Behcet's Disease Research Articles

Reduction of Neutrophil Activation by Phosphodiesterase 4 Blockade in Behçet's Disease.

Behçet's disease (BD) is a systemic vasculitis with inflammatory lesions mediated by cytotoxic T cells and neutrophils. Apremilast, an orally available small-molecule drug that selectively inhibits phosphodiesterase 4 (PDE4), has been recently approved for the treatment of BD. We aimed to investigate the effect of PDE4 inhibition on neutrophil activation in BD. We studied surface markers and reactive oxygen species (ROS) production by flow cytometry, and neutrophil extracellular traps (NETs) production and molecular signature of neutrophils by transcriptome analysis before and after PDE4 inhibition. Activation surface markers (CD64, CD66b, CD11b, and CD11c), ROS production, and NETosis were up-regulated in BD patient neutrophils compared to healthy donor neutrophils. Transcriptome analysis revealed 1,021 significantly dysregulated neutrophil genes between BD patients and healthy donors. Among dysregulated genes, we found a substantial enrichment for pathways linked to innate immunity, intracellular signaling, and chemotaxis in BD. Skin lesions of BD patients showed increased infiltration of neutrophils that colocalized with PDE4. Inhibition of PDE4 by apremilast strongly inhibited neutrophil surface activation markers as well as ROS production, NETosis, and genes and pathways related to innate immunity, intracellular signaling, and chemotaxis. We highlight key biologic effects of apremilast on neutrophils in BD.

Serum Elafin as a Potential Marker of Disease Activity in Behçet's Disease.

Elafin is a serine protease inhibitor with anti-inflammatory properties. It is expressed in various epithelial tissues with increased production under inflammatory conditions. Increased tissue elafin expression in Behçet's disease (BD) lesions has previously been demonstrated. We hypothesised that serum elafin might be increased in patients with BD and aimed to assess the relationship of serum elafin with disease activity and organ involvement in BD. Fifty-four BD patients (29 active, 25 inactive) and 30 healthy controls were included in this single-centre case-control study. Serum elafin was measured using ELISA. Complete blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) tests were also performed. Serum elafin levels were significantly higher in patients with BD (1.58 ± 0.47 ng/ml, range: 0.67-2.96) compared to controls (1.10 ± 0.28 ng/ml, range: 0.65-1.49) (P < 0.001). Patients with active BD had higher elafin levels than patients with inactive BD (P = 0.008). Active arthritis was associated with an increase in elafin (P = 0.012), while the presence of mucocutaneous symptoms was not. Serum elafin correlated significantly with ESR (P = 0.001). The ideal cut-off value for the diagnosis of BD was determined as 1.24 ng/ml with a sensitivity and specificity of 72.2% and 70.0%, respectively. Serum elafin is significantly increased in patients with BD. It may serve as a marker of disease activity, especially articular involvement.

Paracentral Acute Middle Maculopathy in Behçet's Disease.

To report a novel presentation of bilateral paracentral acute middle maculopathy (PAMM) and peripheral vascular occlusions in Behçet's disease (BD). A retrospective case report with multimodal imaging studies of a patient with BD. A 58-year-old Chinese man presented with a paracentral scotoma, fever, arthralgias and skin rash. HLA typing revealed HLA-B51 positivity. Ophthalmic examination showed peripheral retinal hemorrhages and fluorescence angiography (FA) demonstrated vascular occlusions in the peripheral retina bilaterally. Optical coherence tomography (OCT) showed classic acute PAMM lesions in both eyes. PAMM and peripheral vascular occlusion are infrequent and unconventional presentations of BD. To the best of our knowledge, this is the first report in the ophthalmic literature of PAMM and peripheral vascular occlusion in BD.

