To investigate the clinical, psychological, and functional determinants of kinesiophobia and to examine their interrelationships in patients with systemic lupus erythematosus (SLE). This cross-sectional study included 60 patients with SLE. Demographic characteristics, disease-related variables, laboratory parameters [e.g., C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] and disease activity were recorded. Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK). Central sensitization, personality, mental health, quality of life, and sleep were evaluated by the Central Sensitization Inventory (CSI), Type D Scale-14 (DS14), Hospital Anxiety and Depression Scale (HADS), Short Form-12 (SF-12), and Jenkins Sleep Evaluation Scale (JSS), respectively. Serial multiple mediation analysis were performed to examine factors associated with kinesiophobia. A mean age of patients with SLE was 39.7 ± 13.8 years. Kinesiophobia was present in 70% of the study population. Patients with kinesiophobia had significantly higher ESR and CRP, DS14 total and negative affectivity scores, and greater psychological distress across all HADS subscales (p < 0.05, for all). TSK scores correlated positively with CRP, ESR, pain, CSI, DS14, and HADS subscales (correlation coefficients ranged between 307 and 522) and negatively with SF-12 Physical Component Summary score (correlation coefficient=-0.414). Serial mediation analysis explained 40% of TSK score variance (R[2]=0.40). CRP had a significant direct effect on kinesiophobia (B = 0.87, p = 0.002), independent of age and sex. Neither DS14 nor CSI significantly mediated this association. Kinesiophobia is highly prevalent in patients with SLE and associated with inflammatory, psychological, and functional parameters. Systemic inflammation, reflected by CRP, appears to be independently associated with fear of movement in SLE. These findings underscore the importance of monitoring inflammatory markers in SLE management and integrating personality and central sensitization assessments into a comprehensive biopsychosocial approach.

Primary neurologic involvement represents one of the most serious manifestations of systemic autoimmune diseases, yet the influence on pregnancy outcomes remains poorly characterized across disorders. To describe neurologic disease activity and maternal-fetal outcomes in pregnancies occurring after the onset of systemic autoimmune-associated neurologic involvement. A retrospective case series was conducted within the Mass General Brigham healthcare system (2010-2025), including women with systemic autoimmune disease and objectively characterized neurologic involvement who experienced pregnancy following neurologic disease onset. Neurologic disease activity across the peripartum period and associated maternal and fetal outcomes were explored. Thirteen patients with systemic lupus erythematosus (SLE; 38 pregnancies), 20 with Sjögren's disease (SJD; 45 pregnancies), and 5 with sarcoidosis (14 pregnancies) met inclusion criteria; no eligible Behçet's disease cases were identified. In SLE, central nervous system involvement occurred in 69.2%, while neurologic worsening occurred during pregnancy in 38.5% and postpartum in 23.1%. Among 25 viable SLE deliveries, hypertensive disorders of pregnancy occurred in 24.0% and preterm delivery in 20.0%. In SJD, peripheral nervous system involvement occurred in 90.0% and autonomic dysfunction in 55.0%; neurologic worsening occurred during pregnancy in 5.0% and postpartum in 30.0%. Among 33 viable SJD deliveries, preterm delivery occurred in 9.1% and hypertensive disorders of pregnancy in 6.1%. Among 5 patients with sarcoidosis, peripheral and central nervous system involvement occurred in 60.0% and 40.0%, respectively; among 9 viable deliveries, hypertensive disorders of pregnancy occurred in 33.3% and preterm delivery in 22.2%. Medication exposures were heterogeneous across diseases and reproductive stages. Peripartum women with systemic autoimmune diseases and related neurologic involvement represent a clinically heterogeneous and medically complex population. Distinct disease-specific neurologic phenotypes may influence patterns of obstetric morbidity and postpartum neurologic vulnerability, highlighting the need for prospective multicenter studies with standardized neurologic phenotyping and longitudinal postpartum follow-up.

