Cases Of Juvenile Dermatomyositis Research Articles

Decoding the genetic landscape of juvenile dermatomyositis: insights from phosphorylation-associated single nucleotide polymorphisms.

Genome-wide association studies (GWASs) have identified genetic susceptibility loci associated with juvenile dermatomyositis (JDM). Single nucleotide polymorphisms related to phosphorylation (phosSNPs) are critical nonsynonymous mutations exerting substantial influence on gene expression regulation. The aim of this study was to identify JDM susceptibility genes in the GWAS loci by the use of phosSNPs. We explored quantitative trait loci (QTLs) among the phosSNPs associated with JDM using data from eQTL (bulk tissues and single-cell) and pQTL studies. For gene expression and protein levels significantly influenced by JDM-associated phosSNPs, we assessed their associations with JDM through MR analyses. Additionally, we conducted differential expression gene analyses, incorporating single-cell transcriptomic profiling of 6 JDM cases and 11 juvenile controls (99,396 cells). We identified 31 phosSNPs situated in the 6p21 locus that were associated with JDM. Half of these phosSNPs showed effects on gene expression in various cells and circulating protein levels. In MR analyses, we established associations between the expression levels of pivotal JDM-associated genes, including MICB, C4A, HLA-DRB1, HLA-DRB5, and PSMB9, in skin, muscle, or blood cells and circulating levels of C4A, with JDM. Utilizing single-cell eQTL data, we identified a total of 276 association signals across 14 distinct immune cell types for 28 phosSNPs. Further insights were gained through single-cell differential expression analysis, revealing differential expression of PSMB9, HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQA1, HLA-DQB1, and HLA-DRB1 in immune cells. The present study pinpointed phosSNPs within susceptibility genes for JDM and unraveled the intricate relationships among these SNPs, gene expression levels, and JDM.

Over Activation of IL-6/STAT3 Signaling Pathway in Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is characterized by persistent non-purulent inflammation in the muscle and skin. The underlying mechanisms still remain uncertain. This study aims to elucidate the mechanism of interleukin-6 (IL-6) activation of Janus kinase/signal transducer and activator of transcription 3 pathway (JAK/STAT3), contributing to the pathogenesis of JDM. Serum IL-6 levels were compared between 72 newly diagnosed patients with JDM and the same patient cohort in treatment remission. Single-cell RNA sequencing (scRNA-seq) was employed to identify differential signaling pathway expression in muscle biopsy samples from two patients with JDM and healthy controls. Immunohistochemistry was used to examine differences in STAT3 phosphorylation between JDM and control muscle tissues. In vitro, skeletal muscle cell lines were stimulated with IL-6, and the transcription levels of genes related to mitochondrial calcium channels were quantified via reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) production was measured in both IL-6 treated and untreated groups. ROS levels were then compared between IL-6 receptor antagonist pre-treated skeletal muscle cells and untreated cells. IL-6 levels in newly onset patients with JDM were significantly higher compared to the same patient cohort in remission states (p < 0.0001). Serum IL-6 was significantly increased in patients with negative myositis specific antibody (MSA), positive melanoma differentiation associated protein 5 (MDA5) and positive nuclear matrix protein 2 (NXP2), yet not for JDM with positive transcriptional intermediary factor γ(TIF1γ), based on subgroup analysis. ScRNA-seq analysis of muscle biopsies from patients with MDA5-positive JDM and patients with MSA negative JDM revealed abnormal activation of the JAK/STAT3 pathway in skeletal myocytes, macrophages, and vascular endothelial cells. The phosphorylation levels of STAT3 were elevated in active JDM cases. Transcription of the calcium channel modulation gene sarcolipin (SLN) was significantly higher in JDM primary skeletal muscle cells compared to normal cells. In vitro, IL-6 enhanced SLN transcription and induced ROS production, and blocking the IL-6 receptor resulted in decreased ROS generation in skeletal muscle cells. IL-6/JAK/STAT3 signaling pathway was abnormally activated in patients with JDM. IL-6 may be involved in the pathogenesis of muscle damage by triggering the development of calcium overload and production of ROS. Blockade of the IL-6/JAK/STAT3 pathway can be a potential treatment option for JDM, especially MDA5-positive patients and those who are negative for MSA.

