Modern Rheumatology最新文献

Objectives: Eosinophilic granulomatosis with polyangiitis (EGPA) causes complications in various organs. Cardiac involvement affects the prognosis but is difficult to detect during subclinical stages. We compared the results of cardiac magnetic resonance imaging with those of other imaging studies and biomarkers for patients with EGPA and suspected cardiac involvement.

Methods: This retrospective observational study included 29 patients diagnosed with and treated for EGPA at our hospital between 2015 and 2022. Of these patients, 16 with suspected cardiac involvement and cardiac magnetic resonance images were selected. Symptoms, autoantibodies, biomarkers, echocardiography, and other test results were compared with imaging findings.

Results: Of the 16 patients who underwent cardiac magnetic resonance imaging, eight had findings of cardiac involvement. A univariate analysis indicated significant differences in troponin I, creatine kinase-MB, and N-terminal pro-brain natriuretic peptide between patients with and without findings of cardiac involvement. A multivariate analysis identified creatine kinase-MB as an independent predictive factor for cardiac involvement.

Conclusions: Cardiac magnetic resonance imaging used to diagnose subclinical cardiac lesions possibly improved the prognosis of patients with EGPA.

Objectives: Osteonecrosis of the femoral head (ONFH) is a progressive hip disorder often misdiagnosed owing to overlapping symptoms and radiographic findings. MicroRNAs (miRNAs) have emerged as potential diagnostic biomarkers; however, their role in ONFH remains unclear. This study analysed miRNA expression in synovial fluid and hip joint tissues of patients with ONFH to identify diagnostic markers.

Methods: Synovial fluid and hip joint tissues were collected from 24 patients with ONFH and 12 patients with osteoarthritis (OA) undergoing total hip arthroplasty. MiRNA expression was assessed using microarray and validated using real-time polymerase chain reaction (PCR). Statistical analyses compared ONFH and OA groups and examined clinical factor correlations. Tissue-specific expression was evaluated in subchondral and cancellous bone, synovia, and labrum.

Results: Real-time PCR revealed significant upregulation of miR-210 (P < .01), miR-296, miR-659, and let-7c (P < .05) in ONFH synovial fluid compared to that of OA. Expression patterns were independent of clinical factors. MiR-210 was also significantly upregulated in cancellous bone of the reparative zone in patients with ONFH (P < .05).

Conclusions: MiR-210, miR-296, miR-659, and let-7c upregulation in ONFH synovial fluid independent of clinical factors indicates their potential as diagnostic markers. Localized increase in miR-210 in cancellous bone may indicate its role in ONFH pathophysiology.

Objectives: To validate the MCK model's prognostic utility in patients with idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD).

Methods: This retrospective study included 242 patients with IIM-associated ILD from the multicentre MYKO cohort. Patients were classified as anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive or antibody-negative. The MCK score was defined by the number of criteria met: C-reactive protein (CRP) ≥ 0.8 mg/dL and Krebs von den Lungen 6 (KL-6) ≥ 1000 U/ml for MDA5-positive patients; CRP ≥ 1.1 mg/dL and KL-6 ≥ 1000 U/ml for MDA5-negative patients. Outcomes included all-cause mortality, disease flares, and infections requiring hospitalisation, which were assessed via Kaplan-Meier and Cox regression analyses.

Results: Amongst MDA5-positive patients, an MCK score of 2 did not significantly predict mortality. However, in MDA5-negative patients, an MCK score of 2 was significantly associated with an increased risk of all-cause mortality, disease flares, and infections requiring hospitalisation. Subgroup analyses from 2018 onward showed similar patterns, although statistical significance was not maintained.

Conclusions: The MCK model demonstrates strong predictive performance for all-cause mortality and disease complications, particularly in patients with MDA5-negative IIM. However, its predictive utility may have declined in recent years, possibly due to advancements in treatment approaches.

Objectives: To investigate the standardized mortality ratio (SMR), causes of death, and mortality risk factors in Japanese patients with rheumatoid arthritis (RA) between 2007 and 2021, representing the biological disease-modifying antirheumatic drug (bDMARD) era.

Methods: We analysed Japanese patients in the Institute of Rheumatology, Rheumatoid Arthritis cohort. The SMR was calculated using the Japanese General Population Life Table. Multiple imputation methods were used for sensitivity analysis of lost-to-follow-up cases. Risk factors were analysed using a time-dependent Cox proportional hazards model.

Results: Among 10,613 patients with RA, 915 deaths occurred for 99,364.8 patient-years. Major causes of death were malignancy (27.8%), respiratory disease (22.3%), and cardiovascular disease (16.3%). The SMR varied based on lost-to-follow-up assumptions: 0.92 [95% confidence interval (CI): 0.86-0.98] assuming all survived, 1.57 (95% CI: 1.47-1.68) assuming lost cases had equal mortality to followed cases, and 1.68 (95% CI: 1.58-1.79) assuming 1.65 times higher mortality than followed cases, respectively. Time-dependent analysis revealed protective associations with methotrexate (MTX) and bDMARDs, while even low-dose glucocorticoids showed increased mortality risk.

