functional properties of vessels in BD using carotid-femoral pulse wave velocity (PWV) and echo-tracking system. METHODS: BD patients without traditional cardiovascular risk factors (hypertension, diabetes, smoking, and obesity) were consecutively selected. All BD patients performed PWV and carotid ultrasound. BD patients were divided according to the presence or not of systemic (vascular and/or ocular and/or central nervous system involvement) and vascular involvement. Healthy controls age- and sex-matched with the same exclusion criteria were selected. RESULTS: The twenty-three BD patients (11 male, mean age 35.0±7.6 years), had a significantly higher PWV levels compared to control group (8.4±1.1 vs. 7.5±1.4 m/s, p=0.017). Intima-media thickness (594.8±138.6 vs. 561.0±134.2 m, p=0.371), diastolic diameter (6383.7±960.4 vs. 6447.6±1159.7 m, p=0.840), distension (401.9±117.7 vs. 337.9±175.3 m, p=0.225), and relative distension (6.2±2.8 vs. 5.4±2.4 m, p=0.293) were similar in both groups. Multivariate linear regression analysis identified triglycerides as the most important factor in increasing PWV levels (p=0.001) in BD. Systemic disease group had significant higher levels of PWV (8.7±1.2 vs. 7.8±0.7 m/s, p=0.036) compared to those with exclusive mucocutaneous manifestations. BD patients with vascular involvement had similar PWV and echo-tracking parameters compared to those without, but had higher total and LDL cholesterol levels (p=0.019 and p=0.012, respectively). CONCLUSIONS: PWV is more useful than carotid ultrasound in detecting...

The Prevalence and Clinical Characteristics of Esophageal Involvement in Patients with Behcet's Disease: A Single Center Experience in Korea

While a significant amount of clinical information has been reported concerning intestinal involvement in Behcet's disease (BD), esophageal involvement in BD has not yet been studied extensively. The aim of this study was to evaluate the prevalence of esophageal involvement in BD and its clinical characteristics. We retrospectively reviewed the medical records of 842 patients diagnosed with BD at a single tertiary institution in Korea between January 1990 and June 2006. Of the 842 patients with BD, 129 patients (15.3%) experienced upper gastrointestinal symptoms that required inspection through esophagogastroduodenoscopy. Esophageal involvement was found in 6 (4.7%) of the 129 patients. The activity index of Behcet's disease did not differ among patients with or without esophageal involvement. All patients with esophageal involvement responded well to medical treatment and no one experienced serious complications. The results of our study demonstrate that the prevalence of esophageal involvement in BD is very low and that most patients with such involvement face few complications and respond well to medical treatment.

Antinuclear Antibodies in Patients with Behcet's Disease / 대한피부과학회지

BACKGROUND: Behcet's disease has features consistent with an immunopathogenic mechanism, but the autoreactivity in pathogenesis is unclear. OBJECTIVE: This study was to investigate the association of antinuclear antibodies (ANA) with Behcet's disease. METHODS: The patients in this study were diagnosed at Severance Hospital Behcet's Disease Specialty Clinic from May, 1998 to May, 2002. We evaluated the frequency, titers and immunofluorescence patterns of ANA in patients with Behcet's disease, and compared the frequency with a healthy control group. According to the positivity of ANA, we compared the frequency of minor symptoms to investigate the association of the severity of disease with ANA. RESULTS: 1. Of the 554 cases of Behcet's disease, 46 cases (8.3%) were ANA positive, however, of the 271 cases of healthy control group, only 5 cases (1.8%) were ANA positive. (p=0.0003) 2. In ANA titers 38 cases (82.6%) showed low titer (1: 40+, 1: 160-), 5 cases (10.9%) intermediate titer (1: 160+, 1: 640-), and 3 cases high titer (>1: 640+). There was no significant difference in intermediate and high titers between complete (17.9%) and incomplete type (14.3%). 3. In immunofluorescence patterns of ANA, 17 cases (37%) were speckled pattern, 5 cases (10.9%) homogeneous pattern, 3 cases (6.5%) centromere pattern, 2 cases (4.3%) nucleolar pattern and 19 cases (41.3%) unknown pattern. 4. Of 508 cases with negative ANA patients, 272 cases (53.5%) had minor symptoms, however, of 46 cases with positive ANA patients, 14 cases (30.4%) had minor symptoms (p=0.0027). CONCLUSION: From this study ANA was more prevalent in Behcet's disease. However, it was not related to severity of disease and most of them were low titer. ANA, herein, might play a minor role in pathogenesis of Behcet's disease.

