Behçet’s Disease Research Articles

Assessment of liver x receptor messenger RNA beta and microRNA-146a in a group of Egyptian patients with Behçet’s disease

Abstract Background and objectives Behçet’s disease (BD) is an ongoing systemic vasculitis with mouth and genital ulceration and eye, skin, and systemic affection. It has considerable morbidity and mortality, and a high incidence and a higher male-to-female affection characterize Egypt. We aimed to evaluate liver x receptor messenger RNA beta (LXR β) and microRNA-146a (miR-146a) gene expression in Behçet’s disease cases in Egypt to relate them with clinicopathological features. Subject and method Eighty Egyptian individuals were split into two groups for the current study: Forty Behçet’s disease cases and forty healthy controls matched by age and gender from the Rheumatology Department at Helwan University Hospital, Egypt. The transformed score, also known as the Behçet’s Disease Current Activity Form (BDCAF), was utilized to measure disease activity. To assess the amounts of LXR β and miR-146a serum expression via real-time PCR, a blood sample was obtained. Results There was a downregulation of both LXR β and miR-146a levels that significantly differed between the BD group and the control group (p = 0.0001 and 0.0001, respectively). There is a noteworthy inverse relationship between the expression level of LXR β and BDCAF Patients Index (r = − 0.79 and p = 0.0001) was found. Regarding miR-146a, it had a reverse correlation with BDCAF Patients Index (r = − 0.89 and p = 0.0001). Conclusion LXR β and miR-146a were found to be significant non-invasive predictor biomarkers for Behçet’s disease and can indicate disease activity.

A proliferation-inducing ligand (APRIL) level among risk factors of ocular involvement in patients with Behçet’s disease

IntroductionOcular involvement is quite common in Behçet’s disease (BD) and may cause crucial functional complications. Even though the mechanisms of BD remain unclear, advances in gene­tic and immunological fields have improved our understanding of the immunopathogenesis of BD ocular involvement. Little is known about the expression of a proliferation-inducing ligand (APRIL) in terms of ocular involvement in BD. The objective of this study was to determine whether serum APRIL concentrations are associated with ocular involvement in patients with BD.Material and methodsThe study included 60 patients diagnosed with BD matched by age and sex to 30 healthy individuals. Every patient underwent a clinical evaluation, and the Behçet’s Disease Current Activity Form (BDCAF) was utilized to quantify disease activity. All patients underwent a comprehensive ophthalmological assessment. Serum APRIL was assessed for patients as well as controls.ResultsOne or more ocular manifestations were found in 42 BD patients (70%), while 18 patients (30%) had no ocular involvement. The mean level of serum APRIL levels was markedly elevated in BD patients, particularly those with ocular involvement, compared to both BD patients without ocular involvement and healthy individuals. A statistically significant association was determined between high APRIL concentration and development of uveitis, cataract, and hypopyon. Cutaneous lesions and arthritis were strong independent predictors for ocular involvement in BD patients.ConclusionsOverexpression of APRIL in patients with BD, particularly in terms of uveitis, cataract, and hypopyon, lends credence to the idea that B cell activating factors have an important function in BD. These findings may indicate that serum APRIL concentrations can differentiate a clinical subgroup of BD patients with ocular disease. As a result, finding a new therapeutic strategy targeting the APRIL pathway might be beneficial in BD patients suffering from ocular involvement.

Potential biomarkers in Behçet’s disease: monocyte, neutrophil, platelet, and C-reactive protein to albumin ratios

