RARE DISEASE
Juvenile dermatomyositis
Juvenile dermatomyositis
Juvenile dermatomyositis
Synonyms: Juvenile DM
Synonyms: Juvenile DM
Synonyms: Juvenile DM
Drug discovery
581
papers
On emerging therapies
Overview
Juvenile dermatomyositis (JDM) is a rare autoimmune vasculopathy characterized by chronic inflammation of proximal muscles and pathognomonic skin rashes (e.g., heliotrope rash, Gottron papules). It involves systemic vascular damage, leading to complications like calcinosis, dysphagia, and interstitial lung disease. Diagnosis combines clinical criteria (rash, muscle weakness), elevated muscle enzymes, MRI, and/or biopsy. Treatment focuses on immunosuppression (corticosteroids, methotrexate) and biologic therapies for refractory cases, alongside physical rehabilitation [1][6][11].
Burden
Hospitalization costs are 2–3× higher than non-JDM admissions, with longer stays in non-white populations [4][9].
Chronic complications: Calcinosis (20–40%), lipodystrophy (10%), and cardiovascular risks from prolonged steroid use [7][14][15].
Long-term morbidity: Up to 40% of patients have active disease >2 years; minority groups face persistent functional impairment [2][12][17].
Therapies
First-line: High-dose corticosteroids (e.g., prednisone) combined with methotrexate [3][6][16].
Refractory disease: Biologics (rituximab, abatacept), IV immunoglobulin, or cyclophosphamide [3][8][12].
Adjunctive: Physical therapy, sun protection (SPF 30+), and calcium/vitamin D supplementation [1][7][16].
Categories: rare neurological diseases, rare renal diseases, rare respiratory diseases, rare skin diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
581 drug discovery papers about Juvenile dermatomyositis, with 4 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
581 drug discovery papers about Juvenile dermatomyositis, with 4 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-22 | Engineered pediatric human muscle models the interferon-driven transcriptome of juvenile dermatomyositis
Abstract Juvenile dermatomyositis (JDM) is a rare pediatric autoimmune disease characterized by a strong type I interferon (IFN) signature in muscle. Mechanistic and therapeutic discovery has been limited by the lack of a clinically relevant disease model. To address this, we tested whether IFN treatment of a human muscle-derived microphysiological system (myobundles) recapitulates the transcriptional profile of JDM muscle. Principal component analysis of RNA sequencing from healthy and JDM muscle along with IFN-treated and untreated myobundles revealed separation of healthy and untreated samples from JDM and IFN-treated samples. JDM muscle exhibited 4,121 differentially expressed genes (DEGs, p adj <0.05) compared to healthy muscle, of which 56.2% showed concordant differential expression in IFNβ-treated and 30.0% in IFNα-treated myobundles. Hallmark pathway analysis demonstrated concordant directional changes between JDM muscle and IFN-treated myobundles. IFN and inflammatory pathways were most upregulated; oxidative phosphorylation, fatty acid metabolism, and adipogenesis were downregulated, though not reproducible across sites. Normalized enrichment score correlations between JDM muscle and IFN-treated myobundles were strongly positive ( r = 0.63, p =1 × 10 − 6 for IFNα; r = 0.67, p = 1.3 × 10 − 7 for IFNβ). These findings indicate that IFN-treated myobundles, particularly with IFNβ, mirror key transcriptional features of JDM muscle and provide a needed muscle-centric platform to study IFN-driven mechanisms and therapeutic targets.
2026-09-17 | Catching up with calcinosis: analysis of clinical characteristics, myositis-specific autoantibodies, and response to therapy in juvenile dermatomyositis.
This study aims to evaluate the clinical, laboratory, and treatment profiles of juvenile dermatomyositis (JDM) patients with calcinosis. A retrospective study was conducted at a tertiary-care referral centre in India (1992-2024), analysing JDM patients per modified Bohan and Peter criteria. Clinical data, myositis- specific autoantibody (MSA) profiles, and treatment details were compared between those with and without calcinosis. Calcinosis severity and treatment response were evaluated. Statistical analysis was performed using SPSS v. 29 software. Out of 157 JDM patients, 44 (28%) had calcinosis. These patients had a long diagnostic delay (12 months) and were more likely to be NXP2-positive (41%). Lipodystrophy was significantly associated with presence of calcinosis (39% vs. 5%). Severe calcinosis is linked to early age of onset of disease. Four children presented with calcinosis alone without clinically obvious skin or muscle disease, two of them were NXP2-positive. Patients with TIF1- gamma positivity predominantly had superficial calcinosis around large joints with skin ulceration, whereas NXP2 positivity had extensive and severe calcinosis. Among all patients with calcinosis, 39% improved while 61% had static/progressive disease. Analysis of drug response showed that the medications targeting calcium/phosphorus metabolism are linked to improvement in the calcinosis lesions over time. Calcinosis in JDM is associated with NXP2 autoantibody positivity and delayed diagnosis; however, severity correlates with early disease onset and specific MSA patterns. A subset of patients may present with calcinosis alone, underscoring diagnostic challenges. Drugs targeting calcium/phosphorus metabolism may be of benefit in reducing the severity of calcinosis in JDM.
2026-09-16 | Tissue calcinosis in dermatomyositis - potential role of combination therapy with JAK inhibitors. Case report and literature review
Calcinosis is a disabling and difficult-to-treat complication of adult dermatomyositis (DM), juvenile dermatomyositis (JDM), and systemic sclerosis (SSc), for which no standardized therapy is currently available. Growing evidence implicating JAK/STAT signaling in dermatomyositis has prompted interest in Janus kinase inhibitors (JAKi) as a therapeutic option. We describe a 52-year-old woman with long-standing juvenile-onset dermatomyositis and extensive, treatment-refractory calcinosis who received off-label baricitinib after multiple previous therapies. After one month, the patient reported improved general well-being and no new skin ulcerations. During the four-month treatment course, pre-existing microcytic anemia worsened and required blood transfusion, prompting discontinuation of baricitinib because a treatment-related contribution could not be excluded. This case provides a hypothesis-generating observation of possible early symptomatic benefit during JAK inhibition while highlighting the uncertainty regarding efficacy and safety. Prospective studies using standardized clinical, functional, imaging, and safety outcomes are required.
2026-09-15 | Clinical features and a Nomogram for predicting clinical response in juvenile dermatomyositis associated interstitial lung disease.
Juvenile dermatomyositis (JDM) is a rare autoimmune disease and accompany by interstitial lung disease (ILD), a major cause of morbidity and mortality. However, data on clinical features and prognosis of JDM-ILD in Chinese pediatric populations remain limited. The aim is to characterize the clinical features, treatment options and prognosis of JDM-ILD in Chinese pediatric patients, and to develop a nomogram for predicting clinical response. We retrospectively enrolled 244 JDM-ILD patients from Beijing Children's Hospital (May 2015-January 2026). Demographic, clinical, laboratory, treatment, and prognostic data were collected. Clinical response was assessed through a combination of PRINTO-defined clinical inactive disease (CID) , respiratory symptoms and HRCT. Independent prognostic factors were identified using Cox regression analysis and incorporated into a nomogram. Model performance was assessed using C-index, calibration curves and decision curve analysis (DCA). Among 244 patients (55.7% female, median onset age 5.7 years), anti-MDA5 (32.0%) and anti-NXP2 (13.9%) were the most prevalent autoantibodies. At last follow-up visit, 202 patients (82.8%) achieved CID, with CID rates increasing progressively over time. A total of three patients who tested positive for anti-MDA5 antibody died of RP-ILD (median survival 2.7 months). Multivariable Cox regression identified combination therapy with JAK inhibitors (HR 2.09, 95%CI 1.25-3.50) or IL-6 inhibitors (HR 1.83, 95%CI 1.07-3.12) and Gottron's sign (HR 1.80, 95%CI 1.10-2.96) as favorable factors for CID, while high-risk status (HR 0.23, 95%CI 0.10-0.57), higher DAS skin score (HR 0.71, 95%CI 0.48-1.00), and higher neutrophil-to-lymphocyte ratio (NLR) (HR 0.84, 95%CI 0.72-0.97) predicted lower probability of CID. The nomogram showed predictive performance in both training cohort (AUC: 0.67, 0.77, and 0.78 at 1, 3, and 5 years) and testing cohort (AUC: 0.60, 0.78 and 0.77 at 1, 3, and 5 years). This nomogram for predicting clinical response in Chinese pediatric JDM-ILD patients integrates clinical features and treatment variables to enable individualized risk stratification. Combination therapy with JAK or IL-6 inhibitors demonstrates promising efficacy and may improve outcomes.
