Treatment of Behçet's Disease: An Algorithmic Multidisciplinary Approach

Behçet's disease (BD) is a chronic, relapsing inflammatory, multisystem disease of unknown etiology. The disease has a wide clinical spectrum of mucocutaneous lesions and ocular, vascular, articular, neurologic, gastrointestinal and cardiac involvement. Although the number of effective drugs used in the disease's treatment has increased in recent years, BD is still associated with severe morbidity because of mainly mucocutaneous, articular and ocular symptoms and an increased mortality because of large vessel, neurological, gastrointestinal and cardiac involvement. Many factors are associated with a more serious course, such as male gender and a younger age of onset. While the severity of the disease is more pronounced in the first years of the disease, it decreases in most patients after the age of forties. The primary goal of treatment should be the prevention of irreversible organ damage. Therefore, early diagnosis and appropriate treatment and close follow-up are mandatory to reduce the morbidity and mortality of the disease. Treatment varies depending on the organ involved and the severity of the involvement. For all these reasons, the treatment should be personalized and arranged with a multidisciplinary approach according to the organs involved. Treatment is mainly based on suppression of the inflammatory attacks of the disease using local and systemic immunomodulatory and immunosuppressive drugs. In this review, based on the mainly controlled studies and personal experience in clinical practice and basic research in this field, we propose a stepwise, symptom-based, algorithmic approach for the management of BD with a holistic perspective

Antioxidant and antimutagenic activities of Viscum album fruit ethanolic extract in human lymphocytes

Polyphenolic compounds are widely distributed in plants and known to be excellent antioxidants in vitro. They have the capacity to reduce free-radical formation by scavenging free-radicals. In this studywe have evaluated the antioxidant and antimutagenic potencies of polyphenolic compounds of Viscum album against trichloroethylene (TCE)-induced oxidative and genotoxic damage. V. album extract (VAE0.5 g/ml) protected human lymphocytes against TCE. In chromosomal aberration (CA) analysis, no significant increase in total aberrations were found after treatment with TCE and all VAE concentrations. The mitotic index (MI) showed significant increase in 0.5 ìg/ml VAE samples whencompared with TCE-treated (2 ìM) group. VAE (0.5 ìg/ml) reduced the levels of malondialdehyde (MDA) significantly wherease VAE (1.0 and 2.0 ìg/ml) samples increased MDA concentrations significantly. We have also shown that the various DNA effects of TCE treatment seem to be DNA damages, but not mutations as TCE treated profiles were reverted back to the control like profiles by most probably DNA repair mechanisms in VAE 0.5 g/ml treated group

Genital ulcer severity score and genital health quality of life in Behçet's disease

Background: Behçet's Disease (BD) is a chronic auto-inflammatory, multisystem relapsing/remitting disorder of unknown aetiology. Oro-genital ulceration is a key feature of the disease and has a major impact on the patients' quality of life. Other clinical manifestations include ocular inflammation, rheumatologic and skin involvement, while CNS and vascular complications can lead to considerable morbidity. The availability of a valid monitoring tool for BD activity is crucial in evaluating the impact of the disease on daily life activity. The aims of this study were to validate a novel tool for monitoring genital ulceration severity in BD and to assess the impact of genital ulcers on the Genital Health Quality of Life (GHQoL). Methods: Genital Ulcer Severity Score (GUSS) was developed using six genital ulcer characteristics: number, size, duration, ulcer-free period, pain and site. A total of 207 BD patients were examined, (137 females: mean age∈±∈SD: 39.83∈±∈13.42 and 70 males: mean age∈±∈SD: 39.98∈±∈11.95) from the multidisciplinary Behçet's Centre of Excellence at Barts Health NHS Trust. GUSS was used in conjunction with Behçet's Disease Current Activity Form (BDCAF). Results: The over-all score of GUSS showed a strong correlation with all genital ulcer characteristics, and the strongest correlation was with the pain domain (r∈=∈0.936; P∈2: 0.600; P∈<∈0.0001). Conclusions: This study established the practicality of GUSS as a severity monitoring tool for BD genital ulcers and validated its use in 207 patients. Genital ulcers of BD have a considerable impact on the patients GHQoL

Empirical Bolometric Correction Coefficients for Nearby Main-Sequence Stars in Gaia Era

