Clinical and experimental rheumatology最新文献

Objectives: To evaluate microcirculation abnormalities and their clinical association in patients with BS, especially with vascular manifestations.

Methods: A cross-sectional study was carried out using nailfold videocapillaroscopy (NVC) to evaluate the microcirculation in patients with BS.

Results: A total of 65 patients were included in the study. Thirty-four (52.3%) were men, and 84.6% were European Caucasian. Vascular involvement was present in 24 (36.9%) patients. Qualitative abnormalities in NVC were observed in 47.7% of patients. The most frequent were tortuous and branched capillaries (21.5%), followed by microhaemorrhage (12.3%), enlarged capillary (7.7%) and giant capillary (3.1%). We found a significant relationship between the presence of tortuous and branched capillaries and previous superficial thrombophlebitis (ST) (p=0.025). The presence of ≥2 qualitative abnormalities in NVC was associated with vascular involvement (p=0.031), mainly with venous thrombotic events (p=0.024) and particularly with ST (p=0.003). No specific Cutolo's pattern was observed. No association was observed between NVC and Raynaud's phenomenon or ANA, although patients with positive ANA presented more frequent non-specific capillaroscopic abnormalities (p=0.003).

Conclusions: The presence of ≥2 qualitative abnormalities in NVC is associated with Vasculo-Behçet. NVC might be a potential tool for early detection of patients at risk of vascular events.

Objectives: The HLA-B51 locus has the strongest association with Behçet's syndrome (BS). The presence of a CpG island in the HLA-B gene led us to examine the role of epigenetic regulation in BS.

Methods: HLA-B51 genotyping was performed via sequence-specific PCR in 15 index familial BS cases, 17 affected relatives, 26 unaffected relatives, 46 sporadic BS cases, and 41 healthy controls. HLA-B methylation level was determined using the Zymo OneStep qMethyl kit, and HLA-B51 mRNA level was assessed by quantitative real-time PCR in 14 index familial BS cases, 15 affected relatives, 15 unaffected relatives, 11 sporadic BS cases, and 10 healthy controls.

Results: HLA-B51 carrier ratio was 13/15 in index familial cases, 13/17 in affected relatives, 22/26 in unaffected relatives, 8/25 in healthy controls, and 35/47 in sporadic BS cases. HLA-B51 expression level in HLA-B51+ BS cases was 2.2-fold higher than in their unaffected relatives (p=0.0149) and 1.3-fold higher than in healthy controls (p=0.0188), while sporadic BS cases had a 2.7-fold higher level than healthy controls (p=0.0487). HLA-B promoter methylation was significantly lower in HLA-B51+ familial BS cases than in unaffected relatives (0.4-fold, p=0.01), affected relatives (0.36-fold, p=0.0219), and healthy controls (0.34-fold, p=0.0371) and slightly lower in HLA-B51+ sporadic BS cases than in healthy controls (0.71-fold, p=0.2347). There was an inverse correlation between HLA-B promoter methylation and HLA-B51 expression in HLA-B51+ sporadic BS cases (p=0.0164).

Conclusions: This study indicates epigenetic involvement associated with the HLA-B51 locus in BS, both in familial and sporadic cases. Further studies with larger sample sizes are needed to confirm our results.

Objectives: To evaluate common femoral vein thickness (CFVT) as a diagnostic tool in Brazilian patients with Behçet's disease (BD) and to analyse associations between increased CFVT and disease features.

Methods: A cross-sectional study was performed including 100 BD patients and 100 controls. The CFVT and the diameters of great saphenous vein (GSV), and small saphenous vein (SSV) were measured by Doppler ultrasound.

Results: BD patients had higher right CFVT [0.600mm (0.500-0.700) vs. 0.525mm (0.450-0.637); p=0.012] and left CFVT [0.550mm (0.450-0.650) vs. 0.500mm (0.450-0.550); p=0.004] compared to controls. Vascular involvement of BD and previous deep venous thrombosis were associated with increased CFVT (p<0.05). The number of vascular events correlated with right and left CFVT (Rho = 0.475 p=0.030 and Rho = 0.429 p=0.052, respectively). The 0.575mm cut-off point of right and left CFVT had area under the curve (AUC) of 0.602; 95% confidence interval (95% CI): 0.524-0.680 and AUC: 0.615; 95% CI: 0.537-0.693, respectively. The right and left CFVT had a sensitivity for BD diagnosis of 52% and 43%, and a specificity of 64% and 77%, respectively. No significant differences were found between BD patients and controls regarding the GSV and SSV diameters in both legs (p>0.05).

Conclusions: In this study, CFVT measurement was not shown to be a reliable diagnostic test for BD. CFVT was increased in BD patients presenting vascular involvement and correlated with the number of previous events.

Objectives: Hughes-Stovin syndrome (HSS) is a rare inflammatory condition defined as pulmonary artery aneurysms (PAA) associated with deep vein thrombosis. It is similar to vascular involvement of Behçet's syndrome (BS), but differs in the absence of typical skin-mucosal findings. Whether HSS is a distinct entity or a form fruste of BS is debated. We formally compared HSS cases retrieved from the literature to BS patients with PAI followed by a tertiary centre.