IgA vasculitis (IgAV) is the most common systemic vasculitis in childhood. Its seasonal distribution and frequent respiratory or gastrointestinal prodromes implicate environmental exposures. However, microbiological detection temporally proximate to disease onset is insufficient to establish causality in an individual patient. To critically evaluate infectious exposures associated with pediatric IgAV, we distinguished epidemiological associations from incidental detection and infectious mimics, and separate direct IgAV evidence from mechanisms extrapolated from IgA nephropathy or general mucosal immunology. PubMed and MEDLINE were searched from inception through 6 August 2026 and supplemented by backward and forward citation tracking. Controlled-vocabulary and free-text terms addressed IgAV, pediatric populations, infection, specific pathogens, microbiota, vaccination, and immune mechanisms. The broad query retrieved 1,174 records before deduplication. Because screening was not prospectively logged, deduplicated screening and full-text counts could not be reconstructed; accordingly, no systematic-review or PRISMA completeness claim is made. Comparative evidence was most consistent for group A streptococcal exposure and population-level circulation of seasonal respiratory bacteria. Evidence for Mycoplasma pneumoniae, Helicobacter pylori in selected phenotypes, SARS-CoV-2, and specific enteric or parasitic infections was of lower certainty and was frequently case-based. Pediatric vaccine studies did not demonstrate a consistent excess risk. Evidence supports convergence of mucosal IgA induction, IgA1-containing immune complexes, complement activation, FcαRI-mediated myeloid signaling, neutrophil extracellular traps, and endothelial injury. Causal attribution requires integrated assessment of temporality, anatomical source, microbiological specificity, background exposure prevalence, and alternative diagnoses. Infectious investigations should be restricted to circumstances in which identification of a treatable infection, persistent antigen source, or immunosuppression-related hazard would alter management.

T-cell redirecting therapies (TCRTs), including Chimeric antigen receptor (CAR)-T cells and T-cell engagers (TCEs), are emerging as transformative treatments for autoimmune diseases. However, clinical application is currently restricted to specialized centers, leaving most clinicians with limited first-hand experience. We aimed to assess the knowledge, perception, and barriers regarding TCRTs among German rheumatologists. A prospective, web-based survey was distributed to German rheumatologists via congresses and digital channels from September 2024 through January 2025. Drafting the design and reporting of the survey results was performed regarding international recommendations as the "checklist for reporting results of internet e-surveys" (CHERRIES). Statistical analysis was conducted with SPSS. Of 98 participants (median age 43 years) the majority was based at university hospitals (46.3%) and 94.8% were willing to refer patients to specialized centers. However, respondents considered only 5% of their patients suitable for TCRT, primarily those with severe, refractory connective tissue diseases. The main barriers cited were high costs (82%), limited clinical experience (65.5%) and applicability in only a limited number of patients (35.4%). Knowledge of side effects (e.g., cytokine release syndrome, infections, hypogammaglobulinemia) and contraindications (e.g. heart failure, chronic infections) was generally accurate. Yet, the self-appraisal of existing knowledge on TCRT was only seen as medium by the questioned rheumatologists (median of 4.86, on a 0 to 10 scale with 10 is best knowledge). Participating German rheumatologists demonstrated a high willingness to refer patients for TCRTs and appeared to possess good safety knowledge. However, the therapy is currently viewed as a niche option for highly active, refractory cases, with costs and limited data serving as primary barriers to broader implementation.

To describe real-world management of connective tissue disease-associated interstitial lung disease (CTD-ILD) and explore associations between progressive pulmonary fibrosis (PPF) onset and clinical outcomes. This international, retrospective cohort included adults with rheumatoid arthritis (RA), systemic sclerosis (SSc), mixed connective tissue disease, and other CTD with associated ILD. PPF was identified using INBUILD and/or ATS/ERS/JRS/ALAT criteria applied in routine care. Analyses were descriptive and exploratory; time-to-event methods assessed selected outcomes and factors associated with PPF onset. Among 357 patients (mean age 61.6 years; 58% female), SSc-ILD (31%) and RA-ILD (29%) were most common. At ILD diagnosis, 21.6% had no respiratory symptoms. During a mean follow-up of 60.5 months, 147 patients (41.2%) met the PPF criteria, at a median of 30.6 months after CTD-ILD diagnosis. Following PPF onset, the most frequently prescribed therapies were corticosteroids (72.8%), mycophenolate mofetil (52.4%), and antifibrotics (51.0%). Lung function data were available for 37.8% at diagnosis and 53.7% at year 5. PPF was associated with greater observed lung function decline compared to non-PPF patients. ILD-related hospitalizations was numerically more frequent within PPF patients (37.4% vs. 28.6%), but the difference was not statistically significant (P = 0.078). Among patients with PPF, earlier versus later onset, defined by a subtype-specific median split, was associated with poorer observed survival (P < 0.001). In this retrospective cohort, PPF was observed frequently in CTD-ILD patients, particularly those with SSc-ILD, and was associated with greater lung function decline and higher healthcare utilisation. Earlier PPF onset was associated with higher mortality risk, but missing lung function data, surveillance differences, time-related bias, and residual confounding limit causal interpretation. Prospective studies using harmonised PPF adjudication and time-dependent analyses are needed.