2026-09-11 | Therapeutic expansion of JAK inhibitors in Chinese dermatological practice: beyond atopic dermatitis to novel autoimmune frontiers.
Janus kinase inhibitors (JAKi) have demonstrated clinical utility in managing atopic dermatitis (AD), yet their broader potential across immune-mediated dermatoses remains inadequately explored, particularly within China's restrictive regulatory landscape for dermatologic indications. This review examines pathogenic mechanisms and emerging evidence supporting JAKi repositioning in seven dermatological conditions beyond AD: alopecia areata (AA), vitiligo, psoriasis, dermatomyositis (DM), pemphigus, bullous pemphigoid (BP), and chronic spontaneous urticaria (CSU)-with emphasis on therapeutic gaps and opportunities specific to Chinese practice. We delineate disease-specific JAK-STAT dysregulation, including IFN-γ-driven cytotoxicity in AA/vitiligo, IL-23/STAT3 activation in psoriasis, and type I interferon hyperactivation in DM. Key clinical findings from rigorous trials indicate that oral tofacitinib achieves PASI75 in 58% of psoriatic patients within 16 weeks and topical ruxolitinib induces facial repigmentation exceeding 75% in vitiligo. In contrast, while current evidence is substantially limited to isolated case reports, emerging data suggest that baricitinib may resolve steroid-refractory BP lesions within one month. Persistent limitations include reliance on small-scale studies for pemphigus and CSU, along with unresolved safety concerns regarding thrombosis risks in susceptible populations. Crucially, we identify therapeutic gaps in segmental vitiligo and juvenile DM where clinical data are absent. This synthesis advocates for randomized controlled trials to validate JAKi efficacy against biologics in high-burden diseases currently dependent on glucocorticoids.
proteins
2025-06-27 | Efficacy and safety of rhGH in juvenile dermatomyositis children with glucocorticoid-related growth failure.
To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) in children with JDM experiencing glucocorticoid (GC)-induced growth failure. A retrospective cohort study included 16 refractory JDM patients treated with rhGH (0.10-0.15 IU/kg/day) for 6-24 months. Outcomes including height Z-score, growth velocity (GV), biochemical markers, disease activity and adverse events were recorded and analysed. After 6 months of rhGH treatment, the height Z-score improved from -2.37 ± 1.15 at baseline to -1.73 ± 1.06 (P < 0.001), and GV increased from 2.74 ± 1.53 cm/year to 13.05 ± 3.64 cm/year (P < 0.001). Serum insulin-like growth factor 1 and alkaline phosphatase levels rose significantly (from 264.13 ± 81.24-351.59 ± 123.41 ng/ml and 242.40 ± 42.25-318.70 ± 86.12 U/l, respectively; P < 0.05). Creatine kinase levels increased but remained within the normal range (from 79.33 ± 27.56-111.60 ± 42.84 U/l; P < 0.01). Only one patient (1/16, 6.25%) experienced JDM relapse, a rate lower than the reported recurrence rate (31.6%) in JDM patients not receiving rhGH treatment. No adverse metabolic or endocrine effects were observed. In JDM patients with growth failure, rhGH therapy may be considered as a potential treatment option, supported by preliminary evidence. Our study suggests an acceptable safety profile and potential efficacy in improving growth parameters, even in refractory cases. Further larger-scale multicentre studies will be necessary to confirm its application value in JDM.
2025-03-12 | Effect of abatacept added to mycophenolate mofetil for refractory calcinosis in juvenile dermatomyositis.
Calcinosis is an intractable condition in juvenile dermatomyositis (JDM). The effect of abatacept on calcinosis remains controversial. We describe a case of an 8-year-old boy in whom the addition of abatacept to mycophenolate mofetil was effective against calcinosis in JDM. The patient with antinuclear matrix protein 2 autoantibody suffered from refractory jJDM despite long-term treatment with corticosteroids and various immunosuppressive agents. Subcutaneous calcinosis with repeated spontaneous pain at the calcinosis site emerged 2 years after the start of treatment and gradually increased despite clinical improvement in muscle symptoms. The addition of intravenous abatacept to mycophenolate mofetil at the age of 6 years halted the increase in calcinosis. Spontaneous pain in calcinosis disappeared within 2 months. The calcinosis had significantly decreased by 1 year. An important strategy on calcinosis in JDM is getting complete control of the inflammation. Our case report suggests that abatacept may contribute to the improvement of calcinosis in JDM, at least as part of combination therapy with mycophenolate mofetil.
2024-01-17 | Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study
Abstract Background Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study. Methods ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0–16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16–40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented. Results The 95 patients enrolled were randomised to receive IVIg ( N = 47) or placebo ( N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4–15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred. Conclusions Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors. Trial registration ProDERM study (NCT02728752).
2023-11-05 | A Case of Anti-NXP2 Antibody-positive Juvenile Dermatomyositis with Characteristic Fascial Thickening on Muscle Ultrasound and Improvement with Immunotherapy
We herein report a 12-year-old boy who presented with a fever, erythematous rash on the cheeks, back pain, and dysphagia. Blood tests revealed increased creatine kinase levels, and muscle ultrasonography (MUS) revealed characteristic fascial thickening in the lumbar paraspinal muscles, where myalgia was prominent. Sarcoplasmic expression of myxovirus-resistant protein A on a muscle biopsy and the presence of anti-nuclear matrix protein 2 (NXP2) antibodies confirmed the diagnosis of dermatomyositis. Prednisolone and intravenous immunoglobulin therapy improved the clinical and laboratory parameters as well as fascial thickening. MUS is useful for evaluating fasciitis associated with anti-NXP2 autoantibodies and monitoring therapeutic efficacy.
2023-10-01 | Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study
Dermatomyositis (DM) is a rare autoimmune disease characterized by skin involvement, with or without proximal muscle weakness. Recently, following the ProDERM study, intravenous immunoglobulin (IVIg) was approved for treatment of DM. Until ProDERM evidence from large, placebo-controlled studies supporting its use for dermatological symptoms, was lacking. Here we present efficacy data from ProDERM of IVIg versus placebo for treatment of the cutaneous aspect of DM.ProDERM was a double-blind, randomized, multicenter, Phase 3 study. In the First Period (Weeks 0-16), adults with active DM received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label Extension Period (Weeks 16-40), all patients received IVIg for 6 additional cycles. Cutaneous disease was assessed using measures including modified cutaneous DM disease area and severity index activity (CDASI-A) and damage (CDASI-D) scores, and myositis disease activity assessment tool (MDAAT) including visual analogue scale (VAS). This trial is registered with ClinicalTrials.gov, NCT02728752.The study took place from February 2017 to November 2019. 95 patients received IVIg (N = 47) or placebo (N = 48) in the First Period. Together, 664 IVIg infusion cycles were administered (median dose, 2.0 g/kg). At Week 16, mean CDASI-A change from baseline was -9.36 (95% CI: -12.52, -6.19) in the IVIg group versus -1.16 (-3.32, 0.99) in placebo group (p < 0.0001). At the end of the Extension Period, mean changes from baseline were -10.44 (95% CI: -13.94, -6.94) and -10.03 (-13.12, -6.94), respectively. Similar changes were seen for CDASI-D and VAS of MDAAT. These observations were seen regardless of baseline disease severity.ProDERM is the first large prospective, randomized trial to demonstrate the efficacy of IVIg to improve the cutaneous manifestations of DM. IVIg treatment significantly improved dermatological symptoms in patients with DM, regardless of disease severity before treatment, suggesting that IVIg is effective for even the most severe cutaneous DM.This study was sponsored by Octapharma Pharmazeutika Produktionsges m.b.H.
antibodies
2026-07-31 | Juvenile Dermatomyositis: A Review of the Literature
Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy of childhood, characterized by proximal muscle weakness, pathognomonic cutaneous findings, and multisystem involvement. Over the past decade, significant advances have been made in pathogenesis and treatment of JDM. This review provides a comprehensive update on the etiopathogenesis, clinical features, autoantibody profiles, and treatment of JDM. Type I interferon signaling, vasculopathy, and mitochondrial dysfunction have emerged as interconnected pathogenic mechanisms, and their identification has informed the development of targeted therapeutic strategies. In particular, elucidation of the type I interferon pathway has contributed to disease diagnosis, monitoring of disease activity through interferon-related biomarkers, and the development of novel targeted therapies. Myositis-specific autoantibodies (MSA), detected in approximately 70% of patients, define clinically distinct subgroups; for example, anti-NXP2 is associated with calcinosis, and anti-MDA5 positivity carries a risk of interstitial lung disease. Importantly, MSA subtype influences not only clinical phenotype but also treatment response, underscoring the value of systematic autoantibody testing in guiding therapeutic decisions. A treat-to-target approach and close monitoring of disease activity are recommended. In refractory disease, conventional immunosuppressants and biologic agents are escalated sequentially, with Janus kinase (JAK) inhibitors targeting the type I interferon pathway. More selective interferon blockade with anifrolumab and next-generation B-cell depletion with chimeric antigen receptor T-cell (CAR-T) cell therapy represent emerging options for patients with refractory disease. Calcinosis remains without a standardized treatment procedure, and evidence-based management is limited by the lack of pediatric randomized controlled trials. Prospective, multicenter studies are needed to establish treatment algorithms and improve long-term outcomes in this rare disease. Cite this article as: Aslan E, Kisla Ekinci RM, Torunoglu Z, Akay N, Kasapcopur O. Juvenile dermatomyositis: A review of the literature. ArchRheumatol. Published online July 31, 2026. doi: 10.5152/ArchRheumatol.2026.26552.
2026-07-10 | Vedolizumab as a rescue therapy for severe gastrointestinal involvement in anti-NXP2 positive juvenile dermatomyositis
Şengül Çağlayan, Ulaş Emre Akbulut, Tangül Pınarcı, Muhammed Gültekin Kutluk, Hasan Serdar Kıhtır; Vedolizumab as a rescue therapy for severe gastrointesti
2026-05-25 | Reversibility of calcinosis in anti-NXP2-positive refractory dermatomyositis treated with TNF-α blockade: a brief report.
Calcinosis cutis is one of the most refractory complications of dermatomyositis (DM), particularly in patients with anti-nuclear matrix protein 2 (NXP2) autoantibodies. Whether tumor necrosis factor-alpha (TNF-α) blockade is associated with regression of established calcinosis remains uncertain. We conducted a retrospective, single-center study of nine patients with refractory dermatomyositis or juvenile dermatomyositis treated with TNF-α inhibitors (infliximab or adalimumab). Myositis-specific autoantibodies, longitudinal muscle strength (MMT8, CMAS), glucocorticoid exposure, and serial imaging of calcinosis were evaluated. Calcinosis change was analyzed as an exploratory endpoint. Three patients were anti-NXP2 positive, and six were negative for tested myositis-specific autoantibodies. TNF-α blockade was associated with sustained clinical improvement and a marked steroid-sparing effect, with median daily prednisolone dose decreasing from 40 mg at baseline to 5 mg at 12 months. Radiographic regression of calcinosis, defined a priori as a ≥20% reduction in maximal lesion diameter on serial imaging, was observed in 2 of 3 anti-NXP2-positive patients after prolonged treatment (12-20 months): notably, calcinosis was absent at baseline in all anti-NXP2-negative patients, precluding assessment of regression in this subgroup. One patient with pre-existing interstitial lung abnormalities experienced pulmonary deterioration, leading to treatment discontinuation. In this small retrospective cohort, prolonged TNF-α blockade was associated with radiographic regression of calcinosis in a subset of anti-NXP2-positive patients, while calcinosis was absent at baseline in antibody-negative patients. These findings generate a hypothesis that antibody-defined subgroups may differ in calcinosis responsiveness and warrant prospective validation.
2026-03-28 | Transaminitis as the initial presentation of anti-MDA5 positive juvenile dermatomyositis: A case report
Anti-MDA5 positive JDM is associated with rapidly progressive ILD, causing high morbidity and mortality. We present a case of a child with anti-MDA5 positive JDM who presented with transaminitis and elevated CPK, leading to an original diagnosis of infective myositis of multiple sites. Seven days after the initial encounter, the patient returned with classic JDM symptoms of skin erosions, heliotrope rash, and Gottron’s papules, leading to a diagnosis of anti-MDA5 positive JDM with ILD. Why should an emergency physician be aware of this? Liver dysfunction is a growing concern among anti-MDA5 positive JDM and may be associated with risk factors that lead to poorer prognosis. Because this patient did not originally present with classic skin findings of JDM, diagnosis and treatment of her condition was delayed. Early identification of anti-MDA5 positive JDM is crucial to prevent rapidly progressive ILD.
2026-02-01 | Lung Involvement in MDA5‐Positive Juvenile Dermatomyositis: A Case of Misdiagnosed Pneumonia in a Toddler
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
cell therapies
2026-05-11 | Case Report: Juvenile dermatomyositis complicated by acute myeloid leukemia: achievement of sustained remission through hematopoietic stem cell transplantation.
Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron's papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.
2026-04-03 | CAR T-cell therapy and indications for pediatric rheumatology: Structured overview of applications, risks, and considerations.
This chapter offers an overview of CAR T-cell therapy and its emerging role in pediatric rheumatology, particularly the potential impact on severe refractory autoimmune conditions in children. It examines criteria for patient eligibility, safety concerns, and potential long-term effects for young rheumatology patients, while stressing the importance of personalized and prolonged follow-up. The possibility of achieving drug-free remission in pediatric cases appears to be a possible in refractory patients; however, further studies should focus on standardizing pre-treatment protocols for children with rheumatic diseases, reducing the intensity of conditioning regimens, and implementing extended surveillance to assess therapy duration and lasting outcomes.
2025-11-14 | Juvenile dermatomyositis: new insights into pathogenesis and clinical applications.
Juvenile dermatomyositis (JDM), the most common inflammatory myopathy of childhood, is a complex autoimmune condition with significant disease burden and variable treatment responses. While conventional immunosuppression remains standard, advances in immunopathology are revealing new therapeutic and biomarker opportunities. This review provides emerging insights into JDM pathogenesis. Interferon (IFN)-stimulated gene (ISG) expression, and IFN-related emerging biomarkers which may be valuable for monitoring disease activity and treatment response. Mitochondrial dysfunction, involving oxidative stress and oxidized mtDNA, contributes to systemic pathology and offers new therapeutic targets. Other critical pathogenic processes include pyroptosis, neutrophil extracellular traps, and abnormal B-cell activity. Novel treatments targeting IFN pathways, B cells, and mitochondrial oxidation are under investigation. CAR T-cell therapies have shown early promise in refractory cases. Ongoing research is transforming our understanding of JDM, enabling biomarker-driven precision medicine and targeted therapies. These advances offer the potential to improve outcomes and achieve durable remission, even in refractory or high-risk disease subsets.
