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BackgroundIdiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complementC4in IIM pathology was unknown.MethodsWe elucidated the gene copy number (GCN) variations of totalC4,C4AandC4B, longandshort genesin 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion.ResultsThe large study populations helped establish the distribution patterns of variousC4GCN groups. Low GCNs ofC4T(C4T=2+3) andC4Adeficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28–2.91), p=5.0×10−53forC4T, and 2.82 (2.48–3.21), p=7.0×10−57forC4Adeficiency. Contingency and regression analyses showed that among patients withC4Adeficiency, the presence ofHLA-DR3became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% hadHLA-DR3with an OR of 11.02 (1.44–84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies.ConclusionsC4Adeficiency is relevant in dermatomyositis,HLA-DRB1*03is important in IBM and bothC4Adeficiency andHLA-DRB1*03contribute interactively to risk of polymyositis.

To identify predictors of response to immunosuppressive therapy after 1 year, with a focus on autoantibodies, in patients newly diagnosed with idiopathic inflammatory myopathies (IIM) followed longitudinally in an electronic registry.We assessed the association between autoantibody-defined groups and improvement according to American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 response criteria.We identified 156 patients; of those, 111 (71%) were positive for any autoantibody tested, 90% received glucocorticoid treatment at baseline, and 78% received immunosuppressive drugs at some follow-up point. After 1 year from the index date, the overall median improvement score was 27.5 (interquartile range 10-51). No differences were observed in the total improvement score between the autoantibody-defined groups. Overall, 62% of patients (n = 96) showed a minimal response, 38% (n = 60) achieved a moderate response, and 19% (n = 30) achieved a major response. Regarding the different levels of response, dermatomyositis-specific autoantibodies were associated with a moderate response versus the seronegative group (reference), odds ratio 4.12 (95% confidence interval 1.2-16.5). In addition, dysphagia, time from symptom onset to diagnosis, and initial glucocorticoid dose were significant predictors of response after 1 year of follow-up.Patients with DM-specific autoantibodies achieved better levels of response compared to other autoantibody-defined groups. Dysphagia, a shorter time span from symptom onset to diagnosis, and intensive initial immunosuppressive treatment were associated with a higher response rate after 1 year of pharmacologic treatment from the index date, regardless of autoantibody status.

Objectives: Autoantibodies are thought to play a key role in the pathogenesis of idiopathic inflammatory myopathies (IIM). However, up to 40% of IIM patients, even those with clinical manifestations of anti-synthetase syndrome (ASSD), test seronegative to known myositis-specific autoantibodies. We hypothesized the existence of new potential autoantigens among human cytoplasmic aminoacyl tRNA synthetases (aaRS) in patients with IIM. Methods: Plasma samples from 217 patients with IIM according to 2017 EULAR/ACR criteria, including 50 patients with ASSD, 165 without, and two with unknown ASSD status were identified retrospectively, as well as age and gender-matched sera from 156 population controls, and 219 disease controls. Patients with previously documented ASSD had to test positive for at least one of the five most common anti-aaRS autoantibodies (anti-Jo1, -PL7, -PL12, -EJ, and -OJ) and present with one or more of the following clinical manifestations: interstitial lung disease, myositis, arthritis, Raynaud's phenomenon, fever, or mechanic's hands. Demographics, laboratory, and clinical data of the IIM cohort (ASSD and non-ASSD) were compared. Samples were screened using a multiplex bead array assay for presence of autoantibodies against a panel of 117 recombinant protein variants, representing 33 myositis-related proteins, including all nineteen cytoplasmic aaRS. Prospectively collected clinical data for the IIM cohort were retrieved and compared between groups within the IIM cohort and correlated with the results of the autoantibody screening. Principal component analysis was used to analyze clinical manifestations between ASSD, non-ASSD groups, and individuals with novel anti-aaRS autoantibodies. Results: We identified reactivity towards 16 aaRS in 72 of the 217 IIM patients. Twelve patients displayed reactivity against nine novel aaRS. The novel autoantibody specificities were detected in four previously seronegative patients for myositis-specific autoantibodies and eight with previously detected myositis-specific autoantibodies. IIM individuals with novel anti-aaRS autoantibodies (n = 12) all had signs of myositis, and they had either muscle weakness and/or muscle enzyme elevation, 2/12 had mechanic's hands, 3/12 had interstitial lung disease, and 2/12 had arthritis. The individuals with novel anti-aaRS and a pathological muscle biopsy all presented widespread up-regulation of major histocompatibility complex class I. The reactivities against novel aaRS could be confirmed in ELISA and western blot. Using the multiplex bead array assay, we could confirm previously known reactivities to four of the most common aaRS (Jo1, PL12, PL7, and EJ (n = 45)) and identified patients positive for anti-Zo, -KS, and -HA (n = 10) that were not previously tested. A low frequency of anti-aaRS autoantibodies was also detected in controls. Conclusion: Our results suggest that most, if not all, cytoplasmic aaRS may become autoantigenic. Autoantibodies against new aaRS may be found in plasma of patients previously classified as seronegative with potential high clinical relevance. publishedVersion

