ACR open rheumatology最新文献

Objective: Methotrexate (MTX) is a cornerstone in treating juvenile idiopathic arthritis (JIA). The long-term impact of MTX, particularly on pulmonary and liver function, remains a concern. We longitudinally examined the effects of MTX on pulmonary and hepatic function in the largest reported cohort to date.

Methods: In this retrospective, single-center study, patients with JIA receiving MTX (10-15 mg/m²) between 1993 and 2023 were analyzed. Pulmonary function tests (PFTs), including body plethysmography and diffusing capacity for carbon monoxide (DLCO), were performed annually (±3 months) starting at age 5-6 years by professional lung function technicians according to international guidelines. Hepatic enzymes (glutamate pyruvate transaminase [GPT]/alanine aminotransferase) were assessed quarterly with annual abdominal ultrasounds. Data points were compared using paired t-tests against baseline and prior values.

Results: A total of 274 patients with JIA (189 female patients and 85 male patients) with a mean age at disease onset of 7.8 years were treated with MTX for a mean duration of 42.7 months (maximum 14.3 years), corresponding to 918 treatment-years. No clinically relevant MTX-associated lung disease occurred, and spirometric, lung volume, and diffusion parameters remained stable over time. One-third of the 274 pt hat RANSIENT liver enzyme elevations in liver enzyme levels that resolved after dose adjustment or temporary interruption; only 17 of 63 affected patients required permanent discontinuation due to recurrent transaminase elevations. No structural hepatic pathology was detected. Overall, MTX was discontinued in 59% of patients, most commonly due to sustained remission (53%). Other reasons included GPT elevation, nausea, cytopenia, inefficacy, and noncompliance and accounted for only a small minority of patients.

Conclusion: In children with JIA, long-term treatment with MTX appears to be safe regarding the pulmonary outcome. Hepatic involvement was frequent but transient, occasionally requiring dose adjustment or discontinuation without long-term complications.

Objective: To assess current beliefs and clinical practice in rheumatology around cognitive screening and neuropsychological evaluation in youth with childhood-onset systemic lupus erythematosus (cSLE).

Methods: A cross-sectional survey study was conducted among rheumatologists and trainees of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) who care for individuals with cSLE <21 years old. This survey assessed provider knowledge, beliefs, and practices around cognitive screening and neuropsychological evaluation. The presence and absence of barriers to screening (n = 11) and evaluation (n = 8) were also assessed.

Results: Of 443 eligible CARRA members, 109 (25%) completed the survey. The majority of respondents thought that cognitive dysfunction was common in cSLE (94%), had long-term effects on a patient's health (100%), and that the medical literature supported routine screening for cognitive dysfunction (93%). However, only 61% routinely asked about or screened for cognitive concerns during clinic visits, and only 28% felt able to adequately address cognitive concerns. Barriers to performing cognitive screening included uncertainty with administration, interpreting results, billing, and the time available to complete it. Routine neuropsychological evaluation was rare (8%), and more than half (54%) reported that their patients were rarely or never evaluated. Barriers to neuropsychological evaluation included difficulty accessing these services and the time required for the assessment.

Conclusion: Rheumatologists believe cognitive screening and neuropsychological evaluation are important components of care for youth with cSLE but face multiple barriers related to limited training, time, and access to appropriate services. Future work addressing these barriers will support these providers and improve care for patients with cSLE.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects numerous organs. Neutrophil extracellular traps (NETs) contribute to sterile inflammation and autoantibody generation in SLE. Isolevuglandins (isoLGs) are reactive oxygen species that are formed during NETosis and contribute to chromatin expansion. Scavenging of isoLGs attenuates SLE disease activity and hypertension in murine models of SLE. We hypothesized that isoLGs drive NETosis in SLE.

Methods: Neutrophils were isolated from patients with SLE (n = 6), treated with the isoLG scavenger ethyl-2-hydroxybenzylamine (Et-2-HOBA), and evaluated for NETosis by immunofluorescence. Single-cell sequencing was performed on lymphoid tissue from SLE-prone B6.SLE123 mice treated with the isoLG scavenger 2-hydroxybenzylamine (2-HOBA). Flow cytometry was performed to quantify neutrophils and NETs in B6.SLE123 mice (n = 11-15).

Results: In neutrophils isolated from patients with SLE, Et-2-HOBA prevented NETosis (P < 0.05). In SLE-prone mice, 2-HOBA reduced neutrophil counts, inflammatory gene expression, circulating neutrophil counts (P < 0.0001), and aortic NETosis (P < 0.05).

Conclusion: These findings suggest that isoLGs contribute to systemic autoimmunity and vascular inflammation by driving neutrophil migration and NETosis in SLE.

Objective: Systemic sclerosis (SSc) is a severe autoimmune disease, with occupational exposure being a significant risk factor. Because CD146 was recently identified as a driver of fibrosis in SSc through regulation of the Wnt/reactive oxygen species interplay, we hypothesized that it is a major autoimmune target in this disease.

