Disease Activity Of Behçet's Disease Research Articles

Association of high disease activity and serum IL-6 levels with the incidence of inflammatory major organ events in Behçet disease: a prospective registry study.

Little is known about the relationship between the disease activity of Behçet disease (BD) and the incidence of inflammatory major organ events. In this prospective registry study, we investigated the association between the Behçet Disease Current Activity Form (BDCAF) and incidence of inflammatory major organ events, defined as the inflammation of the ocular, central nervous, intestinal, and vascular systems in BD. We enrolled participants from Japanese multicenter prospective cohorts. The BDCAF was evaluated annually. BD-related symptoms, including inflammatory major organ events, were monitored. The association between BDCAF and inflammatory major organ events was analyzed by time-to-event analysis. An unsupervised clustering of the participants' BDCAF, therapeutic agents, and multiple serum cytokines was also performed to examine their association with inflammatory major organ events. A total of 260 patients were included. The patients had a median BDCAF score of 2 [Interquartile range, 1-3] at the enrolment and remained disease active at 1- and 2-year follow-ups, indicating residual disease activity in BD. Patients with a BDCAF score of 0 had a longer inflammatory major organ event-free survival at 52 weeks than those with a score of 1 or higher (p=2.2 x 10-4). Clustering analysis revealed that patients who did not achieve remission despite treatment with tumor necrosis factor inhibitors had high serum inflammatory cytokine levels and incidences of inflammatory major organ events. Among the elevated cytokines, IL-6 was associated with inflammatory major organ events. This study suggests that treatment strategies targeting overall disease activity and monitoring residual serum IL-6 may help prevent inflammatory major organ events in BD.

Does Behcet’s disease affect the quality of sleep?

This research aimed to evaluate the sleep quality (QoS) in individuals with Behçet's disease (BD) compared to a control group of healthy individuals. Additionally, it sought to investigate any possible correlation between BD activity and sleep quality. In this case-control study, individuals with BD and healthy controls, matched for age and gender, were enrolled. The study collected demographic information, body mass indexes (BMI), and disease durations. The BD Behcet disease current activity form (BDCAF) was employed to gauge the disease activity of BD, while the Pittsburgh Sleep Quality Index (PSQI) was utilized to evaluate the QoS. PSQI scores were compared between the patients and controls and the possible correlation between PSQI and BDCAF scores were investigated. Besides, demographic features, disease characteristics, total score and sub parameters of disease activity were compared between BD cases with and without poor QoS. Among 56 BD patients and 56 controls, there were no significant differences in age, gender distribution, or BMI. BD cases demonstrated significantly higher QoS scores than controls (PSQI score: 6.5±4.84 in cases, 3.7±1.48 in controls, p=0.022). While no correlation was observed between PSQI, demographic characteristics, and disease duration, a notable positive correlation emerged between PSQI and BDCAF total score (p=0.037, r=0.458). No statistical difference was determined between demographic data, disease duration, and BDCAF sub parameters between patients with poor (24 patients, 42%) and without poor QoS (32 patients, 58%); however, the total score of BDCAF was significantly higher than those of BD with low QoS (p= 0.021). Our study data suggest that impaired sleep quality in BD cases may be linked to overall disease activity, irrespective of the specific form of involvement. Consideration of QoS in the management of BD will contribute to a holistic approach to the disease.

Characterisation of circulating endothelial microparticles in Behçet's disease: new markers of chronic endothelial damage?

Endothelial cell-derived microparticles (EMPs) are directly indicative of endothelial cell activation or apoptosis, and may also reflect endothelial inflammation, increased coagulation, and vascular tone. The aim of this study is to investigate whether EMPs would be able to evaluate system involvement and be a new indicators of disease activity in Behçet's disease (BD). Thirty-nine consecutive BD patients (who fulfilled the modified 1990 International Study Group on Behçet's disease or the 2006 International Criteria for Behçet's Disease) and 30 age- and sex-matched healthy controls were enrolled. The plasma levels of EMPs were measured by flow cytometry utilising specific labels for endothelial MPs (CD31+ and CD42b-). The levels of circulating EMPs (CD31+ and CD42b-) were significantly elevated in the case group compared with the healthy control group (p =0.000). Moreover, BD patients plasma EMPs were positively correlated with BD current activity form (r=0.802, p =0.000). Vascular and gastrointestinal involvement in BD patients were significantly increased (p=0.004 and p=0.011, respectively) with respect to patients without vascular and gastrointestinal EMPs. Levels of circulating EMPs are elevated in BD patients and correlate with the disease activity; the elevated EMPs may be a potential indicator to predict disease activity of BD. The plasma level of EMPs was increased, which indicated the increased risk of vascular and digestive tract involvement in BD.

