Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

An immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment.

BACKGROUND: In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. CASE PRESENTATION: Here, we report a rare case of Behcet's-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet's-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control. CONCLUSIONS: In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.

Coexistence of ankylosing spondylitis and Behçet's disease: Successful treatment with upadacitinib.

BACKGROUND: Ankylosing spondylitis (AS) and Behçet's disease (BD) are distinct inflammatory disorders, but their coexistence is a rare clinical entity. This case sheds light on managing this complex scenario with Janus kinase (JAK) inhibitors. CASE PRESENTATION: A 42-year-old woman presented with a decade-long history of lower back pain, nocturnal spinal discomfort, recurrent eye issues, oral and genital ulcers, hearing loss, pus formation in the left eye, and abdominal pain. Multidisciplinary consultations and diagnostic tests confirmed AS (HLA-B27 positivity and sacroiliitis) and BD (HLA-B51). Elevated acute-phase markers were observed. CONCLUSION: This case fulfills diagnostic criteria for both AS and BD, emphasizing their coexistence. Notably, treatment with upadacitinib exhibited promising efficacy, underscoring its potential as a therapeutic option in patients with contraindications for conventional treatments. Our findings illuminate the intricate management of patients presenting with these two diverse systemic conditions and advocate for further exploration of JAK inhibitors in similar cases.

Folliculitis might be associated with pathergy-positivity in patients with Behçet syndrome.

Pathergy test indicates nonspecific hyper-reactivity of the skin to aseptic trauma in Behçet syndrome (BS) and is considered as an adjunctive diagnostic test with a good specificity albeit with low sensitivity. We tested the hypothesis that a relationship exists between active clinical manifestations of BS and the pathergy-positivity when performed simultaneously. Pathergy test and detailed dermatologic examination were done in 105 BS patients (60M/45F); who were seen consecutively at the multi-disciplinary BS outpatient clinic in a single tertiary center. Information regarding demographic and clinical characteristics, pathergy test results at diagnosis, and details about treatment were obtained from patient charts. Disease activity was assessed using Behçet Disease Current Activity Form. Among 105 patients, 27 (25.7%) were pathergy-positive at the time of the study visit whereas 40.9% were pathergy-positive at the time of the diagnosis. There was no relation between pathergy test and patient age or disease duration, either. Pathergy-positivity was significantly more common in patients with folliculitis compared to those without folliculitis (40.7% vs 19.2%; P = .026). The test was also positive in all 3 patients with leg ulcers due to venous stasis. We found that among all skin-mucosa lesions only the presence of folliculitis was associated with pathergy positivity with statistical significance. It was also remarkable that the current pathergy was positive in all 3 patients with active leg ulcers but this finding warrants further studies because of the low patient numbers.

Pan-immune-inflammation value could be a new marker to differentiate between vascular Behçet's disease and non-vascular Behçet's disease.

OBJECTIVE: Behçet's disease etiology is uncertain, and no specific diagnostic markers exist in the laboratory. This retrospective study aimed to evaluate the role of inflammatory and hematological parameters, mainly Pan-Immune-Inflammation-Value (PIV), in predicting vascular Behçet's disease (VBD). PATIENTS AND METHODS: A total of 85 patients with VBD and 92 patients without vascular involvement (non-VBD) were included in this study. Neutrophil, monocyte, platelet, and lymphocyte subsets are all included in the PIV, a new blood-based biomarker. RESULTS: The optimal cut-off values for the PIV were determined to be ≥261.6. White blood cell, neutrophil, monocyte, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (MCHC), red cell distribution, platelet, plateletcrit, PIV, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, sedimentation, c-reactive protein (CRP) values were significantly associated with VBD in univariate analysis. After multivariate analysis, PIV [odds ratio (OR): 2.758; 95% confidence interval (CI): 1.327-5.736; p=0.007] and CRP (OR: 4.029; 95% CI: 1.924-8.438; p<0.001) were found to be a positive predictor for VBD, while MCHC (OR: 0.722; 95% CI: 0.530-0.983; p=0.039) was seen as a negative predictor. CONCLUSIONS: Based on our results, PIV, an easily accessible, cost-effective, and new composite biomarker, has a significant predictive value in VBD.

Long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha treatment for patients with Behcet's uveitis: A systematic review and meta-analysis.

