OBJECTIVE To assess for novel markers of muscle damage using urinary muscle metabolites by 1H magnetic resonance spectroscopy in patients with juvenile idiopathic inflammatory myopathy (IIM). METHODS Creatine (Cr), choline (Cho), betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other metabolites were measured in first morning void urine samples from 45 patients with juvenile IIM and from 35 healthy age-matched controls, and correlated with measures of myositis disease activity and damage. Urinary metabolite to age-adjusted creatinine (Cn) ratios were examined. RESULTS Age-adjusted initial Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios were higher in patients with juvenile IIM than controls (P < 0.01). Cr:Cn ratios showed significant correlations with physician-assessed global disease damage (Spearman rs = 0.37; P = 0.01), Steinbrocker functional class (rs = 0.35; P = 0.02), serum Cr (rs = 0.72; P = 0.001), and lactate dehydrogenase (rs = 0.34; P = 0.03) levels. Cho:Cn (rs = 0.3; P = 0.05), Gly:Cn (rs = 0.33; P = 0.03), and TMAO:Cn (rs = 0.36; P = 0.02) ratios showed a significant correlation with serum aldolase levels. Cho:Cn ratios also showed a significant correlation with aspartate aminotransferase levels (rs = 0.35; P = 0.02). A linear regression model was used to evaluate the factors influencing urinary Cr:Cn ratios in the 43 patients with data sets available at the initial visit. The regression model explained 73% of the variation in Cr:Cn ratios. The most significant factor was the physician-assessed global disease damage (R2 = 0.50, P = 0.015). CONCLUSION Urinary Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios are elevated in juvenile IIM and Cr:Cn correlates strongly with global disease damage. The Cr:Cn ratio may have potential utility as a marker of myositis disease damage.

OBJECTIVE To document and evaluate the scores that normal, healthy children achieve when performing 9 maneuvers of the Childhood Myositis Assessment Scale (CMAS). METHODS A total of 303 healthy children, 4-9 years of age, were scored as they performed 9 CMAS maneuvers. The data were then evaluated to determine whether normal scores for some maneuvers are age and sex dependent. RESULTS All children were able to achieve maximum possible scores for the supine to prone, supine to sit, floor sit, floor rise, and chair rise maneuvers. All but 2 4-year-olds achieved a maximum possible score for the arm raise/duration maneuver. Performance of the head lift and sit-up maneuvers varied significantly, depending primarily on age. Children in all age groups had less difficulty performing the leg lift than the head lift or sit-up. CONCLUSION The normative data generated by this study are of value for interpreting the serial CMAS scores of children with idiopathic inflammatory myopathies.

OBJECTIVETo examine the measurement characteristics of the Childhood Myositis Assessment Scale (CMAS) in children with juvenile idiopathic inflammatory myopathy (juvenile IIM), and to obtain preliminary data on the clinical significance of CMAS scores.METHODSOne hundred eight children with juvenile IIM were evaluated on 2 occasions, 7-9 months apart, using various measures of physical function, strength, and disease activity. Interrater reliability, construct validity, and responsiveness of the CMAS were examined. The minimum clinically important difference (MID) and CMAS scores corresponding to various degrees of physical disability were estimated.RESULTSThe intraclass correlation coefficient for 26 patients assessed by 2 examiners was 0.89, indicating very good interrater reliability. The CMAS score correlated highly with the Childhood Health Assessment Questionnaire (C-HAQ) score and with findings on manual muscle testing (MMT) (r(s) = -0.73 and 0.73, respectively) and moderately with physician-assessed global disease activity and skin activity, parent-assessed global disease severity, and muscle magnetic resonance imaging (r(s) = -0.44 to -0.61), thereby demonstrating good construct validity. The standardized response mean was 0.81 (95% confidence interval 0.53, 1.09) in patients with at least 0.8 cm improvement on a 10-cm visual analog scale for physician-assessed global disease activity, indicating strong responsiveness. In bivariate regression models predicting physician-assessed global disease activity, MMT remained significant in models containing the CMAS (P = 0.03) while the C-HAQ did not (P = 0.4). Estimates of the MID ranged from 1.5 to 3.0 points on a 0-52-point scale. CMAS scores corresponding to no, mild, mild-to-moderate, and moderate physical disability, respectively, were 48, 45, 39, and 30.CONCLUSIONThe CMAS exhibits good reliability, construct validity, and responsiveness, and is therefore a valid instrument for the assessment of physical function, muscle strength, and endurance in children with juvenile IIM. Preliminary data on MID and corresponding levels of disability should aid in the clinical interpretation of CMAS scores when assessing patients with juvenile IIM.

