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Frontiers in Immunology 2022To explore the clinical features and prognoses of dermatomyositis (DM) associated with a double-positive anti-MDA5 and anti-aminoacyl-tRNA synthetase (anti-ARS) antibody...
OBJECTIVE
To explore the clinical features and prognoses of dermatomyositis (DM) associated with a double-positive anti-MDA5 and anti-aminoacyl-tRNA synthetase (anti-ARS) antibody presentation.
METHODS
We retrospectively analyzed 1280 consecutive patients with idiopathic inflammatory myopathy (IIM). Individuals with anti-MDA5 and anti-ARS antibodies (anti-MDA5+/ARS+) were compared to anti-MDA5-/ARS+ and anti-MDA5+/ARS- control individuals based on clinical, pulmonary radiological characteristics, treatment, and follow-up information.
RESULTS
Six individuals (0.47%) presented with anti-MDA5+/ARS+; of these, 2 (33.3%) were anti-PL-12+, 2 (33.3%) were anti-Jo-1+, 1 (16.7%) was anti-EJ+, and 1 (16.7%) was anti-PL-7+. Hallmark cutaneous manifestations, including Gottron's sign (100%), heliotrope rash (50%), mechanic's hand (66.7%), and skin ulcers (16.7%) were common. Anti-MDA5+/ARS+ patients tended to have higher ferritin levels (p = 0.038) than anti-MDA5-/ARS+ group, and higher CD4+ T-cell counts (p = 0.032) compared to the anti-MDA5+/ARS- group. Radiologically, NSIP with OP overlap was predominant (60%). Consolidation (60%), ground-glass attenuation (GGA) (80%), traction bronchiectasis (80%), and intralobular reticulation (100%) were common in anti-MDA5+/ARS+ individuals. All were diagnosed with ILD and 50% were categorized as RPILD. All patients received glucocorticoids combined with one or more immunosuppressants. Most (83.3%) had a good prognosis following treatment, but there was no difference in the survival rate between the three subgroups.
CONCLUSION
Presentation with anti-MDA5+/ARS+ DM was rare. The clinical and radiological characteristics of anti-MDA5+/ARS+ DM combined the features of anti-MDA5+ and anti-ARS+ individuals. Individuals with anti-MDA5+/ARS+ antibodies may respond well to glucocorticoid therapy; glucocorticoids combined with one or more immunosuppressants may be considered a basic treatment approach.
Topics: Amino Acyl-tRNA Synthetases; Autoantibodies; Dermatomyositis; Ferritins; Glucocorticoids; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Prognosis; Retrospective Studies
PubMed: 36110863
DOI: 10.3389/fimmu.2022.987841 -
Discovery Medicine Jun 2015Polymyositis (PM) and dermatomyositis (DM) are the two major forms of inflammatory muscle diseases. They are characterized clinically primarily by proximal muscle... (Review)
Review
Polymyositis (PM) and dermatomyositis (DM) are the two major forms of inflammatory muscle diseases. They are characterized clinically primarily by proximal muscle weakness. The disease mechanisms that cause muscle damage and dysfunction are not fully understood. However, because of the association with other autoimmune diseases, the presence of autoantibodies, and response to immunosuppressive medication, they are believed to be autoimmune in origin. Recent studies have highlighted the importance of the innate immune system and non-immune mechanisms and described novel adaptive immune-based pathways in the pathogenesis of polymyositis and dermatomyositis. Stimulation of Toll-like receptors (TLRs) by endogenous antigens, e.g., aminoacyl-tRNA synthetase enzyme, may trigger activation of signaling pathways and thereby induces expression of multiple genes involved in the inflammatory response. High-mobility group box-1 (HMGB1) might interact with the same receptors and cause skeletal muscle inflammation. In addition, this protein may be involved in T lymphocyte survival in muscle tissue. A newly described T cell subset, CD28(-) T cells, may have strong myotoxic properties and comprises the predominant muscle-infiltrating T cell phenotype. Future studies should focus more on understanding the relative contribution of each pathway to the pathogenesis of inflammatory myopathies. Given the connections between the pathways, targeting multiple pathways through combination therapies may be beneficial.
