RARE DISEASE
Juvenile polymyositis
Juvenile polymyositis
Juvenile polymyositis
Synonyms: Juvenile PM
Synonyms: Juvenile PM
Synonyms: Juvenile PM
Drug discovery
0
drugs
With orphan designations
Overview
Juvenile polymyositis (JPM) is a rare autoimmune disorder characterized by chronic inflammation of skeletal muscles, leading to progressive proximal muscle weakness and systemic complications such as dysphagia or respiratory impairment. Diagnosis integrates clinical evaluation, elevated muscle enzymes (CK, aldolase), MRI, and muscle biopsy. Treatment focuses on immunosuppression (corticosteroids, DMARDs, biologics) and physical therapy to mitigate disability. Unlike juvenile dermatomyositis, JPM lacks pathognomonic skin findings, requiring careful differentiation from other myopathies [1][6][11].
Burden
Economic: Annual hospitalization costs exceed $49 million for juvenile myositis, with frequent specialist visits and prolonged immunosuppression [4][19].
Morbidity: Chronic weakness (30–40% of cases), dysphagia, and steroid-related complications (e.g., osteoporosis, growth delay) [1][9][14].
Mortality: 3–10% mortality linked to interstitial lung disease, infections, or cardiovascular complications [9][14][19].
Therapies
First-line: High-dose corticosteroids (oral/IV) combined with methotrexate or mycophenolate mofetil [1][8][18].
Refractory cases: Biologics (rituximab), IV immunoglobulin, or cyclophosphamide [6][13][19].
Adjuncts: Aggressive physical therapy to prevent contractures and improve functional outcomes [3][13].
Categories: rare neurological diseases, rare renal diseases, rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
142 drug discovery papers about Juvenile polymyositis. Recent publications:
142 drug discovery papers about Juvenile polymyositis. Recent publications:
categories:
Small molecules
small molecules
2026-04-01 | E113 Prioritising drug targets for idiopathic inflammatory myopathies via QTL-based Mendelian randomisation and colocalisation
Abstract Background/Aims Idiopathic inflammatory myopathies (IIM) are rare autoimmune disorders with incompletely defined genetic mechanisms. Identifying causal genes and proteins may accelerate therapeutic target discovery. Methods We performed two-sample Mendelian randomisation (MR) with molecular quantitative trait loci (QTLs) and colocalisation to evaluate the causal effects of 1,064 proteins and 8,415 genes on overall IIM and clinical subtypes, including polymyositis (PM), dermatomyositis (DM), juvenile DM and anti-Jo-1. cis-protein QTLs (pQTLs) from Fenland serum protein study and cis-expression QTLs (eQTLs) from GTEx skeletal muscle and eQTLGen whole blood were used in two-sample MR. Bonferroni correction accounted for multiple testing. Significant MR signals after correction were assessed by colocalization to confirm shared causal variants (PP4>0.8). Drug target tractability was assessed via the Open Targets Platform. Results Four targets emerged after MR significance correction and colocalisation. pQTL-based MR implicated TLR1 (OR = 0.21, 95% CI: 0.10-0.44, P = 3.17 × 10-5) and NFKB1 (OR = 3.19, CI: 1.96-5.21, P = 3.37 × 10-6), with concordant eQTL-based MR in whole blood. eQTL-based MR additionally identified DCAKD (skeletal muscle; IIM: OR = 0.57, CI: 0.46-0.70, P = 1.22 × 10-7) and PTPN22 (whole blood; PM: OR = 3.43, CI: 2.14-5.48, P = 2.63 × 10-7). No significant signals were observed for DM, juvenile DM, or anti-Jo-1. Colocalisation confirmed shared causal variants for: (i) IIM with serum levels of TLR1 and NFKB1, and expression levels in skeletal muscle of DCAKD; and (ii) PM with expression levels in whole blood of PTPN22. Drug target assessment indicated tractability for TLR1, NFKB1, and PTPN22 with varying clinical readiness, while DCAKD emerged as a novel target with limited tractability. Conclusion Integrating QTL-based MR with colocalisation highlights TLR1, NFKB1, DCAKD, and PTPN22 as candidate regulators in IIM and PM, implicating innate immune sensing, NF-κB signalling, and proteostasis pathways. These findings nominate tractable therapeutic targets and demonstrate a scalable framework for causal drug target prioritisation in rare autoimmune disease. Disclosure G. Chen: None. H. Chinoy: None. S.S. Zhao: None. A.S. Morris: None. J.A. Lamb: None.
2025-08-21 | [Clinical characteristics of anti-melanoma differentiation associated gene 5 antibody-positive juvenile dermatomyositis].
Objective: To analyze the clinical characteristics of anti-melanoma differentiation associated gene 5 (MDA5) antibody-positive juvenile dermatomyositis (JDM) patients. Methods: A retrospective case-control study was conducted. The positive group included 18 children with anti-MDA5 antibody-positive JDM who were admitted to the Department of Rheumatology and Immunology at Capital Center for Children's Health with Capital Medical University between January 2016 and January 2023. Another 36 children with anti-MDA5 antibody-negative JDM hospitalized during the same period were enrolled as the negative group. Based on the extent of pulmonary involvement and pulmonary CT scores, the MDA5-positive group was further divided into severe pulmonary involvement and non-severe pulmonary involvement subgroups. Chi-square test and Kruskal-Wallis test were used to compare clinical features, laboratory test results between groups. Results: Among the 18 patients in the MDA5-positive group, 7 were male and 11 were female, with an age of onset of 5.0 (2.6, 9.4) years and disease duration of 6.0 (4.0, 9.3) months. The MDA5-negative group included 36 cases (14 male, 22 female), with an age of onset of 4.9 (2.0, 7.0) years and disease duration of 5.0 (1.8, 7.0) months. The MDA5-positive group exhibited significantly higher rates of arthritis, skin ulcers, and interstitial lung disease (ILD), along with elevated serum ferritin (SF) and erythrocyte sedimentation rate levels compared to the MDA5-negative group (9/18 vs. 11% (4/36), 6/18 vs. 3% (1/36), 16/18 vs. 33% (12/36), 327 (141, 518) vs. 131 (68, 257) μg/L, 17.5 (12.5, 26.8) vs. 11.0 (5.0, 13.0) mm/1 h, χ²=7.92, 7.41, 14.84, Z=2.50, 2.87, all P<0.05). Conversely, the MDA5-positive group had lower rates of muscle weakness and lower creatine kinase levels (5/18 vs. 75% (27/36), 58.5 (49.3, 97.5) vs. 225.0 (68.0, 695.5) U/L, χ²=11.08, Z=-2.94, both P<0.05). Severe pulmonary involvement 6 cases and non-severe pulmonary involvement subgroups 12 cases. Among the MDA5-positive patients, those in the severe pulmonary involvement subgroup had an older age at onset and higher rates of muscle weakness as well as hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), SF, and Krebs von den Lungen-6 (KL-6) compared to the non-severe subgroup (all P<0.05). In the MDA5-positive group, 17 patients improved after treatment with glucocorticoids combined with immunosuppressants, while One died due to rapidly progressive ILD. Conclusions: Anti-MDA5 antibody-positive JDM is characterized by typical skin rashes, a high incidence of arthritis and skin ulcers, relatively mild muscle involvement, but is prone to ILD. Among MDA5-positive patients, those with older age at onset, muscle involvement (manifested as muscle weakness and elevated muscle enzymes (LDH, HBDH)), or significantly elevated KL-6 and SF levels are more likely to develop severe pulmonary complications.
