Behçet's Disease Group Research Articles

No apparent correlation between Behçet’s disease and oxidative stress disturbance

Behçet's disease (BD) is a chronic, progressive and inflammatory multisystemic disease, that significantly affects the cardiovascular system. Oxidative stress (OS) is a disturbance in oxidant/antioxidant balance in favor of oxidants. The OS that increases acutely and chronically due to the inflammatory process plays an important role in the pathogenesis of the cardiovascular system effects of the disease by causing endothelial dysfunction in vascular structures. The aim of our study was to investigate the relationship between OS and myocardial perfusion, which is based on microvascular dysfunction, in BD. Twenty-seven patients with BD (16 M, 11 F, mean age: 38.7 +/- 9.4 years) and 22 healthy volunteers (12 M, 10 F, mean age: 35.8 +/- 6.5 years) participated in our study. Technetium-99m methoxyisobutylisonitrile single photon emission computed tomography (Tc-99m MIBI SPECT) stress-rest test was performed with two-day protocol. Myocardial perfusion scores (summed stress score, summed rest score, summed difference score, fix defect score) and perfusion defect prevalence (stress, rest, ischemic and fixed) were determined as the percentage of left ventricle. Coronary angiography was performed in patients with abnormal myocardial perfusion scintigraphy. For OS analysis, the blood samples were taken immediately before the first imaging procedure and were studied for malondialdehyde, glutathione, nitrite, nitrate, vitamin C, retinol, and carotene. In the BD group, a total of 9 patients had abnormal findings in their stress and rest electrocardiography. Perfusion defect in myocardial perfusion scintigraphy was observed in 14 patients (51.8%). Twelve patients accepted coronary angiography, and their results were normal. In the comparison of myocardial perfusion scores, perfusion defect prevalence and OS parameters, there was a significant difference between the BD and control groups. In the BD group, no correlation was observed between myocardial perfusion scores, perfusion defect prevalence and OS parameters. Defects in myocardial perfusion and increase in OS were observed in BD; however, there was no correlation between the two findings in the inactive period. In other words, the prevalence and intensity of myocardial perfusion defects can vary at different OS levels.

Hyperhomocysteinaemia in Behçet's Disease

Objectives. The aim of this study was to investigate if hyperhomocysteinaemia is a contributive risk factor for the pathogenesis and the activity of Behçet's disease (BD). Design and Methods. Fifty four patients fullfiling the criteria of the International Study Group for BD were enrolled. Fifty healthy volunteers matched for age and sex with the BD group were included as a negative control group. Patients, with any condition that might affect plasma homocysteine concentration, were excluded. Results. Mean serum homocysteine concentration was significantly higher in patients with BD than in the healthy controls (P < .001), in patients with active disease (P = .04), and in masculine gender (P = .05). There was no significant difference between homocysteine level and clinical involvement. Conclusions. We demonstrated that plasma total homocysteine level (tHcy) is increased in BD and correlated with disease activity. No association was found between homocysteine levels and clinical involvement.

Inflammatory mediators and posterior segment involvement in ocular Behçet disease

To assess the serum level of mediators and their relation with posterior ocular involvement in patients with Behcet disease (BD). This study was a prospective, institutional clinical trial including 43 patients with ocular BD. Patients were divided into two subgroups: those with active posterior segment involvement (Group A) and those with inactive ocular BD (Group B). Group A included patients with posterior uveitis (vitritis or chorioretinal involvement), while Group B included patients with no active intraocular inflammation within the last 3 months. Serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were measured by sandwich enzyme-linked immunosorbent assay and spectrophotometric assay and compared among the groups by independent sample t test and Mann-Whitney U-test. Serum levels of the mediators in Group A (IL-6 [23.1 pg/mL], IL-8 [161.1 pg/mL], TNF-alpha [30.5 pg/mL], VEGF [455.9 pg/mL], MDA [10.7 microm]) were found to be significantly higher than those in Group B (IL-6 [12.2 pg/mL], IL-8 [48.4 pg/mL], TNF-alpha [18.6 pg/mL], VEGF [138.0 pg/mL], MDA [5.1 microm]). This study demonstrated that increased serum levels of inflammatory mediators including IL-6, IL-8, TNF-alpha, VEGF, and MDA were possibly involved in the development of posterior uveitis in BD.

