Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood.

OBJECTIVES: To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory groupings. METHODS: This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory. RESULTS: A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analyzed. We studied 4,725 visits (1,471 patient-years). We identified 3 latent classes of longitudinal disease activity, as measured by the modified disease activity score (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity, and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity. CONCLUSION: High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.

Lengthening sleep reduces pain in childhood arthritis: a crossover randomised controlled trial.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a common chronic childhood disease and chronic pain is a debilitating feature. A strong link has been shown between poor sleep and pain in JIA. However, the causal direction is unknown. This study's aim was to determine if, in adolescents with JIA, a recommended healthful sleep duration leads to reductions in pain when compared with the restricted sleep (RS) duration that is commonly seen. METHODS: Patients with JIA (12-18 years old; pain score of ≥1 on a visual analogue scale) participated in a randomised, crossover sleep manipulation protocol. The 3-week protocol comprised a baseline week (BL), a week with healthy sleep duration (HSD; 9.5 hours in bed/night) and a RS week (RS; 6.5 hours in bed/night). After BL, participants were randomly assigned to either HSD or RS, and then crossed over to the other condition. Pain was self-assessed using the iCanCope with Pain app. We used Bayesian hierarchical models to estimate the effect of sleep duration on pain. RESULTS: Participants (n=31; mean age=15.0±1.8 years) averaged 1.4 (95% credible interval (CrI) 1.2-1.6) more hours of sleep per night during HSD relative to RS. Compared with RS, HSD resulted in a favourable effect on pain scores (OR 0.61, 95% CrI 0.39-0.95). CONCLUSION: It is possible to have adolescents with childhood arthritis get a healthier sleep duration, and this longer sleep results in reduced pain. These findings complement prior correlational studies and confirm a causal relationship between reduced sleep duration and increased pain. TRIAL REGISTRATION NUMBER: NCT04133662.

The clinical features of juvenile dermatomyositis: A single-centre inception cohort.

INTRODUCTION: Juvenile Dermatomyositis (JDM), a severe and rare autoimmune disease, is the most common idiopathic inflammatory myopathy in children. We describe the clinical features of a large single-centre cohort. METHODS: We studied an inception cohort (0-18 years old) referred for diagnosis to the JDM clinic at The Hospital for Sick Children (SickKids), between January 1989 and September 2017. Probable or definite diagnosis of JDM was done according to the 2017 ACR/EULAR Criteria. We excluded children who had treatment started at another hospital. The data were collected retrospectively from clinical charts and the SickKids JDM database. RESULTS: 172/230 (74.8%) patients were included. They were most often female (female:male = 1.8:1); the age at diagnosis was 8.5±4.3 years. There was a positive family history for autoimmune disease in 52%, mainly rheumatoid arthritis. No patient died. The most common signs at inception were muscle weakness (85.5%), nailfold capillary abnormalities (83.4%), Gottron papules (78.5%), heliotrope rash (66.3%), abnormal gait (55.8%), and malar/facial rash (54.7%). The prevalence of Gottron papules, heliotrope rash, facial/malar rash, nailfold capillary abnormalities, Raynaud phenomenon, dysphonia/dysphagia (a frequent cause of hospitalization), mouth ulcers, calcinosis, eye problems, joint involvement, acanthosis nigricans and lipodystrophy increased during follow-up. Muscle enzymes, namely CK, ALT, AST, were often normal or only slightly raised despite active muscle disease; conversely LD was often high. Anti-Nuclear Autoantibodies were positive in 49.7% of patients at diagnosis. The course of the disease was: 29.1% monocyclic, 5.3% polycyclic, 33.1% chronic. The course of 56 patients (32.5%) was not classifiable due to length of follow-up. Corticosteroids were used as treatment in almost all our patients and 30% required intravenous therapy due to the severity of the presentation; methotrexate was added in 64%, more often in recent years. Unresponsive patients were treated mostly with intravenous immunoglobulins (IVIG). CONCLUSIONS: The information obtained from this relatively large number of patients adds to the growing knowledge base of this rare disease. TRIAL REGISTRATION: SickKids Research Ethics Board approved the study.

Early Abnormal Nailfold Capillary Changes Are Predictive of Calcinosis Development in Juvenile Dermatomyositis.

OBJECTIVE: The long-term outcomes of juvenile dermatomyositis (JDM) are more favorable in recent years. However, calcinosis is still among the complications that can cause serious functional impairment. Little is known about the pathogenesis and risk factors of calcinosis. The aim of this study is to determine risk factors for the development of calcinosis in JDM. METHODS: This was a single-center, retrospective cohort study. All patients were diagnosed and followed at the multidisciplinary JDM clinic of The Hospital for Sick Children, from January 1, 1989, until May 31, 2018. To investigate predictors of incident calcinosis, Cox regression analysis was performed. RESULTS: A total of 172 patients met inclusion criteria, with a median age at diagnosis of 7.7 years (IQR 4.9-12.1), and a median follow-up of 8.5 years (IQR 3.4-12.6, range 0.1-28.3). The only risk factor significantly associated with the development of calcinosis in the univariate analysis was nailfold abnormality at baseline (hazard ratio [HR] 4.86, P = 0.03). In multivariable analysis, including nailfold abnormality, age of diagnosis, sex, and duration from onset to diagnosis, the only statistically significant risk factor for calcinosis was the presence of nailfold abnormalities (HR 4.98, P = 0.03). Further, calcinosis was significantly increased in patients with a chronic course (chi-square 25.8, P < 0.001). CONCLUSION: The presence of abnormal nailfold capillary changes at baseline is predictive for the development of calcinosis in children with idiopathic inflammatory myopathies.

Feasibility of the wingate anaerobic exercise test as a clinical measure in patients with juvenile dermatomyositis.

BACKGROUND: Core sets, while widely adopted for clinical assessment in juvenile dermatomyositis (JDM), have some drawbacks - they are time consuming, were developed primarily for research, and require an experienced multidisciplinary team. We propose the Wingate Anaerobic Test, a 30-s all out test performed on a cycle ergometer, as a potential alternative; it is valid and reliable in this patient population. We aimed to determine the feasibility of performing the Wingate test as part of a typical clinic visit, and to determine if it is correlated to current measures of disease activity. METHODS: Patients 5-18 years of age, with JDM, were recruited from the JDM clinic at a large Canadian academic children's hospital. Participants underwent a standard clinic assessment, then completed a Wingate test at the end of the visit. RESULTS: Twenty-six patients participated in the study, representing a recruitment rate of 81%; of those, 88% were able to complete the Wingate test. Patients liked the Wingate test and felt it should be included as a regular clinic test. Absolute peak power (watts) on the Wingate test was strongly correlated to the manual muscle test (MMT-8) and the timed squat test. Relative peak power (watts/kg) on the Wingate test was strongly correlated to the timed squat test and the Childhood Myositis Assessment Scale (CMAS). Exploratory principal components analysis revealed that Wingate relative average power explained almost 2/3 of the variance of the CMAS, MMT and timed squats combined. CONCLUSION: The Wingate test is a feasible test for children with JDM and correlates well with standard clinical assessments. Given its brevity, it has the potential to replace more standard measures of physical function currently used in clinical assessments for children with JDM. Future work should focus on how best to operationalize Wingate testing in clinic without the use of dedicated personnel.

Tibia stress injury and the imaging appearance of stress fracture in juvenile dermatomyositis: six patients' experiences.