Methods: A systemic literature search using 'Hughes Stovin syndrome' as the key word covering the period between 2000 and 2023 revealed 58 (43 M/15 F) case reports (PROSPERO: CRD42023413537). We identified 74 (62M/12 F) BS patients with PAI followed up in a tertiary centre in Turkey from 2000 until 2020. We evaluated two cohorts head-to-head in terms of demographic and clinical features.

Results: BS and HSS patients were found to be comparable with regard to several demographic, clinical and histopathological features. However, PAA were significantly more frequent and isolated pulmonary artery thrombosis (PAT) less common in HSS than that found in BS. Moreover, patients with HSS were more likely to be treated with anti-coagulants and vascular or surgical interventions, whereas less likely to receive immunosuppressive treatment.

Conclusions: Our study indicates that HSS is indeed an 'incomplete form of BS'. It can be considered as evidence supporting the notion that the vascular phenotype develops independently from skin-mucosa lesions and uveitis in BS. However, HSS has been described mainly focusing on aneurysms, overlooking the aspect of in-situ thrombosis.

Behçet's syndrome (BS) is a rare multisystem vasculitis involving blood vessels of any size. BS aetiology is still unclear to date, and the heterogeneity of clinical expression among ethnics and genders make early diagnosis challenging. However, so far, considerable efforts have been made toward the understanding of BS, leading researchers to agree that the coexistence of some environmental triggers and a genetical susceptibility both underlie BS aetiopathogenesis. In particular, viral agents, oral microbial flora, and mucosal microbiota have been widely explored in this regard, but still no specific microorganism has been definitely linked to the disease aetiology. Likewise, the concept that some environmental factors may play a role in BS clinical presentation has emerged based on the growing evidence that disease severity is usually higher in male patients, and that diet and fatigue may be involved in disease recurrence, especially in mucocutaneous manifestations. Moreover, smoke cessation is acknowledged as a risk factor for oral ulcerations, although the underlying mechanism is still not clear. All those environmental factors play their effects through epigenetic mechanisms. The aim of this review is to discuss the evidence on the role of environmental factors in BS aetiopathogenesis and clinical course.

Objectives: Behçet's disease (BD) is a systemic vasculitis affecting all sizes of arteries and veins. Approximately 5-10% of patients with BD are present during childhood. The chronic nature of the disease may lead to serious cardiovascular complications over time including early atherosclerosis. Increased levels of epicardial adipose tissue (EAT) and carotid intima-media thickness (CIMT) are considered early signs of subclinical atherosclerosis. Ongoing chronic inflammation may cause to increase in both EAT and CIMT. In this study, we aimed to evaluate CIMT and EAT in children with BD and determine their relationship with the clinical manifestations and course of the disease.

Methods: This cross-sectional study evaluated 30 patients with juvenile-onset BD and age-sex-matched 20 healthy controls. The CIMT and EAT thickness were measured by the same paediatric cardiologist. The association between clinical features, baseline disease activity, disease duration, EAT thickness and CIMT was also evaluated.

Results: Thirty children with BD and 20 age-sex-matched healthy volunteers enrolled in the study. The most common BD-related feature was oral aphthous (n=30), followed by mucocutaneous findings (n=22). Uveitis was observed in 5 patients, vascular involvement in 4, neurological involvement in 4, and gastrointestinal involvement in 2. All patients were inactive at the time of evaluation. The EAT thickness was significantly higher in patients while CIMT levels revealed no significant differences. However, there was no correlation between disease duration, baseline disease activity, and EAT thickness.

Conclusions: Increased EAT thickness may be a risk factor for early atherosclerosis in patients with BD. The EAT thickness was found to be significantly higher in paediatric BD patients. Confirmation of results in larger series may provide better insight into early screening for risk factors in these patients.

Objectives: Tocilizumab has been increasingly reported as an alternative therapeutic agent in the management of Behçet's syndrome (BS) and it has been mostly tried in BS patients with neurological and eye involvement. As therapeutic responses to each drug may vary across different types of BS involvement, we aimed to report seven patients with large vessel involvement treated with tocilizumab.

Methods: We enrolled seven BS patients with vascular involvement who were given tocilizumab at the Behçet's Disease Research Centre in Istanbul University-Cerrahpaşa between 2000 and 2022. Demographic information, BS features, types of vascular involvement, previous and concomitant medications, C-reactive protein (CRP) levels, imaging modality results, and outcomes were documented from the patients' medical records.

Results: Within a median of 6 months after the initiation of tocilizumab, 5 patients experienced vascular relapses. These relapses included the emergence of new bilateral pulmonary artery aneurysms, a new pulmonary artery thrombus, parenchymal lung involvement, deep vein thrombosis in the lower extremity, and pseudotumor cerebri in one patient each. CRP levels were normal in 4 of the 5 patients at the time of vascular relapse. One of these 5 patients and another patient with aortitis had an exacerbation of mucocutaneous symptoms. In the last patient, venous ulcers did not respond to tocilizumab and were complicated with infection.

Conclusions: Tocilizumab could potentially exacerbate vascular manifestations, similar to what is observed with mucocutaneous lesions in BS patients. Furthermore, CRP levels appear to be ineffective in monitoring these patients.