Olcay Tiryaki Aydintug

Characteristics of vascular involvement in Behçet's disease.

Objective: Behçets disease (BD) is a multisystemic inflammatory disorder classified among the vasculitides, which can affect all types and sizes of blood vessels. Vascular involvement may be seen in 25–50% of BD patients. In this study, we examined the characteristics of vascular involvement in patients with BD. Methods: One hundred and eighty patients with BD were included in the study. The diagnosis of vascular involvement was made on clinical signs, by Doppler ultrasonography and/or angiography using computed tomographic or magnetic resonance techniques where appropriate. Detailed clinical characteristics were recorded for each patient. Results: Seventy‐one patients (39.4%) had vascular involvement. In patients with vascular lesions, the frequency of male sex was significantly higher than in patients without vascular lesions (89.8% vs. 63.3%, respectively; p<0.001). Of 71 BD patients with vascular involvement, 68 had venous lesions (95.8%). Three patients had arterial lesions without venous thrombosis. Eleven patients had arterial involvement with venous thrombosis. The most frequent type of vascular involvement was deep venous thrombosis in the lower extremities (n = 56, 78.9%). There was a significant association between deep venous thrombosis and superficial thrombophlebitis (r = 0.325, p<0.01). Twenty‐four patients (33.8%) had vena cava thrombosis and two had vena hepatica thrombosis. In patients with vascular involvement, the frequency of erythema nodosum was significantly higher (p = 0.001) and the frequency of ocular involvement was significantly lower (p<0.05) than in patients without vascular involvement. Conclusion: Our study illustrates the frequency and significance of vascular involvement in BD.

Cytokine inhibitors: soluble tumor necrosis factor receptor 1 and interleukin-1 receptor antagonist in Behçet’s disease

Serum levels of proinflammatory cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor alpha, (TNF-α), and their inhibitors, IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor 1 (sTNFR1), were determined by enzyme-linked immunosorbent assay in 104 patients with Behçet’s disease (65 active, 39 inactive) and 40 healthy controls. The levels of IL-1β and IL-1ra were significantly higher in both active and inactive patients than in control subjects (P<0.01 and P< 0.01, respectively). The concentrations of TNF-α and sTNFR1 were found to be higher in active patients than in controls (P< 0.01 and P< 0.001, respectively). There were no significant differences in the serum levels of these cytokines and their inhibitors between active and inactive patients. Significant increases in mean C-reactive protein level and erythrocyte sedimentation rate were found in patients with active vs inactive disease (P< 0.001 and P< 0.05, respectively). C-reactive protein values correlated with erythrocyte sedimentation rate but not with cytokines or their inhibitors. Our conclusion is that elevated serum TNF-α and sTNFR1 seem to be important inflammatory mediators in Behçet’s disease. The statistically significant increase in these levels may arise from the severity of inflammation in the tissue or organ involved.

A multicenter study of patients with adult-onset Still’s disease compared with systemic juvenile idiopathic arthritis

Adult-onset Still’s disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.

Serum homocysteine level is higher in Behçet’s disease with vascular involvement

ObjectiveBehçet’s disease (BD) is a multisystemic inflammatory disorder of unknown etiology that is sometimes associated with thrombosis. However, the mechanism of hypercoagulability is not known. In this study, we investigated whether hyperhomocysteinemia, being a well-known risk factor for thrombosis, is also a contributing risk factor to venous and arterial thromboses of BD.MethodsForty-five patients with BD and 40 healthy subjects were included in the study. Sixteen patients had vascular involvement. Serum homocysteine levels were determined by fluorescence polarization immunoassay.ResultsIn male patients, the frequency of vascular involvement was significantly higher than in females (46.7% vs 13.3%, P<0.05). Serum homocysteine levels were significantly higher in patients with BD than healthy controls (P<0.01), in patients with vascular involvement than those with mucocutaneous involvement (P<0.01) and healthy controls (P=0.001), and in male patients than in female patients (P<0.001). There was no significant difference in homocysteine levels between the BD patients with mucocutaneous involvement and healthy subjects. In multiple regression analysis, serum homocysteine level was independently associated with thrombosis (odds ratio 1.29, P<0.01), but male sex was not.ConclusionsThis preliminary study suggests that elevated serum homocysteine levels may play some role in the development of venous and arterial thromboses in BD.

Adhesion molecule expression in erythema nodosum-like lesions in Behçet's disease A histopathological and immunohistochemical study

Abstract Behçets (BD) is a systemic inflammatory di-sease with histological evidence for vasculitis. Leucocyte-leucocyte and leucocyte-endothelial cell interactions are critical in inflammatory reactions that are influenced by the expression, activation and shedding of adhesion molecules. We investigated the expression of some adhesion molecules (E- and L-selectin, VLA-4, ICAM-1, PECAM-1, VCAM-1 and CD18 and CD11c chains of beta-2 integrins) on endothelial and inflammatory cells by immunohistochemistry on cryostat sections of erythema nodosum lesions taken from 15 patients with BD and 12 patients with erythema nodosum of unknown cause. Hematoxylin-eosin stained sections of all specimens were also assessed. The major histopathological findings were perivascular mononuclear cell infiltration and secondary vasculitic changes with no difference between the two groups (P>0.05). However, the frequency of thrombophlebitis was higher in BD (P<0.001). Endothelial and inflammatory cell adhesion molecule expression did not show any significant diffe-rence between groups (P>0.05). Although VCAM-1 expression and intensity on endothelial cells of BD patients seemed to be lower, this did not reach statistical significance (P=0.056). We concluded that subcutaneous thrombophlebitis is an important feature of erythema nodosum like lesions in BD, which is almost impossible to understand by physical examination alone. Colchicine, which is known to have some influence on adhesion molecules, might have affected our results, as these showed no signi-ficant difference regarding adhesion molecules between the two groups.