Introduction of a New Therapeutic Modality for the Chronic Behcets Disease Patients: Synchronization of Plasmapheresis with Immune Modulation Therapy-

The Behcets disease patients with uveitis are oftern suffering from chronic recurrent inflammation resulting in the blindness. Etiology, prognosis, treatment modalities of this disease are various, and the factors, affecting the chronic long term prognosis are not clearly identified. Current treatment for Behcets disease is combination therapy : steroid with colchicine, cyclophosphamide, or cyclosporin. But these kinds of treatment was insufficient to change the disease process and often produced severe complications. Authors treated 4 cases of Behcets patients who had chronic progressive steroid resistent uveitis, with synchronizatin of plasmapheresis and immune modulation therapy. All of them showed marked improvement in uveal inflammatory reaction and visual acuity.

T Lymphocyte Subsets and Binding of T lymphocyte to Human Dermal Microvascular Endothelial Cells in Behcet's Disease / 대한피부과학회지

BACKGROUND: Behcets disease represents a polysymptomatic, recurrent vasculitis' with a chronic course. Its etiology and pathogenesis still remains unclear. Several immunological abnormalities have been described in this disease and altered cell mediated immunity especially has been suggested to play an important role in the pathogenesis. Recently, suppressor-inducer (naive, CD4-CD45RA+ ) and helper-inducer (memory, CD4-CD45RO+) human T cell subsets have been identified by their relevant monoclonal antibodies. It has heen suspected that human dermal microvascular endothelial cells(HDMEC) are an important part in the pathogenesis of Behcets disease. However, there was no report for HDMEC-T lymphocyte adhesion in Behcets disease, OBJECTIVE: We have investigated the subpopulation differences in CD4- T lymphocytes and the adhesiveness of T lymphocytes to cultured HDMEC in the presence of IL-1 alpha, or TNF-alpha using T lymphocytes isolated from normal human subjects and Behcets disease patients respectively. METHODS: T lymphocyte subsets were evaluated by the two-color immuno-fluorescence flow cytometric analysis using anti CD4-, CD8-, CD45RA- and CD45RO monoclonal antibodies. The binding assay of T lymphocytes to HDMEC was performed before and after stimulating HDMEC with IL-l alpha or TNF-alpha. RESULTS: 1. The number of CD4- T cells and the CD4+ to CD8+ ratio decreased in patients with Behcets disease compared to normal controls. 2. In the CD4+ T cell subpopulation, there was a significant decrease in the CD4+CD45RA+cell number with a slight increase in the CD4+ CD45RO+ cell number. 3. After stimulating HDMEC with IL-la and TNF-a, the degree of T lymphocyte-HDMEC adhesion generally increased in an E:T ratio dependent, manner in patients with Behcets disease compared to normal controls. 4. Increased binding of CD4+ CD45RA+ naive T lymphocytes and CD4+CD45RO+ memory T lymphocytes to HDMEC was induced after stimulation with IL-1 alpha and TNF-alpha in both patients and normal controls. The increasing rate was higher in Behcets disease patients than in normal controls. There was no difference in T lymphocyte-HDMEC adhesion between memory and naive T lymphocytes. CONCLUSION: From these findings it can be postulated that the decrease in the CD4+CD45RA+ count may lead to the inactivation of CD8 suppressor cells resulting in abnormal immune suppression shown in Behcets disease. Proinflammatory cytokines may also play an integral role in the pathogenesis of Behcet's disease by activating endothelial cells increasing the interaction between T lymphocytes and endothelial cells. Increasing the interaction between T lymphocytes and HDMEC may be indirect evidence of activation of cell-mediated immunity.

