Modern Rheumatology最新文献

Objectives: To clarify the impact of orthopaedic surgery on the quality of life (QOL) in patients with rheumatoid arthritis (RA), by comparing surgical cases with matched non-surgical controls using multicenter data from the Fukuoka Rheumatoid Arthritis NetworK (FRANK) registry.

Methods: A retrospective cohort study was conducted using FRANK registry data (2018-2022). Sixty-three surgical cases and non-surgical controls were analysed after propensity score matching for age, sex, disease duration, disease activity, and medication. Changes in disease activity (DAS28-ESR), activities of daily living (modified health assessment questionnaire), and QOL (EuroQol 5-Dimensional Questionnaire, EQ-5D) over 1 year were compared using paired and independent t-tests. Regression analyses identified predictors of QOL improvement.

Results: The majority of patients were in low disease activity (DAS28-ESR < 3.2). The surgical group showed a statistically significant improvement in EQ-5D (+0.04; P < 0.05), while no change was observed in the non-surgical group. Lower preoperative EQ-5D was the predictor of improvement. Mobility and anxiety/depression domains contributed most to QOL gains.

Conclusions: Orthopaedic surgery significantly improves QOL in RA patients, even in those with a low DAS-ESR28. Patients with lower baseline QOL benefit most. These findings support the importance of surgical intervention as a complementary strategy in holistic RA management.

Objectives: To evaluate the real-world effectiveness of rituximab (RTX) and intravenous cyclophosphamide (IVCY) compared to non-use for remission induction in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).

Methods: This observational study emulated a target trial using data from the Japan Collaborative Registry of ANCA-associated Vasculitis. Patients aged ≥20 years with newly diagnosed or relapsing MPA or GPA (2017-23) were included. RTX or IVCY use within 4 weeks defined the treatment group; others formed the control group. The primary outcome was failure to achieve remission at week 24 (Birmingham Vasculitis Activity Score = 0 and prednisolone ≤ 10 mg/day). Secondary outcomes included a composite of death, kidney failure, and relapse, and serious infection. In inverse probability weighted population, risk ratios were estimated using modified Poisson regression.

Results: Among 544 patients (MPA: 413, GPA: 131), 63.6% received RTX or IVCY. The risk ratio for failure to achieve remission was 0.72 (95% CI: 0.61-0.85), and for the composite outcome was 0.57 (95% CI: 0.33-0.97), and for serious infection was 1.03 (95% CI: 0.47-2.25). Results were robust in sensitivity analyses.

Conclusions: RTX and IVCY improved short-term outcomes in MPA and GPA without increasing infection risk, supporting their recommendation as standard therapy.

Objectives: To inform the 2024 updates of the Japanese College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis of the safety of maternal and paternal exposure to disease-modifying antirheumatic drugs (DMARDs).

Methods: We searched the databases of PubMed, the Cochrane Library, and the Japana Centra Revuo Medicina for articles published between 2019 and 2022 and combined them with our previous systematic review. Two independent reviewers screened articles, evaluated core outcomes, and performed meta-analyses for each clinical question.

Results: The relative effects (odds ratio (OR) [95% confidence interval (95% CI)]) of tumour necrosis factor inhibitor (TNFi) exposure on the infants of pregnant women with rheumatoid arthritis were as follows: major birth defects, 1.51 [0.89, 2.58]; and serious neonatal infections, 1.20 [0.84, 1.71]. The relative effects (OR [95% CI]) of paternal antirheumatic drugs exposure on major birth defect in infants were 1.30 [0.28, 6.14] for TNFi and 0.94 [0.38, 2.33] for methotrexate.

Conclusions: This systematic review provided the latest evidence on effects of maternal and paternal exposure to DMARDs on their infants for the 2024 update of the clinical practice guidelines.

Objectives: To clarify the effectiveness and safety of subcutaneous injections (SC) of methotrexate (MTX) in Japanese patients with rheumatoid arthritis using real-world data.

Methods: In this retrospective observational study, 82 patients with rheumatoid arthritis were administered SC MTX at our department and affiliated facilities for 24 weeks after approval in September 2022. Drug continuation rate, disease activity, clinical symptoms including adverse events, and glucocorticoid dose after SC MTX administration were retrospectively examined.

