Hughes-Stovin syndrome (HSS) is a rare and aggressive type of systemic vasculitis which is characterized by peripheral venous thrombosis and pulmonary artery aneurysms (PAAs) at the onset of the disease, as well as the absence of recent or previous attacks of uveitis. The onset of HSS and its dominant clinical disease presentations differ in many aspects from those observed in Behçet’s disease (BD). The absence of uveitis is a mandatory exclusion criterion in the preliminary diagnostic criteria proposed by the HSS International Study Group (HSSISG), to avoid misclassification between HSS and BD. The presence of PAAs is an obligatory “entry criterion” for diagnosis, while vascular thrombotic events are a “major criterion” after excluding other causes of coagulopathy-induced thrombosis. The HSSISG regards HSS and BD as one disease, yet exhibiting distinct patterns of disease expression, particularly at disease onset. Differentiating HSS from BD is especially important for early diagnosis and optimal management. While the presence of HLA-B51 is the strongest genetic risk factor for BD, it is not used as a criterion to confirm a diagnosis because it lacks sufficient specificity. The prevalence of HLA-B51 in HSS is relatively low, suggesting that different genetic drivers might exist or that HSS is a unique entity with overlapping features with BD. In HSS, both HLA-B51 positive and negative cases have been described; thus, it cannot be a hallmark of the syndrome, and it does not play a role in the diagnostic criteria.
Objective To investigate CD177 + PMN dysregulation on endothelial cells in Behçet disease (BD), a chronic systemic vasculitis characterized by polymorphonuclear neutrophil (PMN) activation and endothelial dysfunction. Methods We reanalyzed BD PMN RNA‐sequencing data and quantified CD177 + PMN in BD peripheral (n = 38) and vascular tissue. We then analyzed BD and healthy control CD177 + PMN using RNA sequencing (n = 7) and measured neutrophil extracellular trap (NET) production, which were used to stimulate vascular endothelial cells (VECs) for RNA‐sequencing analysis. Differentially expressed proteins in NETs were determined by mass spectrometry. Senescence, senescence‐associated secretory phenotype (SASP), and PMN chemotaxis of VECs treated with BD CD177 + PMN‐derived NETs were assessed. Results Transcriptome analysis revealed BD PMN overexpressed CD177. CD177 + PMN subset was expanded in active and severe systemic BD and accumulated in BD aortic walls. Enhanced NETosis and oxidative phosphorylation in BD CD177 + PMN were noted in RNA sequencing, which were confirmed in both resting and activated BD CD177 + PMN. BD CD177 + PMN‐derived NETs promoted senescence, SASP, and PMN chemotaxis in VECs using RNA‐sequencing analysis, which were validated by up‐regulated IL‐6, CXCL8, ICAM‐1, p21, SA‐β‐gal, and cell proliferation arrest. Mass spectrometry identified that BD CD177 + PMN‐derived NETs contained more histone 3.1 (H3.1). H3.1 induced senescence, SASP, and PMN chemotaxis in VECs via Toll‐like receptor 4 signaling, which was attenuated by senolytics. Conclusion Increased CD177 + PMN in patients with BD promotes senescence and SASP in VECs through secreting H3.1‐enriched NETs, which recruit PMN and collectively contribute to vasculitis in BD.
The development and implementation of genetic testing has revolutionized the diagnostic landscape of autoinflammatory diseases, leading to an exponential increase in the identification of disease-associated genetic variants. Yet a substantial proportion of these are considered variants of uncertain significance (VUS), complicating both diagnosis and therapeutic decision-making. This challenge is relevant not only for monogenic systemic autoinflammatory diseases, but also in the context of genetically complex disorders that can involve multiple low-penetrance variants. Advances in protein structure prediction tools, machine learning and artificial intelligence provide powerful computational frameworks for the classification of variants; however, their predictive accuracy must be benchmarked against functional assays, particularly with respect to gain-of-function variants. Functional screening approaches benefit from both technological progress and expanding knowledge of the innate immune pathways underlying systemic autoinflammatory diseases. Large-scale analyses of variants including multiplexed functional assays and deep mutational scanning experiments have enabled the assessment of hundreds of variants, notably in NLRP3, MEFV and ADA2, generating datasets that improve variant interpretation and genetic diagnosis. Altogether, these advances increase the potential of accurately predicting in the near future the effects of missense VUS, although numerous challenges remain to be addressed, especially those concerning our understanding of the influence of non-coding VUS in systemic autoinflammatory diseases.