2025-11-10 | Therapeutic plasma exchange in autoimmune diseases: a retrospective study in a tertiary pediatric hospital in Mexico.
To describe the use and mortality-associated factors of therapeutic plasma exchange (TPE) in children with autoimmune diseases at a tertiary pediatric hospital in Mexico. Retrospective cross-sectional study including patients under 18 years old with autoimmune diseases who underwent TPE between 2022 and 2025 at the Hospital Infantil de México Federico Gómez. Demographic, clinical, therapeutic, and laboratory data were analyzed. Clinical response and mortality-associated factors were assessed. Forty-one patients were included (68% female; median age: 12 years). The most frequent indications for TPE were systemic lupus erythematosus (SLE) (56.1%) and autoimmune encephalitis (14.6%). Other diagnoses included macrophage activation syndrome (MAS) (n = 3), overlap syndromes (n = 3), juvenile dermatomyositis (n = 2), and single cases of ANCA-associated vasculitis, Takayasu arteritis, antiphospholipid syndrome (APS), and Kawasaki disease. Complete or partial remission was achieved in 85.4% of cases, with variable responses depending on the underlying condition. TPE was well tolerated, with few adverse events. Overall mortality was 14.6% (n = 6), all due to sepsis (p < 0.001). Deceased patients had higher pre-TPE levels of CRP, procalcitonin, and ferritin, though not statistically significant. Longer disease duration was significantly associated with increased mortality in both univariable (OR 1.05, 95% CI 1.01-1.10; p = 0.04) and multivariable analysis adjusted for age, sex, and SLE diagnosis (OR 1.06; 95% CI 1.01-1.14; p = 0.04). Among SLE patients without sepsis, MEX-SLEDAI scores improved significantly. TPE was safe and beneficial in children with severe autoimmune diseases. Mortality was related to disease duration rather than the procedure itself.
2025-07-03 | CAR T cell therapy for children with rheumatic disease: the time is now.
Initial success with B cell-targeted chimeric antigen receptor (CAR) T cells for the treatment of systemic lupus erythematosus and other rheumatic diseases has generated enthusiasm for the broad application of this technology outside of the field of oncology. Paediatric patients with severe rheumatic diseases require lifelong therapy with a substantial toxicity burden and a high cost of care. Paradigm-shifting treatments, including CAR T cells, are desperately needed. Although CAR T cell therapy shows promise for paediatric rheumatic diseases, there are unique aspects of care compared with adults, which require careful consideration and expertise. In response, we established the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group, comprising international experts in the fields of paediatric rheumatology, oncology and cellular therapy, immunology and nephrology, to address the challenges of introducing cell therapies to patients with paediatric-onset autoimmune diseases. Given the possible benefits, we advocate for the study of CAR T cells in paediatric patients with rheumatic diseases who carry a lifelong risk of morbidity and mortality from chronic illness and medication toxicity. As this patient population is relatively small, consensus around definitions of success, robust study of predictors of response and uniform assessment and reporting of toxicities are critical to advancing the field.
other
2023-04-20 | Single-cell profiling of peripheral blood and muscle cells reveals inflammatory features of juvenile dermatomyositis
Introduction: Juvenile dermatomyositis (JDM) is a rare yet serious childhood systemic autoimmune condition that primarily causes skin rashes and inflammatory myopathy of the proximal muscles. Although the associated immune response involves the innate and adaptive arms, a detailed analysis of the pertinent immune cells remains to be performed. This study aims to investigate the dynamic changes of cell type, cell composition and transcriptional profiles in peripheral blood and muscle tissues, and in order to clarify the involvement of immune cells in the pathogenesis of JDM and provide a theoretical reference for JDM. Methods: Single-cell RNA sequencing combined with bioinformatic analyses were used to investigate the dynamic changes in cell composition and transcriptional profiles. Results: Analysis of 45,859 cells revealed nine and seven distinct cell subsets in the peripheral blood and muscle tissues respectively. IFITM2+ and CYP4F3+ monocytes were largely produced, and CD74 + smooth muscle cells (SMCs) and CCL19+ fibroblasts were identified as inflammatory-related cell subtypes in JDM patients, exhibiting patient-specific cell population heterogeneity.The dynamic gene expression patterns presented an enhanced type I interferon response in peripheral blood monocytes and T-cells, and SMCs and fibroblasts in muscle of untreated JDM patients. EGR1 and IRF7 may play central roles in the inflammation in both CD74 + SMCs and CCL19+ fibroblasts. Moreover, inflammatory-related monocytes could regulate T-cells, and the interaction between immune cells and SMCs or fibroblasts in muscle was enhanced under the inflammatory state. Conclusions: Immune dysregulation is one of the key pathogenic factors of JDM, and type I interferon responses are significantly enhanced in peripheral blood Monos and T cells as well as SMCs and fibroblasts. EGR1 and IRF7 may play central roles in the inflammation and are considered as potential therapeutic targets for JDM.
2021-09-18 | Identification of Vital Hub Genes and Potential Molecular Pathways of Dermatomyositis by Bioinformatics Analysis
Dermatomyositis is an autoimmune disease characterized by severe symmetrical muscle dysfunction and pain. This study was aimed at discovering vital hub genes and potential molecular pathways of DM through bioinformatics analysis, which contributes to identifying potential diagnostic or therapeutic biomarkers and targets. In this study, a total of 915 DEGs in DM samples including 167 upregulated genes and 748 downregulated genes were screened out by the limma package based on the GSE142807 dataset from the Gene Expression Omnibus (GEO) database. Furthermore, the results of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that these downregulated genes were highly associated with the immune-related biological processes and pathways. Therefore, 41 genes closely related to DM were extracted for further study based on the subcluster analysis through the Molecular Complex Detection (MCODE) software plugin in Cytoscape. Ultimately, 10 hub genes (including ISG15, DDX58, IFIT3, CXCL10, and STAT1) were identified as the potential candidate biomarkers and targets. Besides, we found that the identified hub genes directly or indirectly communicated with each other via molecular signaling pathways on the protein and transcription level. In general, under the guidance of bioinformatics analysis, 10 vital hub genes and molecular mechanisms in DM were identified and the expression of proinflammatory factors and interferon family proteins and genes showed high association with DM, which might help provide a theoretical foundation for the development of point-to-point targeted therapy in the future treatment of DM.
2020-04-06 | Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies
Abstract Background Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with a prominent interferon (IFN) signature, but the pathogenesis of JDM and the etiology of its IFN signature remain unknown. The Mendelian autoinflammatory interferonopathies, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) and STING-Associated Vasculopathy with onset in Infancy (SAVI), are caused by genetic mutations and have extremely elevated IFN signatures thought to drive pathology. The phenotypic overlap of some clinical features of CANDLE and SAVI with JDM led to the comparison of a standardized interferon-regulated gene score (IRG-S) in JDM and myositis-specific autoantibody (MSA) JDM subgroups, with CANDLE and SAVI. Methods A peripheral 28-component IRG-S assessed by NanoString™ in 57 JDM patients subtyped by MSA was compared with IRG-S in healthy controls (HC) and CANDLE/SAVI patients. Principal component analysis (PCA) was performed, and individual genes were evaluated for their contribution to the score. IRG-S were correlated with disease assessments and patient characteristics. Results IRG-S in JDM patients were significantly higher than in HC but lower than in CANDLE or SAVI. JDM IRG-S overlapped more with SAVI than CANDLE by PCA. Among MSA groups, anti-MDA5 autoantibody-positive patients’ IRG-S overlapped most with SAVI. The IFI27 proportion was significantly higher in SAVI and CANDLE than JDM, but IFIT1 contributed more to IRG-S in JDM. Overall, the contribution of individual interferon-regulated genes (IRG) in JDM was more similar to SAVI. IRG-S correlated moderately with JDM disease activity measures ( r s = 0.33–0.47) and more strongly with skin activity ( r s = 0.58–0.79) in anti-TIF1 autoantibody-positive patients. Weakness and joint disease activity (multinomial OR 0.91 and 3.3) were the best predictors of high IRG-S. Conclusions Our findings demonstrate peripheral IRG expression in JDM overlaps with monogenic interferonopathies, particularly SAVI, and correlates with disease activity. Anti-MDA5 autoantibody-positive JDM IRG-S were notably more similar to SAVI. This may reflect both a shared IFN signature, which is driven by IFN-β and STING pathways in SAVI, as well as the shared phenotype of vasculopathy in SAVI and JDM, particularly in anti-MDA5 autoantibody-positive JDM, and indicate potential therapeutic targets for JDM.
