Juvenile Idiopathic Inflammatory Myopathies Research Articles

Deciphering the Role of Maternal Microchimerism in Offspring Autoimmunity: A Narrative Review.

Feto-maternal microchimerism is the bidirectional transfer of cells through the placenta during pregnancy that can affect the health of both the mother and the offspring, even in childhood or adulthood. However, microchimerism seems to have different consequences in the mother, who already has a developed immune system, than in the fetus, which is vulnerable with immature defense mechanisms. Studies have shown that the presence of fetal microchimeric cells in the mother can be associated with reduced fetal growth, pre-eclampsia, miscarriage, premature birth, and the risk of autoimmune disease development in the future. However, some studies report that they may also play a positive role in the healing of maternal tissue, in cancer and cardiovascular disease. There are few studies in the literature regarding the role of maternal microchimeric cells in fetal autoimmunity. Even fewer have examined their association with the potential triggering of autoimmune diseases later in the offspring's life. The objectives of this review were to elucidate the mechanisms underlying the potential association between maternal cells and autoimmune conditions in offspring. Based on our findings, several hypotheses have been proposed regarding possible mechanisms by which maternal cells may trigger autoimmunity. In Type 1 diabetes, maternal cells have been implicated in either attacking the offspring's pancreatic β-cells, producing insulin, differentiating into endocrine and exocrine cells, or serving as markers of tissue damage. Additionally, several potential mechanisms have been suggested for the onset of neonatal lupus erythematosus. In this context, maternal cells may induce a graft-versus-host or host-versus-graft reaction in the offspring, function as effectors within tissues, or contribute to tissue healing. These cells have also been found to participate in inflammation and fibrosis processes, as well as differentiate into myocardial cells, potentially triggering an immune response. Moreover, the involvement of maternal microchimeric cells has been supported in conditions such as juvenile idiopathic inflammatory myopathies, Sjögren's syndrome, systemic sclerosis, biliary atresia, and rheumatoid arthritis. Conversely, no association has been found between maternal cells and celiac disease in offspring. These findings suggest that the role of maternal cells in autoimmunity remains a controversial topic that warrants further investigation.

Clinicopathological features and treatment outcome of juvenile idiopathic inflammatory myopathies with anti-melanoma differentiation associated gene 5 antibodies: A case series study.

To characterize the clinicopathological features and treatment outcomes of juvenile idiopathic inflammatory myopathies (JIIM) with anti-melanoma differentiation associated gene 5 (MDA5) antibodies in a Chinese cohort. Anti-MDA5 antibody was detected by immunodot assay and indirect immunofluorescence assay on HEK293 cells in a series of Chinese JIIM cohort between 2005 and 2022. The clinical features, histological findings, and treatment outcomes of these anti-MDA5-antibody-positive patients were summarized. Of 59 JIIM patients, 3 (5.08%) were found to be anti-MDA5-antibody-positive. The frequency of anti-MDA5 antibody did not show significant difference between adult idiopathic inflammatory myopathies and JIIM cohorts (P = .720). The disease duration in patients with anti-MDA5 antibody was 2.83 ± 1.04 months. All 3 patients had typical skin lesions including Gottron sign and heliotrope rash, while interstitial lung disease and arthritis was only found in 1 patient. All 3 patients showed normal creatine kinase levels. On muscle biopsy, diffuse major histocompatibility complex class-I expression was seen in 3 patients and myxovirus-resistance protein A expression was found in 2 patients. All patients received long-term follow-up (6.42 ± 4.01 years). They were all drug-free and showed favorable treatment outcome with prednisone and additional immunosuppressant. Our study indicates that anti-MDA5 antibodies may not be common in Chinese JIIM. Anti-MDA5-positive JIIMs are characterized by typical skin lesions of dermatomyositis, normal CK levels, and increased major histocompatibility complex class-I expression. JIIMs with anti-MDA5 generally have good response to immunotherapies.

Diagnostic Value of Whole-Body MRI in Pediatric Patients with Suspected Rheumatic Diseases.