Results: The patients' background: age 59.8 years, male/female 16/66, disease duration 8.6 years, stage I/II/III/IV 36/32/2/11, DAS28-ESR 3.5, Clinical Disease Activity Index 10.4, and Simplified Disease Activity Index 11.2. The SC MTX continuation rate after 24 weeks (primary endpoint) was 86.6%. In 72 of 82 patients (87.8%), oral MTX was switched to SC MTX. Mean oral MTX dose before the switch was 10.6 mg/week. The mean maximum dose after switching to SC was 12.0 mg/week. Adverse events were observed in 30 patients (36.6%), with a total Common Terminology Criteria for Adverse Events grade of 2 or lower. Clinical symptoms such as nausea, liver dysfunction, and stomatitis improved in 15 (20.8%) patients. In 53 patients who switched from oral to SC MTX, the disease activity scores were improved, and the glucocorticoid dose could be reduced.

Conclusion: In real-world setting, switching from oral to SC MTX is useful in Japanese patients with rheumatoid arthritis.

Objectives: This study aimed to evaluate capillaroscopic findings in children with Raynaud's phenomenon (RP) referred to a paediatric rheumatology clinic and compare them to healthy controls to identify RP-related patterns.

Methods: Sixty-six patients aged 0-18 years with RP and 65 age- and sex-matched healthy controls were included. Standardized capillaroscopic assessments followed the 2020 recommendations of EULAR study group on microcirculation in rheumatic diseases. Capillaroscopic patterns of 62 primary RP patients were compared with controls.

Results: Two patients were diagnosed with systemic sclerosis and two with systemic lupus erythematosus. Among 62 primary RP patients (median age 14.92 years, 62.9% female), antinuclear antibody positivity was 11.29%. Capillaroscopy revealed increased apical loop diameter (18.74 ± 4.40 vs. 15.20 ± 2.98, P < .001), dilated capillaries (82.3% vs. 15.40%, P < .001), abnormal capillaries (53.2% vs. 18.5%, P < .001), microhemorrhages (17.7% vs. 1.5%, P = .002) in primary RP patients compared to controls. The predominant pattern was non-specific (56.5%) in RP patients and normal pattern in controls (87.7%, P < .001). No correlation was found between capillaroscopy patterns and antinuclear antibody positivity or medication use.

Conclusions: Patients with primary RP showed a unique capillaroscopy pattern. Follow-up studies are needed to assess the proportion who may develop secondary RP and how capillaroscopic findings evolve.

This study explored the role of cellular senescence in the progression of rheumatoid arthritis (RA) and evaluated the targeting of Cyclin E2 (CCNE2) in synovial fibroblasts as a potential therapeutic approach. A risk prediction model for RA was developed using LASSO regression analysis, which involved analyzing differential gene expression and performing Gene Set Enrichment Analysis (GSEA). The model was validated using the Receiver Operating Characteristic (ROC) curve. CCNE2 expression was examined via Western blotting. Knockdown of CCNE2 in RA synovial fibroblasts (RASFs) using shRNA resulted in reduced cell viability, increased apoptosis, and elevated levels of senescence markers such as p16, p21, and p53. Additionally, senescence-associated β-galactosidase (SA-β-Gal) activity and H3K9me3 fluorescence intensity were significantly increased. In vivo, Adeno-Associated Virus (AAV)-mediated intra-articular injection of shCCNE2 in a collagen-induced arthritis (CIA) mouse model significantly reduced the arthritis index, alleviated joint inflammation, and suppressed CCNE2 expression. Furthermore, the secretion of SASP factors such as MMP-3 and IL-8 was significantly enhanced. These findings suggest that targeting CCNE2 induces senescence in RASFs and may offer a novel strategy to mitigate RA progression and inflammation.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology that is influenced by environmental and genetic factors. The disease is associated with severe clinical manifestations, including renal involvement, skin, nervous system, and cardiovascular system complications. Given the severity of these symptoms, there is a need for effective treatments with minimal side effects. Current treatments, such as corticosteroids, result in significant adverse outcomes and show limited efficacy. As a result, new therapeutic approaches are being investigated. Among these, cell-based therapies, especially stem cell therapy, have attracted attention due to the immunomodulatory and regenerative properties of stem cells. However, several challenges limit the clinical success of mesenchymal stem cell (MSC) therapies. These challenges include lack of targeted transduction, limited survival and proliferation of transplanted cells, and difficulties in maintaining therapeutic properties and function. To overcome these limitations and improve efficacy, strategies for modifying MSCs have been developed, such as genetic engineering via gene therapy, nanotechnology-based drug delivery systems to enhance targeting and homing, and pretreatment of MSCs with anti-inflammatory agents or compounds that enhance survival and migration. This review explores strategies for modifying MSCs to enhance their therapeutic potential in the treatment of systemic lupus erythematosus.

