皮膚筋炎／多発性筋炎

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.

BACKGROUND: Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease primarily affecting children, with a female predominance. While muscle fiber inflammation has been extensively investigated, the contribution of the neuromuscular junction (NMJ) and its cellular microenvironment to JDM pathogenesis remains poorly understood. This study aimed to characterize NMJ-related gene expression patterns in JDM to identify potential pathogenic mechanisms and candidate biomarkers. METHODS: An integrated transcriptomic analysis was conducted using two publicly available microarray datasets comprising 40 JDM patients and 22 healthy controls. Twenty-one genes representing five major NMJ functional categories were analyzed: cholinergic transmission, nicotinic acetylcholine receptors, extracellular matrix components, glial markers, and postsynaptic signaling molecules. Differential expression, discriminatory performance, correlation, clustering, and tissue deconvolution analyses were performed. RESULTS: Eighteen of the 21 NMJ-related genes were significantly differentially expressed in JDM (FDR-adjusted p < 0.05). Among these, MBP showed the most pronounced dysregulation and high discriminatory performance (AUC = 0.976, p = 6.10 × 10-16), with marked downregulation associated with increased muscle weakness. Other genes also demonstrated strong discriminatory performance, including AGRN (AUC = 0.941), NID1 (AUC = 0.932), CHRNA1 (AUC = 0.927), NRXN3 (AUC = 0.916), and RYR1 (AUC = 0.913). Correlation analyses revealed disruption of physiological co-expression patterns and the emergence of disease-specific interactions, including altered associations between glial markers and cholinergic components. CHRNA1 expression correlated with both muscle and skin disease activity scores, whereas GFAP expression was associated with disease duration. Clustering analysis indicated a reorganization of NMJ-related gene networks in JDM. Tissue deconvolution suggested that CHRNA1 expression may reflect a shift from inflammatory cell infiltration toward preservation of muscle cell identity. CONCLUSIONS: These findings reveal widespread NMJ-associated transcriptomic remodeling in JDM, involving synaptic, cholinergic, and neuroglial components. The identification of candidate transcriptional biomarkers, particularly MBP and CHRNA1, which show association with disease activity, may warrant further evaluation as potential monitoring tools in independent cohorts. Overall, this study supports a role for NMJ-associated transcriptomic remodeling in JDM pathophysiology and suggests new avenues for mechanistic investigation.

BACKGROUND: Nailfold capillaroscopy is a non-invasive method to visualize altered microcirculation in pediatric rheumatic disease, with potential to aid in diagnostic differentiation and disease monitoring. We used nailfold video capillaroscopy (NVC) and machine learning to identify patterns of capillaroscopic features in juvenile dermatomyositis (JDM) and associations of capillaroscopic features with clinical data. METHODS: NVC features were quantified using automated neural network-based software in 76 individuals, including 18 controls, 33 JDM, 17 childhood-onset systemic lupus erythematosus (cSLE), and 8 overlap myositis (OM) patients. Unsupervised cluster analysis by capillaroscopic features was performed, and clinical features were characterized by cluster. Differences in capillaroscopic features between disease groups were assessed using the Kruskal-Wallis test. For JDM and OM patients, capillaroscopic and clinical feature associations were assessed using Spearman correlation. In 10 treatment-naïve myositis patients (JDM + OM), changes in capillaroscopic features between diagnosis and 3-month follow-up were evaluated. RESULTS: Cluster analysis identified three patient clusters, characterized by the presence of either branched or enlarged capillaries, or absence of these abnormalities. The "branched" cluster was most frequently assigned among JDM and OM and consisted of no controls. The majority of TIF1y+ JDM (4/5) were in the "branched" cluster. In JDM and OM, microhaemorrhage density correlated with disease duration (r = -.45, p = .0033), physician global assessment score (r = .6, p = .0004), lactate dehydrogenase (r = .43, p = .01), von Willebrand factor antigen (r = .51, p = .043), and neopterin (r = .69, p = .01). In 10 myositis patients, microhaemorrhage density decreased while capillary density increased from diagnosis to three months post-treatment. CONCLUSIONS: A branched capillaroscopic pattern was observed more frequently in JDM and OM, particularly TIF1y+ JDM patients within our cohort. Microhaemorrhage density was the most changeable capillaroscopic feature and associated with markers of increased disease activity.