Panuveitis

Behçet's disease is a systemic inflammatory disorder of unknown etiology. The disease manifests with diverse clinical symptoms, most commonly recurrent oral and genital ulcers, skin lesions, and uveitis, though it can affect multiple organ systems. Diagnosis is primarily clinical due to the lack of a definitive diagnostic test, and management involves a multidisciplinary approach to control inflammation and manage symptoms. Current treatment strategies involve corticosteroids, immunosuppressive agents, and, increasingly, biological therapies. Behçet's disease exhibits a higher prevalence along the Silk Road, suggesting a role of environmental and genetic factors. Despite significant progress in understanding its clinical characteristics and treatment approaches, gaps remain in our understanding of its pathogenesis. Future research is needed to elucidate the disease's pathophysiology and optimize treatment strategies.

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.

Behçet's uveitis (BU) is a severe ocular manifestation of Behçet's disease, typically accompanied by abnormal neutrophil infiltration and hyperactivation. However, the underlying causes of excessive neutrophil extracellular traps (NETs) production and mechanisms by which NETs contribute to the pathogenesis of BU remain incompletely understood. Neutrophils from BU patients exhibit a higher propensity for NETs release compared to healthy controls. In the experimental autoimmune uveitis (EAU), neutrophils are observed to exert pro-inflammatory effects through NETs. Clearing NETs can inhibit T helper 17 (Th17) cell differentiation and significantly alleviate EAU symptoms. In vivo and in vitro experiments demonstrate neutralizing IL-17A markedly reducing neutrophil infiltration and NETs formation in EAU. Single-cell RNA sequencing confirms that CD44 plays a key role in mediating interactions between NETs and Th17 cells. Antagonizing CD44 inhibits the proportion of Th17 cells and NETs formation. Multiplex immunofluorescence and cell communication analyses further demonstrate interactions and colocalization between NETs and CD44highCD4+T cells in EAU. NETs induce Th17 differentiation via upregulating CD44, and in turn, Th17 cells secrete IL-17A to recruit neutrophils and promote NETs formation. Interrupting NETs-CD44-IL-17A feedback loop may be a potential therapeutic target for BU.

PurposeBehçet's disease (BD) is a multisystem autoinflammatory disorder that may present during childhood. Pediatric BD is challenging to diagnose due to heterogeneous clinical manifestations and the lack of standardised pediatric classification criteria. This study aimed to evaluate the association between systemic inflammatory biomarkers-including the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and C-reactive protein (CRP)/albumin ratio-and systemic organ involvement in children with BD. To our knowledge, no prior study has investigated these markers in pediatric BD.MethodsIn this retrospective study, 41 pediatric patients diagnosed with BD according to the 2015 PEDBD criteria and followed jointly by dermatology and rheumatology departments were included. Age- and sex-matched healthy controls (n = 41) undergoing elective surgery were also enrolled. Inflammatory indices (NLR, SII, PIV, CRP/albumin) were calculated from pre-treatment blood samples. Cut-off values for systemic involvement were determined via ROC analysis. Statistical analyses included the Kolmogorov-Smirnov test, independent t-test or Wilcoxon test, Chi-square and McNemar tests, correlation analysis, logistic regression, and ROC analysis.ResultsSystemic involvement was observed in 28 (68.3%) patients, including neurological involvement in 4 (9.8%), vascular involvement in 5 (12.2%), and other major organ involvement in 19 (46.3%). Inflammatory indices-PIV, SII, NLR, and CRP/albumin-were significantly higher in patients with systemic, neurological, and vascular involvement (all p ConclusionSystemic inflammatory biomarkers such as NLR, SII, PIV, and CRP/albumin ratio may serve as useful indicators of systemic organ involvement in pediatric BD. Routine assessment of these markers could facilitate earlier recognition and more targeted management of systemic manifestations in this population.