Conclusions: Japanese patients with RA show excess mortality despite bDMARD-era treatments. MTX and bDMARDs were protective, while glucocorticoids increased mortality risk.

Objectives: To examine real-world clinical practices in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) across Japan and evaluate concordance with national treatment guidelines.

Methods: A cross-sectional, web-based survey was conducted between 14 and 19 February 2024. Physicians from rheumatology, pulmonology, and neurology departments who had treated EGPA within the past 24 months were invited to complete a 17-item questionnaire. The survey assessed actual prescribing behaviour, future treatment preferences, responses to two clinical scenarios, and the frequency of guideline use.

Results: Among 220 respondents (110 rheumatologists, 55 neurologists, and 55 pulmonologists), cyclophosphamide (77.3%) and mepolizumab (73.2%) were frequently used with glucocorticoids (GCs) for remission induction. GC monotherapy was the most commonly selected option overall (31.4%), but its use decreased to 14.8% for severe cases. GC + mepolizumab was the most frequently selected regimen for both maintenance and relapse. Responses to clinical scenarios revealed partial divergence from guideline-based recommendations, particularly regarding the limited use of immunosuppressants and the preferential use of mepolizumab.

Conclusions: This study identified a modest but clear evidence-practice gap in EGPA management in Japan. Broader dissemination of updated guidelines and enhanced interdisciplinary collaboration may help align clinical practice with evidence-based standards and improve patient care.

Objectives: To identify risk factors for myocardial involvement in idiopathic inflammatory myopathy (IIM) and evaluate their prognostic value.

Methods: We analysed 92 IIM patients with abnormal cardiac troponin T (cTnT). Myocardial involvement was diagnosed by late gadolinium enhancement on cardiovascular magnetic resonance. All-cause mortality was recorded during follow-up.

Results: Myocardial involvement occurred in 68.5% and was associated with higher cTnT/creatine kinase (CK) ratios and anti-Ro52 positivity. Anti-Ro52-positive patients exhibited higher rates of late gadolinium enhancement and increased E/e'. Both cTnT/CK [odds ratio (OR) = 1.030, P = .024] and anti-Ro52 (OR = 5.629, P = .003) independently predicted myocardial involvement. A cTnT/CK cutoff > 19.3% predicted myocardial involvement [area under the curve (AUC) = 0.660], rising to 0.780 when combined with anti-Ro52. Subgroup analysis showed cTnT/CK was discriminative only in anti-Ro52-negative individuals. During a 36-month follow-up, 18 deaths occurred. Adjusted Cox regression identified cTnI positivity [hazard ratio (HR) = 7.395, P = .001] and cTnT/CK (HR = 1.012, P = .037) as independent mortality predictors. Time-dependent receiver operating characteristic at 3 years showed AUCs of 0.68 (cTnI) and 0.64 (cTnT/CK). Kaplan-Meier analysis confirmed worse survival with positive cTnI or a high cTnT/CK.

Conclusions: The cTnT/CK ratio identifies myocardial involvement and predicts mortality in IIM patients with abnormal cTnT. Combining it with anti-Ro52 antibodies improves the detection of myocardial involvement.

Rheumatoid Arthritis (RA) is a progressive autoimmune disorder with substantial global health and economic impacts. Despite advancements in conventional therapies, biologics, and targeted drugs, challenges such as adverse effects, cost, and interindividual heterogeneity underscore the need for safer, precision-based treatments. Notably, emerging evidence highlights the pivotal role of the gut microbiota-immune axis in RA pathogenesis. Affected individuals typically exhibit gut dysbiosis, marked by increased pro-inflammatory taxa and reduced anti-inflammatory species, which disrupts immune homeostasis through Th17/Treg imbalance, molecular mimicry, and compromised gut barrier integrity. These processes drive systemic inflammation, exacerbating both articular destruction and extra-articular manifestations. Probiotics demonstrate therapeutic potential by modulating this axis via microbiota restoration, barrier reinforcement, and immune regulation. Strain-specific effects have been documented in both preclinical and clinical studies, although efficacy varies depending on host genetics, baseline microbiota composition, and intervention protocols-a variability underscoring the need for personalized probiotic selection. This review consolidates current knowledge on gut microbiota-immune crosstalk in RA and explores probiotics as precision therapeutics. Integrating multi-omics (metagenomics, metabolomics) with targeted probiotic strategies could enable the development of personalized interventions. While translational obstacles persist, including mechanistic complexity and limited clinical validation, the gut microbiota-immune axis offers a novel paradigm for RA management. Future priorities include large-scale trials, biomarker discovery, and combinatorial approaches to advancing microbiome-guided precision medicine in autoimmune diseases.