Behçet syndrome is a complex systemic immune-mediated form of vasculitis characterized by diverse clinical manifestations and a variable disease course. The treat-to-target (T2T) concept has emerged as a pivotal approach in managing various systemic autoimmune rheumatic diseases; however, its application in Behçet syndrome requires further work. Despite the limited literature on this subject, advancements from clinical trials have underscored the necessity for a T2T approach in Behçet syndrome. This article proposes an evidence-based perspective on the T2T strategy in Behçet syndrome, featuring a multidisciplinary and comprehensive collaboration of international experts, including rheumatologists, immunologists, ophthalmologists, gastroenterologists and neurologists. By adopting an organ-based approach to tackling crucial challenges, we aim to define treatment goals for organ involvement, discuss outcome measures that can be used as targets and definitions of remission and relapse, and also propose monitoring strategies (including treatment targets). The goal of this Perspective is to pave the way for future research and clinical practice, enhance the management of this complex condition and ultimately improve patient outcomes.
A newsletter discute o uso de canabinoides na osteoartrite, destacando que o CBD tópico apresenta melhores sinais de eficácia que a via oral, embora ainda faltem evidências robustas para prescrição rotineira. O conteúdo também aborda novos protocolos de ultrassom para coluna vertebral, o potencial terapêutico da liraglutida e os marcadores de gravidade em uma coorte de 10 anos de Doença de Still.
A newsletter destaca que a prednisolona adjuvante não reduziu lesões coronarianas na Doença de Kawasaki, embora tenha diminuído a necessidade de terapia de resgate. Além disso, discute como o dano histológico crônico é o principal preditor de perda renal no lúpus e o aumento significativo de flares de artrite reumatoide no período pós-parto.
Behçet’s disease (BD) is a multisystemic inflammatory disorder in which treatment decisions are largely driven by the pattern and severity of organ involvement. This review provides a practical, organ-based overview of current therapeutic strategies for severe and refractory BD, with an emphasis on treatment selection and timing in routine clinical practice. Recent evidence supports an upfront, intensive treatment approach for life-threatening or damage-prone organ involvement, particularly neurological, vascular, and ocular disease, where delays in inflammation control are closely associated with irreversible damage. Anti–tumour necrosis factor agents form the core of therapy in these settings, supported by the strongest disease-specific data, while other biologic and targeted therapies are increasingly used in refractory cases. In contrast, mucocutaneous and articular manifestations predominantly affect quality of life and are commonly managed with stepwise strategies. Colchicine remains a widely used first-line treatment in routine practice and provides effective control of mucocutaneous and joint manifestations in a substantial proportion of patients, with escalation to additional systemic or targeted therapies guided by persistence, refractoriness, and patient burden. Importantly, treatment responses vary across organ systems, and benefit in one domain cannot be assumed to translate to others, reinforcing the need for organ-specific treatment planning. Optimal management of BD depends on matching treatment intensity to organ-specific risk, prioritising early aggressive therapy for major organ involvement while adopting proportionate, stepwise approaches for non–life-threatening disease. Improved outcomes are likely to be achieved through timely recognition of patients at risk of progression and early use of appropriately targeted therapies to prevent irreversible organ damage.
A newsletter aborda o risco quase dobrado de câncer em pacientes com Síndrome VEXAS, destacando a importância da genotipagem de UBA1 e marcadores inflamatórios. Apresenta o novo guideline brasileiro para fibromialgia com recomendações atualizadas e analisa um ensaio clínico sobre o abatacepte em miopatias inflamatórias, que sugeriu benefício clínico em subtipos específicos como polimiosite e miopatia necrosante.