small molecules
2026-09-22 | Engineered pediatric human muscle models the interferon-driven transcriptome of juvenile dermatomyositis
Abstract Juvenile dermatomyositis (JDM) is a rare pediatric autoimmune disease characterized by a strong type I interferon (IFN) signature in muscle. Mechanistic and therapeutic discovery has been limited by the lack of a clinically relevant disease model. To address this, we tested whether IFN treatment of a human muscle-derived microphysiological system (myobundles) recapitulates the transcriptional profile of JDM muscle. Principal component analysis of RNA sequencing from healthy and JDM muscle along with IFN-treated and untreated myobundles revealed separation of healthy and untreated samples from JDM and IFN-treated samples. JDM muscle exhibited 4,121 differentially expressed genes (DEGs, p adj <0.05) compared to healthy muscle, of which 56.2% showed concordant differential expression in IFNβ-treated and 30.0% in IFNα-treated myobundles. Hallmark pathway analysis demonstrated concordant directional changes between JDM muscle and IFN-treated myobundles. IFN and inflammatory pathways were most upregulated; oxidative phosphorylation, fatty acid metabolism, and adipogenesis were downregulated, though not reproducible across sites. Normalized enrichment score correlations between JDM muscle and IFN-treated myobundles were strongly positive ( r = 0.63, p =1 × 10 − 6 for IFNα; r = 0.67, p = 1.3 × 10 − 7 for IFNβ). These findings indicate that IFN-treated myobundles, particularly with IFNβ, mirror key transcriptional features of JDM muscle and provide a needed muscle-centric platform to study IFN-driven mechanisms and therapeutic targets.
2026-09-17 | Catching up with calcinosis: analysis of clinical characteristics, myositis-specific autoantibodies, and response to therapy in juvenile dermatomyositis.
This study aims to evaluate the clinical, laboratory, and treatment profiles of juvenile dermatomyositis (JDM) patients with calcinosis. A retrospective study was conducted at a tertiary-care referral centre in India (1992-2024), analysing JDM patients per modified Bohan and Peter criteria. Clinical data, myositis- specific autoantibody (MSA) profiles, and treatment details were compared between those with and without calcinosis. Calcinosis severity and treatment response were evaluated. Statistical analysis was performed using SPSS v. 29 software. Out of 157 JDM patients, 44 (28%) had calcinosis. These patients had a long diagnostic delay (12 months) and were more likely to be NXP2-positive (41%). Lipodystrophy was significantly associated with presence of calcinosis (39% vs. 5%). Severe calcinosis is linked to early age of onset of disease. Four children presented with calcinosis alone without clinically obvious skin or muscle disease, two of them were NXP2-positive. Patients with TIF1- gamma positivity predominantly had superficial calcinosis around large joints with skin ulceration, whereas NXP2 positivity had extensive and severe calcinosis. Among all patients with calcinosis, 39% improved while 61% had static/progressive disease. Analysis of drug response showed that the medications targeting calcium/phosphorus metabolism are linked to improvement in the calcinosis lesions over time. Calcinosis in JDM is associated with NXP2 autoantibody positivity and delayed diagnosis; however, severity correlates with early disease onset and specific MSA patterns. A subset of patients may present with calcinosis alone, underscoring diagnostic challenges. Drugs targeting calcium/phosphorus metabolism may be of benefit in reducing the severity of calcinosis in JDM.
2026-09-16 | Tissue calcinosis in dermatomyositis - potential role of combination therapy with JAK inhibitors. Case report and literature review
Calcinosis is a disabling and difficult-to-treat complication of adult dermatomyositis (DM), juvenile dermatomyositis (JDM), and systemic sclerosis (SSc), for which no standardized therapy is currently available. Growing evidence implicating JAK/STAT signaling in dermatomyositis has prompted interest in Janus kinase inhibitors (JAKi) as a therapeutic option. We describe a 52-year-old woman with long-standing juvenile-onset dermatomyositis and extensive, treatment-refractory calcinosis who received off-label baricitinib after multiple previous therapies. After one month, the patient reported improved general well-being and no new skin ulcerations. During the four-month treatment course, pre-existing microcytic anemia worsened and required blood transfusion, prompting discontinuation of baricitinib because a treatment-related contribution could not be excluded. This case provides a hypothesis-generating observation of possible early symptomatic benefit during JAK inhibition while highlighting the uncertainty regarding efficacy and safety. Prospective studies using standardized clinical, functional, imaging, and safety outcomes are required.
2026-09-15 | Clinical features and a Nomogram for predicting clinical response in juvenile dermatomyositis associated interstitial lung disease.
Juvenile dermatomyositis (JDM) is a rare autoimmune disease and accompany by interstitial lung disease (ILD), a major cause of morbidity and mortality. However, data on clinical features and prognosis of JDM-ILD in Chinese pediatric populations remain limited. The aim is to characterize the clinical features, treatment options and prognosis of JDM-ILD in Chinese pediatric patients, and to develop a nomogram for predicting clinical response. We retrospectively enrolled 244 JDM-ILD patients from Beijing Children's Hospital (May 2015-January 2026). Demographic, clinical, laboratory, treatment, and prognostic data were collected. Clinical response was assessed through a combination of PRINTO-defined clinical inactive disease (CID) , respiratory symptoms and HRCT. Independent prognostic factors were identified using Cox regression analysis and incorporated into a nomogram. Model performance was assessed using C-index, calibration curves and decision curve analysis (DCA). Among 244 patients (55.7% female, median onset age 5.7 years), anti-MDA5 (32.0%) and anti-NXP2 (13.9%) were the most prevalent autoantibodies. At last follow-up visit, 202 patients (82.8%) achieved CID, with CID rates increasing progressively over time. A total of three patients who tested positive for anti-MDA5 antibody died of RP-ILD (median survival 2.7 months). Multivariable Cox regression identified combination therapy with JAK inhibitors (HR 2.09, 95%CI 1.25-3.50) or IL-6 inhibitors (HR 1.83, 95%CI 1.07-3.12) and Gottron's sign (HR 1.80, 95%CI 1.10-2.96) as favorable factors for CID, while high-risk status (HR 0.23, 95%CI 0.10-0.57), higher DAS skin score (HR 0.71, 95%CI 0.48-1.00), and higher neutrophil-to-lymphocyte ratio (NLR) (HR 0.84, 95%CI 0.72-0.97) predicted lower probability of CID. The nomogram showed predictive performance in both training cohort (AUC: 0.67, 0.77, and 0.78 at 1, 3, and 5 years) and testing cohort (AUC: 0.60, 0.78 and 0.77 at 1, 3, and 5 years). This nomogram for predicting clinical response in Chinese pediatric JDM-ILD patients integrates clinical features and treatment variables to enable individualized risk stratification. Combination therapy with JAK or IL-6 inhibitors demonstrates promising efficacy and may improve outcomes.
2026-09-11 | Therapeutic expansion of JAK inhibitors in Chinese dermatological practice: beyond atopic dermatitis to novel autoimmune frontiers.