Methods: We developed an in-house ELISA test to detect anti-CD146 autoantibodies (AACD146), which was confirmed by immunoprecipitation and Western blotting. AACD146 positivity was assessed in the sera of patients with SSc compared with healthy controls. A validation cohort of workers exposed to asbestos or silica was evaluated and compared to patients with pulmonary cancer and healthy controls without any occupational exposure.

Results: Detection of AACD146 was assessed by ELISA and confirmed with Western blot and an absorption test. In the first cohort, the prevalence of positive AACD146 was significantly higher in patients with SSc (n = 14 of 93; 15%) than in controls (n = 2 of 40; 5%). Interestingly, among patients with SSc, positive AACD146 were associated with male sex (P = 0.04) and occupational exposure to silica (P = 0.009), with a sensitivity of 57% and specificity of 88% for occupational exposure. Results were confirmed in a validation cohort, in which positive AACD146 were found in 57% (n = 13 of 23) of patients with professional exposure. The frequency of AACD146 was significantly higher compared to controls (P = 0.03) and to patients with a history of cancer (P = 0.02).

Conclusion: We demonstrated that AACD146 are detectable in patients with SSc and are linked to male workers with occupational dust exposure. AACD146 are the first biomarkers associated with occupational exposure in SSc, with potential implications for preventive medicine.

Objective: This systematic review aimed to describe the prevalence, incidence, and associated factors of unmet health care needs among adults with osteoarthritis.

Methods: We searched Medline (Ovid), Embase (Ovid), CINAHL (EBSCO), and PsycINFO (Ovid) from inception through May 15, 2024. Eligible studies were cross-sectional, cohort, and case-control studies investigating the prevalence, incidence, associated factors, or risk factors of unmet health care needs in adults with osteoarthritis. We restricted to articles published in English, French, Italian, and Chinese for feasibility. Reviewers independently screened articles, assessed risk of bias using the Joanna Briggs Institute Checklists, and extracted data. We descriptively synthesized results from low/moderate risk-of-bias studies, stratifying results by age (<60 vs ≥60 years).

Results: Of 3,589 citations screened, 7 cross-sectional studies with low/moderate risk-of-bias were included in the synthesis (3 from South Korea, 4 from the United States). In South Korea, the 12-month prevalence of unmet health care needs was 31.6% (95% confidence interval [CI] 29.9%-33.3%) among adults aged ≥50 years with osteoarthritis and 31% (95% CI 30.9%-31.1%) among those aged ≥65 years with arthritis. In the United States, the 12-month prevalence of unmet needs in the general population due to unaffordability ranged from 15% to 30% in adults with osteoarthritis or arthritis. Prevalence was higher among those who exclusively used complementary and alternative medicine and varied during the COVID-19 pandemic, peaking in the summer of 2020. Evidence suggests that unmet needs are associated with lower income, no insurance, and activity limitations.

Conclusion: Unmet health care needs are common in adults with osteoarthritis, particularly those facing socioeconomic disadvantages or functional limitations. Given the paucity of high-quality studies, additional research is needed.

Objective: The physician global assessment of lung disease (PGALD) is a recently proposed disease activity measure for patients with systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD). This study evaluates the reliability and construct validity of the PGALD.

Methods: Fifty-seven pediatric rheumatologists and pulmonologists with experience caring for children with SJIA-LD were invited to rate 20 clinical vignettes using the PGALD, a 10-point Likert scale (0 = inactive SJIA-LD; 10 = highly active SJIA-LD). Raters were also asked to rate a subset of eight repeat vignettes. Interrater and intrarater reliability were assessed using intraclass correlation coefficients (ICCs), whereas SJIA-LD features influencing PGALD ratings were assessed using univariate analysis.

Results: The ICC for all raters was 0.68 (95% confidence interval [CI] 0.54-0.82), indicating moderate to good interrater reliability. The retest ICC was 0.86 (95% CI 0.82-0.89), indicating good intrarater reliability. Factors associated with higher mean PGALD scores included the presence of crackles on auscultation (5.7 vs 2.9; P = 0.001), hypoxemia on pulse oximeter (5.6 vs 3.2; P = 0.01), current oxygen requirement (6.3 vs 3.5; P = 0.04), suggestive diagnostic imaging features (P ≤ 0.01), and three or more prescribed medications for SJIA-LD (P ≤ 0.01). Pulmonary function measures demonstrated significant negative correlations with PGALD scores: forced vital capacity (r = -0.71; P = 0.01), total lung capacity (r = -0.92; P = 0.01), and lung diffusion capacity (r = -0.97; P = 0.0002). Only C-reactive protein was weakly to moderately correlated with PGALD scores (r = 0.39; P = 0.09), whereas other laboratory markers (ferritin, interleukin 18, CXCL9, and sIL-2R) were not significantly correlated.

Conclusions: The PGALD is a novel measure of SJIA-LD activity. Its initial validation suggests acceptable construct validity and reliability. Additional studies are needed to assess its responsiveness to change over time.