Treatment Of Juvenile Dermatomyositis Research Articles

Advances in the diagnostics and treatment of juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is by far the most frequent inflammatory myopathy in childhood and adolescence. It is clinically characterized by inflammatory changes of the skin and muscles but as amultisystemic disease can also affect the skeletal system, the gastrointestinal tract, lungs and heart. Intrinsic (multigenetic risk) and extrinsic factors (triggers) are involved in the pathogenesis resulting in endothelial damage, involvement of fascies, activation of the interferon system and autoimmune reactions including formation of myositis-specific autoantibodies (MSA). In contrast to dermatomyositis in adults, in children and adolescents there are no associations with malignant diseases. The variable expression, the rarity of the disease and the risk of long-term damage and complications necessitate pediatric rheumatological experience in the diagnostics and treatment. Recently, new approaches in drug treatment have substantially improved the outcome and prognosis but amultidisciplinary treatment (including physicians, physiotherapists, psychologists, social workers) is mandatory, especially in the first phases of the disease. Particularly important is aprofessionally correct treatment of the functional sequelae, which are aparticular focus of this article.

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.

Chinese guidelines for the diagnosis and treatment of juvenile dermatomyositis

幼年皮肌炎（JDM）是儿童期发病的一种慢性自身免疫性疾病，以特征性皮疹和对称性近端肌无力为主要临床特征，可并发心肺、胃肠道及神经等多系统损伤。“中国幼年皮肌炎诊断与治疗指南”由中华医学会儿科学分会免疫学组、中华儿科杂志编辑委员会和儿童风湿免疫病联盟联合发起，形成了JDM诊断、评估、治疗和预后管理等方面的推荐建议，以期提高JDM诊疗的规范性及科学性，指导临床实践。.

Juvenile dermatomyositis. Where are we now?

Juvenile onset idiopathic inflammatory myopathy (IIM) has many similarities and distinct differences from adult-onset disease. This review will focus on recent developments in understanding and treatment of juvenile dermatomyositis (JDM), the most common disease sub-type of IIM in childhood. JDM is a systemic immune mediated vasculopathy, increasingly recognised as a group of distinct phenotypes with variable presentation and outlook. This overview will describe long-term outlook and disease course including health-related quality of life and emerging treatments.

Crowdsourcing as a means of fundraising for juvenile dermatomyositis.

This study used the crowdsourcing platform GoFundMe to analyze the financial hardships associated with treatment of juvenile dermatomyositis. Uncovered medical expenses, travel costs, and loss of income were all commonly cited reasons for fundraising, demonstrating high out-of-pocket costs and significant economic hardship associated with this disease, even among families with health insurance.

Juvenile Dermatomyositis: Advances in Pathogenesis, Assessment, and Management.

Juvenile dermatomyositis is the most common inflammatory myopathy in the pediatric age group and a major cause of mortality and morbidity in individuals with childhood rheumatic diseases. Mounting evidence suggests that early diagnosis and timely aggressive treatment are associated with better outcomes. The purpose of this article is to provide readers with an update on the evaluation, diagnosis, and the treatment of juvenile dermatomyositis. A PubMed search was performed in Clinical Queries using the key term "juvenile dermatomyositis" in the search engine. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Juvenile dermatomyositis is a chronic autoimmune inflammatory condition characterized by systemic capillary vasculopathy that primarily affects the skin and muscles with possible involvement of other organs. In 2017, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) developed diagnostic criteria for juvenile idiopathic inflammatory myopathies and juvenile dermatomyositis. In the absence of muscle biopsies which are infrequently performed in children, scores (in brackets) are assigned to four variables related to muscle weakness, three variables related to skin manifestations, one variable related to other clinical manifestations, and two variables related to laboratory measurements to discriminate idiopathic inflammatory myopathies from non-idiopathic inflammatory myopathies as follows: objective symmetric weakness, usually progressive, of the proximal upper extremities (0.7); objective symmetric weakness, usually progressive, of the proximal lower extremities (0.8); neck flexors relatively weaker than neck extensors (1.9); leg proximal muscles relatively weaker than distal muscles (0.9); heliotrope rash (3.1); Gottron papules (2.1); Gottron sign (3.3); dysphagia or esophageal dysmotility (0.7); the presence of anti-Jo-1 autoantibody (3.9); and elevated serum levels of muscle enzymes (1.3). In the absence of muscle biopsy, a definite diagnosis of idiopathic inflammatory myopathy can be made if the total score is ≥7.5. Patients whose age at onset of symptoms is less than 18 years and who meet the above criteria for idiopathic inflammatory myopathy and have a heliotrope rash, Gottron papules or Gottron sign are deemed to have juvenile dermatomyositis. The mainstay of therapy at the time of diagnosis is a high-dose corticosteroid (oral or intravenous) in combination with methotrexate. For mild to moderate active muscle disease, early aggressive treatment with high-dose oral prednisone alone or in combination with methotrexate is the cornerstone of management. Pulse intravenous methylprednisolone is often preferred to oral prednisone in more severely affected patients, patients who respond poorly to oral prednisone, and those with gastrointestinal vasculopathy. Other steroid-sparing immunosuppressive agents such as cyclosporine and cyclophosphamide are reserved for patients with contraindications or intolerance to methotrexate and for refractory cases, as the use of these agents is associated with more adverse events. Various biological agents have been used in the treatment of juvenile dermatomyositis. Data on their efficacy are limited, and their use in the treatment of juvenile dermatomyositis is considered investigational.

Investigating genetic drivers of juvenile dermatomyositis pathogenesis using bioinformatics methods.

Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. The pathogenic mechanisms remain ill-defined. The purpose of this study was to identify key genes related to JDM. Microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEG) were identified. Then, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction (PPI) network were carried out. In addition, the hub genes were selected by cytoHubba. The expression profile and diagnostic capacity (receiver-operator curve [ROC]) of interested hub genes were verified. Gene set enrichment analysis (GSEA) was also carried out. Moreover, the signature of hub genes was then used as a search query to explore the Connectivity Map (CMAP). A total of 128 DEG were identified. The enriched functions and pathways of the DEG include response to virus, negative regulation of cell migration, cadmium ion transmembrane transport, defense response to Gram-negative bacterium, positive regulation of megakaryocyte differentiation, and negative regulation of angiogenesis. Twenty-one hub genes were identified. The expression levels of the interested genes were also confirmed. ROC analysis confirmed that the expression of these genes can distinguish JDM from controls. GSEA showed that these genes are mainly related to "inflammatory response", "complement", "interferon-α response", "IL6/JAK/STAT3 signaling", "TGF-β signaling", "IL2/STAT5 signaling" and "TNF-α signaling via NF-κB". The CMAP research found some compounds with the potential to counteract the effects of the dysregulated molecular signature in JDM. In this study, bioinformatics methods were used to identify DEG, which helps us understand the molecular mechanisms of JDM and provide candidate targets for diagnosis and treatment of JDM.

Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment

Juvenile dermatomyositis (JDM) is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin, muscle and vital organs. But the clinical features and treatment of JDM have not been fully clarified. Databases underwent through PubMed for articles about the clinical features, myositis-specific antibodies of JDM and its treatment, and we selected publications written in English which were relevant to the topic of this review. Clinical features and myositis-specific antibodies may predict the severity and prognosis of disease. Although the mortality rate has been lower with traditional treatments, such as corticosteroid, intravenous immunoglobulin, and disease-modifying anti-rheumatic drugs such as methotrexate, their usages are variable. Novel biological therapies seem to be effective for refractory JDM patients, but more clinical trials are necessary. JDM is a sever disease of childhood. We need to better understand recent advances of JDM in the context of clinical features including skin manifestations, muscle weakness and organ damage, myositis-specific antibodies and their associated outcomes and the treatment of disease.

Anthropometric Effects of Intravenous Methylprednisolone Versus Oral Corticosteroids in the Treatment of Juvenile Dermatomyositis

Background: Oral corticosteroids (OCS) and intravenous methylprednisolone (IVMP) remain the backbone of therapeutic intervention for juvenile dermatomyositis (JDM).

Juvenile dermatomyositis-what's new?

Juvenile dermatomyositis (JDM) is the most common chronic inflammatory myopathy of childhood, which is still frequently characterized by acomplicated disease course. In this review, novel findings relating to JDM are presented based on areview of the literature. Myositis-specific antibodies are often detected and may correlate with clinical phenotypes and disease course. Activation of typeI interferon pathways plays an important pathogenic role and relates to the main clinical manifestations of the disease. This may lead to targeted therapies in the future. Currently, there are no treatments specifically approved for the treatment of JDM. Standard therapy is currently considered to include glucocorticoids and methotrexate based on arandomized controlled study and expert consensus. Several medications are commonly used in cases of refractory JDM, including azathioprine, ciclosporin, intravenous immune globulins, mycophenolate mofetil, and rituximab. An optimal treatment of JDM has not yet been established; however, there are national and international consensus recommendations and treatment plans that may aid in the decision-making process. Several validated tools are available to assess disease activity, disease damage, and treatment responses. Such tools should be routinely used in patients with JDM, and ideally be documented in registries in order to allow comparative effectiveness studies. The PRO-KIND initiative of the German Society for Pediatric Rheumatology has developed adiagnostic and atreat-to-target strategy based on apractice- and consensus-based process.