Low prevalence of NOD2 SNPs in Behcet's disease suggests protective association in Caucasians

It has been shown previously that three nucleotide-binding oligomerization domain containing 2 (NOD2) variants (Arg702Trp, Gly908Arg and Lue1007fs) are associated with Crohn's disease (CD), a disorder clinically resembling Behçet's disease (BD). We studied the frequency of these variants in BD patients. DNA samples of 200 BD patients [59 Caucasians, 139 Middle Easterns (MEs) of Arab descent and 2 Asians] and 520 healthy controls (444 Caucasians and 76 MEs) were genotyped using a Taqman assay. Both the Arg702Trp and Leu1007fs (frameshift) variants were significantly less frequently present among BD patients compared with healthy controls (0.5 vs 5.8%; P < 1.10(-5) and 0.0 vs 1.8%; P < 0.007, respectively). In the Caucasian subpopulation, Arg702Trp was significantly less frequent in the BD group as compared with the controls (P = 0.04); whereas in the ME subpopulation, a trend was observed (P < 0.06). Of the three CD-associated single nucleotide polymorphisms, one of the variant NOD2 alleles, was found to be present significantly less in Caucasian BD patients.

Neutrophil hyperchemotaxis in Behçet’s disease: a possible role for monocytes orchestrating bacterial-induced innate immune responses

Increased neutrophil chemotaxis and hyperresponsiveness to streptococci have been considered to play a role in Behçet's disease (BD) pathogenesis. Our aim was to correlate TLR2 expression and chemotactic responses stimulated by bacterial lipoteichoic acid (LTA) in BD neutrophils. Thus, we assessed expressions of TLR2 and the correlate receptors CD14, CD114 (G-CSF receptor), CD116 (GM-CSF receptor) and also TLR4 on circulating neutrophils and monocytes of patients with active BD. Serum concentration of soluble CD14 (sCD14) was also measured. Neutrophil chemotactic responses from BD patients and healthy controls under LTA stimulation were assessed. Disease activity was evaluated by Behçet's Disease Current Activity Form (BDCAF). Receptor expressions were measured by flow cytometry, neutrophil chemotaxis was assessed in a Boyden chamber and sCD14 was measured by enzyme-linked immunosorbent assay. TLR2 expression was higher only on BD monocytes compared with healthy controls (39.9 +/- 13.1 vs. 33.6 +/- 5.3, p = 0.019). Expressions of all other receptors were similar in BD and control group. Of particular interest, TLR2 expression on neutrophils was similar in both groups and, when stimulated with LTA, BD neutrophils showed chemotactic responses similar to the controls. Neutrophils exhibited increased chemotaxis only when incubated with BD plasma. Serum sCD14 concentration was higher in BD patients than in controls (1,920.8 +/- 563.6 vs. 1,623.2 +/- 391.3 ng/ml, p = 0.008), and it was positively correlated with both CD14 expression on circulating monocytes membrane (p = 0.035) and BDCAF scores (p = 0.025). In conclusion, isolated BD neutrophils do not overexpress TLR2 neither overreact to LTA. However, because TLR2 expression was higher on BD monocytes, sCD14 from monocyte origin correlated with disease activity and neutrophil hyperchemotaxis occurred on strict dependence of plasmatic soluble factors, we suggest a possible role for bacterial stimulation of monocytes via TLR2 producing neutrophil-stimulating pro-inflammatory factors in BD.

The relationship between disease activity and depression in patients with Behcet disease and rheumatoid arthritis

Disease activity may be questioned as a possible related factor to depression in patients with rheumatoid arthritis (RA) and Behcet disease (BD). Our aims were to determine and compare the depression levels of patients with RA and BD and to investigate a possible association between disease activity and depression scores of the patients. A total of 30 RA and 30 BD patients were included in this study. In RA patients; pain, morning stiffness duration, systemic involvement, tender-swollen joints, the physician-patient global assessments and DAS28 scores were determined. In patients with BD, the BD Current Activity Form was assessed for disease activity. Beck depression inventory (BDI) was used for the evaluation of patient groups. BDI score above 13 was considered as cut-off point for depression. Pearson's correlation and Mann-Whitney U tests were used for statistical analysis. In RA patients, in spite of no correlation between disease activity and depression, a significant correlation between BDI scores and pain was determined (p < 0.000; r = 0.615). In BD group; positive correlations between BDI scores and patient's impression of disease activity and arthralgia were determined (p < 0.014 and p < 0.001, respectively). Number of BD patients with higher BDI scores than cut-off point was significantly more than those in RA group (p < 0.039). Pain in RA patients, and patient's impression of disease activity and joint involvement in BD patients were found as related factors to the depression scores. The greater ratio of BD patients with higher depression score than those in RA indicates the need for increased awareness of depressive symptoms in patients with BD.