A Case of Behcet's Disease Associated with Intestinal Ulcers / 대한피부과학회지

Behcets disease is a chronic systemic disease of unknown etiology, which is characterized by the recurrent orogenital ulcers, eye involvement and skin manifestations. In addition to the major symptoms, it includes arthritis, vasculitis, neurologic manifestations and gastrointestinal lesions. We report a case of Behcets disease associated with intestinal ulcers. The patient, a 45-year-old female, who had been treated under the diagnosis of Behcets disease for 4 years, presented with swallowing difficulty, vaginal discharge and persistent right lower abdominal pain. Colonoscopic examination showed multiple ulcers on the ileocecal region which is reported as the most common site of gastrointestinal Behcets disease. Gastrointestinal evaluation can be useful in diagnosis of Behcets disease, especially in a patient with gastrointestinal symptoms.

The Pathergy Test in Behcet' s Disease and Recurrent Aphthous Stomatitis / 대한피부과학회지

BACKGROUND: Pathergy, or skin hypersensitivity to needle puncture has been reported as a diagnostic test for Behcets ciisease. But the positivity of pathergy test in recurrent aphthous stomatitis which can be a comporent of Behcets disease is obscure. In recent years it has been noted that the positivity of the test has decreased. It is possible to say that the disposable needles used nowadays are less trauniatic to initiate the reaction than are the nondisposable ones used in the preAIDS ara by some uthors. OBJECTIVE: It is the porpose of this study to clarify the value of pathergy test in differentiating Behcets disease from recurrent aphthous stomatitis and to evaluate the difference of positivity using various kinds of needles, and finally to suggest the most profitable one. METHODS: 34 patients with Behcets disease according to the diagnostic criteria of Shimizu(revisecl) 25 ones in case of applying that of International study group for Behcets disease(ISG) and 21 ones with recurrent aphthous stomatitis, and 25 normal controls were selected. A pathergy test, i.e., intradermal injection of 0.1 ml physiological saline by using 26 gauge & 20 gauge disposable needles and 26 gauge & 20 gauge nondisposable ones were given and the evaluation was made after 24 hours and 48 hours. RESULTS: 1. The positive rates of pathergy test using all kinds of needles in Behcets disease were significantly higher than thoen recurrent aphthous stomatitis and normal controls(p=0.00000-0.03600). The sensitivity were 29.4% 64.7% (Shimizu) and 32.0% 76.0% (ISG), respectively, and the specificity were 91.3%-100.0% for all of them. 2. In Behcets disease, the positive rates of the pathergy test using 26 gauge disposable needles were not significantly different from that of using ZO gauge disposable needles in total and active patients after 24 and 4.3 hours and so were 26 gauge R 20 gauge nondisposable ones(p=0.40134 -0.80603(Shimizu), 0.37551-0.77078(ISG) ). 3. In Behcets disease, the positive rates of pathergy test using 26 gauge nondisposable needles were 59%-68%(Shimiu) and 64% 79% (ISG), which were significantly different, from the test using 20 gauge disposable needles, i.e. 29%-36%(Shimizu), 40%-46%(ISG) in total and active patients(p==0.00753-0.01512) after 24 and 48 hours except for those by the criteria of ISG after 24 hours(p=0.14573-0.15597). CONCLUSION: This study shows that the pathergy test is obviously useful in differentiating Behcets disease from ecurrent aphthous stomatitis and we recommend the intradermal injection of 0.1 ml physiological saline by using 26 gauge nondisposable needle and the evaluation after 48 hours as a standard mithod of pathergy test.

Clinical and histopathologic findings of pathergy test sites in patients with Behcet's disease / 대한피부과학회지

Through the clinicopathologic study of pathergy test sites of 16 patients with Behrets disease in the active or inactive stage, the following results were obtained; 1. In the active stage, six of 16 patients (37.5%) showed positive reactions in clinical pathergy tests, which are much higher than that in the inactive stage when only one patient showed a positive reaction. The severity of the ciniral pathergy reaction was directly related to the activity of the disease. 2. The characteristic histopathologic finding in the active stag was a dermal inflammatory cellular infiltration composed mainly of polymorphonuclear lukocytes and of lymphomononuclear cells accompanied by leukoctocylasia. Two of 16 patients showed true leukocytoclastic vasculitis. 3. Although the type of disease and the reactivity of the clinical pathergy test were related in terms of the severity of the histopathologic findings, there were some notible histopathologic changes even in the cases with negative clinical pathergy reactions. We concluded that the histopathologic findings of the pathergy test sites were more reliable for the diagnosis of Behcet's disease than the clinical findinigs.