Pediatric Rheumatology最新文献

Background: Patient-reported outcomes (PROs) are critical assessment tools for clinical practice, observational studies, and interventional trials. While families of children with systemic juvenile idiopathic arthritis (SJIA) and SJIA-associated lung disease (SJIA-LD) report significant limitations in their quality of life, existing PROs for juvenile idiopathic arthritis may not properly measure the full impact of these disorders. Our objective was to utilize a newly developed lung symptom survey as well as existing, validated Patient-Reported Outcomes Measurement Information System (PROMIS) measures in children with SJIA with and without LD.

Methods: Participants were parents/guardians of SJIA patients ≤ 18 years and were invited to participate using the Cincinnati Children's Hospital Medical Center (CCHMC) JIA Registry, and memberships in the Systemic JIA Foundation, and SJIA Facebook Group. Participants provided proxy-reports for their child using several PRO questionnaires [CCHMC Lung Symptom Survey; PROMIS Asthma Impact, Sleep Disturbance, Sleep Impairment Forms] and selected demographic and SJIA specific information.

Results: There were 139 responses, of which 40.3% (n = 57) reported some lung disease including 12.9% (n = 20) with interstitial lung disease (ILD), pulmonary alveolar proteinosis (PAP) and/or pulmonary artery hypertension (PAH). All SJIA patients with any lung disease and those with ILD/PAP/PAH had significantly higher total questionnaire scores than patients without lung disease on the CCHMC Lung Symptoms Survey. Both the full survey and individual questions showed good ability to distinguish patients with ILD/PAP/PAH from those without (area under the curve (AUC) > 0.7). The majority of patients reported some level of sleep disturbance (n = 71/139 = 51.1%) and sleep impairment 53.2% (n = 74) regardless of presence or absence of lung disease, including moderate to severe sleep impairment and/or disturbance in 48% of SJIA patients.

Conclusions: Children with SJIA and lung problems had higher scores on the CCHMC Lung Symptom Survey; however, these measures did not discriminate between SJIA-LD and other pulmonary conditions such as asthma. Based on PROMIS measures, a majority of children with SJIA had sleep disturbance and impairment, regardless of steroid use or presence of lung disease.

Background: Uveitis is a serious complication of juvenile idiopathic arthritis (JIA). Despite its seriousness, a comprehensive understanding of its incidence and early risk factors remains elusive. This knowledge gap poses challenges for formulating tailored clinical early identification and prevention strategies. Therefore, our study aims to review the incidence and risk factors of uveitis in JIA patients, and provide evidence-based insights for developing specific clinical risk identification and prevention strategies.

Methods: We systematically searched databases including PubMed, Cochrane, Embase, and Web of Science until December 31, 2023. The quality of included studies was assessed through the Newcastle-Ottawa Scale (NOS). Incidence data were synthesized from cohort studies, and meta-analysis was conducted through R language.

Results: Our review encompassed 28 original studies involving 22,834 JIA patients, among whom 3,381 developed uveitis during the follow-up period. Meta-analysis revealed an overall prevalence of uveitis at 12.7% (95% CI: 10.5 - 15.1%), with rates of 14.3% (95% CI: 11.9 - 15.1%) in European populations, 6.5% (95% CI: 4.0 - 9.5%) in Asian populations, and 13.4% (95% CI: 9.5 - 17.8%) in North America. Identified risk factors for the development of uveitis included early age at JIA onset, ANA-positive, and increased ESR.

Conclusion: The notable prevalence of uveitis in JIA demands clinical vigilance. Our study findings highlight that age, ANA status, and ESR correlate with risk of complicated uveitis. Future research endeavors could focus on constructing a concise risk assessment tool incorporating more potent independent factors. Such a tool would enhance screening efficacy within this demographic, facilitating tailored preventive strategies.

Background: Pain and fatigue are cardinal symptoms in adolescents with Hypermobility Spectrum Disorder (HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS). Adolescents with HSD/hEDS are assumed to be less physically active as compared to healthy peers, possibly contributing to poorer health, but objectively measured data are lacking. The primary study aim was to investigate physical activity patterns (daytime and nighttime movement behavior) using accelerometers in adolescents with HSD/hEDS versus a control group. The secondary aim was investigation of any association between fatigue and movement behavior, acknowledging pain catastrophizing as a confounder.

Methods: Thirty-seven adolescents with HSD/hEDS and 45 healthy adolescents (aged 13-17 years) participated. Physical activity was measured with Axivity AX3 triaxial accelerometer and an activity-sleep diary was used for assessing time in bed. Fatigue was assessed with the Pediatric Quality of Life Inventory - Multidimensional Fatigue Scale and pain catastrophizing with the Pain Catastrophizing Scale for children.

Results: Adolescents with HSD/hEDS spent significantly more time in sedentary behavior (SED), less time in moderate-to-vigorous physical activity (MVPA) and exhibited significantly more sleep movement during night compared to the control group. An association between fatigue and SED, MVPA daytime or sleep movement in adolescents with HSD/hEDS, with pain catastrophizing as confounder, could not be confirmed.

Conclusion: According to this study, adolescents with HSD/hEDS exhibited physical activity behaviors at levels that are associated to poorer health compared to healthy peers. Measures need to be taken to design health promoting programs for these adolescents, including physical activity and sleep health, using a biopsychosocial approach that considers physical, psychological, and social factors.

