Relationship between erythrocyte sedimentation rate and choroidal and retinal thickness in Behçet's disease / A relação entre a taxa de sedimentação eritrocitária, espessuras de coroide e retina na doença de Behçet

ABSTRACT Purpose: To compare retinal and choroidal thickness in patients with Behçet's disease with and without ocular involvement as well as to evaluate the correlation between erythrocyte sedimentation rate and choroidal thickness among patients with Behçet's disease. Methods: This was a prospective interventional study investigating erythrocyte sedimentation as well as choroidal and retinal thickness among patients with Behçet's disease. Patients who were diagnosed based on The International Criteria for Behçet's Disease with (Group A) or without (Group B) ocular involvement and a matched control group (Group C) participated in the study. Optical coherence tomography measurements and blood tests were performed on the same day. Retinal and choroidal thickness were measured using spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany), and central macular thickness, central subfoveal choroidal thickness, and retinal nerve fiber layer thickness were measured using optical coherence tomography. Results: Average erythrocyte sedimenta­tion values were 9.89 mm/h in Group A, 16.21 mm/h in Group B, and 3.89 mm/h in Group C; average central subfoveal choroidal thickness values were 350.66, 331.74, and 325.95 mm, respectively. Average central macular thickness and retinal nerve fiber layer thickness values of patients in Groups A, B and C were 226.39 and 225.97mm; 234.11 and 92.00 mm; and 97.58 and 99.84 mm, respectively. No significant difference was seen between Group A and B patients in central subfoveal choroidal thickness, central macular thickness, or retinal nerve fiber layer thickness values. Central macular thickness was statistically significantly thinner in Groups A and B than in Group C (p=0.016). Group A had thinning in the nasal quadrant of the retinal and general retinal nerve fiber layers when compared with those in Group C (p=0.010 and 0.041, respectively). A connection could not be established between the erythrocyte sedimentation, central subfoveal cho­roidal thickness, central macular thickness, and retinal nerve fiber layer thickness in the patients with Behçet's disease. Conclusion: The erythrocyte sedimentation rate is typically used to test for activation of Behçet's disease and assess treatment response. In our study, we could not establish a connection between the erythrocyte sedimentation rate and central subfoveal choroidal thickness, central macular thickness, and retinal nerve fiber layer thickness in patients with systematically active Behçet's disease without ocular involvement.

RESUMO Objetivos: Comparar a espessura da retina e da coroide em pacientes com doença de Behçet, com e sem acometimento ocular e avaliar a correlação entre a taxa de sedimentação de eritrócitos e a espessura da coroide em pacientes com doença de Behçet. Métodos: Estudo prospectivo intervencional que investigou a sedimentação de eritrócitos, espessura de coroide e da retina em pacientes com doença de Behçet. Os pacientes que foram diagnosticados com base nos Critérios Internacionais para a Doença de Behçet com (Grupo A) ou sem (Grupo B) envolvimento ocular e um grupo controle correspondente (Grupo C) participaram do estudo. Medidas de tomografia de coerência óptica e exames de sangue foram realizados no mesmo dia. As espessuras da retina e da coroide foram medidas utilizando tomografia de coerência óptica de domínio espectral (Spectralis, Heidelberg Engineering, Hidelberg, Germany) e a espessura macular central, a espessura coroidal subfoveal central e a espessura da camada de fibra nervosa da retina foram medidas usando tomografia de coerência óptica. Resultados: Os valores médios de sedimentação de eritrócitos foram de 9,89 mm/h no Grupo A, 16,21 mm/h no Grupo B e 3,89 mm/h no Grupo C; os valores médios da espessura da coroide subfoveal central foram 350,66, 331,74 e 325,95 mm respectivamente. Os valores médios da espessura macular central e da espessura da camada de fibra nervosa da retina dos pacientes nos grupos A, B e C foram de 226,39, 225,97, 234,11 mm e 92,00, 97,58, 99,84 mm respectivamente. Não houve diferença significativa entre pacientes do Grupo A e B na espessura da coroide subfoveal central, espessura macular central ou valores da espessura da camada de fibra nervosa da retina. A espessura macular central foi estatisticamente significativamente mais fina nos Grupos A e B do que no Grupo C (p=0,016). O Grupo A apresentou afinamento na porção nasal das camadas retiniana e geral da fibra nervosa da retina quando comparado com o Grupo C (p=0,010, p=0,041, respectivamente). Não foi possível estabelecer uma conexão entre a sedimentação dos eritrócitos, a espessura subfoveal central da coroide, a espessura macular central e espessura da camada de fibras nervosas da retina nos pacientes com doença de Behçet. Conclusão: A taxa de sedimentação de eritrócitos é comumente utilizada para testar a ativação da doença de Behçet e avaliar a resposta ao tratamento. Em nosso estudo, não foi possível estabelecer uma conexão entre a taxa de sedimentação de eritrócitos e a espessura da coroide subfoveal central, espessura macular central e espessura da camada de fibras nervosas da retina em pacientes com doença de Behçet sistematicamente ativa sem envolvimento ocular.

