Although AE can present with dramatic, life-threatening neuropsychiatric deficits, the potential for recovery with prompt treatment is remarkable. First- and second-line therapies for AE lead to clinical improvement in the majority of patients, including full recoveries in many. Early treatment and escalation to second-line therapy in those with refractory disease improves patient outcomes. Novel treatments including IL-6 blockade and proteasome inhibitors have shown promising results in patients with refractory disease.
Objective
The study objective was to identify differences in gene expression between treatment responders (TRs) and treatment non‐responders (TNRs) diagnosed with juvenile dermatomyositis (JDM).
Methods
Gene expression analyses were performed using whole blood messenger RNA sequencing in patients with JDM (n = 17) and healthy controls (HCs; n = 10). Four analyses were performed (A1‐4) comparing differential gene expression and pathways analysis exploiting the timing of sample acquisition and the treatments received to perform these comparative analyses. Analyses were done at diagnosis and follow‐up, which averaged 7 months later in the cohort.
Results
At diagnosis, the expression of 10 genes differed between TRs and TNRs. Hallmark and canonical pathway analysis revealed 11 and 60 pathways enriched in TRs and 3 and 21 pathways enriched in TNRs, respectively. Pathway enrichment at diagnosis in TRs was strongest in pathways involved in metabolism, complement activation, and cell signaling as mediated by IL‐8, p38/microtubule associated protein kinases (MAPK)/extracellular signal‐regulated kinases (ERK), Phosphatidylinositol 3 Kinase Gamma (PI3Kγ), and the B cell receptor. Follow‐up hallmark and canonical pathway analysis showed that 2 and 14 pathways were enriched in TRs, whereas 24 and 123 pathways were enriched in treatment TNRs, respectively. Prior treatment with glucocorticoids significantly altered expression of 13 genes in the analysis of subjects at diagnosis with JDM as compared with HCs.
Conclusion
Numerous genes and pathways differ between TRs and TNRs at diagnosis and follow‐up. Prior treatment with glucocorticoids prior to specimen acquisition had a small effect on the performed analyses.
Certain pediatric rheumatic diseases are known to affect the heart, sometimes requiring surgical intervention. The Pediatric Cardiac Care Consortium database was used to characterize cardiac surgical intervention among children with rheumatic diseases from 1985 to 2005. From this large database, the records for patients younger than 21 years who underwent cardiac surgery for any rheumatic disorder were extracted. The data collected included the type of procedure performed, the age at the time of the procedure, and the year the procedure was performed. The 261 pediatric patients identified underwent 361 cardiac surgical procedures for complications of rheumatic heart disease (RHD; 160 patients), neonatal lupus (NLE; 53 patients), Kawasaki disease (KD; 28 patients), systemic lupus erythematosus (SLE; 13 patients), and juvenile rheumatoid arthritis (JRA; 7 patients). Multiple procedures were performed for 23% of the patients. The most common procedures included pacemaker implantations among infants with NLE, coronary artery bypass grafts for KD primarily in 5- to 15-year-olds, and cardiac valve operations among adolescents with RHD, SLE, and JRA. Six perioperative deaths occurred. The proportion of annual pediatric cardiac surgical volume attributable to rheumatic diseases did not change during the period studied. Despite advances in their medical care, children with rheumatic diseases continue to sustain measurable morbidity and mortality due to the cardiovascular manifestations of their disease.
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