Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet's disease.

Behçet's disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors. We observed prominent expansion and transcriptional changes in monocytes in PBMCs from BD patients. Deciphering the monocyte heterogeneity revealed the accumulation of C1q-high (C1qhi) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1qhi monocyte-ended trajectory. Further experiments showed that C1qhi monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1qhi monocytes were induced by activated interferon-γ (IFN-γ) signaling in BD patients and were decreased by tofacitinib treatment. Our study illustrates the BD immune landscape and the unrecognized contribution of C1qhi monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.

Identification of biomarkers for abdominal aortic aneurysm in Behçet's disease via mendelian randomization and integrated bioinformatics analyses.

Behçet's disease (BD) is a complex autoimmune disorder impacting several organ systems. Although the involvement of abdominal aortic aneurysm (AAA) in BD is rare, it can be associated with severe consequences. In the present study, we identified diagnostic biomarkers in patients with BD having AAA. Mendelian randomization (MR) analysis was initially used to explore the potential causal association between BD and AAA. The Limma package, WGCNA, PPI and machine learning algorithms were employed to identify potential diagnostic genes. A receiver operating characteristic curve (ROC) for the nomogram was constructed to ascertain the diagnostic value of AAA in patients with BD. Finally, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were conducted. The MR analysis indicated a suggestive association between BD and the risk of AAA (odds ratio [OR]: 1.0384, 95% confidence interval [CI]: 1.0081-1.0696, p = 0.0126). Three hub genes (CD247, CD2 and CCR7) were identified using the integrated bioinformatics analyses, which were subsequently utilised to construct a nomogram (area under the curve [AUC]: 0.982, 95% CI: 0.944-1.000). Finally, the immune cell infiltration assay revealed that dysregulation immune cells were positively correlated with the three hub genes. Our MR analyses revealed a higher susceptibility of patients with BD to AAA. We used a systematic approach to identify three potential hub genes (CD247, CD2 and CCR7) and developed a nomogram to assist in the diagnosis of AAA among patients with BD. In addition, immune cell infiltration analysis indicated the dysregulation in immune cell proportions.

The safety and efficacy of TNF inhibitors in patients with Behçet's disease: Retrospective study from eastern Turkey.

OBJECTIVE: We aimed to evaluate the clinical features, disease course, and associated factors for outcome in severe/refractory BD patients receiving TNF-i treatment. MATERIAL AND METHODS: This retrospective study was conducted by reviewing medical records from a tertiary referral center in Van province in Eastern Turkey. Data were obtained from patients' charts followed up between June 2019 and June 2022. RESULTS: We included 469 BD patients (59.3% male) whose 80 patients (17%) received TNF-i treatment in the study. The mean ± standard deviation of the patient age was 36.7 ± 10.1 years and the median (IQR) disease duration was 12 (12) years. IFX and ADAwere initiated in 67.5% (n = 54) and 32.5% (n = 26) patients, respectively. Overall and first-line retention rates of TNF-i were 84.7% and 92.6% for IFX and 83.3% and 80.8% for ADA, respectively. IFX was discontinued in 9 patients which were in 2 patients due to allergic reaction and tuberculosis, 3 patients for inefficacy, one patient for heart failure, and one patient for orbital zona. Although no serious adverse event was observed with ADA, 5 patients switched to IFX due to inefficacy. Overall, 72 patients (90%) resumed TNF-i at the end of the study; TNF-i was discontinued in 3 patients (3.8%) due to severe adverse events and in 5 patients (6.2%) with prolonged remission. CONCLUSION: In our study, no case of death was observed in TNF-i receiving patients. Most patients achieved attack-free and CS-free disease and retained TNF-i treatment. TNF inhibitors appear to be safe and effective in patients with severe/refractory Behçet's disease.

"Deficiency in ELF4, X-Linked": a Monogenic Disease Entity Resembling Behçet's Syndrome and Inflammatory Bowel Disease.

Defining monogenic drivers of autoinflammatory syndromes elucidates mechanisms of disease in patients with these inborn errors of immunity and can facilitate targeted therapeutic interventions. Here, we describe a cohort of patients with a Behçet's- and inflammatory bowel disease (IBD)-like disorder termed "deficiency in ELF4, X-linked" (DEX) affecting males with loss-of-function variants in the ELF4 transcription factor gene located on the X chromosome. An international cohort of fourteen DEX patients was assessed to identify unifying clinical manifestations and diagnostic criteria as well as collate findings informing therapeutic responses. DEX patients exhibit a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum. Patients have been predominantly treated with anti-inflammatory agents, with the majority of DEX patients treated with biologics targeting TNFα.