BACKGROUND: Tibial stress injuries are frequent injuries of the lower extremity and the most common causes of exercise-induced leg pain among athletes and military recruits. They sometimes occur in patients with pathological conditions of bone metabolism such as osteoporosis or rheumatoid arthritis, but there are previously no cases reported in juvenile dermatomyositis (JDM). Here we report 6 JDM patients who presented with shin pain, and the imaging appearance of tibial stress fractures or stress reactions. CASE PRESENTATION: All 6 patients with JDM presented with shin pain or tenderness in the anterior tibia without any evidence of excessive exercise or traumatic episode. They were diagnosed with tibial stress injuries based on a combination of radiographs, three-phase bone scans, and magnetic resonance imaging (MRI), and 5 out of 6 patients had been treated with prednisone and/or methotrexate at onset of tibial stress injuries. In one patient, we could not find any abnormalities in his radiograph, but the subsequent MRI showed tibial stress reaction. In all 6 patients, the tibial stress injuries improved with only rest and/or analgesics. CONCLUSION: We experienced 6 children with JDM who presented with shin pain, and who were diagnosed with tibial stress fractures or stress reactions. Their underlying disease and weakness, treatment with glucocorticoid and methotrexate, or inactivity may have resulted in these tibial injuries, and made these patients more predisposed than other children. In addition to preventing JDM patients from getting osteoporosis, we need to consider stress reactions when children with JDM complain of sudden shin pain.

Correlation of a Modified Disease Activity Score (DAS) with the Validated Original DAS in Patients with Juvenile Dermatomyositis.

OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare disease in children that is treatable, but patients may suffer from long-term effects. Clinical trials are needed to find better treatments for affected patients. Among validated tools for evaluating disease activity clinically is the Disease Activity Score (DAS), but it is not routinely collected in all clinics. We developed a modified DAS (DASmod), which can be scored using data routinely collected by our clinical staff and has been used in previous studies. The aim of this study was to determine if our DASmod correlates with the validated DAS in patients with JDM. METHODS: In this study, we used DASmod (scored 0-12) and DAS (scored 0-20) scores for patients with JDM in our clinic. We analyzed the correlation between the DASmod and the validated DAS. RESULTS: For 51 patients seen in our JDM clinic, the median (IQR) DASmod score was 2.0 (0-4.0) and the DAS score was 3.0 (0-5.5). Scores on the 2 tools were highly positively correlated (r = 0.94, P < 0.001, 95% CI 0.89-0.96). The linear regression was significant [R2 = 0.88, F (1, 49) = 357.60, P < 0.001] and in this dataset, the tools can be used interchangeably with the regression equation: DAS score = -0.26 + 1.5*DASmod. CONCLUSION: If the regression equation from this dataset is successfully tested against future datasets, then further research collaborations between centers that collect different data related to disease activity in children with JDM will be facilitated.

The Effect of Creatine Supplementation on Muscle Function in Childhood Myositis: A Randomized, Double-blind, Placebo-controlled Feasibility Study.

OBJECTIVE: To evaluate the feasibility of studying creatine in juvenile dermatomyositis (JDM). Secondary objectives were to determine the effect of creatine on muscle function and metabolism, aerobic capacity, fatigue, physical activity, and quality of life (QOL), as well as its safety. METHODS: We conducted a 6-month, double-blind, randomized, multiple-baseline design; patients were assigned to creatine or placebo. Feasibility was assessed using attended study visits, completed study procedures, and adherence. Muscle function, aerobic capacity, and muscle strength were assessed with standardized exercise tests. Muscle metabolism was assessed using a 31-Phosphorus Magnetic Resonance Spectroscopy protocol. Fatigue, physical activity, and QOL were assessed by questionnaires. Statistical significance was estimated using a randomization (permutation) test. Changes in outcome measures taken at baseline and end-of-study were calculated using paired t-tests. RESULTS: Median (range) adherence to the study drug was 88.5% (20.5-95.5%) and the proportion of subjects with 80% adherence or higher was 76.9%. There were no missed study visits. There were no statistically significant changes in muscle function, strength, aerobic capacity, disease activity, fatigue, physical activity, or QOL while subjects were receiving creatine compared to placebo. There were statistically significant adaptations in muscle metabolism (e.g., decrease in change in muscle pH following exercise, and decrease in phosphate/phosphocreatine ratio) at the end-of-study compared to baseline. There were no significant adverse effects. CONCLUSION: Creatine supplementation in children with JDM is feasible to study, and is safe and well-tolerated; it may lead to improvements in muscle metabolism.

