Helga Sanner

Clinical Features, Treatment, and Outcome of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A Multinational, Multicenter Study of 362 Patients

To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA).

Cumulative organ damage and prognostic factors in juvenile dermatomyositis: a cross-sectional study median 16.8 years after symptom onset

OBJECTIVE To describe cumulative organ damage in juvenile dermatomyositis (JDM) patients and to identify patient characteristics and early disease variables that predict organ damage. METHODS An inception cohort of 60 patients diagnosed with JDM from 1970 to 2006 was examined, median 16.8 (2.0-38.1) years after disease onset. Disease activity was measured by the disease activity score (DAS), organ damage by the myositis damage index (MDI) and physical function by the childhood or adult HAQ (CHAQ/HAQ). Medical records were reviewed for early disease variables at diagnosis, and 6 and 12 months post-diagnosis. RESULTS Fifty-four (90%) patients had a cumulative MDI total score >or=1 at follow-up (mean 4.2 +/- 3.1). Damage occurred most frequently in cutaneous, muscular and skeletal domains (77, 65 and 57%, respectively). Early predictors of damage were DAS and MDI 6 months post-diagnosis (beta = 0.334; P = 0.002 and 0.382, P < 0.001, respectively). Follow-up time also correlated with MDI (P = 0.010). Calcinosis, seen in 47% of the patients, was predicted by male gender [odds ratio (OR) 3.8; 95% CI 1.2, 12.1], and DAS 6 months post-diagnosis (OR 1.2; 95% CI 1.1, 1.4). The MDI score correlated with CHAQ/HAQ and DAS at follow-up (r(s) = 0.355; P = 0.005 and 0.446, P < 0.001, respectively). The DAS decreased during the first-year post-diagnosis, whereas the MDI increased over time. CONCLUSIONS The majority of JDM patients had cumulative organ damage at follow-up, which was predicted by high disease activity and organ damage 6 months post-diagnosis.

Long-term muscular outcome and predisposing and prognostic factors in juvenile dermatomyositis: A case–control study

To compare muscle strength, physical health, and HLA–DRB1 allele carriage frequencies in patients with longstanding juvenile dermatomyositis (DM) with that of controls, and to determine the presence of and risk factors for muscle weakness and magnetic resonance imaging (MRI)–detected muscle damage in juvenile DM patients.

Pulmonary outcome in juvenile dermatomyositis: a case-control study

Objectives To compare pulmonary function in patients with juvenile dermatomyositis (JDM) with that of matched controls; and to examine associations between pulmonary function impairment, high-resolution CT (HRCT) abnormalities and other disease variables in patients with JDM. Methods A total of 59 patients with JDM clinically examined a median 16.8 years (range 2–38 years) after disease onset were compared with 59 age-matched and sex-matched controls. Pulmonary function tests included spirometry, diffusing capacity for carbon monoxide (DLCO) and body plethysmography. In patients with JDM, HRCT scans were performed and cumulative organ damage and patient-reported health status assessed. Results Patients with JDM had lower total lung capacity (TLC) and DLCO compared to controls (p=0.003 and <0.001, respectively). A low TLC was found in 26% of patients versus 9% of controls (p=0.026), and a low DLCO in 49% of patients versus 9% of controls (p<0.001). HRCT abnormalities were found in 37% of patients, and included interstitial lung disease (ILD) (14%), chest wall calcinosis (14%) and airway disease (15%). Three patients were diagnosed as having ILD prior to the follow-up visit. A low TLC was more often found in patients with than without abnormal HRCT (50% vs 12%, p=0.002). HRCT abnormality correlated with cumulative organ damage (rs=0.346, p=0.008) and patient-reported health status at follow-up (p<0.005). Conclusions Patients with JDM had smaller lung volumes than controls; a restrictive ventilatory defect was found in 26% and HRCT abnormality in 37% of the patients, and these findings were associated. Although mostly subclinical, the relatively high frequency of pulmonary involvement highlights the systemic nature of JDM.