Nearby detached double-lined eclipsing binaries with most accurate data were studied and 290 systems were found with at least one main-sequence component having a metallicity $0.008\leq Z\leq 0.040$. Stellar parameters, light ratios, Gaia DR2 trigonometric parallaxes, extinctions and/or reddening were investigated and only 206 systems were selected eligible to calculate empirical bolometric corrections. NASA-IPAC Galactic dust maps were main source of extinctions. Unreliable extinctions at low Galactic latitudes $|b|\leq5^o$ were replaced with individual determinations, if they exist in the literature, else associated systems are discarded. Main-sequence stars of remaining systems were used to calculate bolometric corrections ($BC$) and to calibrate $BC-T_{eff}$ relation, which is valid in the range 3100-36000 K. De-reddened $(B-V)_0$ colours, on the other hand, allowed us to calibrate two intrinsic colour effective temperature relations, where the linear one is valid for $T_{eff}>10000$ K, while the quadratic relation is valid for $T_{eff}<10000$ K, that is, both are valid in the same temperature range $BC-T_{eff}$ relation is valid. New $BC$ computed from $T_{eff}$ and other astrophysical parameters are tabulated, as well.Comment: 16 pages, including 10 figures and 6 tables, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Clinical Features and Natural Course of Hidradenitis Suppurativa in Turkey: A Multicenter Study

Introduction:The natural history, the progression of a diseaseprocess in an individual over time, has not yet been fully elu-cidated in hidradenitis suppurativa (HS). In this large multicenterstudy, we aimed to investigate the natural history of HS and itsgender differences.Methods:This cross-sectional study in-cluded 827 patients. The chronological order of the clinicalmanifestations for each patientwas recorded retrospectively.Sociodemographic characteristics, triggering factors, clinical,treatment, and prognostic features were also evaluated.Results:The mean age of disease onset was significantly younger inwomen than in men (22.42 +/- 9.28 vs. 27.06 +/- 20.56,p<0.001)and those with a family history (p<0.0001). The mean diseaseduration was 91.17 +/- 83.64 months. The most commonsymptom was purulent discharge (81%). The mean duration ofabscess was shorter in women than in men (3.11 +/- 2.65 vs.3.75 +/- 3.75,p= 0.01). The axilla was the most common onsetarea followed by the inguinal and gluteal regions. The diseaseran a more severe course in men. Abscess/inflammatory nodulewas defined in the last 6 months in 88.6% of the patients;however, thefirst 5 years of the disease were the most activedisease period in 67.5% of the patients. Multivariate analysisrevealed being male, older age, family history, involvement ofthe axillary, inguinal, and perianal regions independently as-sociated with HS severity. While antibiotic use was the mostimportant factor in improving thedisease symptoms, stress wasthe most common aggravating factor. Biological therapy in men,laser epilation and pregnancy in women were significant alle-viating factors, whereas weight gain was a more commonaggravating factor for women.Conclusion:HS shows a re-lentlessly progressive course with inflammatory attacks, but thefirst years of the disease are the most active period. This studyconfirms that environmental and hormonal factors may play animportant role in the disease course, probably with other en-dogenous or exogenous factors.(c) 2024 S. Karger AG, Base

Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy

<p>Abstract</p> <p>Background</p> <p>The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer <it>TIRAP </it>has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.</p> <p>Methods</p> <p>We assessed the <it>TIRAP </it>S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh.</p> <p>Results</p> <p>In Ghana, the <it>TIRAP </it>S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous <it>TIRAP </it>180L tend to increase the risk of sepsis in the German study (<it>P </it>= 0.04).</p> <p>Conclusion</p> <p>A broad protective effect of <it>TIRAP </it>S180L against infectious diseases <it>per se </it>is not discernible.</p

Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients

Objectives: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. Methods: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. Results: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10−8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10−8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10−7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. Conclusions: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease

Chromatin remodelling comes into focus

ATP-dependent chromatin remodelling enzymes are molecular machines that act to reconfigure the structure of nucleosomes. Until recently, little was known about the structure of these enzymes. Recent progress has revealed that their interaction with chromatin is dominated by ATPase domains that contact DNA at favoured locations on the nucleosome surface. Contacts with histones are limited but play important roles in modulating activity. The ATPase domains do not act in isolation but are flanked by diverse accessory domains and subunits. New structures indicate how these subunits are arranged in multi-subunit complexes providing a framework from which to understand how a common motor is applied to distinct functions.</p

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients