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.

Surgical Intervention for Giant Pulmonary Artery Aneurysm in Behcet Disease: A Case Report.

BACKGROUND Pulmonary artery aneurysm (PAA), defined as a pathologic dilatation of the PA greater than 1.5-fold the normal diameter, is a rare complication of Behçet disease. It is due to a weakening of the vessel wall for a great vessels' vasculitis, often asymptomatic and incidentally diagnosed on imaging studies. However, if ignored, it can lead to life-threatening complications such as rupture and massive hemoptysis. We report the case of a giant fast-growing PAA in a young patient with a history of Behçet disease in which an inadequate follow-up and poor patient information could had led to life-threatening complications. CASE REPORT A 37-year-old man with a history of Behçet disease presented to our Emergency Department with hemoptysis due to a right inferior lobar artery aneurysm measuring 52×33 mm. The aneurysm was detected years before, measuring 18 mm, but the patient and physicians missed the subsequent follow-up. After several attempts at embolization, the multidisciplinary board suggested to proceed with surgical intervention. Surgery was performed with an extracorporeal circulation system kept on stand-by due to the high hemorrhagic risk. By opening the fissure, the dilatation of the inferior lobar artery was clearly identified up to the origin of the middle lobar branch. Thus, a lower-middle bilobectomy was performed after the introduction of a suction cannula in the aneurysm, which facilitated its emptying and the subsequent maneuvers. CONCLUSIONS PAA is a rare disease, generally treated with medical therapy or interventional procedures. However, giant and fast-growing aneurysms are more likely to entail complications and often required immediate treatment. In this case, primary surgical intervention with a pulmonary bilobectomy appeared mandatory to avoid life-threatening events.

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The patient 1, a 13-year-old boy, was admitted due to "recurrent oral ulcers for 3 years, abdominal pain for 8 months, and perianal ulcers for 10 days"; The patient 2, a 3-year-old boy, was admitted due to "recurrent abdominal pain, diarrhea, and fever for over 3 months". Genetic testing of both patients revealed "deficiency in ELF4, X-linked" (DEX), and the patients were diagnosed with Behcet's disease-like syndrome due to deficiency in ELF4, accordingly. The patient 1 was successively given intravenous methylprednisolone pulses and oral prednisone and mesalazine for symptomatic treatment. The patient 2 was successively treated with corticosteroids combined with enteral nutrition, as well as oral mercaptopurine. Subsequently, both patients showed improvements in symptoms and were discharged.

Development of neuro-Behcet's disease in a patient with operable HER2-positive breast cancer during neoadjuvant chemotherapy: A case report.

BACKGROUND: Neuro-Behcet's disease (NBD) is a variant of Behcet's disease (BD). To our knowledge, there have been no previous reports on concurrent NBD in breast cancer patients undergoing chemotherapy. CASE PRESENTATION: Our patient had a history of BD and was asymptomatic. She was diagnosed with human epidermal growth factor receptor 2-positive breast cancer by core needle biopsy and was administered neoadjuvant chemotherapy. After four courses, in addition to the aggravation of the existing adverse events, headache, fever, dysarthria, and muscle weakness in the upper left and lower extremities appeared. On admission, she was diagnosed with acute NBD, and steroid therapy was initiated. After her symptoms improved gradually, she was discharged. Then, she underwent mastectomy and axillary lymph node dissection for breast cancer. Trastuzumab and pertuzumab plus tamoxifen were administered postoperatively. Two years postoperatively, no recurrence of breast cancer and NBD was noted. CONCLUSION: When chemotherapy is administered to breast cancer patients with a history of BD, it is necessary to select chemotherapy with as few adverse events as possible and to continue with treatment while paying attention to the risk of NBD.

Blue Toe Syndrome in Behçet's Disease: A Case Report.

BACKGROUND Vascular Behçet's disease (VBD) is a rare but potentially life-threatening subtype of Behçet's disease that is characterized by multisystemic vasculitis. It primarily affects males with ancestry traced back to regions along the ancient Silk Road. Both arteries and veins, regardless of size, may exhibit complications, including aneurysmal degeneration or occlusion. While venous involvement is observed in two-thirds of VBD cases, arterial complications are notably the most severe and lethal. Arterial aneurysmal degeneration is more common than occlusive complications, with larger arteries being predominantly affected in VBD. Data regarding isolated small-vessel arterial occlusive disease in VBD are limited. Given the rarity of this presentation in this patient population, it becomes mandatory to thoroughly evaluate such patients to differentiate small-vessel vasculitis from other similar diseases, such as Raynaud's phenomenon, which has a different etiology and management and generally has a more benign course. Here, we delineate the concept of isolated small-vessel vasculitis as a cause of blue toe syndrome in patients with VBD. CASE REPORT This report describes a distinctive case of vascular Behçet's disease in a 51-year-old man who initially exhibited unilateral blue toe syndrome, which swiftly progressed to dry gangrene of the toes. Despite reports of large-vessel involvement, there is a paucity of data on isolated small-vessel vasculitis-induced digital ischemia in VBD. CONCLUSIONS This atypical case underscores the necessity of clinical discernment in differentiating inflammatory microvascular occlusive disease from vasospastic Raynaud's syndrome, both of which can complicate Behçet's disease.

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.

Behcet's-like disease induced by secukinumab in a patient with psoriasis: a case report and literature review.

