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Objectives: We aimed to identify conditions mimicking nervous system involvement among patients with Behçet's syndrome (BS) and to determine clinical, laboratory and imaging findings that may help in the differential diagnosis. Methods: We screened the charts of 500 consecutive BS patients to identify those who were referred to neurology at any time during their follow-up. The final diagnoses, presenting signs and symptoms, laboratory and imaging results were retrieved from patient charts. Patients who did not have a follow-up visit during the last 3 months were invited to the clinic. Results: Among the 500 BS patients, 116 (23%) had been referred to neurology. Among these, 29 (5.8%) were diagnosed with typical central nervous system involvement of BS (NeuroBS). The type of NeuroBS was parenchymal involvement in 21 patients, cerebral venous sinus thrombosis in 7 patients, and both in 1 patient. 30 patients (6%) had other conditions related to the nervous system, 46 (9.2%) did not have a nervous system disorder, and their symptoms recovered spontaneously, and 11 (2.2%) were lost to follow-up without a definite diagnosis. Of the 30 BS patients who were diagnosed with another nervous system condition, 14 (46%) had primary headache syndromes, 6 (20%) had psychiatric disorders, 2 had entrapment neuropathy, and 1 each had epilepsy, glial tumor, multiple sclerosis, Meniere's disease, optic neuritis, neuroretinitis, steroid myopathy and polyneuropathy. Conclusion: Nervous system conditions other than NeuroBS are frequent among BS patients referred to neurology. Caution is required to avoid misdiagnosis of these patients as NeuroBS. [ABSTRACT FROM AUTHOR]

Evidence evaluating the association between pre-frailty and frailty, and risk of adverse health outcomes in patients with Behçet's syndrome (BS) is limited in the literature. The aim of this study was to characterize the prevalence of frailty and associated factors in a single-centre cohort of patients with BS. Based on the International Study Group's criteria, this was a monocentric cross-sectional study of BS patients. The Fried frailty criteria were used to define frailty. The Turkish version of the Behçet's Disease Current Activity Form was used to measure the disease activity of BS. Damage index was assessed with the Behçet's Syndrome Overall Damage Index. Forty-four patients were enrolled. According to Fried frailty criteria, patients were classified as 13.6% frail, 59% pre-frail, and 27.2% robust, respectively. Compared to pre-frail and robust patients, frail patients had higher levels of inflammatory markers at the time of diagnosis. CRP levels at time of diagnosis and at the last visit were higher in the frail group than in the pre-frail and robust groups (p = 0.039 and p = 0.023, respectively). When active drugs for BS were evaluated, systemic glucocorticoid (50%, p = 0.030) and cyclophosphamide (33.3%, p = 0.006) treatments were higher in the frail group. Frailty and pre-frailty are commonly detected even in younger patients with BS. Inflammation can be described as potential determinants of frailty status. [ABSTRACT FROM AUTHOR]

Cardiovascular involvement in Behçet's disease (BD) is considerably related to morbidity and mortality. However, the cardiovascular manifestation is sometimes difficult to distinguish from those of other causes. The suspicion of BD and proper treatment is pivotal in the management of BD. Histology demonstrates perivasculitis. Neutrophil seems to play an important role in the inflammation of BD. It is thought that inflammation causes venous thrombosis and arterial aneurysm. Characteristically, BD involves both arteries and veins of variable size in any region. Venous thrombosis needs immunosuppression, and inferior vena cava thrombosis and Budd-Chiari syndrome require intensive immunosuppressive therapy. Arterial involvement causes aneurysm which usually is treated by surgical or endovascular intervention with immunosuppression. Pulmonary artery aneurysm and cardiac involvement require multimodal managements. [ABSTRACT FROM AUTHOR]

Behcet's syndrome (BS) is a vasculitis characterized by immune dysregulation. Biomarkers are valuable for assessing clinically atypical pathogenesis. We aimed to investigate the distribution of different biomarkers and their effects on the clinical features of patients with BS in a large-scale, real-world study. This is a retrospective, single-center study. In total, 502 patients diagnosed with BS were enrolled in this study. We analyzed the clinical features of this cohort and divided patients' symptoms into six categories, including mucocutaneous, articular, neurological, gastrointestinal, vascular, and ocular involvements. HLA-B51 cells, autoantibodies, and subsets of immune cells from the patients were tested. Pearson's correlation, Wilcoxon rank sum test and multivariate logistic regression were used for data analysis. Various autoantibodies were detected in the serum of 40.8% of patients with BS. The positivity rate of anti-endothelial cell antibodies (AECA) was the highest among autoantibodies and was found in 23.5% (118/502) of patients with BS. The positivity rate of HLA-B51 in patients with BS was 27.1%. Tumor necrosis factor (TNF)-α, IL-2, and IL-4 producing CD4+ T cells were positively correlated with the gastrointestinal BS. Increased IL-4+CD4+ T cell was a risk factor for gastrointestinal BS (P = 0.006, Overall rate [OR] = 2.491, 95% Confidence interval [CI]: [1.317, 5.100]). Various autoantibodies can be detected in patients with BS. HLA-B51 and AECA are the most common biomarkers. Increased IL-4+ CD4+ T cell was a risk factor for gastrointestinal involvement in BS. [ABSTRACT FROM AUTHOR]

Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon‐γ‐inducible protein 16 (IFI16) was reported to be involved in the pathogenesis of Behçet's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real‐time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor‐α (TNF‐α) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (P = 0.012). The plasma TNF‐α protein level in intestinal BS was significantly higher than in healthy controls (HCs; P = 0.009). PBMCs of intestinal BS patients and HCs were co‐cultured with human normal IECs (NCM460) to explore the interaction between immunological cells and IECs. Using IFI16 knockdown, PBMC‐NCM460 co‐culture, TNF‐α neutralizing monoclonal antibody (mAb), stimulator of interferon genes (STING) agonist 2′3′‐cGAMP, and the PLK1 inhibitor SBE 13 HCL, we found that PLK1 promotes the secretion of TNF‐α from PBMCs of intestinal BS patients, which causes overexpression of IFI16 and induces apoptosis of IECs via the STING–TBK1 pathway. The expressions of IFI16, TNF‐α, cleaved caspase 3, phosphorylated STING (pSTING) and phosphorylated tank binding kinase 1 (pTBK1) in the intestinal ulcer tissue of BS patients were significantly higher than that of HCs (all P < 0.05). PLK1 in PBMCs of intestinal BS patients increased TNF‐α secretion, inducing IEC apoptosis via activation of the IFI16–STING–TBK1 pathway. PLK1 and the IFI16–STING–TBK1 pathway may be new therapeutic targets for intestinal BS. [ABSTRACT FROM AUTHOR]