Objectives: Diffuse idiopathic skeletal hyperostosis (DISH) may reduce spinal mobility and affect muscle quantity and quality, increasing sarcopenia risk. However, longitudinal data are limited. We investigated muscle quantity, quality, and their changes in DISH using computed tomography (CT) and bioelectrical impedance analysis (BIA).

Methods: We analysed health screening data, including data of participants who underwent CT and BIA twice over 5 years. We identified 143 DISH patients (58.0 ± 8.4 years, 19 females) and 143 age- and sex-matched controls (58.4 ± 8.8 years, 19 females). At L3, psoas and posterior paraspinal muscle (PSM) areas were measured on CT and normalized to height squared as muscle index (MI, cm2/m2). Muscle density was assessed in Hounsfield units (HU). The skeletal muscle mass index (SMI, kg/m2) was obtained from BIA.

Results: At baseline, DISH had a higher MI (psoas: 347.5 ± 86.0 vs 294.8 ± 81.7, P < .001; PSM: 809.3 ± 146.2 vs 758.8 ± 130.7, P = .002) but lower HU (psoas: 36.0 ± 9.1 vs 40.9 ± 5.2, P < .001; PSM: 39.0 ± 8.8 vs 42.0 ± 7.4, P = .002). SMI was similar (7.9 ± 0.9 vs 7.7 ± 0.9, P = .212). Over 5 years, the DISH MI declined (psoas: 334.3 ± 94.9, P = .006; PSM: 782.6 ± 166.4, P = .007), while controls showed no change (psoas: 294.7 ± 94.1, P = .695; PSM: 757.2 ± 170.3, P = .776).

Conclusions: DISH patients have greater muscle mass but lower quality and trend towards decline, suggesting sarcopenia risk.

Objectives: Juvenile psoriatic arthritis (JPsA), a subtype of juvenile idiopathic arthritis, is a chronic inflammatory disease characterized by joint and skin involvement. Microvascular alterations, including endothelial dysfunction and inflammation, are thought to contribute to its pathophysiology. Nailfold videocapillaroscopy (NVC) is a noninvasive technique for assessing microvascular changes. This study aimed to evaluate NVC findings in children with JPsA compared to healthy controls, investigating the potential diagnostic and monitoring utility of NVC.

Methods: This cross-sectional study included 25 children with JPsA and 33 age- and sex-matched healthy controls. NVC was performed on eight fingers per participant, focusing on capillary density, morphology, and the presence of microhaemorrhages. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score-27. Statistical analyses compared capillaroscopic findings between groups and explored correlations with clinical parameters.

Results: In JPsA patients, tortuous capillaries (84% vs 24%, P < .001), crossed capillaries (100% vs 63.6%, P = .001), and microhaemorrhages (28% vs 0%, P = .002) were significantly more frequent compared to controls. No specific capillaroscopy pattern was detected in the JPsA cohort. The capillary density and apical loop widths did not differ significantly between groups (P = .92 and P = .93, respectively). Disease duration negatively correlated with capillary density (r = -0.484, P = .014), suggesting progressive microvascular changes over time.

Conclusions: Nailfold videocapillaroscopy revealed distinct microvascular abnormalities in children with JPsA, including increased tortuosity and microhaemorrhages, highlighting its potential as a diagnostic and monitoring tool. Longitudinal studies with larger cohorts are warranted to validate these findings and clarify the prognostic significance of NVC in JPsA.

Objectives: To assess rheumatologists' awareness of social insurance, welfare systems, and home medical care for rheumatoid arthritis (RA) patients in Japan.

Methods: An anonymous, web-based questionnaire was distributed to 5 128 members of the Japan College of Rheumatology between April 11 and 30, 2024. The survey covered demographics, knowledge of support systems, and attitudes towards home medical care.

Results: A total of 478 rheumatologists responded (response rate 9.3%). Whilst over 80% had some understanding of the High-Cost Medical Expense Benefit and Long-Term Care Insurance systems, knowledge of the Disability Pension and long-term care facility characteristics was limited. About 73% reported facing difficulties in patient support due to insufficient knowledge. Medical Social Workers played a central role in providing patient support; however, their availability was limited in smaller clinics. Although 95.3% of respondents recognized the growing need for home medical care, only 24.5% had practical experience. Major concerns included the lack of RA expertise amongst physicians caring for patients living at home and challenges in medication management after care transition.

Conclusions: Despite recognizing the importance of integrating social support and medical care, significant gaps remain in rheumatologists' knowledge and engagement, especially in home care settings. Educational and systemic improvements are needed.