A possible role of lncRNA MEG3 and lncRNA MAFG-AS1 on miRNA 147-b in the pathogenesis of Behcet's disease.

Behcet's disease (BD) is a multisystem disease with altered Toll-like receptors (TLRs) on macrophages. Long noncoding RNA Maternally expressed gene 3 (lncRNA MEG3) and lncRNA Musculoaponeurotic fibrosarcoma oncogene family, protein G antisense 1 (MAFG-AS1) are regulators of microRNA (miRNA) 147-b, which is induced upon TLR stimulation. We included fifty BD patients, and fifty age and sex-matched controls. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of serum lncRNA MEG3, lncRNA MAFG-AS1, and miRNA 147-b. LncRNA MEG3 and lncRNA MAFG-AS1 were significantly downregulated while miRNA 147-b was significantly upregulated in the BD patients' serum compared to the controls with p-value <0.001. Receiver operation characteristics (ROC) curve analysis revealed that the three biomarkers can discriminate between BD and control subjects with 76%, 100%, and 70% sensitivity respectively, and 100% specificity for all of them. There was a lower expression level of lnc RNA MEG3 among patients who had new eye involvement in the last month in comparison to those without new eye involvement (p-value=0.017). So, LncRNA MEG3, lncRNA MAFG-AS1, and miRNA147-b are promising diagnostic markers and therapeutic targets for BD patients. LncRNA MEG3 can be used as a predictor for new BD ocular involvement.

Decoding Behcet's Uveitis: an In-depth review of pathogenesis and therapeutic advances.

Behcet's disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet's uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients.

Exploring relief for Behçet's disease refractory oral ulcers: a comparison of TNF inhibitors versus apremilast.

OBJECTIVES: Oral and genital ulcers are the hallmark manifestation of Behçet's disease (BD), significantly impacting patients' quality of life. Our study focuses on comparing the effectiveness and safety of TNF inhibitors (TNFis) and apremilast in controlling oral ulcers of BD, aiming to provide evidence-based guidance for physicians in selecting appropriate treatment modalities. METHODS: A retrospective analysis was performed on BD patients treated between December 2016 and December 2021 with TNFis or apremilast for refractory oral ulcers. The study assessed treatment response by the absence of oral ulcers at 3 and 6 months, with additional evaluations for genital ulcers and articular involvement. RESULTS: The study included 78 patients, equally allocated between TNFis and apremilast treatments. Both groups showed significant oral ulcer reduction at 3 (p< 0.001) and 6 months (p= 0.01) with no significant difference between the treatments. Apremilast had a notable corticosteroid-sparing effect by the 3-month follow-up, persisting through 6 months. Both treatments were equally effective in reducing genital ulcers, with TNFis showing greater effectiveness in addressing articular involvement. Apremilast had a higher discontinuation rate due to gastrointestinal side effects. CONCLUSION: TNFis and apremilast are both effective for treating BD refractory oral ulcers. While TNFis may offer broader benefits for other disease manifestations, apremilast is distinguished by its corticosteroid-sparing effect, especially for patients with a milder disease phenotype. Treatment selection should consider individual disease severity and clinical features to ensure a personalized and effective management strategy.

Shelterin dysfunction promotes CD4+ T cell senescence in Behçet's disease.