IntroductionThe objective of this cross-sectional study was to evaluate the monocyte to albumin ratio (MAR), neutrophil to albumin ratio (NAR), platelet to albumin ratio (PAR), and C-reactive protein to albumin ratio (CAR) as potential biomarkers for disease activity in patients with Behçet’s disease (BD).Material and methodsBoth BD cases and healthy controls were enrolled in this study. Demographic characteristics, disease duration, and current medications were recorded for all participants. The BD Current Activity Form (BDCAF) was utilized to assess the activity of BD. Additionally, ery­throcyte sedi­mentation rate, CRP, and serum albumin levels were measured. The MAR, NAR, PAR, and CAR were compared between the two groups. Correlation analysis and receiver operating characteristic curves (ROC) were employed to establish cut-off points for these biomarkers.ResultsIn the study, both BD cases and 45 controls were included, totaling 90 participants. Significant differences were observed in the mean ±SD values of ESR, MAR, PAR, CAR, and albumin between the BD cases and controls (<i>p</i> = 0.008, <i>p</i> = 0.009, <i>p</i> = 0.029, <i>p</i> = 0.034, <i>p</i> = 0.006, respectively). However, despite these differences, no significant correlation was detected between BDCAF and the parameters under investigation. The cutoff point was determined as 150.59 (sensitivity 46.67%, specificity 82.22%, <i>p</i> = 0.008, AUC = 0.655) for MAR; as 62,013.73 (sensitivity 60.00%, specificity 66.67%, <i>p</i> = 0.03, AUC = 0.629) for PAR; and as 1.16 (sensitivity 35.56%, specificity of 95.567%, <i>p</i> = 0.03, AUC = 0.629) for CAR. The results were not able to define any cut-off points for active-inactive BD.ConclusionsSignificantly higher levels of MAR, PAR, and CAR were observed in patients with BD than controls. Monocyte to albumin ratio, PAR, and CAR were notably elevated in patients with active BD. This finding suggests that these parameters possess discriminative ability and could potentially serve as biomarkers to aid in the clinical evaluation of BD.

TNF inhibitors target a mevalonate metabolite/TRPM2/calcium signaling axis in neutrophils to dampen vasculitis in Behçet’s disease

TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet’s disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD.

The burden of mental health issues in Behçet’s disease: implications for patient quality of life

ABSTRACT Introduction Depression and anxiety are among the most prevalent mental health conditions in Brazil. Both are associated with poor quality of life (HRQoL) and challenges in disease management for chronic illnesses, including Behçet’s disease (BD). This study aimed to evaluate depression, anxiety, and HRQoL in BD patients from a non-endemic area. Research design and methods This case-control study included adult BD patients from Brazilian tertiary center and healthy controls (HC). All patients fulfilled the ISG and ICBD diagnostic criteria. Depression, anxiety and quality of life were assessed using BDI, HADS, SF-36, and physical capacity with the HAQ. Results We enrolled 58 BD patients (60% female, mean age 46.1) and 96 HC (74% female, mean age 44). High rates of depression and anxiety were observed in BD patients, correlating with disease activity, younger age, absence of a partner, shorter disease duration, and lower income. BD patients showed significant HRQoL restrictions, particularly in physical and emotional roles, compared to HC. Longer disease duration was correlated with better HRQoL. Conclusion High rates of depression and anxiety were observed in BD patients, negatively impacting HRQoL, particularly in those with higher disease activity. Further study and clinical attention are warranted to enhance patient care and outcomes.

Protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene polymorphisms (rs2542151, rs7234029) in Egyptian Behçet’s disease patients: a preliminary report

Single nucleotide polymorphisms (SNPs) of the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene have been documented to be linked with several autoimmune disorders including Behçet’s disease (BD). PTPN2 SNPs rs2542151 and rs7234029 have been assessed using real-time PCR in 96 BD patients and 50 controls matched by age and gender. Patients were categorized into groups according to the disease phenotypes and severity. A total of 94.8% of patients were males. The patients’ mean age at onset was 26.1 ± 8 years. The median (IQR) disease duration was 8.5(4–13) years. No difference was observed between the patients and controls concerning the frequency of the two SNPs’ different genotypes, models, and alleles. Moreover, neither disease phenotypes nor severity were associated with rs2542151 or rs7234029 SNPs. PTPN2 rs2542151 and rs7234029 SNPs do not seem to have associations with BD occurrence, phenotypes, or severity in the Egyptian patients.Key Points• PTPN2 rs2542151 and rs7234029 SNPs do not seem to have associations with BD occurrence, phenotypes, or severity in the Egyptian patients.• Further studies involving a larger sample size with variable clinical diversity are recommended to verify the results.