Objectives: Behçet's syndrome (BS) is a rare disease of unknown etiology, with limited reports especially in pediatric BS. The clinical characteristics and phenotypes of pediatric BS as a highly heterogeneous variable vessel vasculitis were investigated in this study. Methods: A cross-sectional study was conducted to compare clinical variables and descriptive characteristics of BS by age of onset and gender. Cluster analysis was then performed to identify the phenotypes of pediatric BS. Results: A total of 2082 BS patients were included in this study, 1834 adults and 248 children. Compared with adult-onset BS, pediatric BS had a higher incidence of folliculitis [relative risks (RR) and 95% confidence interval (CI) 1.3 (1.0–1.5)], uveitis of the left eye [RR and 95% CI 2.3 (1.0–5.0)], intestinal ulcer complications [RR and 95% CI 2.1 (1.1–4.2)], pericarditis [RR and 95% CI 2.5 (1.0–6.2)], and psychiatric disorders [RR and 95% CI 2.8(1.0–7.9)], while the incidence of thrombocytopenia was lower [RR 0.2 (0.1–1.0)]. Among pediatric BS, females had more genital ulcers, while males were more likely to have skin lesions, panuveitis, vascular involvement, venous lesions, cardiac involvement, and aortic aneurysms. Cluster analysis classified pediatric BS into five clusters (C1–C5): C1 (n = 61, 24.6%) showed gastrointestinal (GI) involvement; C2 (n = 44, 17.7%) was the central nervous system (CNS) type where 23 cases overlapped joint involvement; in C3 (n = 35, 14.1%), all patients presented with arthritis or arthralgia; all patients in C4 (n = 29, 11.7%) manifested ocular involvement, with a few patients overlapping with GI involvement or joint damage; C5 (n = 79, 31.9%) was the mucocutaneous type, presenting both oral ulcers, genital ulcers, and skin lesions. Conclusions: The clinical features of pediatric and adult BS differ significantly. Male and female pediatric BS also have a distinct demography. Five phenotypes including GI, CNS, joint, ocular, and mucocutaneous types were identified for pediatric BS. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate whether the ferroptosis is involved in intestinal Behçet's syndrome (IBS), and to identify if miR-141-3p could attenuate RAS-selective lethal 3 (RSL3)-induced ferroptosis and intestinal epithelial to mesenchymal transition (EMT) via directly inhabits zinc fnger E-box binding homeobox 1 (ZEB1). The expressions of ferroptosis-related proteins in the intestinal tissues of patients with IBS were investigated by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Malondialdehyde (MDA) contents of the intestinal tissues and cells were detected. Serum from IBS patients and RSL3 were co-cultured with intestinal epithelial cells in vitro. In order to investigate whether RSL3-induced ferroptosis can be ameliorated by miR-141-3p, the intestinal epithelial cells were firstly stimulated with RSL3 and then incubated with miR-141-3p mimics. Western blot was used to measure the expression of EMT and ferroptosis-related proteins. Expression of GPX4 (22.51% ± 2.05%, 51.75% ± 3.47%, t = − 7.77, p = 0.000) and xCT (17.49% ± 1.57%, 28.73% ± 1.75%, t = − 4.38, p = 0.003) were significantly lower in intestinal mucosal tissues of patients with IBS compared with HC group. Compared with the HC samples, the IBS specimens had significantly higher MDA (t = 4.32, p = 0.01). Moreover, the relative mRNA levels of ferritin light chain (FTL) (t = 4.07, p = 0.02) and ferritin heavy chain (FTH) (t = 8.82, p = 0.001) in the intestinal tissues were significant higher in IBS patients than in HC group. Serum from IBS patients could induce intestinal epithelial cell ferroptosis in vitro. Moreover, miR-141-3p could attenuate intestinal epithelial cell ferroptosis-induced by RSL3 and intestinal EMT via targeting ZEB1 in vitro. Ferroptosis were induced in patients with IBS. Moreover, the serum from IBS patients could induce ferroptosis in vitro. miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1. Therefore, miR-141-3p may open new avenues for the treatment of IBS in the future. Key Points • Ferroptosis in IBS is first reported in this study. • In this study, we explored that the serum from IBS patients could induce ferroptosis in vitro and miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1. [ABSTRACT FROM AUTHOR]

Behçet's syndrome (BS) is a variant vasculitis that can involve multiple organs with inflammatory manifestations. This study aimed to provide a more comprehensive analysis of the clinical phenotypes and characteristics of BS patients. We enrolled 2792 BS patients referred from China nationwide to Huadong Hospital Affiliated to Fudan University from October 2012 to December 2022. Detailed assessments of demographic information, clinical manifestations, laboratory results, gastroscopy, and medical imaging were conducted. Cluster analysis was performed based on 13 variables to determine the clinical phenotypes, and each phenotype was characterized according to the features of BS patients. A total of 1834 BS patients were included, while 958 invalid patients were excluded. The median age at onset was 31 years (IQR, 24–40 years), and the median disease duration was 10 years (IQR, 5–15 years). Eight clusters were identified, including mucocutaneous (n = 655, 35.7%), gastrointestinal (n = 363, 19.8%), articular (n = 184, 10%), ocular (n = 223, 12.2%), cardiovascular (n = 119, 6.5%), neurological (n = 118, 6.4%), vascular (n = 114, 6.2%), and hematological phenotype (n = 58, 3.2%). Ocular (RR = 1.672 (95% CI, 1.327–2.106); P < 0.001), gastrointestinal (RR = = 1.194 (95% CI, 1.031–1.383); P = 0.018), cardiovascular (RR = = 2.582 (95% CI, 1.842–3.620); P < 0.001), and vascular (RR = = 2.288 (95% CI, 1.600–3.272); P < 0.001) involvement were more prevalent in male BS patients, while the hematological (RR = 0.528 (95% CI, 0.360–0.776); P = 0.001) involvement was more common among female patients. BS presents significant heterogeneity and gender differences. The eight phenotypes of BS patients we propose hold the potential to assist clinicians in devising more personalized treatment and follow-up strategies. Key Points • This cluster analysis divided adult-onset BS into eight clinical phenotypes. • BS demonstrates a high level of clinical heterogeneity and gender differences. • Hematologic phenotypes of BS present distinctive clinical characteristics. [ABSTRACT FROM AUTHOR]

Rheumatologists are increasingly utilizing ultrasound for suspected giant cell arteritis (GCA) or Takayasu arteritis (TAK). This enables direct confirmation of a suspected diagnosis within the examination room without further referrals. Rheumatologists can ask additional questions and explain findings to their patients while performing ultrasound, preferably in fast-track clinics to prevent vision loss. Vascular ultrasound for suspected vasculitis was recently integrated into rheumatology training in Germany. New European Alliance of Associations for Rheumatology recommendations prioritize ultrasound as the first imaging tool for suspected GCA and recommend it as an imaging option for suspected TAK alongside magnetic resonance imaging, positron emission tomography and computed tomography. Ultrasound is integral to the new classification criteria for GCA and TAK. Diagnosis is based on consistent clinical and ultrasound findings. Inconclusive cases require histology or additional imaging tests. Robust evidence establishes high sensitivities and specificities for ultrasound. Reliability is good among experts. Ultrasound reveals a characteristic non-compressible 'halo sign' indicating intima-media thickening (IMT) and, in acute disease, artery wall oedema. Ultrasound can further identify stenoses, occlusions and aneurysms, and IMT can be measured. In suspected GCA, ultrasound should include at least the temporal and axillary arteries bilaterally. Nearly all other arteries are accessible except the descending thoracic aorta. TAK mostly involves the common carotid and subclavian arteries. Ultrasound detects subclinical GCA in over 20% of polymyalgia rheumatica (PMR) patients without GCA symptoms. Patients with silent GCA should be treated as GCA because they experience more relapses and require higher glucocorticoid doses than PMR patients without GCA. Scores based on intima-thickness (IMT) of temporal and axillary arteries aid follow-up of GCA, particularly in trials. The IMT decreases more rapidly in temporal than in axillary arteries. Ascending aorta ultrasound helps monitor patients with extracranial GCA for the development of aneurysms. Experienced sonologists can easily identify pitfalls, which will be addressed in this article. Plain language summary: Diagnosing vasculitis with ultrasound Rheumatologists use ultrasound to diagnose two types of blood vessel inflammation: giant cell arteritis (GCA) or Takayasu arteritis (TAK). They can do this right in their office during the examination, without sending patients elsewhere. During the ultrasound, rheumatologists can talk with patients about what they see. This is especially helpful in fast-track clinics to prevent vision loss. In Germany, doctors training to become rheumatologists learn how to use ultrasound to check for problems like these. An organization called 'European Alliance of Associations for Rheumatology (EULAR)' recommends using ultrasound as the main way to look for GCA and, if needed, for TAK. Ultrasound is also an important part of the new classification criteria for GCA and TAK. However, doctors do not rely on ultrasound alone. They also look what patients are feeling and do other medical tests. If ultrasound is not clear enough, doctors might need to do more tests like taking a small piece of tissue (biopsy) or using other kinds of imaging like MRI or CT scans. Ultrasound can show some characteristic signs of blood vessel inflammation, like a 'halo sign,' which tells doctors that the blood vessel walls are thicker than normal. It can also spot other problems like blockages or bulges in the blood vessels. When doctors suspect GCA, they should at least examine the arteries at the forehead and at the armpit. Most of the time, these areas are easy to see with ultrasound, but some areas might be harder to reach. Sometimes, people can have blood vessel inflammation without feeling any typical symptoms. Ultrasound can still find this silent inflammation in more than 20% of people with a condition called polymyalgia rheumatica (PMR). Even though these patients do not have typical symptoms of GCA, it is important to treat them the same way as those with GCA. Otherwise, they may have more flare-ups and need higher doses of glucocorticoids. Doctors may measure the thickness of the artery walls over time in research studies. This helps them to see if treatments are working well. The wall thickness decreases faster in arteries of the head than in larger arteries outside the head. Ultrasound of the aorta close to heart helps to find out if a widening of the aorta develops. This can be dangerous because of rupture. [ABSTRACT FROM AUTHOR]

