Giulia Camilla Varnier

Antinuclear antibody–positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis

OBJECTIVEnWe undertook this study to test the hypothesis that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), patients with similar characteristics can be classified into different categories. We sought to investigate whether antinuclear antibody (ANA)-positive patients having disease in the ILAR categories of oligoarthritis, rheumatoid factor-negative polyarthritis, psoriatic arthritis, and undifferentiated arthritis share homogeneous features and to compare these features with those of ANA-negative patients having the same categories of disease.nnnMETHODSnWe identified JIA patients who had been followed up during a 22-year period. ANA positivity was defined as ≥2 positive results at a titer of ≥1:160. Demographic and clinical features were recorded retrospectively and compared between ANA-positive and ANA-negative patients.nnnRESULTSnOf a total of 971 patients, 711 were ANA positive, 149 were ANA negative, and 111 had an indeterminate ANA status. Patients with indeterminate ANA status were excluded. ANA-positive patients in the different ILAR categories were similar in terms of age at disease presentation, female-to-male ratio, and frequency of asymmetric arthritis and iridocyclitis. Compared with ANA-positive patients, the ANA-negative group was older at disease presentation and had a lower prevalence of females, a lower frequency of iridocyclitis and asymmetric arthritis, a greater number of affected joints over time, and a different pattern of arthritis. The close relationship between the presence of ANAs and younger age at disease presentation, female predominance, asymmetric arthritis, development of iridocyclitis, lower number of affected joints over time, and lack of hip involvement was also confirmed by multivariate and multiple correspondence analysis.nnnCONCLUSIONnOur findings substantiate the hypothesis that ANA-positive patients classified into different JIA categories by current ILAR criteria constitute a homogeneous patient population.

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.

Advances in biomarkers for paediatric rheumatic diseases

The search for biomarkers in paediatric rheumatic diseases, particularly juvenile idiopathic arthritis (JIA), childhood lupus nephritis (LN), and juvenile idiopathic inflammatory myopathies (JIIMs) is attracting increased interest. In JIA, a number of biomarkers have shown potential for predicting clinical phenotype, disease activity and severity, clinical remission and relapse, response to treatment, and disease course over time. In systemic JIA, measurement of biomarkers that reflect the degree of activation and expansion of T cells and macrophages might be helpful for detecting subclinical macrophage activation syndrome. Urine biomarkers for childhood LN hold promise for facilitating early diagnosis and improving disease monitoring and assessment of response to therapy. Myositis-specific autoantibodies define distinct serological subgroups of JIIMs, albeit with similar clinical features, responses to therapy, and prognoses. Use of biomarkers may potentially help to avoid invasive procedures, such as renal biopsy in systemic lupus erythematosus and muscle biopsy in juvenile dermatomyositis. Incorporation of effective and reliable biomarkers into routine practice might facilitate adoption of a stratified approach to investigation and management, foster the implementation of research into the design of personalized and targeted therapies, and ultimately lead to more rational and effective clinical care.

Takayasu arteritis in childhood: retrospective experience from a tertiary referral centre in the United Kingdom