There have been a number of advances in the clinical and translational understanding of cutaneous lupus and dermatomyositis, which both disproportionately affect women. These advances have involved ongoing collaborations between dermatology and rheumatology that highlight the importance of the skin in these disorders, with improvement in the education of trainees and clinical management of these complex multisystem diseases. In addition, a new disease classification has allowed inclusion of patients with skin-predominant dermatomyositis, frequently associated with systemic findings, in the spectrum of idiopathic inflammatory myopathies. Validated outcome measures allow translational research and facilitate progress toward better and more targeted therapeutics. Clinical trials using disease severity tools, such as the Cutaneous Lupus Erythematosus Area and Severity Index and the Cutaneous Dermatomyositis Disease Area and Severity Index, allow measurement of improvement in the skin. Recent results of phase 2 and 3 trials clearly show that patients will benefit from collaborative interactions and studies between dermatology and rheumatology.

This is an up-to-date review on external environmental factors for adult-onset idiopathic inflammatory myopathies (IIMs). Environmental factors with suggestive evidence including ultraviolet radiation, smoking, infectious agents (viruses in particular), pollutants, medications (ie, statin) and vitamin D deficiency are discussed. We also discuss the potential implications of environmental factors in IIM development, identify current challenges, and provide insight into future investigations.

The idiopathic inflammatory myopathies (IIM) are heterogeneous diseases, thought to be initiated by immune activation in genetically predisposed individuals. In this study we imputed variants from the Immunochip array using a large reference panel to fine-map associations and identify novel associations in IIM.We analysed 2,565 Caucasian IIM samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically-matched controls. We imputed 1,648,116 variants from the Immunochip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM, and clinical and serological subgroups.The human leukocyte antigen (HLA) locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, three in the whole IIM cohort (SDK2 and LINC00924 - both novel, and STAT4), with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM, for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells.We report novel and strong associations in IIM and PM, and localise signals to single genes and immune cell types. This article is protected by copyright. All rights reserved.

PURPOSE OF REVIEW To summarize information on polymyositis; diagnosis, definitions, published data and opinions. RECENT FINDINGS Polymyositis originally referred to inflammatory muscle diseases presenting with muscle weakness and inflammatory cell infiltrates on muscle tissue visible by microscopy. Over time and with improved technology to immunophenotype infiltrating inflammatory cells and characterize muscle fibres, the meaning of polymyositis changed and became more specific. There is ongoing controversy over the term polymyositis, with proponents for a strict definition based on histopathological and immunohistochemical features on muscle biopsies whereas others advocate for a broader clinical and histopathological phenotype. Over the past decades, the discovery of several myositis-specific autoantibodies together with distinct histopathological features have enabled the identification of new subsets previously labelled as polymyositis notably the antisynthetase syndrome and the immune-mediated necrotizing myopathies thus reducing the number of patients classified as polymyositis. SUMMARY There are still a small number of patients among the idiopathic inflammatory myopathies that can be classified as polymyositis as discussed in this review but the entity is now considered relatively rare.

Familial associations can be indicators of shared genetic susceptibility between two diseases. Previous data on familial autoimmunity in patients with idiopathic inflammatory myopathies (IIM) are scarce and inconsistent.To investigate which autoimmune diseases (ADs) may share genetic susceptibility with IIM, we examined the familial associations between IIM and different ADs.In this Swedish population-based family study, we assembled 7615 first-degree relatives (FDRs) of 1620 patients with IIM and 37,309 relatives of 7797 matched individuals without IIM. Via register linkages, we ascertained rheumatoid arthritis, other rheumatic inflammatory diseases (RIDs), multiple sclerosis, inflammatory bowel diseases (IBD), type 1 diabetes mellitus, autoimmune thyroid diseases (AITD), coeliac disease (CeD) and myasthenia gravis among the FDRs. We estimated the familial association between IIM and each AD using conditional logistic regression and performed subgroup analyses by kinship.Patients with IIM had significantly higher odds of having ≥1 FDR affected by other RIDs (adjusted odds ratio [aOR] = 1.40, 95% confidence interval [CI] 1.11-1.78) and greater odds of having ≥2 FDRs affected by CeD (aOR = 3.57, 95% CI 1.28-9.92) compared to the individuals without IIM. In the analyses of any FDR pairs, we observed familial associations for other RIDs (aOR = 1.34, 95% CI 1.14-1.56), IBD (aOR = 1.20, 95% CI 1.02-1.41), AITD (aOR = 1.10, 95% CI 1.02-1.19) and CeD (aOR = 1.37, 95% CI 1.08-1.74) while associations for other ADs were not statistically significant.The observed familial associations may suggest that IIM shares genetic susceptibility with various ADs, information that may be useful for clinical counselling and guiding future genetic studies of IIM.