2025-08-11 | Spatial transcriptomic analysis of muscle biopsy from patients with treatment-naive juvenile dermatomyositis reveals mitochondrial abnormalities despite disease-related interferon-driven signature.
This study aimed to investigate the spatial transcriptomic landscape of muscle tissue from patients with treatment-naive juvenile dermatomyositis (JDM) in comparison to healthy paediatric muscle tissue. Muscle biopsies from 3 patients with JDM and 3 age-matched controls were analysed using the Nanostring GeoMx Digital Spatial Profiler. Regions of interest were selected based on muscle fibres without immune cells, immune cell infiltration and CD68+ macrophage enrichment. Differential gene expression, pathway analysis and pathways clustering analysis were conducted. Key findings were validated in 19 cases of JDM using immunohistochemistry and chemical stains, and a bulk RNAseq dataset of 4 cases of JDM. JDM muscle tissues exhibited significant interferon pathway activation and mitochondrial dysfunction compared to controls. A 15-gene interferon signature was significantly elevated in JDM muscle and macrophage-enriched regions, correlating with clinical weakness. In contrast, mitochondrial dysregulation, characterised by downregulated respiratory chain pathways, was present regardless of interferon activity or muscle strength. The interferon-driven and mitochondrial signatures were replicated in an independent RNAseq dataset from JDM muscle; the lack of association between interferon signature and mitochondrial dysregulation was validated in 19 cases by conventional staining methods. Clustering analysis revealed distinct transcriptomic profiles between JDM and control tissues, as well as between patients with JDM with varying clinical phenotypes. This study highlights mitochondrial dysfunction as a consistent pathological feature in JDM muscle, which may be independent of interferon-driven inflammation. These findings highlight the potential for mitochondrial-targeted therapies in JDM management and emphasise the need for further studies to explore their therapeutic value.
2025-07-23 | Updates in juvenile dermatomyositis: pathogenesis and therapy.
This review provides updates on juvenile dermatomyositis pathogenesis and treatment. JDM pathogenesis research updates in genetic risk factors include C4 copy number. Studies clarify myositis-specific autoantibodies' (MSA) role in disease pathogenesis and more myositis-associated antibody (MAA) clinical associations. Recent studies validate an interferon (IFN)-regulated gene score and an IFN-related monocyte surface protein marker, SIGLEC-1. Vasculopathy and mitochondrial dysfunction evidence increases, both with ties to IFN. Studies point to not only T and B cells, but monocytes, macrophages, and neutrophils as dysregulated in JDM. Regarding treatment, there are growing reports of success with therapies targeting IFN-signaling (Janus kinase inhibitors), dazukibart (anti-IFN-beta), and anifrolumab (anti-IFNAR1). Chimeric antigen receptor (CAR) T-cell therapy targeting B-cells in a growing number of adult myositis patients and one JDM patient have dramatic reports of achieving drug-free remission. Growing evidence show genetic markers, MSA, IFN, vasculopathy, varied immune cells, and mitochondrial dysfunction having important roles in JDM pathogenesis. Some refractory patients show benefit with newer IFN pathway-targeted therapies and cellular CAR-T-cell therapy. Further collaborative research on disease pathogenesis, treatment targets, and innovate clinical trial design is needed to increase access to more efficacious treatments in JDM.
2025-07-07 | Efficacy of hydroxychloroquine treatment for the skin manifestations of juvenile dermatomyositis.
Juvenile dermatomyositis (JDM) is the most popular subtype of juvenile idiopathic inflammatory myopathies clinically characterised by skin manifestations and myositis. Some patients with JDM present predominantly with skin symptoms without significant muscle weakness. Furthermore, some patients exhibit residual skin disease even after showing improvement of muscle symptoms with systemic glucocorticoids (GCs) and immunosuppressants. Topical GCs and/or tacrolimus are recommended for the patients with skin predominant JDM. Furthermore, systemic use of GCs and methotrexate (MTX) are indicated in refractory cases. However, some patients show refractory skin disease to even systemic use of GCs and MTX. Hydroxychloroquine (HCQ) has been reported to improve skin manifestations associated with JDM and is used globally for JDM. However, HCQ is not approved by the Ministry of Health, Labour and Welfare of Japan for treatment of JDM. Herein, we report two patients with JDM presenting with residual skin disease after taking systemic GC and immunosuppressants, which was successfully treated with HCQ. HCQ was effective for treating a case with skin symptoms without significant muscle weakness at relapse and for a case with residual skin symptoms after showing improvement of muscle symptoms with systemic GCs and immunosuppressants. No adverse events were observed in their clinical courses. Thus, HCQ may be an effective choice as an adjunctive therapy for refractory skin symptom-dominant JDM.
cell therapies
2026-05-18 | Case Report: Sustained immune and pulmonary recovery three years after hematopoietic stem cell transplantation for ITCH E3 ubiquitin ligase deficiency.
Itchy E3 ubiquitin ligase deficiency (ITCH deficiency) is a rare monogenic immune dysregulation syndrome characterized by early-onset multisystem autoimmunity and significant morbidity and mortality. Only one prior case report has described a patient treated with hematopoietic stem cell transplantation (HSCT) with clinical improvement, and no established disease-modifying or curative therapy algorithm exists. We describe a female patient who presented in early childhood with chronic lung disease requiring tracheostomy and long-term mechanical ventilation and later developed progressive muscle weakness. She was diagnosed with steroid-responsive juvenile polymyositis and subsequently accumulated multiple autoimmune manifestations including autoimmune hepatitis, enteropathy, psoriasis, inflammatory arthritis, and Sjögren's-like parotitis. Genetic testing ultimately identified compound heterozygous pathogenic variants in ITCH. Despite prolonged treatment with multiple immunosuppressive and biologic therapies, she remained prednisone dependent with poor disease control and substantial treatment-related morbidity. At 20 years of age, she underwent allogeneic hematopoietic stem cell transplantation. Following transplantation, she achieved sustained resolution of autoimmune disease activity, was successfully weaned from all immunosuppressive therapy, and was decannulated from chronic mechanical ventilation, with marked improvement in functional status and quality of life. This is the second reported case demonstrating the benefit of hematopoietic stem cell transplant (HSCT) in ITCH deficiency and provides evidence of durable multisystem clinical remission and recovery of long-standing pulmonary and musculoskeletal disease. These findings support consideration of HSCT as a therapeutic option in carefully selected patients with severe, refractory autoimmune manifestations due to ITCH deficiency and raise the possibility that earlier consideration in the disease course may mitigate cumulative disease- and treatment-related morbidity.