Systemic sclerosis (SSc) frequently causes visible changes in physical appearance that may adversely affect body image and quality of life. Although dermocosmetic and aesthetic procedures are increasingly used to improve appearance and function in selected patients with SSc, little is known about patients' knowledge, attitudes, and expectations regarding these interventions. This study aimed to evaluate patients' attitudes toward dermocosmetic and aesthetic procedures using a purpose-designed questionnaire. In this cross-sectional study, 70 patients fulfilling the 2013 ACR/EULAR classification criteria for SSc completed a purpose-designed questionnaire. Demographic data were obtained from the questionnaire, while clinical characteristics were verified using medical records. The questionnaire evaluated knowledge, attitudes, previous experiences, future intentions, appearance-related concerns, perceived effects on self-confidence, willingness to consult a rheumatologist before aesthetic procedures, and preferred anatomical sites for potential interventions. The mean age was 54.6 ± 13.3 years, 90.0% were female, and 55.7% had diffuse cutaneous SSc. Disease-related changes in physical appearance were reported by 70.0% of participants, and 41.4% expressed discomfort with these changes. Nearly half (47.1%) reported no knowledge of any dermocosmetic procedure, and 85.7% had not previously undergone a dermocosmetic/medical aesthetic procedure. Nevertheless, 61.4% expressed positive attitudes toward dermocosmetic procedures, and 64.3% believed that these procedures could improve self-confidence. Nearly all participants (97.2%) stated that they would consult their rheumatologist before undergoing a dermocosmetic or aesthetic procedure. After false discovery rate (FDR) correction, diffuse cutaneous SSc remained associated with greater appearance-related discomfort than limited disease (53.8% vs. 25.8%; FDR-adjusted p = 0.032). Participants with at least a high school education more frequently expressed positive attitudes (83.9% vs. 43.6%; FDR-adjusted p = 0.014) and reported plans for future dermocosmetic/medical aesthetic (45.2% vs. 20.5%; FDR-adjusted p = 0.038) and surgical aesthetic procedures (22.6% vs. 2.6%; FDR-adjusted p = 0.032). In multivariable logistic regression adjusted for age and SSc subtype, higher education remained independently associated with a positive attitude (adjusted OR 6.43, 95% CI 1.73-23.91, p = 0.006). Appearance-related concerns are common among patients with SSc and represent an important yet often overlooked aspect of patient care. Despite limited knowledge, patients generally expressed favorable attitudes toward dermocosmetic and aesthetic procedures and strongly preferred consulting their rheumatologists before considering such interventions. These findings support the integration of appearance-related counselling into routine, patient-centered rheumatology care.

Patients with autoimmune and inflammatory diseases most often exhibit sympathetic overactivity and dominance at the expense of the parasympathetic system, including the vagus nerve. It leads to dysfunction of the negative feedback mechanism within the hypothalamic-pituitary-adrenal axis, resulting in impaired regulation of cortisol levels, stress responses, and pro-inflammatory cytokines. Furthermore, vagal dysfunction affects the mechanism by which acetylcholine binds to α7 nicotinic receptors on macrophage surfaces, thereby inhibiting the release of TNF-α and other pro-inflammatory cytokines. The aim of this review was to identify reports elucidating the mechanisms underlying the anti-inflammatory effects of the vagus nerve and to evaluate the efficacy of VNS as a potential method for modulating autonomic nervous system function. A literature search was conducted using the electronic databases PubMed, focusing on the role of the vagus nerve in autoimmune disorders, and on vagus nerve stimulation (VNS). Based on the collected data, a reduction in inflammatory activity and decreased production of pro-inflammatory cytokines were observed following vagus nerve stimulation. Moreover, the authors of the studies analyzed reported additional therapeutic effects, including pain modulation, suppression of disease activity, and a reduction in fatigue. Vagus nerve stimulation represents a promising alternative therapeutic modality for the treatment of rheumatologic diseases. However, further high-quality studies conducted in substantially larger cohorts are required, taking into account variability in stimulation parameters and their differential impact on clinical outcomes.

