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Objectives: The magnitude of the genetic contribution to idiopathic inflammatory myopathies (IIMs) is unknown. In this project, we aimed to investigate the familial aggregation and heritability of IIM.Methods: This is a family-based study using nationwide healthcare register data in Sweden. We matched each patient with IIM to individuals without IIM, identified their first-degree relatives and determined the IIM status among all first-degree relatives. We estimated the adjusted ORs (aORs) of familial aggregation of IIM using conditional logistic regression. In addition, we used tetrachoric correlation to estimate the heritability of IIM.Results: We included 7615 first-degree relatives of 1620 patients with IIM diagnosed between 1997 and 2016 and 37 309 first-degree relatives of 7797 individuals without IIM. Compared with individuals without IIM, patients with IIM were more likely to have ≥1 first-degree relative affected by IIM (aOR=4.32, 95% CI 2.00 to 9.34). Furthermore, the aOR of familial aggregation of IIM in full siblings was 2.53 (95% CI 1.62 to 3.96). The heritability of IIM was 22% (95% CI 12% to 31%) among any first-degree relatives and 24% (95% CI 12% to 37%) among full siblings.Conclusions: IIM has a familial component with a risk of aggregation among first-degree relatives and a heritability of about 20%. This information is of importance for future aetiological studies and in clinical counselling. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated safety and effectiveness of rituximab in anti-synthetase antibody positive and negative patients with idiopathic inflammatory myopathy (IIM). Topics explored include the clinical characteristics and prevalence of IIM, the selection and evaluation of patients from the Swedish Rheumatology Quality Register, and brief details about the rituximab dosage administered and patient outcomes observed.

Objective. Alterations in phenotype and function of endothelial progenitor cells (EPCs) have been associated with poor vascular outcomes and impaired vascular repair in various conditions. Our hypothesis was that patients with PM and DM have dysregulation of EPCs driven by type I IFN and IL-18 similar to other autoimmune diseases. Methods. Quantification of circulating EPCs was performed by flow cytometry in patients with PM/DM and matched healthy controls. The ability of EPCs to differentiate into mature endothelial cells was investigated by light and fluorescence microscopy quantification in the presence or absence of PM/DM or control serum, neutralizing antibodies to type I IFN receptor or IL-18. Serum type I IFN activity was quantified by induction of type I IFN-inducible genes in HeLa cells. Circulating IL-18 concentrations were assessed by ELISA. Results. Circulating EPCs were significantly lower in PM/DM patients compared with controls. PM/DM EPCs displayed a decreased capacity to differentiate into mature endothelial cells and PM/DM serum significantly inhibited differentiation of control EPCs. This effect was reversed in the majority of samples with neutralizing antibodies to IL-18 or to type I IFN receptor or by a combination of these antibodies. Patients with associated impairments in EPC function had higher type I IFN serum activity. Conclusion. PM/DM is associated with dysregulation of EPC phenotype and function that may be attributed, at least in part, to aberrant IL-18 and type I IFN pathways. The implication of these vasculopathic findings for disease prognosis and complications remains to be determined. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are rare, chronic inflammatory diseases leading to muscle weakness and low muscle endurance. The muscle weakness may lead to restrictions in daily activities and low health-related quality of life. OBJECTIVES: This study aimed to investigate the work situation, work ability, work-related risk factors, and influence of the physical and psycho-social work environment in patients with PM and DM. METHODS: Patients with PM/DM were assessed using the Work Ability Index (WAI), and the Work Environment Impact Scale (WEIS). RESULTS: Forty-eight patients (PM n = 25 and DM n = 23) participated (women/men: 29/19) with a mean age of 54 years (range 28-67 years, SD.10) and mean disease duration of nine years (SD.9). Forty-four percent worked full-time, 31% part-time and 25% were on full-time sick leave. More than 50% self-rated work ability as "poor" or "less good". Physically strenuous work components were present "quite to very often" in 23-79% and more in patients on sick leave ≥2 years. For those working, the interfering factors in the work environment concerned task and time demands. Supporting factors concerned meaning of work, interactions with co-workers and others. Self-rated work ability correlated moderately-highly positive with percentage of full-time employment, work-related risk factors and opportunities and constraints in the work environment. CONCLUSIONS: Poor self-rated work ability is common in patients with PM/DM indicating a need to identify interfering risk factors and support patients to enhance work performance. [ABSTRACT FROM AUTHOR]