Background and Objectives: The diagnosis of rheumatic diseases in children is challenging and requires the use of advanced imaging examinations such as whole-body magnetic resonance imaging (MRI). Whole-body MRI allows visualization of bone marrow edema (BME), muscle edema, joint effusion and changes in the soft tissues surrounding the joints. The aim of this study was to collect and compare whole-body MRI findings, laboratory results and clinical manifestations of pediatric patients with suspected rheumatic disease. Materials and methods: In this retrospective single-center study, 33 patients who underwent whole-body MRI were included. Their age ranged from 9 to 17 years, and 24 (72.73%) of the patients were female. Patients were diagnosed as follows: juvenile idiopathic arthritis (27.27%), juvenile idiopathic inflammatory myopathies (21.21%), chronic nonbacterial osteomyelitis (21.21%) and other medical conditions (30.30%), such as arthritis associated with infection, scleroderma, Takayasu arteritis, polyarteritis nodosa and joint damage. Results: The most common symptom reported by 26 (79.79%) patients was pain. On physical examination, the limitation of joint mobility was examined in 17 (51.51%), swelling of the joints was observed in 12 (36.36%) patients and decreased muscle strength was noticed in 11 (33.33%) patients. An increase in the C-reactive protein (12%), erythrocyte sedimentation rate (9%), leukocyte count (9%) and creatine kinase (CK) (18%) was observed. Whole-body MRI revealed myositis (30%), joint effusion (27%) and BME (24%). The statistical analysis showed a significant relationship between myositis and the elevated CK level (p < 0.05). Conclusions: The most common symptom in the studied population was pain, while the limitation of joint mobility was found in more than half of patients. Myositis was the most commonly imaged lesion on the whole-body MRI and it was related to an increase in the CK level.

Clinical and genetic analysis of macrophage activation syndrome complicating juvenile idiopathic inflammatory myopathies.

Macrophage activation syndrome (MAS) is a serve complication of juvenile idiopathic inflammatory myopathies (JIIMs). This study delineates the clinical manifestations and genetic underpinnings of JIIM-MAS patients. We retrospectively analysed clinical and UNC13D gene from JIIM patients admitted to our centre between 2011 and 2021 to identify cases of MAS. Additionally, a literature review summarising reported cases of JIIMs and MAS was performed. Of 773 JIIM patients, 10 (1.3%) were diagnosed with MAS. All patients presented with persistent fever and hyperferritinaemia. Seventy percent of patients met the HLH-2004 criteria, while 90% met the 2016 sJIA-MAS criteria. Most patients received combined treatment of corticosteroids and immunosuppressants. UNC13D gene analysis was performed in six patients. A homozygous pathogenic mutation (c.2588G>A) was detected in one patient with recurrent MAS, and twenty-eight single-nucleotide polymorphisms (SNPs) were detected. Eighty percent of patients exhibiting a consistent combination of ten SNPs compared to JIIM patients without MAS (35%). MAS is an early and often overlooked complication of JIIMs. The 2016 sJIA-MAS criteria may facilitate early diagnosis. Combined corticosteroid and immunosuppressant therapy prove effective. An increased prevalence of UNC13D gene polymorphisms was observed in JIIM-MAS patients, highlighting the necessity for further investigations. This study aimed to delineate the clinical manifestations and genetic underpinnings of macrophage activation syndrome (MAS) in ten patients with juvenile idiopathic inflammatory myopathies (JIIMs). MAS has been recognised as a complication of JIIMs. However, only a few case reports provide comprehensive descriptions of MAS in JIIM patients, and there are few reports related to UNC13D mutations in these patients. This article offers single-centre clinical insights to enhance the identification and management of MAS in JIIM patients, while also highlighting the potential association between MAS occurrence and UNC13D gene polymorphisms.

Current efforts and historical perspectives on classification of idiopathic inflammatory myopathies.

The classification of idiopathic inflammatory myopathies is challenging due to the large number of clinical, serological, histopathological and genetic findings, as well as the latest findings and developments in the field of myositis research. The latest official classification criteria are the 2017 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies, which have been extensively reviewed in recent years for their applicability, sensitivity and specificity. The sensitivity and specificity of the 2017 ACR/EULAR criteria are sometimes performing better, but usually at the same level as the previous criteria. A large number of further suggestions for amendments to the criteria have been made. In particular there is a need to revise the criteria with regard to the addition of new myositis-specific autoantibodies, newly defined subgroups (especially antisynthetase syndrome, immune medicated necrotizing myopathy and overlap myositis) and possibly the addition of further diagnostic procedures (for instance, muscle MRI or PET CT) to improve the accuracy and timeliness of the criteria. Efforts to optimize the myositis classification criteria have been extensive in recent years and a new global interdisciplinary collaboration of clinicians is currently taking place based on the previous results with the aim of revising the 2017 EULAR/ACR classification criteria.

Clinical relevance of positively determined myositis antibodies in rheumatology: a retrospective monocentric analysis

BackgroundThe increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955–64. https://doi.org/10.1136/annrheumdis-2017-211468.). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice.MethodsA monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out.ResultsIn the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed.ConclusionsIn our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.

A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

Inclusion Body Myositis in Children: Does it Exist?

