Importance of serum amyloid-A in Behçet’s disease

Clinical Rheumatology -     

Coronary involvement in patients with Behçet’s disease

Clinical Rheumatology - To investigate the clinical features and potential risk factors of coronary involvement in Behçet’s disease (BD). In this case-control study, we retrospectively...     

Bone mineral density in patients with Behçet’s disease

Behçets disease is a complex, multisystemic, inflammatory disorder characterized clinically by recurrent oral and genital ulcerations as well as uveitis, sometimes leading to blindness. The etiology and pathogenesis of this syndrome remain obscure. However, various factors are suspected, including genetic propensity, infectious precipitants, and immunological abnormalities. Considering the chronicity and unclear etiology of the disease, we conducted a prospective investigation of a possible alteration in the bone mineral density of affected persons. Thirty-five patients (18 males and 17 females, mean age 38.02±7.93 years) diagnosed with Behçets disease and 33 sex- and age-matched healthy controls (14 males and 19 females, mean age 40.06±7.66 years) were seen on an outpatient basis, and bone densitometry measurements were done from June 2000 to December 2002 at the Mersin University Hospital in Turkey. Postmenopausal women with Behçets disease and patients receiving oral corticosteroid therapy were excluded from the study. The mean disease duration was 6.68±7.05 years. Bone mineral density was measured with dual X-ray absorptiometry at the lumbar spine and right femur. The mean Z scores of the patient and control groups were –0.50±1.06 and –0.13±0.92 at the lumbar spine, respectively, and 0.38±1.07 and 0.45±1.20 at the right femur, respectively. No significant differences in bone mineral density values were detected in the groups at either the lumbar (P=0.15) or right femur (P=0.82) site. Body mass index and disease duration did not influence bone mineral density, and age had a positive correlation with bone mineral density in patients with Behçets disease. In conclusion, although it is difficult to draw definite conclusions due to the relatively small sample size, our study confirms that bone mineral density in Behçets disease was not lower than in healthy subjects.     

Serum-soluble selectin levels in patients with Behçet’s disease

Soluble forms of selectins may play a regulatory role in inflammatory responses. The aim of this study was to examine the levels of serum-soluble (s) selectins in Behçet’s disease (BD) patients and to evaluate the associations of these molecules to disease activity, clinical findings, and drugs taken for BD, mainly colchicine. Serum sE-, sL-, and sP-selectins levels were measured by sandwich enzyme-linked immunosorbent assay in 28 BD patients and 22 healthy subjects. The BD patients were classified according to the disease activity, clinical findings, and therapy. Ten patients were newly diagnosed and were not taking any therapy. Remainder were on colchicine (n?=?18) and immunosuppressive drugs (n?=?5). In BD patients, the levels of sL- and sP-selectins were significantly lower than those of healthy controls, but sE-selectin level was similar to that of the controls. The patients on the therapy had significantly lower levels of sE- and sL-selectins and insignificantly lower level of sP-selectin than the patients not receiving therapy. The BD patients with active disease had significantly higher levels of sE-, sL-, and sP-selectins compared with the patients with inactive disease. There were no significant differences in the levels of selectins between the treated active patients and inactive patients. However, the untreated patients with active disease had significantly higher selectin levels than the inactive patients. There were no significant differences in all selectin levels between the patients with or without vascular involvement. Serum sL-selectin was found to be significantly higher in patients with erythema nodosum. In conclusion, our findings suggest that the levels of soluble selectin molecules in BD patients seem to be modified by the drugs taken for BD. The colchicine therapy is associated with lower selectin levels.     

Association between serum homocysteine and arterial stiffness in patients with Behçet’s disease