Interstitial lung disease can be the first sign of systemic autoimmune disease. If associated with myositis, interstitial lung disease may be the only symptom, with no presence of muscular weakness or other extramuscular manifestations. ANA-testing performed with indirect immune fluorescence may be negative. Testing for myositis antibodies should be considered as a step in the diagnostic process when strong clinical suspicion of interstitial lung disease of unknown origin is present. If interstitial lung disease is suspected, the patients should be referred to a specialist clinic for further investigation and, if possible, for discussion within a multidisciplinary team. Early suspicion of systemic inflammatory disease, rapid diagnosis and early start of treatment are crucial for future prognosis, quality of life and survival.

Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.

Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases. There are distinct subgroups, including antisynthetase syndrome, dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and sporadic inclusion body myositis. In patients with IIM, autoantibodies are present in up to 80% of the patients. These autoantibodies are often characterized as myositis-specific autoantibodies (MSA) or myositis-associated autoantibodies (MAA). The recognition of the importance of autoantibodies, especially MSA, is increasing in recent years. In this chapter, we provide an overview of the MSAs, including some new autoantibodies of interest as they target mainly muscle-specific autoantigen, in clinical classification, the measurement of the disease activity, and a possible role in the pathogenesis in the patients with IIM.

ObjectivesThe 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.MethodsThis 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.ResultsWe 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.ConclusionsIIM 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.

ObjectivesAutoantibodies are thought to play a key role in the pathogenesis of idiopathic inflammatory myopathies (IIM). However, up to 40% of IIM patients, even those with clinical manifestations of anti-synthetase syndrome (ASSD), test seronegative to all known myositis-specific autoantibodies (MSAs). We hypothesized the existence of new potential autoantigens among human cytoplasmic aminoacyl tRNA synthetases (aaRS) in patients with IIM.MethodsPlasma samples and clinical data from 217 patients with, 50 patients with ASSD, 165 without, and two with unknown ASSD status were included retrospectively, as well as serum from 156 age/sex-matched population controls. Samples were screened using a multiplex bead array assay for presence of autoantibodies against a panel of 118 recombinant protein variants, representing 33 myositis-related proteins, including all 19 cytoplasmic aaRS.ResultsWe identified reactivity towards 16 aaRS in 72 of the 217 patients. Twelve patients displayed reactivity against nine novel aaRS. The novel autoantibody specificities were detected in four patients previously seronegative for MSAs and in eight with previously detected MSAs. We also confirmed reactivity to four of the most common aaRS (Jo1, PL12, PL7, and EJ (n=45)) and identified patients positive for anti-Zo, -KS, and -HA (n=10) that were not previously tested. A low frequency of anti-aaRS autoantibodies was detected in controls.ConclusionOur results suggest that most, if not all, cytoplasmic aaRS may become autoantigenic. Autoantibodies against new aaRS may be found in plasma of patients previously classified as seronegative with potential high clinical relevance.

Background/Aims Anti-synthetase syndrome (ASS) represents a distinct entity within myositis spectrum disorders; however, correct classification of patients with anti-tRNA synthetase autoantibodies and skin manifestations akin to dermatomyositis (DM) remains uncertain. Our aim was to compare clinical characteristics, skin involvement, and malignancy, between patients with ASS and DM, classified by disease-specific autoantibodies. Methods Data from 05/2009-03/2016 from 9 countries from the prospective, myositis EuroMyositis registry were downloaded. Those with anti-tRNA synthetase autoantibodies (Jo-1/PL-7/PL-12/OJ/EJ/KS) were classified as ASS, and those with Mi-2/TIF1-γ/NXP2/SAE/MDA5 autoantibodies as DM. Clinical phenotypes including malignancies (except skin malignancies) were tabulated. Characteristics of patients with skin involvement (excluding mechanic’s hands and Raynaud’s phenomenon) were compared using Fisher’s exact test with Bonferroni corrected p-values. Results Of 3,067 patients, 2,028 had autoantibody profiling results (66.1%), of which 783 (38.6%) were positive for at least one of the autoantibodies being considered. Five patients with dual autoantibody specificities were excluded. Of the remaining 778, 320 (41.1%) were classified as DM, and 458 (58.9%) as ASS. Median age at diagnosis was 48.2 years (interquartile range [IQR] 37.5 to 57.8) in the DM cohort and 49 (IQR 38.3 to 62.2) in the ASS cohort. Skin involvement was present in 277 (86.6%) DM patients (DM skin) vs 204 (44.5%) ASS patients (ASS skin) (pcorr Conclusion Patients with ASS have frequent skin involvement but also a distinct clinical phenotype compared to DM. These findings may inform the development of future classification criteria for ASS. Disclosure R.M. Hum: None. J.B. Lilleker: None. J.A. Lamb: None. W.E. Ollier: None. G. Wang: None. L.R. Wedderburn: None. L.P. Diederichsen: None. J. Schmidt: None. P. Oakley: None. O. Benveniste: None. M.G. Danieli: None. K. Danko: None. N.T.P. Thuy: None. M.V.D. Mercado: None. H. Andersson: None. B.D. Paepe: None. J.L.D. Bleecker: None. B. Maurer: None. L.J. McCann: None. N. Pipitone: None. N. McHugh: None. P. New: None. J. Vencovsky: None. I.E. Lundberg: None. H. Chinoy: None.