Context: Sporadic inclusion body myositis (sIBM) is a rare type of juvenile idiopathic inflammatory myopathies (JIIMs). It mainly affects skeletal muscles but can also affect the skin and other organs in the body. Sporadic inclusion body myositis prevalence in children under 18 years old is very rare. Objectives: This review provides an overview of the evidence of sIBM in children, discusses the possible clinical and pathological features, and explores the proposed pathogenesis. Methods: A literature review of over 44 articles in PubMed and other medical libraries, such as Google Scholar and Web of Science, was carried out using terms such as JIIM, IBM, Inflammatory Myopathies in Children, and Inherited IBM. Two documented reports for sIBM were found, and the rest included the disease pathogenesis, prevalence of inherited IBM, and other myopathies in children. Results: This review discussed the prevalence and incidence of JIIM, in particular sIBM in children. While IBM is typically sporadic, there have been rare cases where it is familial and inherited. Genetic susceptibility factors are believed to play a role in sIBM. Most patients with sIBM are over 50 years old and experience significant weakness in the quadriceps; however, patients with inherited IBM (h-IBM) typically present earlier in adulthood with a distinct pattern of weakness. Sporadic inclusion body myositis can be misdiagnosed as other forms of myopathies, such as juvenile dermatomyositis (JDM) or limb-girdle muscular dystrophy (LGMD), during the early stages of the disease. The exact causes of sIBM are still unknown; however, environmental factors, genetic predispositions, and immune dysregulation might contribute to the pathogenesis of the disease. Conclusions: Sporadic inclusion body myositis is a rare form of JIIMs. Its early diagnosis in children can be challenging due to the presence of other coexisting diseases. Discussions have revolved around potential environmental factors, such as viral infections, specific myositis-specific antibodies (MSAs), such as anti-Ro52, and possibly certain human leukocyte antigen (HLA) haplotypes. Given the rarity of reported cases of sIBM in children, it is important to encourage further studies to better understand the underdiagnosed instances of this condition.

Magnetic resonance imaging of the musculoskeletal system in the diagnosis of rheumatic diseases in the pediatric population.

Magnetic resonance imaging (MRI) of the musculoskeletal system is an examination increasingly performed for suspected juvenile idiopathic arthritis, chronic nonbacterial osteomyelitis and juvenile idiopathic inflammatory myopathies, as well as other rheumatic diseases of developmental age. T1-, T2- and PD-weighted with or without fat suppression or short tau inversion recovery/turbo inversion recovery magnitude (STIR/TIRM) sequences and post-contrast sequences are evaluated to diagnose pathological changes in the synovial membrane, subchondral bone marrow and surrounding soft tissues. Magnetic resonance imaging allows detection of synovitis, tenosynovitis, bursitis, and enthesitis as well as bone marrow edema and soft tissue edema. Several pediatric-specific MRI scoring systems have been developed and validated to standardize and facilitate the assessment of the extent of the inflammatory process and disease activity in MRI. Early detection of inflammatory changes allows the inclusion of comprehensive pharmacotherapy giving the possibility of permanent remission and objective measurement of the effectiveness of treatment.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

The impact of the COVID-19 pandemic on patients with juvenile idiopathic inflammatory myopathies

BackgroundThroughout the COVID-19 pandemic, there have been concerns regarding the risks of infection in patients with autoimmune disease. In this study, we investigated the impact of the pandemic on patients with juvenile idiopathic inflammatory myopathies (JIIM).MethodsData were collected using a patient/caregiver survey via Research Electronic Data Capture (REDCap) database. Eligibility included JIIM diagnosis and current age less than 21 years old. Surveys were distributed via the CureJM organization, social media, Childhood Arthritis and Rheumatology Research Alliance (CARRA) network and Dr. Peter Dent Pediatric Rheumatology Bulletin Board.ResultsEighty-four respondents accessed the survey, 70 (83%) consented to participate, and 54 out of 70 completed the full survey (77%). Twenty-seven out of 57 patients (47%) tested positive for COVID-19, with 7 (12%) testing positive more than once. Despite broad usage of immunosuppressive medications, 24 out of 27 (89%) reported mild symptoms with none requiring hospitalization. Four patients reported a flare of JIIM symptoms after COVID-19; three of whom held immunomodulatory medications during their infection. Thirty-seven out of 54 respondents (69%) reported vaccination against COVID-19, with 9 out of 37 (24%) reporting minor vaccine side effects and one reporting JIIM flare post vaccination. Twenty-one out of 54 (39%) respondents reported psychosocial concerns related to the COVID-19 pandemic.ConclusionsPatients with JIIM, including those on multiple immunosuppressive medications, had mild symptoms related to COVID-19. Most patients tolerated COVID-19 vaccination well. Few patients had disease flare post-COVID-19 or vaccination. Mental health concerns were demonstrated in JIIM patients during the COVID-19 pandemic.