Ovarian dysfunction in adolescent girls with autoimmune rheumatic diseases

ObjectiveTo explore the different menstrual and pubertal abnormalities in adolescent females with systemic autoimmune rheumatic diseases (ARD).MethodsThe study included adolescent girls aged 13–18 years with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE), and juvenile dermatomyositis (JDM) classified according to their international classification criteria. Data were collected from our patients’ files and interpreted with respect to the demographic, clinical, disease assessment parameters, medications used, and the hormonal profile. The aspects of puberty and menstruation were assessed by a gynaecologist with ultrasound evaluation as well. The girls were classified according to their menstrual pattern into those with regular cycles versus abnormal ones. The subgroups were compared and significant variables entered into a logistic regression model to detect the independent predictors.ResultsTwenty-one girls with JSLE were included, besides 23 JIA and 8 JDM cases. Ten patients with JSLE (47.6%) had menstrual abnormalities, whereas only four JIA (17.4%) and 1 JDM girls had these alterations without significant difference between the three groups. The median of the SLICC/ACR damage index was statistically higher in JSLE with abnormal menstrual cycles, similarly were the cumulative steroid dose and puberty onset. No difference was observed between JIA or JDM subgroups concerning the disease parameters, hormonal profile, ultrasound assessment or the treatment lines. The most significant predictor for menstrual abnormalities in JSLE was the SLICC/ACR damage index.ConclusionMenstrual abnormalities is a common disturbance among adolescent girls with ARDs. The SLICC/ACR damage index is the main determinant for menstrual abnormalities rather than the cumulative steroid use or disease duration in JSLE.

Biologic drugs in the treatment of juvenile dermatomyositis: a literature review.

There is no clear consensus in the literature regarding the choice of biologic therapies and efficacy in juvenile dermatomyositis (JDM). In this review, we aimed to examine previous studies regarding biologic drug use in JDM patients. We screened MEDLINE and Scopus for articles involving JDM patients treated with biologic drugs. We identified 74 articles describing 495 JDM patients treated with biologic drugs (538 biologic treatments) during our literature search. The median (min-max) age of these patients was 9.8 (1-17) years (F/M:1.8). The most frequently used biologic drugs were rituximab (RTX, 50%) and tumor necrosis factor (TNF) inhibitors (34.8%). In a few cases, abatacept (4.3%), anti-interleukin-1 agents (0.9%), tocilizumab (0.9%), bortezomib (0.4%), ustekinumab (0.2%), eculizumab (0.2%), and golimumab (0.2%) were used. RTX was most frequently preferred in patients with severe skin involvement (46.3%). Improvement with RTX was obtained in 60.1% of RTX treatments. Infliximab was most frequently preferred in calcinosis (43.3%), while adalimumab in skin involvement (50%) and etanercept in resistant/recurrent diseases (80%). Improvement was achieved in 44.4% of anti-TNF treatments. Adverse events were observed in 46.8% (58/124) of all treatments. Our results suggest that biologic agents may be a promising alternative for the treatment of particularly resistant JDM cases. Controlled studies are required to provide higher level of evidence for the timing of biologic use in JDM treatment. Key Points • There is no consensus on the choice and efficacy of biologic therapies in JDM. • RTX and TNF inhibitors are the most commonly used biologic drugs. • Biologics were especially preferred in severe skin involvement, calcinosis, and resistant diseases.

Juvenile idiopathic inflammatory myopathies: results of an open single-center retrospective study