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 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.

Objectives To examine pregnancy outcomes among births to women with idiopathic inflammatory myopathy (IIM) in relation to time of IIM diagnosis using population-based data. Methods This study used Swedish nationwide registers to identify all singleton births that occurred between 1973 and 2016 among women diagnosed with IIM between 1998 and 2016 and among women unexposed to IIM. We classified births according to the IIM status of the mother at time of delivery: post-IIM (n = 68), 1–3 years pre-IIM (n = 23), >3 years pre-IIM (n = 710) and unexposed to IIM (n = 4101). Multivariate regression models were used to estimate relative risks of adverse pregnancy outcomes in post-IIM births and pre-IIM births separately, in comparison with their non-IIM comparators. Results We found that post-IIM births had increased risks of caesarean section [adjusted relative risk (aRR) = 1.98; 95% CI: 1.08, 3.64], preterm birth (aRR = 3.35; 95% CI: 1.28, 8.73) and low birth weight (aRR = 5.69; 95% CI: 1.84, 17.55) compared with non-IIM comparators. We also noticed higher frequencies of caesarean section and instrumental delivery in 1–3 years pre-IIM births than in the non-IIM comparators. Conclusion Women who gave birth after IIM diagnosis had higher risks of caesarean section, preterm birth and low birth weight. These results further underline the importance of special care and close monitoring of women with IIM. Higher frequencies of caesarean section and instrumental delivery in pre-IIM births highlight the need for future research on the influence of subclinical features of IIM on pregnancy outcomes.

Objective: Pain interference, fatigue, and impaired physical function are common features of idiopathic inflammatory myopathies (IIM). The objective of this study was to evaluate the construct validity and test-retest reliability of the Patient Reported Outcome Information System (PROMIS) Pain Interference 6av1.0, Fatigue 7av1.0, and Physical Function 8bv2.0 instruments. Methods: Patient-Reported Outcome Measures (PROMs) were deployed to adult IIM patients from OMERACT Myositis Working Group (MWG) international clinic sites via two online surveys (2019, 2021). Internal consistency of each PROM was analyzed by Cronbach's α. Construct validity was determined by a priori hypotheses generated by the MWG with >75% agreement for each hypothesis and calculated with Pearson correlations. Test-retest reliability was assessed using intraclass correlation coefficient with PROMIS instruments administered at time zero and 7 days. Results: Surveys were sent to 368 participants in total; participants who completed each questionnaire varied (n=65 to 263). For construct validity, 10 out of 13 a priori hypotheses were met supporting construct validity of PROMIS instruments (Pain Interference 3/4, fatigue 4/4, and Physical Function 3/5). Test-retest reliability was strong for all PROMIS instruments. All PROMIS instruments demonstrated excellent internal consistency. None of the measures demonstrated any ceiling or floor effects except for a ceiling effect in the Pain Interference instrument. Conclusions: This study presents test-retest reliability and construct validity evidence supporting PROMIS Pain Interference (6a v1.0), Fatigue (7a v1.0), and Physical Function (8b v2.0) using a large international cohort of patients with IIM. Internal consistency of these instruments was excellent. A ceiling effect was noted in the Pain Interference instrument.

