2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

OBJECTIVE: To develop response criteria for juvenile dermatomyositis (DM). METHODS: We analyzed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. RESULTS: Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute percent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (P = 0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (P < 0.006). CONCLUSION: The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute percent change in core set measures, with thresholds for minimal, moderate, and major improvement.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

To develop response criteria for juvenile dermatomyositis (DM). We analysed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute per cent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (p=0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (p<0.006). The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute per cent change in core set measures, with thresholds for minimal, moderate, and major improvement.

Treatment approaches to juvenile dermatomyositis (JDM) across North America: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Treatment Survey.

OBJECTIVE: There are a number of different approaches to the initial treatment of juvenile dermatomyositis (JDM). We assessed the therapeutic approaches of North American pediatric rheumatologists to inform future studies of therapy in JDM. METHODS: A survey describing clinical cases of JDM was sent to pediatric rheumatologists. The cases described children with varying severity of typical disease, disease with atypical features, or refractory disease. Three open-ended questions were asked following each case: (1) What additional investigations would you order; (2) What medicine(s) would you start (dose, route, frequency, adjustment over time); and (3) What nonmedication treatment(s) would you start. RESULTS: The response rate was 84% (141/167). For typical cases of JDM, regardless of severity, almost all respondents used corticosteroids and another medication, methotrexate (MTX) being the most commonly used. The route and pattern of corticosteroid administration was variable. Intravenous immunoglobulin (IVIG) was used more frequently for more severe disease, for refractory disease, and for prominent cutaneous disease. Hydroxychloroquine was often used in milder cases and cases principally characterized by rash. Cyclophosphamide was reserved for ulcerative disease and JDM complicated by lung disease. CONCLUSION: For the majority of North American pediatric rheumatologists, corticosteroids and MTX appear to be the standard of care for typical cases of JDM. There is variability, however, in the route of administration of corticosteroids and use of IVIG and hydroxychloroquine.

Validation of manual muscle testing and a subset of eight muscles for adult and juvenile idiopathic inflammatory myopathies.

OBJECTIVE: To validate manual muscle testing (MMT) for strength assessment in juvenile and adult dermatomyositis (DM) and polymyositis (PM). METHODS: Patients with PM/DM (73 children and 45 adults) were assessed at baseline and reevaluated 6-9 months later. We compared Total MMT (a group of 24 proximal, distal, and axial muscles) and Proximal MMT (7 proximal muscle groups) tested bilaterally on a 0-10 scale with 144 subsets of 6 and 96 subsets of 8 muscle groups tested unilaterally. Expert consensus was used to rank the best abbreviated MMT subsets for face validity and ease of assessment. RESULTS: The Total, Proximal, and best MMT subsets had excellent internal reliability (Total MMT r(s) = 0.91-0.98), and consistency (Cronbach's alpha = 0.78-0.97). Inter- and intrarater reliability were acceptable (Kendall's W 0.68-0.76, r(s) = 0.84-0.95). MMT subset scores correlated highly with Total and Proximal MMT scores and with the Childhood Myositis Assessment Scale, and correlated moderately with physician global activity, functional disability, magnetic resonance imaging, and axial and distal MMT scores, and, in adults, with creatine kinase level. The standardized response mean for Total MMT was 0.56 in juveniles and 0.75 in adults. Consensus was reached to use a subset of 8 muscles (neck flexors, deltoids, biceps, wrist extensors, gluteus maximus and medius, quadriceps, and ankle dorsiflexors) that performed as well as the Total and Proximal MMT, and had good face validity and ease of assessment. CONCLUSION: These findings aid in standardizing the use of MMT for assessing strength as an outcome measure for myositis.

Protocols for the initial treatment of moderately severe juvenile dermatomyositis: results of a Children's Arthritis and Rheumatology Research Alliance Consensus Conference.

OBJECTIVE: To use juvenile dermatomyositis (DM) survey data and expert opinion to develop a small number of consensus treatment protocols, which reflect current initial treatment of moderately severe juvenile DM. METHODS: A consensus meeting was held in Toronto, Ontario, Canada on December 1-2, 2007. Nominal group technique was used to achieve consensus on treatment protocols, which represented typical management of moderately severe juvenile DM. Consensus was also reached as to which patients these protocols would be applicable (inclusion and exclusion criteria), which initial investigations should be done prior to initiating one of these protocols, which data should be collected to evaluate these protocols, and the concomitant interventions required or recommended. RESULTS: Three protocols that described the first 2 months of treatment were developed. All protocols included corticosteroids and methotrexate. One protocol also included intravenous gamma globulin. Consensus was achieved for all issues that were addressed by conference participants, although there were some areas of controversy. CONCLUSION: Despite considerable variation in clinical practice, it is possible to achieve consensus on the initial treatment of juvenile DM. Once these protocols are extended beyond 2 months, these protocols will be available for clinical use. By using methods that account for differences between patients (confounding by indication), the comparative effectiveness of the protocols will be evaluated. In the future, the goal will be to identify the optimal treatment of moderately severe juvenile DM.

Preliminary validation and clinical meaning of the Cutaneous Assessment Tool in juvenile dermatomyositis.