Topics: Autoimmune Diseases; Dermatomyositis; Humans; Immunity, Cellular; Muscle, Skeletal; T-Lymphocytes
PubMed: 26175404
DOI: No ID Found -
JAMA Dermatology Dec 2022Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians.
IMPORTANCE
Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians.
OBJECTIVE
To study the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single center from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021.
INTERVENTIONS
Apremilast 30 mg orally twice daily was added to ongoing treatment regimens.
MAIN OUTCOMES AND MEASURES
The primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0.
RESULTS
Among 8 patients with recalcitrant cutaneous dermatomyositis (all women; mean [SD] age, 54 [15.9] years), a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%). The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P < .001). Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied. Of 39 076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes). Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) pathways. In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signaling pathway for the downregulated cytokines.
CONCLUSIONS AND RELEVANCE
These findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03529955.
Topics: Humans; Female; Middle Aged; Dermatomyositis; Skin; Thalidomide; Treatment Outcome; Severity of Illness Index
PubMed: 36197661
DOI: 10.1001/jamadermatol.2022.3917 -
The British Journal of Dermatology May 2019Diagnostic criteria are used to identify a patient having a disease in a clinical setting, whereas classification criteria create a well-defined population for research... (Review)
Review
BACKGROUND
Diagnostic criteria are used to identify a patient having a disease in a clinical setting, whereas classification criteria create a well-defined population for research purposes. The diagnosis and classification of amyopathic dermatomyositis (ADM) have not been recognized by most existing criteria for idiopathic inflammatory myopathies (IIMs). To address this, several criteria were proposed to define ADM either as a distinct disease entity or as a subset of the spectrum of IIMs.
OBJECTIVES
To discuss the diagnosis and classification of ADM and to assesses the available criteria in identifying cases of ADM and/or distinguishing it from dermatological mimickers such as lupus erythematosus.
METHODS
We conducted an extensive literature search using the PubMed database from June 2016 to August 2018, using the search terms 'amyopathic dermatomyositis', 'diagnosis' and 'classification'.
RESULTS
The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, which are the only validated classification criteria for adult and juvenile IIM and their major subgroups, include three cutaneous items (Göttron sign, Göttron papules, heliotrope rash) to be able to classify ADM. This international and multispecialty effort is a huge step forward in the classification of skin-predominant disease in dermatomyositis. However, about 25% of the population with ADM do not meet two out of the three skin features and are misdiagnosed or classified as having a different disease entity, most commonly lupus erythematosus.
CONCLUSIONS
These gaps rationalize the continuous assessment and improvement of existing criteria and/or the development of validated, separate and skin-focused criteria for DM.
Topics: Dermatology; Dermatomyositis; Diagnosis, Differential; History, 20th Century; History, 21st Century; Humans; Lupus Erythematosus, Cutaneous; Rheumatology; Skin
PubMed: 30561064
DOI: 10.1111/bjd.17536 -
Clinical Rheumatology Mar 2022Since new consensus on polymyositis (PM) and dermatomyositis (DM) were released in Japan, an updated evidence on treatment landscape and PM/DM burden was essential. This... (Observational Study)
Observational Study
INTRODUCTION/OBJECTIVES
Since new consensus on polymyositis (PM) and dermatomyositis (DM) were released in Japan, an updated evidence on treatment landscape and PM/DM burden was essential. This study evaluates treatment burden and overall treatment cost of PM/DM-related inpatient and outpatient visits, treatments, and procedures/patient/year.
METHOD
This retrospective, observational study analyzed insurance claims from Japan Medical Data Center (JMDC) database. Patients with at least one PM/DM diagnosis/one dispensation of treatment between 1 January 2009 and 31 December 2019 were enrolled. Patient characteristics, treatment patterns and sequence, treatment choices, healthcare resource utilization (HCRU), and related costs were assessed. Chi-square test and linear regression model were used to assess impact of patient characteristics on treatment choice.