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.
2024-10-19 | Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current Treatment, and Emerging Targeted Therapies.
Juvenile dermatomyositis is a rare systemic inflammatory autoimmune disease involving muscle, skin, and vessels. Most patients do not fully respond to initial therapy, instead having a chronic refractory or polycyclic disease course. Pathogenesis is not completely understood, but immune cell dysregulation, particularly of B cells, mitochondrial dysfunction, changes in neutrophils and neutrophil extracellular traps (NETs), and increased type I and type II interferon (IFN) signaling have been described. There are limited randomized controlled trials of drugs in juvenile dermatomyositis (JDM), and treatment is largely based on lower-quality data such as case series, retrospective studies, and open-label prospective studies. These data have been compiled into expert recommendations or consensus treatment plans, which help guide therapy. While initial therapy is more standard with most including corticosteroids (high-dose oral and/or pulse intravenous methylprednisolone) and methotrexate, for refractory patients, guidelines are more varied with multiple options or combinations, including biologic therapies. There is a clear need for more efficacious and personalized therapy in JDM. Emerging treatment options worthy of further study in JDM include targeting IFN-signaling (JAK, IFNAR1, IFN beta), B-cells (CD20, CD19, BAFF, TACI, CD38, BCMA) including Chimeric Antigen Receptor (CAR)-T cell therapy, mitochondrial dysfunction, and NETs.
2022-10-17 | CD8+ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.
CD8+ T cells are cytotoxic lymphocytes that destroy pathogen infected and malignant cells through release of cytolytic molecules and proinflammatory cytokines. Although the role of CD8+ T cells in connective tissue diseases (CTDs) has not been explored as thoroughly as that of other immune cells, research focusing on this key component of the immune system has recently gained momentum. Aberrations in cytotoxic cell function may have implications in triggering autoimmunity and may promote tissue damage leading to exacerbation of disease. In this comprehensive review of current literature, we examine the role of CD8+ T cells in systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, polymyositis, and dermatomyositis with specific focus on comparing what is known about CD8+ T cell peripheral blood phenotypes, CD8+ T cell function, and CD8+ T cell organ-specific profiles in adult and juvenile forms of these disorders. Although, the precise role of CD8+ T cells in the initiation of autoimmunity and disease progression remains to be elucidated, increasing evidence indicates that CD8+ T cells are emerging as an attractive target for therapy in CTDs.
2018-12-11 | Long-term follow-up of autologous hematopoietic stem cell transplantation for refractory juvenile dermatomyositis: a case-series study.
To follow up the refractory juvenile dermatomyositis (JDM) with autologous hematopoietic stem cell transplantation (AHSCT) in a long time and to investigate whether AHSCT is effective and safe to treat refractory JDM. We collected the AHSCT and follow-up data of three patients with refractory JDM who received autologous peripheral blood CD34+ cell transplantation in our hospital between June 2004 and July 2015. Those data include: hight, weight, routine blood and urine tests, ESR, CK, ALT, AST, LDH, renal functional tests, lymphocyte subpopulations, HRCT and muscle MRI. The last follow-up was done in June 2017. All three patients had complete remission and could stop prednisone after 3-12 months. None of them relapsed at 144, 113 and 23 months follow-up. Twelve months after their AHSCT, all of their monitoring indexes have returned to normal and they have stopped all medications. Until the date of this article, none of them relapsed or need medicine. Our study suggests that AHSCT is safe and effective in treating refractory JDM, and it can provides long term drug-free survival. However, more cases are needed for further confirmation.
antibodies
2025-12-12 | Clinical use of intravenous immunoglobulin in juvenile dermatomyositis: indications, treatment course, and clinical outcomes.
To evaluate indications, clinical response, outcomes, and tolerability of intravenous immunoglobulin (IVIG) therapy in patients with juvenile dermatomyositis (JDM) in a multicenter cohort. This retrospective multicenter study included 29 patients with JDM who received IVIG. Demographic data, clinical features, laboratory parameters, and standardized disease activity scores were recorded at disease onset, before and after IVIG treatment, and at final follow-up. Treatment response and adverse events were analyzed. IVIG was initiated a median of 1.2 months (IQR: 0.1-18.9) after diagnosis and continued for a median of 8.2 months (IQR: 5.6-21.6). Indications included refractory muscle weakness, persistent skin disease, calcinosis, and interstitial lung disease (ILD). IVIG therapy was associated with significant improvements in disease activity measures and laboratory parameters (p < 0.001). Calcinosis partially or completely resolved in 3 of 6 patients, while no change was observed in the single ILD case. IVIG was well tolerated, with only mild adverse effects. IVIG appears to be a safe and effective treatment option for JDM, particularly in refractory or skin-predominant disease. Although causal inferences are limited by the retrospective design and the absence of a control group, these real-world findings support the inclusion of IVIG in an individualized treatment approach.
2025-07-30 | Treatment outcomes in 63 cases of juvenile dermatomyositis-associated calcinosis.
We performed a multi-institutional retrospective review of patients treated for juvenile dermatomyositis (JDM)-associated calcinosis to analyse the association between treatment outcomes and patient, disease, and treatment characteristics. Childhood Arthritis and Rheumatology Research Alliance investigators searched their electronic health records for patients with JDM and calcinosis treated between 2003 and 2019 and analysed data at JDM diagnosis, calcinosis diagnosis, and calcinosis treatment. Statistical methods included univariable and multivariable analyses, Kaplan-Meier estimates, and multivariable Cox models. Data were collected for 63 patients from 11 institutions. Median (IQR) age was 7.8 (4.1-11.1) years at JDM diagnosis and 9.4 (5.7-13.3) years at calcinosis diagnosis. Calcinosis was present at JDM diagnosis in 32% of patients (n=20). JDM was active in 76% of patients (47/62) at calcinosis diagnosis. Anti-nuclear matrix protein 2 (anti-NXP2) antibody was the most commonly detected myositis autoantibody (38%, 12/32). The presence of anti-NXP2 or anti-melanoma differentiation-associated gene 5 autoantibody did not significantly affect the probability of any calcinosis improvement (p=0.30). Patients received 103 unique treatment regimens of immunomodulatory agents with or without calcium-modifying agents, but those who received both had the greatest probability of improvement. Intravenous immunoglobulin (IVIG) was associated with a significantly higher probability of calcinosis improvement (p=0.02) than treatments without IVIG. Overall, 79% of patients (n=50) showed improved calcinosis. Despite wide variations in treatment, many patients showed calcinosis improvement over time, especially those treated with IVIG. Studies using validated outcomes assessments may be needed to develop effective treatment plans for JDM-associated calcinosis.
2024-06-06 | Elevated type I IFN signalling directly affects CD8+ T-cell distribution and autoantigen recognition of the skeletal muscles in active JDM patients.