IntroductionTakayasu arteritis (TA) is an idiopathic large-vessel vasculitis affecting the aorta and its major branches. Although the disease rarely affects children, it does occur, even in infants. The objective of this study was to evaluate the clinical features, disease activity, treatment and outcome of childhood TA in a tertiary UK centre.MethodsWe analysed a retrospective case series of children fulfilling the TA classification criteria of the European League against Rheumatism, the Paediatric Rheumatology European Society and the Paediatric Rheumatology International Trials Organisation. Data regarding demographics, clinical features, treatments and outcomes were recorded. Descriptive statistics are expressed as median and range. Fisher’s exact test was used for group comparisons. The Paediatric Vasculitis Activity Score (PVAS), Paediatric Vasculitis Damage Index (PVDI), Disease Extent Index-Takayasu (DEI.Tak) and Indian Takayasu Arteritis Activity Score (ITAS2010) were calculated retrospectively.ResultsA total of 11 children (64% female) with age at diagnosis of 11.8 (1.3 to 17) years were identified over a 23-year period. The median time to diagnosis was 17 (0 to 132) months. The most common clinical features at presentation were arterial hypertension (72.7%), systemic features (36%) and cardiovascular (45%), neurological (36%), pulmonary (27%), skin (9%), renal (9%) and gastrointestinal (9%) involvement. At presentation, PVAS was 5/63 (1 to 13); DEI.Tak was 7/81 (2 to 12) and ITAS2010 was 9/57 (6 to 20). Treatment included corticosteroids (81.8%), combined with methotrexate in most cases (72.7%). Cyclophosphamide (36.4%) and biologic agents (45.5%) were reserved for severe and/or refractory cases. PVDI at latest follow-up was 5.5/72 (3 to 15). Mortality was 27%. Young age at disease onset (<5 years old) and permanent PVDI scores ≥3 were significantly associated with mortality risk (Pu2009=u20090.024).ConclusionTA is a rare and potentially life-threatening large-vessel vasculitis. Improved awareness of TA is essential to secure a timely diagnosis. Although the evidence base for the treatment of TA in children is weak, we found that it is essential to treat it aggressively because our data emphasise that the mortality and morbidity in the paediatric population remains high.

Development and initial validation of composite parent‐ and child‐centered disease assessment indices for juvenile idiopathic arthritis

To develop and validate a parent‐centered and a child‐centered composite disease assessment index for juvenile idiopathic arthritis (JIA): the Juvenile Arthritis Parent Assessment Index (JAPAI) and the Juvenile Arthritis Child Assessment Index (JACAI), respectively.

Glucocorticoids in Juvenile Idiopathic Arthritis

Glucocorticoid (GC) drugs are a potent and rapidly effective therapeutic option for the treatment of juvenile idiopathic arthritis (JIA). These medications are mainly used for the management of the extra-articular features of systemic-onset disease. A course of low-dose prednisone may be considered for achieving a rapid disease control in patients with severe polyarthritis refractory to other therapies or while awaiting the full therapeutic effect of a recently initiated disease-modifying antirheumatic drug or biologic agent. Short-term systemic GC administration may also be indicated for chronic iridocyclitis unresponsive to topical therapy. The general objective of GC therapy is to limit the maximum dose and exposure to the highest doses to what is needed to achieve disease control, and then to gradually taper the dose until the minimum level sufficient to maintain disease quiescence over time is reached. High-dose intravenous ‘pulse methylprednisolone administration is sometimes chosen to treat the most severe or acute disease manifestations of systemic JIA, particularly macrophage activation syndrome. Intra-articular GC injection is a safe and rapidly effective treatment for synovitis in children with chronic arthritis. Triamcinolone hexacetonide is the optimal GC preparation for pediatric patients. Local injection therapy is used most frequently to treat oligoarthritis, but the strategy of performing multiple injections to induce disease remission, while simultaneously initiating therapy with second-line or biologic agents, has also been proposed for children with polyarticular JIA. Administration of GCs is associated with potentially deleterious adverse effects, some of which can be irreversible. This highlights the need of a judicious use of these medications and careful monitoring of their toxicity. The recently published recommendations for the management of JIA provide useful guidance to the clinicians for the administration of GCs in children with chronic arthritis.

Development and testing of a hybrid measure of muscle strength in juvenile dermatomyositis for use in routine care

To develop and test a hybrid measure of muscle strength for juvenile dermatomyositis (JDM), which is based on the combination of the Manual Muscle Testing in 8 muscles (MMT‐8) and the Childhood Myositis Assessment Scale (CMAS) but is more comprehensive than the former and more feasible than the latter.

PReS-FINAL-2012: Introducing a new approach to clinical care of juvenile dermatomyositis: the juvenile dermatomyositis multidimensional assessment report

In recent years, there has been an increasing interest in parent/child-reported outcomes (pcros) in pediatric rheumatology practice. Incorporation of these measures in patient assessment is deemed important as they reflect the parents and childrens perception of the disease course and the effectiveness of therapeutic interventions. Although several measures of single pcros have been developed, to date a clinical measure that groups all pcros used in the assessment of children with juvenile dermatomyositis (JDM) does not exist. Such measure would provide a physician with a thorough and systematic overview of the patient status to be scanned at the start of the visit. This would facilitate focus on matters that require attention, leading to more efficient and effective clinical care.