2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups

Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) ‘probable IIM’, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to ‘definite IIM’. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as ‘possible IIM’. Conclusions The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of ‘definite’, ‘probable’ and ‘possible’ IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

In juvenile dermatomyositis, cardiac systolic dysfunction is present after long-term follow-up and is predicted by sustained early skin activity

Objective To compare systolic cardiac function in patients with juvenile dermatomyositis (JDM) with matched controls and examine associations between systolic and diastolic cardiac function and disease variables. Methods Fifty-nine patients, examined at follow-up, median 16.8 years (2–38 years) after disease onset, were compared with 59 age-matched and sex-matched controls. Echocardiography was performed and analysed blinded to patient information. We used mitral annulus displacement to assess the relative long-axis shortening of the left ventricle (long-axis strain) and early diastolic tissue velocity (e′), as markers for systolic and diastolic function, respectively. Disease activity and organ damage were assessed at follow-up by clinical examination and retrospectively by chart review. Results Long-axis strain was reduced in patients compared with controls (16.6% (2.5) vs 17.7% (2.0), mean (SD), p=0.001), whereas no difference was seen between patients with active and inactive disease. Disease duration correlated with systolic and diastolic function (rsp=−0.50 and rsp=−0.73, both p<0.001) and so did Myositis Damage Index (MDI) 1 year (rsp=−0.36 and rsp=−0.46) and MDI at follow-up (rsp=−0.33 and rsp=−0.60), all p<0.01. High early disease activity score (DAS) in skin (DAS skin 1 year), but not in muscle, predicted systolic (standardised β=−0.28, p=0.011, R2=48%) and diastolic dysfunction (β=−0.36, p<0.001, R2=72%) at follow-up. Conclusions Long-axis strain was reduced in JDM patients compared with controls, suggesting systolic dysfunction. Impaired systolic and diastolic function was predicted by DAS skin 1 year. This indicates a common pathway to two different cardiac manifestations in JDM, perhaps with similar pathogenesis as skin affection.

Cardiac involvement in adult and juvenile idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIM) include the main subgroups polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and juvenile DM (JDM). The mentioned subgroups are characterised by inflammation of skeletal muscles leading to muscle weakness and other organs can also be affected as well. Even though clinically significant heart involvement is uncommon, heart disease is one of the major causes of death in IIM. Recent studies show an increased prevalence of traditional cardiovascular risk factors in JDM and DM/PM, which need attention. The risk of developing atherosclerotic coronary artery disease is increased twofold to fourfold in DM/PM. New and improved diagnostic methods have in recent studies in PM/DM and JDM demonstrated a high prevalence of subclinical cardiac involvement, especially diastolic dysfunction. Interactions between proinflammatory cytokines and traditional risk factors might contribute to the pathogenesis of cardiac dysfunction. Heart involvement could also be related to myocarditis and/or myocardial fibrosis, leading to arrhythmias and congestive heart failure, demonstrated both in adult and juvenile IIM. Also, reduced heart rate variability (a known risk factor for cardiac morbidity and mortality) has been shown in long-standing JDM. Until more information is available, patients with IIM should follow the same recommendations for cardiovascular risk stratification and prevention as for the corresponding general population, but be aware that statins might worsen muscle symptoms mimicking myositis relapse. On the basis of recent studies, we recommend a low threshold for cardiac workup and follow-up in patients with IIM.

Quality of life in adults with juvenile-onset dermatomyositis: a case-control study.

To compare quality of life in adults diagnosed with juvenile dermatomyositis (DM) with that of matched controls, and to analyze the association with other disease parameters in patients.

2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups

To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.

In juvenile dermatomyositis, heart rate variability is reduced, and associated with both cardiac dysfunction and markers of inflammation: a cross-sectional study median 13.5 years after symptom onset.

OBJECTIVES Low heart rate variability (HRV) is a well-established predictor of cardiac death. The aim of this study was to investigate arrhythmias and HRV in patients with JDM, and associations between HRV and inflammatory markers, echocardiographic measurements and disease parameters. METHODS Fifty-five patients with JDM were examined 2-34 years (median 13.5 years) after disease onset, and compared with 55 age and sex matched controls. Holter ECG monitoring and echocardiography were analysed blinded to patient information. Arrhythmia and HRV (six parameters) were analysed by standard software, finally adjudicated by an experienced cardiologist. Markers of inflammation (ESR, high sensitivity (hs)CRP and cytokines) were analysed. Disease activity and organ damage were assessed by clinical examination at follow-up and retrospectively by chart review. RESULTS In two out of six HRV parameters, JDM patients had lower values than controls. No difference in arrhythmias was found between the groups. In patients, but not in controls, there were significant negative correlations between five out of six HRV parameters, and ESR and hsCRP (Spearman correlation coefficient, -0.306 to -0.470; P, 0.023 to <0.001). Also, in patients, negative correlations were found between three out of six HRV parameters and systolic and diastolic function. Active disease and low HRV were associated. Patients with hsCRP in the highest quartile (Q4) had lower HRV in all parameters compared with those in pooled Q1-3 (P < 0.001). CONCLUSION JDM patients had reduced HRV, which was associated with elevated inflammatory markers, active disease and reduced myocardial function. This suggests reduced vagal control of the heart; further studies are needed to determine whether this is also associated with cardiac morbidity or mortality.