The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of elevated type I IFN signaling on CD8+ T cell-associated muscle damage in juvenile dermatomyositis (JDM). This study used flow cytometry (FC) and RT‒PCR were used to examine the circulating cell ratio and type I IFN response. And scRNA-seq was used to examine peripheral immunity in 6 active JDM patients, 3 stable JDM patients, 3 juvenile IMNM patients and 3 age-matched healthy children. In vivo validation experiments were conducted using a mouse model induced by STING agonists and an experimental autoimmune myositis model (EAM). In vitro experiments were conducted using isolated CD8+ T-cells from JDM patients and mice. We found that active JDM patients showed an extensive type I IFN response and a decreased CD8+ T-cell ratio in the periphery (P < 0.05), which was correlated with muscle involvement (P < 0.05). Both new active JDM patients and all active JDM patients showed decreased CD8+ TCM cell ratios compared with age and gender matched stable JDM patients (P < 0.05). Compared with new pediatirc systemic lupus erythematosus (SLE) patients, new active JDM patients displayed decreased CD8+ T-cell and CD8+ TCM cell ratios (P < 0.05). Active JDM patient skeletal muscle biopsies displayed an elevated type I IFN response, upregulated MHC-I expression and CD8+ T-cell infiltration, which was validated in EAM mice. sc-RNAseq demonstrated that type I IFN signalling is the kinetic factor of abnormal differentiation and enhances the cytotoxicity of peripheral CD8+ T cells in active JDM patients, which was confirmed by in vivo and in vitro validation experiments. In summary, the elevated type I IFN signalling affected the differentiation and function of CD8+ T cells in active JDM patients. Skeletal muscle-infiltrating CD8+ T cells might migrate from the periphery under the drive of type I IFN and increased MHC I signals. Therapies targeting autoantigen-specific CD8+ T cells may represent a potential new treatment direction.
2024-01-05 | Local injection of infliximab into calcinosis lesions in patients with juvenile dermatomyositis (JDM): a clinical trial.
Juvenile Dermatomyositis (JDM) is a rare autoimmune disorder that primarily affects muscles and skin. One of the severe complications associated with JDM is calcinosis, and treating this condition presents significant challenges. This study aimed to evaluate the efficacy and safety of local injection of infliximab into calcinosis lesions in patients with JDM. In this clinical trial, five patients diagnosed with JDM and calcinosis lesions were enrolled. The primary treatment consisted of weekly infliximab injections for 16 weeks, targeting all four sides of each lesion. Lesion dimensions, including length and width, were documented and monitored weekly. Before the intervention, patients underwent radiographic imaging. After the final injection in week 16, a follow-up radiographic assessment was performed. Data were analyzed using the Generalized Estimating Equation (GEE) method. The lesions' size significantly decreased in both length and width during each visit. On average, the lesion length reduced by 2.66%, and the width shrank by 3.32% per visit. Based on radiographic findings, the average length and width of lesions at the initial visit were 12.09 ± 5.05 mm (range: 6.00-25.50 mm) and 6.35 ± 3.00 mm (range: 2.00-16.00 mm), respectively. The average length and width at the last visit were 5.59 ± 7.05 mm (range: 0-23.00 mm) and 3.41 ± 4.05 mm (range: 0-13.00 mm), respectively. No specific side effects related to the treatment were reported. The results suggest that the direct administration of infliximab into the calcinosis lesions of patients with JDM could be a safe and effective treatment approach. Name of the registry: The effect of infliximab injection into calcinosis lesions on patients with juvenile dermatomyositis (JDM), Trial registration number: IRCT20210808052107N1, Registration date: 2022-07-22, URL of trial registry record: https://en.irct.ir/trial/58329 .
2023-12-22 | Lung infection or inflammation-a puzzling case of MDA-5 associated juvenile dermatomyositis.
Juvenile dermatomyositis (JDM) is an uncommon inflammatory myopathy predominantly affecting children under 18 years of age. Diagnosis relies on identifying specific clinical features, such as muscle weakness, skin rash, elevated muscle enzymes, and MRI and muscle biopsy findings. Autoantibodies associated with inflammatory myopathy offer valuable prognostic insights and can indicate the risk of internal organ involvement, though they are relatively rare in childhood myopathies. JDM can progress to interstitial lung disease (ILD) if associated with MDA5 antibodies, and immunosuppressive therapy constitutes the primary treatment approach. We present a unique case of JDM complicated by disseminated histoplasmosis in a 12-year-old African American male cross-country runner with no prior medical history. He presented with unintentional weight loss and a rash on his hands, genitals, and fingertips, which persisted despite previous treatments. Diagnosis of JDM was confirmed through clinical and laboratory evaluations. Over time, the patient developed recurrent fevers, thrombocytopenia, and signs of ILD, leading to the identification of disseminated histoplasmosis as a complicating factor. Appropriate antifungal treatment resolved the infectious condition, while continued immunosuppression aided in managing JDM and ILD. Juvenile dermatomyositis (JDM) remains a rare and intricate autoimmune disorder affecting young individuals. The presence of MDA5 antibodies in JDM patients can lead to severe complications like ILD, necessitating vigilant monitoring. Management includes immunosuppressive therapy, with glucocorticoids and mycophenolate mofetil proving effective, particularly in Clinically Amyopathic Dermatomyositis (CADM) cases. In cases of refractory disease, intravenous immunoglobulin (IVIG) plays a crucial role, offering a safe and beneficial adjunct to treatment. We emphasize the importance of recognizing atypical presentations of JDM, as it can lead to delays in diagnosis and treatment. Our case highlights the complexities of managing dual lung pathology, where a secondary infection exacerbated lung nodules and thrombocytopenia, while ILD was a consequence of atypical myopathy. Combining antifungal treatment with immunosuppression effectively managed both conditions and follow-up evaluations demonstrated improvement in ILD. Awareness of potential fungal infections in immunosuppressed JDM patients is crucial for successful treatment and patient outcomes.
proteins
2025-09-08 | Discovery of tissue-specific proteomic signatures in juvenile dermatomyositis highlights pathways reflecting persistent disease activity, clinical heterogeneity, and myositis-specific autoantibody subtype.
Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune condition needing targeted treatment approaches and improved understanding of molecular mechanisms driving clinical phenotypes. We utilised exploratory proteomics from a longitudinal North American cohort of patients with new-onset JDM to identify biological pathways at disease onset and follow-up, tissue-specific disease activity, and myositis-specific autoantibody (MSA) status. We measured 3072 plasma proteins (Olink panel) in 56 patients with JDM within 12 weeks of starting treatment (from the Childhood Arthritis and Rheumatology Research Alliance Registry and 3 additional sites) and 8 paediatric controls. Twenty-four patients with JDM who had 6-month follow-up samples were assessed. We identified differentially expressed proteins (DEPs) between groups by fitting linear mixed effects models and associated DEPs with validated disease activity measures. We assessed for cell/tissue specificity using the Human Protein Atlas and JDM muscle single nuclei and skin single-cell transcriptomic datasets. Differences within MSA subgroups were also analysed. We uncovered persistent dysregulation of innate immune activation, cell death, and redox signalling at 6 months despite multidrug immunosuppression. By leveraging tissue and cell-specific proteomes, we identified overrepresentation of circulating endothelial proteins associated with disease activity and verified endothelial cell marker expression in JDM muscle and skin. We discovered pathways associated with MSA subtypes that reflect JDM phenotypes. NXP2+ JDM-associated proteins reflected angiogenesis and extracellular matrix remodelling and were expressed in endothelial cells and fibroblasts. MDA5+ JDM was associated with circulating type III interferon and surfactant proteins. These proteomic findings will inform future biomarker and treatment development considering the unique tissue- and autoantibody-associated inflammation in JDM.
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.
small molecules
2026-04-01 | E113 Prioritising drug targets for idiopathic inflammatory myopathies via QTL-based Mendelian randomisation and colocalisation
Abstract Background/Aims Idiopathic inflammatory myopathies (IIM) are rare autoimmune disorders with incompletely defined genetic mechanisms. Identifying causal genes and proteins may accelerate therapeutic target discovery. Methods We performed two-sample Mendelian randomisation (MR) with molecular quantitative trait loci (QTLs) and colocalisation to evaluate the causal effects of 1,064 proteins and 8,415 genes on overall IIM and clinical subtypes, including polymyositis (PM), dermatomyositis (DM), juvenile DM and anti-Jo-1. cis-protein QTLs (pQTLs) from Fenland serum protein study and cis-expression QTLs (eQTLs) from GTEx skeletal muscle and eQTLGen whole blood were used in two-sample MR. Bonferroni correction accounted for multiple testing. Significant MR signals after correction were assessed by colocalization to confirm shared causal variants (PP4>0.8). Drug target tractability was assessed via the Open Targets Platform. Results Four targets emerged after MR significance correction and colocalisation. pQTL-based MR implicated TLR1 (OR = 0.21, 95% CI: 0.10-0.44, P = 3.17 × 10-5) and NFKB1 (OR = 3.19, CI: 1.96-5.21, P = 3.37 × 10-6), with concordant eQTL-based MR in whole blood. eQTL-based MR additionally identified DCAKD (skeletal muscle; IIM: OR = 0.57, CI: 0.46-0.70, P = 1.22 × 10-7) and PTPN22 (whole blood; PM: OR = 3.43, CI: 2.14-5.48, P = 2.63 × 10-7). No significant signals were observed for DM, juvenile DM, or anti-Jo-1. Colocalisation confirmed shared causal variants for: (i) IIM with serum levels of TLR1 and NFKB1, and expression levels in skeletal muscle of DCAKD; and (ii) PM with expression levels in whole blood of PTPN22. Drug target assessment indicated tractability for TLR1, NFKB1, and PTPN22 with varying clinical readiness, while DCAKD emerged as a novel target with limited tractability. Conclusion Integrating QTL-based MR with colocalisation highlights TLR1, NFKB1, DCAKD, and PTPN22 as candidate regulators in IIM and PM, implicating innate immune sensing, NF-κB signalling, and proteostasis pathways. These findings nominate tractable therapeutic targets and demonstrate a scalable framework for causal drug target prioritisation in rare autoimmune disease. Disclosure G. Chen: None. H. Chinoy: None. S.S. Zhao: None. A.S. Morris: None. J.A. Lamb: None.
2025-08-21 | [Clinical characteristics of anti-melanoma differentiation associated gene 5 antibody-positive juvenile dermatomyositis].
Objective: To analyze the clinical characteristics of anti-melanoma differentiation associated gene 5 (MDA5) antibody-positive juvenile dermatomyositis (JDM) patients. Methods: A retrospective case-control study was conducted. The positive group included 18 children with anti-MDA5 antibody-positive JDM who were admitted to the Department of Rheumatology and Immunology at Capital Center for Children's Health with Capital Medical University between January 2016 and January 2023. Another 36 children with anti-MDA5 antibody-negative JDM hospitalized during the same period were enrolled as the negative group. Based on the extent of pulmonary involvement and pulmonary CT scores, the MDA5-positive group was further divided into severe pulmonary involvement and non-severe pulmonary involvement subgroups. Chi-square test and Kruskal-Wallis test were used to compare clinical features, laboratory test results between groups. Results: Among the 18 patients in the MDA5-positive group, 7 were male and 11 were female, with an age of onset of 5.0 (2.6, 9.4) years and disease duration of 6.0 (4.0, 9.3) months. The MDA5-negative group included 36 cases (14 male, 22 female), with an age of onset of 4.9 (2.0, 7.0) years and disease duration of 5.0 (1.8, 7.0) months. The MDA5-positive group exhibited significantly higher rates of arthritis, skin ulcers, and interstitial lung disease (ILD), along with elevated serum ferritin (SF) and erythrocyte sedimentation rate levels compared to the MDA5-negative group (9/18 vs. 11% (4/36), 6/18 vs. 3% (1/36), 16/18 vs. 33% (12/36), 327 (141, 518) vs. 131 (68, 257) μg/L, 17.5 (12.5, 26.8) vs. 11.0 (5.0, 13.0) mm/1 h, χ²=7.92, 7.41, 14.84, Z=2.50, 2.87, all P<0.05). Conversely, the MDA5-positive group had lower rates of muscle weakness and lower creatine kinase levels (5/18 vs. 75% (27/36), 58.5 (49.3, 97.5) vs. 225.0 (68.0, 695.5) U/L, χ²=11.08, Z=-2.94, both P<0.05). Severe pulmonary involvement 6 cases and non-severe pulmonary involvement subgroups 12 cases. Among the MDA5-positive patients, those in the severe pulmonary involvement subgroup had an older age at onset and higher rates of muscle weakness as well as hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), SF, and Krebs von den Lungen-6 (KL-6) compared to the non-severe subgroup (all P<0.05). In the MDA5-positive group, 17 patients improved after treatment with glucocorticoids combined with immunosuppressants, while One died due to rapidly progressive ILD. Conclusions: Anti-MDA5 antibody-positive JDM is characterized by typical skin rashes, a high incidence of arthritis and skin ulcers, relatively mild muscle involvement, but is prone to ILD. Among MDA5-positive patients, those with older age at onset, muscle involvement (manifested as muscle weakness and elevated muscle enzymes (LDH, HBDH)), or significantly elevated KL-6 and SF levels are more likely to develop severe pulmonary complications.
2025-08-11 | Spatial transcriptomic analysis of muscle biopsy from patients with treatment-naive juvenile dermatomyositis reveals mitochondrial abnormalities despite disease-related interferon-driven signature.