Immune-mediated cochleovestibular dysfunction has gained recognition as an important yet frequently overlooked entity in recent decades. These disorders-ranging from isolated inner-ear syndromes to cochleovestibular manifestations of systemic autoimmune diseases-exhibit humoral or cellular immune attacks on inner-ear structures, commonly accompanied by microvascular injury and inflammatory cascades. Despite increasing awareness, the precise pathophysiological mechanisms remain incompletely understood for most conditions, and diagnostic and therapeutic approaches vary considerably. This narrative review summarizes current evidence on immune-mediated cochleovestibular disorders, dividing them into two main categories (1): primary Isolated disorders (delayed endolymphatic hydrops, bilateral vestibulopathy, and Ménière's disease with established or suspected autoimmune features) (2) cochleovestibular manifestations of rheumatologic diseases (systemic lupus erythematosus, multiple sclerosis, autoimmune thyroid disease, Behçet's disease, Vogt-Koyanagi-Harada disease, psoriasis, Cogan's syndrome, Susac syndrome, Sarcoidosis, Rheumatoid arthritis, Necrotizing vasculitides with polyangiitis and Giant cell arteritis). We examine their clinical features, proposed immune and microvascular mechanisms, diagnostic evaluation, and current management strategies, with particular emphasis on immunomodulatory and immunosuppressive therapies. Systemic corticosteroids at high doses are the primary treatment for most of these disorders, though the ideal duration, tapering protocols, and indications for steroid-sparing medications differ significantly across various syndromes. Evidence supporting many adjunctive therapies is limited or conflicting, underscoring the need for higher-quality clinical trials. Early recognition and prompt immunomodulatory treatment can often reverse or stabilize symptoms in immune-mediated cochleovestibular dysfunction. This review offers a clinically oriented synthesis of current evidence, elucidating the complex immunological underpinnings and the corresponding therapeutic landscape of these disorders. By integrating otologic and rheumatologic perspectives, we aim to heighten awareness, promote earlier diagnosis, and inform more effective treatment of patients presenting with vertigo, hearing loss, or imbalance suggestive of immune-mediated inner-ear pathology.
To evaluate the diagnostic yield of whole-exome sequencing (WES) vs targeted gene panel (TGP) testing in patients evaluated for autoinflammation at the Great Ormond Street Hospital Autoinflammation Centre of Excellence. We retrospectively analysed 476 patients who underwent TGP testing between 2015 and 2022, and 210 patients who underwent WES between 2022 and 2025. Analysis of WES data combined: (i) a virtual gene panel of genes (germline and somatic) associated with inflammation; (ii) agnostic filtering according to ClinVar classification of pathogenicity; (iii) copy number variant analysis using ExomeDepth; and (iv) phenotype-driven prioritization using Exomiser. TGP testing identified molecular diagnoses in 71/476 patients (14.9%). WES increased the molecular diagnostic yield to 41/210 patients (19.5%). WES also enabled the discovery of novel genotype-phenotype associations. Significant incidental findings were identified in 29/210 (13.8%) of the cases, including variants predisposing to cancer or cardiomyopathy. In patients with suspected autoinflammation, WES increased diagnostic yield compared with TGP testing, while providing additional clinical value through novel gene discovery and capacity for future systematic reanalysis of unsolved cases. Incidental findings required careful and explicit a priori patient counselling and informed consent before offering WES. While there will be an inevitable shift from WES to whole-genome sequencing in the future, significant challenges remain for WGS, including costly large-data handling and storage, and uncertainty about the interpretation of variants in non-exonic regions. Our findings, therefore, demonstrate the significant clinical impact of WES for the work-up of autoinflammation, with pragmatic utility for timely return of results.
To compare the sensitivity of International Study Group (ISG, 1990), International Criteria for Behçet's Disease (ICBD, 2014) and the Paediatric Behçet's Disease (PEDBD, 2016) classification criteria in paediatric Behçet's disease (pBD) within an endemic cohort and to assess organ involvement, treatment patterns, outcomes and cumulative damage using the Behçet's Syndrome Overall Damage Index. We retrospectively analysed 69 consecutive children with clinician-diagnosed pBD (symptom onset ≤18 years) at a tertiary centre in Türkiye (2020-2025). Classification criteria were applied at the last visit. The primary outcome was sensitivity versus clinician diagnosis; secondary outcomes included sex-stratified risks, therapies/adverse events and cumulative damage. ICBD classified 97.1% of cases, compared with 58.0% for ISG and 53.6% for PEDBD. Neurovascular involvement occurred in 18.8% (mainly cerebral venous thrombosis), vascular in 20.3% and ocular in 17.4% (posterior-segment 11.6%). Boys had higher risks of neurovascular disease, while girls more often had genital ulcers. Treatment followed steroid-sparing pathways (colchicine 98.6%, azathioprine 63.8%, antitumour necrosis factor 21.7%); adverse events occurred in 15.9% and non-adherence in 11.6%. Cumulative damage was low to moderate, with a mean BODI score of 0.45 (range 0-3). In this endemic paediatric cohort, ICBD demonstrated superior sensitivity, while ISG and PEDBD classified only half of cases. Morbidity was driven by neurovascular events and, less frequently, posterior-segment ocular disease. Findings support an ICBD-anchored approach with co-reporting of ISG/PEDBD for comparability. Low-threshold neuro-ophthalmic evaluation and timely steroid-sparing escalation are critical for sight/central nervous system-threatening disease. Targeted vascular imaging and adherence-focused adolescent care remain priorities.