Regulatory role of the lncRNAs MIAT and PVT1 in Behçet’s disease through targeting miR-93-5p and miR-124-3p

BackgroundNoncoding RNAs play pivotal roles in the process of autoimmune diseases. However, the definite contributions of these molecules to Behçet’s disease (BD) are still unknown. This study aimed to explore the clinical value of a novel competing endogenous (ce) RNA network in the pathogenesis of BD and to assess its use in primary diagnosis.MethodsBioinformatic analysis was applied to construct a BD-related ceRNA network: lncRNA (MIAT and PVT1)-miRNA (miR-93-5p and miR-124-3p)-mRNA (SOD-2 and MICA). Blood was obtained from 70 BD patients and 30 healthy subjects, and the serum expression of the tested RNAs was estimated via quantitative real-time PCR (qPCR). Serum tumor necrosis factor-alpha (TNF-α) levels were also determined. The associations between these RNAs were further analyzed, and receiver operating characteristic (ROC) curve and logistic regression analyses were employed to validate their diagnostic and prognostic values.ResultsThe expression levels of the lncRNAs PVT1 and miR-93-5p were significantly increased, whereas those of the lncRNAs MIAT and miR-124-3p, as well as those of the SOD-2 and MICA mRNAs, were significantly decreased in BD patients compared with controls. BD patients had significantly higher serum TNF-α levels than controls did. ROC curve analysis indicated that the selected RNAs could be candidate diagnostic biomarkers for BD. Moreover, the highest diagnostic efficiency was achieved with the combination of MIAT and miR-93-5p or PVT1 and miR-124-3p with either SOD-2 or MICA. Logistic regression analysis revealed that all RNA expression levels could be predictors for BD.ConclusionMechanistically, our research revealed a novel ceRNA network that is significantly disrupted in BD. The findings reported herein, highlight the noncoding RNA-molecular pathways underlying BD and identify potential targets for therapeutic intervention. These insights will likely be applicable for developing new strategies for the early diagnosis, management and risk assessment of BD as well as the design of novel preventive measures.Trial registration The protocol for the clinical studies was approved by Cairo University’s Faculty of Pharmacy’s Research Ethics Committee (approval number: BC 3590)

Clinical Features of Behçet’s Disease Uveitis

Abstract: Behçet’s disease (BD) is a chronic, multisystemic vasculitis first described by Professor Hulusi Behçet in 1937. It is characterized by recurrent inflammatory attacks affecting multiple organs, with uveitis being a significant and severe complication that can lead to blindness. BD typically emerges between the ages of 20 and 30 years, with a higher prevalence in males and rare occurrences in children. The prevalence and severity of BD and its ocular symptoms tend to diminish with age. In Turkey, BD is a leading cause of noninfectious uveitis, and its prevalence varies across different regions. Ocular involvement, seen in up to 90% of BD patients, often appears 2–4 years after disease onset and may be the initial sign in 10%–20% of cases. BD uveitis is characterized by recurrent nongranulomatous panuveitis and retinal vasculitis, typically affecting both eyes. Diagnostic tools such as fluorescein angiography (FA), optical coherence tomography (OCT), and laser flare photometry (LFP) are essential for monitoring disease activity and guiding treatment. FA is crucial for identifying occlusive and leaky vasculitis, while OCT helps in detecting macular complications and visualizing retinal infiltrates and their sequelae. LFP quantitatively evaluates intraocular inflammation. Recognizing the ocular manifestations of BD early is vital for accurate diagnosis and effective management. This review highlights the clinical features, diagnostic tools, and importance of early diagnosis in managing BD uveitis.