Background/aim: Our primary aim was to investigate the effects of concomitant celiac disease (CD) on the clinical characteristics of Behçet’s syndrome (BS) patients. Materials and method: The study was a retrospective, nationwide, multicenter study. Turkish Ministry of Health National Electronic Database (e-Nabız) is used under Health Ministry’s supervision to extract the subject’s data. Statistical analysis: Statistical analyses were made by the Statistical Package for Social Sciences (SPSS) software version 20 (IBM Corp., Armonk, New York). Continuous variables were presented by mean ± standard derivation (SD) or median (min–max) according to normality and compared by student-t test. A binary logistic regression analysis was performed to further investigating the relation between having a concomitant CD with each BD manifestation and comorbidity, frequencies of which were detected to be significantly different in the student–test. Results: A total of 84,241 patients diagnosed with BS were analyzed, and CD was identified in 175 (0.21 %) patients. The group with CD had a mean age of 41.30 ± 13.69 which was significantly younger. the prevalence of females was significantly higher (71.4%). The mean age of first admission for BS was also significantly younger in the group with CD (36.64 ± 13.28). BS patients with CD had a significantly higher prevalence of inflammatory bowel disease (27.2% vs. 7.3%, p < 0.001). When comorbid conditions were investigated depression (35.4% vs. 23.3%, p < 0.001), migraine (7.4 % vs. 2.6%, p < 0.001), fibromyalgia (10.9% vs. 4.5%, p < 0.001) and osteoporosis (12.6% vs. 6.6%, p = 0.001) were significantly more frequent in BS patients with CD. Conclusion: Our results suggest coexistence of CD in BS patients is related to female dominance and probably to an earlier disease onset. Several CD-related comorbidities as well as inflammatory bowel disease were more frequent in the CD group which implied an increased overall disease burden. [ABSTRACT FROM AUTHOR]

Purpose: Studies on intestinal Behçet’s disease (BD) complicated by myelodysplastic syndrome (MDS) are rare, and no established therapeutic guidelines exist. This study aimed to evaluate the clinical presentation and outcomes of patients with intestinal BD complicated by MDS (intestinal BD–MDS) and suggest a treatment strategy. Materials and Methods: Data from patients with intestinal BD–MDS from four referral centers in Korea who were diagnosed between December 2000 and December 2022 were retrospectively analyzed. Clinical features and prognosis of intestinal BD–MDS compared with age-, sex-matched intestinal BD without MDS were investigated. Results: Thirty-five patients with intestinal BD–MDS were included, and 24 (70.6%) had trisomy 8. Among the 35 patients, 23 (65.7%) were female, and the median age at diagnosis for intestinal BD was 46.0 years (range, 37.0–56.0 years). Medical treatments only benefited eight of the 32 patients, and half of the patients underwent surgery due to complications. Compared to 70 matched patients with intestinal BD alone, patients with intestinal BD–MDS underwent surgery more frequently (51.4% vs. 24.3%; p=0.010), showed a poorer response to medical and/or surgical treatment (75.0% vs. 11.4%; p<0.001), and had a higher mortality (28.6% vs. 0%; p<0.001). Seven out of 35 patients with intestinal BD–MDS underwent hematopoietic stem cell transplantation (HSCT), and four out of the seven patients had a poor response to medical treatment prior to HSCT, resulting in complete remission of both diseases. Conclusion: Patients with intestinal BD–MDS frequently have refractory diseases with high mortalities. HSCT can be an effective treatment modality for medically refractory patients with intestinal BD–MDS. [ABSTRACT FROM AUTHOR]

Behçet’s syndrome (BS) is a rare chronic multi-systemic inflammatory disorder that usually involves adults between third and fourth decades of life, while pediatric and juvenile onset are relatively rare. BS young patients (YP) often develop a full-blown disease late after onset, requiring careful diagnostic workup and regular follow-up while they grow up. In this regard, the purpose of transitional programs is to ensure continuous high-quality care to YP with chronic conditions, providing them with the skills necessary to become independent and empowered adults able to chronically self-manage their disease. EULAR/PReS released the first set of standards and recommendations for transitional care (TC) of YP with juvenile-onset rheumatic diseases, but the appropriate timing for transition, the tools to evaluate patients’ readiness, and indicators of transition plans effectiveness still need to be identified. Although little is known regarding TC in BS, it is easy to assume that BS YP will benefit from developmentally and disease-specifically appropriate transition plans, which may promote continuity of care, improve perceived quality of life and prevent poor disease outcomes. This perspective article discusses the key concepts and the goals of TC, addressing the potential challenges and opportunities of TC for YP with BS in clinical practice.