High levels of endothelial progenitor cells and circulating endothelial cells in patients with Behçet's disease and their relationship to disease activity

Abstract: Background: Behçet's disease is a multisystemic vasculitis, associated with vascular endothelial dysfunction. Currently, the prognosis is unpredictable, because there is still no valid laboratory marker indicating the disease activity in Behçet's disease. Endothelial progenitor cells and circulating endothelial cells are newly introduced hematological markers which are presumed to take part in the pathogenesis of vasculitis. Objectives: To evaluate the levels of endothelial progenitor cells and subtypes and circulating endothelial cells in patients with Behçet's disease and to describe their relationship with the disease activity. Methods: A total of 45 patients with Behçet's disease and 28 healthy controls were included in the study. Endothelial progenitor cells (CD34+CD133+KDR+ as early endothelial progenitor cells and CD34+KDR+ as late endothelial progenitor cells), and circulating endothelial cells (CD34+CD133+) were measured by flow cytometry. Results: The mean plasma level of endothelial progenitor cells and circulating endothelial cells, vascular endothelial growth factor, matrix metalloproteinase-9, C-reactive protein, and erythrocyte sedimentation rate were significantly higher in patients with Behçet's disease. All of these parameters except circulating endothelial cells were also found to be higher in patients with active disease than in patients with inactive disease. Early endothelial progenitor cells showed significant correlations with C-reactive protein and circulating endothelial cells. Study Limitations: The cross-sectional nature of the study and patient characteristics such as being under treatment, which can affect endothelial progenitor cells numbers. Conclusion: The increase in endothelial progenitor cells may play an essential role in the repair of endothelial injury in Behçet's disease, especially in the active period of the disease. Thus, endothelial progenitor cells can indicate the disease activity. In addition, endothelial progenitor cells and circulating endothelial cells can be used as endothelial repair and injury markers for Behçet's disease, respectively.

Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Behcet's Disease in Actual Clinical Practice

BACKGROUND/AIMS: Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behcet's disease (BD) in actual clinical practice. METHODS: We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. RESULTS: Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behcet's Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (> or =40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). CONCLUSIONS: Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.

Correlation between Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Endoscopic Activity in Intestinal Behcet's Disease

PURPOSE: The serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have recently been shown to be correlated highly with disease activity in patients with intestinal Behcet's disease (BD). However, it remains unclear whether sTREM-1 levels reflect endoscopic activity in intestinal BD. This study aimed to evaluate the correlation of sTREM-1 levels with endoscopic activity in intestinal BD. MATERIALS AND METHODS: A total of 84 patients with intestinal BD were enrolled. Endoscopic activity was compared with sTREM-1 levels as well as other laboratory findings, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: sTREM-1 levels were significantly increased in intestinal BD patients compared with controls (37.98+/-27.09 pg/mL vs. 16.65+/-7.76 pg/mL, p=0.002), however, there was no difference between endoscopically quiescent and active diseases (43.53+/-24.95 pg/mL vs. 42.22+/-32.68 pg/mL, p=0.819). Moreover, serum sTREM-1 levels did not differ in terms of number, shape, depth, size, margin, or type of ulcer in patients with intestinal BD. However, mean ESR and CRP levels in patients with active disease were significantly higher than those in patients with quiescent disease (p=0.001, p<0.001, respectively). In addition, endoscopic activity scores for intestinal BD were correlated significantly with both CRP levels (gamma=0.329) and ESR (gamma=0.298), but not with sTREM-1 levels (gamma=0.166). CONCLUSION: Unlike CRP levels and ESR, serum sTREM-1 levels were not correlated with endoscopic activity in patients with intestinal BD.

Serum Level of Interleukin-33 and Soluble ST2 and Their Association with Disease Activity in Patients with Behcet's Disease

Interleukin (IL)-33 is an important mediator of innate immunity. Behcet's disease (BD) is an autoinflammatory disorder characterized by hyperactivity of the innate immune response. We measured serum levels of IL-33 and its receptor soluble ST2 (sST2) in patients with BD to investigate their association with disease activity. Serum levels of both IL-33 and sST2 were higher in patients with BD compared with those in normal controls (IL-33: 594.48+/-175.04 pg/mL in BD and 224.23+/-56.64 pg/mL in normal controls [P=0.048], sST2: 99.01+/-15.92 pg/mL in BD and 23.56+/-3.25 pg/mL in normal controls [P<0.001]). IL-33 and sST2 expression in skin tissue, as shown by immunohistochemistry, was higher in patients with BD compared with that in the normal controls. Serum sST2 level correlated significantly with the BD currently active form (BDCAF), Iranian BD dynamic activity measure (IBDDAM), erythrocyte sedimentation rate and C-reactive protein. Multiple linear regression showed that serum sST2 was an independent factor associated with IBBDAM (regression coefficient, 0.374; P=0.004), and BDCAF (regression coefficient, 0.236; P=0.047). These results demonstrate that IL-33 and sST2 are highly expressed in patients with BD and that serum sST2 is an independent factor associated with IBDDAM and BDCAF, suggesting a potential role for sST2 as a surrogate marker of disease activity in patients with BD.