Association between IL and 6 gene polymorphisms and circulating IL-6 levels in Behcet’s disease: A meta-analysis

ObjectivesThis study aimed to investigate the association between circulating interleukin-6 (IL-6) levels and Behçet’s disease (BD), and associations between polymorphisms in IL-6 gene and BD susceptibility. MethodA search of relevant articles was conducted in the Medline, Embase, and Web of Sciences databases. Subsequently, a meta-analysis was performed to assess circulating IL-6 levels in both the BD and control groups. Additionally, we investigated the association between the functional IL-6 promoter −174 G/C polymorphism and the risk of developing BD. ResultsNineteen studies involving 923 patients with BD and 910 controls were included in this meta-analysis. The results demonstrated a significant elevation in circulating IL-6 levels in the BD group than in the control group (standardized mean difference [SMD] = 1.600, 95 % confidence interval [CI] = 0.732–2.496, P<0.001). Furthermore, IL-6 levels were significantly higher in the active disease group than in the inactive disease group (SMD=1.292, 95 % CI=0.059–2.525, P<0.001). Intriguingly, the meta-analysis revealed an association between BD and the IL-6 CC+CG genotype in Arabs (odds ratio [OR] = 0.588, 95 % CI=0.393–0.881, P=0.010), whereas no such association was observed in European or Asian populations. ConclusionsOur meta-analysis revealed significantly higher circulating IL-6 levels in patients with BD and found evidence of association between IL and 6 promoter −174 G/C and BD susceptibility.

Destructive Arthritis in Paediatric Behçet’s Disease: A Case Report

Abstract Introduction Behçet’s disease (BD) is a systemic inflammatory disease that affects blood vessels of any calibre and has a relapsing and remitting course. Its main features include recurrent oral and genital ulcers, other skin lesions such as pseudo-folliculitis and erythema nodosum, but also uveitis and arthritis. Arthritis in BD is usually described as mono or oligoarticular, non-erosive, affecting mainly large peripheral joints of lower limbs. In paediatric BD, up to forty percent of patients have articular involvement. We present a rare case of a patient who was diagnosed with mucocutaneous, ocular and articular involvement at the age of 15. He initially received treatment with prednisolone and colchicine. However, at the age of 20, he failed to attend follow-up appointments and discontinued his treatment. At the age of 42, he saw a rheumatologist due to joint complaints associated with functional limitations. The medical assessment confirmed polyarthritis with extensive erosive arthropathy detected on imaging. Conclusions This case report exemplifies a joint involvement rarely found in BD and even less in paediatric BD. We should be aware of this unusual involvement and treat patients accordingly since this condition can occur with a dramatic impact on the patient’s functional prognosis as in other inflammatory rheumatic arthropathies.

Clinical characteristics of pediatric noninfectious uveitis and risk factors for severe disease: a single-center study

ObjectivesWe aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment.MethodPatients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease.ResultsThe study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795–0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439–6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet’s disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765–72.231, p = 0.001).ConclusionWe suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease.Key Points• Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease.• Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease.• Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet’s disease.

Exploration of effective biomarkers for venous thrombosis embolism in Behçet’s disease based on comprehensive bioinformatics analysis

Behçet’s disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein–protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723–0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

Canakinumab is effective for refractory Entero-Behçet’s disease with compound heterozygous variants of the MEFV gene: A case report

Rationale: Behçet’s disease (BD) is characterized by recurrent oral ulcers, skin lesions, genital ulcers, and ocular inflammation, with uncontrolled gastrointestinal manifestations potentially leading to fatal complications. Human leukocyte antigen (HLA) class I alleles such as HLA-B51 and HLA-A26 are genetic risk factors for BD, and interleukin-1β activation plays a key role in BD pathogenesis. Familial Mediterranean fever, another autoinflammatory disease caused by MEFV gene mutations, shares similarities with BD, including enhanced interleukin-1β production. Patient concerns: We present a case of BD with severe gastrointestinal ulcers and MEFV variants treated with canakinumab. Diagnoses: A 69-year-old Japanese woman with a history of malignant lymphomas and nontuberculous mycobacterial arthritis developed BD symptoms, including oral and gastrointestinal ulcers. Interventions: Despite after treatments with 2 tumor necrosis factor inhibitors, her oral and gastrointestinal ulcers persisted. Genetic analysis revealed L110P/E148Q MEFV variants, prompting the administration of canakinumab and granulocyte and monocyte adsorption apheresis. Outcomes: Continuous treatment with canakinumab improved the oral and gastrointestinal ulcers. Lessons: This case highlights the potential efficacy of canakinumab in treating severe gastrointestinal ulcers in BD patients with MEFV variants.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders

ABSTRACT Purpose The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet’s disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. Methods Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. Results Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). Conclusions Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

Salivary Levels of Human Neutrophil Peptide (HNP) 1-3 in Patients with Recurrent Aphthous Stomatitis and Behçet’s Disease: A Cross-sectional Study in Iran

Background: Recurrent oral ulcers are the most common complaint of patients with Behçet’s disease (BD) and recurrent aphthous stomatitis (RAS). Enhanced innate immune response and neutrophilic activity might be a possible etiopathogenesis of BD. This study aimed to determine the significance of salivary human neutrophil peptide (HNP 1-3) in BD and RAS patients and detect their correlation with different clinical presentations, disease activity, and characteristics of oral ulcers. Methods: This cross-sectional study included 25 BD patients and 25 RAS patients as well as 25 healthy participants. Five cubic centimeters of unstimulated saliva was collected and levels of HNP 1-3 were measured by ELISA. Other data were obtained through interviews, examinations, and reviews of medical records. Finally, data analysis was performed using SPSS 25.0 software. Results: Salivary HNP 1-3 levels were not significantly different between the study groups (P=0.282). Duration of oral ulcers did not correlate with HNP 1-3 levels in RAS and BD patients (P &gt; 0.05). Also, BD patients with involvements other than oral ulcers were not found to have different levels of HNP 1-3 compared to those who did not manifest these conditions. Conclusion: The validity of HNP 1-3 to be used as a probable biological marker for evaluation, diagnosis, and estimation of disease activity in patients with BD and RAS is still questionable according to our results.

Psoriasiform Drug Eruption Associated with Carbamazepine

Behçet’s disease (BD) is a chronic systemic inflammatory vasculitis of unknown etiology characterized by recurrent episodes of oral aphthous ulcers, genital ulcers, skin lesions, ocular lesions, and other manifestations. This disease affects many organs and systems and shows a wide range of clinical manifestations. The prevalence of anxiety, depression, and general psychiatric symptoms is higher among patients with BD compared with healthy individuals. However, syndromes such as psychosis appear to be less frequent. Therefore, we present a case of BD complicated by schizophrenia-like symptoms.

Value of Serum Asymmetric Dimethylarginine (ADMA) As a Novel Biomarker for Uveitis in Behçet’s Disease

ABSTRACT Purpose To evaluate the serum asymmetric dimethylarginine (ADMA) level as a biomarker for uveitis in Behçet’s Disease (BD). Methods In this cross-sectional study, two groups of BD patients were examined: 33 with uveitis and 27 without uveitis. All patients were clinically evaluated, with disease activity measured by Behçet’s Disease Current Activity Form (BDCAF) score. They also underwent thorough ophthalmic evaluation, and routine laboratory investigations, including serum ADMA. Results Patients with BD who experienced active or inactive uveitis had higher levels of serum ADMA compared to those without uveitis. Anterior (ρ = 0.34, p < 0.01), posterior (ρ = 0.3, p < 0.05), and pan uveitis (ρ = 0.35, p < 0.01) were significantly correlated with serum ADMA levels. However, there was no significant correlation between ADMA and other BD manifestations. ROC curve analysis showed that increased serum ADMA levels in BD patients predicted uveitis with a sensitivity of 61.8%, specificity of 96.2%, and AUC of 0.78(95% CI: 0.66–0.9, p < 0.001). Conclusion Serum ADMA level can serve as a novel biomarker of uveitis in BD and its severity with good diagnostic accuracy, regardless of its site or activity.

