Persistent premature mortality gap in dermatomyositis and polymyositis: a United Kingdom general population-based cohort study.
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ABSTRACT: Objective
DM and PM are associated with substantial morbidity and mortality. We aimed to examine recent trends.Methods
Using The Health Improvement Network, we identified patients with incident DM/PM (defined by ≥1 Read diagnosis code) aged 18-89 years with ≥1 year of continuous enrolment prior to the cohort entry date and up to 10 comparators matched on age, sex and entry year. The cohort was divided in two based on the year of DM/PM diagnosis: the early cohort (1999-2006) and late cohort (2007-2014). We calculated multivariable hazard ratios (HR) for death using a Cox-proportional hazards model and multivariable rate differences (RD) using an additive hazard model.Results
We identified 410 DM cases (mean age: 58 years, 66% female) and 407 PM cases (mean age: 59 years, 61% female). Both DM cohorts had excess mortality compared with the comparison cohorts (71.5 vs 12.9 deaths/1000 person-years [PY] in the early cohort and 49.1 vs 10.4 deaths/1000 PY in the late cohort). The multivariable HRs were 7.51 (95% CI: 4.20, 13.42) in the early cohort and 5.42 (95% CI: 3.11, 9.45) in the late cohort (P-value for interaction = 0.59), and multivariable RDs were 56.2 (95% CI: 31.8, 81.2) in the early cohort and 36.3 (95% CI: 19.6, 53.0) in the late cohort (P-value for interaction = 0.15). A similar trend existed in PM.Conclusion
The premature mortality gap in DM/PM has not considerably improved in recent years, highlighting an unmet need for therapeutic improvement.
SUBMITTER: D'Silva KM
PROVIDER: S-EPMC8213423 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:MicroRNAs (miRNAs) are involved in the regulation of key biological processes and have been implicated in various diseases, including autoimmune disorders. The pathogenesis of polymyositis (PM) and dermatomyositis (DM) is considered to be mediated by autoimmune reactions. To determine miRNA role in the development and progression of PM and DM, we performed plasma miRNA profiling in PM/DM patients before and after treatment. Methods:Total RNA was isolated from plasma of 10 patients before and after treatment with prednisolone, or, in case of prednisolone resistance or complications, with the combination of calcineurin inhibitors (cyclosporine or tacrolims) and/or pulse intravenous cyclophosphamide. The expression of miRNAs was determined using miRNA microarray and validated by qRT-PCR. Results:More differentially expressed miRNAs were found in plasma of DM patients compared to PM patients before and after treatment, and their profiles were different. Among the differentially expressed plasma miRNA identified by microarray, the levels of hsa-miR-4442 were confirmed by qRT-PCR to be significantly decreased by treatment. In addition, plasma hsa-miR-4442 content in active PM/DM significantly exceeded that in other active autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, as well as in healthy individuals. The level of plasma hsa-miR-4442 was positively correlated with Skeletal Disease Activity in MITAX (Myositis Intention to Treat Activity Index). Conclusion:This is the first report describing plasma miRNA expression profiles in PM/DM patients. The present data suggest that plasma levels of miRNAs may be associated with polymyositis/dermatomyositis and hsa-miR-4442 could be used as a biomarker for PM/DM diagnosis and/or disease activity.
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Project description:ObjectiveTo describe the distribution and severity of muscle weakness using manual muscle testing (MMT) in 172 patients with PM, DM and juvenile DM (JDM). The secondary objectives included characterizing individual muscle group weakness and determining associations of weakness with functional status and myositis characteristics in this large cohort of patients with myositis.MethodsStrength was assessed for 13 muscle groups using the 10-point MMT and expressed as a total score, subscores based on functional and anatomical regions, and grades for individual muscle groups. Patient characteristics and secondary outcomes, such as clinical course, muscle enzymes, corticosteroid dosage and functional status were evaluated for association with strength using univariate and multivariate analyses.ResultsA gradient of proximal weakness was seen, with PM weakest, DM intermediate and JDM strongest among the three myositis clinical groups (P < or = 0.05). Hip flexors, hip extensors, hip abductors, neck flexors and shoulder abductors were the muscle groups with the greatest weakness among all three clinical groups. Muscle groups were affected symmetrically.ConclusionsAxial and proximal muscle impairment was reflected in the five weakest muscles shared by our cohort of myositis patients. However, differences in the pattern of weakness were observed among all three clinical groups. Our findings suggest a greater severity of proximal weakness in PM in comparison with DM.
