Alessandro Consolaro

Development and validation of a composite disease activity score for juvenile idiopathic arthritis

OBJECTIVE To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS). METHODS The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0-101), 27-joint (range 0-57), or 10-joint (range 0-40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI). RESULTS The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change. CONCLUSION The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.

An international consensus survey of diagnostic criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis.

Objective. To identify candidate diagnostic criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) using international consensus formation through a Delphi questionnaire survey. Methods. A questionnaire listing 28 clinical, laboratory, and histopathologic features of MAS elicited by literature review was sent to 505 pediatric rheumatologists worldwide. Respondents were asked to select the 10 features that they felt were most important and useful in the diagnosis of MAS, and to order the 10 selected features by assigning the number 10 to the most important, and ending with 1 as the least important. Results. The response rate was 46% (232 physicians from 47 countries). The items selected by more than 50% of respondents were, in order of frequency, falling platelet count, hyperferritinemia, evidence of macrophage hemophagocytosis in the bone marrow, increased liver enzymes, falling leukocyte count, persistent continuous fever ≥ 38°C, falling erythrocyte sedimentation rate, hypofibrinogenemia, and hypertriglyceridemia. Conclusion. Our process led to identification of features that were felt to be most important as candidate diagnostic criteria for MAS by a large sample of international pediatric rheumatologists.

A New Approach to Clinical Care of Juvenile Idiopathic Arthritis: The Juvenile Arthritis Multidimensional Assessment Report

Objective. To develop and test a new multidimensional questionnaire for assessment of children with juvenile idiopathic arthritis (JIA) in standard clinical care. Methods. The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) includes 15 parent or patient-centered measures or items that assess well-being, pain, functional status, health-related quality of life, morning stiffness, disease activity, disease status and course, joint disease, extraarticular symptoms, side effects of medications, therapeutic compliance, and satisfaction with illness outcome. The JAMAR is proposed for use as both a proxy-report and a patient self-report, with the suggested age range of 7–18 years for use as a self-report. From March 2007 to September 2009, the questionnaire was completed by the parents of 618 children with JIA in 1814 visits and by 332 children in 749 visits. Results. The JAMAR was found to be feasible and to possess face and content validity. All parents and children reported that the questionnaire was simple and easy to understand. Completion and scoring appeared to be quick, requiring < 15 minutes. There were very few missing data. Parents’ proxy-reported and children’s self-reported data were remarkably concordant. The JAMAR provided thorough information for the study patients about recent medical history and current health status. It performed similarly across different children’s ages and characterized the level of disease activity and disability well. Conclusion. The development of the JAMAR introduces a new approach in pediatric rheumatology practice. This new questionnaire may help enhance the quality of care of children with JIA.

Evaluation of 21-Numbered Circle and 10-Centimeter Horizontal Line Visual Analog Scales for Physician and Parent Subjective Ratings in Juvenile Idiopathic Arthritis

Objective. To evaluate the measurement properties of 21-numbered circle visual analog scales (VAS) and traditional 10-cm horizontal line VAS for physician and parent subjective ratings in children with juvenile idiopathic arthritis (JIA). Methods. We studied 2 patient samples in whom physician global rating of overall disease activity, parent global rating of the child’s overall well-being, and parent rating of intensity of child’s pain were performed using traditional 10-cm horizontal line VAS (n = 397) or 21-numbered circle VAS (n = 471). The measurement performances of the 2 VAS formats were examined by assessing construct validity, score distribution, responsiveness to change over time, and minimal clinically important difference (MCID). Results. Most Spearman correlations with other JIA outcome measures yielded by 21-numbered circle VAS were greater than those obtained with 10-cm horizontal line VAS, revealing that the circle VAS format has better construct validity. Ceiling effects (i.e., score = 0) for physician and parent global ratings were 43.7% and 32.9%, respectively, on 21-numbered circle VAS, and 31.6% and 35.3%, respectively, on 10-cm horizontal line VAS. Responsiveness of 21-numbered circle VAS was good (standardized response mean > 0.8) or moderate (standardized response mean > 0.6) among patients classified as improved or worsened, respectively, by the physician or the parent. Overall, MCID values for 21-numbered circle VAS tended to be greater for worsening than for improvement. Conclusion. The 21-numbered circle VAS are a suitable alternative to the 10-cm horizontal line VAS and may facilitate incorporation of physician and parent subjective ratings in standard clinical practice.

Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH‐2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)–associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.

Parent and child acceptable symptom state in juvenile idiopathic arthritis.

Objective. To explore the parent and child acceptable symptom state in juvenile arthritis (JA-PASS and JA-CASS, respectively) and estimate the JA-PASS and JA-CASS cutoff values for outcome measures. Methods. Children with juvenile idiopathic arthritis (JIA) and their parents completed a multi-dimensional questionnaire that included parent-reported and child-reported outcomes and a question about whether they considered the disease state as satisfactory. Additional assessments included demographic data, physician-reported outcomes, and acute-phase reactant levels. Stepwise logistic regression was used to assess contributors to JA-PASS and JA-CASS. Cutoff values of outcome measures that defined JA-PASS and JA-CASS were determined using both 75th percentile and receiver-operating characteristic (ROC) curve methods. Testing procedures included evaluation of discriminative and construct validity of the satisfaction question and assessment of reliability of JA-PASS and JA-PASS cutoffs. Results. Of 584 parents, 385 (65.9%) considered their child in JA-PASS. Of 343 children, 236 (68.8%) considered themselves in JA-CASS. Significant contributors to being in either JA-PASS or JA-CASS were absence of active joints, better rating of overall well-being, and better physical function or health. Cutoff values yielded by 75th percentile and ROC curve methods were similar. Parent, child, and physician global ratings yielded the lowest percentage of false-positive misclassification and the best tradeoff between sensitivity and specificity. The satisfaction question showed good discriminative and construct validity and the JA-PASS and JA-PASS cutoffs were found to be stable over time. Conclusion. The acceptable symptom state is a relevant concept for children with JIA and their parents and constitutes a valid outcome measure that is potentially applicable in routine practice and clinical trials.

Seeking insights into the EPidemiology, treatment and Outcome of Childhood Arthritis through a multinational collaborative effort: Introduction of the EPOCA study

The epidemiology of juvenile idiopathic arthritis (JIA) is variable worldwide. In particular, a wide disparity exists in the prevalence of the diverse disease subtypes across different geographic areas. The therapeutic approach to JIA is not standardized and no established and widely accepted guidelines are available. In the past decade, there have been important progresses in the management of the disease, but the availability of the novel and costly biologic medications is not uniform throughout the world. This issue may have significant impact on disease prognosis, with children living in poorer countries being at greater risk of accumulating disease- and treatment-related damage than children followed in Western pediatric rheumatology centers. The multinational study of the EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA study) is aimed to obtain information on the frequency of JIA subtypes in different geographic areas, the therapeutic approaches adopted by pediatric rheumatologists practicing in diverse countries or continents, and the disease and health status of children with JIA currently followed worldwide. Parent- and child-reported outcomes are meant to be recorded through the administration of a new multidimensional questionnaire, the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). The first step of the study is based on the translation and cross-cultural adaptation of the questionnaire in the national language of each participating country. Each center is, then, asked to enroll a sample of consecutive JIA patients, who should undergo a retrospective assessment and a cross-sectional evaluation, including completion of the JAMAR, a standardized joint examination, and the assessment of articular and extra-articular damage. At the end of May 2012, 124 centers in 55 countries have agreed to participate in the study. The JAMAR has been or is currently being translated in 38 national languages. The target patient sample is more than 10,000 JIA children worldwide.