Juvenile idiopathic inflammatory myopathies (JIIM) are rare diseases in which the prognosis is largely determined by timely diagnosis, timing of prescription and effectiveness of therapy.Objective: to characterize the clinical phenotypes, the results of paraclinical examination methods, the spectrum of autoantibodies, as well as therapeutic options in patients with JIIM.Patients and methods. The retrospective study included 37 patients with JIIM hospitalized in the pediatric department of the V.A. Nasonova Research Institute of Rheumatology from 2016 to 2020. All patients underwent a standard clinical and laboratory-instrumental examination in accordance with the diagnosis and severity of the condition.Results and discussion. Twenty-three of the 37 JIIM patients had juvenile dermatomyositis (JDM), 1 had polymyositis, and 13 had overlap-myositis (OM). The ratio of boys and girls was 1:1.7. The median age of onset for JDM was 6.9 years, and OM was 11.3 years. All patients had skeletal muscles involvement, dysphagia was detected in 52.2% of cases of JDM and in 15.4% of cases of OM. An increase in the level of creatine phosphokinase at the time of diagnosis was observed in 72.9% of patients, of lactate dehydrogenase – in 81.1%, of alanine aminotransferase - in 67.6%, of aspartate aminotransferase – in 75.7%. Heliotrope rash and/or Gottron's syndrome were observed in 100% of patients with JDM and in 30.8% with OM. Lung involvement was found in 27% of children. The myopathic capillaroscopic changes were present in 95.2% of patients with JDM and 53.8% with OM. Myositis-specific autoantibodies were found in 10.8% of patients with JIIM.All patients received glucocorticoids, 81.0% methotrexate, 18.9% hydroxychloroquine, 8.1% cyclophosphamide, 8.1% cyclosporine, 2.7% mycophenolate mofetil, 2.7% azathioprine, 67.6% - intravenous immunoglobulin. Biologic disease modifying antirheumatic drugs (bDMARDs) were prescribed to 26% of patients with JDM and to all patients with OM (only in 51.3% of cases with JIIM). The median duration of illness before initiation of bDMARDs therapy was 2.25 years. 58.8% of patients were treated with rituximab (RTM), 41.2% with abatacept (ABA). In 1 patient with OM, represented by a combination of systemic lupus erythematosus and JDM, three bDMARDs were used sequentially: ABA, etanercept and RTM. All patients achieved inactive disease status.Conclusion. JDM is the most common phenotype of JIIM, which is characterized by an earlier age of onset, skin involvement that precedes the development of myopathy, and typical capillaroscopic changes. The conclusion was made about the high efficacy and acceptable safety profile of bDMARDs therapy in children with JIIM, with careful monitoring of its tolerability. bDMARDs can be prescribed even in the early stages of the disease in the presence of unfavorable prognostic factors.

Successful rituximab treatment for severe rapidly progressive interstitial lung disease with anti-MDA5 antibody-positive juvenile dermatomyositis: a case report and literature review

BackgroundRapidly progressive (RP) interstitial lung disease (ILD) is a life-threatening complication of juvenile dermatomyositis (JDM); however, it is generally refractory to treatment; to the best of our knowledge, no evidence-based treatment has been established for RP-ILD yet. We present the case of a 2-year-old girl with RP-ILD who showed resistance to treatment with methylprednisolone, cyclosporine A, cyclophosphamide, immunoglobulin, and plasma exchange (PE) and was finally treated with extracorporeal membrane oxygenation. We further present a literature review of 18 cases of JDM with RP-ILD.Case presentationA 2-year-old girl presented with malar rash, mild muscle weakness, and weight loss for a few months before admission. She had a history of dry cough and dyspnea for a few days, followed by rapid respiratory failure. The patient was diagnosed with JDM with RP-ILD through physical examination (malar rashes and Gottron’s sign) and based on the finding of myositis on femoral magnetic resonance imaging, elevated levels of serum muscle enzymes, positive anti-melanoma differentiation-association gene 5 (MDA5) antibody (> 7,500 index), elevated level of Krebs von den Lungen-6 glycoprotein (KL-6; 3,420 U/mL), and extensive ground-glass opacities with consolidation in the bilateral lungs on chest high-resolution computed tomography. She received combination therapy, including methylprednisolone pulse therapy, followed by oral prednisolone and intravenous cyclosporine A, cyclophosphamide, and immunoglobulin. On day 11 of hospitalization, she was placed on ventilation support and PE was initiated. However, her respiratory condition continued to deteriorate and veno-venous extracorporeal membrane oxygenation was started on day 24 of hospitalization. Rituximab was administered on day 28. After 2 weeks of rituximab therapy initiation, her respiratory condition showed gradual improvements. Eventually, on day 52 of hospitalization, the patient could be weaned off extracorporeal membrane oxygenation. Finally, she was discharged with minimal ventilation support and no neurological complications 11 months after admission.ConclusionsOur literature review suggest that JDM with RP-ILD has a high mortality rate. In JDM, rituximab may be a promising treatment option for RP-ILD. In the future, the efficacy of rituximab in the early phases of ILD should be investigated.

