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.

There is evidence that the slope of the change in oxygen uptake accompanying changes in work rate (Delta(V) over dot O-2/DeltaW) during moderate incremental exercise is influenced by fitness (peak (V) over dot O-2). We set out to determine whether Delta(V) over dot O-2/DeltaW was related to fitness in a group of healthy children and in children with juvenile dermatomyositis (JDM), a condition associated with decreased peak (V) over dot O-2 We also hypothesized that Delta(V) over dot O-2/DeltaW would be significantly decreased in children with JDM compared to healthy children. Methods: Twelve children (2 boys) with JDM, mean age 11.6 +/- 3.6 yrs, and 20 healthy children (4 boys), mean age 11.3 +/- 2.9 years, performed an incremental exercise test using a cycle ergometer A Delta(V) over dot O-2/DeltaW below the anaerobic threshold was analyzed using linear regression. Correlations between peak (V) over dot O-2 and Delta(V) over dot O-2/DeltaW were calculated, and differences between the JDM and healthy groups were analyzed using independent t-tests. Results: The Delta(V) over dot O-2/DeltaW was significantly correlated with peak (V) over dot O-2 for children with JDM (r = 0.71, p < 0.01), healthy children (r = 0.53, p < 0.01), and all children combined (r = 0. 78, p < 0.001). The Delta(V) over dot O-2/DeltaW (7.4 +/- 1.4 vs. 10.8 +/- 1.2 ml O-2.min(-1.)watt(-1)) and peak oxygen uptake ((V) over dot O(2)peak) (19.2 +/- 5.0 vs. 31.4 +/- 7.2 ml O-2. kg(-1). min(-1)) were significantly lower in children with JDM than in healthy children, respectively (all p less than or equal to 0.001). Conclusion: Fitness is significantly related to Delta(V) over dot O-2/DeltaW in healthy children and those with JDM. Children with JDM have a significantly lower Delta(V) over dot O-2/DeltaW than healthy children. Further study is needed to identify specific factors influencing Delta(V) over dot O-2/DeltaW.

OBJECTIVE:To assess the utility of magnetic resonance imaging (MRI) of skin, subcutaneous tissue, and fascia in evaluating disease activity in juvenile dermatomyositis (DM).METHODS:Short tau inversion recovery (STIR) MRI of the proximal thighs and buttocks, cutaneous assessment, and other measures of disease activity were prospectively obtained in 26 children meeting criteria for probable or definite juvenile DM. Also undergoing STIR MRI assessment were 8 subjects who were being evaluated for muscle disorders and who were not diagnosed as having juvenile DM.RESULTS:Skin, subcutaneous, or fascial edema of the thighs and buttocks were seen on STIR MRI in up to 85% of juvenile DM patients at baseline evaluation compared with no more than 38% of the comparison group without juvenile DM. In juvenile DM, STIR MRI skin and subcutaneous edema scores correlated (r(s) = 0.51, P = 0.008), as did fascial and muscle edema scores (r(s) = 0.58, P = 0.002). Skin global disease activity scores correlated with MRI skin edema scores (r(s) = 0.41, P = 0.04), and serum aldolase levels correlated with both MRI skin and subcutaneous edema scores (r = 0.44 and 0.40, P = 0.03 and 0.05 respectively). The extent and severity of STIR MRI changes in the skin, subcutaneous tissue, and fascia were not predicted by most other measures of juvenile DM disease activity. Five juvenile DM patients with thigh MRI subcutaneous edema developed clinically apparent calcinosis at the same location within 9 months.CONCLUSION:Edema or inflammation in the skin, subcutaneous tissue, and fascia, found on STIR MRI, is common in juvenile DM patients and is often undetected by standard assessments. These MRI changes can precede the development of calcinosis. STIR MRI may be a useful adjunct for assessing disease activity and guiding the treatment of juvenile DM.

We have sought to examine the response to immunosuppressive therapeutic intervention in inclusion body myositis (IBM) in a retrospective review of prior responses to therapy and in an open, randomized crossover trial. We collected information on the response to prior therapy on 25 patients, and for prospective therapy on 11 of these patients. All met criteria for a definite idiopathic inflammatory myopathy and had biopsy-proven IBM. Clinical and laboratory results were assessed by interviews of patients and by chart review in the retrospective trial. Manual muscle strength was assessed by a single trained observer; the patients' activities of daily living were assessed by questionnaire; and serum tests of muscle-associated enzymes were measured in the prospective trial. In the retrospective review, prednisone appeared to have been of some, albeit modest, clinical benefit in 10 of 25 (40%) patients. Other therapies, primarily azathioprine and methotrexate, also appeared to have halted the progression of weakness in 8 of 35 trials (23%). In the prospective study, combination therapy of oral azathioprine and methotrexate and a biweekly infusion of high-dose intravenous methotrexate with leucovorin rescue were given for 3 to 6 months in an open, crossover design. Both the oral and the intravenous regimens were clinically effective in some patients. There was clinical improvement in 3 trials, stabilization in 11 trials, and worsening in 5 trials, out of a total of 19 completed (22 intended) trials. The presence of active inflammation at entry into the prospective therapeutic protocol, either directly observed on muscle biopsy or indirectly indicated by serum creatine kinase level, may have been associated with clinical improvement. A complete laboratory response with normalization of creatine kinase and other muscle-associated enzymes did not, however, significantly predict clinical responsiveness in the prospective trial. In this first report, to our knowledge, of a prospective trial of immunosuppressive therapy for this disease, stabilization and even slight improvement of strength and functional abilities appeared to be achieved in some patients. We believe that prednisone and other immunosuppressive therapies were of modest benefit in about half of patients with inclusion body myositis, especially those with some evidence of active inflammation. Stabilization of an otherwise inexorably deteriorating course appears, therefore, to be an attainable goal in some patients with IBM.