RESULTS
Patients (836/4,961) receiving a relevant treatment were analyzed. Heart disease (35%), interstitial lung disease (27%), and diabetes mellitus (26%) were frequently identified as comorbidities. Concomitant dispensation of immunosuppressants and systemic steroids was largely found in first and second line of treatment (LoT) while systemic steroids remained as single dominant treatment across all LoTs. HCRU was very low for inpatient visits (0.68 [1.43]) or rehabilitation (4.74 [14.57]). The mean (SD) number of inpatient visits decreased from first (1.23 [2.32]) to third year (0.11 [0.54]). Total mean (SD) healthcare cost per patients per year was ¥ 3,815,912 (7,412,241), with overall drug dispensation compounding to 80% of total cost.
CONCLUSIONS
High concomitant immunosuppressant and systemic steroid prescriptions in first LoT recommend early optimal treatment to manage PM/DM. Although inpatient costs are low, outpatient dispensation costs increase overall economic burden.
Topics: Cost of Illness; Dermatomyositis; Humans; Japan; Polymyositis; Retrospective Studies
PubMed: 34677707
DOI: 10.1007/s10067-021-05939-6 -
Chinese Medical Journal Jan 2024
Topics: Humans; Dermatomyositis; Vascular Diseases
PubMed: 37415507
DOI: 10.1097/CM9.0000000000002788 -
Scientific Reports Sep 2023Dermatomyositis is a rare disease characterized by progressive muscle weakness and skin rashes. Estimates of incidence and prevalence are fundamental measures in...
Dermatomyositis is a rare disease characterized by progressive muscle weakness and skin rashes. Estimates of incidence and prevalence are fundamental measures in epidemiology, but few studies have been conducted on dermatomyositis. To address this knowledge gap, we conducted a population-based study to determine the contemporary incidence (between 2013 and 2019) and prevalence (2019) of adults living with dermatomyositis using administrative health data in Alberta, Canada. We also described disease-related medication use, as there are very few approved medications for the treatment of dermatomyositis, and no Canadian therapeutic guidelines. The average age- and sex-standardized annual incidence of dermatomyositis was 2.8-3.0 cases per 100,000 adults, and prevalence was 28.6 cases per 100,000 adults, which is greater than reported in other cohorts. Dermatomyositis-related medication use decreased from 73% in the first year to 46% in the eighth year after diagnosis. Glucocorticoids were the most commonly used drug class, often taken concurrently with various immunomodulatory agents; this medication use aligns with empirically-based recommendations and the few therapeutic guidelines for dermatomyositis. Considering that Alberta may have one of the highest rates of dermatomyositis among adults, further research on the burden of disease is warranted for planning within the health care system.
Topics: Humans; Adult; Alberta; Dermatomyositis; Prevalence; Incidence; Cohort Studies
PubMed: 37777591
DOI: 10.1038/s41598-023-43880-7 -
Paediatric Drugs Oct 2017The idiopathic inflammatory myopathies of childhood consist of a heterogeneous group of autoimmune diseases characterised by proximal muscle weakness and pathognomonic... (Review)
Review
The idiopathic inflammatory myopathies of childhood consist of a heterogeneous group of autoimmune diseases characterised by proximal muscle weakness and pathognomonic skin rashes. The overall prognosis of juvenile myositis has improved significantly over recent years, but the long-term outcome differs substantially from patient to patient, suggestive of distinct clinical phenotypes with variable responses to treatment. High doses of corticosteroids remain the cornerstone of therapy along with other immunosuppressant therapies depending on disease severity and response. The advent of biological drugs has revolutionised the management of various paediatric rheumatologic diseases, including inflammatory myopathies. There are few data from randomised controlled trials to guide management decisions; thus, several algorithms for the treatment of juvenile myositis have been developed using international expert opinion. The general treatment goals now include elimination of active disease and normalisation of physical function, so as to preserve normal growth and development, and to prevent long-term damage and deformities. This review summarises the newer and possible future therapies of juvenile inflammatory myopathies, including evidence supporting their efficacy and safety.