Homocysteine levels in patients with Behçet’s disease and patients with recurrent aphthous stomatitis

The mechanism for vascular involvement of Behçet disease (BD) includes arterial and venous thrombosis. Although the exact etiology of systemic vasculitis and thrombosis is still unknown, many hypotheses have been suggested. One of these hypotheses is that hyperhomocysteinemia causes vascular disease and thrombosis. The aim of this study was to compare the levels of homocysteine, vitamin B(12), and folic acid of BD patients with those of recurrent aphthous stomatitis (RAS) patients and healthy controls. Forty-five BD patients, 47 RAS patients, and 69 healty control subjects were included in this study. Vitamin B(12), folic acid, and homocysteine levels of the patients and controls were measured, and statistical differences among the groups were determined. BD patients had mostly cutaneous symptoms. Arthritis and ocular and vascular involvement were seen in 24.4%, 22%, and 11% of BD patients, respectively. No significant difference was detected among the groups in the levels of vitamin B(12), folic acid, and homocysteine. There was no significant difference in any parameters according to sex and age of the patients and activity of BD and if the patients with BD were treated or not. Homocysteine level inversely correlated with vitamin B(12) and folic acid levels in the BD group. We could not find any differences in homocysteine, vitamin B(12), and folic acid levels between BD and RAS patients and controls. This may be due to the fact that our patients mostly had cutaneous symptoms rather than vascular involvement.

A histopathological approach: when papulopustular lesions should be in the diagnostic criteria of Behçet's disease?

BACKGROUNDPapulopustular lesions (PPL) are commonly seen cutaneous lesions in Behçet's disease (BD). Some authorities do not recommend using cutaneous lesions for diagnostic criteria because these lesions are confused with acne vulgaris. Objective To understand if PPL have diagnostic value in BD. Biopsy was performed on papulopustular lesions of Behçet's patients for histopathological examination to compare with the control group composed of patients with acne vulgaris. Forty two patients with BD and 21 control patients with acne vulgaris were enrolled in the study. Histopathological findings were classified as leukocytoclastic vasculitis, lymphocytic vasculitis, superficial and/or deep perivascular infiltration, and folliculitis and/or perifolliculitis. Of the specimens from 42 Behçet's disease patients, 7 (16.7%) revealed leukocytoclastic vasculitis and 3 (7.1%) had lymphocytic vasculitis, 15 (35.7%) had superficial perivascular and/or interstitial infiltration, 12 (28.6%) had superficial and deep perivascular and/or interstitial infiltration, 5 (11.9%) had folliculitis or perifolliculitis. Of the control group patients, 9 (42.9%) had folliculitis or perifolliculitis, 8 (38.1%) revealed superficial perivascular inflammation and 4 (19.0%) revealed mixed superficial and deep perivascular inflammation. Vasculitis was not encountered in any control group specimens. Vasculitis ratio was statistically higher in Behcet's disease patients (P = 0.016). We evaluated more patients than previous related studies reported in the literature. Histopathological findings of vasculitis were encountered only in BD group. Non-vasculitis histopathological findings were also encountered in the control group patients. In conclusion, PPL can be used as a diagnostic criterion of BD subsequent to finding vasculitis in histopathological examination of the biopsy specimen of the PPL.