Neurosarcoidosis is a rare inflammatory disease with a heterogeneous presentation. Psychiatric manifestations may precede neurological involvement, but their prevalence, diagnostic pattern, and treatment outcomes remain insufficiently defined. PubMed, Web of Science and Scopus databases were searched on July 8, 2025, to identify all published case reports reporting psychiatric manifestations in patients with sarcoidosis or neurosarcoidosis without language or publication year restriction. All relevant data were extracted based on study characteristics, patient demographics, clinical history, psychiatric and neurological manifestations, diagnostic investigations, treatment modalities, and clinical outcomes. Eighty-nine studies describing 93 patients' cases were included. The mean age was 45.48 ± 14.46 years, with a male predominance (58.1%). 74.2% had systemic sarcoidosis, while 25.8% presented with isolated neurosarcoidosis. Diagnosis was confirmed by histopathology in 84.9% of patients. Psychiatric symptoms preceded neurological manifestations in 78.5% of cases. The most common psychiatric manifestation was cognitive impairment followed by personality changes (88.2%, 65.6% respectively). MRI frequently showed parenchymal lesions (66.7%) and leptomeningeal enhancement (57.7%), while CSF analysis commonly revealed elevated protein (80%) and pleocytosis (71.3%). Corticosteroids were used in (93.5%) of patients, with 58.1% achieving complete remission. Acute psychiatric onset (48.1% vs. 15.4%, p = 0.002) and delirium (70.4% vs. 41.0%, p = 0.013) were observed with higher remission. Isolated neurosarcoidosis (33.3% vs. 16.7%, p = 0.040), parenchymal lesions (59.0% vs. 50.0%, p = 0.034) and basal ganglia involvement (30.8% vs. 16.7%, p = 0.045) were significantly more common among patients who did not achieve complete remission. Systemic sarcoidosis is more frequently linked with higher remission rates due to earlier recognition and less irreversible CNS damage. Neuropsychiatric presentations are heterogeneous, with delirium associated with favorable remission outcomes. Corticosteroids remain the mainstay of therapy. Further prospective studies are needed to phenotype and optimize management strategies. PROSPERO: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251140210 .

Specialized pregnancy counselling improves maternal and infant outcomes in women with inflammatory rheumatic and musculoskeletal diseases (iRMDs). As such services are not universally available, large language models (LLMs) may increasingly serve as an accessible source of information for patients seeking guidance on family planning, pregnancy, and lactation. This highlights the need to evaluate this software in terms of their adequacy, accuracy and overall reliability. The aim of the analysis is to evaluate the possibility of using LLMs as reliable sources of information regarding female patients suffering from iRMD and going through the period of pregnancy. 54 questions were formulated, which concern the impact and general relationship between pregnancy and rheumatic diseases. The questions were given to four LLMs, ChatGPT, DeepSeek, Gemini and Grok, and the corresponding answers were obtained. The responses were rated across three clinical domains on a 5-point Likert scale (ranging from 1 = strongly disagree/very poor to 5 = strongly agree/excellent) by ten European rheumatology experts and with the help of appropriate statistical indicators calculated, the reliability of the LLMs was assessed. 2160 items were evaluated. All models demonstrated high performance in "Clinical Safety" (Means > 4.10). For "Clinical Accuracy", DeepSeek and ChatGPT scored highest (Median 4.40 for both). Significant deviations were observed in "Completeness and Relevance", where DeepSeek dominated (Mean 4.24, 95% CI 4.17-4.30) and Gemini showed the lowest performance (Mean 3.46, 95% CI 3.27-3.64). Inter-rater agreement was poor to slight (Fleiss' kappa range: -0.043 to 0.059) and moderate for ICC (range: 0.259 to 0.692). LLMs currently exhibit uniformly strong safety behaviors when providing medical information about family planning, pregnancy and lactation in iRMD. However, significant differences exist regarding completeness and relevance, where DeepSeek and ChatGPT are currently the most reliable and complete models for this domain. Furthermore, the variability in responses and low inter-rater agreement highlight that LLMs require further parameterization, are useful tools for routine care, but cannot replace expert medical judgment.

Childhood-onset rheumatic diseases including Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (jSLE), and Juvenile Dermatomyositis (JDM) could impact growth, but this is not well described within the UK population, particularly over the long term. This study aims to compare the growth patterns of patients with JIA, jSLE, and JDM to those of their peers. This population-based cohort study used primary care data from the Clinical Practice Research Datalink (CPRD) with follow up through to March 2023. Patients diagnosed with JIA, JDM and jSLE, were matched with up to five healthy controls by age, sex and general practice. Age and sex standardised Z-scores were calculated for height and weight. Linear mixed models were used to investigate differences in growth patterns over time. Height measurements from 3736, 182 and 111 children with JIA, jSLE and JDM and weight measurements from 5088, 251 and 144 children with JIA, jSLE and JDM respectively were extracted. JIA patients showed significant baseline differences in height compared to healthy controls (Estimate= -0.061, 95% CI 0.002, 0.121) but this initial reduction was countered by an increased rate of catch up growth over time. Similar patterns were observed in jSLE and JDM, although differences were less consistent and largely confined to specific subgroups. Overall, weight trajectories were broadly similar to those of matched controls across all three diseases. Stratified analyses suggested that growth patterns varied according to age at disease onset, with the clearest differences observed in JIA. Children with JIA, jSLE and JDM demonstrated altered longitudinal growth patterns, with the clearest evidence observed in JIA. Growth trajectories varied according to age at disease onset, particularly during the pre and peri-pubertal period, suggesting that the timing of disease onset may influence long-term growth. These findings support the importance of longitudinal growth monitoring, particularly among children diagnosed during key developmental periods.