OBJECTIVES: To investigate the potential role of shelterin dysfunction in naïve CD4+ T cells in the pathogenesis of Behçet's disease (BD). METHODS: Naïve CD4+ T cells were isolated from 40 BD patients and 40 sex- and age-matched healthy controls (HC). Senescent profiles, shelterin subunits expression, telomere length, telomerase activity and critical DNA damage response (DDR) were evaluated. Telomere repeat factor-2 (TRF2) silencing was conducted for further validation. RESULTS: Compared with HC, BD patients had significantly decreased naïve CD4+ T cells, increased cell apoptosis, senescence, and productions of TNF-α and IFN-γ upon activation. Notably, BD naïve CD4+ T cells had shortened telomere, impaired telomerase activity, and expressed lower levels of shelterin subunits TRF2, TRF1- and TRF2-Interacting Nuclear Protein 2 (TIN2) and Repressor/Activator Protein 1 (RAP1). Furthermore, BD naïve CD4+ T cells exhibited significantly increased DDR, evidenced by elevated phosphorylated ataxia telangiectasia (AT) mutated (pATM), phosphorylated p53 (pp53) and p21. Finally, TRF2 silencing markedly upregulated DDR, apoptosis and proinflammatory cytokines production in HC naïve CD4+ T cells. CONCLUSION: Our study demonstrated that TRF2 deficiency in BD naïve CD4+ T cells promoted cell apoptosis and senescence, leading to proinflammatory cytokines overproduction. Therefore, restoring TRF2 might be a promising therapeutic strategy for BD.

Endothelial dysfunction and complement activation are independently associated with disease duration in patients with systemic vasculitis.

OBJECTIVES: Systemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV. METHODS: We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group. RESULTS: We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity. CONCLUSION: Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.

NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis: case report and review of literature.

BACKGROUND: We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet's. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic. CASE: The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet's disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity. LITERATURE REVIEW: We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later. CONCLUSION: As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.

Novel Serum Markers that Distinguish Behcet's Disease from Idiopathic Recurrent Aphthous Stomatitis.

BACKGROUND: Behcet's disease (BD) is a rare and recurrent autoinflammatory disorder characterized by systemic vasculitis, frequently manifested as recurrent aphthous stomatitis (RAS). We aim to identify specific serum proteins to discriminate between BD and idiopathicRAS. METHOD: Peripheral blood was collected from 12 BD patients, 12 idiopathic RAS patients, and 21 healthy volunteers. The serum samples underwent Tandem Mass Tag-based mass spectrometry analysis. Differentially expressed proteins (DEPs) were identified for KEGG pathway enrichment, Gene Ontology (GO), and protein-protein interaction (PPI) analyses. ELISA was utilized to verify two BD-specific DEPs in another cohort consisting of 18 BD patients, 18 idiopathic RAS patients, and 18 controls. RESULTS: Compared with RAS serum, BD serum showed 242 DEPs. 49 proteins were differentially expressed in BD but not RAS serum compared to healthy controls. KEGG pathway and GO analyses revealed that DEPs in BD and RAS have similar biological functions and cellular distributions, featuring a significant association with pathways regulating blood coagulation and immune response. When comparing DEPs between BD and RAS, several keratins emerged as markers that distinguish RAS from BD. We also identified multiple DEPs in BD but not RAS patients. PPI analysis uncovered that lipoprotein metabolism regulators serve as hub proteins, indicating their potentially essential roles in BD pathology. In addition, ELISA results confirmed the elevated LRG1 and SOD3 levels in BD, but not RAS patients, compared to healthy donors. CONCLUSION: Our data uncovered novel serum proteins that distinguish BD from RAS, which may potentially be useful in BD diagnosis and treatment.

Role of Optical Coherence Tomography in Vasculitis-Associated Pulmonary Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Identifying and understanding the microstructural changes within the wall of the pulmonary artery (PA) is crucial for elucidating disease mechanisms and guiding treatment strategies. We assessed the utility of optical coherence tomography (OCT) in identifying such changes within segmental/subsegmental PAs and compared the morphological variations in WHO group 4 pulmonary hypertension associated with Behcet Disease (BD), Takayasu arteritis (TA) and chronic thromboembolic pulmonary hypertension (CTEPH). Idiopathic pulmonary arterial hypertension (IPAH) patients served as controls.Methods and Results: A total of 197 cross-sectional images were analyzed from 20 consecutive patients. BD patients exhibited lower %wall area and mean wall thickness (MWT) compared with CTEPH, TA and, IPAH patients. TA patients showed a notably higher %wall area, which was significant in IPAH and BD patients. Variations in %wall area measurements were observed across distinct cross-sectional segments of the PA within individual patients (22% in CTEPH, 19% in BD, 16% in TA, 23% in IPAH patients). Intravascular webs, bands, and thrombi were observed in BD and CTEPH patients. OCT provided clear delineation of vascular wall calcifications and adventitial vasa vasorum. No procedure-related complications were observed. CONCLUSIONS: PA involvement differs among the various etiologies of PH, with the PA being heterogeneously affected. OCT offers promise in elucidating microstructural vascular wall changes and providing insights into disease mechanisms and treatment effects.