Cerebral venous thrombosis in Behçet’s disease compared to those associated with other etiologies

Cerebral venous thrombosis (CVT) is caused by various etiologies. In Mediterranean and Middle Eastern countries, Behçet's disease (BD) is one of the leading causes of CVT. We aimed to evaluate any differences in CVT patients with and without BD. All registered patients with CVT were evaluated retrospectively. Clinical, neuroradiological findings and follow-up data were compared between patients with BD and patients with other etiologies. There were 36 patients with CVT and BD, and 32 patients with CVT related to other etiological causes. BD patients were younger (median age at onset 26 vs. 39 years; P < 0.001), and there was a male preponderance (28 males, 8 females) as compared to the non-BD group (10 males, 22 females; P < 0.001). Onset was frequently acute in the non-BD group, and it was subacute or chronic in the BD group. Hemi/quadriparesis, aphasia and seizures were significantly more common (P < 0.001) in the non-BD group. In the BD group 94% of the patients presented with symptoms of isolated intracranial hypertension (P < 0.001). Venous infarcts were observed in 63% of the patients with other causes and in 6% of the patients with BD (P < 0.001). At admission 97% of the patients in the BD group and 41% of the patients in the non-BD group had a modified Rankin score of 0-2. Outcome was good in all of the patients with BD and in 91% of patients with other causes. Clinical recurrences were seen in six patients with BD and in one patient without BD. CVT associated with BD has a subacute onset, mostly presents with signs of isolated intracranial hypertension and venous infarction rarely develops; these features distinguish CVT due to BD from those with other causes.

Serum levels of malonyldialdehyde (MDA) and paraoxonase activities in patients with Behcet's disease

Objective The present study was undertaken to evaluate the levels of MDA as a marker of oxidative stress and activities of PON1 which may have a role as an antioxidant in Behcet's Disease (BD). Design & Methods In the present study, 16 patients of BD (7 male, 9 female, mean age: 31.26 ± 16.67) and 17 healthy individuals (7 male, 10 female, mean age: 32.7 ± 15.53) were included in the evaluation. Patients with BD were identified at the Dermatology Clinic of Dicle University Medicine Faculty Hospital. Diagnosis of BD was performed according to the criteria of the International Study Group on Behcet's Disease. Results In BD group, the medians of serum PON1 and MDA levels were 82.63 U/L and 2.25 nmol/ml, respectively. In the control group, median serum PON1 and MDA levels were 122.99 U/L and 1.43 nmol/ml, respectively. There was a statistically significant decrease in serum PON1 levels (82.63 ± 24.42 versus 122.99 ± 31.28; p p p > 0.05) and MDA levels (2.29 ± 0.71 versus 2.14 ± 0.24; p > 0.05) did not show any statistically significant difference. Conclusion Endothelial damage and increased polymorphonuclear leukocyte activity in the BD could result in decreased PON1 activity and increased MDA.

CTLA‐4 +49A/G polymorphism is associated with Behçet’s disease in a Tunisian population

The involvement of excessive T-helper cell functions in the pathogenesis of Behçet's disease (BD) has been reported. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays a role in T-cell downregulation. In this report, we investigated the possible association between BD patients and the CTLA-4 +49A/G polymorphism in Tunisian population. A total of 135 Tunisian BD patients and 151 healthy blood donors from the same geographic area were genotyped by polymerase chain reaction for the CTLA-4 +49 A/G polymorphism. A highly significant difference between Tunisian BD patients and healthy controls was found regarding the distribution of CTLA-4 +49 A allele [P < 10(-7); chi(2) = 75.63; odds ratio (OR) = 4.63; 95% confidence interval (CI) = 3.20-6.72] and genotype frequencies (P < 10(-7); chi(2) = 71.02). Furthermore, in the BD group, the A allele was predominant in males (76.3%) when compared with females (62%), (P = 0.014; chi(2) = 5.97; OR = 1.99; 95% CI = 1.10-3.59). No relationship was found between the studied genotype and clinical manifestations. Our results show a gene dose effect of the A allele on the BD. The A allele exerts a stronger effect on disease susceptibility in males compared with females.