This study aimed to investigate the spatial transcriptomic landscape of muscle tissue from patients with treatment-naive juvenile dermatomyositis (JDM) in comparison to healthy paediatric muscle tissue. Muscle biopsies from 3 patients with JDM and 3 age-matched controls were analysed using the Nanostring GeoMx Digital Spatial Profiler. Regions of interest were selected based on muscle fibres without immune cells, immune cell infiltration and CD68+ macrophage enrichment. Differential gene expression, pathway analysis and pathways clustering analysis were conducted. Key findings were validated in 19 cases of JDM using immunohistochemistry and chemical stains, and a bulk RNAseq dataset of 4 cases of JDM. JDM muscle tissues exhibited significant interferon pathway activation and mitochondrial dysfunction compared to controls. A 15-gene interferon signature was significantly elevated in JDM muscle and macrophage-enriched regions, correlating with clinical weakness. In contrast, mitochondrial dysregulation, characterised by downregulated respiratory chain pathways, was present regardless of interferon activity or muscle strength. The interferon-driven and mitochondrial signatures were replicated in an independent RNAseq dataset from JDM muscle; the lack of association between interferon signature and mitochondrial dysregulation was validated in 19 cases by conventional staining methods. Clustering analysis revealed distinct transcriptomic profiles between JDM and control tissues, as well as between patients with JDM with varying clinical phenotypes. This study highlights mitochondrial dysfunction as a consistent pathological feature in JDM muscle, which may be independent of interferon-driven inflammation. These findings highlight the potential for mitochondrial-targeted therapies in JDM management and emphasise the need for further studies to explore their therapeutic value.
2025-07-23 | Updates in juvenile dermatomyositis: pathogenesis and therapy.
This review provides updates on juvenile dermatomyositis pathogenesis and treatment. JDM pathogenesis research updates in genetic risk factors include C4 copy number. Studies clarify myositis-specific autoantibodies' (MSA) role in disease pathogenesis and more myositis-associated antibody (MAA) clinical associations. Recent studies validate an interferon (IFN)-regulated gene score and an IFN-related monocyte surface protein marker, SIGLEC-1. Vasculopathy and mitochondrial dysfunction evidence increases, both with ties to IFN. Studies point to not only T and B cells, but monocytes, macrophages, and neutrophils as dysregulated in JDM. Regarding treatment, there are growing reports of success with therapies targeting IFN-signaling (Janus kinase inhibitors), dazukibart (anti-IFN-beta), and anifrolumab (anti-IFNAR1). Chimeric antigen receptor (CAR) T-cell therapy targeting B-cells in a growing number of adult myositis patients and one JDM patient have dramatic reports of achieving drug-free remission. Growing evidence show genetic markers, MSA, IFN, vasculopathy, varied immune cells, and mitochondrial dysfunction having important roles in JDM pathogenesis. Some refractory patients show benefit with newer IFN pathway-targeted therapies and cellular CAR-T-cell therapy. Further collaborative research on disease pathogenesis, treatment targets, and innovate clinical trial design is needed to increase access to more efficacious treatments in JDM.
2025-07-07 | Efficacy of hydroxychloroquine treatment for the skin manifestations of juvenile dermatomyositis.
Juvenile dermatomyositis (JDM) is the most popular subtype of juvenile idiopathic inflammatory myopathies clinically characterised by skin manifestations and myositis. Some patients with JDM present predominantly with skin symptoms without significant muscle weakness. Furthermore, some patients exhibit residual skin disease even after showing improvement of muscle symptoms with systemic glucocorticoids (GCs) and immunosuppressants. Topical GCs and/or tacrolimus are recommended for the patients with skin predominant JDM. Furthermore, systemic use of GCs and methotrexate (MTX) are indicated in refractory cases. However, some patients show refractory skin disease to even systemic use of GCs and MTX. Hydroxychloroquine (HCQ) has been reported to improve skin manifestations associated with JDM and is used globally for JDM. However, HCQ is not approved by the Ministry of Health, Labour and Welfare of Japan for treatment of JDM. Herein, we report two patients with JDM presenting with residual skin disease after taking systemic GC and immunosuppressants, which was successfully treated with HCQ. HCQ was effective for treating a case with skin symptoms without significant muscle weakness at relapse and for a case with residual skin symptoms after showing improvement of muscle symptoms with systemic GCs and immunosuppressants. No adverse events were observed in their clinical courses. Thus, HCQ may be an effective choice as an adjunctive therapy for refractory skin symptom-dominant JDM.
cell therapies
2026-05-18 | Case Report: Sustained immune and pulmonary recovery three years after hematopoietic stem cell transplantation for ITCH E3 ubiquitin ligase deficiency.
Itchy E3 ubiquitin ligase deficiency (ITCH deficiency) is a rare monogenic immune dysregulation syndrome characterized by early-onset multisystem autoimmunity and significant morbidity and mortality. Only one prior case report has described a patient treated with hematopoietic stem cell transplantation (HSCT) with clinical improvement, and no established disease-modifying or curative therapy algorithm exists. We describe a female patient who presented in early childhood with chronic lung disease requiring tracheostomy and long-term mechanical ventilation and later developed progressive muscle weakness. She was diagnosed with steroid-responsive juvenile polymyositis and subsequently accumulated multiple autoimmune manifestations including autoimmune hepatitis, enteropathy, psoriasis, inflammatory arthritis, and Sjögren's-like parotitis. Genetic testing ultimately identified compound heterozygous pathogenic variants in ITCH. Despite prolonged treatment with multiple immunosuppressive and biologic therapies, she remained prednisone dependent with poor disease control and substantial treatment-related morbidity. At 20 years of age, she underwent allogeneic hematopoietic stem cell transplantation. Following transplantation, she achieved sustained resolution of autoimmune disease activity, was successfully weaned from all immunosuppressive therapy, and was decannulated from chronic mechanical ventilation, with marked improvement in functional status and quality of life. This is the second reported case demonstrating the benefit of hematopoietic stem cell transplant (HSCT) in ITCH deficiency and provides evidence of durable multisystem clinical remission and recovery of long-standing pulmonary and musculoskeletal disease. These findings support consideration of HSCT as a therapeutic option in carefully selected patients with severe, refractory autoimmune manifestations due to ITCH deficiency and raise the possibility that earlier consideration in the disease course may mitigate cumulative disease- and treatment-related morbidity.
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.
2024-10-19 | Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current Treatment, and Emerging Targeted Therapies.
Juvenile dermatomyositis is a rare systemic inflammatory autoimmune disease involving muscle, skin, and vessels. Most patients do not fully respond to initial therapy, instead having a chronic refractory or polycyclic disease course. Pathogenesis is not completely understood, but immune cell dysregulation, particularly of B cells, mitochondrial dysfunction, changes in neutrophils and neutrophil extracellular traps (NETs), and increased type I and type II interferon (IFN) signaling have been described. There are limited randomized controlled trials of drugs in juvenile dermatomyositis (JDM), and treatment is largely based on lower-quality data such as case series, retrospective studies, and open-label prospective studies. These data have been compiled into expert recommendations or consensus treatment plans, which help guide therapy. While initial therapy is more standard with most including corticosteroids (high-dose oral and/or pulse intravenous methylprednisolone) and methotrexate, for refractory patients, guidelines are more varied with multiple options or combinations, including biologic therapies. There is a clear need for more efficacious and personalized therapy in JDM. Emerging treatment options worthy of further study in JDM include targeting IFN-signaling (JAK, IFNAR1, IFN beta), B-cells (CD20, CD19, BAFF, TACI, CD38, BCMA) including Chimeric Antigen Receptor (CAR)-T cell therapy, mitochondrial dysfunction, and NETs.