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Project description:ObjectiveThe objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM.MethodsPatient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data.ResultsMyositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference.ConclusionConsensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.
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Project description:OBJECTIVE:The idiopathic inflammatory myopathies dermatomyositis (DM) and polymyositis (PM) are autoimmune diseases that can affect females of childbearing potential. We assessed pregnancy outcomes in DM and PM patients compared with the general obstetric population. METHODS:The Nationwide Inpatient Sample (NIS) (1993-2007) was used to identify delivery-associated hospitalizations in women with DM or PM (DM/PM, n = 853). Controls were from the general obstetric population delivery-associated hospitalizations matched to each case by year of delivery. Pregnancy outcomes included hospital length of stay (LOS), hypertensive disorders (HTN), premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), and cesarean delivery. Multivariate regression analyses were performed using maternal age, race/ethnicity, and diabetes mellitus as covariates. RESULTS:On multivariate analysis, patients with DM/PM had longer LOS compared to controls (p < 0.001). DM/PM was associated with an increased risk of hypertensive disorders compared to controls (OR = 2.90, 95% CI: 2.00-4.22). There were no differences in rates of PROM, IUGR, or cesarean section in patients with DM/PM compared with controls. Independent of a DM/PM diagnosis, African-American race, older age, and diagnosis of diabetes increased the hospital LOS (p < 0.001). African-American race and diabetes increased the risk of hypertensive disorders (OR = 1.38, 95% CI: 1.19-1.60; OR = 2.94, 95% CI: 2.04-4.23, respectively) compared to controls. CONCLUSION:These data suggest that patients with inflammatory myopathies are at increased risk of hypertensive disorders of pregnancy and longer length of hospitalization. Vigilant monitoring of blood pressure is advisable in pregnant patients with DM or PM.
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Project description:Polymyositis and dermatomyositis (PM/DM) are systemic autoimmune diseases with multiple organ involvements that manifest as muscular and cutaneous disorders, interstitial lung disease (ILD) and malignancies. However, information concerning the outcomes and associated factors for PM/DM patients who are hospitalized is limited.We retrospectively reviewed the medical charts of PM/DM patients admitted to a Chinese tertiary referral hospital (Peking Union Medical College Hospital, PUMCH) from 2008 to 2014. The deceased group included 63 patients who had "deceased discharge" status or were confirmed to have died within two weeks of hospital discharge. The demographic data, clinical manifestations, and direct causes of death were analyzed retrospectively. Medical records for 126 age- and sex-matched PM/DM patients were selected as controls from 982 inpatients successively admitted to the same center during the same period. In addition to the comparison of clinical manifestations between the two groups, binary logistic regression was conducted to explore the risk factors related to PM/DM mortality.Over the past 6 years at PUMCH, the in-hospital mortality rate of PM/DM patients was 4.58%. The male gender and the elder patients had a high risk of death (P = 0.031 and P = 0.001 respectively). The three most frequent causes of death for PM/DM patients were pulmonary infection (35%), ILD exacerbation (21%) or both conditions (25%). Pulmonary infection (P<0.001, OR = 5.63, 95% CI, 2.37-13.36), pneumomediastinum (P = 0.041, OR = 11.02, 95%CI, 1.10-110.54), Gottron's papules (P = 0.010, OR = 3.24, 95%CI, 1.32-7.97), and elevated erythrocyte sedimentation rate (ESR) (P = 0.005, OR = 9.9, 95%CI 2.0-49.0) were independent risk factors for in-hospital mortality of PM/DM patients.PM/DM patients continue to display high in-hospital mortality. Pulmonary infection is the strongest predictor of poor prognosis in PM/DM patients, followed by pneumomediastinum, Gottron's papules, and elevated ESR.