Topics: Adrenal Cortex Hormones; Child; Dermatomyositis; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Janus Kinases; Randomized Controlled Trials as Topic
PubMed: 28550457
DOI: 10.1007/s40272-017-0240-6 -
The Israel Medical Association Journal... Oct 2020The reported mortality rates of patients with polymyositis and dermatomyositis are highly variable worldwide. The excess mortality of patients with... (Comparative Study)
Comparative Study
BACKGROUND
The reported mortality rates of patients with polymyositis and dermatomyositis are highly variable worldwide. The excess mortality of patients with polymyositis/dermatomyositis has not been evaluated in an Israeli population.
OBJECTIVES
To investigate the overall mortality in a large and well-established cohort of patients with polymyositis/dermatomyositis as compared to the mortality expected in the matched general population in a tertiary medical center.
METHODS
In this retrospective cohort study, the mortality of 166 patients with polymyositis/dermatomyositis was compared to age- and sex-matched control subjects in the general population. All-cause standardized mortality ratios (SMRs) were estimated.
RESULTS
Overall, 47 (28.3%) deaths were observed among patients with polymyositis/dermatomyositis during a mean follow-up period of 5.8 ± 4.8 years, which was 7 times higher than in the control group (SMR 7.4, 95% confidence interval [95%CI] 5.5-9.8). The SMRs were comparable in patents with polymyositis (7.7, 95%CI 4.8-12.3) and dermatomyositis (7.2, 95%CI 5.0-10.3). The 1-, 5-, 10-, and 15-year overall survival rates were 90.0%, 82.8%, 51.5%, and 26.1%, respectively, in patients with polymyositis, and 80.3%, 59.6%, 40.0%, and 17.1%, respectively, in patients with dermatomyositis.
CONCLUSIONS
The overall mortality among Israeli patients with polymyositis/dermatomyositis is 7.4 times greater than for the general population. Although long-term mortality was comparable between patients with dermatomyositis and polymyositis, patients in the former group died at a notably earlier stage.
Topics: Adult; Age Factors; Case-Control Studies; Cause of Death; Dermatomyositis; Female; Humans; Israel; Male; Middle Aged; Polymyositis; Prognosis; Reference Values; Retrospective Studies; Severity of Illness Index; Sex Factors; Survival Analysis; Tertiary Care Centers; United Kingdom
PubMed: 33070486
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Jun 2021Idiopathic inflammatory myositis (IIM) is an umbrella term for diseases of unknown origin that cause muscle inflammation. Dermatomyositis and polymyositis are IIMs that... (Review)
Review
Idiopathic inflammatory myositis (IIM) is an umbrella term for diseases of unknown origin that cause muscle inflammation. Dermatomyositis and polymyositis are IIMs that commonly cause interstitial lung disease (ILD). When a patient presents with ILD, the evaluation of whether the case displays the characteristics of myositis should be determined by interview, physical examination, imaging findings, the measurement of myositis-related antibodies, and the determination of disease severity after diagnosis. Rapidly progressing anti-melanoma differentiation-associated gene 5 antibody-positive ILD may require rapid multi-drug therapy, while anti-aminoacyl tRNA synthetase (ARS) antibody-positive ILD can be treated with anti-inflammatory drugs. Importantly, however, anti-ARS antibody-positive ILD often recurs and sometimes develops into fibrosis. Early diagnosis is crucial for treatment, and we therefore need to clarify the features of myositis associated with ILD and suspect these pathologies early. This section reviews what clinicians need to look for and what findings are evaluated in patients when diagnosing myositis associated with ILD.
Topics: Autoantibodies; Dermatomyositis; Humans; Lung Diseases, Interstitial; Myositis; Physicians; Retrospective Studies
PubMed: 34200737
DOI: 10.3390/medicina57060599