Abstract Background Autoimmune responses have been suggested to involvement in patients with Behcet’s syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. Methods We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. Results The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P

Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención. To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Although age at disease onset is considered to be a significant factor in the prognosis of Crohn's disease, little is known about its influence on the long‐term prognosis of those with intestinal Behçet's disease (BD). This study aimed to evaluate the long‐term clinical outcomes of patients with intestinal BD according to age of disease onset. Methods: Patients diagnosed with intestinal BD at < 18, 18–60, and > 60 years of age were classified into early‐onset, adult‐onset, and late‐onset groups, respectively. The influence of disease onset time on clinical prognosis, including specific medical requirements, BD‐related intestinal surgery, hospitalization, and emergency room visits, was compared using the log–rank test in a large cohort of patients with intestinal BD. Results: Among 780 patients, 21 (2.7%), 672 (86.2%), and 87 (11.1%) comprised the early‐onset, adult‐onset, and late‐onset groups, respectively. Patients in the early‐onset group were more likely to require immunosuppressants than those in the adult‐onset group (P = 0.048). Nine (42.9%), 158 (23.5%), and 18 (20.7%) patients in the early‐onset, adult‐onset, and late‐onset groups, respectively, underwent intestinal resection. The early‐onset group exhibited a higher risk for intestinal resection than the late‐onset (P = 0.043) and adult‐onset (P = 0.030) groups. The late‐onset group exhibited a higher risk for BD‐related hospitalization than the adult‐onset group (P = 0.023). Conclusions: Age at diagnosis affected the clinical course of intestinal BD, including intestinal surgery, hospitalization, and specific medical requirements. Different treatment strategies should be established according to age at diagnosis. [ABSTRACT FROM AUTHOR]

Mucocutaneous lesions are the most common manifestation and hallmark of Behçet's Syndrome (BS). They show a significant impact on patients' quality of life and more importantly, may occur concurrently with major organ involvement. Colchicine is the first-line therapy for patients with mucocutaneous involvement because of its good tolerability and safety profile. The literature lacks clear data on the duration of treatment of mucocutaneous symptoms and the prognosis of patients who interrupt colchicine therapy. This study was planned to observe differences in mucocutaneous findings, joint findings and disease activity, in the colchicinefree period of the patients who were followed up with the diagnosis of BS without active major organ involvement and who were in remission and discontinued colchicine treatment. Our study demonstrated a significant increase in the rate of patients who developed aphthae after the discontinuation of colchicine treatment, which is the primary endpoint, and in the number of newly developed aphthae, which is the secondary endpoint. A significant increase was observed in the rate of patients who developed erythema nodosum in the first and second months. There was no significant difference in the development of genital ulcers after discontinuation of colchicine. The rate of nodular lesion development in female patients increased during the colchicine-free period. Due to the low number of patients who developed joint complaints, we could not demonstrate the efficacy of colchicine in our study. [ABSTRACT FROM AUTHOR]

We present a case in which cerebral infarction was seen and Behcet's syndrome was diagnosed. Following investigation and monitoring, we identified that the cause was a progressive obliterative focal arteritis of the middle cerebral artery. Such an entity has not previously been reported, although similar cases are described which explain the pathophysiology of the disorder. [ABSTRACT FROM AUTHOR]

Abstract Background Intestinal Behçet’s disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. Methods This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet’s disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). Results A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953–0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). Conclusion Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

OBJECTIVE: This study aimed to investigate Behçet's syndrome (BS) patients' regarding anthropometric measurements, daily energy and nutrient intake, and the MD adherence of patients. METHODS: 100 consecutive patients with BS were prospectively enrolled in two rheumatology outpatient clinics. Mid Upper Arm circumference (MUAC), Triceps skinfold thickness (TST), Mid Upper Arm Muscle Circumference (MUAMC), and Mid Upper Arm Muscle Area (MUAMA) measurements of patients were compared with Turkish reference values. Participants' daily energy and nutrient intake were categorized by the 'MD Adherence Score.' RESULTS: Thirty patients (30%) had only mucocutaneous involvement. According to reference values, 47%, 36%, 14%, and 27% of the participants had low percentile values (<50. percentile) for MUAC, TST, MUAMC, and MUAMA, respectively. Walnuts (35%), eggplant (35%), and tomatoes (13%) were reported as the most prominent foods for symptom exacerbations. The mean MD adherence score was 23.5±6.5 (male: 23.2±6.9; female: 24.2±5.9) points and the adherence status was average (60%) and poor (35%) in the majority of the patients. CONCLUSIONS: Food consumption is important regarding symptom occurrence and multidisciplinary management of BS. Some participants had poor adherence to the MD. Increased waist/hip ratio, BMI, and decreased TST and MUAMA may indicate body muscle mass and unhealthy eating patterns. Patients with BS need encouragement for healthy eating habits. [ABSTRACT FROM AUTHOR]

Background: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. Methods: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). Results: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953–0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). Conclusion: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs. [ABSTRACT FROM AUTHOR]

Behçet's syndrome is a recurring inflammatory multiorgan disorder affecting the skin, mucosa, eyes, joints, stomach, and central nervous system. Behçet's syndrome epidemiology varies greatly among populations (0.64–420/100,000), and Behçet's syndrome has gained increasing international acclaim in the recent 50 years due to raising awareness of the syndrome, although it is rare in most population. In addition to the unclear etiology of the syndrome, the diagnosis of Behçet's syndrome is complicated by a vague clinical presentation, phenotypic heterogeneity and/or incomplete representation, and the lack of any specific laboratory, radiographic, or histological findings. There exists a dire need to elucidate factors that contribute to disease pathogenesis and/or are associated with clinical features of Behçet's syndrome and the classification of different forms of the syndrome. The identification of such molecular, cellular, and/or clinical factors are crucial for timely diagnosis and efficacious management of Behçet's syndrome. We discuss recent advances in the clinical diagnosis of Behçet's syndrome and related contributions of genetics, epigenetics, microbiome, inflammasomes, and autoantibodies to the improved diagnosis, management, and understanding of Behçet's syndrome. [ABSTRACT FROM AUTHOR]

Objective To investigate the differential diagnostic spectrum in patients with suspected Behçet's syndrome (BS) in low prevalence regions. In addition, the number of patients fulfilling the ICBD criteria despite not having BS was evaluated. Methods This retrospective analysis was performed in two referral centres for BS. Patients with confirmed BS (clinical diagnosis with fulfilment of ISG criteria or a score of ≥5 points in the ICBD criteria) were excluded. The remaining patients were divided into 11 differential diagnosis categories. If no definitive alternative diagnosis could be established, patients were termed 'probable BS' in case of (i) relapsing orogenital aphthosis in the absence of other causes and either HLA-B51 positivity, or origin from an endemic area or presence of an additional typical BS symptom that is not part of the classification criteria, or (ii) with 3–4 points scored in the ICBD criteria. Results In total 202 patients were included and categorized as follows: 58 patients (28.7%) as 'probable BS', 57 (28.2%) skin disease, 26 (12.9%) chronic pain syndrome, 14 (6.9%) eye disease, 11 (5.4%) spondyloarthropathy, 9 (4.5%) gastrointestinal disease, 7 (3.5%) neurological disease, 4 (2%) arthritis, 3 (1.5%) auto-inflammation, 3 (1.5%) connective tissue disease and 10 (5.0%) miscellaneous disease. HLA-B51 was positive in 55/132 (41.7%); 75/202 (37.1%) of the patients fulfilled the ICBD criteria. Conclusion In a low disease prevalence setting, the straightforward application of the ICBD criteria may lead to overdiagnosis of BS. The differential diagnosis of BS is enormously broad. Clinicians should be aware that HLA-B51 positivity is still not considered as a diagnostic feature in BS. [ABSTRACT FROM AUTHOR]

Behçet's uveitis (BU) is a debilitating manifestation of Behçet's disease, often requiring prompt and aggressive treatment to prevent vision loss. Glucocorticoids (GCS) serve as a first-line therapy for BU; however, their long-term, high-dose use can result in significant adverse effects. This review summarizes the efficacy, adverse effects, and advances in combination therapy involving GCS for the management of BU. We discuss the benefits and drawbacks of various GCS administration routes, including periocular and intravitreal injections, intravitreal sustained-release devices, and systemic therapy, highlighting the role of fluocinolone acetonide and dexamethasone as primary sustained-release formulations. Moreover, we underscore the importance of combining GCS with immunosuppressive drugs and biological agents to minimize adverse reactions and optimize therapeutic outcomes. The review concludes that, while GCS remain a crucial component of BU treatment, careful consideration of their administration and combination with other therapies is essential to achieve long-term remission and improved visual outcomes for patients with BU. [ABSTRACT FROM AUTHOR]