Aim of the workTo study the effects of serum homocysteine (Hcy) on arterial wall properties, as a contributing risk factor for arterial atherosclerosis and thrombosis.Patients and methodsFifty Behçet's disease (BD) patients (M/F:37/13; age:34.8 ± 8.5 years) along with 50 healthy controls (M/F:32/18; age:31.9 ± 8.1 years) matched for age, sex, blood pressure, heart rate, height, total cholesterol and glucose levels were included. All were recruited Zagazig University Hospitals between January 2018 and December 2018. Disease activity was assessed using the Behçet's Disease Current Activity Form (BDCAF). Total Hcy was assayed by the Axis-Shield Homocysteine Enzyme Immunoassay (EIA) in serum. All subjects underwent carotid Doppler ultrasound to measure carotid artery intima-media thickness (C-IMT), arterial distensibility coefficient, Beta-stiffness index (ß) and carotid- femoral pulse wave velocity (PWV).ResultsThe main findings were significantly increased C-IMT (0.75 ± 0.71 mm), beta stiffness index (3.55 ± 0.34) and PWV (6.55 ± 1.07 m/second) and decreased distensibility (23.39 ± 1.89·10⁻³ × kPa⁻¹) in patients compared to control (p < 0.001, p < 0.001, p = 0.02 and p < 0.001 respectively). The Hcy level was significantly higher in BD patients (17.3 ± 4.2 μmol/L) vs control (8.9 ± 2.3 μmol/L). The Hcy level > 15 μmol/L significantly correlated with the C-IMT (r = 0.54, p < 0.001), ß index (r = 0.78, p < 0.001), PWV (r = 0.56, p < 0.001) and distensibility (r = −0.65, p < 0.001) as well as with the presence of vascular lesions (r = 0.59, p < 0.001) with a tendency to correlate with the BDCAF (r = 0.11, p = 0.07).ConclusionsThese findings suggest higher risk for development of atherosclerosis and endothelial dysfunction in BD patients and highlights that future researches should focus on identification and prophylactic treatment of patients at risk of cardiovascular disease.     

Risk factors of disease activity in patients with Behçet’s syndrome

Clinical Rheumatology - To investigate the clinical characteristics and laboratory data in Behçet’s syndrome (BS) patients in China and analyze the risk factors of disease activity. A...     

Serum homocysteine level and eye involvement in Egyptian patients with Behçet’s disease

Aim of the workTo investigate the possible role of serum homocysteine in the eye involvement in Egyptian patients with Behçet’s disease (BD).Patients and methodsA case–control study was made on 27 patients with BD (17 males and 10 females with a mean age of 32.11 ± 7.16 years) and 19 healthy control subjects. All patients fulfilled the criteria of the International Study Group for BD. The patients were categorized as BD with eye involvement (n = 12), or BD without eye involvement (n = 15). Serum homocysteine and C-reactive protein levels were studied in all patients and controls.ResultsThe mean serum homocysteine concentrations were significantly higher in BD patients than in healthy controls (15.56 ± 3.52 and 7.32 ± 1.38 μmol/L, respectively; P < 0.001). Also, the mean serum homocysteine concentrations were significantly higher in BD patients with eye involvement compared to those without eye involvement (18.50 ± 3 and 13.2 ± 1.61 μmol/L, respectively; P < 0.001). CRP, as a marker of disease activity was significantly higher in BD patients than in controls (14.33 ± 8.28 and 3.21 ± 1.72 mg/L, respectively; P < 0.001), however, no significant difference (P = 0.213) in CRP levels was found between BD patients with or without eye involvement.ConclusionHomocysteine may play a role in BD patients with ocular involvement. Assessment of homocysteine may be important in the investigation and management of patients with BD, especially with ocular disease.     

Levels of soluble E-selectin in patients with active Behçet’s disease

Behçets disease is a systemic vasculitis of unknown aetiology. Endothelial cell injury plays an important role in the pathogenesis and immunopathology of Behçets disease. E-selectin is expressed by activated endothelial cells. Because the selectin adhesion molecules are shed from activated cells, soluble forms of these proteins can be used as activation markers of endothelium (E-selectin). The pathogenesis of Behçets disease (BD) is closely related to endothelial cells, leucocyte functions and immunity. The aim of this study was to investigate circulating E-selectin adhesion molecules, which are known to play a significant part in the immune response especially by regulating interaction of the leucocytes with endothelium in BD. Plasma E-selectin concentrations were evaluated in 23 patients with BD and 20 healthy control subjects. The disease activity was evaluated by clinical manifestations (oral aphthous ulcer, genital ulceration, positive pathergy test, skin lesions, eye involvement, thrombophlebitis and arthritis) and by laboratory investigations [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]. The patients were newly or previously diagnosed cases not taking any drug for BD. Levels of E-selectin were measured with commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kits using human sE-selectin (cat. no: BMS 205). Plasma E-selectin concentrations of patients and controls were compared with the Mann-Whitney U test. Statistical significance was assigned to p values lower than 0.05. Serum levels (mean±SD) of soluble E-selectin (sE-selectin) were significantly higher in 23 patients with BD than in 20 healthy controls (53.2±18.2 ng/ml vs 33.8±7.5 ng/ml, p<0.0001). A statistically significant positive correlation was observed between sE-selectin levels and CRP and ESR in patients with BD (r=0.78, p<0.001 and r=0.56, p<0.01, respectively). Increases in the E-selectin in BD may be a direct consequence of the leucocyte and endothelium activations observed during the disease process. The noninvasive investigations can be used as biochemical markers for inflammation. This may provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.     