Systemic calcineurin inhibitors tacrolimus and voclosporin: A review of off-label dermatologic uses.

BACKGROUND: Systemic calcineurin inhibitors, cyclosporine, tacrolimus, and voclosporin, have been utilized in various dermatologic conditions. Although there have been numerous off-label dermatologic indications with published guidelines for cyclosporine, there is no established strong consensus for tacrolimus and voclosporin. OBJECTIVE: To conduct a review of off-label use of systemic tacrolimus and voclosporin in various dermatoses to better inform treatment methods. METHODS: A literature search was conducted using PubMed and Google Scholar. Relevant clinical trials, observational studies, case series, and reports regarding off-label dermatologic uses of systemic tacrolimus and voclosporin were included. RESULTS: Tacrolimus shows promise for numerous dermatologic conditions, including psoriasis, atopic dermatitis/eczema, pyoderma gangrenosum, chronic urticaria, and Behcet's disease. Randomized controlled trial data are only available for voclosporin in psoriasis, which showed efficacy but did not meet noninferiority to cyclosporine. LIMITATIONS: Data were limited and extracted from published papers. Studies differed in methodology, and nonstandardized outcomes limited the conclusions drawn. CONCLUSIONS: In comparison to cyclosporine, tacrolimus can be considered for treatment-refractory disease or in patients with cardiovascular risk factors or inflammatory bowel disease. Voclosporin has only been utilized in psoriasis currently, and clinical trials in psoriasis show voclosporin's efficacy. Voclosporin can be considered for patients with lupus nephritis.

Upper gastrointestinal involvement of Behçet's disease in Japan: endoscopic findings and clinical features.

AIM: Behçet's disease (BD) can involve any gastrointestinal (GI) tract site. We analyzed the characteristics, risk factors, and treatment responses to upper GI (UGI) involvement in patients with BD. METHODS: This retrospective cohort study analyzed UGI findings in 101 patients with BD who underwent endoscopy between April 2005 and December 2022 at the University of Tokyo Hospital. The patients were divided into two groups based on the presence or absence of UGI findings. Patient backgrounds, clinical symptoms, colonoscopy (CS) findings, and blood test findings were compared between the groups. RESULTS: In total, 18.8% (19/101) of the patients had UGI lesions. The prevalence rates in the esophagus, stomach, and duodenum were 6.9%, 6.9%, and 8.9%, respectively. Of these 19 patients, BD treatment were intensified in 10 (52.6%) patients after esophagogastroduodenoscopy (EGD), and all showed improvement in symptoms or endoscopic findings. In the multivariate analysis, symptoms (OR: 37.1, P < 0.001), CRP > 1 mg/dL (OR: 11.0, P = 0.01), and CS findings (OR: 5.16, P = 0.04) were independent predictors of UGI involvement in BD patients. The prediction model for UGI involvement using these three factors was highly accurate, with an AUC of 0.899 on the ROC curve. In the subgroup analysis of intestinal BD, symptoms (OR: 12.8, P = 0.01) and ESR > 20 mm/h (OR: 11.5, P = 0.007) were independent predictors. CONCLUSIONS: EGD should be conducted in BD patients with high CRP, GI symptoms, and lower GI involvement, which leads to better management of BD in terms of improving symptoms and endoscopic findings.

Association between COVID-19 infection and uveitis flare in patients with Behcet's disease, a retrospective multicenter cohort study.