Ultrasonographic Evaluation of Hand and Foot Tendons in Behçet's Disease

There have been few studies in the literature evaluating the effect of Behçet's disease (BD) on tendons. Thus, we planned to search for the involvement of hand and foot tendons in BD by using ultrasonography and to determine the relation of tendon involvement with clinical measurements. The study consisted of 33 randomly selected BD patients and 36 voluntary healthy controls matched by age and body mass index. Sonographic evaluations were performed from hands (flexor digitorum süperficialis (2-5), flexor digitorum profundus (2-5), flexor carpi radialis) and Achilles tendons of the nondominant extremities using an 8-10 MHz linear array probe. Grip strength and crepitation were also measured on the nondominant side. Mean hand and foot tendon thickness values of BD patients were significantly higher than in control group (p=0.00). Disease duration, age, and presence of crepitation were not correlated with tendon thickness in the BD group (all p values>0.05). Grip strength values were lower in the BD group than in control group but the difference was not statistically significant (p=0.344). Grip strength values were not correlated with hand tendon thicknesses in BD groups (all p values>0.05). Because tendons tears and thicknesses are associated with inflammation, awareness of tendon pathologies is very important in rheumatic diseases. It would be of value to investigate this relationship in future studies in order to determine if this increment in tendon thickness is an indicator of disease activity and affects prognosis. The physician should be on alert about tendon involvement even if the patient has no complaints.

Ghrelin and Obestatin Levels in Rheumatoid Arthritis

Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients. Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet's disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay. Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (p<0.05 for both), but when compared with HC group differences were not significant. There was no difference across groups in terms of acylated ghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-alpha in the HC group (r=0.400, p<0.05; r=0.412, p<0.05, r=0.543, p<0.01 and r=0.528, p<0.05, respectively). Our results did not show a significant correlation between circulating ghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.

Carotid artery intima-media thickness in Behcet's disease patients without significant cardiovascular involvement

Background/AimsBehcet's disease (BD) is a systemic disorder associated with a characteristic vasculitis that can involve both veins and arteries of all sizes. Endothelial activation or injury is a characteristic feature of BD. Endothelial dysfunction is widely regarded as being the initial lesion in the development of atherosclerosis. The carotid artery intima-media thickness (IMT) is a widely accepted marker of subclinical atherosclerosis. We aimed to determine the carotid IMT in BD patients with using high-resolution B-mode Doppler ultrasonography.MethodsWe studied 40 patients (24 males, mean age: 39.1±8.5 years) who were diagnosed by the international diagnostic criteria of Behcet's disease and 20 healthy controls (13 males, mean age: 40.2±5.1 years), and the two groups were matched by age and gender. No subject in either group had a history of atherosclerosis or its complications. The clinical data, including the age of onset, the duration of disease, a history of medication, the activity score and the laboratory data were analyzed.ResultsThe carotid IMT in the BD group was significantly higher than that in the control group (0.71±0.22 mm vs. 0.59±0.09 mm, respectively, p<0.01). Cardiac and major vessel involvements were not identified in the BD group. However, minor vascular involvements were documented in 2 patients with deep vein thrombosis, in 4 patients with superficial thrombophlebitis and in 2 patients with pseudoaneurysm. The carotid IMT in the patients with posterior uveitis or retinal vasculitis was higher than that of the patients without these findings (0.85±0.21 mm vs. 0.64±0.10 mm, respectively, p=0.007), but there was no difference of the IMT according to minor vascular involvement.ConclusionsDespite that there was no significant cardiovascular involvement in the BD patients, the carotid IMT was significantly higher in the BD patients as compared with the healthy controls.

Evaluation of myocardial perfusion and function by gated SPECT in patients with Behçet’s disease