IntroductionBehcet’s syndrome is a rare, chronic, systemic condition often categorized within the group of vasculitides. It presents a diagnostic challenge due to its varied clinical manifestations and the absence of a definitive laboratory test. Its etiology remains unclear but may involve genetic, infectious, and environmental factors.Case presentationWe report the case of a 16-year-old male who presented with deep vein thrombosis, followed by recurrent episodes of breakthrough thrombosis, despite adequate anticoagulant therapy. The patient did not meet the International Study Group (ISG) criteria nor the International Criteria for Behcet’s syndrome (ICBD) due to the absence of characteristic features such as oral aphthous ulcers, genital ulcers, and uveitis. Later in the disease course, after ruling out other causes of breakthrough thrombosis, he tested positive for HLA-B51, an allele associated with Behcet’s syndrome, and exhibited a pathergy reaction.DiscussionThe patient’s clinical course underlines the diagnostic complexity associated with Behcet’s syndrome and highlights the importance of maintaining a broad differential diagnosis in cases of recurrent thrombosis. Although HLA-B51 testing is not routinely recommended, it played a pivotal role in our case, underscoring the value of an integrated diagnostic approach. Furthermore, this case reinforces the potential for atypical presentations of Behcet’s syndrome, necessitating vigilant clinical awareness. After establishing the diagnosis, we successfully treated the patient with immunosuppressive therapy, significantly improving his condition.

Mitochondrial DNA (mtDNA) leakage into the cytoplasm can occur when cells are exposed to noxious stimuli. Specific sensors recognize cytoplasmic mtDNA to promote cytokine production. Cytoplasmic mtDNA can also be secreted extracellularly, leading to sterile inflammation. However, the mode of secretion of mtDNA out of cells upon noxious stimuli and its relevance to human disease remain unclear. Here, we show that pyroptotic cells secrete mtDNA encapsulated within exosomes. Activation of caspase‐1 leads to mtDNA leakage from the mitochondria into the cytoplasm via gasdermin‐D. Caspase‐1 also induces intraluminal membrane vesicle formation, allowing for cellular mtDNA to be taken up and secreted as exosomes. Encapsulation of mtDNA within exosomes promotes a strong inflammatory response that is ameliorated upon exosome biosynthesis inhibition in vivo. We further show that monocytes derived from patients with Behçet's syndrome (BS), a chronic systemic inflammatory disorder, show enhanced caspase‐1 activation, leading to exosome‐mediated mtDNA secretion and similar inflammation pathology as seen in BS patients. Collectively, our findings support that mtDNA‐containing exosomes promote inflammation, providing new insights into the propagation and exacerbation of inflammation in human inflammatory diseases. Synopsis: Mitochondrial DNA (mtDNA) secreted by pyroptotic cells is encapsulated within exosomes and induces excessive inflammation resembling symptoms seen in patients with Behçet's syndrome. In pyroptotic cells, the activation of caspase‐1 and subsequent action of gasdermin‐D promote the efflux of mtDNA from the mitochondria into the cytoplasm.Activation of caspase‐1 promotes the formation of intracellular vesicles (ILVs), mtDNA uptake into ILVs, and its release into the extracellular space via exosomes.The encapsulation of mtDNA within exosomes promotes inflammation, leukocyte mobilization, and cytokine production.Patients with Behçet's syndrome show increased mtDNA in the blood and caspase‐1‐mediated mitochondrial damage in the isolated monocytes.In patients with Behçet's syndrome monocytes secrete mtDNA‐containing exosomes that induce pathological inflammation in an NLRP3‐ and TLR9‐dependent manner. [ABSTRACT FROM AUTHOR]

Objective: Behçet's syndrome (BS) is a systemic vasculitis that can affect both veins and arteries. In this study, we aimed to review the demographic and clinical characteristics, treatments of patients who were followed up with the diagnosis of BS in our newly established clinic, and mainly focus on vascular BS cases. Methods: The data of 127 patients who applied between July 2020 and December 2022 and were followed up with the diagnosis of BS were retrospectively reviewed. Of the patients, 78 (61%) were male, 49 (39%) were female. There was vascular involvement in 49 (39%) patients. Results: Three of them had isolated dural sinus thrombosis and these patients were excluded. Of 46 patients, 37 (80.4%) had lower extremity vein thrombosis, 12 (26%) had pulmonary artery involvement. Three patients had coronary artery involvement and four had intracardiac thrombus. In addition to glucocorticoids, azathioprine was the first preferred immunosuppressive agent in patients with venous thrombosis. Until 2022, our treatment choice in pulmonary artery involvement was cyclophosphamide followed by azathioprine or infliximab maintenance. In 2022, treatment was started directly with the infliximab and azathioprine in 4 patients with pulmonary artery involvement. In patients with coronary artery involvement, treatment was started with cyclophosphamide. Two of the patients had died and both were male (central nervous system in one, coronary artery and pulmonary artery involvement in the other). Conclusion: Vascular involvement continues to be an important cause of morbidity and mortality in BS. Early recognition and treatment of these patients is important. [ABSTRACT FROM AUTHOR]

Objectives Behçet's syndrome (BS) is a chronic multisystemic inflammatory disorder of unclear aetiology. The predominant BS susceptibility locus was identified within HLA-B*51. HLA-B*51 subtypes were previously studied as disease susceptibility markers. Few data are now available about the relationship between B*51 subtypes and clinical phenotype. The aim of this study was to genotype HLA-B*51 subtypes in a series of Italian BS patients and to test the association with clinical manifestations and disease severity (Krause's index). Methods HLA-B*51 subtype genotyping for 63 alleles (B*51:01–B*51:63) was performed by PCR after DNA extraction from whole blood of BS patients. The correlation of disease clinical manifestations and severity (Krause's index) with the HLA-B*51 allele and its subtypes was analysed. Results We enrolled 241 (140 male and 101 female) BS patients, and HLA-B*51 frequency was 62.7% (151 of 241). One hundred and eight of the HLA-B*51-positive patients carried the B*51:01 subtype (108 of 151, 71.5%), 39 of 151 (25.8%) the B*51:08 subtype, 2 of 151 (1.3%) the B*51:02 subtype, 1 of 151 (0.7%) the B*51:05 subtype, and 1 of 151 (0.7%) the B*51:07 subtype. We found that ocular involvement was statistically associated with HLA-B*51 positivity and with B*51:01 and B*51:08 subtypes (P  < 0.05). We also found that disease severity was higher in HLA-B*51-positive patients than in negative patients, but without statistical significance (median Krause's index 5.1 vs 4.1, P  > 0.05). Conclusion Here, we confirm a high frequency of the HLA-B*51 allele in our group of BS patients. B*51:01 and B*51:08 were found to be the most common subtypes, and an association of both subtypes with ocular involvement was also underlined. [ABSTRACT FROM AUTHOR]