PURPOSE: To explore if COVID-19 infection and its subsequent immunosuppressant adjustment as well as previous vaccination status are associated with higher risks of uveitis flare in patients with Behcet's disease. METHODS: This retrospective multicenter cohort study was conducted in January 2023 among patients with Behcet's uveitis, during the second wave of the COVID-19 pandemic in China, with an anticipated sample size of 250. The primary objective was to examine the association between COVID-19 infection and the occurrence of uveitis flare. The potential impact of other exposures, including the patient's vaccination status and treatment adjustments to the risk of uveitis flare and the course of COVID-19 infection were also analyzed. RESULTS: 207 patients with COVID-19 infection and 47 patients without COVID-19 infection were included. A total of 127 uveitis flares occurred in the observational period (14.29 events per 100 person-month). COVID-19 infection was found to be significantly associated with a higher rate of uveitis flare (adjusted rate ratio = 4.8, 95% CI 3.7 to 6.3, P < 0.001). However, neither systemic immunosuppressive adjustment nor COVID-19 vaccination status showed a significant association with uveitis flare or the course of COVID-19 infection. CONCLUSIONS: This study provides evidence of an association between COVID-19 infection and an increased risk of uveitis flare in patients with Behcet's disease. However, there was no significant evidence to support that baseline immunosuppressive therapy regimens, treatment adjustment after COVID-19 infection, or vaccination status were associated with higher risks of uveitis flare or prolonged COVID-19 course.

COVID 19 vaccination as a trigger of acute genital ulcers in an immunocompromised adolescent-case study and literature review.

Acute genital ulcers can affect females of all ages. In children, they often appear as an emergency and remain a diagnostic challenge for pediatricians, gynecologists and dermatologists. Prompt diagnosis and identification of disease- related factors help to implement appropriate treatment. Firstly, it is crucial to properly compile the past medical history of the patient. Past infectious, autoimmune, malignant or traumatic conditions, as well as vaccinations may contribute to the occurrence of acute genital ulcers. Moreover, new infectious agents, such as severe acute respiratory syndrome coronavirus 2 and vaccinations against Coronavirus disease of 2019, may play a significant role in the development of atypical clinical symptoms. Here we present a case of a 12-year-old girl with acute genital ulcers. Additional symptoms accompanying the ulcer included: abdominal pain, nausea, vomiting, dysuria, vulvar pain and fever. Blood test showed leukocytosis, especially neutrophilia and monocytosis and increased levels of c-reactive protein and procalcitonin. Serological tests for the most common infections were negative. Moreover, the patient had a history of autoimmune diseases. She had periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome, and IgA vasculitis, also known as Henoch-Schönlein purpura in her past medical history. Additionally, she was vaccinated against SARS-CoV-2 shortly before the lesions appeared.

Quantitative urinary proteome analysis reveals potential biomarkers for disease activity of Behcet's disease uveitis.

PURPOSE: Behçet's disease-associated uveitis (BDU) is a severe, recurrent inflammatory condition affecting the eye and is part of a systemic vasculitis with unknown etiology, making biomarker discovery essential for disease management. In this study, we intend to investigate potential urinary biomarkers to monitor the disease activity of BDU. METHODS: Firstly, label-free data-dependent acquisition (DDA) and tandem mass tag (TMT)-labeled quantitative proteomics methods were used to profile the proteomes of urine from active and quiescent BDU patients, respectively. For further exploration, the remaining fifty urine samples were analyzed by a data-independent acquisition (DIA) quantitative proteomics method. RESULTS: Twenty-nine and 21 differential proteins were identified in the same urine from BDU patients by label-free DDA and TMT-labeled analyses, respectively. Seventy-nine differentially expressed proteins (DEPs) were significantly changed in other active BDU urine samples compared to those in quiescent BDU urine samples by IDA analysis. Gene Ontology (GO) and protein-protein interaction (PPI) analyses revealed that the DEPs were associated with multiple functions, including the immune and neutrophil activation responses. Finally, seven proteins were identified as candidate biomarkers for BDU monitoring and recurrence prediction, namely, CD38, KCRB, DPP4, FUCA2, MTPN, S100A8 and S100A9. CONCLUSIONS: Our results showed that urine can be a good source of biomarkers for BDU. These dysregulated proteins provide potential urinary biomarkers for BDU activity monitoring and provide valuable clues for the analysis of the pathogenic mechanisms of BDU.

Trends in health care of patients with vasculitides, including giant cell arteritis, Takayasu arteritis, ANCA-associated vasculitis and Behçet's disease: cross-sectional data of the German National Database 2007-2021.