Clinical trial registration: linicalTrials.gov PRS: Protocol Section NCT05633225.

Background: Proinflammatory cytokines are central to disease mechanisms and important therapeutic targets in inflammatory chronic diseases. This exploratory study aimed to compare cytokine concentrations in saliva, serum, and temporomandibular joint (TMJ) synovial fluid in children with juvenile idiopathic arthritis (JIA) and controls.

Methods: In this cross-sectional study, we included consecutive children with JIA and TMJ arthritis, planned for a TMJ corticosteroid injection, and non-JIA controls from three different centers in Norway. Data on demographics, disease activity, presence of TMJ arthritis, and medication were obtained. Samples of unstimulated saliva, serum, and TMJ synovial fluid were collected. The amount of recovered synovial fluid in each sample, collected by the push-and-pull technique, was quantified with the hydroxocobalamin method. Cytokine levels were analyzed using Luminex xMAP technology.

Results: Fifteen patients with JIA and TMJ arthritis (JIA-TMJ) (median age 15.0 (interquartile range (IQR) 11.0-16.0) years) and 34 controls (median age 13.0 (IQR 9.8-15.0) years) were consecutively recruited. Samples of saliva (JIA-TMJ, n = 13, and controls, n = 28), serum (JIA-TMJ, n = 11, and controls, n = 16), and TMJ synovial fluid (JIA-TMJ, n = 8) were collected. In saliva from JIA-TMJ, we found significantly higher levels of the cytokines IL-1β, IL-4, IL-5, IL-9, IL-10, IL-12, IL-13, IL-17, Eotaxin, FGF basic, GM CSF, PDGF bb, TNF, and RANTES, while IP-10 was found in significantly lower concentration compared to controls. In serum, there were no significant differences in these cytokine concentrations between JIA-TMJ and controls. Three TMJ synovial samples fulfilled the strict sampling criteria and were included in the analysis. The level of detected cytokines in TMJ synovial samples was higher in JIA-TMJ compared to controls, as described in a previous Nordic study.

Conclusions: In this exploratory study, several proinflammatory cytokines were found in higher concentrations in saliva in JIA-TMJ compared to saliva from the controls. No differences were seen in serum between the groups. Some pro- and anti-inflammatory cytokines detected in JIA-TMJ synovial fluid were found in higher concentrations compared to TMJ synovial fluid from healthy adult reference data.

Objective: Previous research has identified the significant roles of non-coding RNAs (ncRNAs) in Kawasaki disease (KD). This systematic review aims to elucidate the involvement and significance of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in the pathogenesis and progression of KD.

Study design: A systematic search was conducted across four databases (PubMed, Embase, Scopus, and Web of Science) up to June 19, 2023, without year restrictions. The risk of bias was assessed using the Newcastle-Ottawa Scale.

Results: This review included 9 studies encompassing a total of 1894 individuals diagnosed with KD. Seven lncRNAs-Slco4a1, SOCS2-AS1, SRA, HCG22, MHRT, XLOC_006277, and HSD11B1-AS1-were found to be associated with KD, including polymorphisms such as lncRNA rs1814343 C > T and AC008392.1 rs7248320. Additionally, four circRNAs-circRNA-3302, circ7632, circANRIL, and hsa_circ_0123996-were associated with KD.

Conclusions: Both linear lncRNAs and circRNAs play critical roles in unraveling the mechanisms underlying KD, contributing to biomarker identification and potential therapeutic advances.

Background: Juvenile localized scleroderma is a rare pediatric inflammatory disease that primarily affects the skin and subcutaneous tissue but also has the potential to impact deeper tissues and can be associated with extracutaneous manifestations, leading to substantial impairment and disability. Management approaches vary, but in recent years, expert groups have attempted to streamline the approach to care with consensus treatment plans.

Methods: This retrospective cohort study included pediatric juvenile localized scleroderma patients with ≥ 3 years of follow-up identified within a 21-year period (1999-2020) at a single tertiary care pediatric hospital in the USA. Data on demographics, disease characteristics, and treatment trends were analyzed, with a focus on systemic versus topical therapy and treatment trends before and after the publication of the Childhood Arthritis and Rheumatology Research Alliance juvenile localized scleroderma consensus treatment plan in 2012.

Results: A total of 101 juvenile localized scleroderma patients fulfilled our inclusion criteria. Sixty-three patients were treated with systemic therapy, and 38 were treated with topical therapy. Patients on systemic therapy were more commonly treated in a combined rheumatology-dermatology program (67%) or rheumatology clinic (30%), whereas those on topical therapy were primarily treated in a dermatology clinic (71%). Starting in 2013, a significantly greater percentage of all patients were treated in the combined program (47% vs. 20%, p = 0.008), and a significantly greater percentage of patients received systemic therapy (78% vs. 55%, p < 0.05).

Conclusion: This juvenile localized scleroderma cohort is one of the largest reported from a single center and demonstrated an increase in the use of systemic therapy following the publication of the Childhood Arthritis and Rheumatology Research Alliance juvenile localized scleroderma consensus treatment plan in 2012. Further studies on long-term treatment outcomes and therapeutic approaches utilized when first-line treatment failures occur are warranted.