Dermatologic Manifestations of Systemic Diseases in Childhood

Dermatologic Manifestations of Systemic Diseases in Childhood

P052 Juvenile dermatomyositis, a multi-faceted disease

Abstract Background Dermatomyositis is a rare disease. In children, the incidence is 2–3 per million habitants. It is a serious disease whose mortality is &amp;lt; 5% but whose complications and long-term prognosis remain pejorative for some children. The objective is to report the epidemiological, clinical, therapeutic options and the course of a retrospective series carried out at the CHU pediatric center of Sétif (Algeria) comprising 8 cases of juvenile dermatomyositis. Methods The mean age of onset is 7.7 years (0–15.5 years), The sex ratio was 0.1; The diagnosis delay averaged at 4, 4 months. At disease onset, 100% had rash, 84% a eyelids telangiectasias, 40% Gottron nodules, 90% muscular weakness, 40% arthritis, 13% fever, and 25% dysphagia. The muscular enzymes were increased in 8 cases. The DNA antibodies were present in one patient with myositis overlap, NXP was positive in one child. The electromyogram is myogenic in all patients. Seven patients underwent a histopathological exam, showing interstitial and parenchymal myositis. Treatment regimens were variable depending on the severity of the disease onset. All children were treated with steroids as the first line. Methotrexate was prescribed in 5 cases (62.5%). The immunoglobulin was indicated in 2 cases. The failure to thrive was observed in 2 (25%), and one child died following aspiration pneumonia. Results The dermatomyositis diagnosis is based on the Bohan and Peter criteria. The clinical characteristics of our series are in line with the literature data with a predominance of cutaneous and muscular involvement. However, some specificities are individualized: a case of overlapping myositis with lupus, a case of extensive calcinosis. The treatment was based on corticosteroids and methotrexate. Conclusion Dermatomyositis juvenile is a rare disease with a pejorative prognosis requiring a multidisciplinary management.

Cutaneous Manifestations of Juvenile Dermatomyositis: A Case Series

Juvenile Dermatomyositis (JDM) is an idiopathic inflammatory myopathy characterized by the weakness of skeletal muscle and pathognomonic skin rashes. Studies focusing on the cutaneous manifestations of JDM are sparse. The objectives of the study were (1) to describe cutaneous changes seen in JDM and (2) to observe nailfold capillaroscopy (NFC) changes in patients with JDM. This was a retrospective case series. All children under the age of 15 years who were diagnosed to have dermatomyositis according to the Bohan and Peter criteria and on histopathology presenting to the dermatology outpatient department during a period of 1.5 years (January 2017–June 2018) were included in the series. Details including clinical features and finding from investigations such as NFC, muscle magnetic resonance imaging, electromyography, muscle enzymes, and biopsy were noted. Statistical analysis was performed on the basis of measures such as percentage and frequency of cutaneous manifestations. A total of eight cases of JDM were included, with average age at presentation being 7.62 years. Among the cutaneous manifestations, the most common presenting features were heliotrope rash and Gottron's papule. Facial telangiectasias, calcinosis cutis, and hypertrichosis were seen in 37.5% of cases. Other cutaneous features seen were confluent and reticulate violaceous erythema, cutaneous ulcer, and periungual telangiectasia with cuticular overgrowth. NFC was suggestive of scleroderma-dermatomyositis pattern in all six patients in whom it was conducted. JDM has classic, pathognomonic skin manifestations that may or may not correspond with muscle inflammation. To avoid complications, early diagnosis and prompt treatment is the mainstay. NFC acts as an important diagnostic tool and also helps to characterize the phase of disease.

Two Cases of Juvenile Dermatomyositis: Case Series and Review of the Literature

Two Cases of Juvenile Dermatomyositis: Case Series and Review of the Literature

MicroRNA-10a Regulation of Proinflammatory Mediators: An Important Component of Untreated Juvenile Dermatomyositis.