Survey of Factor V Leiden and Prothrombin Gene Mutations in Systemic Lupus Erythematosus

Abstract The two most common hereditary risk factors for thrombosis are factor V Leiden mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency in patients with systemic lupus erythematosis (SLE) and it is not always associated with antiphospholipid antibodies. We aimed to determine the relationship between both factor V Leiden and prothrombin gene mutations and SLE. Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene mutations were evaluated in 55 patients (20 children and 35 adults) with SLE. Although seven patients were found to have factor V Leiden mutation in the heterozygous state, two had the heterozygous G→A (20210) prothrombin gene mutation. Although one had these two mutations concurrently, these two patients did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was higher than that of our general population (7.1%). On the other hand, seven of the patients with SLE had a thrombotic event. Although of these seven, four (57%) had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no thrombotic history, only three had the factor V mutation (6.25%). The prevalence of the factor V Leiden mutation in SLE patients with and without thrombosis was significantly different by Fisher’s exact test (p<0.05). The risk of venous thrombosis in patients with factor V Leiden increased threefold compared to that in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99–133.6). Although factor V Leiden mutation seems to play a role in the development of venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial.

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with systemic lupus erythematosus.

SummaryCirculating sICAM-1 is known to be elevated in various inflammatory disorders. It is further suggested that elevated levels correlate well with disease activity in several autoimmune disorders. The objectives of this study are to determine the serum sICAM-1 levels in patients with systemic lupus erythematosus (SLE) and correlate sICAM-1 levels with clinical and laboratory (ESR, CRP, anti-dsDNA) measures of disease activity. Forty-one patients (34 female, 7 male) all fulfilling 1982 ARA classification criteria for SLE and 16 healthy controls (8 female, 8 male) were included in the study. Disease activity was measured according to SLEDAI. sICAM-1 was determined by ELISA. Mean sICAM-1 in SLE patients (339±161 ng/ml) were significantly higher than in the controls (216±85 ng/ml) (p<0.005). Although slightly elevated in active patients, there was no statistically significant difference between mean sICAM-1 levels of active and inactive SLE patients (349±183 ng/ml and 316±103 ng/ml respectively) (p>0.05). We could not find a correlation between sICAM-1 levels and any organ involvements. Similarly, no significant correlation was found between ESR, CRP, anti-ds-DNA and sICAM-1. These results suggest that although higher than normal, sICAM-1 levels in SLE do not provide additional information over conventional activity markers.

Increase in soluble E-selectin level after PTCA and stent implantation: a potential marker of restenosis

BACKGROUND E-Selectin is expressed only on activated endothelial cells, and may be used as a marker of endothelial activation. The relationship between soluble form of E-selectin (sE-selectin) and development of restenosis after balloon angioplasty (PTCA) is controversial, and there are no data for after stent implantation. We evaluated the role of serially measured sE-selectin levels in predicting the development of restenosis after PTCA and stent implantation. METHODS In sixty-one patients with stable angina pectoris who underwent PTCA (n=20) or stent implantation (n=41), peripheral blood samples were taken just before (baseline), at 3 and at 24 h after the intervention. sE-Selectin levels were measured by ELISA. Coronary angiography was repeated at 4-6 months after the intervention, and > or =50% stenosis at the site of the intervention was regarded as restenosis. Levels and time course of sE-selectin after the intervention were compared in patients with and those without restenosis. RESULTS sE-Selectin levels of the patients with and those without restenosis were similar at each of the three measurements, and significantly increased after the intervention both in the PTCA and stent groups (P<0.001 for both groups). Posthoc analysis showed that sE-selectin levels increased significantly at 3 h after PTCA (P=0.024) and stent implantation (P=0.018), and did not change thereafter in patients with restenosis. In the nonrestenotic group, sE-selectin did not change significantly in the 24 h following PTCA, however, a significant difference was observed only by comparing the values at baseline with those at 24 h after stent implantation (P=0.021). CONCLUSIONS A substantial increase in sE-selectin levels early (at 3 h) after PTCA and stent implantation may predict development of restenosis.

Plasma thrombomodulin levels in patients with Behçet's disease

Abstract. The plasma levels of thrombomodulin in 54 patients with Behçets disease (BD) and 20 healthy control subjects were studied. The mean thrombomodulin (TM) level was significantly higher in active BD patients than in inactive patients and healthy controls (P<0.001 and <0.01, respectively). Plasma TM levels did not show a significant relation with clinical manifestations. Increased plasma TM levels are associated with active disease and may reflect the presence of endothelial cell activation and/or injury.

Update on ocular Behçet’s disease

Behçet’s disease is among the chronic-relapsing, multisystemic inflammatory disorders that ARE characterized by obliterative vasculitis. Although it may affect almost all/any systems or organs, the key clinical manifestations are recurrent oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Although most prevalent along the ancient Silk Route, extending from eastern Asia to the Mediterranean, Behçet’s disease is seen worldwide. This article aims to give a brief review on various aspects of Behçet’s disease, but particularly ocular involvement, with updated information.