Clinical features and outcomes of children’s interstitial lung disease accompanied with connective tissue disease: A prospective cohort study

BackgroundMedical complexity of childhood interstitial lung disease (chILD) with connective tissue disease (CTD) poses a considerable challenge to pediatricians. MethodsClinical characteristics, laboratory findings, pulmonary function tests (PFTs), treatments and outcomes obtained for patients with CTD-chILD were analyzed in a prospective study. ResultsPatients’ median age at diagnosis was 7 years old. About 29.4% (15/51) suffered rapidly progressive childhood ILD (RP-chILD) with a high mortality rate (33.3%, 5/15), and the incidence of RP-chILD in juvenile idiopathic inflammatory myopathies was as high as 41.6% and the mortality rate was 30% (3/10). More than 70% patients had decreased diffusion capacity. The mean interval from symptoms-onset to diagnosis was 11.3 months. Compared to chILD with known CTD, the chILD proceeded CTD had a longer diagnosis interval, higher mortality, hospital stays and costs (P < 0.05). Lung imaging (33.3%) and lung function (72.7%) were partially reversible. The average survival time was 68.6 months. Cox univariate analysis showed that HRCT score ≥3, experiencing RP-chILD, cyanosis, acute respiratory distress syndrome (ARDS) and CD4 T cell <200 were significant predictors of death for chILD, whereas Cox multivariate analysis showed that ARDS was significant predictor of death for CTD-chILD, while IVIG support combined with corticosteroids and immunosuppressants was a protective factor. ConclusionsCare providers should conduct an assessment for CTD in chILD as a longer interval between the diagnosis of chILD and the CTD is associated with increased mortality. Complications as ARDS predict poor outcome in CTD-chILD, while IVIG support combined with corticosteroids and immunosuppressants is a protective factor.

Impact of SARS-CoV-2 on the clinical presentation of juvenile idiopathic inflammatory myopathies

BackgroundGrowing evidence suggests that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger idiopathic inflammatory myopathies (IIM). Few studies have described individual juvenile IIM (JIIM) cases following SARS-CoV-2 infection, and none explored its potential effects on JIIM clinical presentation. We aim to investigate the impact of SARS-CoV-2 on JIIM in patients diagnosed before and after the onset of the Coronavirus Disease 2019 (COVID-19) pandemic.MethodsPatients diagnosed with JIIM before age 19 at The Children’s Hospital at Montefiore were included. Demographics, clinical and laboratory data, and evidence of SARS-CoV-2 exposure were collected retrospectively. Patients were grouped by pre-COVID-19 (before January 1, 2020) and post-COVID-19 (January 1, 2020, or later). Descriptive statistics were used to summarize each variable. Non-parametric testing was performed using Fischer’s exact test and Mann-Whitney U test.ResultsFifty-one patients were included, 13 (25%) diagnosed in the post-COVID-19 era. Of these, 10 (77%) had onset of JIIM symptoms after January 1, 2020; 6 (60%) with known or suspected SARS-CoV-2 exposure. Though not statistically significant, post-pandemic patients tended to be older, female, and have non-specific cutaneous manifestations. Despite reported delays in care for other pediatric diagnoses during the pandemic, fewer post-pandemic patients had delays in JIIM diagnosis.ConclusionsThis is the first study to explore the effects of SARS-CoV-2 on JIIM clinical presentation. While our exploratory single-center study did not find significant differences in JIIM diagnosed pre- and post-pandemic, larger prospective multicenter studies are warranted to evaluate this association and to explore clinical variances over time.

Alternative Therapies to Immunoglobulin for Idiopathic Inflammatory Myopathies

&#x0D; We did not find any evidence regarding the clinical effectiveness and safety of alternative treatments to IV Immunoglobulin (IVIG) compared to IVIG or placebo for idiopathic inflammatory myopathies (IIM) that met our inclusion criteria for this review.&#x0D; Three evidence-based guidelines provide recommendations regarding IVIG and other drugs to manage IIM. However, we did not find any recommendations regarding alternative treatments to IVIG specifically.&#x0D; Rituximab may be considered as another option to IVIG to treat IIM-related skeletal muscle inflammation (1 guideline) or skin manifestations (1 guideline) resistant to treatment with steroids.&#x0D; In juvenile IIM, rituximab or IVIG can be used as adjunct care in case of treatment failure.&#x0D;

Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care.