2022-10-17 | CD8+ T Cell Phenotype and Function in Childhood and Adult-Onset Connective Tissue Disease.
CD8+ T cells are cytotoxic lymphocytes that destroy pathogen infected and malignant cells through release of cytolytic molecules and proinflammatory cytokines. Although the role of CD8+ T cells in connective tissue diseases (CTDs) has not been explored as thoroughly as that of other immune cells, research focusing on this key component of the immune system has recently gained momentum. Aberrations in cytotoxic cell function may have implications in triggering autoimmunity and may promote tissue damage leading to exacerbation of disease. In this comprehensive review of current literature, we examine the role of CD8+ T cells in systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, polymyositis, and dermatomyositis with specific focus on comparing what is known about CD8+ T cell peripheral blood phenotypes, CD8+ T cell function, and CD8+ T cell organ-specific profiles in adult and juvenile forms of these disorders. Although, the precise role of CD8+ T cells in the initiation of autoimmunity and disease progression remains to be elucidated, increasing evidence indicates that CD8+ T cells are emerging as an attractive target for therapy in CTDs.
2018-12-11 | Long-term follow-up of autologous hematopoietic stem cell transplantation for refractory juvenile dermatomyositis: a case-series study.
To follow up the refractory juvenile dermatomyositis (JDM) with autologous hematopoietic stem cell transplantation (AHSCT) in a long time and to investigate whether AHSCT is effective and safe to treat refractory JDM. We collected the AHSCT and follow-up data of three patients with refractory JDM who received autologous peripheral blood CD34+ cell transplantation in our hospital between June 2004 and July 2015. Those data include: hight, weight, routine blood and urine tests, ESR, CK, ALT, AST, LDH, renal functional tests, lymphocyte subpopulations, HRCT and muscle MRI. The last follow-up was done in June 2017. All three patients had complete remission and could stop prednisone after 3-12 months. None of them relapsed at 144, 113 and 23 months follow-up. Twelve months after their AHSCT, all of their monitoring indexes have returned to normal and they have stopped all medications. Until the date of this article, none of them relapsed or need medicine. Our study suggests that AHSCT is safe and effective in treating refractory JDM, and it can provides long term drug-free survival. However, more cases are needed for further confirmation.
antibodies
2025-12-12 | Clinical use of intravenous immunoglobulin in juvenile dermatomyositis: indications, treatment course, and clinical outcomes.
To evaluate indications, clinical response, outcomes, and tolerability of intravenous immunoglobulin (IVIG) therapy in patients with juvenile dermatomyositis (JDM) in a multicenter cohort. This retrospective multicenter study included 29 patients with JDM who received IVIG. Demographic data, clinical features, laboratory parameters, and standardized disease activity scores were recorded at disease onset, before and after IVIG treatment, and at final follow-up. Treatment response and adverse events were analyzed. IVIG was initiated a median of 1.2 months (IQR: 0.1-18.9) after diagnosis and continued for a median of 8.2 months (IQR: 5.6-21.6). Indications included refractory muscle weakness, persistent skin disease, calcinosis, and interstitial lung disease (ILD). IVIG therapy was associated with significant improvements in disease activity measures and laboratory parameters (p < 0.001). Calcinosis partially or completely resolved in 3 of 6 patients, while no change was observed in the single ILD case. IVIG was well tolerated, with only mild adverse effects. IVIG appears to be a safe and effective treatment option for JDM, particularly in refractory or skin-predominant disease. Although causal inferences are limited by the retrospective design and the absence of a control group, these real-world findings support the inclusion of IVIG in an individualized treatment approach.
2025-07-30 | Treatment outcomes in 63 cases of juvenile dermatomyositis-associated calcinosis.
We performed a multi-institutional retrospective review of patients treated for juvenile dermatomyositis (JDM)-associated calcinosis to analyse the association between treatment outcomes and patient, disease, and treatment characteristics. Childhood Arthritis and Rheumatology Research Alliance investigators searched their electronic health records for patients with JDM and calcinosis treated between 2003 and 2019 and analysed data at JDM diagnosis, calcinosis diagnosis, and calcinosis treatment. Statistical methods included univariable and multivariable analyses, Kaplan-Meier estimates, and multivariable Cox models. Data were collected for 63 patients from 11 institutions. Median (IQR) age was 7.8 (4.1-11.1) years at JDM diagnosis and 9.4 (5.7-13.3) years at calcinosis diagnosis. Calcinosis was present at JDM diagnosis in 32% of patients (n=20). JDM was active in 76% of patients (47/62) at calcinosis diagnosis. Anti-nuclear matrix protein 2 (anti-NXP2) antibody was the most commonly detected myositis autoantibody (38%, 12/32). The presence of anti-NXP2 or anti-melanoma differentiation-associated gene 5 autoantibody did not significantly affect the probability of any calcinosis improvement (p=0.30). Patients received 103 unique treatment regimens of immunomodulatory agents with or without calcium-modifying agents, but those who received both had the greatest probability of improvement. Intravenous immunoglobulin (IVIG) was associated with a significantly higher probability of calcinosis improvement (p=0.02) than treatments without IVIG. Overall, 79% of patients (n=50) showed improved calcinosis. Despite wide variations in treatment, many patients showed calcinosis improvement over time, especially those treated with IVIG. Studies using validated outcomes assessments may be needed to develop effective treatment plans for JDM-associated calcinosis.
2024-06-06 | Elevated type I IFN signalling directly affects CD8+ T-cell distribution and autoantigen recognition of the skeletal muscles in active JDM patients.