An investigation of the relationship between rheumatological diseases and soluble receptor for advanced glycation end products.

Soluble receptor for advanced glycation end products (sRAGE) is one of the forms of RAGE. It is a trap receptor that has a role in inhibiting pro-inflammatory processes that will occur with the combination of RAGE and its ligands. Our study aims to examine the level of sRAGE in rheumatological inflammatory diseases and its relationship with these diseases. A total of 60 patients with Behçet's disease (BD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and 22 healthy control individuals were included in the study. Comorbidity status, sRAGE levels, disease activity scores, demographic and laboratory data of the patients were recorded. Serum sRAGE levels in these diseases and healthy controls were determined by Enzyme-Linked Immunosorbent Assay (ELISA) kit spectrophotometrically. Serum sRAGE levels in the patient groups were significantly higher when compared to the healthy control group (p < 0.001 for all). On the other hand, when the patient groups were compared with each other in terms of sRAGE levels, there was no significant difference (p > 0.05 for all). The serum sRAGE levels were not correlated with C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and disease activity scores (p > 0.05 for all). Serum sRAGE levels increased in BD and in other inflammatory rheumatological diseases. However, this increase does not directly correlate with inflammatory markers and disease activity scores. These results suggest that serum sRAGE level may not be used as a biomarker for disease activity in BD and in other rheumatological diseases.

Nanocurcumin supplementation ameliorates Behcet’s disease by modulating regulatory T cells: A randomized, double‐blind, placebo‐controlled trial

Current research was designed to assess the effects of nanocurcumin supplementation on regulatory T (Treg) cells frequency and function in Behçet's disease (BD). In this randomized double-masked, placebo-controlled trial, 36 BD subjects were randomly put into two groups to take one 80 mg nanocurcumin capsule or placebo daily for 8 weeks. Before and after trial, disease activity, Treg cells frequency and expression of related immunologic parameters including forkhead box protein P3 (Foxp3) transcription factor messenger RNA (mRNA) and microRNAs (miRNAs) such as miRNA-25 and miRNA-106b as well as cytokines including transforming growth factor (TGF)-β and interleukin (IL)-10 were studied. Thirty-two patients (17 in the nanocurcumin and 15 in the placebo groups) completed the trial. Treg cells frequency increased significantly in the nanocurcumin group compared with baseline (P < 0.001) and placebo group (P < 0.001). Moreover, FoxP3, TGF-β, IL‐10, miRNA-25, and miRNA-106b mRNA expression levels increased considerably in the nanocurcumin group compared to baseline (P < 0.001) and placebo group (P < 0.001, P < 0.001, P = 0.025, P = 0.011, and P < 0.001, respectively). Significant increases in serum TGF-β and IL-10 were seen in nanocurcumin group compared with baseline (P < 0.001) and placebo group (P = 0.001 and P < 0.001, respectively). Significant decrease in disease activity was found in nanocurcumin group compared with placebo group (P = 0.044). Our study provided a promising view for desirable effects of nanocurcumin supplementation in improving immunological parameters and disease activity in BD.

Development of an Arabic version of the Behçet's Disease Current Activity Form (Ar-BDCAF): cross-cultural adaptation and validation initiative in Egypt.