BackgroundTo address the reactivity and affinity against histidyl-transfer RNA synthetase (HisRS) autoantigen of anti-Jo1 autoantibodies from serum and bronchoalveolar lavage fluid (BALF) in patients with idiopathic inflammatory myopathies/anti-synthetase syndrome (IIM/ASSD). To investigate the associations between the reactivity profile and clinical data over time.MethodsSamples and clinical data were obtained from (i) 25 anti-Jo1+patients (19 sera with 16 longitudinal samples and 6 BALF/matching sera at diagnosis), (ii) 29 anti-Jo1−patients (25 sera and 4 BALF/matching sera at diagnosis), and (iii) 27 age/gender-matched healthy controls (24 sera and 3 BALF/matching sera). Reactivity towards HisRS full-length (HisRS-FL), three HisRS domains (WHEP, antigen binding domain (ABD), and catalytic domain (CD)), and the HisRS splice variant (SV) was tested. Anti-Jo1 IgG reactivity was evaluated by ELISA and western blot using IgG purified from serum by affinity chromatography. In paired serum-BALF, anti-Jo1 IgG and IgA reactivity was analyzed by ELISA. Autoantibody affinity was measured by surface plasmon resonance using IgG purified from sera. Correlations between autoantibody reactivity and clinical data were evaluated at diagnosis and longitudinally.ResultsAnti-Jo1 IgG from serum and BALF bound HisRS-FL, WHEP, and SV with high reactivity at the time of diagnosis and recognized both conformation-dependent and conformation-independent HisRS epitopes. Anti-HisRS-FL IgG displayed high affinity early in the disease. At the time of IIM/ASSD diagnosis, the highest autoantibody levels against HisRS-FL were found in patients ever developing interstitial lung disease (ILD) and arthritis, but with less skin involvement. Moreover, the reactivity of anti-WHEP IgG in BALF correlated with poor pulmonary function.Levels of autoantibodies against HisRS-FL, HisRS domains, and HisRS splice variant generally decreased over time. With some exceptions, longitudinal anti-HisRS-FL antibody levels changed in line with ILD activity.ConclusionHigh levels and high-affinity anti-Jo1 autoantibodies towards HisRS-FL were found early in disease in sera and BALF. In combination with the correlation of anti-HisRS-FL antibody levels with ILD and ILD activity in longitudinal samples as well as of anti-WHEP IgG in BALF with poor pulmonary function, this supports the previously raised hypothesis that the lung might have a role in the immune reaction in anti-Jo1-positive patients.

Objective The aim of this study was to determine the frequency of clinical and subclinical atherosclerosis in Vietnamese patients with SSc and the risk factors for subclinical atherosclerosis. Methods A case–control study of 46 patients with SSc who met the ACR criteria for the disease and 42 healthy age- and sex-matched controls of Kinh ethnicity was conducted. Clinical data including cardiovascular disease (CVD) events were collected. Serum levels of blood lipids and high-sensitivity CRP were determined. Carotid artery intima–media thickness (IMT) and carotid plaques were measured by carotid Doppler ultrasonography. Results Patients with SSc, of whom 96% had dcSSc, reported a higher number of CVD events compared with the controls (21.7 vs 0%; P = 0.0065). They exhibited low serum levels of high-density lipoprotein cholesterol and high levels of total cholesterol compared with controls (P = 0.01 and P = 0.03, respectively). Common carotid artery IMT was significantly higher in SSc patients compared with controls [mean (s.d.): 0.61 (0.12) vs 0.47 (0.07) mm; P Conclusion We confirmed an increased risk of CVD events and signs of subclinical atherosclerosis in patients with SSc of Kinh ethnicity and both traditional and disease-related risk factors for CVD.

Anti-synthetase syndrome (ASSD) is an autoimmune disease characterized by the presence of autoantibodies targeting one of several aminoacyl t-RNA synthetases (aaRSs) along with clinical features including interstitial lung disease, myositis, Raynaud's phenomenon, arthritis, mechanic's hands, and fever. The family of aaRSs consists of highly conserved cytoplasmic and mitochondrial enzymes, one for each amino acid, which are essential for the RNA translation machinery and protein synthesis. Along with their main functions, aaRSs are involved in the development of immune responses, regulation of transcription, and gene-specific silencing of translation. During the last decade, these proteins have been associated with cancer, neurological disorders, infectious responses, and autoimmune diseases including ASSD. To date, several aaRSs have been described to be possible autoantigens in different diseases. The most commonly described are histidyl (HisRS), threonyl (ThrRS), alanyl (AlaRS), glycyl (GlyRS), isoleucyl (IleRS), asparaginyl (AsnRS), phenylalanyl (PheRS), tyrosyl (TyrRS), lysyl (LysRS), glutaminyl (GlnRS), tryptophanyl (TrpRS), and seryl (SerRS) tRNA synthetases. Autoantibodies against the first eight autoantigens listed above have been associated with ASSD while the rest have been associated with other diseases. This review will address what is known about the function of the aaRSs with a focus on their autoantigenic properties. We will also describe the anti-aaRSs autoantibodies and their association to specific clinical manifestations, and discuss their potential contribution to the pathogenesis of ASSD.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of complex autoimmune conditions characterized by inflammation in skeletal muscle and extramuscular compartments, and interferon (IFN) system activation. We undertook this study to examine the contribution of genetic variation to disease susceptibility and to identify novel avenues for research in IIMs.METHODS: Targeted DNA sequencing was used to mine coding and potentially regulatory single nucleotide variants from ~1,900 immune-related genes in a Scandinavian case-control cohort of 454 IIM patients and 1,024 healthy controls. Gene-based aggregate testing, together with rare variant- and gene-level enrichment analyses, was implemented to explore genotype-phenotype relations.RESULTS: Gene-based aggregate tests of all variants, including rare variants, identified IFI35 as a potential genetic risk locus for IIMs, suggesting a genetic signature of type I IFN pathway activation. Functional annotation of the IFI35 locus highlighted a regulatory network linked to the skeletal muscle-specific gene PTGES3L, as a potential candidate for IIM pathogenesis. Aggregate genetic associations with AGER and PSMB8 in the major histocompatibility complex locus were detected in the antisynthetase syndrome subgroup, which also showed a less marked genetic signature of the type I IFN pathway. Enrichment analyses indicated a burden of synonymous and noncoding rare variants in IIM patients, suggesting increased disease predisposition associated with these classes of rare variants.CONCLUSION: Our study suggests the contribution of rare genetic variation to disease susceptibility in IIM and specific patient subgroups, and pinpoints genetic associations consistent with previous findings by gene expression profiling. These features highlight genetic profiles that are potentially relevant to disease pathogenesis.