Anti-Cyclic Citrullinated Peptide Antibodies and Joint Involvement in Behcet's Disease

PURPOSE: We aimed to determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in a large group of Korean patients with Behcet's disease (BD), with and without joint involvement, and to compare these findings with the prevalences of anti-CCP antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We tested 189 patients with BD, 105 with RA, and 36 with SLE for anti-CCP antibodies and IgM rheumatoid factor in serum. We reviewed the medical records of patients with BD to investigate their personal and clinical characteristics as well as their laboratory test results. RESULTS: Anti-CCP antibodies were detected in seven of the 189 BD patients (3.7%), at a mean titer of 30.6+/-44.4 U/mL, in 86 of the 105 RA patients (81.9%) with a mean titer of 198.8+/-205.7 U/mL, and in nine of the 36 SLE patients (25%) with a mean titer of 180.4+/-113.9 U/mL. One of the seven anti-CCP-positive BD patients fulfilled the diagnostic criteria for both BD and RA. Five of the seven anti-CCP-positive BD patients (71.4%) had polyarticular joint involvement, and the other two patients (28.6%) had oligoarticular involvement. CONCLUSION: We determined the prevalence of anti-CCP antibodies in a large group of Korean BD patients with and without joint involvement. Negative anti-CCP test in patients with BD may help to differentiate BD from RA and SLE, all of which present with similar clinical features.

Vitamin D status in patients with Behcet's Disease

OBJECTIVES: This study investigated the serum 25-hydroxyvitamin D levels of patients with Behcet's Disease. DESIGN AND METHODS: Thirty-two patients with Behcet's Disease and 31 matched healthy controls were enrolled in this study. The erythrocyte sedimentation rate (ESR) and the levels of C-reactive protein (CRP), serum 25-hydroxyvitamin D, calcium (Ca), phosphate (P), and total alkaline phosphatase (ALP) were measured in both groups. RESULTS: There were no significant differences between the two groups regarding demographic data. The serum 25-hydroxyvitamin D levels of patients and controls were 13.76 (range: 4.00-35.79) and 18.97 (range: 12.05-36.94) ng/ml, respectively. In patients with Behcet's Disease, 25-hydroxyvitamin D values were significantly lower than those of the healthy controls (p<0.001). Serum Ca, P, and ALP levels were similar in both groups. Serum ESR and CRP levels were significantly higher in patients than controls (p<0.05). There was no correlation between 25-hydroxyvitamin D levels and age, body mass index (BMI), disease duration, ESR, or CRP levels. Multivariate regression analysis parameters showed that smoking, alcohol intake, and use of colchicine were the main predictors of 25-hydroxyvitamin D levels. Of the parameters studied, the largest impact was due to colchicine therapy (p<0.001). We did not find a significant relationship between the use of corticosteroids and 25-hydroxyvitamin D levels. CONCLUSION: Our results suggest that serum 25-hydroxyvitamin D levels are decreased in patients with Behcet's Disease. Smoking, alcohol intake, and use of colchicine appear to affect vitamin D levels.

Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose etiopathogenesis is not well understood. Although soluble (s) forms of 4-1BB (s4-1BB) and 4-1BB legand (s4-1BBL) have been detected in the sera of RA patients, their significance is not known. We compared the serum levels of s4-1BB and s4-1BBL in RA patients with those in systemic lupus erythematosus (SLE) and Behcet's disease (BD) patients. Serum levels of s4-1BB and s4-1BBL were significantly higher in RA patients compared with healthy controls, SLE or BD patients, and the abundance was correlated with disease severity in patients with RA. The serum levels of s4-1BB in RA patients were inversely corroborated with 4-1BB expression levels on activated T lymphocytes. In addition, there was a correlation between serum levels of s4-1BB and s4-1BBL. The augmented secretion of s4-1BB and s4-1BBL levels into the serum may reflect the clinical symptoms of RA and levels of s4-1BB and s4-1BBL in sera at the time of diagnosis may be indicative of the severity and outcome of RA.