Treatment of Juvenile Dermatomyositis: An Update.

The idiopathic inflammatory myopathies of childhood consist of a heterogeneous group of autoimmune diseases characterised by proximal muscle weakness and pathognomonic skin rashes. The overall prognosis of juvenile myositis has improved significantly over recent years, but the long-term outcome differs substantially from patient to patient, suggestive of distinct clinical phenotypes with variable responses to treatment. High doses of corticosteroids remain the cornerstone of therapy along with other immunosuppressant therapies depending on disease severity and response. The advent of biological drugs has revolutionised the management of various paediatric rheumatologic diseases, including inflammatory myopathies. There are few data from randomised controlled trials to guide management decisions; thus, several algorithms for the treatment of juvenile myositis have been developed using international expert opinion. The general treatment goals now include elimination of active disease and normalisation of physical function, so as to preserve normal growth and development, and to prevent long-term damage and deformities. This review summarises the newer and possible future therapies of juvenile inflammatory myopathies, including evidence supporting their efficacy and safety.

Retinal Manifestations of Juvenile Dermatomyositis: Case Report of Bilateral Diffuse Chorioretinopathy with Paracentral Acute Middle Maculopathy and Review of the Literature

ABSTRACTPurpose: To review a case of bilateral diffuse chorioretinopathy as a presenting sign of juvenile dermatomyositis (JDM) and review the literature regarding retinal manifestations associated with this disease.Methods: Review of case record and literature regarding retinal manifestations related to juvenile dermatomyositis.Results: A 13-year-old girl presented with bilateral diffuse chorioretinopathy as the presenting sign of juvenile dermatomyositis. A review of the literature suggests that retinopathy associated with JDM is a rare finding that is symptomatic to patients and often responds to systemic treatment of juvenile dermatomyositis. This is also the first documented case of paracentral acute middle maculopathy in the setting of juvenile dermatomyositis.Conclusion: Chorioretinopathy is a rare finding in juvenile dermatomyositis. While all patients with JDM likely do not warrant screening ophthalmologic examinations, any patient who has visual symptoms should have a careful dilated examination to evaluate for retinopathy or steroid-induced cataracts.

Consensus-based recommendations for the management of juvenile dermatomyositis

BackgroundIn 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for...

Progress in the treatment of juvenile dermatomyositis

Progress in the treatment of juvenile dermatomyositis

SHARE – workpackage 5: evidence based recommendations for diagnosis and treatment of juvenile dermatomyositis

Juvenile Dermatomyositis is a rare Pediatric Rheumatic Disease, associated with significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician’s experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases.

PReS-FINAL-2130-A: Effectiveness of intravenous cyclophosphamide in severe or refractory juvenile dermatomyositis - a national cohort study UK and Ireland

Evidence suggests that early and aggressive treatment in Juvenile Dermatomyositis (JDM) improves outcome and prevents complications. Cyclophosphamide has been used as a second-line agent in the treatment of severe or refractory JDM. Published data on the effectiveness of cyclophosphamide in JDM are limited to a previous small case series and case reports.

PReS-FINAL-2013: Sodium thiosulfate for the treatment of Juvenile Dermatomyositis complicated by calcinosis

Juvenile Dermatomyositis (JDM) is an inflammatory myopathy with a predilection for proximal muscles and skin. Current treatment of JDM includes early aggressive use of corticosteroids coupled with immunosuppressive drugs such as methotrexate, cyclosporine and intravenous immune globulins (IVIG). Delay to diagnosis and inadequate treatment increase the risk of developing calcinosis. However, once estabilished, this complication is difficult to treat.

