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OBJECTIVE: The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM. RESULTS: Four bDMARD CTPs were proposed: tumor necrosis factor α (TNFα) inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67 of 72]) as well as for patient characteristics, assessments, outcome measures, and follow-up. By weighted average, respondents indicated that they would most likely administer rituximab, followed by abatacept, TNFα inhibitor, and tocilizumab. CONCLUSION: CTPs for the administration of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.
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OBJECTIVE: Our objectives were to quantify the relationships among fatigue, pain interference, and physical disability in children with juvenile idiopathic arthritis (JIA) and to test whether fatigue mediates the relationship between pain interference and physical disability in JIA. METHODS: Patients enrolled within three months of JIA diagnosis in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry between February 2017 and May 2023 were included. Their parents completed the Patient-Reported Outcomes Measurement Information System fatigue and pain interference short proxy questionnaires and the Childhood Health Assessment Questionnaire disability index at registry enrollment. Associations were assessed using Pearson correlations and multiple linear regression. Structural equation modeling (SEM) was used to test if fatigue mediates the relationship between pain interference and physical disability. RESULTS: Among 855 patients (61.4% female, 44.1% with oligoarthritis), most reported fatigue and pain interference scores similar to those in the reference population, but 15.6% reported severe fatigue and 7.3% reported severe pain interference, with wide variation across JIA categories. Fatigue was strongly correlated with pain interference (r = 0.72, P < 0.001) and with physical disability (r = 0.60, P < 0.001). Pain interference (ß = 0.027, P < 0.001) and fatigue (ß = 0.013, P < 0.001) were both associated with physical disability after controlling for each other and potential confounders. SEM supported our hypothesis that fatigue partially mediates the relationship between pain interference and physical disability. CONCLUSION: Our findings suggest both fatigue and pain interference are independently associated with physical disability in children newly diagnosed with JIA, and the effect of pain interference may be partly mediated by fatigue.
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OBJECTIVE: To report the interim 5-year safety and effectiveness of abatacept in patients with juvenile idiopathic arthritis (JIA) in the PRINTO/PRCSG registry. METHODS: The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% confidence interval [CI]: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections (IR 1.48 [95% CI: 0.88, 2.34]). As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improved over 5 years across JIA categories. CONCLUSION: Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01357668.
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OBJECTIVE: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. METHODS: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. RESULTS: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. CONCLUSION: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.
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BACKGROUND: This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA). METHODS: We conducted a discrete-choice experiment among adolescents with JIA in the United States (US) (n = 197) and United Kingdom (UK) (n = 100) and caregivers of children with JIA in the US (n = 207) and UK (n = 200). In a series of questions, respondents chose between experimentally designed profiles for hypothetical JIA treatments that varied in efficacy (symptom control; time until next flare-up), side effects (stomachache, nausea, and vomiting; headaches), mode and frequency of administration, and the need for combination therapy. Using a random-parameters logit model, we estimated preference weights for these attributes, from which we derived their conditional relative importance. RESULTS: On average, respondents preferred greater symptom control; greater time until the next flare-up; less stomachache, nausea, and vomiting; and fewer headaches. However, adolescents and caregivers in the US were generally indifferent across varying modes and frequencies of administration. UK adolescents and caregivers preferred tablets, syrup, or injections to intravenous infusions. US and UK adolescents were indifferent between treatment with monotherapy or combination therapy; caregivers in the UK preferred treatment with combination therapy to monotherapy. Subgroup analysis showed preference heterogeneity across characteristics including gender, treatment experience, and symptom experience in both adolescents and caregivers. CONCLUSIONS: Improved symptom control, prolonged time to next flare-up, and avoidance of adverse events such as headache, stomachache, nausea, and vomiting are desirable characteristics of treatment regimens for adolescents with JIA and their caregivers.