The aim of this study is to present the current care situation of patients with giant cell arteritis (GCA), Takayasu arteritis (TAK), ANCA-associated vasculitis (AAV) and Behçet's disease (BD). Trends over the last 15 years will reflect improvements and remaining deficits in the management of vasculitides. Consecutive cross-sectional data from patients with vasculitides from the German National Database (NDB) of the Collaborative Arthritis Centres between 2007 and 2021 were included. Medication, physician- and patient-reported outcomes on disease activity and disease burden, inpatient stays and occupational participation are compared for different vasculitis entities and over time. Employment rates were compared to German population rates. Between 502 and 854 vasculitis patients were annually documented. GCA and AAV were the most common vasculitides. Median disease duration ranged from 2 to 16 years. Over the years, glucocorticoids decreased in proportion and dose, most markedly in GCA and TAK, while biologic therapies increased up to 27%. Physicians rated disease activity as low for the vast majority of patients, while patients-reported moderate outcomes in many dimensions. PROs remained largely unchanged. The proportion of employed patients (< 65 years) increased from 47 to 57%. In recent years, biologics are increasingly used in patients with vasculitides, while glucocorticoids decreased significantly. PRO's have not improved. Work participation increased but remains lower than that in the German population.

A patient with Behcet's disease and IgA nephropathy in China.

BACKGROUND: Behcet's disease (BD) is an inflammatory disorder of unknown cause that is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Local vasculitis can cause damage to the visceral system, but it is rare in kidney patients, especially those with IgA nephropathy (IgAN). In China, a small number of related cases have been reported. Here we present a case of co-occurrence of BD and IgAN. CASE PRESENTATION: An 18-year-old female who presented with a history of recurrent oral ulcers was found ten years ago. Four years later, the patient presented with reddish nodules on the skin of both lower limbs and then presented with vulvar ulcers. This patient was clinically diagnosed with Behcet's disease after left calf skin biopsy and presented severe proteinuria and hematuria during this period. IgAN was diagnosed after percutaneous renal biopsy. The patient was treated with hormonal, anti-inflammatory, immunomodulatory, kidney protective, and protein-lowering urine agents. After 3 years of follow-up, the patient reappears oral ulcers, reddish nodules on the skin of both lower limbs and renal dysfunction. CONCLUSIONS: BD is less common in China and is clinically prone to missed diagnosis and misdiagnosis. BD with IgAN is rarer. We should regularly pay attention to the routine urine and renal function of BD patients for early detection and treatment and to prevent further progression of the disease.

Evaluation of right ventricular function in patients with Behcet's disease by four-dimensional echocardiography.

AIM: Behcet's disease (BD) is a systemic disorder characterized by vasculitis, resulting in thickened vascular walls that reduce elasticity and impair function. BD can involve the cardiovascular system in three ways: cardiac, arterial, and venous. In this study, our objective was to evaluate the efficacy of pulmonary arterial stiffness (PAS) and pulmonary pulse transit time (PPTT) measures in demonstrating right ventricular functions in asymptomatic BD patients. We aimed to objectively evaluate right ventricular function in patients with BD using four-dimensional echocardiography (4DE). METHOD: This study included 40 patients diagnosed with BD and 40 healthy subjects. Demographic, clinical, laboratory, and echocardiographic parameters were compared. In addition to standard transthoracic echocardiographic evaluation, right ventricle quantification (RVQ) by using the 4DE and 2D-speckle tracking echocardiography were performed. RESULTS: The sPAP, 4D RVQ, and right ventricular strain values exhibited significant differences between the BD and control groups. Right ventricular end-diastolic diameter (RVDD), right ventricular end-systolic diameter (RVSD), right atrium (RA) area, right ventricular myocardial performance index (RVMPI), and PAS were increased in BD patients compared to the control group. Right ventricular ejection fraction (RVEF), right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), Tricuspid S', and PPTT were decreased in BD patients compared to control subjects. PPTT correlated with right ventricular free wall strain (RV-FWS) and PAS. In a multivariate linear regression analysis, PAS and RVFAC were found to be independent predictors of RVFWS. In addition, RVFAC and TAPSE are independent predictors for PPTT. CONCLUSION: Patients with BD may have elevated pulmonary arterial stiffness (PAS) in correlation with decreased PPTT. To ascertain the prognosis for these individuals, right ventricular (RV) functions must be evaluated. Measurements of RVFAC and RVEF via 4DE and deformation imaging techniques may be more useful in identifying subclinical impairment of RV. Individuals with BD, PAS, and PPTT may suggest a link between early pulmonary vascular remodeling and RV subclinical impairment.