This study aimed to analyse long term outcomes and risk factors for endovascular repair of aortic pseudoaneurysms in patients with vascular Behçet's disease (BD). Medical records of 26 aortic vascular BD patients who underwent endovascular treatment at the vascular department of Peking Union Medical College Hospital between January 2002 and December 2021 were reviewed retrospectively. Erythrocyte sedimentation rate (ESR) and C reactive protein were used to assess BD activity. Computed tomography angiography (CTA) was obtained pre- and post-operatively for almost all patients. Univariable logistic regression analysis was used to analyse risk factors for endovascular repair, such as inflammatory indicators, drug usage, and stent graft parameters. The abdominal aorta (n = 17) was the most common site of 27 vascular BD pseudoaneurysms in this study. CTA also revealed one aortic arch pseudoaneurysm, seven descending thoracic aortic pseudoaneurysms, one thoraco-abdominal aortic pseudoaneurysm, and one pseudoaneurysm at the aortic bifurcation. Most of the pseudoaneurysms were treated with covered stent grafts. The technical success rate was 96% and no deaths occurred during hospital stay. The mean follow up was 5.8 ± 5.5 years and 31% (8/26) experienced post-operative complications. Overall one, three, and five year event free survival rates were 87%, 78%, and 74%, respectively. Univariable logistic regression analysis revealed that pre-operative ESR ≥ 16.0 mm/h (p =.040), pre-operative glucocorticoid (GC) use ≤ 11.5 days (p =.024), pre-operative immunosuppressant use ≤ 15.5 days (p =.028), and length of proximal landing zone ≤ 1.95 cm (p =.034) were associated with a worse prognoses following endovascular treatment. Proximal oversize ≥ 9.5% (p =.074) was also regarded as a risk factor, although not statistically significant. This study further confirmed the feasibility of endovascular repair for aortic vascular BD patients. Risk factors predicting poor prognoses included elevated pre-operative ESR, insufficient pre-operative GC use or immunosuppressant use, inadequate proximal landing zone, and larger proximal oversize percentage. [ABSTRACT FROM AUTHOR]

Abstract Background and objectives Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) has been reported as a spectrum of autoimmune, inflammatory central nervous system disorders. Linear perivascular radial gadolinium enhancement patterns on brain magnetic resonance imaging (MRI) are a hallmark of these disorders. GFAP-A is associated with cerebrospinal fluid (CSF) GFAP antibody (GFAP-Ab), while the association with serum GFAP-Ab is less clear. This study aimed to observe the clinical characteristic and MRI changes of GFAP-Ab-positive optic neuritis (ON). Methods We performed a retrospective, observational case study at the department of neurology, Beijing Tongren Hospital, from December 2020 to December 2021. The serum of 43 patients and CSF samples of 38 patients with ON were tested for GFAP-Ab by cell-based indirect immune-fluorescence test. Results Four patients (9.3%) were detected GFAP-Ab positive, and in three out of the four patients, GFAP-Abs were detected only in serum. All of them demonstrated unilateral optic neuritis. Three patients (1, 2, and 4) experienced severe visual loss (best corrected visual acuity ≤ 0.1). Two patients (2 and 4) had experienced more than one episode of ON at the time of sampling. MRI showed optic nerve hyperintensity on T2 FLAIR images in all GFAP-Ab positive patients, and orbital section involvement was the most common. During follow-up (mean 4.5 ± 1 months), only Patient 1 had a recurrent ON, and no patient developed new other neurological events or systemic symptoms. Conclusion GFAP-Ab is rare in patients with ON and may manifest as isolated, relapsing ON. This supports the notion that the GFAP-A spectrum should comprise isolated ON.

Abstract Background Behçet Syndrome (BS) has a significant psychological and social impact on patients, caregivers and families. The present study aims at exploring disease perception in BS patients, using both a co-designed survey and the narrative medicine (NM) approach. Methods An ad-hoc questionnaire was co-designed by clinicians expert in BS, BS patients and caregivers and BS adult patients were invited to answer the online questionnaires. Cluster analysis was used to analyse data from the survey and to identify groups of patients with diverse disease perception. To further explore real-life perspectives, the stories of illness of a smaller group of adult BS patients were anonymously collected online and analysed by means of text, sentiment and qualitative analysis. Results Two hundred and seven patients answered the survey and forty-three stories were collected. The cluster analysis highlighted that accepting or not the disease has a strong impact on the daily life, on how BS patients perceive themselves and in terms of hope for the future. The stories revealed that patients often address common issues, such as the long and complex journey faced from the disease onset until the BS diagnosis, which was strongly connected to the concept of time and perceived as an exhausting period of their lives. Conclusion To our knowledge, this is the first study that addressed disease perception also applying the NM principles in BS. The current perception that BS patients have of their disease should encourage the BS scientific and patient community in joining forces in order to improve the journey of BS patients.

Background: Behçet's disease (BD) is a rare chronic auto-inflammatory systemic disease with non-specific oral manifestations, categorised as generalised variable vessel vasculitis that requires an interdisciplinary approach to diagnose due to its phenotypic heterogeneity. Whilst the oral lesions that reoccur in BD underpin the complex diagnostic process, the crucial role of dental professionals is highlighted in a case report summarised herein. We present a case of a 47-year-old male referred to the Oral Medicine Department by a rheumatologist after previous hospitalization for thrombosis of the iliac vein and inferior vena cava. He had elevated inflammatory C-reactive protein biomarker and an increased erythrocyte sedimentation rate. Recurrent episodes of folliculitis, oral and genital ulcers were reported. Clinical examination revealed multiple ulcerations in the oral mucosa. The complementary, histopathological analysis performed to rule out other disorders, based on excisional biopsy, showed non-keratinised stratified squamous epithelium with areas of exocytosis and ulceration. The connective tissue presented an intense mixed inflammatory infiltrate, congested blood vessels, haemorrhage, vasculitis, and HLA-B genotyping identified the expression of HLA-B15, further supporting the BD diagnosis. Treatment was initiated with colchicine, prednisolone, and weekly subcutaneous administration of methotrexate and resulted in the complete remission of oral lesions and no recurrence of other manifestations. Conclusions: This BD case report emphasizes the importance of a multidisciplinary approach in diagnosing BD, including the use of histopathological assessment and genetic profiling. It highlights the significance of thorough intraoral assessment and referral to a multidisciplinary team for diagnosis. The oral manifestations of BD as the primary symptoms often indicate underlying major systemic pathologies. The authors stress the need for a structured diagnostic algorithm to facilitate timely and effective management of BD. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the frequency of trisomy 8 and other potential chromosomal abnormalities among Behçet's syndrome (BS) patients with gastrointestinal system (GIBS) involvement and those without myelodysplastic syndrome. Methods: Between September 2014 and April 2015, 29 GIBS patients and 23 healthy controls were enrolled. Peripheral blood samples were collected from these patients for conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) analysis specifically targeting chromosomes 8 and 9. Results: Conventional cytogenetic analysis of 29 GIBS patients revealed clonal chromosome losses in 14 patients. One patient had a clonal del(8)(q11q13), and one patient had a constitutional t(5;10) (q33;p13). Polyploid metaphases were observed in 27 of 29 patients. In 7 of 23 control cases clonal aneuploidies were observed, and in two cases structural abnormalities along with numerical ones were detected. No clonal anomaly was observed in 14 cases. Polyploidy was detected in 13 of 23 cases in the control group. While trisomy 8 and 9 were detected in one patient by FISH analysis, only trisomy 9 was detected in one patient. The patient with trisomy 8 was diagnosed with polycythemia vera. Conclusion: The frequency of chromosomal abnormalities observed in GIBS patients was found to be consistent with the literature. Trisomy 8 does not seem to be a feature of GIBS unless there is a hematologic condition. However, its presence strongly suggests the possibility of such a condition. [ABSTRACT FROM AUTHOR]

Abstract Background Vascular involvement is an infrequent clinical manifestation of Behçet’s syndrome. Owing to the rarity of arterial involvement in Behçet’s syndrome, there is limited experience in managing this phenomenon. Case presentation Here, we report a 28-year-old Iranian man with a Behçet’s syndrome background, who presented with shoulder pain and hoarseness. Chest computed tomography angiography was conducted with a suspicion of a vascular pathology causing pressure on the recurrent laryngeal nerves. The patient was diagnosed with a ruptured innominate artery pseudoaneurysm. An innominate artery to the right common carotid artery bypass was performed, and the pseudoaneurysm was excised and replaced with an expandable polytetrafluoroethylene graft. Eventually, the patient was discharged after an uneventful hospital course. Conclusion It appears that we are still a long way from finding the optimal treatment for Behçet’s syndrome vascular involvement, and a combination of surgical and medicinal treatments is required.