Behçet's disease (BD) is a systemic multi-system vasculitis that can have a wide range of effects on the cardiovascular system. To determine the existence of myocardial perfusion defects caused by coronary microvascular dysfunction in BD and to evaluate coronary arterial distribution and left ventricular systolic function by gated single-photon emission computed tomography (SPECT). The study population consisted of 23 (15 men and 8 women) patients with BD and 20 healthy controls (12 men and 8 women). Technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) gated SPECT studies were performed at stress and rest in a 2-day protocol. Stress and rest left ventricular ejection fraction (LVEF) were calculated. Using non-gated SPECT images myocardial perfusion scores [summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), and fix defect score (FDS)] and perfusion defect extent as percentage (stress, rest ischemic, and fix %LV) were determined. Using gated SPECT images, wall motion score indices (stress wall motion score indices and rest wall motion score indices) were calculated. Coronary angiography (CAG) was applied to patients with abnormal myocardial perfusion scintigraphy (MPS). The mean ages of the BD and control groups were 39.3 +/- 10.6 years and 36.2 +/- 8.3 years, respectively. No statistically significant differences were observed between the two groups regarding clinical features and cardiologic findings. Abnormal MPS was found in 13 (56.5%) of the BD patients; 3 patients had non-transmural infarcts and 10 patients reversible perfusion defects. Reversible perfusion defects were also found in two controls (10.0%). When the two groups were compared regarding the gated SPECT findings, differences were determined in the following parameters; SSS, SRS, SDS, FDS, stress and rest LVEF, stress and rest %LV, and stress and rest WMSI. In the BD group, when gated SPECT results were compared between those with and without abnormal MPS, differences were determined in SSS, SRS, SDS, FDS, stress and rest %LV, and stress and rest WMSI. Epicardial coronary arteries were normal in CAG. Myocardial perfusion and function are disturbed owing to influenced coronary microvascularity in BD, and CAG is frequently observed to be normal. Gated SPECT is a non-invasive reliable method that simultaneously evaluates the existence, extent and severity of myocardial ischemia or infarction and the wall movements in cardio-Behçet.

Serum levels of natriuretic peptides in patients with Behcet’s disease

The objective of our study was to elucidate serum levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) in Behcet's disease (BD) patients with active and inactive period. The multicenter study included 53 patients with active (n = 28) and inactive (n = 25) BD (mean age, 34.3 +/- 9 years; 15 men and 38 women) satisfying the International Study Group criteria and 26 healthy controls (mean age, 34.4 +/- 6.1 years; seven men and 19 women) matched for age and gender from a similar ethnic background. Serum natriuretic peptides levels were determined by enzyme immunoassay kit. Mean serum ANP concentrations in the active patients (4.01 +/- 1.21 ng/ml) were significantly lower than in the healthy controls (5.76 +/- 1.99 ng/ml, p = 0.004). Mean serum BNP levels were found to be significantly higher in both the active (6.19 +/- 2.97 ng/ml) and inactive (6.49 +/- 2.88 ng/ml) BD groups compared with the control group (3.82 +/- 1.1 ng/ml, p = 0.004 and p = 0.001, respectively). Mean serum CNP concentrations in the active patients (0.49 +/- 0.12 ng/ml) were significantly lower than in the inactive patients (0.65 +/- 0.2 ng/ml, p = 0.017) and the healthy controls (0.8 +/- 0.27 ng/ml, p < 0.001). Our results suggest that changes in natriuretic peptide levels may be associated with vasculitis that play role in the etiopathogenesis of the BD.

Th1 polarization of the immune response in uveitis in Behçet's disease

Background: It has been reported that abnormalities in the balance of T-helper cells type 1/2 (Th1/Th2) may account for the pathophysiology of human autoimmune diseases. The purpose of this study was to define the role of the Th1/Th2 balance in the pathogenesis of uveitis in Behçet's disease (BD). Methods: From February 2003 to August 2005, we studied 31 patients with active BD. Of these patients, 21 (12 female, 9 male; mean age 35.5 [SD 10] years) presented with acute uveitis, and 10 (7 female, 3 male; mean age 34 [SD 11] years) presented with inflammatory arthritis but no prior uveitis attack.The control group consisted of 10 (7 female, 3 male; mean age 34.7 [SD 8] years) age-matched, healthy individuals. CD4+ CD26+ and CD4+ CD30+ cell surface expression of the peripheral blood CD4+ T lymphocytes was evaluated by analytic flow cytometry in order to determine percentages of Th1 and Th2 lymphocyte subsets. Results: The mean percentage of CD4+ CD26+ and CD4+ CD30+ cells was 26.27 (SD 6.18) % and 2.56 (SD 0.82) %, 17.42 (SD 5.90) % and 2.86 (SD 0.72) %, and 14.99 (SD 3.96) % and 3.11 (SD 1.25) % in BD with active uveitis, BD with inflammatory arthritis but no prior uveitis attack, and control groups, respectively. T-helper 1 (Th1) cell percentage was significantly higher in the BD with active uveitis group than the BD with arthritis and no prior uveitis attack group ( p = 0.001). With respect to the percentage of CD30+ Th2 cells, there was no statistical difference between the 2 BD groups ( p = 0.529) or among the 3 groups ( p = 0.375). Interpretation: Th1 lymphocyte dominance in peripheral circulating blood may play a role in the pathogenesis of BD uveitis.

