Advances in Rheumatology最新文献

Background: Tuberculosis (TB) remains a global health challenge, especially in low- and middle-income countries. Tumor necrosis factor alpha (TNFα) plays a crucial role in the immune response to TB. TNF inhibitors were the first biologic agents approved for treating chronic inflammatory diseases such as psoriasis (PsO), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Despite their efficacy, TB risk is a concern. The development of new biological therapies, as IL-17 inhibitors, has improved these diseases' management; however, data regarding TB risk remain scarce. This study assessed TB incidence in Brazilian patients with PsO, axSpA and PsA treated with secukinumab.

Methods: This real-world retrospective study included Brazilian patients treated for at least 24 months, aged ≥ 18 years, without confirmed tuberculosis diseaseTBD. Data were extracted from medical charts. Descriptive analyses used mean or median, standard deviations, and quartiles for continuous variables and absolute frequencies and percentages for categorical variables with 95% confidence intervals calculation, as applicable.

Results: 152 participants were included, with a mean follow-up of 40.1 months, predominantly PsA (n = 90) and white (84.6%), with an average age of 52 years (IQR: 42-61) and a slightly male predominance (50.7%). Hypertension for PsA (11.9%) and PsO (16.3%), and fibromyalgia for axSpA (16.0%) patients were the most common comorbidities. PsO patients had the longest disease duration (184.6 months). Secukinumab loading doses were administered to 141 patients, with 78% receiving 300 mg. Maintenance doses were 300 mg for 77% of the patients. Secukinumab treatment was discontinued in 18 patients (11.8%). On average, patients were on 3.35 concomitant medications before secukinumab, dropping to 2.26 afterward, with methotrexate being the most used medication before secukinumab. No TBD cases were recorded. Tuberculosis infection (TBI) testing showed some positive results, and preventiveantibiotic therapy was administered as needed. Most patients remained negative for TBI after treatment. No safety-related information was detailed.

Conclusion: This real-world evidence study demonstrated that no TBD cases were recorded even after receiving secukinumab, and most patients were negative for TBI. Further studies are recommended to enhance the knowledge of TB prevention among patients with axSpA, PsO, and PsA.

Background: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by the dysregulation of multiple cytokines. In RA, Interleukin (IL)-4 levels fluctuate throughout disease progression, exerting a pathogenic role at onset and an anti-inflammatory role in later stages. Evidence suggests that IL-4 levels also differ between sexes and may be associated with disease severity. Thus, this study aimed to assess sex-based differences in IL-4 serum levels among patients with RA and determine whether these differences correlate with clinical parameters.

Methods: A total of 51 patients with RA (34 females and 17 males) and a control group of 24 sex- and age-matched individuals were included. IL-4 serum levels were quantified using a multiplex bead-based assay, and clinical parameters-including disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), disease activity score (DAS28), and health assessment questionnaire disease index (HAQ-DI)-were analyzed using the Mann-Whitney U test and Spearman's correlation coefficient. Non-parametric effect size was determined using the Hodges-Lehmann estimator of the median difference, and a multivariate linear regression analysis was performed to account for potential confounding variables.

Results: IL-4 levels were significantly lower in RA patients compared to controls (p < 0.0001), with male patients exhibiting higher IL-4 levels than female patients (p = 0.001). IL-4 levels were negatively correlated with RF (p = 0.037) and DAS28 (p = 0.005) in the overall population, with disease duration in female patients (p = 0.033), and with CRP (p = 0.046) and DAS28 (p = 0.024) specifically in male patients.

Conclusions: Higher IL-4 levels in males with RA may contribute to reduced inflammation, which is associated with lower disease activity. Conversely, lower concentrations of this cytokine in females may exacerbate disease progression. However, further studies are needed to confirm these findings.

Background: Septic arthritis (SA) is a rare but serious disease. There is no reliable marker for rapid diagnosis. Synofast® is a new device that analyses synovial fluid and can accurately rule out SA within 15 minutes.

Objective: To evaluate the diagnostic performance of Synofast® in routine practice in patients with suspected SA and to assess its impact on patient care.

Method: This was a monocentric prospective study of patients with acute arthritis of possible septic origin. In addition to the usual blood and synovial bacteriological tests, a drop of synovial fluid was taken for the Synofast® test, which provides three SA risk probabilities: "low", "possible" or "high". The physician recorded the management he would have given before the test and the management he actually gave after the test, knowing the diagnostic performance reported in previous studies.

Results: Over one year, 43 patients were included, of whom eight had SA (18.6%). Sensitivity, negative predictive value (PV) and negative likelihood ratio (LR) were respectively of 75%, 93% and 0.32 when analysing for "high" and "possible" septic risk while specificity, positive PV and positive LR were respectively of 94%, 67% and 8.75 when analysing for "high" septic risk only. The test helps to avoid hospitalisations in 1/29 patients and to defer antibiotic in 1/7 patients. Follow-up and drug management remained unchanged in 95% and 89% of patients, respectively.

Conclusion: Synofast® seems to be a valuable tool for the exclusion of SA. The results need to be confirmed in a larger population, especially the impact on management.

