Search

Objectives: To assess the efficacy and safety of branched chain amino acids (BCAAs) in the treatment of PM/DM prior to official approval of their use in Japan., Methods: Treatment naïve adults with PM/DM were enrolled in a randomized, double-blind trial to receive either TK-98 (drug name of BCAAs) or placebo in addition to conventional treatment. After 12 weeks, patients with an average manual muscle test (MMT) score <9.5 were enrolled in an open label extension study for a further 12 weeks. The primary endpoint was the change of the MMT score at 12 weeks. The secondary endpoints were the clinical response and the change of functional index (FI)., Results: Forty-seven patients were randomized either to the TK-98 (n = 24) or placebo (n = 23) group. The changes of MMT scores at 12 weeks were 0.70 (0.19) [mean (s.e.m.)] and 0.69 (0.18), respectively (P = 0.98). Thirteen patients from the TK-98 group and 12 from the placebo group were enrolled in the extension study. The MMT scores in both groups improved similarly. The increase of the FI scores of the shoulder flexion at 12 weeks was significantly greater in the TK-98 group [27.9 (5.67) vs 12.8 (5.67) for the right shoulder flexion, and 27.0 (5.44) vs 13.4 (5.95) for the left shoulder; P < 0.05]. Frequencies of adverse events up to 12 weeks were similar., Conclusion: BCAAs showed no effect on the improvement of the muscle strength evaluated by MMT and the clinical response. However, they were partly effective for improving dynamic repetitive muscle functions., Trial Registration: UMIN-CTR Clinical Trial, https://center6.umin.ac.jp/, UMIN000016233., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Dermatomyositis (DM) is an idiopathic inflammatory myopathy which often involves the lungs. DM is likely to be associated with aberrant T- and B-cell activation in the pathogenesis because of the proven effectiveness of T- and B-cell-targeted treatments. Assuming that the aberrant activation is reflected by biases in the lymphocyte subset repertoires, we aimed to elucidate these biases, especially in relation to clinical features of DM., Method: Based on the immunophenotyping standardized by the Human Immunology Project Consortium, untreated 13 DM patients, including seven patients with interstitial lung disease (ILD), and 18 age-matched healthy donors (HDs) were examined for proportions of peripheral blood lymphocyte subsets. Six DM patients were examined before and after successful induction of remission., Results: Naïve CD4 + T cells and naïve B cells were more abundant, while there were fewer naïve CD8 + T cells, central memory CD8 + T cells, effector memory CD4 + T cells, Th1 cells, Tfh cells, and memory B cells in DM patients than in HDs. When the patients were subgrouped according to the presence of ILD, the lymphocyte subset repertoires in the patients with ILD contributed to the statistical differences in all the biased lymphocyte subset proportions. After treatment, transitional B cells vanished and there was an increase in memory B cells., Conclusion: The lymphocyte subset repertoires in the DM patients were biased, and were associated with the presence of ILD and disease activity of DM.

Although rheumatologists, neurologists and dermatologists see patients with polymyositis (PM) and dermatomyositis (DM), their management appears to vary depending on the physician's specialty. The aim of the present study was to establish the treatment consensus among specialists of the three fields to standardize the patient care. We formed a research team supported by a grant from the Ministry of Health, Labor and Welfare, Japan. Clinical questions (CQ) on the management of PM and DM were raised. A published work search on CQ was performed primarily using PubMed. Using the nominal group technique, qualified studies and results in the published work were evaluated and discussed to reach consensus recommendations. They were sent out to the Japan College of Rheumatology, Japanese Society of Neurology and Japanese Dermatological Association for their approval. We reached a consensus in 23 CQ and made recommendations and a decision tree for management was proposed. They were officially approved by the three scientific societies. In conclusion, a multidisciplinary treatment consensus for the management of PM and DM was established for the first time.

Idiopathic inflammatory myopathies (IIMs) are heterogeneous disorders that affect the skeletal muscles. Polymyositis, dermatomyositis, and inclusion body myositis are major IIM subsets. Immune-mediated necrotizing myopathy became recognized as a potentially new IIM subset. Since the new classification criteria published by the International Myositis Classification Criteria Project have higher sensitivity and specificity for IIM classification and subclassification than the previous criteria, they should help precise diagnosis. It should be noted that several tests available in current clinical practice, such as electromyography, magnetic resonance imaging, and other myositis-specific autoantibodies than anti-Jo-1 antibodies, were not included in the new criteria. As for treatment, glucocorticoids are used empirically as the first-line treatment despite their various adverse effects. Concomitant treatment with steroid-sparing immunosuppressive agents, including methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, and cyclophosphamide, reduces successfully initial glucocorticoid doses for the remission induction, the relapse risk during glucocorticoid tapering, and adverse effects of glucocorticoids. Treatment with biologics, including rituximab and abatacept, seems promising in some IIM patients. Multi-target treatment with glucocorticoids and several steroid-sparing immunosuppressive agents is effective in refractory IIM patients. Considering proven steroid-sparing efficacy and tolerability of multi-target treatment in patients with other autoimmune diseases, it should be a good therapeutic option for IIMs.