Vascular endothelial growth factor and carotid intima-media thickness in patients with Behçet’s disease

There is morphologic evidence of subclinical atherosclerosis in Behçet's disease (BD) patients obtained by high-resolution B-mode ultrasonography (US). Vascular endothelial growth factor (VEGF) is a potent angiogenetic factor and a marker for endothelial dysfunction. VEGF could contribute to the pathological events in BD. VEGF could also be an important factor in the progression of atherosclerosis. In this study, we investigated whether there is correlation between intima-media thickness (IMT) of the carotid arteries and serum VEGF levels in BD patients and healthy controls. Twenty-one patients with BD (male/female: 15/6, mean age: 35.8 +/- 8.6 years) were individually matched to control subjects on the basis of age (within 3 years) and sex. Carotid IMT of the subjects was measured by high-resolution B-mode US. Mean IMT values of common carotid arteries were 0.86 +/- 0.18 mm for patients with BD, and 0.57 +/- 0.14 mm for healthy controls (p < 0.001). Mean VEGF levels were 130.41 +/- 58.28 pg/ml for patients with BD and 82.69 +/- 25.03 pg/ml for healthy controls (p < 0.001). There was no correlation between VEGF levels in the control group and in the BD group, but there was a significant correlation between VEGF levels and mean carotid IMT in the whole group (r = 0.317, p < 0.05). In conclusion, elevation of VEGF appears as a feature of the inflammatory reaction during the course of BD, not a direct determinant of subclinical atherosclerosis. On the other hand, the significant correlation between carotid IMT and serum VEGF levels in the whole group suggests that association between VEGF levels and carotid IMT warrants further investigation with larger sample sizes.

The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: comparison between recurrent aphthous ulcers and the oral ulcers of Behçet's disease

Hyaluronic acid (HA) is a primary component of the extracellular matrix, and the efficacy of HA on oral ulcers is rarely reported. To observe the efficacy and safety of the topical application of 0.2% HA gel on recurrent oral ulcers and to compare its effects in patients with recurrent aphthous ulcers (RAU) and the oral ulcers of Behçet's disease (BD). Thirty-three outpatients with recurrent oral ulcers were included in the study (17 patients: BD, 16 patients: RAU). The patients used topical 0.2% HA gel twice daily for 2 weeks. The subjective parameters of patients [number of ulcers, healing period, visual analogue scale (VAS) for pain] were investigated and objective assessments (number of ulcers, maximal area of ulcer and inflammatory signs) were inspected by a physician. A subjective reduction in the number of ulcers was observed in 72.7% of the patients. A decrease in the ulcer healing period was observed in 72.7% of the patients; 75.8% experienced improvement in VAS for pain. Objective inspection of the ulcers showed a reduction of numbers in 57.6% of the patients, and 78.8% of the ulcers showed a decrease in area. Among the inflammatory signs, swelling and local heat were significantly improved after treatment. No significant differences were found between the BD group and RAU group in subjective and objective parameters, except for inflammatory signs. No side-effects were observed. The topical application of 0.2% HA gel seems to be an effective and safe therapy in patients with recurrent oral ulcers; the study supports the use of HA in BD with oral ulcers.

PTPN22 gene polymorphism in Behçet’s disease

A functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the protein tyrosine phosphatase has been reported to be associated with autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus and type I diabetes. PTPN22 R620W polymorphism has a wide variation of allelic frequencies among different populations. This polymorphism is investigated in Turkish patients with Behçet's disease (BD), a systemic vasculitis with immune activation. DNA samples from 134 patients with BD and 177 healthy controls are genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism method for the SNP (rs2476601, A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with XcmI enzyme. The frequency of heterozygous genotype (AG) was 5.1% (9/177) in control group, whereas polymorphic allele was not present in the whole BD group (P = 0.012, OR 0.65, 95% confidence interval 0.0-1.1). Both the lower prevalence in the general population and the absence in BD show the limited role of PTPN22 polymorphism in the pathogenesis of autoimmunity in Turkey.