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...     

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.     

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.     

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...     

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.     

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.     

Serum Prolactin Levels in Behçet’s Syndrome

Since prolactin (PRL) has been implicated as playing a role in the pathogenesis of certain autoimmune diseases and since Behcet's Syndrome (BS) is a unique systemic vasculitis, we investigated serum PRL levels in patients with BS. We found that mean PRL levels in patients with clinically active BS, were not significantly higher than patients with clinically inactive BS and healthy controls. This finding may be regarded as evidence that a contribution of hyperprolactinemia to the aetiopathogenesis of BS seems unlikely.     

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.     

Importance of serum amyloid-A in Behçet’s disease

Clinical Rheumatology -     

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.     

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.     

Evaluation of pulmonary function and bicycle ergometry tests in patients with Behçet’s disease

Behçet’s disease (BD) has well-defined pulmonary complications, but cardiopulmonary exercise testing and the strength of the respiratory muscles have not been studied in detail. We aimed to investigate the pulmonary functions tests, inspiratory and expiratory muscle strength and endurance, cardiopulmonary exercise test response, and the relationship of these parameters in patients with BD. Forty BD patients and 20 healthy control subjects were recruited for this study. Mean age was 32.95?±?7.66 years for the BD group and 33.85?±?6.63 years for the control group with no statistically significant difference. The ratios of slight obstructive ventilatory impairment were 32.5% for the BD group. When the values of pulmonary function tests were compared, no statistically significant difference was found in FEV₁/FVC (Forced expiratory volume during the first second/forced vital capacity), or maximal midexpiratory flow rate (all in percent) values between patient and control groups. Maximal inspiratory and expiratory pressures, peak expiratory flow rate (in percent) and maximal voluntary ventilation (in percent) values were significantly lower than those of the control group. Body’s consumption of peak oxygen (VO_2peak), oxygen consumption (milliliters per kilogram per minute), anaerobic threshold (AT), maximum exercise ventilation (VE_max), work load values, and exercise test time in the bicycle exercise test were significantly higher in control groups than in patients with BD. The values of heart rate reserve, breathing reserve, and VE/VCO₂ at the AT of BD patients were within normal limits We conclude that respiratory and aerobic exercise may be recommended to improve respiratory muscle strength and endurance as well as the aerobic capacity and maximal ventilatory capacity in patients with BD.     

Interleukin-17F gene polymorphisms in Korean patients with Behçet’s disease

IL-17 is a novel cytokine that is characterized by an ability to induce several types of cells to secrete proinflammatory cytokines in various inflammatory diseases. This study analyzed the influence of IL-17F gene polymorphisms on disease susceptibility and clinical features. Ninety-nine Behçet’s disease (BD) patients and 114 controls were genotyped to analyze three single nucleotide polymorphisms (SNPs) including A126G, G155A, and A161G of the IL-17F gene using automated sequencing. We compared the frequencies of IL-17F alleles, genotypes, and haplotypes in patients with BD and controls using the chi-square or Fisher’s exact test. Significant differences in the frequencies of allele and genotype in A126G SNP of IL-17 gene were found between BD patients and controls (P < 0.001 and P < 0.001, respectively). None of three IL-17F SNPs were associated with diverse clinical features in BD. The frequency of haplotype AA did not differ between patients with BD and controls (P = 0.985). The haplotypes, AG, and GG, have positive and inverse association with BD susceptibility (P < 0.001 and P < 0.001, respectively). These findings suggest that IL-17 gene SNPs may influence the susceptibility of BD.     

Successful treatment of life-threatening intestinal ulcer in Behçet’s disease with infliximab: rapid healing of Behçet’s ulcer with infliximab

Behçet’s disease is a chronic, relapsing, multisystem inflammatory disorder characterized predominantly by recurrent orogenital ulcers, skin involvement, and uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases, but ocular, gastrointestinal, and central nervous system involvement may occur in severe cases. We report in this study the successful treatment with infliximab of severe life-threatening GI bleeding caused by an ileal ulcer in a patient with Behçet’s disease. Antitumor necrosis factor (TNF) therapy could be an emergency therapeutic option in patients with massively bleeding Behçet’s disease and unstable patients or those with acute bleeding with other TNF-α-mediated autoimmune diseases. Another option for anti-TNF therapy could be as bridging management between conservative and surgical treatment.     

Evaluation of asymptomatic venous disease by Doppler ultrasonography in Behçet’s disease patients

Aim of the work

Evaluation of asymptomatic venous disease in patients with Behçet’s disease (BD) using venous Doppler ultrasonography (US) and its relation to different disease manifestations and activity.

Decreased serum level of antibody against human cytomegalovirus in patients with Behçet’s disease

Behçets disease (BD) is a connective tissue disorder characterized by recurrent orogenital ulcer, uveitis, and skin lesions. Recurrent aphthous ulcer is associated with human cytomegalovirus (HCMV). To investigate the possible role of HCMV in BD, we measured the titers of IgG, IgM, and IgA anti-HCMV antibodies in 73 Korean patients with BD, 50 with scleroderma, 70 with systemic lupus erythematosus, and 50 from healthy controls by indirect immunofluorescent staining. The titer of IgG anti-HCMV antibody was significantly lower in patients with BD than in controls (geometric mean 3115.4 vs 9687.6, P=0.0001 by Wilcoxons rank sum test), as was the titer of IgA anti-HCMV antibody (geometric mean 1.9 vs 15.7, P=0.0001, Wilcoxons rank sum test). In conclusion, we found significantly lower antibody responses to HCMV in patients with BD.     

Assessment of aortic stiffness and ventricular diastolic functions in patients with Behçet’s disease

Background: Behçets disease is a systemic vasculitis in which studies have given conflicting results about ventricular diastolic functions. However, tissue Doppler echocardiography has never been used in any of these studies. Aortic stiffness, a cardiovascular risk factor, may also precede ventricular dysfunction. Objectives: The aim of this study was to assess aortic stiffness and biventricular diastolic functions in patients with Behçets disease. Methods: A total of 26 patients with Behçets disease (mean age; 33±10 years) and 20 age- and sex-matched controls (mean age; 33±7 years) were included. Aortic stiffness was evaluated by aortic strain and distensibility. Ventricular diastolic functions were evaluated with both conventional and tissue Doppler echocardiography. Mitral E and A wave, E/A ratio of E wave, deceleration time, and isovolumic relaxation time were calculated. Results: There was no significant difference in diastolic Doppler parameters between patients and controls. Similarly, there was no significant difference in mitral annular E and A velocities between these two groups. Aortic strain in patients with Behçets disease was found to be significantly less than in the controls (8.3±4.9% and 15.7±2.7% respectively, p<0.001). Aortic distensibility was also significantly low in patients with Behçets disease when compared to controls (0.45±0.28 and 0.78±0.13 respectively, p<0.001). Beta index values were significantly high in Behçets patients (7.23±5.93 and 2.69±0.55 respectively, p<0.001). Conclusion: No significant diastolic dysfunction was found in left and right ventricles in patients with Behçets disease by using both conventional and tissue Doppler echocardiography. However, an increase in aortic stiffness was found, suggesting an inflammatory involvement of proximal aorta.