AIM: This study aims to evaluate the long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha (anti-TNF-α) therapy for patients with Behcet's uveitis (BU) using meta-analysis. METHODS: We searched the Web of Science and PubMed databases for eligible studies up to December 1, 2022. The quality of each identified study was assessed using the Joanna Briggs Institute's case series literature quality assessment tool. Statistical analysis was conducted using Stata 16.0 software with a random-effects model. RESULTS: Twelve studies comprising 1156 patients with BU were included in our analysis. We found that 85.0% of patients achieved ocular inflammation remission after receiving anti-TNF-α treatment, with a 95% confidence interval (CI) ranging from 78.7% to 90.5%. Additionally, 77.4% (95% CI: 57.5%-92.5%) experienced an improvement in visual acuity (VA). Moreover, the pooled dose reduction of glucocorticoids (GCs) was 11.08 mg (95% CI: -13.34 mg to -8.83 mg). Throughout the follow-up period, the cumulative retention rate of the medication was 67.3% (95% CI: 53.7%-79.6%). Serious adverse events occurred in 5.8% (95% CI: 3.1%-8.9%) of cases, with the three most common types being severe infusion or injection reactions (2.7%; 95% CI: 0.8%-5.4%), tuberculosis (1.3%; 95% CI: 0.0%-3.9%), and bacterial pneumonia (1.3%; 95% CI: 0.1%-3.4%). Subgroup analysis revealed that ocular inflammation remission rates were 89.3% (95% CI: 81.2%-95.5%) for adalimumab treatment and 83.7% (95% CI: 75.3%-90.8%) for infliximab treatment. The drug retention rate after adalimumab therapy was 70.3% (95% CI: 62.0%-78.0%) compared to 66.4% (95% CI: 48.6%-82.2%) for infliximab treatment. Furthermore, the incidence of severe infusion or injection reactions was 2.2% (95% CI: 0.1%-5.8%) following adalimumab treatment and 3.5% (95% CI: 0.7%-7.7%) following infliximab treatment. CONCLUSIONS: Anti-TNF-α therapy represents an effective treatment for BU patients with favorable safety profile and high drug retention rate and a potential advantage of adalimumab over infliximab in terms of ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.

Investigation of optic nerve function in Behçet's patients with optic disc hyperfluorescence in fundus fluorescein angiography.

PURPOSE: The aim was to investigate the changes in optic nerve function that may help in the diagnosis of subclinical optic nerve involvement in patients with Behçet's disease (BD) and isolated optic disc (OD) hyperfluorescence in fluorescein angiography (FA). MATERIALS AND METHODS: Three groups were formed; BD patients with isolated OD hyperfluorescence in FA, BD patients without ocular involvement (normal FA) and control group. A total of 88 eyes of 45 patients were included. The groups were compared in terms of OCT-RNFL, contrast sensitivity and VEP latency. RESULTS: When the OCT-RNFL values were compared, there was a significant difference between the control group and Behçet's patients with normal FA. Contrast sensitivity values differed significantly among the groups, and the lowest mean contrast sensitivity was observed in the group with OD hyperfluorescence (p < 0.05). CONCLUSION: As far as we know, this is the first publication that investigates optic nerve function in BD patients with isolated OD hyperfluorescence in FA. Assessment with FA of asymptomatic BD patients with visual complaints and low contrast sensitivity may be helpful at early detection of inflammatory optic neuropathy by close follow-up in patients with OD hyperfluorescence.

Behçet's syndrome.

Behçet's syndrome is a rare, chronic multisystemic inflammatory disorder also known as the Silk Route disease due to its geographical distribution. Behçet's syndrome is a multifactorial disease and infectious, genetic, epigenetic, and immunological factors contribute to its pathogenesis. Its heterogeneous spectrum of clinical features include mucocutaneous, articular, ocular, vascular, neurological, and gastrointestinal manifestations that can present with a relapsing and remitting course. Differential diagnosis is often hampered by the non-specific clinical presentation and the absence of laboratory biomarkers or pathognomonic histological features. The therapeutic approach is tailored on the basis of patient-specific manifestations and relies on glucocorticoids, colchicine, and traditional and biological immunosuppressants. Despite progress in the knowledge and management of the disease, unmet needs in diagnostics, monitoring, prediction, and treatment personalisation challenge clinical practice, making Behçet's syndrome a complex disorder associated with an increased risk of morbidity.

IL-38 in Behçet's disease: Gene expression in bronchoalveolar lavage from patients having pulmonary involvement.

The etiological complexity of Behçet disease (BD), an immune-mediated rare form of vasculitis characterized by multi-organ involvement, is still elusive due to an incomplete understanding of the synergy between genetic susceptibility, environmental triggers, and an abnormal immune response. The diagnosis of BD relies on clinical symptoms. Lung inflammatory disorders are severe conditions of patients with BD, here we focus on the expression of biomarkers in BD patients with pulmonary manifestations. Aiming to identify additional discriminating biomarker patterns, we measured and compared protein and gene expression of IL-38 and a broad panel of selected genes in bronchoalveolar cells of patients suffering from BD with and without pulmonary involvement compared to controls. ELISA and RT-PCR analysis were applied. The first principal analysis highlighted decreased IL-38 level in BD patients compared to Rheumatoid Arthritis (RA) patients and controls: BD patients expressed lower IL-38 levels, particularly in cases with pulmonary involvement. The area under the curve (AUC) of the receiver-operating characteristic curve showed that IL-38 may be an eventual biomarker for BD. Co-cultured recombinant IL-38 and stimulated memory PBMCs of active BD, were able to suppress IL-17 and NLRP3 inflammasome and ameliorate the secretion of IL-10 and TGFß. Transcription factors of the IL-1 family (IL-1ß, IL-18, IL-32, IL-33 and IL-37) along with IFN-γ, IL-17, RORγt, Foxp3, TGFß, IL-10 and NLRP3 inflammasome were the parameters that are the main contributor to the segregation between BD with and without lung involvement. Our results indicate that IL-38 might be involved in the pathogenesis of BD and the combined gene expression in BAL suggests distinct mechanisms governing the inflammatory disorders in the lung.

HLA-B*51 Frequency in Transplant Patients and Donors.

OBJECTIVES: HLA molecules play a crucial role in transplantation. The best treatment modality in patients with end-stage renal disease is renal transplant. HLA mismatches between patients and donors can prolong time for renal transplant therapy, reduce graft survival, and increase mortality. HLA region is the most polymorphic genetic region and is essential for antigen presentation. The main target of the recipient's immune system is HLA molecules on the surface of donor cells. HLA-B*51 is associated with Behcet disease, a rare multisystemic disease characterized by autoimmunity and inflammatory processes. In transplant recipients, inflammation and vasculitis are immunologic mechanisms that are responsible for damage of graft tissue. In this retrospective study, we aimed to investigate the frequency of HLA-B*51 in patients diagnosed with end-stage renal disease and in controls and to investigate correlations with rejection episodes. MATERIALS AND METHODS: Patients who applied to Baskent University Adana Dr. Turgut Noyan Research and Medical Center (between 2010 and 2022) with end-stage renal disease (n = 1732) and a control group (n = 5277) received HLA typing for class I (HLA-A, HLA-B). Sequence-specific primers or sequencespecific oligonucleotides were used. Among patients diagnosed with end-stage renal disease, 321 had kidney transplant. RESULTS: Frequency of HLA-B*51 was 25.92% in patients and 25.22% in controls. No significant differences were found between patients and controls in the frequency of HLA-B*51. Among kidney transplant recipients with HLA-B*51 (n = 72), 38.89% had rejection episodes and 61.11% had no rejection. No significant association was found between HLA-B*51 allele positivity and rejection. CONCLUSIONS: No significant relationship was shown between patients diagnosed with end-stage renal disease and HLA-B*51 positivity. Previous studies support frequency of the HLA-B*51 allele in the control group. Although Behçet disease is known to cause renal vasculitis, HLA-B*51 positivity alone was not associated with vasculitis or inflammation.

Characterization and Management of Amicrobial Pustulosis of the Folds, Aseptic Abscess Syndrome, Behçet Disease, Neutrophilic Eccrine Hidradenitis, and Pyostomatitis Vegetans-Pyodermatitis Vegetans.

Neutrophilic dermatoses are a broadly heterogeneous group of inflammatory skin disorders. This article reviews 5 conditions: amicrobial pustulosis of the folds, aseptic abscess syndrome, Behçet disease, neutrophilic eccrine hidradenitis, and pyostomatitis vegetans-pyodermatitis vegetans.The authors include up-to-date information about their epidemiology, pathogenesis, clinicopathologic features, diagnosis, and management.

Neither hepatic steatosis nor fibrosis is associated with clinical outcomes in patients with intestinal Behçet's disease.

BACKGROUND: Behçet's disease (BD) and nonalcoholic fatty liver disease (NAFLD) are chronic inflammatory diseases that share pathogenetic mechanisms. In this study, we investigated whether NAFLD influences the clinical outcomes in patients with intestinal BD. METHODS: Patients with intestinal BD and available hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) scores were recruited between 2005 and 2022. An HSI of ≥30 and FIB-4 of ≥1.45 were used to diagnose hepatic steatosis and significant liver fibrosis, respectively. The primary outcomes were intestinal BD-related hospitalization, surgery, emergency room visits, or the first use of corticosteroids, immunomodulators, or biologic agents for intestinal BD. RESULTS: A total of 780 patients with BD were selected. The prevalence of hepatic steatosis and significant liver fibrosis were 72.3% and 8.8%, respectively. Multivariate analysis showed that younger age, prior smoking history, concomitant skin lesions, higher white blood cell count, and lower serum albumin levels were independently associated with an increased risk of clinical relapse (all P < 0.05), whereas hepatic steatosis and significant liver fibrosis were not (hazard ratio [HR] = 1.164, 95% confidence interval [CI] 0.923-1.468; P = 0.199 for hepatic steatosis; HR = 0.982, 95% CI 0.672-1.436; P = 0.927 for significant liver fibrosis). CONCLUSION: Hepatic steatosis and liver fibrotic burden were not independently associated with clinical outcomes in patients with intestinal BD.

Pseudotumoral neuro-behcet's disease: case series and review of literature.

BACKGROUND: Behcet's disease (BD) is a multisystem autoimmune relapsing vasculitis with an almost unknown etiology involving both large and small vessels. The neurological involvement called neuro-Behcet's disease (NBD) is rare. NBD can be responsible for tumor-like masses mimicking low-grade gliomas in only a few cases. METHODS: We report here the main characteristics, treatment, and outcome of 43 patients (4 personal cases and 39 patients from the literature) with a pseudotumoral presentation of NBD (PT NBD). We compared our findings with those of the classical form of NBD. RESULTS: The median age was 35.86 (12-59 years) years, with a male predominance (67.4%). PT NBD was the inaugural of the disease in 51.2% of cases. The neurological manifestations included headache (n = 31), pyramidal syndrome (n = 28), cerebellar syndrome (n = 5), behavioral changes (n = 5), and pseudobulbar signs (n = 2). Ophthalmologic examination revealed papilledema in 3 cases. On cerebral imaging, the most affected regions of the brain were the capsulothalamic region (n = 15, 37.5%) and the brainstem (n = 14, 35). Histological analysis revealed necrotic lesions with perivascular inflammatory infiltrate without signs of tumoral or infectious lesions. Treatment consisted of corticosteroids (n = 40, 93%) and immunosuppressive agents (n = 28, 65.11%), leading to complete clinical and imaging remission in 41.5% of patients. CONCLUSION: PT NBD is a rare but life-threatening condition.

Predicting Factors of Long-term Outcome of Gastrointestinal Behçet's Disease: A Chinese Retrospective Study.