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Artritis Juvenil , Niño , Humanos , Adolescente , Estados Unidos , Artritis Juvenil/tratamiento farmacológico , Cuidadores , Cefalea , Náusea , VómitosRESUMEN
BACKGROUND: Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic condition and is associated with symptoms such as joint pain that can negatively impact health-related quality of life. To effectively manage pain in JIA, young people, their families, and health care providers (HCPs) should be supported to discuss pain management options and make a shared decision. However, pain is often under-recognized, and pain management discussions are not optimal. No studies have explored decision-making needs for pain management in JIA using a shared decision making (SDM) model. We sought to explore families' decision-making needs with respect to pain management among young people with JIA, parents/caregivers, and HCPs. METHODS: We conducted semi-structured virtual or face-to-face individual interviews with young people with JIA 8-18 years of age, parents/caregivers and HCPs using a qualitative descriptive study design. We recruited participants online across Canada and the United States, from a hospital and from a quality improvement network. We used interview guides based on the Ottawa Decision Support Framework to assess decision-making needs. We audiotaped, transcribed verbatim and analyzed interviews using thematic analysis. RESULTS: A total of 12 young people (n = 6 children and n = 6 adolescents), 13 parents/caregivers and 11 HCPs participated in interviews. Pediatric HCPs were comprised of rheumatologists (n = 4), physical therapists (n = 3), rheumatology nurses (n = 2) and occupational therapists (n = 2). The following themes were identified: (1) need to assess pain in an accurate manner; (2) need to address pain in pediatric rheumatology consultations; (3) need for information on pain management options, especially nonpharmacological approaches; (4) importance of effectiveness, safety and ease of use of treatments; (5) need to discuss young people/families' values and preferences for pain management options; and the (6) need for decision support. Themes were similar for young people, parents/caregivers and HCPs, although their respective importance varied. CONCLUSIONS: Findings suggest a need for evidence-based information and communication about pain management options, which would be addressed by decision support interventions and HCP training in pain and SDM. Work is underway to develop such interventions and implement them into practice to improve pain management in JIA and in turn lead to better health outcomes.
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Artritis Juvenil , Manejo del Dolor , Adolescente , Niño , Humanos , Artritis Juvenil/complicaciones , Artritis Juvenil/terapia , Dolor , Investigación Cualitativa , Calidad de Vida , Toma de Decisiones ConjuntaRESUMEN
BACKGROUND: Pain is one of the most frequently reported experiences amongst children with Juvenile Idiopathic Arthritis (JIA); however, the management of JIA pain remains challenging. As pain is a multidimensional experience that is influenced by biological, psychological, and social factors, the key to effective pain management lies in understanding these complex relationships. The objective of this study is to systematically review the literature on psychosocial factors of children with JIA and their caregivers 1) associated with and 2) predictive of later JIA pain intensity, frequency, and sensitivity in children 0-17 years of age. METHODS: The Joanna Briggs Institute methodology for etiology and risk and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guided the conduct and reporting of this review. Terms related to pain and JIA were searched in English without date restrictions across various databases (PubMed, CINAHL, PsycINFO, Embase, Scopus, and the Cochrane Central Register of Controlled Trials) in September 2021. Two independent reviewers identified, extracted data from, and critically appraised the included studies. Conflicts were resolved via consensus. RESULTS: Of the 9,929 unique studies identified, 61 were included in this review and reported on 516 associations. Results were heterogeneous, likely due to methodological differences and moderate study quality. Results identified predominantly significant associations between pain and primary and secondary appraisals (e.g., more child pain beliefs, lower parent/child self-efficacy, lower child social functioning), parent/child internalizing symptoms, and lower child well-being and health-related quality of life. Prognostically, studies had 1-to-60-month follow-up periods. Fewer beliefs of harm, disability, and no control were associated with lower pain at follow-up, whereas internalizing symptoms and lower well-being were predictive of higher pain at follow-up (bidirectional relationships were also identified). CONCLUSIONS: Despite the heterogeneous results, this review highlights important associations between psychosocial factors and JIA pain. Clinically, this information supports an interdisciplinary approach to pain management, informs the role of psychosocial supports, and provides information to better optimize JIA pain assessments and interventions. It also identifies a need for high quality studies with larger samples and more complex and longitudinal analyses to understand factors that impact the pain experience in children with JIA. TRIAL REGISTRATION: PROSPERO CRD42021266716.
