Serine, N-acetylaspartate differentiate adolescents with juvenile idiopathic arthritis compared with healthy controls: a metabolomics cross-sectional study.

BACKGROUND: In comparison with the general population, adolescents with juvenile idiopathic arthritis (JIA) are at higher risk for morbidity and mortality. However, limited evidence is available about this condition's underlying metabolic profile in adolescents with JIA relative to healthy controls. In this untargeted, cross-sectional metabolomics study, we explore the plasma metabolites in this population. METHODS: A sample of 20 adolescents with JIA and 20 controls aged 13-17 years were recruited to complete surveys, provide medical histories and biospecimens, and undergo assessments. Fasting morning plasma samples were processed with liquid chromatography-mass spectrometry. Data were centered, scaled, and analyzed using generalized linear models accounting for age, sex, and medications (p-values adjusted for multiple comparisons using the Holm method). Spearman's correlations were used to evaluate relationships among metabolites, time since diagnosis, and disease severity. RESULTS: Of 72 metabolites identified in the samples, 55 were common to both groups. After adjustments, 6 metabolites remained significantly different between groups. Alpha-glucose, alpha-ketoglutarate, serine, and N-acetylaspartate were significantly lower in the JIA group than in controls; glycine and cystine were higher. Seven additional metabolites were detected only in the JIA group; 10 additional metabolites were detected only in the control group. Metabolites were unrelated to disease severity or time since diagnosis. CONCLUSIONS: The metabolic signature of adolescents with JIA relative to controls reflects a disruption in oxidative stress; neurological health; and amino acid, caffeine, and energy metabolism pathways. Serine and N-acetylaspartate were promising potential biomarkers, and their metabolic pathways are linked to both JIA and cardiovascular disease risk. The pathways may be a source of new diagnostic, treatment, or prevention options. This study's findings contribute new knowledge for systems biology and precision health approaches to JIA research. Further research is warranted to confirm these findings in a larger sample.

Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab.

BACKGROUND: Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy. CASE PRESENTATION: We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody. CONCLUSIONS: Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.

Juvenile idiopathic arthritis overview and involvement of the temporomandibular joint: prevalence, systemic therapy.

The temporomandibular joint (TMJ) is one of the many joints involved in the inflammatory arthritides. As imaging of joints has developed, so have the data regarding extent and prevalence of TMJ involvement in these diseases. TMJ disease is especially prevalent in juvenile arthritis. The adult and pediatric inflammatory arthritides share common pathophysiology but are still markedly different. The preponderance of TMJ arthritis research exists in juvenile arthritis. This article discusses classification, treatment, and TMJ involvement in juvenile idiopathic arthritis.

Clinical characteristics of children with juvenile dermatomyositis: the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To investigate aspects of juvenile dermatomyositis (DM), including disease characteristics and treatment, through a national multicenter registry. METHODS: Subjects meeting the modified Bohan and Peter criteria for definite juvenile DM were analyzed from the cross-sectional Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between 2010 and 2012 from 55 US pediatric rheumatology centers. Demographics, disease characteristics, diagnostic assessments, and medication exposure data were collected at enrollment. RESULTS: A total of 384 subjects met the criteria for analysis. At enrollment, the median Childhood Myositis Assessment Scale score was 51 (interquartile range [IQR] 46-52), the median Childhood Health Assessment Questionnaire score was 0 (IQR 0-0.5), and the median physician and subject global assessment scores were 1 (IQR 0-2) and 1 (IQR 0-3), respectively, out of a maximum of 10. Of the diagnostic assessments, magnetic resonance imaging was more likely than electromyography or muscle biopsy to show abnormalities. A total of 329 subjects had ≥2 diagnostic studies performed, and >34% of these subjects reported ≥1 negative study. Ninety-five percent had been treated with corticosteroids and 92% with methotrexate, suggesting that these medications were almost universally prescribed for juvenile DM in the US. CONCLUSION: In 2 years, the ongoing CARRA Registry has collected clinical data on 384 children with juvenile DM and has the potential to become one of the largest juvenile DM cohorts in the world. More research is needed about prognostic factors in juvenile DM, and differences in therapy based on manifestations of disease need to be explored by practitioners. This registry provides the infrastructure needed to advance clinical and translational research and represents a major step toward improving outcomes of children with juvenile DM.

Biologic agents for the treatment of juvenile rheumatoid arthritis: current status.

Biologic therapies, primarily anticytokine therapies, are being increasingly used in patients with juvenile rheumatoid arthritis (JRA). Levels of a variety of proinflammatory cytokines have been shown to be elevated in the peripheral blood and synovial fluid and tissue in children with JRA. In a blinded, randomized, controlled trial in children with severe, long-standing, polyarticular-course JRA not responsive to standard therapies, etanercept showed a statistically significantly greater response rate than placebo. Approximately 75% of these children responded to etanercept. Etanercept has been efficacious in 50-60% of children with active systemic JRA in open clinical trials with acceptable tolerance. Adverse events seen in children treated with etanercept have been similar in type and frequency to those reported in adults. Infliximab has been studied in several open clinical trials in both polyarticular and systemic JRA and found to, overall, have demonstrated efficacy in approximately 60% of patients. Approximately 3-5% of patients have demonstrated infusion reactions or frank allergic reactions and 9% developed new autoantibodies. Anakinra has been studied in children with polyarticular JRA. Approximately 65% of patients developed injection-site reactions and 68% demonstrated a response to the medication. Anakinra may have increased efficacy in systemic JRA. Interleukin (IL)-6 is highly related to the systemic disease manifestations in systemic JRA and two patients treated with a monoclonal antibody to the IL-6 receptor have demonstrated significant improvement with prolonged clinical control with continued treatment. A particular pediatric concern is the effect of immunosuppressive biologics in children who are exposed to or develop varicella. These children should be treated, both in terms of prophylaxis and aggressive antivaricella treatment, as for other immunosuppressed children. Anticytokine biologics have demonstrated great promise in the treatment of JRA and a variety of other pediatric rheumatic diseases, although at this time the randomized, placebo-controlled data are limited only to etanercept in children with polyarticular JRA. Randomized trials are ongoing to better define both the efficacy and safety of these novel treatments for children with JRA and other rheumatic diseases.