Background: Localised scleroderma is a rare autoimmune connective tissue disorder characterized by excessive collagen deposition leading to skin fibrosis. While methotrexate and glucocorticosteroid remain the first-line treatments, their limitations underscore the need to explore targeted biologic therapies. Tocilizumab, an IL-6 receptor antagonist, has shown promise in some systemic autoimmune diseases, but its role in juvenile localised scleroderma remains unclear. This study retrospectively evaluates the efficacy and safety of tocilizumab in juvenile localised scleroderma patients.

Methods: This retrospective study analysed 12 juvenile localised scleroderma patients treated at Anhui Province Children's Hospital between January 2021 and December 2024. Patients were grouped based on early versus delayed initiation of tocilizumab. Clinical response was measured using mLoSSI and LoSDI scores. Laboratory markers (ALT, AST, cholesterol, triglycerides, CRP) and immune indicators (CD4, CD19, IgG) were assessed alongside treatment duration. Safety and glucocorticosteroid usage were also evaluated.

Results: Five patients received tocilizumab from treatment onset, while seven were treated later. The tocilizumab initial use group had a significant lower relapse rate, compared to the delayed group. Longer treatment with tocilizumab had a protective effect on liver function and lipid metabolism, due to less abnormal ALT and triglyceride. No statistically significant relationship was observed between IgG deficiency and the duration of tocilizumab therapy; only one patient developed IgG deficiency, which resolved after a three-week interruption of treatment. Tocilizumab also reduced glucocorticosteroid reuse and duration of usage.

Conclusion: Tocilizumab appears to be a safe and effective adjunctive therapy for juvenile localised scleroderma, particularly when initiated early, as it reduces relapse risk and the need for prolonged glucocorticosteroid use. It remains a promising adjunct in refractory or severe cases requiring long-term management.

Background: Oxidative stress and inflammation contribute to telomere length (TL) attrition, a hallmark of cellular senescence. Systemic lupus erythematosus (SLE) is associated with premature cellular aging; however, the clinical relevance of TL shortening remains unclear. This study aimed to compare the relative TL of SLE patients and healthy controls and explore its association with clinical features and disease burden.

Methods: We conducted a cross-sectional study including adult SLE patients and age- and sex-matched healthy controls (18-60 years). Demographic and clinical data were collected, and TL was measured using quantitative polymerase chain reaction (qPCR). Among SLE patients, disease activity, cumulative damage, fatigue, depression, anxiety, stress, and physical activity were also assessed. Statistical analyses included descriptive statistics, Student's t-test or Mann-Whitney test for group comparisons, Spearman's correlation, and multiple linear regression models selected based on the lowest Akaike information criterion (AIC).

Results: Sixty SLE patients (37 years ± 11.5) and 55 controls (38 years ± 10.5) were enrolled. SLE patients exhibited significantly shorter TL [median (IQR): 0.80 (0.29-2.94)] compared to controls [1.07 (0.38-2.32); p = 0.005]. In multivariate analysis, moderate anxiety was associated with shorter TL compared to none/low anxiety [β= -0.353 (95%CI: -0.645; -0.061); p = 0.019]. An alternative model indicated that moderate stress was also associated with reduced TL [β= -0.411 (95%CI: -0.771; -0.050); p = 0.026]. No significant associations were found between TL and disease activity or cumulative damage.

Conclusions: SLE patients presented significantly shorter telomeres than healthy controls, with anxiety and stress symptoms contributing to TL attrition. Longitudinal studies are warranted to elucidate the clinical implications of TL shortening in SLE.

Objective: To evaluate whether the combination of exercise and intra-articular injection (IAI) effectively improves pain, function, and quality of life in patients with knee osteoarthritis (OA) compared to any control group in the short, medium, and long term through a systematic review.

Methods: A comprehensive search strategy was applied in the databases Embase, PubMed, MEDLINE, CENTRAL, CINAHL, and PEDro. Inclusion criteria focused on randomized controlled trials examining the effects of exercise combined with IAI in patients with knee OA, with outcomes assessed at short-, medium-, and long-term follow-ups. The primary outcomes were pain and function. The quality of the evidence was evaluated using the GRADE system.

Results: Eleven studies, comprising 802 participants, were included. All studies investigated the combination of IAI and exercise. A statistically significant difference in pain was observed: in the short and medium term, the Botulinum toxin IAI group demonstrated superior pain reduction compared to the Hyaluronic acid IAI group (MD -1.32, 95% CI -2.20 to -0.44 and MD -9.09, 95% CI -13.16 to -5.01, respectively). In the medium term, Saline IAI was more effective than Corticosteroid IAI (MD 1.99, 95% CI 0.49 to 1.90). Regarding function, Saline IAI outperformed IAI with any medication in the short term (MD 0.50, 95% CI 0.20 to 0.79). In terms of quality of life, the Corticosteroid IAI group demonstrated superior physical function and mental health outcomes compared to the Saline IAI group in the medium term (MD -0.43, 95% CI -0.77 to -0.08 and MD -0.38, 95% CI -0.76 to -0.01, respectively). In the long term, physical function improved more with IAI combined with exercise compared to exercise alone.

Conclusion: Given the very low quality of the evidence, it is not possible to definitively conclude that the combination of IAI and exercise is more effective than IAI or exercise alone in patients with knee OA. Further high-quality studies are needed to establish more definitive conclusions.

Registration: The International Prospective Register of Systematic Reviews (PROSPERO): CRD42021277729.

Clinical trial number: Not applicable.