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Artritis Juvenil , Niño , Humanos , Artritis Juvenil/diagnóstico , Calidad de Vida , Dolor/etiología , Manejo del Dolor , AcetaminofénRESUMEN
BACKGROUND: Kawasaki Disease (KD) is the leading cause of acquired heart disease in children in developed countries with a variable incidence worldwide. Previous studies reported an unexpectedly high incidence of KD in the Canadian Atlantic Provinces. The goals of our study were to validate this finding in the province of Nova Scotia and to carefully review patients' characteristics and disease outcomes. METHODS: This was a retrospective review of all children < 16 years old from Nova Scotia diagnosed with KD between 2007-2018. Cases were identified using a combination of administrative and clinical databases. Clinical information was collected retrospectively by health record review using a standardized form. RESULTS: Between 2007-2018, 220 patients were diagnosed with KD; 61.4% and 23.2% met the criteria for complete and incomplete disease, respectively. The annual incidence was 29.6 per 100,000 children < 5 years. The male to female ratio was 1.3:1 and the median age was 3.6 years. All patients diagnosed with KD in the acute phase received intravenous immunoglobulin (IVIG); 23 (12%) were refractory to the first dose. Coronary artery aneurysms were found in 13 (6%) patients and one patient died with multiple giant aneurysms. CONCLUSION: We have confirmed an incidence of KD in our population which is higher than that reported in Europe and other regions of North America despite our small Asian population. The comprehensive method to capture patients may have contributed to the detection of the higher incidence. The role of local environmental and genetic factors also deserves further study. Increased attention to regional differences in the epidemiology of KD may improve our understanding of this important childhood vasculitis.
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Síndrome Mucocutáneo Linfonodular , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Aneurisma Coronario/epidemiología , Aneurisma Coronario/etiología , Aneurisma Coronario/diagnóstico , Inmunoglobulinas Intravenosas/uso terapéutico , Incidencia , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/epidemiología , Estudios Retrospectivos , Nueva Escocia/epidemiología , Recién NacidoRESUMEN
OBJECTIVE: We aimed to evaluate the rate of depressive and/or anxiety symptoms in adolescents with juvenile idiopathic arthritis (JIA) and to explore the association with demographic and disease activity measures. METHODS: Depressive and anxiety symptoms were assessed in adolescents with JIA aged 12 to 18 years at a Canadian tertiary care hospital, using the Revised Child Anxiety and Depression Scale (RCADS). The RCADS includes 6 subscales: separation anxiety, social phobia, generalized anxiety, panic disorder, obsessive-compulsive, and major depressive disorder. Scores above clinical threshold on the RCADS subscales indicate that an individual's responses reflect symptoms similar to those diagnosed with the corresponding mental health disorder. Fisher exact test and Mann-Whitney U test were used to compare demographic and disease-related variables between participants who scored above and below clinical threshold on each of the subscales. RESULTS: There were 32/80 (40%) of participants who scored above clinical threshold on at least 1 subscale. Scores above clinical threshold were most frequent for major depressive disorder (23.8%) and panic disorder (22.5%) subscales. Social phobia and separation anxiety followed with 16.3% and 13.8%, respectively. Females were more likely to have scores above clinical threshold on the panic disorder subscale. Participants with higher self-reported disease activity were more likely to have scores above clinical threshold for all anxiety subscales except separation anxiety. CONCLUSION: We report high rates of symptoms of depression and anxiety (panic in particular) in adolescents with JIA. This highlights the ongoing need for mental health screening protocols and services. The relationships between concomitant mental health disorders, disease activity, and patient-reported outcomes requires further research.
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Artritis Juvenil , Trastorno Depresivo Mayor , Trastorno de Pánico , Adolescente , Niño , Femenino , Humanos , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Artritis Juvenil/complicaciones , Artritis Juvenil/epidemiología , Canadá/epidemiología , Trastorno Depresivo Mayor/epidemiología , Trastorno de Pánico/epidemiología , MasculinoRESUMEN
PURPOSE: This pilot study sought to examine the fundamental movement skills (FMS) and physical literacy (PL) of children with juvenile idiopathic arthritis (JIA) and to explore their relationship with physical activity (PA) and parent perceptions of PA-related risks. METHODS: Twenty-five children with JIA and their parents completed questionnaires. Fundamental movement skills were assessed in the laboratory and PA through accelerometry data. RESULTS: Children spent a median of 39.4%, 40.9%, and 18.2% of their day sedentary, in light, and in moderate to vigorous PA, respectively. Fundamental movement skills and PL scores were within the average range, although were related to which joints (upper/lower body) were affected by JIA. Parents who viewed activities such as biking and climbing as risky tended to have children with weaker locomotor skills and lower PL. CONCLUSION: Children with JIA had age-appropriate PA, FMS, and PL; however, parent perceptions of PA-related risks are related to their child's FMS and PL.