INFLUENCE OF SOMATIC STATUS ON THE APPEARANCE OF RECURRENT APHTHOSIS STOMATITIS

Recurrent aphthous stomatitis is a polyetiological inflammatory disease of the oral mucosa, characterized by the appearance of aphthous ulcers. The etiology and pathogenesis of this disease have not been finally revealed. There is an imbalance of immunity observed in patients who are suffering from recurrent aphthous stomatitis caused by the influence of certain trigger factors. The purpose is to summarize the literature data on the relationship of somatic status with the occurrence of recurrent aphthous stomatitis. The review considers the pathogenesis of recurrent aphthous stomatitis, as well as possible trigger factors: genetic predisposition, infections, somatic diseases, allergies, stress, and hypovitaminosis. An obligatory link in the pathogenesis of recurrent aphthous stomatitis is an imbalance of immunity - cellular (the production of pro-inflammatory cytokines increases, and the synthesis of anti-inflammatory heat shock proteins decreases) and humoral (an increase in the number of neutrophils and B-lymphocytes, activation of the complement system). Genetic predisposition, some somatic diseases (Behcet's disease) and viral infections (in particular, COVID-19) lead to an imbalance in the immune system. Provoke the occurrence of recurrent aphthous stomatitis infections, diseases of the gastrointestinal tract, stress and insufficiency of B vitamins and trace elements. The indirect effect of trigger circumstances is due to a decrease in the trophism of the oral mucosa, which leads to a local decrease in the number of factors of cellular and humoral immunity and to hyposalivation and a decrease in the pH of the oral fluid, which provokes the reproduction of opportunistic microflora. Based on the analyzed literature data, it can be concluded that the somatic status influences the development of recurrent aphthous stomatitis. Accordingly, patients suffering from recurrent aphthous stomatitis should be referred to a general doctor for evaluation.

Papulpustular dermatoses of the face, clinicopathological spectrum and response to treatment

The papulopustular rash on face may be a feature of several inflammatory skin disorders. Clinical features may provide clue to the etiology whereas microbiological testing and histopathologic examination confirm the diagnosis. In adults, facial papulopustular dermatoses include rosacea, perioral dermatitis, eosinophilic folliculitis, infections and medication induced. Our aim was to study variable causes of papulopustular lesions of the face. We conducted a prospective study which included 60 dermatology outpatient clinic patients of variable age groups whom presented with papulopustular lesions involving the face and review their clinicopathological findings as well as their response to therapy. Several diseases were reported including rosacea (47%), demodecosis (20%), bacterial folliculitis (13%), drug induced (7%) and periorificial dermatitis (3%). One case of tinea barbae, pityriosporum folliculitis, eosinophilic folliculitis, lupus miliaris disseminatus faciei, Behcet's disease and perforating folliculitis were reported. In conclusions; Papulopustular dermatoses involving the face are an important problem among dermatology patients with an overlapping in signs and symptoms. Awareness of various causes and their clincopathological features is important for accurate diagnosis and proper management.

Treatment with Biologic Drugs in Pediatric Behçet's Disease: A Comprehensive Analysis of the Published Data.

Behçet's disease (BD) is a variable vessel vasculitis. Biologic drugs are increasingly used in the treatment of BD. We aimed to analyze biologic drug use in the treatment of pediatric BD. MEDLINE/PubMed and Scopus databases were searched from the inception of these databases until 15 November 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only reports presenting data of pediatric patients with BD (BD diagnosis < 18 years of age) treated with biologic drugs were included. The demographic features, clinical characteristics, and data on treatment were extracted from the included papers. We included 87 articles including 187 pediatric patients with BD treated with biologic drugs (215 biologic treatments). Tumor necrosis factor (TNF)-α inhibitors (176 treatments) were the most frequently used biologic drugs followed by interferons (21 treatments). Other reported biologic treatments were anti-interleukin-1 agents (n = 11), tocilizumab (n = 4), daclizumab (n = 2), and rituximab (n = 1). The most common indication for biologic drug use was ocular involvement (93 treatments) followed by multisystem active disease (29 treatments). Monoclonal TNF-α inhibitors, adalimumab and infliximab, were preferred over etanercept in ocular and gastrointestinal BD. The improvement rates with any TNF-α inhibitor, adalimumab, infliximab, etanercept, and interferons were 78.5%, 86.1%, 63.4%, 87.5%, and 70%; respectively. The organ-specific improvement rate with TNF-α inhibitors was 76.7% and 70% for ocular and gastrointestinal system involvement. Adverse events have been reported for TNF-α inhibitors, interferons, and rituximab. Six of these were severe [TNF-α inhibitors (n = 4); interferons (n = 2)]. The presented systematic literature search revealed that TNF-α inhibitors followed by interferons were the most frequently used biologic drugs in pediatric BD. Both group of biologic treatments appeared to be effective and have an acceptable safety profile in pediatric BD. However, controlled studies are required for analyzing indications for biologic treatments in pediatric BD.

Characteristics of Patients With Behçet Disease From the Van Province, Eastern Turkey: Definition of Disease Clusters in a Tertiary Referral Center.