The Serum Vitamin C Levels in Behcet's Disease

Behcet's disease (BD) is a chronic inflammatory disorder of unknown aetiology, and recognised as a multi-system vasculitis. It has been postulated that an imbalance of the oxidant and antioxidant systems related to the disease are important in its pathogenesis. Previous publications have reported increased levels of enzymatic antioxidant defence systems in patients with BD. The non-enzymatic antioxidant systems, including vitamin C and uric acid, were looked for in the present study. For this aim, the serum malondialdehyde (MDA), an end product of lipid peroxidation, and vitamin C and uric acid, as endogenous antioxidants, were determined in 20 patients with BD (11 in active and 9 in inactive periods) and 20 healthy subjects. The MDA level was significantly higher in both the active and inactive period patients compared with the control group (p 0.05). There was also no significant difference in uric acid levels between the groups (p > 0.05). In the patients group, a negative correlation was found between the levels of serum MDA and vitamin C (r=-0.517; p < 0.05). Our results indicate that decreased vitamin C and increased MDA levels reflect the increased levels of oxidative stress in BD patients, and this situation may be important in relation with its pathogenesis.

Neuro-Behçet: report of three clinically distinct cases

We report three patients who collectively have very representative clinical forms of neuro-Behçet and different neurological findings. The first case, male, 49 years old, presents symptoms similar to multiple sclerosis. The second case, male 15 years old, presents with parenchymatous compromise and an association with antiphospholipid antibody. And the third case, female 25 years old, presents an acute meningitis. Neuro-Behçet must always be included as a differential diagnosis of neurological disorders that have any difficulties in establishing a definite diagnosis

Clinical analysis of Behcet disease: arthritic manifestations in Behcet disease may present as seronegative rheumatoid arthritis or palindromic rheumatism

OBJECTIVES: To analyze arthritic manifestations in Behcet disease, which is one of the most common manifestations of Behcet disease. METHODS: Among the patients who visited the Rheumatology Division, Keimyung University Dongsan Medical Center, Taegu, Korea from March 1997 to February 1998, 35 patients, with more than 3 months follow-up, were compatible for the diagnosis of Behcet disease according to the Shimizu criteria, after exclusion of uncertain or possible Behcet cases. The presence of various manifestations was evaluated. Regarding the joint manifestations, the involved joint, signs and the pattern of the articular symptoms were examined. Basic laboratory tests, HLA studies and simple radiologic studies were done. RESULTS: All 35 patients had evident, recurrent, painful oral ulcers by the study definition. Genital ulcers were found in 29%, skin lesions in 77%, uveitis in 9%, gastrointestinal ulcerations in 6% and vascular manifestations in 6%. Joint manifestations appeared in 97%. Knee(91%), proximal interphalangeal (53%) and metacarpophalangeal joints(21%) were the main sites. Tenderness was prominent in 91% and swelling in 44%. Polyarticular presentation was found in 47%. In most cases (76.4%), the articular symptom was short-lasting. C-reactive protein was likely to be positive in active Behcet disease. HLA B51 was positive in 46%. CONCLUSIONS: In Behcet disease, various manifestations can be found. The arthritic manifestation seems quite common. It may present as seronegative rheumatoid arthritis. Otherwise, it may present as palindromic rheumatism.

Behcet's disease sera containing antiendothelial cell antibodies promote adhesion of T lymphocytes to cultured human dermal microvascular endothelial cells

Antiendothelial cell antibodies (AECA) have been detected in the sera of patients of autoimmune diseases showing vasculitis. Using IgM-ELISA, we found AECA in 42 (56%) of 75 sera samples from patients with Behcet's disease in a previous study. All of the 15 AECA-positive sera of Behcet's disease patients had an increased expression of the intercellular cell adhesion molecule-1 (ICAM-1), 93.3% of the sera induced the vascular cell adhesion molecule-1 (VCAM-1), and 100% of the serum induced the E-selectin molecule on human dermal microvascular endothelial cells (HDMEC). After stimulation of HDMEC with AECA-positive sera of Behcet's disease patients, the expression of ICAM-1 and VCAM-1 on HDMEC increased significantly at 4 hours, reaching a peak at 16 hours. Expression of E-selectin was induced at 1 hour after stimulation with a peak at 4 hours and it decreased thereafter. Adherence of T lymphocytes to HDMEC increased significantly after stimulation with AECA-positive sera from Behcet's disease patients. Also, the adherence of T lymphocytes to HDMEC increased at 4 hours and returned to its normal level at 48 hours. These results show that AECA-positive sera of Behcet's disease patients are capable of activating HDMEC to promote the adherence of T lymphocytes to increase the expression of ICAM-1, VCAM-1, and E-selectin on the cell surfaces. The whole process may play an important role in the pathogenesis of vasculitis in Behcet's disease.