. Fathi M, Barbasso Helmers S, Lundberg IE (Karolinska University Hospital, Stockholm; Karolinska Institutet, Karolinska University Hospital, Stockholm; and Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Sweden). KL-6: a serological biomarker for interstitial lung disease in patients with polymyositis and dermatomyositis. J Intern Med 2012; 271: 589-597. Objectives. To investigate whether Caucasian patients with polymyositis (PM) or dermatomyositis (DM) and interstitial lung disease (ILD) have elevated serum levels of KL-6 compared with patients without ILD and whether KL-6 could be used as a marker for ILD activity and treatment efficacy of ILD in PM/DM. Design and methods. Thirty patients with PM/DM (seven with ILD) and 17 age- and sex-matched healthy controls were included in a retrospective, cross-sectional analysis. Twelve patients were followed for longitudinal evaluation. ILD was defined as restrictive lung function impairment with radiographic signs of ILD. Serum KL-6 levels were measured using a sandwich enzyme immunoassay kit. Groups were compared by Mann-Whitney U-test. Results. PM/DM patients with ILD had significantly higher median serum KL-6 levels compared with those without ILD: 995 (range 533-2318) versus 322 (range 132-1225) U mL−1 ( P = 0.0002). Median serum levels of healthy controls were 225 (range 136-519) U mL−1. Serum levels of KL-6 were inversely correlated with percentages of forced expiratory volume in 1 s (FEV1), vital capacity (VC), total lung capacity (TLC), forced VC, diffusing capacity of carbon monoxide (DLco), maximal voluntary ventilation at 40 breaths min−1 and residual volume (RV). Changes in KL-6 levels showed a significant inverse correlation with changes in percentage FEV1, TLC, DLco and RV. At a cut-off level of 549 U mL−1 (mean ± 2.5 SD for controls), the sensitivity and specificity for diagnosis of ILD were 83% and 100%, respectively. Conclusion. The level of serum KL-6 may serve as measure of ILD in patients with PM/DM and is a promising biomarker for use in clinical practice to assess clinical response to treatment. [ABSTRACT FROM AUTHOR]

Objectives. The aims of this study were to investigate hand function in PM and DM patients and compare this with reference values in healthy individuals and also to investigate if hand function correlated with activity performance and health-related quality of life.Methods. An observational cross-sectional study was performed in 18 women and 13 men with PM or DM with established disease. Grip force and hand mobility were assessed by Grippit and Escola Paulista de Medicina – Range of Motion scale. Activity performance was measured with myositis activities profile and health-related quality of life by short form-36 (SF-36).Results. Women and men with PM and DM with mean disease duration of 6.8 (5.5) years had a significantly lower grip force than gender- and age-matched healthy individuals (women 71% and men 60%). They also had significantly lower mean values in all dimensions of the health-related quality of life instrument SF-36 compared with the Swedish population. In patients with PM and DM, the grip force correlated significantly with the ability to perform domestic activities. In women with PM and DM, the grip force correlated significantly with the health-related quality of life dimensions vitality and mental health. There were no significant differences between patients with PM and DM regarding grip force, hand mobility, activity performance or health-related quality of life.Conclusions. Patients with PM or DM have reduced grip force that could influence activity performance and health-related quality of life. [ABSTRACT FROM PUBLISHER]

Objectives: The magnitude of the genetic contribution to idiopathic inflammatory myopathies (IIMs) is unknown. In this project, we aimed to investigate the familial aggregation and heritability of IIM., Methods: This is a family-based study using nationwide healthcare register data in Sweden. We matched each patient with IIM to individuals without IIM, identified their first-degree relatives and determined the IIM status among all first-degree relatives. We estimated the adjusted ORs (aORs) of familial aggregation of IIM using conditional logistic regression. In addition, we used tetrachoric correlation to estimate the heritability of IIM., Results: We included 7615 first-degree relatives of 1620 patients with IIM diagnosed between 1997 and 2016 and 37 309 first-degree relatives of 7797 individuals without IIM. Compared with individuals without IIM, patients with IIM were more likely to have ≥1 first-degree relative affected by IIM (aOR=4.32, 95% CI 2.00 to 9.34). Furthermore, the aOR of familial aggregation of IIM in full siblings was 2.53 (95% CI 1.62 to 3.96). The heritability of IIM was 22% (95% CI 12% to 31%) among any first-degree relatives and 24% (95% CI 12% to 37%) among full siblings., Conclusions: IIM has a familial component with a risk of aggregation among first-degree relatives and a heritability of about 20%. This information is of importance for future aetiological studies and in clinical counselling., Competing Interests: Competing interests: IEL has received grants from Swedish Research Council and from Region Stockholm (ALF-project), during the conduct of the study, grants and consulting fee from Bristol Myers Squibb, consulting fee from Corbus Pharmaceutical, grants from Astra Zeneca, research collaboration with aTyr Pharma, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To estimate the annual direct and indirect costs associated with Idiopathic Inflammatory Myopathies (IIM) over time, including the