A Canadian evaluation framework for quality improvement in childhood arthritis: key performance indicators of the process of care.

BACKGROUND: The evaluation of quality of care in juvenile idiopathic arthritis (JIA) is critical for advancing patient outcomes but is not currently part of routine care across all centers in Canada. The study objective is to review the current landscape of JIA quality measures and use expert panel consensus to define key performance indicators (KPIs) that are important and feasible to collect for routine monitoring in JIA care in Canada. METHODS: Thirty-seven candidate KPIs identified from a systematic review were reviewed for inclusion by a working group including 3 pediatric rheumatologists. A shortlist of 14 KPIs was then assessed using a 3-round modified Delphi panel based on the RAND/UCLA Appropriateness Method. Ten panelists across Canada participated based on their expertise in JIA, quality measurement, or lived experience as a parent of a child with JIA. During rounds 1 and 3, panelists rated each KPI on a 1-9 Likert scale on themes of importance, feasibility, and priority. In round 2, panelists participated in a moderated in-person discussion that resulted in minor modifications to some KPIs. KPIs with median scores of ≥ 7 on all 3 questions without disagreement were included in the framework. RESULTS: Ten KPIs met the criteria for inclusion after round 3. Five KPIs addressed patient assessments: pain, joint count, functional status, global assessment of disease activity, and the clinical Juvenile Arthritis Disease Activity Score (cJADAS). Three KPIs examined access to care: wait times for consultation, access to pediatric rheumatologists within 1 year of diagnosis, and frequency of clinical follow-up. Safety was addressed through KPIs on tuberculous screening and laboratory monitoring. KPIs examining functional status using the Childhood Health Assessment Questionnaire (CHAQ), quality of life, uveitis, and patient satisfaction were excluded due to concerns about feasibility of measurement. CONCLUSIONS: The proposed KPIs build upon existing KPIs and address important processes of care that should be measured to improve the quality of JIA care. The feasibility of capturing these measures will be tested in various data sources including the Understanding Childhood Arthritis Network (UCAN) studies. Subsequent work should focus on development of meaningful outcome KPIs to drive JIA quality improvement in Canada and beyond.

Feasibility and effectiveness of an aerobic exercise program in children with fibromyalgia: results of a randomized controlled pilot trial.

OBJECTIVE: To determine the feasibility of conducting a randomized controlled trial of a 12-week exercise intervention in children with fibromyalgia (FM) and to explore the effectiveness of aerobic exercise on physical fitness, function, pain, FM symptoms, and quality of life (QOL). METHODS: FM patients ages 8-18 years were randomized to a 12-week exercise intervention of either aerobics or qigong. Both groups participated in 3 weekly training sessions. Program adherence and safety were monitored at each session. Data were collected at 3 testing sessions, 2 prior to and 1 after the intervention, and included FM symptoms, function, pain, QOL, and fitness measures. RESULTS: Thirty patients participated in the trial. Twenty-four patients completed the program; 4 patients dropped out prior to training and 2 dropped out of the aerobics program. Better adherence was reported in the aerobics group than in the qigong group (67% versus 61%). Significant improvements in physical function, functional capacity, QOL, and fatigue were observed in the aerobics group. Anaerobic function, tender point count, pain, and symptom severity improved similarly in both groups. CONCLUSION: It is feasible to conduct an exercise intervention trial in children with FM. Children with FM tolerate moderate-intensity exercise without exacerbation of their disease. Significant improvements in physical function, FM symptoms, QOL, and pain were demonstrated in both exercise groups; the aerobics group performed better in several measures compared with the qigong group. Future studies may need larger sample sizes to confirm clinical improvement and to detect differences in fitness in childhood FM.