Whole-body MRI in the assessment of disease activity in juvenile dermatomyositis

Objective To compare whole-body MRI (WB-MRI) with clinical examination in the assessment of disease activity in juvenile dermatomyositis (JDM). Methods WB-MR images were obtained from 41 JDM patients and 41 controls using a 1.5 T MRI scanner and short τ inversion recovery sequences. 18 patients had follow-up WB-MRI. Muscle, subcutaneous tissue and myofascial signal abnormalities were scored in 36 muscular groups and on proximal and distal extremities. WB-MRI and clinical assessments were performed concurrently and results compared. Validation procedures included analysis of feasibility, reliability, construct validity, discriminative ability and responsiveness. Results WB-MRI revealed distal legs (26/41 patients) and forearm (19/41 patients) muscle inflammation undetected during clinical examination and allowed an accurate assessment of subcutaneous (23/41 patients) and myofascial involvement (13/41 patients). 27 patients showed a patchy distribution of muscle inflammation while in seven the abnormal hyperintense areas tended to be homogeneously distributed. The inter-reader agreement for muscular, subcutaneous and myofascial WB-MRI scores was excellent. Correlations between WB-MRI muscle score and disease activity measures were excellent (Manual Muscle Test: rs=−0.84, Childhood Myositis Assessment Scale: rs=−0.81). WB-MRI score was higher in JDM active patients when compared with the control group (pB<0.0001) and the inactive patients (pB=0.004), and showed an excellent responsiveness (standardised response mean=1.65). Follow-up WB-MRI showed resolution of inflammation in nine patients whereas clinical criteria for remission were satisfied in five. Conclusions WB-MRI provides additional information to clinical evaluation and represents a promising tool to estimate total inflammatory burden, tailor treatment and monitor its efficacy.

Outcome and predicting factors of single and multiple intra-articular corticosteroid injections in children with juvenile idiopathic arthritis

OBJECTIVES To investigate the efficacy of IA CS (IAC) therapy in single and multiple joints in children with JIA and to seek for predictors of synovitis flare. METHODS The clinical charts of patients who received their first IAC injection between January 2002 and December 2008 were reviewed. The CS used was triamcinolone hexacetonide for large joints and methylprednisolone acetate for small or difficult to access joints. Patients were stratified as follows: one joint injected; two joints injected; and three or more joints injected. Predictors included sex, age at disease onset, JIA category, age and disease duration, ANA status, iridocyclitis, general anaesthesia, number and type of injected joints, acute-phase reactants and concomitant MTX therapy. RESULTS The cumulative probability of survival without synovitis flare for patients injected in one, two, or three or more joints was 70, 45 and 44%, respectively, at 1 year; 61, 32 and 30%, respectively, at 2 years; and 37, 22 and 19%, respectively, at 3 years. On Cox regression analysis, positive CRP, negative ANA and injection in the ankle were the strongest predictors for synovitis flare. The only significant side effect was skin hypopigmentation or s.c. atrophy, which occurred in <2% of patients. CONCLUSION IAC therapy-induced sustained remission of synovitis in a substantial proportion of patients injected either in single or multiple joints, with a good safety profile. The risk of synovitis flare was higher in patients who had positive CRP, negative ANA and were injected in the ankle.

Cross-cultural adaptation and psychometric evaluation of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) in 54 languages across 52 countries: review of the general methodology

The aim of this project was to cross-culturally adapt and validate the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) questionnaire in 54 languages across 52 different countries that are members of the Paediatric Rheumatology International Trials Organisation (PRINTO). This effort was part of a wider project named Epidemiology and Outcome of Children with Arthritis (EPOCA) to obtain information on the frequency of juvenile idiopathic arthritis (JIA) categories in different geographic areas, the therapeutic approaches adopted, and the disease status of children with JIA currently followed worldwide. A total of 13,843 subjects were enrolled from the 49 countries that took part both in the cross-cultural adaptation phase and in the related validation and data collection: Algeria, Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Ecuador, Egypt, Estonia, Finland, France, Georgia, Germany, Greece, Hungary, India, Islamic Republic of Iran, Israel, Italy, Latvia, Libya, Lithuania, Mexico, Netherlands, Norway, Oman, Paraguay, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom and United States of America. 9021 patients had JIA (10.7% systemic arthritis, 41.9% oligoarthritis, 23.5% RF negative polyarthritis, 4.2% RF positive polyarthritis, 3.4% psoriatic arthritis, 10.6% enthesitis-related arthritis and 5.7% undifferentiated arthritis) while 4822 were healthy children. This introductory paper describes the overall methodology; results pertaining to each country are fully described in the accompanying manuscripts. In conclusion, the JAMAR translations were found to have satisfactory psychometric properties and it is thus a reliable and valid tool for the multidimensional assessment of children with JIA.