Neuro-Behçet’s disease with chorea after remission of intestinal Behçet’s disease

Neuro-Behçets disease shows various neuropsychiatric symptoms, but chorea has rarely been reported. We report a case of neuro-Behçets disease in a 67-year-old woman with depression and chorea that occurred 22 years after the onset of intestinal Behçets disease. Brain magnetic resonance imaging (MRI) using a fluid-attenuated inversion-recovery (FLAIR) sequence demonstrated lesions more clearly than did T₂-weighted MRI. Some of the lesions appeared as small ring-like foci, i.e. low-intensity spots rimmed with remarkable hyperintense signals, in the periventricular white matter and basal ganglia. A review of the literature revealed that the onset of chorea in cases of Behçets disease varied from the time of onset of Behçets disease to 31 years after onset of the disease. Psychiatric manifestations have often been associated with neuro-Behçets disease. In the present patient, treatment with prednisolone resolved the chorea, suggesting that the chorea was caused by an autoimmune mechanism. It seems likely that the long-term development of vasculitis in patients with Behçets disease results in the formation of these particular brain lesions on FLAIR MR images. Chorea should be taken into consideration as one of the manifestations of Behçets disease, even many years after remission of the disease.Abbreviations ANCA Antineutrophil cytoplasmic antibodies - FLAIR Fluid-attenuated inversion-recovery - MRI Magnetic resonance imaging     

Comparison of existing disease activity indices in the follow-up of patients with Behçet’s disease

Abstract

The objective of this study was to determine the concordance between the Iranian Behçet’s disease dynamic activity measure (IBDDAM) or the Behçet’s disease current activity form (BDCAF) and expert physician global assessment (PGA) in the evaluation of disease activity changes in Behçet’s disease (BD). In a prospective study, 117 consecutive patients with BD were evaluated in their two consecutive follow-up visits by IBDDAM and BDCAF. The change in disease activity was determined (increased, unchanged or decreased) according to the PGA. We used receiver operating characteristic (ROC) curve to determine an appropriate cutoff point for disease activity change. Comparison was made by Stata and kappa analysis. Comparing the area under the ROC curve showed a significant difference between IBDDAM and BDCAF (p < 0.03). The difference was more significant between nonocular IBDDAM and BDCAF (p < 0.002). Better concordance was also observed for IBDDAM (nonocular and total) with PGA than BDCAF. The difference was not significant for ocular IBDDAM. The best cutoff point for nonocular IBDDAM was 0.45, for ocular IBDDAM was 3.5, and for BDCAF was 1 point. IBDDAM was the preferred method for the evaluation of disease activity change in patients with BD (without ocular involvement) considering a change of at least 0.45.     

Vascular endothelial and basic fibroblast growth factor serum levels in patients with Behçet’s disease

Behçets disease (BD) is a systemic vasculitis of unknown aetiology. Its pathogenesis is related to endothelial cell dysfunction, humoral immune defects, and immune system dysregulation. The aim of this study was to investigate the possible role of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of BD. We also investigated whether disease activity, age, or duration of BD correlates with VEGF and bFGF. We studied 33 patients and 20 healthy controls. Vascular endothelial growth factor and bFGF serum levels were measured by enzyme-linked immunosorbent assay. We measured acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean serum VEGF level was significantly higher in patients with BD (398.8±222.2 pg/ml) than the control group (193.0±122.4 pg/ml) (P=0.002). The levels were similar in both active and inactive BD (P=0.675) but did not correlate with disease duration, CRP, ESR, or age (P>0.05 for each). The bFGF was below detection limits in 18 of 33 patients with BD and ten of 20 controls, and its mean serum level was higher in BD patients (42.4±76.9 pg/ml) than controls (29.0±9.1 pg/ml), but this difference was not statistically significant (P=0.232). The bFGF levels were similar in both active and inactive BD (P=0.09) and, in patients, correlated with disease duration and CRP (r=0.58, P=0.02; r=–0.57, P=0.02, respectively) but not with ESR or age (P>0.05 for each). Vascular endothelial growth factor may be more important in the pathogenesis of BD than bFGF. Neither growth factor is an activity criterion or inflammatory marker in BD.     