pre-diagnostic period., Methods: A cohort of incident adult IIM patients (n = 673) was identified from the Swedish National Patient Register from 2010 to 2016 and matched with general population comparators (n = 3343). Follow-up started at IIM diagnosis and corresponding date in the general population. International Classification of Diseases codes (ICD-10) were used for IIM case definition. Costs were calculated using national register data., Results: The costs related to IIM started to increase 2 years before diagnosis. In the year following diagnosis, the mean annual IIM cost was €21 639 compared to €4816 in the general population. Five years after diagnosis, the mean annual cost in the IIM cohort was €12 796. Outpatient visits, hospitalizations and productivity loss were the components driving the increment in overall annual disease-related expenditures. Indirect costs accounted for a significant portion of IIM long-term societal costs. The highest costs were found in individuals of working age with cancer-associated IIM., Conclusions: The mean annual costs in IIM were 3 to 5 times higher than in the general population in the 5-year period following diagnosis. These costs started to increase long before diagnosis, were at their peak in the year post-diagnosis and remained elevated thereafter. Indirect costs contributed to a substantial portion of this increment. Early in the IIM disease course, clinicians and allied health professionals should aim to improve function, reduce damage and address barriers to return-to-work to mitigate these costs., Competing Interests: Declaration of Competing Interest Dr. Lundberg reports personal fees from Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx BV, and grants from Astra Zeneca. Dr Lundberg has stock shares in Novartis and Roche. No reference is made to specific products in our work, nor do we suggest therapeutic choices in our conclusions. The other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In 2017, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) published new classification criteria for idiopathic inflammatory myopathies (IIM)., Objectives: To [1] assess the performance of the EULAR/ACR criteria in a monocentric cohort of consecutive patients with IIM, compare them with the Bohan and Peter (BP) criteria, and with the physician's diagnosis; and [2] evaluate the effect of including the presence of interstitial lung disease (ILD) as variable in the criteria., Methods: 439 consecutive patients with a diagnosis of IIM followed at the Rheumatology Clinic, Karolinska University Hospital, Sweden were enrolled. The patients were diagnosed as IIM and subclassified by expert physicians. Clinical, laboratory, serological and histopathological data were collected from existing databases (Euromyositis registry and Swedish Rheumatology quality registry) and clinical charts of the patients. The sensitivity of the EULAR/ACR and the BP criteria was calculated., Results: The EULAR/ACR criteria had a higher sensitivity (87.7%) compared to the BP criteria (80.4%). The concordance between the two sets of criteria was low (k = 0.253 p<0.001). The EULAR/ACR criteria showed a very high specificity (>98%) for the major IIM subgroups polymyositis, dermatomyositis, and inclusion body myositis. The sensitivity was variable and was high in inclusion body myositis (98%), dermatomyositis (90%) and lower in polymyositis (73%). When including ILD in the variables of the criteria, six more patients were classified as IIM cases (1.3%)., Conclusion: The EULAR/ACR criteria for IIM are applicable with high sensitivity and specificity using data available from existing databases and clinical charts and represent a major step forward from the previous criteria for IIM and its subgroups. Their application will improve the quality of clinical trials and research studies with IIM patients., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Evidence suggests an increased risk of cardiovascular (CV) diseases, including acute coronary syndrome (ACS), in idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the risk of ACS in an incident IIM cohort compared to the general Swedish population., Methods: A cohort of 655 individuals with incident IIM and 6813 general population comparators were identified from national registries. IIM subjects were diagnosed from 2002 to 2011. Followup started at IIM diagnosis and corresponding date in the general population. ACS, CV comorbidities, and CV risk factors were defined using International Classification of Diseases codes. Incidence rates including 95% CI were calculated. Cox proportional hazards models were used to compare the risk of ACS in patients with IIM and the general population. The competing risk of death was accounted for using competing risk regression models., Results: The incidence rate of ACS in IIM was higher than in the general population, particularly within the first year of diagnosis and in older individuals. The overall ACS incidence rate in IIM was 15.6 (95% CI 11.7-20.4) per 1000 person-years, with an HR of 2.4 (95% CI 1.8-3.2) compared with the general population. When accounting for the competing risk of death, the risk of ACS in IIM remained increased with a cumulative incidence of 7% at 5 years compared to 3.3% in the general population., Conclusion: IIM individuals are at higher risk of ACS, particularly within the first year after diagnosis.