Objectives: Limited information is available on patients with systemic juvenile idiopathic arthritis (sJIA) receiving biologics in Japan. The types of biologics, treatment duration, prior and concomitant treatments, administration route (intravenous [IV] or subcutaneous [SC] injection), treatment sequence, and characteristics of patients receiving biologics were investigated.

Methods: We used data from a Japanese hospital claims database (2008-24).

Results: Of the 2000 sJIA patients in the database, 315 (15.8%) received one or more biologics. For the first biologic, the most common were anti-interleukin-6 (anti-IL-6) drugs (82.5%; tocilizumab, 82.2% [IV, 65.1%; SC, 17.1%]; others, <0.4%), followed by anti-tumour necrosis factor drugs (11.7%; adalimumab SC, 4.4%; infliximab IV, 4.1%; others, < 1.6% each), canakinumab SC (3.8%), and abatacept IV or SC (1.9%). Over 53% of patients received anti-IL-6 drugs for ≥1 year. The most common conventional synthetic disease-modifying antirheumatic drugs administered prior to anti-IL-6 drugs were cyclosporine (11.9%), methotrexate (11.5%), and tacrolimus (6.2%), and those most commonly administered concomitantly with anti-IL-6 drugs were methotrexate (22.7%), cyclosporine (16.9%), and tacrolimus (11.5%). Fifty patients switched from tocilizumab IV to a second biologic (tocilizumab SC, 50.0%; canakinumab SC, 36.0%; others ≤4.0% each).

Conclusions: Our study described the real-world usage of biologics for sJIA in Japan.

Objectives: This study of telemedicine aims to clarify the needs and issues of patients with rheumatic diseases and the medical personnel involved in their care.

Methods: A questionnaire survey, targeting members of the Japan Rheumatology Association and pertinent patients/companions, was conducted on the use of telemedicine in this field.

Results: Questionnaires were collected from 351 internists, 133 orthopaedists, and 144 patients/their companions. According to the internists and orthopaedists, 77.5% and 58.6% of their patients require ≥1 h one-way travel to a medical institution, respectively. Among the patients treated, 28.5% and 19.5% were from remote areas or islands, and 52.1% and 38.3% were from areas with a shortage of specialized medical care. Meanwhile, a positive view of remote medical care was held by 67.2% of the internists, 54.9% of the orthopaedists, and 73.0% of the patients/their companions. Medical personnel who treat patients from remote islands and in areas with a shortage of specialized medical care were especially open to performing remote medical care via telemedicine systems. Medical personnel expressed concerns about the quality of medical care, while the patients expressed concerns about reduced communication.

Conclusions: This study reveals some of the concerns of medical personnel and patients with rheumatic diseases about telemedicine.

Objective: To clarify T/B cell-specific gene expression patterns using RNA-Seq in IgG4-related disease (IgG4-RD).

Methods: Pathologically confirmed submandibular gland (SMG) (n = 3) and peripheral blood mononuclear cells (PBMC) (n = 4) from four treatment-naïve patients with definite IgG4-RD, as well as PBMCs from primary Sjögren syndrome (pSS) (n = 3) and healthy controls (HCs) (n = 3), were collected, and subsequently Pan T and CD19+ B cells were sorted. We conducted RNA sequencing to compare the gene expressions of Pan T and CD19+ B cells in SMGs and PBMCs in IgG4-RD or IgG4-RD versus pSS and HCs in PBMCs. Ingenuity pathway analysis (IPA) and qPCR validation were performed for differentially expressed genes (DEGs).

Results: Principal component analysis (PCA) results showed the gene expression patterns of Pan T and CD19+ B cells derived from SMGs differed from those derived from PBMCs in IgG4-RD. However, the gene expression patterns of Pan T and CD19+ B cells derived from PBMCs were not clustered between groups. A total of 214 upregulated and 50 downregulated DEGs in Pan T cells and 630 upregulated and 109 downregulated DEGs in CD19+ B cells were identified in SMGs compared with PBMCs in IgG4-RD. The upregulated DEGs in SMGs of IgG4-RD included cytokines, chemokines, and transcription regulators. IPA for these DEGs clarified immune system-related pathways were positively regulated in SMGs compared with PBMCs in IgG4-RD. Quantitative PCR validated significantly increased mRNA expression of IL-21 and EGR2 by Pan T cells in SMGs compared with PBMCs of IgG4-RD.

Conclusion: RNA-Seq clarified the DEGs of Pan T and CD19+ B cells from SMGs in comparison with PBMCs, which might contribute to the pathogenesis of IgG4-RD.