Janus kinase inhibitors (JAKi) have demonstrated clinical utility in managing atopic dermatitis (AD), yet their broader potential across immune-mediated dermatoses remains inadequately explored, particularly within China's restrictive regulatory landscape for dermatologic indications. This review examines pathogenic mechanisms and emerging evidence supporting JAKi repositioning in seven dermatological conditions beyond AD: alopecia areata (AA), vitiligo, psoriasis, dermatomyositis (DM), pemphigus, bullous pemphigoid (BP), and chronic spontaneous urticaria (CSU)-with emphasis on therapeutic gaps and opportunities specific to Chinese practice. We delineate disease-specific JAK-STAT dysregulation, including IFN-γ-driven cytotoxicity in AA/vitiligo, IL-23/STAT3 activation in psoriasis, and type I interferon hyperactivation in DM. Key clinical findings from rigorous trials indicate that oral tofacitinib achieves PASI75 in 58% of psoriatic patients within 16 weeks and topical ruxolitinib induces facial repigmentation exceeding 75% in vitiligo. In contrast, while current evidence is substantially limited to isolated case reports, emerging data suggest that baricitinib may resolve steroid-refractory BP lesions within one month. Persistent limitations include reliance on small-scale studies for pemphigus and CSU, along with unresolved safety concerns regarding thrombosis risks in susceptible populations. Crucially, we identify therapeutic gaps in segmental vitiligo and juvenile DM where clinical data are absent. This synthesis advocates for randomized controlled trials to validate JAKi efficacy against biologics in high-burden diseases currently dependent on glucocorticoids.
proteins
2025-06-27 | Efficacy and safety of rhGH in juvenile dermatomyositis children with glucocorticoid-related growth failure.
To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) in children with JDM experiencing glucocorticoid (GC)-induced growth failure. A retrospective cohort study included 16 refractory JDM patients treated with rhGH (0.10-0.15 IU/kg/day) for 6-24 months. Outcomes including height Z-score, growth velocity (GV), biochemical markers, disease activity and adverse events were recorded and analysed. After 6 months of rhGH treatment, the height Z-score improved from -2.37 ± 1.15 at baseline to -1.73 ± 1.06 (P < 0.001), and GV increased from 2.74 ± 1.53 cm/year to 13.05 ± 3.64 cm/year (P < 0.001). Serum insulin-like growth factor 1 and alkaline phosphatase levels rose significantly (from 264.13 ± 81.24-351.59 ± 123.41 ng/ml and 242.40 ± 42.25-318.70 ± 86.12 U/l, respectively; P < 0.05). Creatine kinase levels increased but remained within the normal range (from 79.33 ± 27.56-111.60 ± 42.84 U/l; P < 0.01). Only one patient (1/16, 6.25%) experienced JDM relapse, a rate lower than the reported recurrence rate (31.6%) in JDM patients not receiving rhGH treatment. No adverse metabolic or endocrine effects were observed. In JDM patients with growth failure, rhGH therapy may be considered as a potential treatment option, supported by preliminary evidence. Our study suggests an acceptable safety profile and potential efficacy in improving growth parameters, even in refractory cases. Further larger-scale multicentre studies will be necessary to confirm its application value in JDM.
2025-03-12 | Effect of abatacept added to mycophenolate mofetil for refractory calcinosis in juvenile dermatomyositis.
Calcinosis is an intractable condition in juvenile dermatomyositis (JDM). The effect of abatacept on calcinosis remains controversial. We describe a case of an 8-year-old boy in whom the addition of abatacept to mycophenolate mofetil was effective against calcinosis in JDM. The patient with antinuclear matrix protein 2 autoantibody suffered from refractory jJDM despite long-term treatment with corticosteroids and various immunosuppressive agents. Subcutaneous calcinosis with repeated spontaneous pain at the calcinosis site emerged 2 years after the start of treatment and gradually increased despite clinical improvement in muscle symptoms. The addition of intravenous abatacept to mycophenolate mofetil at the age of 6 years halted the increase in calcinosis. Spontaneous pain in calcinosis disappeared within 2 months. The calcinosis had significantly decreased by 1 year. An important strategy on calcinosis in JDM is getting complete control of the inflammation. Our case report suggests that abatacept may contribute to the improvement of calcinosis in JDM, at least as part of combination therapy with mycophenolate mofetil.
2024-01-17 | Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study
Abstract Background Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study. Methods ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0–16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16–40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented. Results The 95 patients enrolled were randomised to receive IVIg ( N = 47) or placebo ( N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4–15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred. Conclusions Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors. Trial registration ProDERM study (NCT02728752).
2023-11-05 | A Case of Anti-NXP2 Antibody-positive Juvenile Dermatomyositis with Characteristic Fascial Thickening on Muscle Ultrasound and Improvement with Immunotherapy
We herein report a 12-year-old boy who presented with a fever, erythematous rash on the cheeks, back pain, and dysphagia. Blood tests revealed increased creatine kinase levels, and muscle ultrasonography (MUS) revealed characteristic fascial thickening in the lumbar paraspinal muscles, where myalgia was prominent. Sarcoplasmic expression of myxovirus-resistant protein A on a muscle biopsy and the presence of anti-nuclear matrix protein 2 (NXP2) antibodies confirmed the diagnosis of dermatomyositis. Prednisolone and intravenous immunoglobulin therapy improved the clinical and laboratory parameters as well as fascial thickening. MUS is useful for evaluating fasciitis associated with anti-NXP2 autoantibodies and monitoring therapeutic efficacy.
2023-10-01 | Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study
Dermatomyositis (DM) is a rare autoimmune disease characterized by skin involvement, with or without proximal muscle weakness. Recently, following the ProDERM study, intravenous immunoglobulin (IVIg) was approved for treatment of DM. Until ProDERM evidence from large, placebo-controlled studies supporting its use for dermatological symptoms, was lacking. Here we present efficacy data from ProDERM of IVIg versus placebo for treatment of the cutaneous aspect of DM.ProDERM was a double-blind, randomized, multicenter, Phase 3 study. In the First Period (Weeks 0-16), adults with active DM received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label Extension Period (Weeks 16-40), all patients received IVIg for 6 additional cycles. Cutaneous disease was assessed using measures including modified cutaneous DM disease area and severity index activity (CDASI-A) and damage (CDASI-D) scores, and myositis disease activity assessment tool (MDAAT) including visual analogue scale (VAS). This trial is registered with ClinicalTrials.gov, NCT02728752.The study took place from February 2017 to November 2019. 95 patients received IVIg (N = 47) or placebo (N = 48) in the First Period. Together, 664 IVIg infusion cycles were administered (median dose, 2.0 g/kg). At Week 16, mean CDASI-A change from baseline was -9.36 (95% CI: -12.52, -6.19) in the IVIg group versus -1.16 (-3.32, 0.99) in placebo group (p < 0.0001). At the end of the Extension Period, mean changes from baseline were -10.44 (95% CI: -13.94, -6.94) and -10.03 (-13.12, -6.94), respectively. Similar changes were seen for CDASI-D and VAS of MDAAT. These observations were seen regardless of baseline disease severity.ProDERM is the first large prospective, randomized trial to demonstrate the efficacy of IVIg to improve the cutaneous manifestations of DM. IVIg treatment significantly improved dermatological symptoms in patients with DM, regardless of disease severity before treatment, suggesting that IVIg is effective for even the most severe cutaneous DM.This study was sponsored by Octapharma Pharmazeutika Produktionsges m.b.H.