OBJECTIVE: To provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores. METHODS: Children with juvenile DM (n = 113) were assessed at baseline and 7-9 months later (n = 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined. CAT scores corresponding to ordinal global assessments were determined. RESULTS: Item-total correlations ranged from 0.27-0.67 for activity lesions present in > or =10% of patients; item-domain and domain-total correlations ranged from 0.25-0.99. Cronbach's alpha was 0.79 for the CAT activity score and 0.74 for the CAT damage score. As predicted, the CAT activity score correlated strongly with both global disease activity and skin disease activity and moderately with the Childhood Myositis Assessment Scale, whereas the CAT damage score correlated moderately with the physician global disease and skin disease damage scores. Median CAT activity scores of 1, 7, 13, 18, and 31 corresponded to absent, mild, moderate, severe, and extremely severe skin disease activity, respectively. Median CAT damage scores of 0, 1, 2, and 5 correlated with the same descriptions of damage (severe and extremely severe combined). CONCLUSION: Preliminary validation of the CAT demonstrated good internal consistency, nonredundancy, good construct validity, and appropriate responsiveness. The CAT is a comprehensive, semiquantitative assessment tool for skin disease in juvenile DM.

Improving adherence to medical regimens for juvenile rheumatoid arthritis.

Poor adherence to medical regimens can compromise the efficacy of treatments for children and adolescents with juvenile rheumatoid arthritis (JRA). The purpose of this review is to describe medical regimens for the treatment of JRA and the rates of adherence to these regimens. We also summarize and critically the few research studies aimed at improving adherence to regimens for JRA. Finally, we summarize strategies for enhancing adherence in clinical practice.

Juvenile dermatomyositis update.

Recent studies involving juvenile dermatomyositis indicate that the majority of affected children have symptoms suggestive of infection prior to disease onset, damage to skin and muscle each have a distinct pathophysiology, certain urinary muscle metabolites may be useful laboratory markers, and methotrexate used as first line therapy with corticosteroids is associated with greater height velocity and smaller increase in body mass index.

Electronically monitored adherence to medications by newly diagnosed patients with juvenile rheumatoid arthritis.

OBJECTIVE: To describe patterns of adherence to nonsteroidal antiinflammatory drugs (NSAIDs) in newly diagnosed patients with juvenile rheumatoid arthritis (JRA), and to examine demographic and disease-related variables as potential predictors of adherence. METHODS: Adherence to NSAIDs was monitored in 48 children with JRA (mean age 8.6 years) over 28 consecutive days using an electronic monitoring device. Measures of disease activity (active joint counts, morning stiffness) and demographics (age, sex, ethnicity, socioeconomic status) were also obtained. RESULTS: Using an 80% adherence cut point, 25 (52%) patients were classified as adherent and 23 (48%) as nonadherent. There was considerable variability across patients, with full adherence (taking all doses on time) ranging from 0 to 100% of the monitored days. Logistic regression showed that active joint count and socioeconomic status were the only significant predictors. Both were positively related to adherence. The model correctly classified 70.5% of patients as either adherent or nonadherent (Cox and Snell R(2) = 0.295, P = 0.0005). CONCLUSION: Children newly diagnosed with JRA are more likely to adhere to an NSAID regimen if they have a greater number of active joints or their families have higher socioeconomic status. The former finding suggests that children's adherence is symptom-driven, while the latter suggests that families of lower socioeconomic status deserve special attention to address adherence issues.

Normal scores for nine maneuvers of the Childhood Myositis Assessment Scale.

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.

Validation and clinical significance of the Childhood Myositis Assessment Scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies.

OBJECTIVE: To 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. METHODS: One 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. RESULTS: The 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. CONCLUSION: The 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.

Treatment of pulmonary hemorrhage in childhood systemic lupus erythematosus with mycophenolate mofetil.

Systemic lupus erythematosus is a chronic autoimmune disease of unknown etiology with multisystem involvement. Pulmonary hemorrhage is a major life-threatening manifestation in children and adolescents with systemic lupus erythematosus, as well as in adults. Treatment has traditionally been with high-dose corticosteroids, with or without the addition of cytotoxic agents. We report the response of a patient with childhood systemic lupus erythematosus with recurrent pulmonary hemorrhage to treatment with mycophenolate mofetil.

Daily hassles and social support as predictors of adjustment in children with pediatric rheumatic disease.

OBJECTIVE: To test hypotheses that social support moderates the effects of microstressors on the psychosocial adjustment of children with pediatric rheumatic diseases (PRDs) and that among multiple sources of support, classmate and parent support are significant predictors of adjustment, after controlling for demographic and disease severity variables. METHODS: Children with PRDs (N = 160 children; 8-17 years) were recruited from three pediatric rheumatology centers and completed measures of daily hassles, social support, depressive symptoms, and state and trait anxiety; their parents completed measures of internalizing and externalizing behaviors. RESULTS: Fewer daily hassles and higher social support predicted fewer adjustment problems. Among the sources of support, classmate and parent support were significant predictors. Tests for moderation were significant only for a Hassles x Classmate Support interaction in the prediction of depression. A plot of the interaction between hassles and classmate support showed that children with high classmate support had lower levels of depression than children with low classmate support under high or low levels of daily hassles. Furthermore, children with high classmate support had lower levels of depression under conditions of low versus high daily hassles. DISCUSSION: Results are consistent with a main effect rather than buffering model for social support. CONCLUSIONS: Interventions should focus on management of daily hassles and increasing social support for children with PRDs.

Development of the Waldron/Varni pediatric pain coping inventory.

The standardized assessment of pediatric pain coping strategies may substantively contribute to the conceptual understanding of individual differences in pediatric pain perception and report. The Waldron/Varni Pediatric Pain Coping Inventory (PPCI) was developed to be a standardized questionnaire to assess systematically children's pain coping strategies. The PPCI was administered to 187 children and adolescents experiencing musculoskeletal pain associated with rheumatologic diseases. A principal components analysis revealed a five-factor solution for the PPCI: (1) cognitive self-instruction, (2) seek social support, (3) strive to rest and be alone, (4) cognitive refocusing, and (5) problem-solving self-efficacy. The results of this research provide initial evidence that the PPCI is a conceptually valid and internally reliable measure for assessing pediatric pain coping strategies.