PURPOSE: Behçet's disease (BD) is a complex disorder affecting multiple systems and organs, and gastrointestinal BD is poorly understood. We aimed to identify factors influencing the long-term outcomes of patients with gastrointestinal BD. METHODS: Consecutive patients with gastrointestinal BD were analyzed retrospectively. Data on the following clinical characteristics were collected: sex, age at diagnosis, symptoms, endoscopic findings, medical treatments, and surgery. Mucosal healing and surgical rates at 1, 2, and 5 years were evaluated. Log-rank test and Cox proportional hazards regression models were used to evaluate the factors affecting long-term outcomes. FINDINGS: Baseline data of 175 patients with gastrointestinal BD were included. The mean (SD) age at diagnosis was 38.3 (12.9) years. The typical clinical symptoms were oral ulcer (72.6%), abdominal pain (71.4%), and weight loss (41.1%). The most commonly involved location was the ileocecum; isolated oval ulcer was the most common ulcer type. Seventeen patients (9.7%) underwent 18 surgeries after inclusion. The cumulative surgical rates were 8.6% (n/N = 15/175), 8.6% (n/N = 15/175), and 9.1% (n/N = 16/175) in 1, 2, and 5 years, respectively. Data from 101 patients who underwent at least 2 endoscopies were included in the analysis for mucosal healing. Kaplan-Meier curve showed that the cumulative mucosal healing rates at 1, 2, and 5 years were 34.7% (n/N = 35/101), 41.6% (n/N = 42/101), and 61.4% (n/N = 62/101), respectively. We compared cumulative mucosal healing rates between 4 treatment groups, including 5-aminosalicylic acid (3% [n/N = 3/101]), mono-immunosuppressant (31.7% [n/N = 32/101]), combined therapy (36.6% [n/N = 37/101]), and escalation therapy (28.7% [n/N = 29/101]), and found that mono-immunosuppressant achieved earlier mucosal healing than combined therapy (P = 0.0008) and escalation therapy (P = 0.0008). The univariate analysis showed that moderate to severe disease activity (P = 0.013, P = 0.004), diameter of the maximal ulcer >4 cm (P = 0.002), and nonsimple esophageal involvement (P < 0.001) were risk factors, and number of ulcers between 2 and 5 was the protective factor of mucosal healing (P = 0.001). Multivariate regression analysis indicated that nonsimple esophageal involvement (P < 0.001) and the maximal ulcer >4 cm (P = 0.041) were independent risk factors of mucosal healing. IMPLICATIONS: Most patients with gastrointestinal BD need long-term treatment to achieve mucosal healing. The location and size of ulcers have a significant impact on the mucosal healing of gastrointestinal BD.

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.

"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.

Retinal and Conjunctival Vessels in the Diagnosis and Assessment of Behcet's Disease: A New Approach.

BACKGROUND AND OBJECTIVE: The study aimed to investigate the alterations of retinal and conjunctival vessels in patients with Behcet's disease (BD). PATIENTS AND METHODS: In this case-control study, 17 patients (34 eyes) diagnosed with BD and 17 healthy volunteers (34 eyes) matched by age, sex, blood pressure, and intraocular pressure were recruited. Optical coherence tomography angiography examinations were performed to calculate the vessel density of the retina and conjunctiva according to different sizes of vessels and different zones divided by three segmentation methods of the retina: hemispheric segmentation, Early Treatment Diabetic Retinopathy Study, and central annulus segmentation. RESULTS: The vessel densities of the superficial macrovascular (P = 0.050), superficial microvascular (P < 0.001), superficial total microvascular (P < 0.001), deep total microvascular (P < 0.001), and deep total microvascular (P < 0.001) were significantly lower in the BD group. The conjunctival vessel density was significantly higher in the BD group (P < 0.001). The receiver operating characteristic curve analysis showed that the area under the curve of vessel density of the superior right (0.993, 95% CI 0.980-1) and right zones (0.996, 95% CI 0.987-1) were the largest in the superficial and deep retina, respectively. Otherwise, the area under the curve of conjunctival vessel density was 0.728 (95% CI 0.607-0.848). CONCLUSIONS: In patients with BD, retinal vessel density decreases, while conjunctival vessel density increases. Optical coherence tomography angiography provides a new noninvasive and quantitative assessment for retinal and conjunctival vessels. [Ophthalmic Surg Lasers Imaging Retina 2024;55:13-21.].

Efficacy of golimumab in patients with refractory non-infectious panuveitis.

This study investigated the efficacy of golimumab in the management of refractory non-infectious panuveitis. Nineteen patients (38 eyes; mean age, 31 years) were retrospectively reviewed between June 2016 and June 2022. All patients had bilateral eye involvement and Behçet's disease was the most common diagnosis (57.9%). Compared to the period before golimumab treatment, the rate of uveitis relapses after golimumab treatment significantly decreased from 1.73 to 0.62 events per person-years (incidence ratio 0.33, 95% confidence interval 0.19-0.57, P < 0.001). After golimumab therapy, 12 patients (63.2%) were able to reduce the number or dosage of immunosuppressive drugs, and the median dosage of systemic corticosteroids was reduced from 15.0 to 7.5 mg/d (P = 0.013) compared to baseline. The median logMAR visual acuity improved from 0.9 at baseline to 0.6 at the last visit (P = 0.006). Golimumab demonstrated efficacy against refractory non-infectious panuveitis in terms of a corticosteroid-sparing effect and reduced the rate of uveitis relapses to approximately one-third.