Feasibility and safety of a 6-month exercise program to increase bone and muscle strength in children with juvenile idiopathic arthritis

Background: Arthritis in childhood can be associated with muscle weakness around affected joints, low bone mass and low bone strength. Exercise is recognized as an important part of management of children with juvenile idiopathic arthritis (JIA) but the exercise prescription to best promote bone and muscle health is unknown. We therefore aimed to: 1. assess feasibility and safety of a 6-month home- and group-based exercise program for children with JIA; 2. estimate the effect of program participation on bone mass and strength, muscle function and clinical outcomes and 3. determine if any positive changes in bone and muscle outcomes are maintained 6 months later. Methods: We recruited 24 children with JIA who were part of the Linking Exercise, Physical Activity and Pathophysiology in Childhood Arthritis (LEAP) study to participate in a 6-month home-based exercise program involving jumping and handgrip exercises, resistance training and one group exercise session per month. We assessed lumbar spine bone mass (dual energy X-ray absorptiometry), distal tibia and radius bone microarchitecture and strength (high-resolution peripheral quantitative computed tomography), muscle function (jumping mechanography, dynamometry) and clinical outcomes (joint assessment, function, health-related quality of life) at baseline, 6- and 12-months. Adherence was assessed using weekly activity logs. Results: Thirteen children completed the 6-month intervention. Participants reported 9 adverse events and post-exercise pain was rare (0.4%). Fatigue improved, but there were no other sustained improvements in muscle, bone or clinical outcomes. Adherence to the exercise program was low (47%) and decreased over time. Conclusion: Children with JIA safely participated in a home-based exercise program designed to enhance muscle and bone strength. Fatigue improved, which may in turn facilitate physical activity participation. Prescribed exercise posed adherence challenges and efforts are needed to address facilitators and barriers to participation in and adherence to exercise programs among children with JIA. Trial registration: Data of the children with JIA are from the LEAP study (Canadian Institutes of Health Research (CIHR; GRANT# 107535). http://www.leapjia.com/

Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9 ± 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy

Predicting which children with juvenile idiopathic arthritis will not attain early remission with conventional treatment: Results from the Reacch-out cohort

Objective. To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD). Methods. We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcome was clinically inactive disease for ≥ 6 months starting within 1 year of JIA diagnosis in patients who did not receive early biologic agents or triple DMARD. Models were developed in 200 random splits of 75% of the cohort and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and c-index values. Results. Our best Cox logistic model combining 18 clinical variables a median of 2 days after diagnosis had a c-index of 0.69 (95% CI 0.67-0.71), better than using JIA category alone (0.59, 95% CI 0.56-0.63). Children in the lowest probability decile had a 20% chance of remission and 21% attained remission; children in the highest decile had a 69% chance of remission and 73% attained remission. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of subjects as low chance of remission (probability \u3c 0.25), of whom 77% failed to attain remission. Conclusion. Although the model did not meet our a priori performance threshold (c-index \u3e 0.70), it identified 3 times more subjects with low chance of remission than did JIA category alone, and it may serve as a benchmark for assessing value added by future laboratory/imaging biomarkers

Glucocorticoid-related changes in body mass index among children and adolescents with rheumatic diseases

Objective To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (\u3c0.2 mg/kg/day to a maximum of 7.5 mg/day), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical activity, and disease activity on BMI Z scores and on percent body fat was assessed with longitudinal mixed-effects growth curve models. Results The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (P \u3c 0.001). Overall, 50% (95% confidence interval 41-59%) of the children returned to within +0.25 SD of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09. Conclusion In children with rheumatic diseases starting moderate and high doses of GCs, BMI Z scores peaked at 4 months, and only half returned to within +0.25 SD of their baseline BMI Z score after 18 months. Copyright © 2013 by the American College of Rheumatology

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: A national observational study

Objective. To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk. Methods. Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. Results. Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than-2.0 at 12 months compared to 16% of children without IVF (P = 0.011). Conclusion. The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months. © 2012, American College of Rheumatology

The risk and nature of flares in juvenile idiopathic arthritis: Results from the ReACCh-Out cohort

Objective To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis ( JIA) and to identify clinical features associated with an increased risk of flare. Methods We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. Results 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA \u3e30 mm, maximum active joint count \u3e4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. Conclusions In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare

Hemolytic anemia following intravenous immunoglobulin therapy in patients treated for Kawasaki disease: a report of 4 cases

<p>Abstract</p> <p>Background</p> <p>Hemolytic anemia is a rare but reported side effect of intravenous immunoglobulin (IVIG) therapy. The risk of significant hemolysis appears greater in those patients who receive high dose IVIG. The etiology is multifactorial but may relate to the quantity of blood group antibodies administered via the IVIG product.</p> <p>Findings</p> <p>We describe 4 patients with significant hemolytic anemia following treatment with IVIG for Kawasaki disease (KD). Direct antibody mediated attack as one of the mechanisms for hemolysis, in this population, is supported by the demonstration of specific blood group antibodies in addition to a positive direct antiglobulin test in our patients.</p> <p>Conclusions</p> <p>Clinicians should be aware of this complication and hemoglobin should be closely monitored following high dose IVIG therapy.</p

Resolution of unilateral sensorineural hearing loss in a pediatric patient with a severe phenotype of Muckle-Wells syndrome treated with Anakinra: a case report and review of the literature

Abstract Background Muckle-Wells syndrome (MWS) is a rare auto-inflammatory disease characterized by the presence of recurrent urticaria, deafness and amyloidosis. Progressive sensorineural hearing loss (SNHL) is reported to occur in up to 85% of patients occurring in the second and third decades and as early as the first decade in patients with a more severe phenotype, thus potentially having a significant impact on a child’s development. IL-1 inhibitors, such as Anakinra, have been described to improve systemic inflammation, and stabilize or improve hearing status as well. However, complete resolution of hearing loss has been rarely reported. The objective of this article is to highlight the clinical presentation of a pediatric patient with a severe form of MWS and report on the complete resolution of SNHL with the use of Anakinra. Case presentation A 3-year-old boy was referred to our hospital to assess for the possibility of MWS given a history of hives and recurrent episodes of fever with a family history of MWS in his mother. Of note, the patient’s history was significant for conductive hearing loss, speech delay, as well as recurrent acute otitis media episodes. Genetic analysis was performed and diagnosis of MWS was confirmed due to the presence of a NLRP3 gene mutation. Further work-up demonstrated the presence of papilledema and elevation of systemic inflammatory markers for which Canakinumab was initiated. Despite initiation of this treatment, audiogram evaluation demonstrated a new right-sided SNHL. Lumbar puncture also revealed aseptic meningitis. Canakinumab was eventually discontinued and Anakinra initiated. Within 7 months of treatment with Anakinra at 5 mg/kg sc daily, resolution of the SNHL was observed. With further escalation of the Anakinra dose, there was also complete resolution of the aseptic meningitis. Conclusions Progressive hearing loss is a significant finding in patients with MWS. Early screening as well as initiation of Anakinra can lead to complete resolution of SNHL even in a patient with a severe spectrum of MWS. However, as this case demonstrates, longer treatment duration and higher doses of Anakinra may be required to achieve this