To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including additional drugs and adverse outcomes as well as paternal drug safety. According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item. The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. The updated recommendations provide consensus guidance and will help to improve the quality of care of patients during the phases of reproduction, pregnancy, and lactation.
Behçet's disease (BD) is a multisystemic inflammatory disease, and its neurologic involvement represents serious manifestations. This study aimed to elucidate the neurologic manifestations of BD in a large paediatric population and to describe its outcomes and prognosis. This retrospective multicentre study included 75 paediatric patients diagnosed with neuro-Behçet's disease (NBD). Demographic data, clinical features, neuroimaging findings, treatments and disability conditions were reviewed. Neurologic manifestations were observed in 52 patients (69.3%) at initial presentation and in 23 patients (30.7%) at a median of 14 months (8-30) after diagnosis. The distribution of NBD subgroups was as follows: 56 patients (74.7%) with nonparenchymal, 15 patients (20%) with parenchymal and 4 patients (5.3%) with mixed forms. Headache, observed in 70 patients (93.3%), was the most common neurological symptom, being significantly more frequent in the non-parenchymal form (P = 0.028). Paresis, sensory loss and mood/mental health problems were significantly more frequent in the parenchymal form (P = 0.034, P = 0.016, P = 0.005, respectively). Neuroimaging revealed parenchymal lesions in 19 patients (25.3%), and vascular lesions were in 55 patients (73.3%). Azathioprine was the most commonly used immunosuppressor therapy (78.7%). The median follow-up duration of patients was 30 months (17.5-52.5), during which significant clinical improvement was observed, with no deaths reported. Paediatric NBD remains a significant issue in paediatric rheumatology. The non-parenchymal subgroup is the predominant form in children. Paediatric NBD should be confirmed and classified by MRI. The early aggressive immunosuppressive therapy provides clinical improvement. Activity and disability indexes are valuable for treatment and follow-up.
Alemtuzumab is a humanized monoclonal antibody targeting CD52, a glycosylphosphatidylinositol-anchored surface antigen broadly expressed on lymphocytes and other immune cells. Although currently approved for multiple sclerosis and used in selected transplantation settings, alemtuzumab was among the earliest lymphocyte-depleting biologics explored across a wide spectrum of autoimmune rheumatic diseases. With renewed interest in deep immune-depleting strategies, including CAR-T cells and bispecific T-cell engagers, revisiting the immunobiology and clinical experience of alemtuzumab is timely. This review summarizes current knowledge of CD52 structure, expression, and immunological function, highlighting its dual role as both a co-stimulatory and immunoregulatory molecule. We examine the mechanisms underlying alemtuzumab-induced lymphocyte depletion, subsequent immune reconstitution, and the paradoxical development of secondary autoimmunity. Clinical evidence for alemtuzumab use in rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, idiopathic inflammatory myopathies, ocular inflammatory disease, and Behçet's syndrome, is reviewed, with emphasis on efficacy, durability of response, and safety outcomes. Across multiple refractory disease settings, alemtuzumab has demonstrated the capacity to induce rapid clinical improvement and, in some cases, prolonged drug-free remission. However, treatment is limited by risks of infection, delayed immune reconstitution, and immune dysregulation. We conclude that alemtuzumab remains a potent immunomodulatory option in selected refractory rheumatic diseases, provided that careful patient selection, cautious monitoring, and long-term follow-up are implemented.