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Project description:IntroductionPatients with idiopathic inflammatory myopathies (IIMs) are sometimes complicated with life-threatening conditions requiring intensive care unit (ICU) admission. In the past, owing to the low incidence of IIM, little was known about such patients. Our aim was to investigate the clinical features and outcomes of these patients and identify their risk factors for mortality.MethodsA retrospective study was performed of IIM patients admitted over an 8-year period to the medical ICU of a tertiary referral center in China. We collected data regarding demographic features, IIM-related clinical characteristics, reasons for admission, organ dysfunction, and outcomes. Independent predictors of ICU mortality were identified through multivariate logistic regression analysis.ResultsOf the 102 patients in our cohort, polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM) accounted for 23.5%, 64.7%, and 11.7% respectively. The median duration from the onset of IIM to ICU admission was 4.3 months (interquartile range [IQR], 2.6-9.4 months). Reasons for ICU admission were infection alone (39.2%), acute exacerbation of IIM alone (27.5%), the coexistence of both (27.5%), or other reasons (5.8%). Pneumonia accounted for 97% of the infections; 63.2% of infections with documented pathogens were caused by opportunistic agents. Rapid progressive interstitial lung disease (RP-ILD) was responsible for 87.5% of acute exacerbation of IIM. The median Acute Physiology and Chronic Health Evaluation II (APACHE II) score on ICU day 1 was 17 (IQR 14-20). On ICU admission, acute respiratory failure (ARF) was the most common type (80.4%) of organ failure. The mortality rate in the ICU was 79.4%. Factors associated with increased ICU mortality included a diagnosis of DM (including CADM), a high APACHE II score, the presence of ARF, a decreased PaO2/FiO2 ratio, and a low lymphocyte count at the time of ICU admission.ConclusionsThe outcome of IIM patients admitted to the ICU was extremely poor. A diagnosis of DM/CADM, the presence and severity of ARF, and the lymphocyte counts at ICU admission were shown to be valuable for predicting outcome. Opportunistic infections and rapidly progressive interstitial lung disease warrant concern in treating these patients.
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Project description:Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular manifestations of dermatomyositis and polymyositis and is strongly linked to poor prognosis and early mortality. We aimed to characterise the demographic and clinical characteristics, incidence, and treatment of interstitial lung disease in patients with dermatomyositis or polymyositis. We conducted a retrospective cohort study using the Japan Medical Data Center healthcare claims database. Patients in the database with dermatomyositis (International Classification of Disease version 10 M33.0, M33.1, M33.9) or polymyositis (M33.2) from 01-Jan-2011 until 31-Dec-2019 were identified and followed-up for interstitial lung disease (J84.x) until death, dis-enrolment, or study end (31 December 2020). Cumulative risk curves compared interstitial lung disease risk in dermatomyositis versus polymyositis. Risk factors were evaluated by Cox proportional hazard models. There were 886 patients with dermatomyositis and 745 patients with polymyositis included in the cohort analysis. Mean (standard deviation) age at dermatomyositis/polymyositis diagnosis was 46.0 (16.0)/49.7 (13.3) years and 300 (34%)/104 (14%) developed interstitial lung disease during follow-up. The incidence rate of interstitial lung disease per 100 person-years was 18.42 (95% CI 16.42-20.59) for dermatomyositis and 5.39 (95% CI 4.43-6.50) for polymyositis. In the analysis adjusted for sex, age, and comorbidity score, the risk of interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis (hazard ratio 2.72, 95% CI 2.18-3.41). The rate diverged markedly between the groups in the first year after diagnosis. Risk factors for interstitial lung disease were older age in dermatomyositis, female sex and rheumatoid arthritis in polymyositis. Glucocorticoids with/without tacrolimus were the most common newly prescribed drugs after the interstitial lung disease diagnosis. In conclusion, the risk of developing interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis, and risk factors were different in the 2 patient groups.