Behçet's disease (BD), commonly seen in the Silk road countries, is a variable vessel vasculitis with no specific investigation that reflects disease activity. The Behçet's Disease Current Activity Form (BDCAF) is the most famous and acceptable clinical activity score. To develop a cross-cultural adaptation of the BDCAF to the Arabic language (Ar-BDCAF)-Egyptian dialect-across the country and to consider preliminary evaluation of its reliability in assessment of BD activity. The score was translated to Arabic language and revised by 3 rheumatology consultants. Reliability of Ar-BDCAF was tested among 88 BD patients from 9 Egyptian main city centers. Patients were questioned by two specialists at 30min interval to evaluate inter-observer rating and twice by the same physician within 24h to assess the intra-observer rating. Patients were 64 males and 24 females (2.7:1) with a mean age of 35 ± 10.3years. The average time required by the consultant to fill in the form was 5.1 ± 2.2min (1.5-15min). The mean Ar-BDCAF scores were 9.81 ± 6.22 (0-25) and 9.53 ± 6.13 (0-28) with an intra-observer concordance (p = 0.28) and was 9.95 ± 6.47 (0-29) for the inter-observer rating (p = 0.89 and p = 0.66, respectively). The Ar-BDCAF is a measurable, easy to calculate, and reliable index for assessing disease activity in Egyptian BD. The Ar-BDCAF score can be used in daily clinical practice to assess BD activity and its use can be extended to other Arab countries for possible regional validation and adaptations. Key Points • The Arabic version of the BDCAF can be extended to other Arab countries for development of a Pan-Arab score. • This is the first study to provide a reliable and valid Arabic version of the BDCAF-Egyptian dialect for measuring current disease activity in BD patients.

Correlation of clinical signs and symptoms of Behçet's disease with platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR).

Behçet's disease (BD) is a chronic disorder that involves multiple organs and is pathologically considered as a form of vasculitis. The current study aims to assess the metric properties of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in assessing BD disease activity. Three-hundred-nineteen patients with BD were enrolled in this cross-sectional study. Demographic and epidemiological data, including IBDDAM, time since the onset, and medication and manifestation history were recorded. Complete blood counts (CBC), NLR, and PLR were assessed by analyzing blood samples. On the last visit, patients were assessed for active manifestations of disease. IBDDAM and ocular IBDAAM scores were calculated for activity of disease in each patient. Both PLR and NLR were higher in patients with active BD (Mann-Whitney U test, p-value < 0.05). Patients with active ocular manifestation had significantly higher NLR and PLR (Mann-Whitney U test, p-value < 0.05). These ratios, however, were not associated with other active BD manifestations. A value of NLR > 2.58 had 46% sensitivity and 85% specificity for the diagnosis of active ocular manifestations (AUC: 0.690). NLR had a significant, though, weak positive correlation with IBDDAM (Spearman's rho = 0.162; p-value < 0.05) and ocular IBDDAM (Spearman's rho = 0.159; p-value < 0.05). Active Behçet's presented with higher NLR and PLR ratios; however, there was only a modest correlation between NLR and BD activity (IBDDAM score). Also, NLR and PLR have significant relationship with ocular features of BD patients.

Can decreased monocyte to HDL-cholesterol ratio be a marker indicating the anti-inflammatory effect of the colchicine in Behçet's disease? A preliminary study.

Behçet's disease (BD) is an auto-inflammatory disease characterized by systemic vasculitis. Monocyte to HDL-cholesterol ratio (MHR), monocyte to lymphocyte ratio (MLR), and neutrophil to lymphocyte ratio (NLR) are used as inflammatory markers in many disorders. Colchicine decreases inflammation by suppressing the secretion of pro-inflammatory cytokines. This study aims to examine the effects of colchicine treatment on MHR, MLR, and NLR levels of the patients with BD. In this study, 80 patients, who were with mild/moderate/severe BD based on the Krause's Clinical Severity Scoring for BD and received colchicine treatment for at least 3 months, were evaluated retrospectively. The results of MHR, MLR, NLR, and other hematological parameters were assessed in three groups as follows: precolchicine treatment (Group 1), at the end of the 1st month of the treatment (Group 2), and at the end of the 3rd month of the treatment (Group 3). A total of 80 patients involving 39 (48.75%) females and 41 (51.25%) males, who were treated with colchicine due to the diagnosis of BD, were examined in this study. The mean age of the patients was 36.85 ± 10.659 (18-59) years. The findings showed that there was a statistically significant reduction in MHR, MLR, and NLR levels of postcolchicine treatment (P = .0004, P = .0007, and P = .0003, respectively). MHR level was 0.015 ± 0.005 in Group 1, 0.013 ± 0.004 in Group 2, 0.011 ± 0.004 in Group 3, while MLR level was 0.346 ± 0.131 in Group 1, 0.277 ± 0.098 in Group 2, 0.229 ± 0.08 in Group 3, and NLR level was 2.528 ± 0.999 in Group 1, 2.001 ± 0.672 in Group 2, 1.704 ± 0.619 in Group 3. A significant association was found between the MHR value of pretreatment and the clinical severity of BD (P = .04). The findings obtained in this study suggest that we can determine the anti-inflammatory impact of colchicine in BD using MHR, MLR, and NLR markers, and MHR can also be a potential index for assessing the disease activity of BD.