Behçet disease (BD) is a chronic inflammatory systemic disease that affects skin mucosa, joints, eyes, and blood vessels. Behçet disease shows some clinical differences in terms of disease manifestations and prognosis among the Silk Road countries, as well as various ethnicities even in the same country. In this study, we aimed to evaluate the clinical features and disease course of BD using cluster analysis in Van province, Eastern Turkey. This study was carried out in a tertiary referral center in Van province, by reviewing medical records. Seven disease manifestations were included to the cluster analysis as follows: mucocutaneous findings (oral ulcer, genital ulcer, erythema nodosum-like lesions, pseudofolliculitis), uveitis, superficial thrombophlebitis, musculoskeletal involvement, gastrointestinal system involvement, vascular involvement, and parenchymal central nervous system involvement. We identified 467 patients. After the exclusion of 6 patients who had missing data and 17 patients who did not live in Van, 444 patients (59.2% male) included into the study. Meeting the International Study Group and the International Criteria for Behçet Disease criteria were 91.6% and 96%, respectively, and 91.3% (n = 379/415) of these patients met both criteria. Four clusters were identified in the analyses: 132 patients (31.2%) in vascular (C1), 66 patients (15.6%) in ocular (C2), 60 patients (14.2%) in musculoskeletal (C3), and 165 patients (39%) in mucocutaneous (C4) clusters. Male gender ( p = 0.002; odds ratio [OR], 6.5; 95% confidence interval [CI], 2-21.4), superficial thrombophlebitis ( p = 0.001; OR, 4.7; 95% CI, 1.9-11.4), and uveitis ( p = 0.01; OR, 3.6; 95% CI, 1.3-9.9) were associated with vascular involvement in multivariate analysis. In our study, 4 clusters were detected in patients with BD from Van province. The prevalence of severe manifestations of BD may be related to genetic or environmental factors, such as differences in ethnicity and/or geographical differences. Despite the higher proportion of patients with a more severe disease, a favorable outcome was observed in our cohort.

Innate immune responses in Behçet disease and relapsing polychondritis.

Behçet disease (BD) and relapsing polychondritis (RP) are chronic multisystem disorders characterized by recurrent flare-ups of tissue inflammation. Major clinical manifestations of BD are oral aphthae, genital aphthous ulcers, skin lesions, arthritis, and uveitis. Patients with BD may develop rare but serious neural, intestinal, and vascular complications, with high relapse rates. Meanwhile, RP is characterized by the inflammation of the cartilaginous tissues of the ears, nose, peripheral joints, and tracheobronchial tree. Additionally, it affects the proteoglycan-rich structures in the eyes, inner ear, heart, blood vessels, and kidneys. The mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a common characteristic of BD and RP. The immunopathology of these two diseases may be closely related. It is established that the genetic predisposition to BD is related to the human leukocyte antigen (HLA)-B51 gene. Skin histopathology demonstrates the overactivation of innate immunity, such as neutrophilic dermatitis/panniculitis, in patients with BD. Monocytes and neutrophils frequently infiltrate cartilaginous tissues of patients with RP. Somatic mutations in UBA1, which encodes a ubiquitylation-related enzyme, cause vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) with severe systemic inflammation and activation of myeloid cells. VEXAS prompts auricular and/or nasal chondritis, with neutrophilic infiltration around the cartilage in 52-60% of patients. Thus, innate immune cells may play an important role in the initiation of inflammatory processes underlying both diseases. This review summarizes the recent advances in our understanding of the innate cell-mediated immunopathology of BD and RP, with a focus on the common and distinct features of these mechanisms.

Integrated analyses delineate distinctive immunological pathways and diagnostic signatures for Behcet's disease by leveraging gene microarray data.

Behcet's disease (BD) is a chronic inflammatory vasculitis and clinically heterogeneous disorder caused by immunocyte aberrations. Comprehensive research on gene expression patterns in BD illuminating its aetiology is lacking. E-MTAB-2713 downloaded from ArrayExpress was analysed to screen differentially expressed genes (DEGs) using limma. Random forest (RF) and neural network (NN) classification models composed of gene signatures were established using the E-MTAB-2713 training set and subsequently verified using GSE17114. Single sample gene set enrichment analysis was used to assess immunocyte infiltration. After identifying DEGs in E-MTAB-2713, pathogen-triggered, lymphocyte-mediated and angiogenesis- and glycosylation-related inflammatory pathways were discovered to be predominant in BD episodes. Gene signatures from the RF and NN diagnostic models, together with genes enriched in angiogenesis and glycosylation pathways, well discriminated the clinical subtypes of BD manifesting as mucocutaneous, ocular and large vein thrombosis involvement in GSE17114. Moreover, a distinctive immunocyte profile revealed T, NK and dendritic cell activation in BD compared to the findings in healthy controls. Our findings suggested that EPHX1, PKP2, EIF4B and HORMAD1 expression in CD14+ monocytes and CSTF3 and TCEANC2 expression in CD16+ neutrophils could serve as combined gene signatures for BD phenotype differentiation. Pathway genes comprising ATP2B4, MYOF and NRP1 for angiogenesis and GXYLT1, ENG, CD69, GAA, SIGLEC7, SIGLEC9 and SIGLEC16 for glycosylation also might be applicable diagnostic markers for subtype identification.