Ruptured popliteal artery aneurysm: An initial presentation of Behçet’s disease

Behçet’s Disease (BD) is an uncommon systemic vasculitic disorder, that can affect multiple organ systems. Arterial and venous aneurysmal and occlusive manifestations can occur. We report a case of a 25-year-old male presenting with a 4-week history of left leg pain and swelling, with acute deterioration due to ruptured popliteal aneurysm, confirmed on imaging. He underwent emergency popliteal bypass with ipsilateral reversed great saphenous vein. Subsequent workup revealed pulmonary aneurysms and features suggestive of BD. He received aggressive immunosuppressive therapy to good effect. The management of the patient’s popliteal aneurysm, diagnostic procedure and subsequent management are discussed.

Unraveling the microbiome-metabolome nexus: a comprehensive study protocol for personalized management of Behçet's disease using explainable artificial intelligence.

The presented study protocol outlines a comprehensive investigation into the interplay among the human microbiota, volatilome, and disease biomarkers, with a specific focus on Behçet's disease (BD) using methods based on explainable artificial intelligence. The protocol is structured in three phases. During the initial three-month clinical study, participants will be divided into control and experimental groups. The experimental groups will receive a soluble fiber-based dietary supplement alongside standard therapy. Data collection will encompass oral and fecal microbiota, breath samples, clinical characteristics, laboratory parameters, and dietary habits. The subsequent biological data analysis will involve gas chromatography, mass spectrometry, and metagenetic analysis to examine the volatilome and microbiota composition of salivary and fecal samples. Additionally, chemical characterization of breath samples will be performed. The third phase introduces Explainable Artificial Intelligence (XAI) for the analysis of the collected data. This novel approach aims to evaluate eubiosis and dysbiosis conditions, identify markers associated with BD, dietary habits, and the supplement. Primary objectives include establishing correlations between microbiota, volatilome, phenotypic BD characteristics, and identifying patient groups with shared features. The study aims to identify taxonomic units and metabolic markers predicting clinical outcomes, assess the supplement's impact, and investigate the relationship between dietary habits and patient outcomes. This protocol contributes to understanding the microbiome's role in health and disease and pioneers an XAI-driven approach for personalized BD management. With 70 recruited BD patients, XAI algorithms will analyze multi-modal clinical data, potentially revolutionizing BD management and paving the way for improved patient outcomes.

P479 The prevalence and risk factors of hematologic malignancy in patients with intestinal Behçet’s disease

Abstract Background The association of intestinal Behçet’s disease (BD) with the risk of hematologic malignancy is still unclear. We aimed to assess the prevalence and determine risk factors of hematologic malignancy in intestinal BD. Methods Using a cohort of patients with intestinal BD between 1997 and 2021, the prevalence and risk factors of hematologic malignancy were analysed by logistic regression analysis at inflammatory bowel disease centre of Severance Hospital, Seoul, Korea. Results Among 780 intestinal BD patients, 23 patients developed hematologic malignancy. Myelodysplastic syndrome (MDS) (n=12) was the most common hematologic malignancy, followed by aplastic anemia (AA) (n=7), leukemia (n=2), and lymphoma (n=2). Eight patients had developed hematologic malignancy before their intestinal BD diagnosis and 15 patients developed hematologic malignancy after their intestinal BD diagnosis. Of the 772 patients without previous hematologic malignancy, patients smoking history (p-value 0.019, odds ratio [OR] 49.513, 95% confidence interval [CI] 1.925-1273.4), history of at least one emergency room (ER) visit (p-value 0.025, OR 26.360, CI 1.501-462.92), and albumin lower than 3.3g/dL (p-value 0.046, OR 603.013, CI 0.108-328191.23) at diagnosis were positively associated with subsequent hematologic malignancy. Body mass index (BMI) (p-value 0.030, OR 0.569, CI 0.342-0.947) was negatively associated with hematologic malignancy. Conclusion The physicians who care for intestinal BD patients with risk factors should be aware and provide careful monitoring of the elevated risk of hematologic malignancy.