Objectives: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases in which both genetic and environmental factors play important roles. To identify genetic factors of IIM including polymyositis, dermatomyositis (DM) and clinically amyopathic DM (CADM), we performed the first genome-wide association study for IIM in an Asian population., Methods: We genotyped and tested 496 819 single nucleotide polymorphism for association using 576 patients with IIM and 6270 control subjects. We also examined the causal mechanism of disease-associated variants by in silico analyses using publicly available data sets as well as by in in vitro analyses using reporter assays and apoptosis assays., Results: We identified a variant in WDFY4 that was significantly associated with CADM (rs7919656; OR=3.87; P=1.5×10 -8 ). This variant had a cis-splicing quantitative trait locus (QTL) effect for a truncated WDFY4 isoform (tr- WDFY4 ), with higher expression in the risk allele. Transexpression QTL analysis of this variant showed a positive correlation with the expression of NF-κB associated genes. Furthermore, we demonstrated that both WDFY4 and tr-WDFY4 interacted with pattern recognition receptors such as TLR3, TLR4, TLR9 and MDA5 and augmented the NF-κB activation by these receptors. WDFY4 isoforms also enhanced MDA5-induced apoptosis to a greater extent in the tr-WDFY4-transfected cells., Conclusions: As CADM is characterised by the appearance of anti-MDA5 autoantibodies and severe lung inflammation, the WDFY4 variant may play a critical role in the pathogenesis of CADM., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A 57-year-old woman was admitted to our hospital because of a high fever, anemia, and hyperferritinemia. Since a bone marrow examination revealed hemophagocytosis, she was diagnosed with hemophagocytic syndrome (HPS). During treatment of HPS, a heliotrope rash and Gottron's sign appeared with elevated levels of serum aldolase. She also developed heart failure. She was diagnosed with dermatomyositis (DM) and associated myocarditis. Although the administration of glucocorticoids, calcineurin inhibitors, intravenous immunoglobulins, and etoposide ameliorated the clinical findings of DM and cytopenia, the fever and hyperferritinemia remained. The addition of infliximab to glucocorticoids and tacrolimus improved the fever and hyperferritinemia and enabled a reduction in the dose of prednisolone without relapse of the diseases.

Objectives: This study aimed to investigate the clinical characteristics of polymyositis/dermatomyositis (PM/DM) in Japan by analyzing data from the nationwide registration system., Methods: The data of the registration system in 2009 were analyzed to investigate patient numbers, sex, clinical symptoms, therapies, complications, and prognosis of PM/DM., Results: The total number of PM/DM cases was approximately 17,000, and the female/male sex ratio was 2.7:1. Almost all patients improved as a result of therapy, but many suffered from sequelae such as muscle weakness., Conclusions: The results characterize significant aspects of Japanese PM/DM patients. However, a further prospective survey is required to clarify the true epidemiology and natural history of PM/DM.

We describe a case of severe dermatomyositis (DM) complicated by rhabdomyolysis, acute tubular necrosis, and hemophagocytosis. The case failed to respond to corticosteroids, but showed rapid and significant improvement after the addition of intravenous immunoglobulin (IVIG). While the prognosis of DM is poor when it is complicated by rhabdomyolysis, the early administration of IVIG has the potential to be the cornerstone of its management.

Objectives: To estimate the number of patients with polymyositis/dermatomyositis (PM/DM) in Japan and the prevalence rate and incidence rate of the disease., Methods: The electronic database in the nationwide registration system on intractable diseases from 2003 to 2010 was utilized to identify the number of prevalent and incident cases of PM/DM. The electronic data entry rate was used to establish the total number of registered cases., Results: The estimated total number of patients with PM/DM and the prevalence rate in Japan in 2010 were 17,000 and 13.2 per 100,000 population, respectively. The prevalence of PM/DM ranged from 10 to 13 per 100,000 population with a trend toward increasing over time. The incidence of PM/DM was estimated within the range 10-13 per 1,000,000 person-years, except for 2003., Conclusions: We report the prevalence and incidence of PM/DM recently in Japan for the first time at the nationwide population level. Because the prevalence seems to be increasing recently, continued monitoring of these epidemiologic features is required.