Objectives To determine the prevalence and associations of autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), in South Australian patients with histologically-confirmed idiopathic inflammatory myopathies (IIM) and in patients with SSc. Material and methods Sera from patients with IIM (n = 267) from the South Australian Myositis Database (SAMD), SSc (n = 174) from the Australian Scleroderma Cohort Study (ASCS) and healthy controls (HC, n = 100) were analysed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Results Autoantibodies to FHL1 were more frequent in patients with IIM (37/267, 13.8%) compared with SSc (12/174, 7%) (P Conclusions We report a substantial prevalence (13.8%) of anti-FHL1 autoantibodies in a large cohort of patients with histologically confirmed IIM; 75% of these cases did not have a detectable myositis-specific autoantibody. Anti-FHL1 autoantibodies were also detected in a subgroup of patients with SSc (7%), indicating that anti-FHL1 autoantibodies may not be myositis-specific. The trend towards an HLA-DR association might indicate a specific immune response to the FHL1 protein.

Objectives Anti-TIF1-gamma autoantibodies can be detected with immunoprecipitation (IP), line blot (LB) and ELISA. We compared assay performance in patients with DM and the potential of these assays to detect anti-TIF1-gamma positive cancer-associated DM (CADM). Methods We included sera from 131 patients with DM followed at Karolinska University Hospital, Stockholm, Sweden and 82 healthy controls. Serum samples taken at DM diagnosis were tested for anti-TIF1-gamma autoantibodies with IP, two ELISAs (in-house and commercial) and LB. Cancer diagnosis and dates were obtained from the Swedish national cancer register. CADM was defined as a malignancy that developed within 3 years of DM diagnosis. Results Anti-TIF1-gamma autoantibodies were detected in 19/101 (18.8%), 15/113 (13.2%), 34/131 (26%) and 45/131 (34.4%) of the patients with IP, LB, in-house and commercial ELISA, respectively. The anti-TIF1-gamma results from the in-house ELISA were confirmed with IP in 93 of 101 (92%) cases, κ = 0.76, with a commercial ELISA in 110 of 131 (84%) cases, κ = 0.63, and with LB in 101 of 113 (89.3%) cases, κ = 0.67. Anti-TIF1-gamma results with IP were confirmed with LB in 85 of 92 (92.4%) cases, κ = 0.73. For detecting CADM, the anti-TIF1-gamma in-house ELISA had a sensitivity of 58% and specificity of 86%, the commercial ELISA had a sensitivity of 63% and specificity of 82%, IP had a sensitivity of 52% and specificity of 92%, LB had a sensitivity of 40% and specificity of 96%. Conclusion The two anti-TIF1-gamma ELISA assays had advantages both for autoantibody detection and to identify anti-TIF1-gamma-positive CADM.

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Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that IIM are systemic inflammatory disorders. Different myositis-specific auto-antibodies have been identified and, on the basis of clinical, histopathological and serological features, IIM can be classified into several subgroups - dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the auto-antigens of the immune reactions in these subgroups is crucial to improving outcomes. New, more homogeneous subgroups defined by auto-antibodies may help define disease mechanisms and will also be important in future clinical trials for the development of targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.

Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. Methods We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. Results We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. Conclusion The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

Objectives The aim of this study was to investigate cardiac involvement detected by ECG in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate possible associations between the autoantibody profile and ECG changes in these patients. Methods In a Scandinavian cross-sectional study, patients were included from two Danish centres and one Swedish centre. Resting 12-lead ECG was investigated in 261 patients with IIM compared with 102 patients with systemic sclerosis (SSc) and 48 healthy controls (HCs). ECG changes were correlated to clinical manifestations and myositis-specific and myositis-associated autoantibodies (MSAs and MAAs, respectively). Results Patients with IIM had a longer mean corrected QT (QTc) duration and more frequently presented with prolonged QTc (≥450 ms; P = 0.038) compared with HCs. A longer QTc duration was recorded in SSc compared with IIM [433 ms (s.d. 23) vs 426 (24); P = 0.011], yet there was no significant difference in the fraction with prolonged QTc (SSc: 22%, IIM: 16%; P = 0.19). In multivariable regression analyses, anti-Mi2 (P = 0.01, P = 0.035) and anti-Pl-7 (P = 0.045, P = 0.014) were associated with QTc duration and prolonged QTc in IIM. Elevated CRP was associated with prolonged QTc (P = 0.041). Conclusion The presence of QTc abnormalities was as common in patients with IIM as in patients with SSc, including prolonged QTc seen in almost one-fifth of the patients. Anti-Mi2, anti-Pl-7 and elevated CRP may serve as biomarkers for cardiac disease in IIM, but needs to be confirmed in a larger prospective study.

Major advances have been made in the field of idiopathic inflammatory myopathies (IIM), or myositis, that are likely to facilitate development of new therapeutic strategies that have not yet been applied in this group of diseases. These advances include new classification criteria to better identify the patients with IIM, detection of several new myositis-specific autoantibodies that facilitates subgrouping of patients into more specific clinical phenotypes, development of outcome measures for disease activity, and new response criteria. We have learned from clinical studies that exercise is an important part of treatment and that pharmacologic treatment should be combined with exercise.

Objectives To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. Methods Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren’s syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. Results IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. Conclusion We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

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 present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018.Methods.Based on results from international focus groups and Delphi surveys, a draft core set was developed.Results.Domains muscle symptoms, fatigue, level of physical activity, and pain reached ≥ 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018.Conclusion.We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections.

Objective Post-hoc analyses of the Rituximab in Myositis trial indicate that specific autoantibodies profiles may influence treatment response. We compared the efficacy and safety of rituximab in anti-synthetase antibody (ARS-ab) positive and negative patients. Methods Adult idiopathic inflammatory myopathy (IIM) subjects in the Swedish Rheumatology Quality Register who received ⩾ 1 cycle of rituximab were enrolled. Efficacy assessment was based on the International Myositis Assessment and Clinical Studies (IMACS) core set measures and the 2016 ACR/EULAR definition of improvement for PM and DM. Safety assessment included drug-related adverse event and death during study period. Comparisons were done within and between the ARS-ab defined groups before and after first and last cycles. Associations between selected clinical features and improvement after one rituximab cycle were assessed using logistic regression. Results Sixty-five subjects were included and 43 had a follow-up visit within 5-10 months. Seventy-eight percent of ARS-ab positive subjects had moderate/major ACR/EULAR improvement after one cycle compared with 50% in the ARS-ab negative group. After several cycles, 79% of the ARS-ab positive and 67% of the ARS-ab negative patients achieved moderate/major improvement. A significant glucocorticoid-sparing effect was only observed in the ARS-ab positive group (P = 0.001). The most frequent adverse events were infections. One ARS-ab positive and two ARS-ab negative patients died during follow-up period. Conclusion Irrespectively of their autoantibody status, a majority of subjects treated with several rituximab cycles had moderate/major improvement. In addition, ARS-ab positive subjects experienced a significant glucocorticoid-sparing effect.

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.

Background The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). Methods Skin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC). Results Proteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions. Conclusions Using unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.

Objectives: This study aimed to assess the contribution of traditional/disease-related risk factors and biomarkers linked to arterial and venous thrombotic events (TEs) in patients with idiopathic inflammatory myopathies (IIMs). Method: The occurrence of arterial and/or venous TEs at the time of or after IIM diagnosis was retrospectively evaluated in a cohort of 253 patients with IIMs, resulting in a final population of 246 IIM patients, 51 with reported TE (cases) and 195 without a history of TE (comparators). Information on disease characteristics and traditional risk factors for arterial and venous TE (essential hypertension, diabetes, dyslipidaemia, smoking, malignancy) was retrieved. Serum levels of anti-phospholipid antibodies (aPLs) and adhesion molecules were analysed at the time of IIM diagnosis and at the time of the TE in cases. Results: One in five IIM patients (21%) had experienced a TE, arterial TE in 22 and venous TE in 29 patients, with a peak prevalence within 5 years after diagnosis. Among traditional/disease-related risk factors, only older age was associated with both arterial and venous TEs, after adjusting for other covariates. Low serum levels of e-selectin were associated with higher odds of developing a TE, without specific association with either arterial or venous TEs. Only 6% of IIM patients had aPLs, with no significant difference between cases and comparators. Conclusions: An increased risk of both venous and arterial TEs should be considered in IIM patients, particularly close to diagnosis and in elderly people. Low serum levels of e-selectin may predict TE in IIM patients, but the underlying biological mechanism is not known.