Abstract Clustering is an important clinical feature of Behçet’s syndrome (BS) and may have pathogenetic and therapeutic implications. Recent and previous studies on BS phenotype differ substantially in terms of methodology. Correlation matrices and factor analyses were not efficient enough to uncover clusters. Clustering patterns may change according to demographic factors such as age and sex. Clustering patterns may also be profoundly influenced by the misperception of symptoms that are assumed to be secondary to BS, when, in fact, they represent manifestations of BD mimics. This can give rise to misleading conclusions and should be kept in mind when interpreting data obtained by clustering or other phenotype analyses of BS. A true geographical/racial variability in disease expression could be studied in a multinational consensus cohort. Pathogenetic studies in separate clusters of BS have still been lacking.

Abstract Background Behçet’s syndrome (BS) is an immune-mediated disease characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin symptoms. HLA-B51, as well as other genetic polymorphisms, has been reported to be associated with BS; however, the pathogenesis of BS and its relationship to genetic risk factors still remain unclear. To address these points, we performed immunophenotyping and transcriptome analysis of immune cells from BS patients and healthy donors. Methods ImmuNexUT is a comprehensive database consisting of RNA sequencing data and eQTL database of immune cell subsets from patients with immune-mediated diseases and healthy donors, and flow cytometry data and transcriptome data from 23 BS patients and 28 healthy donors from the ImmuNexUT study were utilized for this study. Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify genes associated with BS and clinical features of BS. eQTL database was used to assess the relationship between genetic risk factors of BS with those genes. Results The frequency of Th17 cells was increased in BS patients, and transcriptome analysis of Th17 cells suggested the activation of the NFκB pathway in Th17 cells of BS patients. Next, WGCNA was used to group genes into modules with similar expression patterns in each subset. Modules of antigen-presenting cells were associated with BS, and pathway analysis suggested the activation of antigen-presenting cells of BS patients. Further examination of genes in BS-associated modules indicated that the expression of YBX3, a member of a plasmacytoid dendritic cell (pDC) gene module associated with BS, is influenced by a BS risk polymorphism, rs2617170, in pDCs, suggesting that YBX3 may be a key molecule connecting genetic risk factors of BS with disease pathogenesis. Furthermore, pathway analysis of modules associated with HLA-B51 indicated that the association of IL-17-associated pathways in memory CD8+ T cells with HLA-B51; therefore, IL-17-producing CD8+ T cells, Tc17 cells, may play a critical role in BS. Conclusions Various cells including CD4+ T cells, CD8+ T cells, and antigen-presenting cells are important in the pathogenesis of BS. Tc17 cells and YBX3 may be potential therapeutic targets in BS.

Background and objectives: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) has been reported as a spectrum of autoimmune, inflammatory central nervous system disorders. Linear perivascular radial gadolinium enhancement patterns on brain magnetic resonance imaging (MRI) are a hallmark of these disorders. GFAP-A is associated with cerebrospinal fluid (CSF) GFAP antibody (GFAP-Ab), while the association with serum GFAP-Ab is less clear. This study aimed to observe the clinical characteristic and MRI changes of GFAP-Ab-positive optic neuritis (ON). Methods: We performed a retrospective, observational case study at the department of neurology, Beijing Tongren Hospital, from December 2020 to December 2021. The serum of 43 patients and CSF samples of 38 patients with ON were tested for GFAP-Ab by cell-based indirect immune-fluorescence test. Results: Four patients (9.3%) were detected GFAP-Ab positive, and in three out of the four patients, GFAP-Abs were detected only in serum. All of them demonstrated unilateral optic neuritis. Three patients (1, 2, and 4) experienced severe visual loss (best corrected visual acuity ≤ 0.1). Two patients (2 and 4) had experienced more than one episode of ON at the time of sampling. MRI showed optic nerve hyperintensity on T2 FLAIR images in all GFAP-Ab positive patients, and orbital section involvement was the most common. During follow-up (mean 4.5 ± 1 months), only Patient 1 had a recurrent ON, and no patient developed new other neurological events or systemic symptoms. Conclusion: GFAP-Ab is rare in patients with ON and may manifest as isolated, relapsing ON. This supports the notion that the GFAP-A spectrum should comprise isolated ON. [ABSTRACT FROM AUTHOR]

Behcet's syndrome is a variable vessel vasculitis characterized by recurrent oral and genital ulcers with concomitant skin, ocular, neurologic, gastrointestinal, and joint involvement. Herein, we present a patient who was diagnosed with Behcet's syndrome, which with magnetic resonance angiography showed occlusion of the right subclavian artery at the level of the thoracic outlet and reverse flow in the right vertebral artery consistent with subclavian steal syndrome. In addition, partial narrowing was noted in the left renal artery. The distribution of arterial involvement resembled Takayasu's arteritis, although the presence of mucocutaneous lesions, male gender, history of deep vein thrombosis, and HLA-B51 positivity favored a diagnosis of vasculo-Behçet's syndrome. We treated the patient with methylprednisolone and cyclophosphamide. After the regression of vascular inflammation with immunosuppressive therapy, stenting was performed in the left renal artery. [ABSTRACT FROM AUTHOR]

This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet's syndrome (BS), their association with other disease manifestations, response to therapy, and long-term prognosis. Data were retrieved from the AIDA Network Behçet's Syndrome Registry. Out of a total of 141 patients with juvenile BS, 37 had MSM at disease onset (26.2%). The median age at onset was 10.0 years (IQR 7.7). The median follow-up duration was 21.8 years (IQR 23.3). Recurrent oral (100%) and genital ulcers (67.6%) and pseudofolliculitis (56.8%) were the most common symptoms associated with MSM. At disease onset, 31 subjects had arthritis (83.8%), 33 arthralgia (89.2%), and 14 myalgia (37.8%). Arthritis was monoarticular in 9/31 cases (29%), oligoarticular in 10 (32.3%), polyarticular in 5 (16.1%), axial in 7 (22.6%). Over time, arthritis became chronic-recurrent in 67.7% of cases and 7/31 patients had joint erosions (22.6%). The median Behçet's Syndrome Overall Damage Index was 0 (range 0–4). Colchicine was inefficacious for MSM in 4/14 cases (28.6%), independently from the type of MSM (p = 0.46) or the concomitant therapy (p = 0.30 for cDMARDs, p = 1.00 for glucocorticoids); cDMARDs and bDMARDs were inefficacious for MSM in 6/19 (31.4%) and 5/12 (41.7%) cases. The presence of myalgia was associated with bDMARDs inefficacy (p = 0.014). To conclude, MSM in children with BS are frequently associated with recurrent ulcers and pseudofolliculitis. Arthritis is mostly mono- or oligoarticular, but sacroiliitis is not unusual. Prognosis of this subset of BS is overall favorable, though the presence of myalgia negatively affects response to biologic therapies. ClinicalTrials.gov Identifier: NCT05200715 (registered on December 18, 2021). [ABSTRACT FROM AUTHOR]