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Artritis Juvenil , Acelerometría , Niño , Humanos , Alfabetización , Destreza Motora , Padres , Proyectos PilotoRESUMEN
BACKGROUND: Prolidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used. CASE PRESENTATION: Patient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in the PEPD gene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Treg cells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+ TEM cells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+ CD8+ TEM cells in both patients and overexpression of the activation marker HLA-DR on CD4+ TEM cells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+ Tfh cells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high. CONCLUSIONS: Immunologic abnormalities including skewed frequencies of activated inflammatory CD4+ and CD8+ TEM cells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.
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Juvenile dermatomyositis (JDM) is a rare, severe autoimmune disease and the most common idiopathic inflammatory myopathy of children. JDM and adult-onset dermatomyositis (DM) have similar clinical, biological and serological features, although these features differ in prevalence between childhood-onset and adult-onset disease, suggesting that age of disease onset may influence pathogenesis. Therefore, a JDM-focused genetic analysis was performed using the largest collection of JDM samples to date. Caucasian JDM samples (n = 952) obtained via international collaboration were genotyped using the Illumina HumanCoreExome chip. Additional non-assayed human leukocyte antigen (HLA) loci and genome-wide single-nucleotide polymorphisms (SNPs) were imputed. HLA-DRB1*03:01 was confirmed as the classical HLA allele most strongly associated with JDM [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.46, 1.89; P = 1.4 × 10-14], with an independent association at HLA-C*02:02 (OR = 1.74; 95% CI 1.42, 2.13, P = 7.13 × 10-8). Analyses of amino acid positions within HLA-DRB1 indicated that the strongest association was at position 37 (omnibus P = 3.3 × 10-19), with suggestive evidence this association was independent of position 74 (omnibus P = 5.1 × 10-5), the position most strongly associated with adult-onset DM. Conditional analyses also suggested that the association at position 37 of HLA-DRB1 was independent of some alleles of the Caucasian HLA 8.1 ancestral haplotype (AH8.1) such as HLA-DQB1*02:01 (OR = 1.62; 95% CI 1.36, 1.93; P = 8.70 × 10-8), but not HLA-DRB1*03:01 (OR = 1.49; 95% CR 1.24, 1.80; P = 2.24 × 10-5). No associations outside the HLA region were identified. Our findings confirm previous associations with AH8.1 and HLA-DRB1*03:01, HLA-C*02:02 and identify a novel association with amino acid position 37 within HLA-DRB1, which may distinguish JDM from adult DM.
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Dermatomiositis , Cadenas HLA-DRB1 , Miositis , Adulto , Alelos , Aminoácidos/genética , Niño , Dermatomiositis/diagnóstico , Dermatomiositis/genética , Predisposición Genética a la Enfermedad , Antígenos HLA-C/genética , Cadenas HLA-DRB1/genética , Haplotipos/genética , Humanos , Miositis/diagnóstico , Miositis/genéticaRESUMEN
OBJECTIVE: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. METHODS: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. RESULTS: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). CONCLUSION: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.
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Glucocorticoides/administración & dosificación , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/etiología , Adolescente , Edad de Inicio , Niño , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: Children with juvenile idiopathic arthritis (JIA) are faced with a complex medical journey requiring consistent adherence to treatments to achieve disease management. Parents are intimately involved in JIA treatments; however, little is known about their experiences in this role. This is relevant as many treatments necessitate procedural pain (e.g., self-injections) or side effects (e.g., nausea), which may impact a parents' ability to follow treatment plans. The objective of this study was to explore the lived experiences of parents who identified challenges with their child's JIA treatments. METHODS: Parents of children with JIA who identified challenges with their child's treatments were invited to take part in semistructured interviews. Data were analyzed using interpretative phenomenological analysis. RESULTS: Ten mothers of children with JIA (60% female with a mean age of 11.83 years [range 4-16 years]) participated. Four superordinate themes were present in mothers' experiences: 1) treatments altered mothers' roles within the family, increasing their caregiver burden and advocacy; 2) treatments positively and negatively impacted their relationships (e.g., increased support from others, decreased time with others); 3) treatments elicited various emotional responses (e.g., frustration, grief), which affected their well-being; and 4) treatments were at times a source of internal conflict, affecting mothers' actions and adherence. CONCLUSION: Mothers' experiences with their child's JIA treatments affects them in various ways that can subsequently impact treatment adherence. Results highlight the value of supporting parents through these complex treatment regimens and incorporating their experiences in treatment decisions to help promote optimal outcomes for children with JIA and their families.