antibodies
2026-07-31 | Juvenile Dermatomyositis: A Review of the Literature
Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy of childhood, characterized by proximal muscle weakness, pathognomonic cutaneous findings, and multisystem involvement. Over the past decade, significant advances have been made in pathogenesis and treatment of JDM. This review provides a comprehensive update on the etiopathogenesis, clinical features, autoantibody profiles, and treatment of JDM. Type I interferon signaling, vasculopathy, and mitochondrial dysfunction have emerged as interconnected pathogenic mechanisms, and their identification has informed the development of targeted therapeutic strategies. In particular, elucidation of the type I interferon pathway has contributed to disease diagnosis, monitoring of disease activity through interferon-related biomarkers, and the development of novel targeted therapies. Myositis-specific autoantibodies (MSA), detected in approximately 70% of patients, define clinically distinct subgroups; for example, anti-NXP2 is associated with calcinosis, and anti-MDA5 positivity carries a risk of interstitial lung disease. Importantly, MSA subtype influences not only clinical phenotype but also treatment response, underscoring the value of systematic autoantibody testing in guiding therapeutic decisions. A treat-to-target approach and close monitoring of disease activity are recommended. In refractory disease, conventional immunosuppressants and biologic agents are escalated sequentially, with Janus kinase (JAK) inhibitors targeting the type I interferon pathway. More selective interferon blockade with anifrolumab and next-generation B-cell depletion with chimeric antigen receptor T-cell (CAR-T) cell therapy represent emerging options for patients with refractory disease. Calcinosis remains without a standardized treatment procedure, and evidence-based management is limited by the lack of pediatric randomized controlled trials. Prospective, multicenter studies are needed to establish treatment algorithms and improve long-term outcomes in this rare disease. Cite this article as: Aslan E, Kisla Ekinci RM, Torunoglu Z, Akay N, Kasapcopur O. Juvenile dermatomyositis: A review of the literature. ArchRheumatol. Published online July 31, 2026. doi: 10.5152/ArchRheumatol.2026.26552.
2026-07-10 | Vedolizumab as a rescue therapy for severe gastrointestinal involvement in anti-NXP2 positive juvenile dermatomyositis
Şengül Çağlayan, Ulaş Emre Akbulut, Tangül Pınarcı, Muhammed Gültekin Kutluk, Hasan Serdar Kıhtır; Vedolizumab as a rescue therapy for severe gastrointesti
2026-05-25 | Reversibility of calcinosis in anti-NXP2-positive refractory dermatomyositis treated with TNF-α blockade: a brief report.
Calcinosis cutis is one of the most refractory complications of dermatomyositis (DM), particularly in patients with anti-nuclear matrix protein 2 (NXP2) autoantibodies. Whether tumor necrosis factor-alpha (TNF-α) blockade is associated with regression of established calcinosis remains uncertain. We conducted a retrospective, single-center study of nine patients with refractory dermatomyositis or juvenile dermatomyositis treated with TNF-α inhibitors (infliximab or adalimumab). Myositis-specific autoantibodies, longitudinal muscle strength (MMT8, CMAS), glucocorticoid exposure, and serial imaging of calcinosis were evaluated. Calcinosis change was analyzed as an exploratory endpoint. Three patients were anti-NXP2 positive, and six were negative for tested myositis-specific autoantibodies. TNF-α blockade was associated with sustained clinical improvement and a marked steroid-sparing effect, with median daily prednisolone dose decreasing from 40 mg at baseline to 5 mg at 12 months. Radiographic regression of calcinosis, defined a priori as a ≥20% reduction in maximal lesion diameter on serial imaging, was observed in 2 of 3 anti-NXP2-positive patients after prolonged treatment (12-20 months): notably, calcinosis was absent at baseline in all anti-NXP2-negative patients, precluding assessment of regression in this subgroup. One patient with pre-existing interstitial lung abnormalities experienced pulmonary deterioration, leading to treatment discontinuation. In this small retrospective cohort, prolonged TNF-α blockade was associated with radiographic regression of calcinosis in a subset of anti-NXP2-positive patients, while calcinosis was absent at baseline in antibody-negative patients. These findings generate a hypothesis that antibody-defined subgroups may differ in calcinosis responsiveness and warrant prospective validation.
2026-03-28 | Transaminitis as the initial presentation of anti-MDA5 positive juvenile dermatomyositis: A case report
Anti-MDA5 positive JDM is associated with rapidly progressive ILD, causing high morbidity and mortality. We present a case of a child with anti-MDA5 positive JDM who presented with transaminitis and elevated CPK, leading to an original diagnosis of infective myositis of multiple sites. Seven days after the initial encounter, the patient returned with classic JDM symptoms of skin erosions, heliotrope rash, and Gottron’s papules, leading to a diagnosis of anti-MDA5 positive JDM with ILD. Why should an emergency physician be aware of this? Liver dysfunction is a growing concern among anti-MDA5 positive JDM and may be associated with risk factors that lead to poorer prognosis. Because this patient did not originally present with classic skin findings of JDM, diagnosis and treatment of her condition was delayed. Early identification of anti-MDA5 positive JDM is crucial to prevent rapidly progressive ILD.
2026-02-01 | Lung Involvement in MDA5‐Positive Juvenile Dermatomyositis: A Case of Misdiagnosed Pneumonia in a Toddler
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
cell therapies
2026-05-11 | Case Report: Juvenile dermatomyositis complicated by acute myeloid leukemia: achievement of sustained remission through hematopoietic stem cell transplantation.
Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron's papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.
2026-04-03 | CAR T-cell therapy and indications for pediatric rheumatology: Structured overview of applications, risks, and considerations.
This chapter offers an overview of CAR T-cell therapy and its emerging role in pediatric rheumatology, particularly the potential impact on severe refractory autoimmune conditions in children. It examines criteria for patient eligibility, safety concerns, and potential long-term effects for young rheumatology patients, while stressing the importance of personalized and prolonged follow-up. The possibility of achieving drug-free remission in pediatric cases appears to be a possible in refractory patients; however, further studies should focus on standardizing pre-treatment protocols for children with rheumatic diseases, reducing the intensity of conditioning regimens, and implementing extended surveillance to assess therapy duration and lasting outcomes.
2025-11-14 | Juvenile dermatomyositis: new insights into pathogenesis and clinical applications.
Juvenile dermatomyositis (JDM), the most common inflammatory myopathy of childhood, is a complex autoimmune condition with significant disease burden and variable treatment responses. While conventional immunosuppression remains standard, advances in immunopathology are revealing new therapeutic and biomarker opportunities. This review provides emerging insights into JDM pathogenesis. Interferon (IFN)-stimulated gene (ISG) expression, and IFN-related emerging biomarkers which may be valuable for monitoring disease activity and treatment response. Mitochondrial dysfunction, involving oxidative stress and oxidized mtDNA, contributes to systemic pathology and offers new therapeutic targets. Other critical pathogenic processes include pyroptosis, neutrophil extracellular traps, and abnormal B-cell activity. Novel treatments targeting IFN pathways, B cells, and mitochondrial oxidation are under investigation. CAR T-cell therapies have shown early promise in refractory cases. Ongoing research is transforming our understanding of JDM, enabling biomarker-driven precision medicine and targeted therapies. These advances offer the potential to improve outcomes and achieve durable remission, even in refractory or high-risk disease subsets.
2025-11-10 | Therapeutic plasma exchange in autoimmune diseases: a retrospective study in a tertiary pediatric hospital in Mexico.