To identify differentially expressed microRNA (miRNA) in muscle biopsies (MBx) from 15 untreated children with juvenile dermatomyositis (JDM) compared with 5 controls. Following MBx miRNA profiling, differentially expressed miRNA and their protein targets were validated by quantitative real-time PCR (qRT-PCR) and immunological assay. The association of miRNA-10a and miRNA-10b with clinical data was evaluated, including Disease Activity Score (DAS), von Willebrand factor antigen (vWF:Ag), nailfold capillary end row loops, duration of untreated disease, and tumor necrosis factor (TNF)-α-308A allele. In JDM, 16/362 miRNA were significantly differentially expressed [false discovery rate (FDR) < 0.05]. Among these, miRNA-10a was the most downregulated miRNA in both FDR and ranking of fold change: miRNA-10a = -2.27-fold, miRNA-10b = -1.80-fold. Decreased miRNA-10a and miRNA-10b expressions were confirmed using q -4.16 and -2.59 fold, respectively. The qRT-PCR documented that decreased miRNA-10a expression was related to increased vascular cell adhesion molecule 1 in 13 of these JDM cases (correlation -0.67, p = 0.012), unlike miRNA-10b data (not significant). Concurrent JDM plasma contained increased levels of interleukin (IL) 6 (p = 0.0363), IL-8 (p = 0.0005), TNF-α (p = 0.0011), and monocyte chemoattractant proteins 1 (p = 0.0139). Decreased miRNA-10a, but not miRNA-10b, was associated with the TNF-α-308A allele (p = 0.015). In the 15 JDM, a trend of association of miRNA-10a (but not miRNA-10b) with vWF:Ag and DAS was observed. MiRNA-10a downregulation is an important element in untreated JDM muscle pathophysiology. We speculate that muscle miRNA expression in adult dermatomyositis differs from muscle miRNA expression in untreated childhood JDM.

Dermatomyosite juvénile et nouveaux auto-anticorps : à propos de quatre observations

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children. Its diagnosis is usually made on a clinical basis following the criteria of Bohan and Peter (1975). Recently, the presence of myositis-specific autoantibodies (MSAs) have started to be associated with specific outcome in adult patients; the diagnosis and prognosis value of these autoantibodies remains to be identified in children. We report four cases of JDM with MSAs focusing on clinical, biological, and radiological manifestations, and then we describe associated treatment. The cohort comprises four girls with an average age of 8.5 years. The time to diagnosis was 1 week to 4 months. For these patients, the immunologic study found one patient positive for the MDA5 antibody (or CADM 140), one positive for the TIF1γ antibody (or p155/140), and two patients positive for the NXP2 antibody (or p140/MJ). Each patient showed specific and characteristic cutaneous manifestations. For example, the girl positive for the TIF1γ antibody presented the most severe skin disease with urticaria, face edema, and vascularity of the neck and shoulders. However, regarding muscular features, proximal weakness was present in most of the cohort, except for the child positive for the MDA5 antibody, who presented no sign of muscular disease at the beginning with low CK levels. Importantly, acute pancreatitis also affected this patient. Concerning radiological indications, muscular MRI evidenced hyperinflammation, a sign of diffuse myositis, in all these patients. Treatments consisted in corticosteroids together with methotrexate or mycofenolate mofetil associated or not with intravenous immunoglobulin therapy. This report highlights the importance of systematic detection and analysis of MSA in diagnosis and characterization of JDM, and describes a new approach that would allow more focused treatments and be a useful predictor of clinical complications and prognosis in JDM-affected subjects.

G358 The performance of the new SLICC criteria for the classification of SLE in children

AimsThe Systemic Lupus International Collaborating Clinics (SLICC) have recently suggested a new set of criteria for the classification of SLE. We aimed to compare the sensitivity and specificities of the...

A47: Progress Report on the Development of New Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies

Background/Purpose:Inadequate classification criteria for IIM are a fundamental limitation in clinical studies. An international, multidisciplinary collaboration, the International Myositis Classification Criteria Project (IMCCP), supported by ACR and EULAR, was established to address this problem.Methods:Identification and definition of potential criterionCandidate variables to be included in classification criteria were assembled from published criteria and inclusion criteria in controlled trials of myositis and refined using Nominal Group Technique. Comparator groups confused with IIM were defined.Data collectionWithin this retrospective case control study, clinical and laboratory data from IIM and comparator patients were collected from 47 rheumatology, dermatology, neurology and pediatrics clinics worldwide from 2008–2011.AnalysisCrude pair‐wise associations among all variables measured and between each variable and clinician's diagnosis were assessed. Three approaches for derivation of classification criteria were explored: Traditional: case defined by specified number of items from a set Risk score: patient assigned a probability risk score by summing score‐points associated with the variables (Probability model 1 and 2) Classification tree: case defined by a decision treeA random forest algorithm explored the most important variables. Results obtained with each approach were utilized to improve others iteratively.ValidationInternal validation using bootstrap methods was performed. External validation using extracted data from the Euromyositis register and an UK juvenile myositis register was performed.Results:Data from 973 IIM patients (74% adults;26% children), representing subgroups of IIM (245 polymyositis, 239 dermatomyositis, 176 inclusion body myositis and 246 juvenile dermatomyositis cases) and 629 comparators (81% adults; 19% children) were obtained. The comparators include other myopathies and systemic rheumatic diseases.Two probability score models were developed (Table ): Model 1 comprised clinical variables on muscles, skin, and laboratory measures; Model 2 additionally comprised muscle biopsy variables. Model 1 performed nearly as well as Model 2 and both models performed as well as and often better than, the classification tree that was developed and published criteria.External validation using data on 2363 myositis patients in the Euromyositis register resulted in &gt;99% sensitivity, and using 332 juvenile myositis cases resulted in 100% sensitivity for both probability models. PERFORMANCE OF NEW AND EXISITING CLASSIFICATION/DIAGNOSTIC CRITERIA FOR IIM Probability model Performance(%) Without muscle biopsy data(Model 1) With muscle biopsy data (Model 2) Classification Tree Peter &amp; Bohan [1] Tanimoto et al. [2] Targoff et al.[3] Dalakas &amp; Hohlfeld [4] Hoogendijk et al.[5] Sensitivity 87 88 88 98 96 93 6 51 Specificity 88 89 72 55 31 88 99 96 Correctly classified 87 88 84 86 79 91 45 70 Cut point for probability: 55% Definite and probable polymyositis and dermatomyositis New model for classification criteria for IIM and performance of criteria Probability model Variable Score points 18 ≤ Age of onset of first symptom &lt; 40 1.6 Age of onset of first symptom ≥ 40 2.3 Clinical Muscle Variables Objective symmetric weakness, usually progressive, of the proximal upper extremities 0.7 Objective symmetric weakness, usually progressive, of the proximal lower extremities 0.6 Neck flexors are relatively weaker than neck extensors 1.6 In the legs proximal muscles are relatively weaker than distal muscles 1.5 Skin Variables Heliotrope rash 3.3 Gottronxs papules 2.3 Gottron's sign 3.4 Other Clinical Variables Dysphagia or esophageal dysmotility 0.7 Laboratory Variables Serum creatine kinase activity (CK) activity 1.2 Serum lactate dehydrogenase (LDH) activity or Serum aspartate aminotransferase (ASAT/AST/SGOT) activity or Serum alanine aminotransferase (ALAT/ALT/SGPT) activity Anti‐Jo‐1 (anti‐His) antibody positivity 4.2 Score‐sum from above items 0.9 Muscle Biopsy Variables Endomysial infiltration of mononuclear cells surrounding, but not invading, myofibers 1.4 Perimysial and/or perivascular infiltration of mononuclear cells 1.2 Perifascicular atrophy 1.6 Rimmed vacoules 2.2 When muscle biopsies are available, multiply the score‐sum of all other variables by 0.9 and then add the scores of the positive biopsies. Probability of disease can be obtained using the web calculator: www.imm.ki.se/biostatistics/calculators/iimConclusion:New classification criteria for IIM with readily clinically assessable measurements and symptoms have been developed. They generally show superior performance compared with existing criteria.

P.14.4 Diagnostic role of quantitative NMR imaging exemplified by 3 cases of juvenile dermatomyositis