Objectives: The aim of this study was to describe age, gender distribution, and age at onset of systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), and systemic sclerosis (SSc) in Japan., Methods: We used epidemiological information on 21,405, 6,327, and 10,058 patients with SLE, PM/DM, and SSc, respectively, in a Japanese nationwide registration database of patients with intractable diseases., Results: All three diseases occur predominantly in women, with the female-to-male ratio being 8.2:1, 2.6:1, and 7.7:1 for SLE, PM/DM, and SSc, respectively. The most susceptible age for SLE is 15-44 and 20-39 years for males and females, respectively. For PM/DM it is 45-64 and 40-64 years and for SSc, 50-69 and 40-59 for men and women, respectively., Conclusions: The basic descriptive epidemiological characteristics of SLE, PM/DM, and SSc in Japan, such as gender distribution, present age, and age at onset, were surveyed nationwide for fiscal 2007. It was found that these characteristics were similar to those in Western populations. Our finding provides new information on the natural history of disease development.

Past paradigm that the muscle tissue injury is driven by CD4 T cells and associated humoral immunity in dermatomyositis (DM), and by cytotoxic T cells in polymyositis (PM) is now under challenge. Although pathogenic autoantigens are to be identified, skeletal muscle C-protein was an excellent immunogen to provoke experimental myositis mimicking human PM. Serum antibodies against aminoacyl tRNA synthases appear in PM/DM patients, but more often in interstitial pneumonitis patients. Inflammatory cytokines are obviously involved in the pathogenesis. Animal studies showed that autoimmune myositis occurs without tumor necrosis factor alpha. Indeed, its blockade has yielded inconsistent outcome. Most crucial ones will be therapeutic targets in the future.

The idiopathic inflammatory myopathies, polymyositis (PM) and dermatomyositis (DM), are evaluated as systemic autoimmune diseases without the pathology determined. Past immunohistochemical findings suggested that the effector response is driven predominantly by CD4 T cells and by humoral immunity in DM, and by cytotoxic T cells in PM. However, histological observations of muscle tissue do not necessarily distinguish DM and PM. Thus, the two diseases including amyopathic DM might represent a spectrum of illness in which some patients suffer only from a muscle disease or from a skin disease. In comparison with research studies on other rheumatic diseases, there are much fewer research studies conducted on PM/DM. The relationship between PM and DM is not clear yet. We reviewed past clinical and basic research on the pathology of PM/DM, including research on relevant T cells, B cells and cytokines.

Background: Although dermatomyositis (DM)-associated facial erythema was noted in the nasolabial folds of Japanese patients, DM-associated facial erythema other than heliotrope rash has drawn little attention in previous studies., Objectives: To characterize phenotypical features and frequencies of erythema, especially those in the seborrheic area of the head, in DM patients., Methods: A retrospective study on skin manifestations in 33 DM patients followed up at our department during the past 15 years was conducted., Results: Macular violaceous erythema (MVE) in the seborrheic area of the face was most frequent (67%). Patients with facial MVE had also MVE in the scalp significantly more frequently than those without facial MVE. The pathology of the facial MVE was dominated by DM-associated changes with slight changes compatible with seborrheic dermatitis (SD)., Conclusions: Japanese DM patients had MVE frequently in the seborrheic area of the head. Its phenotypical features suggested that it might be triggered by SD., (2008 S. Karger AG, Basel.)

A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.

We reported the case of a 39-year-old man with dermatomyositis (DM) complicated with subcutaneous emphysema and pneumomediastinum during steroid therapy. The patient had complained of muscle weakness, dyspnea and skin eruption on his anterior chest wall 6 months prior to admission. He was diagnosed as having DM on the basis of an elevation in myogenic enzymes, myogenic changes in electromyography, a skin biopsy and a muscle biopsy. Chest roentgenogram revealed interstitial pneumonia (IP) in the lower lobes of the lungs. The administration of prednisolone (60 mg/day) was initiated, which resulted in improvement of DM. Fifteen days after the initiation of the steroid therapy, the patient developed subcutaneous emphysema and pneumomediastinum. Additional administration of cyclosporin A (CsA) enabled us to rapidly taper the dose of prednisolone without aggravating the diseases. Several reports have shown that vasculitis might be involved in the pathogenesis of pneumomediastinum in DM patients. Infection and tissue fragility due to steroid therapy worsen the outcome of those patients. CsA therapy may improve the outcome through the anti-vasculitic- and steroid sparing-effects.