Determination of serum visfatin levels in patients with Behçet’s disease: A case–control study

Aim of the workBehçet’s disease (BD) is an inflammatory, systemic and chronic disorder with unknown etiology affecting multiple systems. Visfatin is a new adipokine with insulin-mimetic properties and pro-inflammatory function. The serum visfatin levels were evaluated in BD patients to investigate its role in the pathogenesis and clinical manifestations of the disease.Patients and methodsForty BD patients were recruited from the Behçet’s disease clinic at Shiraz University of Medical Sciences in southern Iran and 40 healthy control subjects of matching age, sex and body mass index (BMI) were also included. Serum visfatin level was measured using ELISA.ResultsThe 40 BD patients included 16 males and 24 females. Seventeen had active clinical manifestations; 16 with oral ulcer, 5 with genital ulcer, 6 with arthritis and 2 with uveitis. The mean age of the BD patients was 34.95 ± 9.6 years and mean BMI was 23.98 ± 4.44. There were no significant differences between cases (5.05 ± 3.05 ng/ml) and controls (4.72 ± 2.84 ng/ml) in the visfatin level (p = 0.61). The difference in the visfatin level between patients with active and inactive manifestations did not reach statistical significance (6.13 ± 3.20 and 4.25 ± 2.73, respectively; p = 0.07). There was no significant difference according to the gender of the patients or the presence of clinical manifestations.ConclusionIn view of the results in this study, visfatin levels were not significantly different between cases and controls. There was a tendency to a higher level of serum visfatin in active BD patients compared to the inactive cases; however, the difference was unremarkable.     

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

Objective Behçets 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.Methods Forty-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.Results In 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.Conclusions This preliminary study suggests that elevated serum homocysteine levels may play some role in the development of venous and arterial thromboses in BD.     

The prevalence of fibromyalgia in patients with Behçet’s disease and its relation with disease activity

Behçet’s disease (BD) is a chronic disorder characterized by mucocutaneous and multisystem manifestations. Fibromyalgia (FM) is characterized by widespread musculoskeletal pain and may be present concomitantly with several rheumatic diseases. Our aims were to investigate the prevalence of FM in patients with BD and to evaluate the possible relation of FM presence with BD disease activity. A total of 104 Behcet patients were included in this study. Age, sex, disease durations and the BD Current Activity Form (BDCAF) scores as disease activity evaluation were recorded. Presence of FM and the Fibromyalgia Impact Questionnaire (FIQ) scores was investigated. Also, ESR and CRP concentrations were determined in all patients. Mann–Whitney U test and Pearson’s correlation tests were used for the statistical analysis. There were 60 female and 40 male patients with an age range of 19–51 years. Eighteen of 100 BD patients were diagnosed as FM. Although ages, disease duration and laboratory parameters did not differ between BD patients with and without FM, BD patients with FM were more frequently female (p < 0.000). The presence of FM did not differ significantly between patients with and without systemic manifestations. Also, oral–genital ulcers, erythema nodosum, thrombophlebitis, pustular lesions and doctor’s impression of disease activity scores were not found to be different in BD patients with or without FM. However, there were significant differences in fatigue, headache, arthralgia and patient impression of disease activity (today and last 28 days) between these groups (p < 0.000; p < 0.01; p < 0.01; p = 0.021 and p = 0.027, respectively). Also, there were significant correlations between BDCAF and FIQ items that refer pain and fatigue (p < 0.01). FM is a common and important clinical problem that may represent an additional factor that worsens pain and physical limitations in patients with BD. The higher prevalence of FM in patients with BD seems to be affected by BD itself, rather than its severity.     