Skeletal muscle diagnostic imaging is classically based on visual inspection of T1-weighted NMR images and interpretation of patterns of fatty infiltration. The existence of oedematous/inflammatory/necrotic lesions is subjectively appreciated on T2-weighted images, typically acquired with the STIR sequence to minimize fat confounding effects. Because it relies on identification of hyperintensities between and within muscles, the interpretation risk with T2-weighted images is to miss global, homogenous increases in T2. In this report, we demonstrate this concern to be more than theoretical. Three patients aged 6, 7 and 12 were referred for further investigation of progressive muscle wasting (P1) or clinical suspicion of dermatomyositis (P2, P3). All of them had normal CK values. Whole-body T1w showed no fatty infiltration in muscles. Standard T2w imaging was normal in P1, showed discrete differences in signal intensity, particularly between anterior and posterior leg compartments in P2 and was moderately positive with hyperintense streaks in P3. Quantitative T2 maps were obtained from multi TE spin echo data after extraction of the water component by tri-exponential fitting. In the 3 patients, muscle water T2s were abnormally elevated in the scapular and pelvic girdles, the thighs and the legs: 45/51 muscles of P1, 46/60 of P2 and 47/51 of P3 had T2s higher than 39 ms, the upper normal value. Mean T2s were 42.3, 42.3 and 45.9 ms, with highest T2s measured at 50.0, 51.9 and 53.3 ms in P1, P2 and P3 respectively. Juvenile dermatomyositis was histologically confirmed in all patients. After 3 months on steroid, P1 was rescanned. In the previously inflamed muscles, T2 had on average decreased by 3.4 ms (p < 0.001) and 17 muscles had resumed normal T2 values. Quantitative T2 mapping can be required to detect unambiguously muscle lesions as shown here in juvenile dermatomyositis. It is also essential to monitor response to treatment in the absence of biological biomarkers. Skeletal muscle diagnostic imaging is classically based on visual inspection of T1-weighted NMR images and interpretation of patterns of fatty infiltration. The existence of oedematous/inflammatory/necrotic lesions is subjectively appreciated on T2-weighted images, typically acquired with the STIR sequence to minimize fat confounding effects. Because it relies on identification of hyperintensities between and within muscles, the interpretation risk with T2-weighted images is to miss global, homogenous increases in T2. In this report, we demonstrate this concern to be more than theoretical. Three patients aged 6, 7 and 12 were referred for further investigation of progressive muscle wasting (P1) or clinical suspicion of dermatomyositis (P2, P3). All of them had normal CK values. Whole-body T1w showed no fatty infiltration in muscles. Standard T2w imaging was normal in P1, showed discrete differences in signal intensity, particularly between anterior and posterior leg compartments in P2 and was moderately positive with hyperintense streaks in P3. Quantitative T2 maps were obtained from multi TE spin echo data after extraction of the water component by tri-exponential fitting. In the 3 patients, muscle water T2s were abnormally elevated in the scapular and pelvic girdles, the thighs and the legs: 45/51 muscles of P1, 46/60 of P2 and 47/51 of P3 had T2s higher than 39 ms, the upper normal value. Mean T2s were 42.3, 42.3 and 45.9 ms, with highest T2s measured at 50.0, 51.9 and 53.3 ms in P1, P2 and P3 respectively. Juvenile dermatomyositis was histologically confirmed in all patients. After 3 months on steroid, P1 was rescanned. In the previously inflamed muscles, T2 had on average decreased by 3.4 ms (p < 0.001) and 17 muscles had resumed normal T2 values. Quantitative T2 mapping can be required to detect unambiguously muscle lesions as shown here in juvenile dermatomyositis. It is also essential to monitor response to treatment in the absence of biological biomarkers.

Clinical characteristics of juvenile dermatomyositis complicated with interstitial lung disease

To explore the clinical and laboratory features and the prognosis of juvenile dermatomyositis (JDM) complicated with interstitial lung disease (ILD). Data of 39 cases of JDM complicated with ILD hospitalized in Beijing Children's Hospital from January 2005 to December 2011 were collected. The clinical features, laboratory data and prognosis of these children were analyzed. Of the 39 cases studied, 16 were boys, and 23 girls. The average age of onset was 5.6 years, and 61.5% of the patients' age of onset (24 cases) was under 6 years. Rashes (17 cases, 43.6%), simultaneous eruption of rashes and muscle weakness (14 cases, 35.9%), fever (4 cases, 10.1%), or muscle weakness (3 cases, 7.7%) were common initial symptoms of the disease. Only 51.3% of the patients (20 cases) had the symptoms of respiratory system, but (24 cases) 61.5% were complicated with that of the gastrointestinal system; (27 cases) 69.2% had at the same time electrocardiographic and echocardiographic abnormalities. The chest high resolution computed tomography (HRCT) showed cord or band-like shadows in their lungs of more than half of the cases (25 cases, 64.1%), and other changes included ground glass-like shadow (10 cases, 25.6%), net and lineation-like shadow (9 cases, 23.1%), nodular change (5 cases, 12.8%). The patients complicated with lung essential infiltration accounted for as high as 71.8% (28 cases). These imaging changes were largely seen on both dorsal sides of their lungs. Severe patients also had mediastinal emphysema, pneumothorax, pneumorrhagia or aerodermectasia. Twenty-four patients underwent pulmonary function examination, and 62.5% of the patients' pulmonary function (15 cases) was abnormal. The fatality rate of the cases studied was 10.1%. The imaging changes of patients suffering from JDM with ILD were often more severe as compared to the clinical symptoms, and were often complicated with damages to other systems and organs. The prognosis of those patients was poorer than others. Patients with JDM especially at a younger age of onset and with various organ damages should be examined with chest HRCT examinations as early as possible.