Objective To assess clinical phenotypes of anti-aminoacyl-transfer RNA synthetases (aaRS) autoantibodies in Vietnamese patients of Kinh ethnicity with idiopathic inflammatory myopathies (IIM). Methods In a cross-sectional study 23 patients with anti-aaRS autoantibodies were compared to 36 patients with other myositis-specific antibodies and to 69 seronegative patients with IIM. Assessments included muscle performance, extra-muscular involvement, and disease activity according to the International Myositis Assessment and Clinical Studies (IMACS). Sera were tested by a line immunoassay (Euroline Myositis Profile 4). Results The frequency of anti-Jo-1 antibodies was 56.5%, anti-EJ antibodies 26.1%, and anti-PL-7 antibodies 17.4%, while anti-PL-12 and anti-OJ antibodies were not present in any case. All patients with anti-aaRS autoantibodies had signs of myositis. At time of investigation 22/23 patients had muscle weakness, 52.2% arthritis, 34.8% Raynaud's phenomenon, 73.9% fever, 14.3% mechanic's hands and 56.5% dysphagia. Interstitial lung disease was present in 52.2%, and pulmonary hypertension in 56.5%. The anti-aaRS autoantibody positive group had higher disease activity in the domains of skin and pulmonary disease compared to the seronegative group and had lower disease activity in skeletal disease compared to the anti-melanoma differentiation-associated protein 5-positive patients. The clinical presentation of antisynthetase syndrome was similar between the aaRS autoantibody specificities with the exception of more frequent pulmonary hypertension in anti-Jo-1 positive patients. Conclusions Different aaRS autoantibody specificities may vary between different ethnic populations for reasons that still need to be clarified. Furthermore, the high frequency of pulmonary hypertension is noteworthy but otherwise clinical manifestations associated with aaRS autoantibodies did not differ from other ethnic populations.

Objective To investigate the content validity of several patient-reported outcome measures (PROMs) in patients with idiopathic inflammatory myopathies (IIM). Methods Seven individual PROM instruments were selected by the Outcome Measures in Rheumatology (OMERACT) Myositis Working Group relating to the following domains: pain, fatigue, physical function and physical activity. Twenty patients from the Johns Hopkins Myositis Center were selected for one-on-one face-to-face or phone interviews for cognitive interviewing of individual PROMs to assess comprehension and content validity. Additionally, patients were asked if they thought muscle symptoms, an area originally identified in qualitative studies, were encapsulated by the other four domains. Results The majority of patients (>70%) felt that each of the instruments was clear, easy to read and understand, and could be used for assessment of its domain. Two-thirds (66%) of patients felt that ‘muscle symptoms’ were captured by the other domains. Conclusions We provided evidence to support adequate content validity for several PROMs. Further research is needed to determine whether ‘muscle symptoms’ warrant a separate domain.

Objective To examine the association between idiopathic inflammatory myopathy (IIM) and cancer before and after IIM diagnosis. Methods We used prospectively collected nationwide register data to design a case-control study to investigate the occurrence of cancer before IIM, and a cohort study to investigate the occurrence of cancer after IIM. Patients diagnosed with IIM between 2002 and 2016 in Sweden, were compared to the general population. The association between cancer and IIM was estimated before and after IIM diagnosis via logistic regression and Cox regression models, respectively. Results We included 1419 patients with IIM and 7045 individuals from the general population. The overall odds of cancer before IIM diagnosis were increased in IIM compared to the general population, adjusted odds ratio (AOR) 1.5, 95% confidence interval (CI) 1.3–1.8. This association was also noted after IIM diagnosis, adjusted hazard ratio (AHR) 1.7 (95% CI 1.4–2.0), or one additional cancer in every 125 IIM patients per year. Colorectal (AOR 2.1), lung (AOR 5.4) and ovarian (AOR 7.0) cancers were associated with IIM before diagnosis. Oropharyngeal (AHR 9.1) and cervical (AHR 3.8) cancers, malignant melanoma (AHR 3.2) and non-melanoma skin cancer (AHR 3.1) were associated with IIM after diagnosis. Adenocarcinomas were associated with dermatomyositis before diagnosis and squamous cell cancers after IIM diagnosis. Lymphatic hematopoietic cancers were associated with IIM both before and after diagnosis. Conclusions The cancer types that occur before IIM diagnosis differ from the ones that occur after diagnosis. This may have an impact on screening decisions for IIM.