To describe the use and mortality-associated factors of therapeutic plasma exchange (TPE) in children with autoimmune diseases at a tertiary pediatric hospital in Mexico. Retrospective cross-sectional study including patients under 18 years old with autoimmune diseases who underwent TPE between 2022 and 2025 at the Hospital Infantil de México Federico Gómez. Demographic, clinical, therapeutic, and laboratory data were analyzed. Clinical response and mortality-associated factors were assessed. Forty-one patients were included (68% female; median age: 12 years). The most frequent indications for TPE were systemic lupus erythematosus (SLE) (56.1%) and autoimmune encephalitis (14.6%). Other diagnoses included macrophage activation syndrome (MAS) (n = 3), overlap syndromes (n = 3), juvenile dermatomyositis (n = 2), and single cases of ANCA-associated vasculitis, Takayasu arteritis, antiphospholipid syndrome (APS), and Kawasaki disease. Complete or partial remission was achieved in 85.4% of cases, with variable responses depending on the underlying condition. TPE was well tolerated, with few adverse events. Overall mortality was 14.6% (n = 6), all due to sepsis (p < 0.001). Deceased patients had higher pre-TPE levels of CRP, procalcitonin, and ferritin, though not statistically significant. Longer disease duration was significantly associated with increased mortality in both univariable (OR 1.05, 95% CI 1.01-1.10; p = 0.04) and multivariable analysis adjusted for age, sex, and SLE diagnosis (OR 1.06; 95% CI 1.01-1.14; p = 0.04). Among SLE patients without sepsis, MEX-SLEDAI scores improved significantly. TPE was safe and beneficial in children with severe autoimmune diseases. Mortality was related to disease duration rather than the procedure itself.
2025-07-03 | CAR T cell therapy for children with rheumatic disease: the time is now.
Initial success with B cell-targeted chimeric antigen receptor (CAR) T cells for the treatment of systemic lupus erythematosus and other rheumatic diseases has generated enthusiasm for the broad application of this technology outside of the field of oncology. Paediatric patients with severe rheumatic diseases require lifelong therapy with a substantial toxicity burden and a high cost of care. Paradigm-shifting treatments, including CAR T cells, are desperately needed. Although CAR T cell therapy shows promise for paediatric rheumatic diseases, there are unique aspects of care compared with adults, which require careful consideration and expertise. In response, we established the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group, comprising international experts in the fields of paediatric rheumatology, oncology and cellular therapy, immunology and nephrology, to address the challenges of introducing cell therapies to patients with paediatric-onset autoimmune diseases. Given the possible benefits, we advocate for the study of CAR T cells in paediatric patients with rheumatic diseases who carry a lifelong risk of morbidity and mortality from chronic illness and medication toxicity. As this patient population is relatively small, consensus around definitions of success, robust study of predictors of response and uniform assessment and reporting of toxicities are critical to advancing the field.
other
2023-04-20 | Single-cell profiling of peripheral blood and muscle cells reveals inflammatory features of juvenile dermatomyositis
Introduction: Juvenile dermatomyositis (JDM) is a rare yet serious childhood systemic autoimmune condition that primarily causes skin rashes and inflammatory myopathy of the proximal muscles. Although the associated immune response involves the innate and adaptive arms, a detailed analysis of the pertinent immune cells remains to be performed. This study aims to investigate the dynamic changes of cell type, cell composition and transcriptional profiles in peripheral blood and muscle tissues, and in order to clarify the involvement of immune cells in the pathogenesis of JDM and provide a theoretical reference for JDM. Methods: Single-cell RNA sequencing combined with bioinformatic analyses were used to investigate the dynamic changes in cell composition and transcriptional profiles. Results: Analysis of 45,859 cells revealed nine and seven distinct cell subsets in the peripheral blood and muscle tissues respectively. IFITM2+ and CYP4F3+ monocytes were largely produced, and CD74 + smooth muscle cells (SMCs) and CCL19+ fibroblasts were identified as inflammatory-related cell subtypes in JDM patients, exhibiting patient-specific cell population heterogeneity.The dynamic gene expression patterns presented an enhanced type I interferon response in peripheral blood monocytes and T-cells, and SMCs and fibroblasts in muscle of untreated JDM patients. EGR1 and IRF7 may play central roles in the inflammation in both CD74 + SMCs and CCL19+ fibroblasts. Moreover, inflammatory-related monocytes could regulate T-cells, and the interaction between immune cells and SMCs or fibroblasts in muscle was enhanced under the inflammatory state. Conclusions: Immune dysregulation is one of the key pathogenic factors of JDM, and type I interferon responses are significantly enhanced in peripheral blood Monos and T cells as well as SMCs and fibroblasts. EGR1 and IRF7 may play central roles in the inflammation and are considered as potential therapeutic targets for JDM.
2021-09-18 | Identification of Vital Hub Genes and Potential Molecular Pathways of Dermatomyositis by Bioinformatics Analysis
Dermatomyositis is an autoimmune disease characterized by severe symmetrical muscle dysfunction and pain. This study was aimed at discovering vital hub genes and potential molecular pathways of DM through bioinformatics analysis, which contributes to identifying potential diagnostic or therapeutic biomarkers and targets. In this study, a total of 915 DEGs in DM samples including 167 upregulated genes and 748 downregulated genes were screened out by the limma package based on the GSE142807 dataset from the Gene Expression Omnibus (GEO) database. Furthermore, the results of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that these downregulated genes were highly associated with the immune-related biological processes and pathways. Therefore, 41 genes closely related to DM were extracted for further study based on the subcluster analysis through the Molecular Complex Detection (MCODE) software plugin in Cytoscape. Ultimately, 10 hub genes (including ISG15, DDX58, IFIT3, CXCL10, and STAT1) were identified as the potential candidate biomarkers and targets. Besides, we found that the identified hub genes directly or indirectly communicated with each other via molecular signaling pathways on the protein and transcription level. In general, under the guidance of bioinformatics analysis, 10 vital hub genes and molecular mechanisms in DM were identified and the expression of proinflammatory factors and interferon family proteins and genes showed high association with DM, which might help provide a theoretical foundation for the development of point-to-point targeted therapy in the future treatment of DM.
2020-04-06 | Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies
Abstract Background Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with a prominent interferon (IFN) signature, but the pathogenesis of JDM and the etiology of its IFN signature remain unknown. The Mendelian autoinflammatory interferonopathies, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) and STING-Associated Vasculopathy with onset in Infancy (SAVI), are caused by genetic mutations and have extremely elevated IFN signatures thought to drive pathology. The phenotypic overlap of some clinical features of CANDLE and SAVI with JDM led to the comparison of a standardized interferon-regulated gene score (IRG-S) in JDM and myositis-specific autoantibody (MSA) JDM subgroups, with CANDLE and SAVI. Methods A peripheral 28-component IRG-S assessed by NanoString™ in 57 JDM patients subtyped by MSA was compared with IRG-S in healthy controls (HC) and CANDLE/SAVI patients. Principal component analysis (PCA) was performed, and individual genes were evaluated for their contribution to the score. IRG-S were correlated with disease assessments and patient characteristics. Results IRG-S in JDM patients were significantly higher than in HC but lower than in CANDLE or SAVI. JDM IRG-S overlapped more with SAVI than CANDLE by PCA. Among MSA groups, anti-MDA5 autoantibody-positive patients’ IRG-S overlapped most with SAVI. The IFI27 proportion was significantly higher in SAVI and CANDLE than JDM, but IFIT1 contributed more to IRG-S in JDM. Overall, the contribution of individual interferon-regulated genes (IRG) in JDM was more similar to SAVI. IRG-S correlated moderately with JDM disease activity measures ( r s = 0.33–0.47) and more strongly with skin activity ( r s = 0.58–0.79) in anti-TIF1 autoantibody-positive patients. Weakness and joint disease activity (multinomial OR 0.91 and 3.3) were the best predictors of high IRG-S. Conclusions Our findings demonstrate peripheral IRG expression in JDM overlaps with monogenic interferonopathies, particularly SAVI, and correlates with disease activity. Anti-MDA5 autoantibody-positive JDM IRG-S were notably more similar to SAVI. This may reflect both a shared IFN signature, which is driven by IFN-β and STING pathways in SAVI, as well as the shared phenotype of vasculopathy in SAVI and JDM, particularly in anti-MDA5 autoantibody-positive JDM, and indicate potential therapeutic targets for JDM.
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