Use of prognostic nutritional index in the evaluation of disease activity in patients with Behçet's disease.

Behçet's disease (BD) is a chronic, multisystem disorder that can cause severe morbidity and mortality. Monitoring tools that measure disease activity are required for effective management of BD. We aimed to investigate the association of prognostic nutritional index (PNI) with disease activity in BD. In this cross-sectional study, we enrolled 88 adult patients with BD and 51 healthy controls. The patients were divided into patients with active and inactive BD according to their disease activities. PNI was calculated using the following formula: 10×serum albumin (g/dL)+0.005×peripheral lymphocyte count (per mm3). To evaluate BD activity, the Behçet Disease Current Activity Form was used. The relations of BD activity with PNI, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, erythrocyte sedimentation rate, and C-reactive protein were investigated. A receiver operator characteristic curve analysis was used to define the optimum cutoff value of PNI for active BD. A total of 48 patients were classified as having active BD and 40 as having inactive BD. Patients with active BD had lower mean PNI than patients with inactive BD and healthy controls (51.8±4.2, 57.4±2.9, and 56.6±3.6, respectively; p<0.001). In multivariate analysis, PNI was the only independent predictor of BD activity (odds ratio, -0.687; 95% confidence interval 0.548-0.861; p=0.001). The optimum cutoff of PNI for active BD was 55.35 with 79.2% sensitivity and 77.75% specificity. PNI was significantly associated with BD activity. PNI may be a useful tool for the assessment of disease activity in BD.

Neutrophil-to-lymphocyte ratio, mean platelet volume and platelet-to-lymphocyte ratio in Behçet's disease and their correlation with disease activity: A meta-analysis.

We aimed to evaluate the relationship between mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Behçet's disease (BD). We searched Medline, Embase, and Cochrane databases, and performed a meta-analysis to compare MPV, NLR, and PLR between patients with BD and healthy controls, and to evaluate these parameters in BD according to disease activity and thrombosis. In total, 14 studies were included. MPV was not higher in the BD group than in the control group (standardized mean difference [SMD], 0163; 95% confidence interval [CI], -0.125 to 0.451; P=0.268), while NLR was significantly higher in the BD group than in the control group (SMD, 1.176; 95% CI, 0.392-1.960, P=0.003) and PLR showed a non-significant trend of association with BD (SMD, 0.441; 95% CI, -0.025 to 0.907, P=0.063). MPV did not differ between patients with active and inactive BD (SMD, -0.129; 95% CI, -0.323 to 0.085, P=0.191), and between patients with BD with and without thrombosis (SMD, 0.231; 95% CI, -0.155 to 0.617, P=0.241). Conversely, NLR was significantly higher in patients with active BD than in those with inactive BD (SMD, 1.774; 95% CI, 0.179-3.368, P=0.029), but not significantly higher in patients with BD with thrombosis than in those without thrombosis (SMD, 0.258; 95% CI, -0.277 to 0.792, P=0.345). This finding suggests that NLR may be a potential index to evaluate the disease activity of BD, although there are limitations of small number of studies and heterogeneity of individual characteristics.