Objective: To investigate muscle impairment (isometric and dynamic) and disease activity during the first year after diagnosis of polymyositis (PM) and dermatomyositis (DM), and to study the relationship between muscle impairment, patient-reported health, and disease activity., Methods: Seventy-two patients enrolled in the Swedish Myositis Register, 2003-2010, were followed prospectively. The Manual Muscle test (MMT-8; isometric muscle strength), the Functional Index of myositis test (FI-2; dynamic, repetitive muscle function), and disease activity (6-item core set) were retrieved at the time of diagnosis, and after 6 and 12 months. Self-reported health (Medical Outcomes Study Short Form-36; SF-36) was retrieved at 12 months., Results: At the time of diagnosis, median (Q1-Q3) for the FI-2 was 27.2% (7.9-60.5%) of maximal score compared to 93.8% (92.5-98.8%) of maximal MMT-8. At 12 months, the FI-2 and the MMT-8 improved to 29.4% (16.5-60.7%; p < 0.05) and 96.1% (88.1-99.4%), respectively (p < 0.01). At 12 months, 45% of patients improved ≥ 20%, and 27% worsened ≥ 20% in FI-2 score, while 10% improved ≥ 20% in MMT-8. Physician's global visual analog scale (VAS), Health Assessment Questionnaire, and creatine phosphokinase levels improved significantly at 12 months (p < 0.05-0.001) while patient's global and extramuscular VAS remained unchanged. The SF-36 physical function correlated strongly with the FI-2 (r s = 0.74; CI 0.55-0.85) and moderately with the MMT (r s = 0.54; CI 0.27-0.73), with lower correlations between muscle function and other SF-36 domains., Conclusion: Patients with PM/DM were characterized by impaired dynamic repetitive muscle function (DRMF) that correlated well with patient-reported physical function. Assessment of DRMF adds information regarding muscle impairment in these patients.

Objectives: To investigate the association between infection or respiratory tract disease and future risk of developing idiopathic inflammatory myopathy (IIM)., Methods: A case-control study was performed using Swedish nationwide registers. Adults with newly diagnosed IIM were identified (2002-2011) from the National Patient Register (NPR) and the Swedish Rheumatology Register (n=957). Controls were matched by age, sex and place of residence (n=9476). Outpatient visits and hospitalisations preceding IIM diagnosis indicating infection or respiratory disease were identified from NPR. Conditional logistic regression models were used to calculate OR and 95% CI. Sensitivity analyses were performed by varying the exposure definition, adjusting for previous healthcare consumption and excluding individuals with connective tissue disease, IIM lung phenotype or IIM-associated cancer., Results: Preceding infections were more common in IIM cases compared with controls (13% vs 9%) and were associated with an increased risk of IIM (OR 1.5, 95% CI 1.2 to 1.9). Gastrointestinal and respiratory tract infections were associated with an increased risk of IIM while cutaneous infections were not.Preceding respiratory tract disease was present in 10% of IIM cases and 4% of controls (OR 2.3, 95% CI 1.8 to 3.0). Both upper and lower respiratory tract diseases were associated with an increased risk of IIM.Variations in exposure and outcome definitions did not greatly affect the results., Conclusions: Infections and respiratory tract diseases are associated with an increased risk of IIM which suggests that the triggering of the immune system may take place outside the skeletal muscle., Competing Interests: Competing interests: IL has received honoraria from Bristol Myers Squibb and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)