Handgrip strength (HGS) is a valuable indicator of muscle function that can be used to identify patients with rheumatoid arthritis (RA) at risk of sarcopenia and other functional impairments. The aim of this study was to describe grip strength (HGS) in patients with rheumatoid arthritis (RA), to assess the frequency of low HGS, to quantify grip strength relative to age- and sex-specific reference values, and to identify the clinical factors associated with HGS. In this single-centre cross-sectional study, 70 patients with RA had their HGS measured sequentially on both arms using an electronic hand dynamometer, with three measurements taken per arm; the higher of the HGSmeasurementse was taken as the maximum. Low HGS was defined as < 27 kg for men and < 16 kg for women. The maximum HGS was additionally expressed as an age- and sex-adjusted z-score relative to normative data; deviations from the norm were tested using the Wilcoxon signed-rank test (with an assumed median z = 0). Spearman's correlation and multivariate linear regression were used to determine the presence of an association with the maximum HGS value. The patients were predominantly women (n = 55; 78.6%), with a mean age of 53.6 ± 13.3 years, presenting with a long-standing course of RF-positive, erosive, highly active disease (median DAS28-ESR 5.6). The mean maximum HGS was 23.9 ± 8.8 kg. Low HGS was observed in 28.6% of patients (20% of women, 60% of men). Compared with age- and sex-matched norms, grip strength was significantly lower in men (median z = -1.71, p = 0.001) and in women (median z = -0.55, p < 0.001) . HGS scores were inversely correlated with age (ρ = -0.4, p = 0.001) and current smoking (ρ = -0.41, p = 0.001) and positively associated with body mass index (BMI) (ρ = 0.35, p = 0.003). Older age was the only variable independently associated with lower grip strength (B = -0.21 kg/year, p = 0.012). In this study, grip strength was low relative to established sarcopenia thresholds and age- and sex-specific reference values.

To investigate the relationship between gastrointestinal symptom burden assessed by the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ), fecal calprotectin (FC), a non-invasive biomarker suggestive of intestinal inflammation, disease activity, and clinical characteristics in patients with axial spondyloarthritis (axSpA). In this cross-sectional study, 174 patients with axSpA were enrolled. Gastrointestinal symptom burden was assessed using the DISQ, disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), functional status using the Bath Ankylosing Spondylitis Functional Index (BASFI), and health-related quality of life using the Short Form-36 (SF-36). FC levels were measured by enzyme-linked immunosorbent assay. Correlation analyses, receiver operating characteristic (ROC) analyses, and multivariable logistic regression models were performed. FC levels were normal (< 50 μg/g) in 52.9%, mildly elevated (50-200 μg/g) in 38.5%, and markedly elevated (> 200 μg/g) in 8.6%. DISQ scores demonstrated a moderate positive correlation with BASDAI (rs = 0.432, p < 0.001) and a weak positive correlation with BASFI (rs = 0.248, p < 0.001), while showing moderate inverse correlations with all SF-36 domains (rs = - 0.310 to -0.470, all p < 0.001). In contrast, DISQ scores were not associated with FC levels (rs = 0.066, p = 0.386), ESR (rs = 0.013, p = 0.868), or CRP (rs = 0.029, p = 0.706). ROC analyses demonstrated poor discriminatory performance between DISQ and FC (AUC 0.529 and 0.475, respectively). In multivariable analyses, BASDAI independently predicted clinically significant gastrointestinal symptoms (OR 1.635, 95% CI 1.285-2.081) and elevated FC levels (OR 1.254, 95% CI 1.004-1.567), whereas neither DISQ nor FC independently predicted the other. Gastrointestinal symptom burden assessed by the DISQ was associated with disease activity, functional impairment, and reduced quality of life, but not with FC levels in axSpA.