The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of elevated type I IFN signaling on CD8+ T cell-associated muscle damage in juvenile dermatomyositis (JDM). This study used flow cytometry (FC) and RT‒PCR were used to examine the circulating cell ratio and type I IFN response. And scRNA-seq was used to examine peripheral immunity in 6 active JDM patients, 3 stable JDM patients, 3 juvenile IMNM patients and 3 age-matched healthy children. In vivo validation experiments were conducted using a mouse model induced by STING agonists and an experimental autoimmune myositis model (EAM). In vitro experiments were conducted using isolated CD8+ T-cells from JDM patients and mice. We found that active JDM patients showed an extensive type I IFN response and a decreased CD8+ T-cell ratio in the periphery (P < 0.05), which was correlated with muscle involvement (P < 0.05). Both new active JDM patients and all active JDM patients showed decreased CD8+ TCM cell ratios compared with age and gender matched stable JDM patients (P < 0.05). Compared with new pediatirc systemic lupus erythematosus (SLE) patients, new active JDM patients displayed decreased CD8+ T-cell and CD8+ TCM cell ratios (P < 0.05). Active JDM patient skeletal muscle biopsies displayed an elevated type I IFN response, upregulated MHC-I expression and CD8+ T-cell infiltration, which was validated in EAM mice. sc-RNAseq demonstrated that type I IFN signalling is the kinetic factor of abnormal differentiation and enhances the cytotoxicity of peripheral CD8+ T cells in active JDM patients, which was confirmed by in vivo and in vitro validation experiments. In summary, the elevated type I IFN signalling affected the differentiation and function of CD8+ T cells in active JDM patients. Skeletal muscle-infiltrating CD8+ T cells might migrate from the periphery under the drive of type I IFN and increased MHC I signals. Therapies targeting autoantigen-specific CD8+ T cells may represent a potential new treatment direction.
2024-01-05 | Local injection of infliximab into calcinosis lesions in patients with juvenile dermatomyositis (JDM): a clinical trial.
Juvenile Dermatomyositis (JDM) is a rare autoimmune disorder that primarily affects muscles and skin. One of the severe complications associated with JDM is calcinosis, and treating this condition presents significant challenges. This study aimed to evaluate the efficacy and safety of local injection of infliximab into calcinosis lesions in patients with JDM. In this clinical trial, five patients diagnosed with JDM and calcinosis lesions were enrolled. The primary treatment consisted of weekly infliximab injections for 16 weeks, targeting all four sides of each lesion. Lesion dimensions, including length and width, were documented and monitored weekly. Before the intervention, patients underwent radiographic imaging. After the final injection in week 16, a follow-up radiographic assessment was performed. Data were analyzed using the Generalized Estimating Equation (GEE) method. The lesions' size significantly decreased in both length and width during each visit. On average, the lesion length reduced by 2.66%, and the width shrank by 3.32% per visit. Based on radiographic findings, the average length and width of lesions at the initial visit were 12.09 ± 5.05 mm (range: 6.00-25.50 mm) and 6.35 ± 3.00 mm (range: 2.00-16.00 mm), respectively. The average length and width at the last visit were 5.59 ± 7.05 mm (range: 0-23.00 mm) and 3.41 ± 4.05 mm (range: 0-13.00 mm), respectively. No specific side effects related to the treatment were reported. The results suggest that the direct administration of infliximab into the calcinosis lesions of patients with JDM could be a safe and effective treatment approach. Name of the registry: The effect of infliximab injection into calcinosis lesions on patients with juvenile dermatomyositis (JDM), Trial registration number: IRCT20210808052107N1, Registration date: 2022-07-22, URL of trial registry record: https://en.irct.ir/trial/58329 .
2023-12-22 | Lung infection or inflammation-a puzzling case of MDA-5 associated juvenile dermatomyositis.
Juvenile dermatomyositis (JDM) is an uncommon inflammatory myopathy predominantly affecting children under 18 years of age. Diagnosis relies on identifying specific clinical features, such as muscle weakness, skin rash, elevated muscle enzymes, and MRI and muscle biopsy findings. Autoantibodies associated with inflammatory myopathy offer valuable prognostic insights and can indicate the risk of internal organ involvement, though they are relatively rare in childhood myopathies. JDM can progress to interstitial lung disease (ILD) if associated with MDA5 antibodies, and immunosuppressive therapy constitutes the primary treatment approach. We present a unique case of JDM complicated by disseminated histoplasmosis in a 12-year-old African American male cross-country runner with no prior medical history. He presented with unintentional weight loss and a rash on his hands, genitals, and fingertips, which persisted despite previous treatments. Diagnosis of JDM was confirmed through clinical and laboratory evaluations. Over time, the patient developed recurrent fevers, thrombocytopenia, and signs of ILD, leading to the identification of disseminated histoplasmosis as a complicating factor. Appropriate antifungal treatment resolved the infectious condition, while continued immunosuppression aided in managing JDM and ILD. Juvenile dermatomyositis (JDM) remains a rare and intricate autoimmune disorder affecting young individuals. The presence of MDA5 antibodies in JDM patients can lead to severe complications like ILD, necessitating vigilant monitoring. Management includes immunosuppressive therapy, with glucocorticoids and mycophenolate mofetil proving effective, particularly in Clinically Amyopathic Dermatomyositis (CADM) cases. In cases of refractory disease, intravenous immunoglobulin (IVIG) plays a crucial role, offering a safe and beneficial adjunct to treatment. We emphasize the importance of recognizing atypical presentations of JDM, as it can lead to delays in diagnosis and treatment. Our case highlights the complexities of managing dual lung pathology, where a secondary infection exacerbated lung nodules and thrombocytopenia, while ILD was a consequence of atypical myopathy. Combining antifungal treatment with immunosuppression effectively managed both conditions and follow-up evaluations demonstrated improvement in ILD. Awareness of potential fungal infections in immunosuppressed JDM patients is crucial for successful treatment and patient outcomes.
proteins
2025-09-08 | Discovery of tissue-specific proteomic signatures in juvenile dermatomyositis highlights pathways reflecting persistent disease activity, clinical heterogeneity, and myositis-specific autoantibody subtype.
Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune condition needing targeted treatment approaches and improved understanding of molecular mechanisms driving clinical phenotypes. We utilised exploratory proteomics from a longitudinal North American cohort of patients with new-onset JDM to identify biological pathways at disease onset and follow-up, tissue-specific disease activity, and myositis-specific autoantibody (MSA) status. We measured 3072 plasma proteins (Olink panel) in 56 patients with JDM within 12 weeks of starting treatment (from the Childhood Arthritis and Rheumatology Research Alliance Registry and 3 additional sites) and 8 paediatric controls. Twenty-four patients with JDM who had 6-month follow-up samples were assessed. We identified differentially expressed proteins (DEPs) between groups by fitting linear mixed effects models and associated DEPs with validated disease activity measures. We assessed for cell/tissue specificity using the Human Protein Atlas and JDM muscle single nuclei and skin single-cell transcriptomic datasets. Differences within MSA subgroups were also analysed. We uncovered persistent dysregulation of innate immune activation, cell death, and redox signalling at 6 months despite multidrug immunosuppression. By leveraging tissue and cell-specific proteomes, we identified overrepresentation of circulating endothelial proteins associated with disease activity and verified endothelial cell marker expression in JDM muscle and skin. We discovered pathways associated with MSA subtypes that reflect JDM phenotypes. NXP2+ JDM-associated proteins reflected angiogenesis and extracellular matrix remodelling and were expressed in endothelial cells and fibroblasts. MDA5+ JDM was associated with circulating type III interferon and surfactant proteins. These proteomic findings will inform future biomarker and treatment development considering the unique tissue- and autoantibody-associated inflammation in JDM.
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.
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