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Project description:BACKGROUND:Interstitial lung disease (ILD) is the principal cause of death in polymyositis/dermatomyositis (PM/DM). Here we investigated prognostic factors for death and serious infection in PM/DM-ILD using the multicenter database. METHODS:We retrospectively reviewed baseline demographic, clinical and laboratory findings, treatment regimens and outcomes in patients with PM/DM-ILD. The distribution of ILD lesions was evaluated in four divided lung zones of high-resolution computed tomography images. RESULTS:Of 116 patients with PM/DM-ILD, 14 died within 6 months from the diagnosis. As independent risk factors for early death, extended ILD lesions in upper lung fields (odds ratio (OR) 8.01, p?=?0.016) and hypocapnia (OR 6.85, p?=?0.038) were identified. Serious infection was found in 38 patients, including 11 patients who died of respiratory or multiple infections. The independent risk factors were high serum KL-6 (OR 3.68, p?=?0.027), high initial dose of prednisolone (PSL) (OR 4.18, p?=?0.013), and combination immunosuppressive therapies (OR 5.51, p?<?0.001). CONCLUSION:The present study shows the progression of ILD at baseline is the most critical for survival and that infection, especially respiratory infection, is an additive prognostic factor under the potent immunosuppressive treatment.
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Project description:ObjectivePolymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified.MethodsGene expression data of PM/DM were obtained from Gene Expression Omnibus. We used robust rank aggregation (RRA) to identify differentially expressed genes (DEGs). Gene Ontology functional enrichment and pathway analyses were used to investigate potential functions of the DEGs. Weighted gene co-expression network analysis (WGCNA) was used to establish a gene co-expression network. CIBERSORT was utilized to analyze the pattern of immune cell infiltration in PM/DM. Protein-protein interaction (PPI) network, Venn, and association analyses between core genes and muscle injury were performed to identify hub genes. Receiver operating characteristic analyses were executed to investigate the value of hub genes in the diagnosis of PM/DM, and the results were verified using the microarray dataset GSE48280.ResultsFive datasets were included. The RRA integrated analysis identified 82 significant DEGs. Functional enrichment analysis revealed that immune function and the interferon signaling pathway were enriched in PM/DM. WGCNA outcomes identified MEblue and MEturquoise as key target modules in PM/DM. Immune cell infiltration analysis revealed greater macrophage infiltration and lower regulatory T-cell infiltration in PM/DM patients than in healthy controls. PPI network, Venn, and association analyses of muscle injury identified five putative hub genes: TRIM22, IFI6, IFITM1, IFI35, and IRF9.ConclusionsOur bioinformatics analysis identified new genetic biomarkers of the pathogenesis of PM/DM. We demonstrated that immune cell infiltration plays a pivotal part in the occurrence of PM/DM.
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Project description:Polymyositis (PM) and dermatomyositis (DM) are both classified as idiopathic inflammatory myopathies. They share a few common characteristics such as inflammation and muscle weakness. Previous studies have indicated that these diseases present aspects of an auto-immune disorder; however, their exact pathogenesis is still unclear. In this study, three gene expression datasets (PM: 7, DM: 50, Control: 13) available in public databases were used to conduct meta-analysis. We then conducted expression quantitative trait loci analysis to detect the variant sites that may contribute to the pathogenesis of PM and DM. Six-hundred differentially expressed genes were identified in the meta-analysis (false discovery rate (FDR) < 0.01), among which 317 genes were up-regulated and 283 were down-regulated in the disease group compared with those in the healthy control group. The up-regulated genes were significantly enriched in interferon-signaling pathways in protein secretion, and/or in unfolded-protein response. We detected 10 single nucleotide polymorphisms (SNPs) which could potentially play key roles in driving the PM and DM. Along with previously reported genes, we identified 4 novel genes and 10 SNP-variant regions which could be used as candidates for potential drug targets or biomarkers for PM and DM.
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