A patient-driven registry on Behçet's disease: the AIDA for patients pilot project.

This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet's disease (BD). The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet's Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0-30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1-50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range - 1.8-4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557-1.766], p < 0.001). Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information.

Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration

BackgroundUveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging.MethodsTwo plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents.ResultsIn total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified.ConclusionsThis study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents.

Immunopathogenesis of Behçet's disease

Behçet's disease (BD) is a multi-system inflammatory disorder with vasculitic features. It does not suit any of the current pathogenesis-driven disease classifications well, a unifying concept of its pathogenesis is not unanimously conceivable at present, and its etiology is obscure.Still, evidence from immunogenetic and other studies supports the notion of a complex-polygenic disease with robust innate effector responses, reconstitution of regulatory T cells upon successful treatment, and first clues to the role of an, as of yet, underexplored adaptive immune system and its antigen recognition receptors.Without an attempt to be comprehensive, this review aims to collect and organize impactful parts of this evidence in a way that allows the reader to appreciate the work done and define the efforts needed now. The focus is on literature and notions that drove the field into new directions, whether recent or more remote.

Isolated Papilledema Revealing Behçet's Disease: Case Report and Literature Review

Neuro-Behçet’s disease (NBD) is defined as the primary neurological involvement seen in patients with Behçet's disease (BD). It can be classified as parenchymal or non-parenchymal involvement, with variable manifestation that can be confused with other neuroinflammatory conditions of the nervous system. Papillitis is an inflammation of the optic disk that most often manifests itself with a papilledema. This condition seems to be exceptional during BD, especially as an initial presentation. We report the observation of a neuro-Behçet in a 30-year-old woman who presented with an isolated bilateral papillary edema.

Rheumatologist's Perspective on Non-Infectious Uveitis: Patterns from Tertiary Referral Rheumatologic Clinics in Italy.

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27- patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51- patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.

Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis

BackgroundThis study aimed to investigate the expression profile of immune response-related proteins of Behcet’s disease (BD) patients and identify potential biomarkers for this disease.MethodsPlasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method.ResultsProteomics results showed 43 DEPs between BD patients and HC (P < 0.05). These DEPs were mainly involved in the Toll-like receptor 9 and NF-κB signaling pathways. Five models were constructed using DEPs [interleukin 10 (IL10), Fc receptor like 3 (FCRL3), Mannan-binding lectin serine peptidase 1 (MASP1), NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2), FAM3 metabolism regulating signaling molecule B (FAM3B), and O-6-methylguanine-DNA methyltransferase (MGMT)]. Among these models, the neural network model showed the best performance (AUC = 0.856, recall: 0.692, specificity: 0.857, precision: 0.900, accuracy: 0.750, F1 score: 0.783). BD patients were divided into two subtypes according to the consensus clustering method: one with high disease activity in association with higher expression of tripartite motif-containing 5 (TRIM5), SH2 domain-containing 1A (SH2D1A), phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), hematopoietic cell-specific Lyn substrate 1 (HCLS1), and DNA fragmentation factor subunit alpha (DFFA) and the other with low disease activity in association with higher expression of C–C motif chemokine ligand 11 (CCL11).ConclusionsOur study not only revealed a distinctive immune response-related protein profile for BD but also showed that IL10, FCRL3, MASP1, NF2, FAM3B, and MGMT could serve as potential immune biomarkers for this disease. Additionally, a novel molecular disease classification model was constructed to identify subsets of BD.