This study aims to update the European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of Behçet's syndrome according to the updated EULAR standard operating procedures. The task force comprised 29 members from 11 countries, including 19 rheumatologists, 2 ophthalmologists, 1 dermatologist, 1 gastroenterologist, 1 neurologist, 1 health professional, 2 patient research partners, and 2 Emerging EUlar NETwork members. Research questions were proposed by the task force through a Delphi survey and formulated into patients, interventions, comparison, and outcomes (PICO) questions for the systematic literature review. The results of the systematic literature review were discussed among the task force members. Previous recommendations and overarching principles were modified, and new recommendations were developed as needed. The updated recommendations were voted, and the levels of evidence and levels of agreement were determined. The updated recommendations consist of 5 overarching principles and 12 recommendations that were tabulated according to organ involvement. Among the 12 recommendations, 1 was a new recommendation, 7 recommendations were modified, and only the wording was changed in 4 recommendations. The overarching principles focus on the importance of recognising the relapsing and remitting disease course and individualising treatment according to disease activity and prognostic risk factors, and emphasise the importance of a multidisciplinary approach, patient education, and shared decision making for optimal care. For mucocutaneous and joint involvement, colchicine is recommended as the first-line treatment modality. Apremilast and immunosuppressives such as tumour necrosis factor alpha (TNFα) inhibitors are recommended for refractory patients. For patients with organ involvement, more aggressive treatment with glucocorticoids and immunosuppressives is recommended for rapid induction of remission. Early use of monoclonal antibodies against TNFα is encouraged in patients with organ or life-threatening manifestations. These
Stroke is a major cause of mortality and long-term disability worldwide. Patients with autoimmune rheumatic diseases (ARDs) exhibit a significantly increased risk of both ischemic and hemorrhagic strokes, particularly at younger age. Systemic inflammation, immune-mediated vascular injury, antiphospholipid antibodies, accelerated atherosclerosis, and comorbidities contribute to this elevated cerebrovascular burden. This review aims to comprehensively overview stroke epidemiology, pathophysiological mechanisms, clinical characteristics, prevention strategies, and post-stroke rehabilitation in patients with ARDs. Literature searches were conducted using Medline/PubMed, Scopus, Web of Science, and the Directory of Open Access Journals (DOAJ) databases up to February 1, 2026. Studies evaluating stroke incidence, risk factors, mechanistic pathways, prevention approaches, and rehabilitation in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, ankylosing spondyloarthritis, systemic vasculitides, and Behçet disease were included. Stroke risk is markedly increased across ARDs, with relative risks ranging from 1.3 to 2.5, depending on disease subtype. Systemic lupus erythematosus and systemic vasculitides confer particularly high cerebrovascular risk, often presenting at younger age and associated with worse functional outcomes. Chronic systemic inflammation, endothelial dysfunction, autoantibody-mediated thrombosis, genetic susceptibility, and accelerated atherosclerosis represent central mechanistic pathways. Certain immunomodulatory therapies may mitigate stroke risk through inflammation control, whereas others require careful cardiovascular risk assessment. Post-stroke recovery may be adversely influenced by persistent inflammatory activity and musculoskeletal comorbidities, underscoring the importance of multidisciplinary management. Early risk stratification, tight control of systemic inflammation, individualized immunomodulatory therapy, and structured rehabilitation strategies are essential to improve cerebrovascular outcomes in ARDs. Future research should focus on personalized risk prediction models and targeted preventive interventions in this high-risk population.
Frailty is increasingly recognized as a multidimensional clinical condition associated with impaired quality of life (QoL). However, the prevalence and clinical implications in patients with Behçet's disease (BD) remain unclear. This study aimed to evaluate the frailty status and its association with QoL in Japanese patients with BD. We surveyed 50 patients with BD aged ≥ 40 years. Frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria. QoL was evaluated using the 36-Item Short Form Survey (SF-36) and the Behçet's Disease Quality of Life scale. Associations between the frailty status and QoL were examined using multivariable linear regression models. The mean age of participants was 65.5 years. The prevalences of frailty, pre-frailty, and robustness were 12.0%, 69.0%, and 18.0%, respectively. In the multivariable analyses, frailty was associated with poorer disease-specific QoL, although the association did not reach statistical significance, whereas pre-frailty was not significantly associated with QoL outcomes. Frail patients had significantly lower SF-36 scores across most subscales than pre-frail patients. Slower walking speed was consistently associated with lower physical QoL, whereas weight loss was associated with the mental aspects of QoL. Frailty and pre-frailty are highly prevalent among patients with BD. Frailty is associated with an impaired QoL, particularly in the physical domains. Routine assessment of walking speed and nutritional status may facilitate the early identification of vulnerable patients and inform targeted management strategies to maintain QoL in patients with BD. Key Points • Frailty was observed in 12.0% of Japanese patients with Behçet's disease and 69.0% were classified as pre-frail. • Frailty is associated with impaired quality of life (QoL), particularly reduced physical domains. • Slower walking speed was consistently associated with poorer physical QoL, while weight loss