Clinical significance of endocan in Behçet’s disease patients: A potential marker of disease activity

BackgroundEndothelial cell dysfunction has been described in Behçet disease (BD) not only as a cause of major vascular events but also related to chronic inflammation in different organ systems. Aim of the workTo study the relation of serum endocan, a marker of endothelial dysfunction, with clinical manifestations and disease activity in BD patients. Patients and methodsThis study included 23 BD patients and 23 matched controls. Disease activity was assessed by the Behcet Disease Current Activity Form (BDCAF). Serum endocan was measured in all subjects. ResultsThe mean age of the patients was 32.5 ± 6.8 years and they were 16 males and 7 females (M:F 2.3:1) with mean disease duration of 7 ± 5.2 years. Their mean BDCAF was 2.26 ± 1.32. A significant difference was found between serum endocan level among active patients 328.24 ± 195.3 ng/L, inactive patients (169.8 ± 35.7 ng/L) and controls (160.6 ± 39.7 ng/L)(p = 0.001). Patients with genital ulcers, papulopastular lesions and arthritis at the time of the study had higher serum endocan level than those without (p = 0.002, p = 0.006 and p = 0.0001 respectively). Serum endocan levels correlated significantly with the BDCAF, neutrophil/lymphocyte ratio, platelet lymphocyte ratio and C-reactive protein (r = 0.94, p = 0.0001; r = 0.82, p = 0.0001, r = 0.44, p = 0.04 and r = 0.48, p = 0.02 respectively). The optimum serum endocan cut-off point for active BD was 191.5 ng/L with a sensitivity and specificity of 100% and 86% respectively (area under curve 0.99, 95% confidence interval 0.96-1). ConclusionSerum endocan may serve as a potential marker of disease activity in BD. Patients with genital ulcers, papulopastular lesions and arthritis showed higher serum endocan levels.

Quality of life impairment in Behçet's disease and relationship with disease activity: a prospective study.

Our aim was to prospectively investigate the impact of Behçet's disease (BD), disease activity, and clinical and demographic characteristics on different aspects of quality of life (QoL) measured by the short-form (SF)-36 QoL scale. We administered the SF-36 to 37 consecutive BD patients in different moments of disease activity, and to 23 healthy controls (HC). The eight subcategories of the SF-36 underwent statistical analysis for identifying differences and correlations. Compared to HC, BD patients showed significantly lower mean scores in all SF-36 QoL subscales except mental health and role-emotional. Females showed a poorer QoL compared to males. Disease activity evaluated by the BD Current Activity Form inversely correlated with physical functioning (ρ=-0.68, p<0.0001), bodily pain (ρ=-0.68, p<0.0001), role-physical (ρ=-0.64, p<0.0001), vitality (ρ=-0.64, p<0.0001), general health (ρ=-0.64, p<0.0001), social functioning (ρ=-0.50, p=0.0002), mental health (ρ=-0.48, p=0.0004), and role-emotional (ρ=-0.40, p=0.003). Mucosal, central nervous system (CNS), musculoskeletal and ocular manifestations were the main factors that negatively affected QoL in BD. For ocular disease, physical functioning was significantly impaired in patients with panuveitis compared to other ocular manifestations (p=0.0002). Best-corrected visual acuity was inversely correlated with social functioning (ρ=-0.53, p<0.0001), role-physical (ρ=-0.48, p<0.0001), bodily pain (ρ=-0.46, p=0.02), and mental health (ρ=-0.43, p<0.0001). Patients with BD have a poorer QoL compared to HC, particularly for women, while the decline of QoL is closely related to the overall disease activity of BD. Single organ involvements may affect independently specific SF-36 subscales, especially mucosal, CNS, musculoskeletal, and ocular manifestations.

Increased serum interleukin-32 levels in patients with Behçet's disease.

Interleukin (IL)-32 is known to act as a proinflammatory cytokine and is likely involved in several chronic inflammatory diseases. The aims of this study were to investigate whether serum IL-32 levels are elevated in patients with Behçet's disease (BD) and to identify the correlation between IL-32 levels and disease activity. We enrolled 50 patients with BD and 35 healthy controls. Serum IL-32 levels were measured using an enzyme-linked immunosorbent assay. Serum levels of IL-12p70, IL-17A, IL-1β, IL-6 and IL-8 were measured using a multiplex assay. BD disease activity was determined using the Behçet's Disease Current Activity Form (BDCAF). Serum IL-32 levels were significantly higher in patients with BD (median [interquartile ranges], 0.4 [0.1-736.2] pg/mL) than in healthy controls (0.1 [0.1-14.7] pg/mL, P = 0.041). When patients with BD were divided into active (patient index score ≥ 2 or transformed index score ≥ 5 in the BDCAF) and inactive groups, IL-32 levels tended to be higher in patients with active BD, although this observation was statistically insignificant. Serum levels of IL-12p70, IL-17A, IL-1β, IL-6 and IL-8 did not differ between active and inactive groups. There was a weak positive correlation between serum IL-32 levels and BDCAF scores (R = 0.301, P = 0.033). BD patients with recent arthralgia exhibited higher IL-32 levels than did those without (P < 0.001). These findings suggest that IL-32 may play a minor role in the pathogenesis of BD.