An update on the diagnosis and management of juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is a rare pediatric rheumatic disease. It belongs to the group of idiopathic inflammatory myopathies of childhood. JDM is the most frequent of the idiopathic inflammatory myopathies (it represents 85% of cases) among children. JDM is classified by the Bohan and Peter criteria set in 1975. New criteria are being developed and newly developed diagnostic tools are being used in daily clinical practice. This review focuses on recent publications regarding the epidemiology, pathogenesis, classification and treatment of JDM, and will discuss some relevant publications from the adult myositis literature.

A Retrospective Analysis of a Treatment Protocol of Juvenile Dermatomyositis with Intravenous Methylprednisolone, Intravenous Immunoglobulin, and Methotrexate (P07.219)

Objective: A retrospective study was conducted to assess the efficacy of treatment of juvenile dermatomyositis(JDM) patients with intravenous methylprednisolone(IVMP), intravenous immunoglobulin(IVIG), and methotrexate(MTX). Background JDM is an inflammatory myopathy causing proximal weakness and rash in addition to possible systemic complications including calcinosis. Treatment of JDM is limited by two main factors: 1) No current consensus of treatment and 2) Significant co morbidities of oral prednisone, a mainstay of treatment. Design/Methods: We conducted a chart review of 20 patients from the University of Mississippi Medical Center diagnosed with JDM between 2001 and 2011. The age at diagnosis ranged from 2 to 16 with an average age of 6. All patients had muscle biopsies to confirm their diagnosis and have been followed with manual muscle testing, CPK, modified Rankin scores, and MRIs of the lower extremities to track response to therapy. All were started on IVMP 30mg/kg/week and weekly IV MTX. If the patient responded to treatment based on the above evaluations, then the IVMP was tapered and discontinued when possible. The MTX was transitioned to oral dosing once the patient no longer required weekly IVMP. If the patients did not respond to therapy, then weekly IVIG 400mg/kg was added. Results: Fourteen of twenty patients improved with IVMP and MTX alone. The remaining 30% of patients required IVIG before their symptoms resolved. The patients who are now in remission with no medications (5/11) or with oral MTX alone (6/11)required treatment with IV medications for an average of 2.5 years. If the patients in remission experienced a flare of their symptoms (1/9), or if a patient had a flare of symptoms prior to remission (1/11), then IVIG and IVMP were dosed until the symptoms resolved. Conclusions: This study supports the efficacy of combination therapy with IVMP, MTX and IVIG for JDM to improve clinical outcomes and induce remission. Disclosure: Dr. Witt has nothing to disclose. Dr. Vedanarayanan has nothing to disclose. Dr. Ray has nothing to disclose. Dr. Haque has nothing to disclose.

Therapeutic approaches in the treatment of juvenile dermatomyositis in patients with recent-onset disease and in those experiencing disease flare: An international multicenter PRINTO study

To evaluate response to therapy over a 24-month period in a large prospective international cohort of patients with juvenile dermatomyositis (DM). The study included 145 patients with recent-onset juvenile DM and 130 juvenile DM patients experiencing disease flare, all of whom were <18 years old. Disease activity parameters and therapeutic approaches in 4 geographic areas were analyzed at baseline and at 6, 12, and 24 months. Response was assessed according to the Pediatric Rheumatology International Trials Organization (PRINTO) juvenile DM response criteria, and data were reported "as observed" and in the intent-to-treat (ITT) population. Patients with recent-onset juvenile DM at baseline had higher baseline disease activity and greater improvement over 24 months when compared to juvenile DM patients experiencing disease flare at baseline. Methotrexate (MTX) or high-dose corticosteroids were administered more frequently to patients with recent-onset juvenile DM, compared to juvenile DM patients experiencing disease flare, who were more likely to receive cyclosporine. Compared to patients from Western and Eastern Europe, a higher proportion of patients from South and Central America and North America received pulse steroids, and the average steroid dosage was higher in the North American and South and Central American patients. The use of MTX was similar in all 4 regions, while cyclosporin A was more frequently used in Western Europe. In the "as observed" analysis, 57.9% of the patients with recent-onset juvenile DM and 36.4% of the patients experiencing disease flare (P<0.001) reached at least a 70% response by PRINTO criteria at 6 months; these proportions had increased at month 24 to 78.4% and 51.2%, respectively (P<0.001). Corresponding results of the ITT analysis were much lower, with only one-third of the patients able to maintain the initial assigned therapy over 24 months. Patients with recent-onset juvenile DM are more likely to achieve significant clinical improvement over 24 months, when compared to patients experiencing flares of juvenile DM. Internationally, various therapeutic approaches are used to treat this disease.