OBJECTIVE:We evaluated the utility of neopterin and quinolinic acid (QUIN) as surrogate measures of disease activity in juvenile idiopathic inflammatory myopathies (IIMs).METHODS:Plasma and first morning void urine samples were measured for neopterin and QUIN using commercial ELISA, HPLC, or gas chromatography-mass spectrometry in 45 juvenile IIM patients and 79 healthy controls. Myositis disease activity assessments were obtained.RESULTS:Plasma and urine neopterin and QUIN concentrations were increased in juvenile IIM patients compared with healthy controls (P <0.017). Urine neopterin and QUIN highly correlated with each other (r(s) = 0.73; P <0.0001). Urine neopterin and QUIN correlated moderately with myositis disease activity assessments, including physician and parent global activity assessments, muscle strength testing, functional assessments (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), skin global activity, and edema on magnetic resonance imaging (r(s) = 0.42-0.62; P <0.05), but generally not with muscle-associated enzymes in serum. Urine neopterin or QUIN, in combination with either serum lactate dehydrogenase (LD) or aspartate aminotransferase (AST), significantly predicted global disease activity (R(2) =0.40-0.56; P <0.002), and both were more sensitive to change than these serum enzymes (standardized response means, -0.41 to -0.48).CONCLUSIONS:Urinary neopterin and QUIN are candidate measures of disease activity in juvenile IIM patients and add significantly to the prediction of global disease activity in combination with serum LD or AST values. Measurement of these markers in first morning void urine specimens appears to be as good as, or possibly better than, measurements of their concentrations in plasma.

OBJECTIVE:To examine the validity of the Childhood Health Assessment Questionnaire (CHAQ) in patients with juvenile idiopathic inflammatory myopathy (IIM). METHODS:One hundred fifteen patients were enrolled in a multicenter collaborative study, during which subjects were assessed twice, 7-9 months apart. Physical function was measured using the CHAQ. Internal reliability was assessed using adjusted item-total correlations and item endorsement rates. Construct validity was assessed by comparing predicted and actual correlations of the CHAQ with other measures of physical function and disease activity. Responsiveness was assessed by calculating effect size (ES) and standardized response mean (SRM) in a group of a priori defined "improvers." RESULTS:Item-total correlations were high (rs range = 0.35-0.81), suggesting all items were related to overall physical function. Manual muscle testing and the Childhood Myositis Assessment Scale correlated moderate to strongly with the CHAQ (r = -0.64 and -0.75, both p < 0.001). Moderate correlations were also seen with the physician global assessment of disease activity (rs = 0.58, p < 0.001), parent global assessment of overall health (rs = -0.65, p < 0.001), Steinbrocker function class (rs = 0.69, p < 0.001), and global skin activity (rs = 0.40, p < 0.001), while global disease damage and skin damage had low correlations (rs = 0.13 and 0.07, p > or =0.17). Responsiveness of the CHAQ was high, with ES = 1.05 and SRM = 1.20. CONCLUSION:In this large cohort of patients with juvenile IIM, the CHAQ exhibited internal reliability, construct validity, and strong responsiveness. We conclude that the CHAQ is a valid measure of physical function in juvenile IIM, appropriate for use in therapeutic trials, and potentially in the clinical care of these patients.

OBJECTIVE:To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies.METHODS:The Childhood Myositis Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess muscle function in the areas of strength and endurance across a wide range of ability and ages. The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods. Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study. Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4-15 years) twice in one day (morning and afternoon) on the CMAS. A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups.RESULTS:The CMAS has a potential range of 0-51, with higher scores indicating greater muscle strength and endurance. The observed mean for the 10 patients was 36.4 (median 44, SD 14.1, observed range 5-51). The total score for the CMAS correlated with the physician's global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score. The score on the CMAS was not correlated with patient age. Interrater reliability (Kendall's coefficient of concordance) ranged from 0.77 to 1.0 for individual items (all P < 0.001), and overall, it was 0.95 (P < 0.001). Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 0.97 to 0.99, with an overall correlation for all physicians of 0.98 (all P < 0.001).CONCLUSION:The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability. The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies. It can be used in routine clinical care as well as therapeutic trials.

Objective . To determine the reliability, content validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and patient global ratings. Methods . Sixteen pediatric rheumatologists rated 10 juvenile IIM paper patient cases for global disease activity and damage, and assessed the importance of 51 clinical and laboratory parameters in formulating their global assessments. Then, 117 juvenile IIM patients were enrolled in a protocol to examine the relationship between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability of physician, parent, and patient global ratings. Results . Pediatric rheumatologists demonstrated excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage (97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were comparable in responsiveness (standardized response means −0.56 for disease activity, 0.02 [Likert] and 0.14 [visual analog] for damage, measured over 8 months). Parent global ratings of disease activity correlated with physician assessments, but were not colinear (Spearman's correlation [r] = 0.41−0.45). Patient global disease activity assessments correlated with those done by parents (r = 0.57−0.84) and physicians (r = 0.37−0.63), but demonstrated less responsiveness (standardized response means −0.21 and −0.12, respectively, over 8 months). Conclusion . Physician global assessments of juvenile IIM disease activity and damage demonstrated high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease activity assessments should be considered valuable as quantitative measures for evaluating therapeutic responses in juvenile IIM patients.