CNS Disease as the Presenting Feature in Four Cases of Juvenile Dermatomyositis (P07.218)

Objective: Presentation of four cases of juvenile dermatomyositis with CNS involvement as the initial feature. Background There are very few case reports in the literature of CNS involvement with JD. There are even fewer cases reported in which the initial presentation of CNS vasculitis and demyelinating disease develops into more recognizable JD. Design/Methods: Four patient cases are presented. Results: We present case reports of four patients who presented with CNS lesions and various degrees of encephalopathy who later progressed to meet clinical criteria for the diagnosis of juvenile dermatomyositis. The first patient we report is a 13 year old male who presented with demyelinating lesions of the spinal cord and optic nerves. He went on to develop weakness of the lower extremities. The second patient, a 6 year old female, initially presented with a viral meningitis, and then went on to develop a myriad of brain lesions on MRI. A third patient, a 9 year old female presented with seizures and encephalopathy. She had both cortical and subcortical brain lesions that showed both inflammation and hemorrhage. The final patient, a 16 year old girl presented with demyelinating lesions of the brain stem and spinal cord. All four of the patients went on to develop proximal muscle weakness, primarily of the lower extremities and had muscle biopsies demonstrating perifascisular atrophy and inflammatory changes consistent with juvenile dermatomyositis. All of these patients responded well to immunosuppressive therapy and made substantial recoveries. Conclusions: These reports should encourage investigation into autoimmune disease in general and JD in particular when cases of CNS disease of unknown etiology present in pediatric patients. There are implications for both prognosis and treatment when the disease course is recognized early. Disclosure: Dr. Lee has nothing to disclose. Dr. Bishop has nothing to disclose. Dr. Vedanarayanan has nothing to disclose.

Results of the German ESPED-Recording of New Patients with Juvenile Dermatomyositis (JDM)

In a nation-wide registration project 38 incident cases of juvenile dermatomyositis were collected in Germany over a 2-year-period. Diagnostic methods as well as the primary treatment for these patients were recorded. Detailed information was available for 25 of these patients. Diagnostic as well as therapeutic decisions varied widely. Steroids were used in almost all of the 25 patients either as oral or as parenteral pulse therapy, additional immunosuppressive drugs were used in 52%. We plan to establish national consensus recommendations for diagnostic and therapeutic standards in JDM. Due to the rarity of JDM clinical trials will have to be performed on an international basis.

Treatment Approaches to Juvenile Dermatomyositis (JDM) Across North America: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Treatment Survey

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. 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. 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. 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.

Age-dependent inhibition of ectopic calcification: a possible role for fetuin-A and osteopontin in patients with juvenile dermatomyositis with calcinosis

To assess if age and/or age-dependent variations in the levels of two major calcification regulatory proteins, fetuin-A and osteopontin, could be associated with an increased risk of calcinosis in children with juvenile dermatomyositis (JDM). The frequency of calcinosis was derived from a national UK database of 212 cases of JDM. Serum fetuin-A and plasma osteopontin levels were determined using ELISA in 15 JDM patients with calcinosis and 15 JDM patients without calcinosis. Healthy controls were 19 age-matched children, 24 adolescents and 13 adults. Sixteen patients with juvenile idiopathic arthritis (JIA) were additional paediatric disease controls. Of the 212 JDM cases 10% had calcinosis. Calcinosis patients had younger age of disease onset than those without calcinosis (mean age of 5.3 yrs vs 7.1 yrs, respectively, P = 0.016). No significant difference in fetuin-A or osteopontin could be detected between the two JDM groups. Fetuin-A levels in all groups of children and the adolescent group were much lower than described previously in adults, and there was a significant positive correlation between age and fetuin-A level, and also between osteopontin levels in plasma and serum fetuin-A. Children who develop JDM at an younger age may have increased risk of developing calcinosis. Physiologically low levels of fetuin-A in young children combined with an additional negative acute-phase effect on fetuin-A due to chronic inflammation could explain in part the propensity to develop ectopic calcification observed in JDM patients, and why calcinosis is less frequent in adults with dermatomyositis.