Purpose: The incidence of cutaneous paradoxical reactions associated with IL-17 inhibitors has gained attention in recent literature. Our report aims to investigate the characteristics of one rare paradoxical reaction, presenting as Behcet's disease.Methods: We reported one case of Behcet's-like disease induced by secukinumab in a patient with psoriasis. This patient, a young woman with a long history of psoriasis, showed significant improvement in her psoriatic condition after receiving four doses of secukinumab. Unexpectedly, she developed symptoms such as high fever, painful oral and genital ulcers, facial maculopapules, and erythema nodosum-like lesions on her lower limbs. Despite neutrophilia, there was no evidence of infection found in her laboratory tests. Histological analysis of a skin biopsy highlighted subcutaneous panniculitis and a mixed inflammatory cell infiltrate in the dermis. The patient was consequently diagnosed with secukinumab-induced Behcet's-like disease. Additionally, we have reviewed nine other documented cases of Behcet's-like disease triggered by IL-17 inhibitors.Results: This group showed no significant gender preference, suffering from conditions such as psoriasis, ankylosing spondylitis, and hidradenitis suppurativa. Oral and genital ulcers were prevalent among the paradoxical reactions noted. Marked improvement was observed in all patients upon discontinuation of the IL-17 inhibitors.Conclusions: Our report serves to alert physicians to this uncommon but significant paradoxical effect that may arise with anti-IL-17 treatment.

Parenchymal Neuro-Behçet's disease or Comorbid Behçet's disease with multiple sclerosis: A discriminative analysis of a complex clinical entity.

BACKGROUND: Patients with Behçet's disease (BD) may rarely manifest with cerebral white matter lesions resembling multiple sclerosis (MS). This may result in misdiagnosis due to diagnostic difficulties between parenchymal neuro-BD (pNBD) and MS. This study aims to elucidate the distinguishing features of patients with comorbid BD and MS (BD+MS) in comparison to those with pNBD and MS alone by focusing on clinical and laboratory features. We also aimed to identify the distinctive characteristics of BD+MS patients by comparing them to patients with pNBD and MS. METHODS: The methodology of this study involved a retrospective analysis of patient records followed in the Department of Neurology at the Istanbul Faculty of Medicine, Istanbul University. The study population included patients diagnosed with pNBD, MS, and a comorbid condition of BD and MS (BD+MS). We assessed clinical, radiological, and laboratory data, including disease onset, annual relapse rates, Expanded Disability Status Scale (EDSS) progression, and cerebrospinal fluid examination. Several parameters were examined between the pNBD, MS, and BD+MS patient groups to find similarities and differences between subgroups. RESULTS: Our study included 1,764 patients: 172 with pNBD, 1,574 with MS, and 18 with BD+MS. A predominance of females was noted in the BD+MS (72%, p < 0.001) and MS (69 %, p < 0.001) groups compared to pNBD (30 %). The median age at the onset of neurological symptoms was 35.5 (IQR: 16.8) years for BD+MS, 34.6 (13.6) years for pNBD, and 27.6 (13.3) years for MS (BD+MS vs. MS; p = 0.3, pNBD vs. MS, p = 0.7). Additionally, the number of attacks was notably different, with BD+MS patients experiencing a median of 3.5 (2.0) attacks compared to 3.0 (3.0) for MS patients and only 1.0 (1.0) for pNBD patients, suggesting a more active disease course in the MS and BD+MS groups compared to pNBD (p < 0.001). The median annualized relapse rate for BD+MS was 0.3 (0.2), which was lower than the rate of 0.4 (0.4) in MS (p = 0.048) and equivalent to the rate of 0.2 (0.3) in pNBD (p = 0.2). The time to the first relapse was similar to those with BD+MS and MS, but considerably shorter than in individuals with pNBD (p < 0.0001). The cerebrospinal fluid (CSF) analysis showed no significant differences in neutrophil and lymphocyte counts between BD+MS and MS patients but elevated levels in pNBD patients (p < 0.05). CSF protein levels were consistent across all groups (p = 0.1 and p = 0.7). Oligoclonal bands were detected in all patients with BD+MS, in the majority of MS patients (83.6 %), and a small percentage of pNBD patients (19.7 %), showing a notable distinction between the BD+MS and pNBD groups (p < 0.001). CONCLUSION: Our study underscores the need for a skeptical approach in diagnosing and treating patients with BD who exhibit symptomatic MS-like MRI lesions. Our findings suggest that BD+MS is a distinct clinical entity, warranting specific diagnostic and treatment approaches. Our findings highlight that BD patients with MS-like lesions meeting MS diagnostic criteria should be managed as patients with comorbid MS and BD rather than pNBD.

Recurrent intra-cardiac thrombosis: A rare manifestation of Behçet's disease.

Behçet's disease is a systemic vasculitis characterized by recurrent bipolar aphtosis and ophthalmic disorders. Cardiac involvement is rarely reported and could be associated to poor prognosis. Intracardiac thrombosis is exceptional and represents a therapeutic issue. We report the case of a young man admitted in internal medicine department for management of prolonged fever and recurrent mouth ulcers.

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.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Optimal Treatment Approaches to Intestinal Behçet's Disease Complicated by Myelodysplastic Syndrome: The KASID and KSBD Multicenter Study.

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

Porto-sinusoidal vascular disorder and nephrotic-range proteinuria due to venous vasculitis in Behçet's disease.

Behçet's disease (BD) is an autoinflammatory disease with multifactorial and polygenic etiology, potentially involving arteries and veins of any size resulting in variable vessel vasculitis. We report a case of an Iranian male who presented with porto-sinusoidal vascular disorder due to venous vasculitis as initial manifestation of BD. Despite immunosuppression, anticoagulation and venous recanalization, he subsequently developed severe nephrotic-range proteinuria mimicking a primary renal disease which was completely and immediately ameliorated by stenting of the vena cava. This demonstrates that the proteinuria was caused by increased intraglomerular pressure due to venous outflow obstruction as a consequence of venous vasculitis. To our knowledge, this is the first report of massive proteinuria caused by venous obstruction of the caval vein in the context of BD. Altogether, this case demonstrates the extensive spectrum of vascular disease in BD.