T lymphocytes are the major components of adaptive immunity in Behçet's syndrome (BS) pathology. However, the precise mechanism of T‐cell‐induced inflammatory condition remains to be determined. We applied bulk sequencing of the T‐cell receptor (TCR) β chain in peripheral blood samples from 45 patients with BS and 10 healthy donors as controls. TCR repertoires in BS patients displayed more clonality and less diversity than in healthy donors. Male patients exhibited lower diversity metrics of TCR and had a larger proportion in the top 10 clones than females (p = 0.016). There were no TCR clonality differences in other clinical features, such as age, disease duration, organ involvement, disease severity, and activity. By "Grouping of Lymphocyte Interactions by Paratope Hotspots" (GLIPH2) for antigen prediction, we found distinct 2477 clusters of TCR‐β sequences that potentially recognize similar antigens shared between BS patients. We observed clonal T‐cell expansion in BS patients. Sexual differences in TCR clonal expansion and public TCR groups deserve further study to reveal the underline T‐cell‐mediated immunity in BS. [ABSTRACT FROM AUTHOR]

Background: Behçet Syndrome (BS) has a significant psychological and social impact on patients, caregivers and families. The present study aims at exploring disease perception in BS patients, using both a co-designed survey and the narrative medicine (NM) approach. Methods: An ad-hoc questionnaire was co-designed by clinicians expert in BS, BS patients and caregivers and BS adult patients were invited to answer the online questionnaires. Cluster analysis was used to analyse data from the survey and to identify groups of patients with diverse disease perception. To further explore real-life perspectives, the stories of illness of a smaller group of adult BS patients were anonymously collected online and analysed by means of text, sentiment and qualitative analysis. Results: Two hundred and seven patients answered the survey and forty-three stories were collected. The cluster analysis highlighted that accepting or not the disease has a strong impact on the daily life, on how BS patients perceive themselves and in terms of hope for the future. The stories revealed that patients often address common issues, such as the long and complex journey faced from the disease onset until the BS diagnosis, which was strongly connected to the concept of time and perceived as an exhausting period of their lives. Conclusion: To our knowledge, this is the first study that addressed disease perception also applying the NM principles in BS. The current perception that BS patients have of their disease should encourage the BS scientific and patient community in joining forces in order to improve the journey of BS patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the differential diagnostic spectrum in patients with suspected Behçet's syndrome (BS) in low prevalence regions. In addition, the number of patients fulfilling the ICBD criteria despite not having BS was evaluated. Methods: This retrospective analysis was performed in two referral centers for BS. Patients with confirmed BS (clinical diagnosis with fulfilment of ISG criteria or a score of ≥ 5 points in the ICBD criteria) were excluded. The remaining patients were divided into eleven differential diagnosis categories. If no definitive alternative diagnosis could be established, patients were termed 'probable BS' in case of (1) relapsing orogenital aphthosis in the absence of other causes and either HLA-B51 positivity, origin from an endemic area or presence of an additional typical BS symptom that is not part of the classification criteria or (2) with 3–4 points scored in the ICBD criteria. Results: In total 202 patients were included and categorized as follows: 58 patients (28.7%) as 'probable BS', 57 (28.2%) skin disease, 26 (12.9%) chronic pain syndrome, 14 (6.9%) eye disease, 11 (5.4%) spondyloarthropathy, 9 (4.5%) gastrointestinal disease, 7 (3.5%) neurological disease, 4 (2%) arthritis, 3 (1.5%) auto-inflammation, 3 (1.5%) connective tissue disease, 10 (5.0%) miscellaneous disease. HLA-B51 was positive in 55/132 (41.6%); 75/202 (37.1%) of the patients fulfilled the ICBD criteria. [ABSTRACT FROM AUTHOR]

Abstract Purpose: To investigate the pattern of ocular involvement in Behcet's disease (BD) with predictors of patients' final state of vision. Methods: This historical cohort encompassed the clinical records of 200 patients diagnosed according to the International Criteria for BD (ICBD), over a period of 17 years between 2004 and 2021. Results: The prevalence of Behcet's uveitis (BU) was more common in females and patients in the fourth decade of life. Ninety-five patients (47.5%) had evidence of ocular involvement in the initial ophthalmologic evaluation, and 171 patients (85.5%) manifested evidence of BU during the follow-up visits of which bilateral non-granulomatous panuveitis was the most common anatomical pattern of involvement (32.9%) followed by posterior (27.6%), anterior (26.5%), and intermediate (13.8%) uveitis. The prevalent accompanying signs were oral aphthous (67%), skin lesions (29%), and genital ulcers (19.5%). Cystoid macular edema (CME) was the most frequent ocular complication (62%), followed by cataract (57.5%) and epiretinal membranes (ERM) (36.5%). Univariate analysis showed the following determinants: male gender, younger age at onset, panuveitis, posterior uveitis, retinal vasculitis, and longer duration of uveitis as poorer visual prognostic factors of the disease. Multivariate analysis demonstrated a higher chance of poor visual prognosis of BD in patients with panuveitis, posterior uveitis, retinal vasculitis, and longer duration of uveitis. Conclusion: This cohort study demonstrated an overview on epidemiological patterns of BU along with the visual prognostic factors in Iranian patients.

Behçet’s syndrome is a complex vasculitis involving vessels of all sizes. The typical clinical presentation consists of recurrent oral ulcers associated with genital ulcers, and/or intra-ocular inflammation and/or cutaneous lesions. It may also involve the joints, central nervous system, cardiovascular system and gastrointestinal tract. Muscle involvement associated with Behçet’s syndrome has been rarely described. We here report two cases of muscular manifestations in the setting of Behçet’s syndrome with specific gastrocnemius muscle involvement.

Objectives: This retrospective cohort study aimed to find out predictors and early biomarkers of Infliximab (IFX) refractory intestinal Behçet’s syndrome (intestinal BS). Methods: We collected the baseline clinical characteristics, laboratory parameters, and concomitant therapies of intestinal BS patients treated by IFX from the Shanghai Behçet’s syndrome database. After 1 year IFX therapy, intestinal BS patients with non-mucosal healing (NMH, intestinal ulcers detected by colonoscopy) and/or no clinical remission [NCR, scores of the disease activity index for intestinal Behçet’s disease (DAIBD) ≥20] were defined as IFX refractory intestinal BS. Multivariate logistic regression analysis was performed to evaluate the predictors for NMH and NCR in IFX refractory intestinal BS. Results: In 85 intestinal BS patients, NMH was identified in 29 (34.12%) patients, and NCR was confirmed in 20 (23.53%) patients. Erythrocyte sedimentation rate (ESR; ≥24 mm/h) and free triiodothyronine (fT3; ≤3.3pmol/L) were the independent risk factors of NMH in IFX refractory intestinal BS. Drinking alcohol and the fT3/free thyroxine ratio (fT3/fT4; ≤0.24) were independent risk factors, and thalidomide was an independent protective factor, for NCR in intestinal BS patients treated by IFX. Conclusion: This study may be applicable for adjusting the therapeutic strategy and sidestepping unnecessary exposure to IFX in intestinal BS patients. Routine assessments of ESR, fT3, and fT3/fT4 ratio are helpful to identify high-risk individuals of IFX refractory intestinal BS. Thalidomide is suggested to be a concomitant therapy with IFX for intestinal BS patients. [ABSTRACT FROM AUTHOR]