Serum GDF-15 level in Behçet's disease: relationships between disease activity and clinical parameters.

Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily of cytokines, plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate serum GDF-15 levels and their relationships with disease-related variables in patients with Behçet's disease (BD). Forty-six patients diagnosed with BD and 30 demographically matched healthy control subjects participated in the study. GDF-15 levels were measured in blood samples from patients and controls. The Behçet's Disease Current Activity Form (BDCAF) was used to evaluate the disease activity of BD. There were no significant differences between the two groups in C-reactive protein (CRP) level, mean erythrocyte sedimentation rate (ESR), age, body mass index, and mean GDF-15 levels (P > 0.05). Serum GDF-15 levels were positively correlated with findings for peripheral arthritis and CRP, and with BDCAF erythema nodosum, BDCAF arthralgia, and BDCAF arthritis scores. Patients with BD were divided into two groups according to the presence of peripheral arthritis; nine subjects (20%) were positive for peripheral arthritis. Serum ESR, CRP, white blood cell counts, and GDF-15 levels were significantly higher in the group that was positive for peripheral arthritis (P < 0.05). GDF-15 may play a role in the progression and pathway of Behçet's joint involvement and erythema nodosum that is independent of classic inflammatory response measures.

Paediatric Behçet's disease: a UK tertiary centre experience.

There are currently limited data regarding paediatric Behçet’s disease (BD), particularly in the UK. We describe the clinical spectrum, treatment and outcome of BD, and explore the relative sensitivities of the criteria for the diagnosis of BD in a UK paediatric cohort. Single retrospective case note review of children with a clinical diagnosis of BD presenting between 1987 and 2012. Demographics, clinical features, treatment and outcomes were recorded. The sensitivities of the International Study Group (ISG) and International Criteria for BD (ICBD) criteria were explored. BD disease activity was calculated using the Behçet’s Disease Activity Index (BDAI). Forty-six patients (22 male) were identified. Median age of onset was 4.87 (0.04–15.71) years; median time to diagnosis was 3.74 (0.25–13.48) years. Clinical features were recurrent oral ulceration (97.8 %), recurrent genital ulceration (73.9 %), gastrointestinal (58.7 %), musculoskeletal (47.83 %), cutaneous (23.9 %) involvement and uveitis (2 %). Recurrent genital ulceration was more common in female patients (P = 0.044). Thirty-seven patients (80.4 %) fulfilled the ICBD criteria; only 12 patients (26.1 %) fulfilled the ISG criteria. BDAI score at diagnosis was 7/20 (0–10/20) and significantly decreased to 5/20 (0–9/20) (P < 0.0001) at latest follow-up. The commonest systemic treatment was colchicine (76.1 %); anti-TNFα treatment was reserved for severe cases (15.5 %). Paediatric BD in the UK may present very early in life, sometimes with a family history, and with a low incidence of ocular involvement. Diagnostic delay is common. The majority of our patients required systemic therapy; anti-TNFα was reserved for severe cases and has largely superseded the use of thalidomide.Electronic supplementary materialThe online version of this article (doi:10.1007/s10067-016-3187-z) contains supplementary material, which is available to authorized users.

Serum levels of alpha-1 acid glycoprotein and pentraxin 3 in patients with Behçet's disease and relationship with disease activity.