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Kawasaki disease (KD) is a self-limited febrile illness diagnosed based on various clinical manifestations, including fever. The major complication of KD is systemic vasculitis, particularly involving the coronary artery. The etiology of KD is not clear, but the pathogenesis may be related to excessive activation of the immune system. Immune modulation for KD treatment, including intravenous immunoglobulin (IVIG), is based on the control of immune hyperactivation. Many studies have reported a genetic susceptibility to KD, which is related to immune cell activation (ITPKC, CAPS3, BLK, FCGR2A, etc.). The innate immunity of humans begins to recognize and react through pattern recognition receptors against pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Among receptors, the nucleotide-binding domain and leucine-rich repeat-containing receptor (NLRP) or NOD-like receptor (NLRs) in the cytosol contribute to inflammation as a key component. Cytosolic protein complexes called inflammasomes, assembled by NLRP, activate proinflammatory caspase 1 and 11, which ultimately produce IL-1β and IL-18 or induce cell death. IL-1 serves as an initiator for the recruitment of immune cells and the inflammatory response. Systemic vasculitis, such as Behcet disease, may be related to IL-1 polymorphism, and the expression of NLRP3. Coronary arteritis in KD is associated with an innate immune response, including IL-1. The suggested evidence of innate immunity in KD is related to increased neutrophils and monocytes, high levels of γδT cells, macrophage infiltration in coronary arteries and skin, elevated DAMPs such as S100 or HMGB1, and is sometimes associated with hyperactive innate immunity. The gene of the IL-1 pathway may be related to IVIG-resistant KD, and a clinical trial with IL-1 antagonist is currently ongoing. Adjunctive therapy in KD consists of various strategies, including second IVIG, steroids, and TNF inhibitors. The rationale for adjunctive therapy is based on immune hyperactivation with hypercytokinemia or immune modulation. Further efforts are needed to understand innate immunity and KD, especially in IVIG-resistant cases.

Behcet’s disease presenting with focal fibrosing mediastinitis and cava thrombosis; a case report with a review of the literature

Introduction: Behcet's disease is a rare, multisystemic disease characterized by vasculitis and a triad of recurrent oral and genital mucosa ulcers with uveitis. Mediastinal fibrosis is extremely rare in Behcet's disease. The aim of this paper is to report a case of Behcet’s disease presenting as mediastinal fibrosis. Case presentation: A 26-year-old male presented with a history of headaches and neck engorgement for a week duration. On physical examination, there were tender aphthous ulcers in the mouth, and one ulcer was also observed in the genitalia. Ultrasound of the neck revealed engorged internal jugular veins with a thrombus in the left one. Computed tomography confirmed the ultrasound findings. The patient was diagnosed with a case of Behcet’s disease. The patient was managed conservatively with Rivaroxaban, Prednisolone, and Ibuprofen. Conclusion: Behcet's disease can cause mediastinal fibrosis in rare cases. Computed tomography is an efficient method for detecting mediastinal fibrosis and superior vena cava thrombosis.

Comparison of Serum Levels of SIL-2R, IL-6, IL-10, TNF-α, CRP, ESR and Fibrinogen in Patients with Active and Inactive Behçet’s Disease

Behçet's disease (BD) is a chronic inflammatory illness that affects the entire body and is characterized by recurring episodes of oral aphthae, ocular and cutaneous lesions, and scrotal or vaginal ulcerations. The involvement of other organs and systems increases mortality in addition to the significant morbidity. This study involved a total of 40 participants, 20 of whom were healthy controls and 20 of whom were patients (of the 20 Behçet's patients, 12 (60%) were in the active phase and 8 (40%) were in the inactive phase). There was no therapy being given to any of the 20 patients that would have affected their cytokine levels. Only young men made up the patient and control groups because both early onset and male sex are signs of poor prognosis. The ELISA method was used to measure the levels of serum cytokines. The statistical analysis of the derived numerical values employed the Mann-Whitney U Test. We found a significant correlation between serum cytokine levels and classical acute phase markers in active Behçet’s patients. ESR (P &lt; 0,001), CRP (P &lt; 0,001), fibrinogen (P &lt; 0,001), IL-10 (P &lt; 0,001), IL-6 (P &lt; 0,001), SIL-2R (P &lt; 0,001) and TNFα (P &lt; 0,001). There was no statistically significant difference in serum levels of classical acute phase markers ESR (P = 0,746), CRP (P = 0,476) and fibrinogen (P = 0,940) when inactive Behçet’s patients and healthy controls were compared. However, serum levels of IL-10 (P &lt; 0,001), IL-6 (P = 0,001), SIL-2R (P &lt; 0,001) and TNFα (P = 0,001) were statistically different between inactive Behcet's patients and the control group. Our research shows that even in the inactive phase, serum cytokine levels of Behçet’s patients are much higher than the healthy control group. However, the levels of ESR, CRP and fibrinogen, which are classical acute phase markers, were found at normal levels in Behçet’s patients in the inactive phase. These findings show that measurement of serum interleukin levels will enable us to take preventive measures for morbidity and mortality follow-up of Behçet's patients.