Behçet disease (BD) is an inflammatory disorder with significant ocular involvement. Angiopoietins regulate vascular stability, while EphrinB2/EphB4 interactions are essential for retinal neovascularization and endothelial behavior. Endocan, a marker of endothelial activation, contributes to inflammatory processes by mediating leukocyte migration. This cross-sectional study investigates the role of angiopoietins, EphrinB2/EphB4 signaling, and endocan in the development of active uveitis in BD patients. We recruited 29 BD patients with active eye involvement (group 1), 31 BD patients without eye involvement (group 2), and 30 healthy controls (group 3). Serum tyrosine protein kinase receptor (Tie-2), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), EphrinB2, EphB4, and endocan levels were determined by the enzyme-linked immunosorbent assay method. A statistically significant difference was found between the Ang-1, Ang-2, Tie-2, EphrinB2, EphB4, and endocan levels of the 3 different groups in the study (P < .05). Between the patients with panuveitis and patients with only posterior or anterior uveitis, serum Ang-1 (P < .001), Tie-2 (P < .001), EphrinB2 (P < .001), EphB4 (P = .001), and endocan (P = .002) levels had statistically significant differences. The highest and significant correlation was found between EphrinB2 and EphB4 (r = 0.931, P < .001). This was followed by a high level of significant correlation between Ang-1 and Ang-2 (r = -0.845, P < .001). In the group with active uveitis, EphB4 (r = -0.774), Ang-2 (r = -0.763), and Tie-2 (r = -0.701) were negatively and highly significantly correlated with best corrected visual acuity (P < .001). Ang-1, Ang-2, Tie-2, EphrinB2, EphB4, and endocan regulate vascular stability, retinal neovascularization, and inflammation, potentially contributing to BD-associated uveitis. These findings could have important implications for the diagnosis and management of ocular involvement of BD.
Rheumatic diseases (RDs) are chronic immune-mediated disorders associated with disproportionately increased cardiovascular morbidity and mortality. Accelerated atherogenesis in these diseases is driven by persistent systemic inflammation, autoantibody-mediated endothelial injury, oxidative stress, and dysregulated lipid metabolism, resulting in premature vascular remodeling manifested by increased carotid intima-media thickness, arterial stiffness, impaired flow-mediated dilation, and coronary artery calcification. This review synthesizes evidence regarding subclinical atherosclerosis and cardiometabolic risk across common RDs. In rheumatoid arthritis and systemic lupus erythematosus, vascular alterations correlate with inflammatory burden, disease duration, autoantibody profiles, renal involvement, and glucocorticoid exposure. Emerging biomarkers-including apolipoprotein B48, FIB-4 index, asymmetric dimethylarginine, and adhesion molecules-provide incremental prognostic value beyond traditional lipid parameters. Advanced imaging modalities, such as ^18F-sodium fluoride PET/CT and vascular elastography, enhance early detection of arterial calcification and stiffness. Growing evidence in primary Sjögren syndrome, Behçet disease, systemic sclerosis, and ankylosing spondylitis similarly confirms increased subclinical atherosclerosis and endothelial dysfunction. Importantly, tight disease control and targeted immunomodulatory therapies-including methotrexate, biologic agents, antimalarials, and cytokine-directed treatments-are associated with improved vascular and metabolic profiles and attenuation of disease progression. Subclinical atherosclerosis represents a critical interface between autoimmunity and cardiovascular disease in RDs. Early vascular assessment integrated with disease-specific and metabolic risk stratification is essential to implement precision-based cardiovascular prevention in this high-risk population.
Pregnancy in systemic autoimmune diseases is associated with increased maternal and fetal morbidity, yet the specific impact of neurological involvement remains poorly characterized. This review synthesizes pregnancy outcomes in systemic lupus erythematosus (SLE), Sjögren's syndrome, sarcoidosis, and Behçet's disease, focusing on neurological manifestations. A narrative review (2010-2025) was conducted via PubMed/MEDLINE. Observational cohorts, registries, and systematic reviews reporting maternal, fetal, and neonatal outcomes were included. Across autoimmune conditions, pregnancy risks are significantly elevated, most pronounced in SLE. Meta-analyses in SLE reported preeclampsia rates of 2-35%, preterm birth in 14.7-50%, and fetal loss up to 21.7%. In sarcoidosis, studies showed increased risks of preeclampsia (OR 1.62) and preterm delivery (OR 1.73), while Sjögren's syndrome was associated with congenital heart block in up to 17.9% of at-risk pregnancies. Neurological manifestations are frequently documented but rarely analyzed as independent risk factors; in one study, neuropsychiatric lupus was associated with higher rates of maternal (38.1% vs 14.1%) and fetal complications, although evidence remains limited and should be interpreted with caution. Neurological involvement is a critical but under-studied dimension of pregnancy risk. Improved phenotyping, multidisciplinary care, and prospective registries are needed to optimize risk stratification and maternal-fetal management.