To evaluate the relationship between disease activity and levels of alpha 1-acid glycoprotein and pentraxin 3 in patients with Behçet's disease (BD). Forty-eight patients with BD and 29 age- and gender-matched healthy control subjects were included in the study. Serum pentraxin 3 levels were measured using enzyme-linked immunosorbent assay (ng/ml), and alpha 1-acid glycoprotein levels were measured using nephelometry (mg/dl). Disease activity was assessed using the BD Current Activity Form (BDCAF). Serum alpha-1 acid glycoprotein levels were significantly higher in patients with BD compared to the control group (P = 0.048). There were no significant differences between two groups in terms of levels of pentraxin 3 (P = 0.697). According to Pearson's analysis, alpha 1-acid levels are significantly positively correlated with erythrocyte sedimentation rate, C-reactive protein, and skin lesions and arthritis of BDCAF scores. Pentraxin 3 levels did not correlate with erythrocyte sedimentation rate, C-reactive protein, or any domains of BDCAF scores. The results of the present study demonstrate that serum levels of alpha-1 acid glycoprotein were significantly higher in patients with BD relative to the control group. Alpha-1 acid glycoprotein is greatly associated with skin lesions and arthritis in patients with BD. We did not find high serum levels of PTX3 in patients with BD compared to healthy controls, and pentraxin 3 is not associated with disease activity 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.

Serum levels of GRO‐α are elevated in association with disease activity in patients with Behçet’s disease

Although the etiology of Behçet's disease (BD) is still unknown, neutrophils are implicated in its pathogenesis. Growth-related oncogene-α (GRO-α) is a potent chemoattractant and activator for neutrophils. To determine the role of GRO-α in the pathogenesis of BD, we investigated serum GRO-α levels in patients with BD. Sera from patients with BD (n=57) and control subjects (n=26) were measured by enzyme-linked immunosorbent assay. Serum levels of GRO-α were compared with clinical symptoms. Patients with BD had significantly elevated serum GRO-α levels compared with healthy controls (121.7±79.2pg/ml vs. 75.9±20.6pg/ml, P<0.01). Concerning the subgroups of BD, serum GRO-α levels in active patients with BD (n=35) were significantly higher than in inactive patients with BD (n=22; 139.0±92.8 pg/ml vs. 94.3±36.2pg/ml, P<0.05). Also, as seen in previous studies, serum interleukin-8 levels in patients with BD (52.4±81.8pg/ml) were significantly higher than in controls (13.9±19.7pg/ml, P<0.01). Enhanced GRO-α levels correlated with clinical symptoms such as erythema nodosum. Our results indicate that serum levels of GRO-α are elevated in patients with active stage BD, suggesting that GRO-α may serve as a reliable marker for disease activity of BD.

Granulysin-producing cytotoxic T cells in the mucocutaneous lesions of Behçet disease: a distinct inflammatory response from erythema nodosum

Cytotoxic T lymphocytes (CTLs) have been recognized as an important effector cell in Behçet disease (BD). Granulysin is a cytolytic granule protein expressed by CTLs and natural killer cells. To evaluate the involvement of granulysin-producing T cells in the pathogenesis of BD. Using immunohistochemistry, lymphocyte subsets expressing granulysin were investigated in mucocutaneous lesions of BD. Serum granulysin levels were assayed by ELISA. Granulysin-positive cells were seen in specimens from oral ulcers, genital ulcers and acne-like eruptions, but not erythema nodosum-like lesions. Both CD4+ and CD8+ T cells expressed granulysin. Serum granulysin levels did not correlate with disease activity in BD. Immune reactions mediated by granulysin-positive CTLs may play an important role in the pathogenesis of acne-like eruptions, oral ulcers and genital ulcers in BD.

Pathophysiology of the Behçet's Disease

Behçet's disease (BD) is a multisystemic disease of unknown etiology characterized by chronic relapsing oral-genital ulcers and uveitis. Multiple systemic associations including articular, gastrointestinal, cardiopulmonary, neurologic, and vascular involvement are also observed in BD. Although the etiopathogenesis of the disease remains unknown, increased neutrophil functions such as chemotaxis, phagocytosis, and excessive production of reactive oxygen species (ROS), including superoxide anion, which may be responsible for oxidative tissue damage seen in BD, and also immunological alterations, T lymphocyte abnormalities in both subpopulation and function have been considered to be correlated with the etiopathogenesis of BD. There is some clinical evidence suggesting that emotional stress and hormonal alterations can influence the course and disease activity of BD.