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Artritis Juvenil , Madres , Niño , Femenino , Humanos , Preescolar , Adolescente , Masculino , Madres/psicología , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/psicología , Padres/psicología , Emociones , Cumplimiento y Adherencia al TratamientoRESUMEN
Although bone fragility may already be present at diagnosis of pediatric acute lymphoblastic leukemia (ALL), routine performance of dual-energy X-ray absorptiometry (DXA) in every child is not universally feasible. The aim of this study was to develop and validate a risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤ -2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation. Children with ALL (4-18 years), treated according to the Dutch Childhood Oncology Group protocol (DCOG-ALL9; model development; n = 249) and children from the Canadian Steroid-Associated Osteoporosis in the Pediatric Population cohort (STOPP; validation; n = 99) were included in this study. Multivariable logistic regression analyses were used to develop the prediction model and to confirm the association of low LS BMD at diagnosis with symptomatic fractures during and shortly after cessation of ALL treatment. The area under the receiver operating characteristic curve (AUC) was used to assess model performance. The prediction model for low LS BMD at diagnosis using weight (ß = -0.70) and age (ß = -0.10) at diagnosis revealed an AUC of 0.71 (95% CI, 0.63-0.78) in DCOG-ALL9 and 0.74 (95% CI, 0.63-0.84) in STOPP, and resulted in correct identification of 71% of the patients with low LS BMD. We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR 5.9; 95% CI, 3.2-10.9) and with symptomatic fractures (OR 1.7; 95% CI, 1.3-2.4) that occurred between diagnosis and 12 months following treatment cessation. In meta-analysis, LS BMD at diagnosis (OR 1.6; 95% CI, 1.1-2.4) and the 6-month cumulative glucocorticoid dose (OR 1.9; 95% CI, 1.1-3.2) were associated with fractures that occurred in the first year of treatment. In summary, a prediction model for identifying pediatric ALL patients with low LS BMD at diagnosis, as an important indicator for bone fragility, was successfully developed and validated. This can facilitate identification of future bone fragility in individual pediatric ALL patients. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Osteoporosis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Absorciometría de Fotón , Densidad Ósea , Canadá , Niño , Humanos , Vértebras Lumbares/diagnóstico por imagen , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologíaRESUMEN
Juvenile dermatomyositis (JDM) is a heterogeneous disease with new classification criteria and updates in myositis-specific autoantibody and myositis-associated antibody groups. There are many validated assessment tools for assessing disease activity in JDM. Future studies will optimize these tools and improve feasibility in clinical and research contexts. Genetic and environmental risk factors, mechanisms of muscle pathology, role of interferon, vascular markers, and changes in immune cells provide insights to JDM pathogenesis. Outcomes have improved, but chronic disease, damage, and mortality highlight the need for better outcome predictors and treatments. Increased collaboration of stakeholders may help overcome research barriers and improve JDM treatment.
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Dermatomiositis , Miositis , Autoanticuerpos , Biomarcadores , Dermatomiositis/diagnóstico , Humanos , InterferonesRESUMEN
A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA). The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents. Data from a Canadian cohort of children with new-onset JIA (n= 164, data collection 2007-2012) were compared to Canadian Health Measures Survey (CHMS) data (n=4027, data collection 2007-2011). We compared 25-hydroxy vitamin D (25(OH)D) concentrations with measures of inflammation, vitamin D supplement use, milk intake, and season of birth. Mean 25(OH)D level was significantly higher in patients with JIA (79 ± 3.1 nmol/L) than in healthy controls (68 ± 1.8 nmol/L P <.05). Patients with JIA more often used vitamin D containing supplements (50% vs. 7%; P <.05). The prevalence of 25(OH)D deficiency (<30 nmol/L) was 6% for both groups. Children with JIA with 25(OH)D deficiency or insufficiency (<50 nmol/L) had higher C-reactive protein levels. Children with JIA were more often born in the fall and winter compared to healthy children. In contrast to earlier studies, we found vitamin D levels in Canadian children with JIA were higher compared to healthy children and associated with more frequent use of vitamin D supplements. Among children with JIA, low vitamin D levels were associated with indicators of greater inflammation.