Profiling the microbiome of oral and genital mucosal surfaces in Behçet's disease

Almost 90% of Behçet's patients present with oral and/or genital ulcers which influence the disease outcome. We hypothesised that the dysregulation of the oral and genital microbiome, coupled with dysregulation of the immune response, contributes to the aetiopathogenesis of Behçet's Disease (BD) and drives disease activation. Method152 BD patient samples; 70 matched oral and genital samples plus 12 unmatched samples (Female: Male, 58:12; mean age, 42 ± 13.9: 39.3 ± 10.3) to profile microbial community high-throughput sequencing of the microbiome using 16 s rRNA sequencing targeting the V1/V2 and V3/V4 hyper variable regions were used and results reviewed in relation to disease severity, Work and Social Adjustment Scale (WSAS) outcomes and medication. ResultsAlpha and beta diversity were significantly decreased in genital compared to oral samples; p value<0.05. However, grouping the samples as to whether ulceration was present was not significant. Escherichia-Shigella was the only Amplicon Sequence Variants (ASVs) in the V1/V2 region that was shared between the oral mucosa with ulcer (O_U) and genital mucosa with ulcer (G_U) groups. This was in contrast to the V3/V4 region which indicated that Lachnospiraceae, Saccharimonadales, and Coriobacteriales were shared between the O_U and G_U groups.In addition, gender had no impact on the bacterial abundance in V1/V2 analysis of the oral and genital samples. V3/V4 analysis of genital samples demonstrated that Lactobacilli and Gardnerella were significantly increased in females (20 times) compared to the males in samples; p-adj <0.05. Interestingly in BD patients, Rothia which is commonly found in the mouth was present in both oral and genital samples.Streptococci were significantly increased while Veillonella significantly decreased in the presence of oral ulceration in the BD cohort.The clinical phenotype had no effect on V1/V2 and V3/V4 on the bacterial abundance of oral samples. However, medication e.g. colchicine had a significant effect on the oral microbial abundance (V1/V2; P = 0.020, V3/V4; P = 0.003). There was no relationship between colchicine and the presence/absence of genital ulcers.BD patients with active disease had higher WSAS scores, and their bacterial abundance differed significantly from the non-active BD patients (ADONIS, R2 = 0.05, p value =0.029). ConclusionThe presence of the microbes Streptococcus, Veillonella, Gardnerella, Lactobacillus, Atopobium, Peptoniphilus, Corynebacterium and Staphylococcus may provide early evidence of BD patients are with active disease.

Interleukin-21 receptor gene polymorphism (rs2285452 A/G) is associated with susceptibility to Behçet's disease.

Behçet's disease (BD) is a chronic auto inflammatory disorder of unknown aetiology. Recently, the dysregulation of interleukin-21 receptor (IL-21R) has been incriminated in different autoimmune and auto-inflammatory diseases, such as systemic lupus erythematous, rheumatoid arthritis, and type 1 diabetes. Herein, we aimed to investigate the association of two Il-21R gene polymorphisms with BD. IL-21R rs2214537 and IL-21R rs2285452 genotypings were investigated in a cohort of 110 adult patients with BD and 116 age and gender unmatched healthy controls. Genotyping was performed by mutagenically separated polymerase chain reaction with newly designed primers. IL-21R rs2285452 genotypes and alleles distribution were statistically different between patients with BD and controls. GA and AA genotypes carrying the minor A allele were more frequent in patients with BD than in healthy controls (37.3% and 11.8% vs. 23.3% and 3.4%, respectively). The minor A allele was associated with an increased BD risk (odds ratios =2.42, 95% confidence interval =1.214.87, p =.005). IL-21R rs2214537 GG genotype was found to be associated with susceptibility to BD in the recessive model (GG vs. CC + CG; p =.046, OR = 1.91, 95% CI = 1.003.650. IL-21R rs2285452 and IL-21R rs2214537 were not in linkage disequilibrium (D' =0.42). The AG haplotype was more frequently observed in patients with BD than in controls (0.247 vs. 0.056, p = .0001). This study for the first time reports the association of IL-21R rs2285452 and IL-21R rs2214537 with BD. Functional studies are required to elucidate the exact role of these genetic variants.