The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.

Retinal changes in patients with idiopathic inflammatory myopathies: A case-control study in the MyoCite cohort.

Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with Idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Adult and Juvenile IIM patients (2017 ACR/EULAR criteria), visiting a tertiary care center in 2021 were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6 vs. 4.3%, p < 0.001), AV nicking (14 vs. 2.2%, p = 0.053), and vascular tortuosity (18.6 vs. 2.2%, p = 0.012), besides decreased visual acuity (53.5 vs. 10.9%, p<0.001) and immature cataracts (34.9 vs. 2.2%, p < 0.001). Attenuation of vessels [OR 10.9 (1.7-71), p = 0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p = 0.068], especially attenuation of vessels [14(38%) vs. 0(0), p = 0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Retinal microvasculopathy and diminution of vision occur in nearly one-thirds to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

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

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

Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features.

Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.

Experience with the use of mycophenolate mofetil in juvenile idiopathic inflammatory myopathies.

The objective of this study was to evaluate the efficacy and safety of MMF in juvenile idiopathic inflammatory myopathies (JIIMs). Patients diagnosed with JIIM and treated with MMF enrolled in the Juvenile Dermatomyositis Research Group (JDRG) in the UK or followed at the Giannina Gaslini Institute in Genoa, Italy, were included. The following information was collected retrospectively at MMF initiation, at 3, 6 and 12 months after treatment start, and at last follow-up visit: clinical manifestations, laboratory data, physicians' subjective assessment of disease activity, standardized outcome measures of muscle strength/endurance, cutaneous disease activity, physical function, global disease activity, cumulative damage, and ongoing treatment. Of the 29 patients included, 23 had juvenile DM and 6 had overlap myositis. During administration of MMF, improvement in measures of muscle strength, skin disease activity, and overall disease activity was seen, with an increase in the frequency of normal scores for Manual Muscle Test-8 from 50.0% to 83.3%, Childhood Myositis Activity Score from 53.5% to 88.9%, muscle component of DAS from 55.2% to 84.2%, skin component of DAS from 31.0% to 42.1%, visual analogue scale for skin disease activity from 25.0% to 47.4%, and visual analogue scale for overall disease activity from 7.1% to 42.1%. The number of patients with inactive disease increased from 10.3% at baseline to 68.5% at last follow-up. CS dose was significantly reduced, from 0.3 to 0.1 mg/kg/day. No relevant side effects were reported. Our experience suggests that MMF is a valuable therapeutic option for the management of JIIM.

Performance of the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology Classification Criteria in Patients With Idiopathic Inflammatory Myopathy and Anti-Melanoma Differentiation-Associated Protein 5 Positivity.

This study aimed to evaluate whether the 2017 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) could appropriately classify the diagnosis in adult patients with anti-melanoma differentiation-associated protein 5 (anti-MDA-5)-positive IIM. In addition, this study sought to determine whether a status of anti-MDA-5 positivity could be incorporated into the EULAR/ACR IIM classification criteria set and whether the recently modified criteria based on the presence of myositis-specific autoantibodies (MSAs) could be used to appropriately classify the diagnosis in patients with anti-MDA-5-positive IIM. Consecutive adult patients clinically diagnosed as having anti-MDA-5-positive IIM from 10 hospitals in Hong Kong were retrospectively recruited; patient characteristics were obtained from electronic medical records. We used a commercial line blot immunoassay to detect MSAs. We also determined a proposed set of phenotypic-serologic classification criteria specific for anti-MDA-5. In the patient cohort (n=120; 31.7% with dermatomyositis, 68.3% with clinically amyopathic dermatomyositis [CADM]), the diagnosis could be classified with the EULAR/ACR criteria in 86 patients (71.7%) and with the Bohan and Peter criteria in 49 patients (40.8%). However, when combined with criteria specifically modified for CADM, the diagnosis could be classified by the Bohan and Peter criteria in 76.7% of patients. We observed that the sensitivity of the EULAR/ACR criteria could be improved to 98.3% if anti-MDA-5 antibody-positive status was considered as one of the criteria. The MSA-based criteria had 100% sensitivity. When we applied our proposed specific phenotypic-serologic criteria for the classification of patients with anti-MDA-5 antibodies, 97.5% of patients were able to be classified as having IIM. In this cohort of patients with anti-MDA-5-positive IIM, the diagnosis could not be classified by the EULAR/ACR criteria in almost 30% of patients. We suggest incorporating anti-MDA-5 antibody positivity as a criterion into existing criteria sets or developing specific criteria for patients with anti-MDA-5-positive IIM.