OBJECTIVE:To determine the pattern of bands present on an immunoblot (Western blot) in children with Lyme arthritis. METHODS:Sera from 20 children with Lyme arthritis from an endemic area were assayed, and the results compared with those obtained in 162 control sera from the same area. The study was retrospective, serum bank based. RESULTS:Eighty-seven percent of control sera revealed no bands on immunoblot, and all had < or = 4 bands. All Lyme arthritis sera revealed > or = 5 bands (mean 8.4, range 5-13 bands). Bands of molecular weight 25, 28, 39, 47, 50, and 93 kDa were seen in patients and not in controls. There was no correlation between duration of arthritis or activity of arthritis at presentation and number of bands present. CONCLUSION:Criteria were derived for a positive immunoblot based on the number and molecular weights of bands seen in our laboratory. These are the presence of 5 or more bands, of which at least one is an apparently specific band (25, 28, 39, 47, 50, or 93 kDa). Results of immunoblot are useful to confirm clinically suspected Lyme arthritis.

OBJECTIVETo assess the efficacy and safety of intravenous immunoglobulin (IVIG) in juvenile rheumatoid arthritis (JRA).METHODSThirty-one children with active, refractory, systemic JRA were randomized into a multicentered, double blinded, placebo controlled trial. Patients received infusions of 1.5 g/kg of IVIG or placebo (0.1% albumin) every 2 weeks for 2 months, then monthly for 4 months (total: up to 9 infusions over 6 months). Twenty-nine of the 31 patients were included in the efficacy subset.RESULTSFourteen patients discontinued prematurely from study, 7 in each treatment group. A higher proportion of patients in the IVIG group improved (50 vs 27%) as assessed by the physician's global assessment. However, the sample size was small and this difference was not statistically significant. IVIG was not more effective than placebo in reducing the number of days with fever or other systemic manifestations. Changes from baseline in the joint count, hemoglobin, albumin, platelet count, and erythrocyte sedimentation rate did not differ between treatment groups.CONCLUSIONOur results suggest that high dose IVIG has limited clinical utility in systemic JRA. However, this trial failed to enroll adequate numbers of patients to permit valid statistical intergroup comparisons, and the results must be considered nondefinitive.

Objective. To assess the efficacy and safety of intravenous immunoglobulin (IVIG) in juvenile rheumatoid arthritis (JRA).Methods. Thirty-one children with active, refractory, systemic JRA were randomized into a multicentered, double blinded, placebo controlled trial. Patients received infusions of 1.5 g/kg of IVIG or placebo (0.1% albumin) every 2 weeks for 2 months, then monthly for 4 months (total: up to 9 infusions over 6 months). Twenty-nine of the 31 patients were included in the efficacy subset.Results. Fourteen patients discontinued prematurely from study, 7 in each treatment group. A higher proportion of patients in the IVIG group improved (50 vs 27%) as assessed by the physician's global assessment. However, the sample size was small and this difference was not statistically significant. IVIG was not more effective than placebo in reducing the number of days with fever or other systemic manifestations. Changes from baseline in the joint count, hemoglobin, albumin, platelet count, and erythrocyte sedimentation rate did not differ between treatment groups.Conclusion. Our results suggest that high dose IVIG has limited clinical utility in systemic JRA. However, this trial failed to enroll adequate numbers of patients to permit valid statistical intergroup comparisons, and the results must be considered nondefinitive.

Eighty-eight children with juvenile rheumatoid arthritis (JRA) who completed a double blind, randomized placebo controlled trial of oral gold were entered into an open label extension phase during which they received auranofin (AF) at a dosage of 0.15-0.2 mg/kg/day (9 mg/day maximum). Eleven (12.5%) patients completed 5 years of AF therapy; 77 (87.5%) did not. Fifteen (17%) of the 88 were in disease remission at the final visit. Mean duration of therapy for those who discontinued was 646 days. Parental/patient decision and insufficient therapeutic effect were the 2 most frequent reasons for early termination, followed by adverse effects. Though relatively well tolerated, AF provides adequate longterm management for only a small percentage of patients with JRA.

Eighty-eight children with juvenile rheumatoid arthritis (JRA) who completed a double blind, randomized placebo controlled trial of oral gold were entered into an open label extension phase during which they received auranofin (AF) at a dosage of 0.15-0.2 mg/kg/day (9 mg/day maximum). Eleven (12.5%) patients completed 5 years of AF therapy; 77 (87.5%) did not. Fifteen (17%) of the 88 were in disease remission at the final visit. Mean duration of therapy for those who discontinued was 646 days. Parental/patient decision and insufficient therapeutic effect were the 2 most frequent reasons for early termination, followed by adverse effects. Though relatively well tolerated, AF provides adequate longterm management for only a small percentage of patients with JRA.