Etanercept therapy in Behçet’s disease

Study objective

The goal of the present study was to investigate patient outcome when using the TNF receptor fusion protein etanercept in addition to conventional immunosuppressive drugs in ameliorating disease intensity and reducing relapses in refractory Behçet’s disease (BD).

Patients and methods

A single center, prospective study was conducted over 1 year. A total of 15 patients with the established diagnosis of BS were enrolled (mean age: 36.5?±?6.75 years, mean disease duration: 3.86?±?1.30 years). Clinical features were classified as refractory if the patients failed to achieve the desired response within 6 months of immunosuppressive and oral glucocorticoid therapy or flare of lesions developed while on the maximum tolerable doses of these drugs. The study included 2 patients who were on previous infliximab therapy for refractory disease. Inflammatory biomarkers (ESR and CRP) were investigated.

Results

Baseline clinical features in the study prior to inclusion showed recurrent oro-genital ulcers were observed in 100?% of patients, the pathergy test was positive in 17.6?%, ocular involvement was observed in 86.7?%, and acne lesions were recorded in 73.3?%. The following values were also recorded: mean ESR 22?±?16.97 mm/h, mean CRP level 6.87?±?4.44 mg/l, mean visual analog score 5.46?±?1.55, and mean patient global score 5.13?±?1.30. At the beginning of the study, all patients were on oral prednisolone (mean dose: 20.16?±?11.81 mg/day), azathioprine (mean dose: 126.66?±?25.81 mg/day), and oral colchicine (mean dose: 1.08?±?0.10 mg/day), then etanercept was added at a regular weekly dose of 50 mg subcutaneously for 1 year. By 8 weeks, 100?% of the patients achieve the primary endpoint, which included clinical resolution of refractory mucocutaneous, joint, and active ocular lesions with normalization of the acute phase symptoms.

Conclusion

Patients with refractory BD who received a 12-month treatment with etanercept in addition to conventional immunosuppressive therapy achieved a good therapeutic response with successful reduction of oral prednisolone to a mean dose of 6.66?±?2.24 mg/day. No serious infections or drug-related adverse events reported.     

Serum amyloid-A in Behçet’s disease

Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Behçet’s disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement.     

Cardiovascular involvement in Behçet’s disease

Behçet’s disease is a chronic relapsing systemic vasculitis that can involve almost every organ and systems in the body with extremely different diverse manifestations. Cardiovascular involvement is one of these manifestations, the involvement of which might present in various patterns in itself. Cardiovascular involvement is relatively uncommon in Behçet’s disease; however, Behçet’s disease is relatively rather common in certain parts of the world. Therefore, especially in these locations recognizing such miscellaneous presentations are of critical importance, since cardiovascular involvements exceed other presentation in mortality and morbidity rates. Based on these facts, in this review, we summarized the cardiovascular involvements and its different manifestations in Behçet’s disease.     

Endothelial functions in Behçet’s disease

Behçets disease (BD) is a systemic vasculitis, capable of involving all types of vessels. Endothelial dysfunction (ED) has been previously documented in BD. The aim of the study was to see whether ED was more prominent in Behçets patients with vascular involvement (VI) than in those without. The study population consisted of 65 patients with BD, 27 of whom had VI, and 30 healthy controls. High-resolution ultrasound was used to measure endothelium-dependent vasodilatation (EDVD) of brachial artery. Overall, regardless of VI, EDVD was significantly impaired in patients with BD compared with controls (11.4±6.3 vs 20.4±9.1%,P=0.001); however, EDVD was similar in BD patients with and without VI (9.7±6.3% vs 12.6±6.1%, P=0.07). Patients with BD had significantly-higher plasma homocysteine levels than controls (13±6 mol/L vs 9±3 mol/L, P=0.001). Plasma homocysteine levels were significantly higher in the subgroup with VI than in those without (15±7 mol/L vs 12±4 mol/L, P=0.03); however, we found no positive/significant correlation between plasma homocysteine levels and EDVD. ED is a constant feature of BD, regardless of VI. Etiology of ED in BD is probably multifactorial, including high homocysteine levels. As both ED and elevated homocysteine levels may represent an early atherosclerotic process, a more structured approach to risk factor assessment is needed in BD.