Behçet\'s syndrome (BS) is a rare chronic multisystemic inflammatory disorder of unknown etiopathogenesis. BS is classified as a vasculitis of variable vessel size, which can manifest in both arterial and venous blood vessels. BS commonly presents with mucocutaneous and ocular manifestations. Superficial and deep vein thrombosis is present in 50% of patients, with atypical venous thrombosis affecting the inferior vena cava, superior vena cava, hepatic veins with Budd-Chiari syndrome, portal vein, cerebral sinuses, and right atrium and ventricle. Arterial manifestations include in situ thrombosis, pulmonary artery aneurysms, aneurysms of the abdominal aorta, and aneurysms of visceral and peripheral arteries. This article reports a new case of BS in a 28-year-old female patient who presented with severe dyspnea and hemoptysis. Echocardiography and cardiovascular magnetic resonance imaging led to the diagnosis of endomyocardial fibrosis and a large right ventricular thrombus with pulmonary embolism. Computed tomography angiography revealed multiple pulmonary aneurysms and emboli. Rare findings such as endomyocardial fibrosis and Budd-Chiari syndrome were noted. This case highlights the role of medical imaging modalities in diagnosing rare syndromes such as BS, as demonstrated in the current case.

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.

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.

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.

OBJECTIVE: 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.
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.
CONCLUSIONS: 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.

This case report presents a 20-year-old male patient initially diagnosed with infective endocarditis, later correctly identified as Behçet\'s syndrome. The patient\'s complex clinical presentation, including chest pain, aortic dilation, severe aortic regurgitation, and aortic root abscess, posed significant diagnostic and therapeutic challenges. Despite initial misdiagnosis and treatment difficulties, the patient\'s condition significantly improved with appropriate immunosuppressive therapy, underscoring the potential for successful management of this complex condition. This case serves as a valuable reminder of the diagnostic challenges posed by Behçet\'s syndrome and the importance of considering this condition in patients presenting with symptoms suggestive of infective endocarditis.

OBJECTIVE: 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.

OBJECTIVE: To evaluate the prevalence, magnitude, and potential determinants of work productivity impairment in patients with Behçet\'s Syndrome (BS), focusing on the role of irreversible organ damage.
METHODS: A post-hoc analysis of the BS overall damage index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI: GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI: GH outcomes was evaluated by regression analysis.
RESULTS: Out of 148 patients, 34.5% were unemployed, with age (OR 1.035) and BODI score (OR 1.313 for 1-unit increase) as the only factors significantly (p< 0.05) associated with the unemployment state. An overall work impairment was reported in about 64.2% of the employed patients. Indeed, 22.7% reported missing work h due to their health (absenteeism), with a mean time loss of 34.4%; whereas 60.2% declared a reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (β 0.225); female sex (β 0.260), physician global assessment of disease activity (β 0.502) and an increased BODI score (β 0.166 for 1-point increase) with presenteeism; fibromyalgia (β 0.246), physician global assessment (β 0.469), and musculoskeletal damage (β 0.325) with overall work impairment.
CONCLUSIONS: Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.

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.

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.