Innovative Research Design to Meet the Challenges of Clinical Trials for Juvenile Dermatomyositis

Purpose of ReviewThis paper aims to provide a summary of the recent therapeutic advances and the latest research on outcome measures for clinical trials in juvenile dermatomyositis (JDM).Recent FindingsRecent randomized controlled trials (RCTs) have demonstrated the superiority of the combination of prednisone with methotrexate over other conventional therapies and the potential effectiveness of rituximab in refractory cases. A multinational project has led to develop new criteria for the definition of minimal, moderate, and major improvement in future JDM clinical trials. This effort has been paralleled by the establishment of criteria for clinically inactive disease. The validation of the first composite disease activity score for JDM is in progress.SummaryThe new outcome measures will increase the reliability of assessment of clinical response in JDM clinical trials and foster future multinational RCTs aimed to investigate novel treatment strategies for refractory forms of JDM.

OP0150 Development and Preliminary Validation of a New Composite Disease Activity Measure for Juvenile Dermatomyositis

Background Evaluation of the level of disease activity is a fundamental component of the clinical assessment of children with JDM. The global tools that are currently available for the assessment of the overall disease activity in JDM are centered on physicians evaluation, neglecting parents or childs perception. Furthermore, these instruments are lengthy and complex. There remains the need for a concise and easily administered tool that provides an absolute measure of disease activity for use in future trials in JDM Objectives To develop and test a new composite disease activity score for JDM, named the Juvenile Dermatomyositis Activity Index (JDMAI). Methods The JDMAI includes 4 measures: 1) physician global assessment of disease activity on a 0-10 VAS, 2) parent/patient global assessment of well-being on a 0-10 VAS, 3) muscle strength assessment, and 4) cutaneous disease activity. Validation analyses were conducted on 140 patients included in a multinational study and were based on evaluation of construct validity, responsiveness to change, and discriminant validity. Four versions of the JDMAI were tested, which differed items 3) and 4). Three versions included the hybrid MMT/CMAS (hMC), reversed and divided by 10, as measure of muscle strength (range 0-10), and the cutaneous domain of the DAS (range 0-9) (JDMAI-1), a cutaneous VAS (range 0-10) (JDMAI-2), or the skin involvement type and distribution items of the DAS (range 0-7) (JDMAI-3) as measures of skin activity. A fourth version of the score (JDMAI-4) included the 3 CMAS items of the hMC (head lift; sits up, floor rise) (range 0-20) for muscle strength and the skin involvement and distribution items of the DAS for skin activity. Results Construct validity: Spearmans correlations of all JDMAI versions were: strong (r >0.7) with total DAS (0.80 - 0.90), parents disease activity VAS (0.73 to 0.80), and CHAQ (0.72 to 0.80); moderate (r 0.4-0.7) with CMAS (-0.63 to -0.65, -0.80 for JDMAI-4), pain VAS (0.55 to 0.60), fatigue VAS (0.62 to 0.70); poor (r <0.4) with LDH (0.27 to 0.32), and ESR (0.35 to 0.38). Correlation of all JDMAI versions with the Myositis Damage Index and CPK was not significant. Responsiveness to change between 2 consecutive visits: SRM ranged from 0.72 (JDMAI-1) to 0.78 (JDMAI-4). Discriminant validity: all JDMAI versions discriminated between patients rated in remission, continued active disease, and flare by the physician (p<0.001) and by the parent (p<0.001), and between patients with high, moderate, or low disease activity according to the physician (p<0.001). Conclusions All JDMAI versions showed good construct validity and responsiveness to change, and excellent discriminant validity. We have shown that the JDMAI is a valid instrument for the assessment of disease activity in JDM and is, therefore, potentially applicable in standard clinical care, observational studies, and clinical trials. Disclosure of Interest None declared