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Artritis Juvenil/sangre , Suplementos Dietéticos , Inflamación , Parto , Estaciones del Año , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Animales , Artritis Juvenil/complicaciones , Artritis Juvenil/inmunología , Enfermedades Autoinmunes , Proteína C-Reactiva/metabolismo , Canadá/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Inflamación/etiología , Inflamación/metabolismo , Masculino , Leche , Vitamina D/análogos & derivados , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/inmunologíaRESUMEN
BACKGROUND: Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA). METHODS: In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach. Results in the JIA cohort were compared to normative Pediatric Bone Mineral Accrual Study data derived from healthy children using z-scores. RESULTS: At enrollment, PA z-score levels of study participants were lower than those in the normative population (median z-score - 0.356; p = 0.005). At enrollment, PA raw scores were negatively associated with the psychosocial domain of the Juvenile Arthritis Quality of Life Questionnaire (r = - 0.251; p = 0.023). There was a significant decline in PAQ-C/A raw scores from baseline (median and IQR: 2.6, 1.4-3.1) to 24 months (median and IQR: 2.1, 1.4-2.7; p = 0.003). The linear mixed-effect model showed that PAQ-C/A raw scores in children with JIA decreased as age, disease duration, and ESR increased. The PAQ-C/A raw scores of the participants was also negatively influenced by an increase in disease activity as measured by the JADAS-71 (p < 0.001). CONCLUSION: Canadian children with newly diagnosed JIA have lower PA levels than healthy children. The decline in PA levels over time was associated with disease activity and higher disease-specific psychosocial stress.
Asunto(s)
Artritis Juvenil/complicaciones , Artritis Juvenil/psicología , Ejercicio Físico , Estrés Psicológico/etiología , Adolescente , Niño , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Factores de TiempoRESUMEN
OBJECTIVE: Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to decreased health-related quality of life (HRQoL) in children with JIA. METHODS: Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL [measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ)] at five disease stages: (i) diagnosis, (ii) 3-9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility. RESULTS: We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data. CONCLUSION: Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.
Asunto(s)
Artritis Juvenil/psicología , Gravedad del Paciente , Medición de Resultados Informados por el Paciente , Calidad de Vida , Adolescente , Canadá/epidemiología , Niño , Preescolar , Evaluación de la Discapacidad , Femenino , Estado Funcional , Humanos , Análisis de Clases Latentes , Masculino , Análisis de Mediación , Evaluación de Resultado en la Atención de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND/OBJECTIVES: Clinically amyopathic juvenile dermatomyositis (CAJDM) is an uncommon but important subset of patients with juvenile dermatomyositis, characterized by pathognomonic cutaneous findings without clinically evident muscle weakness. With limited data available and lack of standardized management guidelines for CAJDM, we sought to describe common features, including early indicators that may be associated with progression of muscle disease, and review the course and treatment of these patients. METHODS: A retrospective chart review of patients with CAJDM was conducted at four North American academic centers between the years 2000 and 2015. RESULTS: Twenty-nine patients were included, of whom 21 (72%) were female. After a median follow-up of 4 years (IQR 1.8-5.8 years), 5 of the 29 (17%) patients with CAJDM evolved into classic juvenile dermatomyositis. Median time to develop weakness was 12 months (IQR 8-19 months) after diagnosis. The skin disease of CAJDM patients who did not develop weakness was often found to be recalcitrant with 58% of them requiring multiple systemic therapies to control their cutaneous disease. CONCLUSION: These results highlight the need for long-term monitoring for the development of myositis in CAJDM and for prospective studies on treatment of recalcitrant skin disease.