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ObjectivesInflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICIs) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis.MethodsBulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM and two IBM).ResultsUnsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1 and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed coexisting myocarditis. ICI-MYO2 was composed of patients with predominant necrotising pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway.ConclusionsWe identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICI-DM and ICI-MYO1 and only ICI-MYO1 patients developed myocarditis.

This case report concerns a 63-year-old man affected by metastatic undifferentiated liposarcoma. After receiving pembrolizumab as a second-line treatment in a clinical trial, the patient experienced an immune-mediated myocarditis, myositis and myasteniform syndrome. The last two adverse events showed significant clinical relevance in terms of severity, duration and the required specific treatment.Initial treatment approach consisted in pulses of 1 g of methylprednisolone, followed by 2 mg/kg/day, with clinical improvement. After 12 days, the immune-mediated myasteniform syndrome worsened, with dysphagia, dysphonia, bilateral palpebral ptosis and respiratory difficulty. Due to the refractoriness to glucocorticoid treatment, it was decided to initiate intravenous immunoglobulin at 2 g/kg, followed by 2 mg/kg every 4 weeks once discharged and mycophenolate 500 mg/12 hours, in order to reduce the dose of glucocorticoids.After 2 months, the patient presented an optimal clinical evolution, without muscular weakness and referred to an improvement in dysphagia and speech.

ObjectivesInflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICI) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis.MethodsBulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM, and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (7 ICI-myositis, 4 DM, 3 AS, 6 IMNM, and 2 IBM).ResultsUnsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1, and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed co-existing myocarditis. ICI-MYO2 was composed of patients with predominant necrotizing pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway.ConclusionsWe identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICIDM and ICI-MYO1, and only ICI-MYO1 patients developed myocarditis.

Purpose of review Necrotizing myopathy is a broad term. It includes patients with the recently described immune-mediated necrotizing myopathies (IMNM) who have specific antibodies, such as anti-hydroxy-3-methylglutaryl-CoA reductase or anti-signal recognition particle, seronegative phenotypes that can be associated with cancer, and other types of myositis and connective tissue diseases involving necrotic muscle fibers as a characteristic pathologic feature. Necrotizing myopathies that are not immune-mediated, such as those caused by drugs, dystrophies, infections, or even hypothyroidism are also included. The purpose of this review is to address the differential diagnosis of these disorders. Recent findings New IMNM have been described over the last few years, some of them related with checkpoint inhibitors, drugs that are being increasingly used in cancer treatment. Necrotizing myopathy has also been reported in association with specific phenotypes and autoantibodies (e.g. anti-Mi2 dermatomyositis, antisynthetase syndrome, and myositis associated with antimitochondrial antibodies). Rarer cases associated with graft-versus-host disease and severe acute respiratory syndrome coronavirus 2 infection are also emerging. Summary Differentiation between patients with IMNM and those without the superimposed autoimmune phenomena helps clinicians determine the best individualized approach to use and the appropriate immunosuppressive therapy, whenever needed.

Cancer-associated myositis (CAM) is defined as when cancer appears within 3 years of myositis onset. Dermatomyositis and seronegative immune-mediated necrotizing myopathy are the phenotypes mostly related to cancer. In general, treatment principles in myositis patients with and without CAM are similar. However, some aspects of myositis management are particular to CAM, including (a) the need for a multidisciplinary approach and a close relationship with the oncologist, (b) the presence of immunosuppressive and antineoplastic drug interactions, and (c) the role of the long-term immunosuppressive therapy as a risk factor for cancer relapse or development of a second neoplasm. In this review, we will also discuss immunotherapy in patients treated with checkpoint inhibitors as a treatment for their cancer.Studies on cancer risk in patients treated with long-term immunosuppressive drugs, in autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis, and in solid organ transplant recipients have shed some light on this topic. Immunotherapy, which has been a great advance for the treatment of some types of malignancy, may be also of interest in CAM, given the special relationship between both disorders.Management of CAM is a challenge. In this complex scenario, therapeutic decisions must consider both diseases simultaneously.The online version contains supplementary material available at 10.1007/s40674-022-00197-2.

ObjectivesMyositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients. This study aimed to define the transcriptional profile of muscle biopsies from anti-Mi2-positive DM patients.MethodsRNA sequencing was performed on muscle biopsies (n=171) from patients with anti-Mi2-positive DM (n=18), DM without anti-Mi2 autoantibodies (n=32), AS (n=18), IMNM (n=54) and IBM (n=16) as well as 33 normal muscle biopsies. Genes specifically upregulated in anti-Mi2-positive DM were identified. Muscle biopsies were stained for human immunoglobulin and protein products corresponding to genes specifically upregulated in anti-Mi2-positive muscle biopsies.ResultsA set of 135 genes, includingSCRT1andMADCAM1, was specifically overexpressed in anti-Mi2-positive DM muscle. This set was enriched for CHD4/NuRD-regulated genes and included genes that are not otherwise expressed in skeletal muscle. The expression levels of these genes correlated with anti-Mi2 autoantibody titres, markers of disease activity and with the other members of the gene set. In anti-Mi2-positive muscle biopsies, immunoglobulin was localised to the myonuclei, MAdCAM-1 protein was present in the cytoplasm of perifascicular fibres, and SCRT1 protein was localised to myofibre nuclei.ConclusionsBased on these findings, we hypothesise that anti-Mi2 autoantibodies could exert a pathogenic effect by entering damaged myofibres, inhibiting the CHD4/NuRD complex, and subsequently derepressing the unique set of genes defined in this study.

In recent years, immunotherapy has become an important pillar of cancer treatment, with high response rates regardless of tumour histology or baseline mutations. However, immune activation associated with check-point inhibitors is not selective and a large variety of immune-related adverse events have been associated with anti-PD1, anti-PD-1/L-1 and anti-CTLA-4 agents. Though diagnosis and treatment of these toxicities have been established according to the recommendations from clinical trials and in line with the autoimmune disorders that they mimic, increasing real-world data is coming up showing that these adverse events may have differential characteristics and management, especially in terms of the use of corticoids, second-line treatments, salvage therapy for life-threatening cases and reintroduction of immunotherapy. Herein we present a comprehensive review of current recommendations and real-world data on the main immune-related adverse events of immunotherapy.

Objetivos Describir la metodología del Registro de pacientes con miopatía inflamatoria idiopática (MII) de España (Myo-Spain), así como sus fortalezas y limitaciones. El objetivo principal del proyecto es analizar la evolución y el manejo clínico de una cohorte de pacientes con MII. Material y método Estudio observacional, longitudinal, ambispectivo y multicéntrico de una cohorte de pacientes con MII atendidos en servicios de reumatología de España. Se incluirán todos los pacientes con diagnóstico de MII en seguimiento habitual por los centros participantes, sin tener en cuenta la edad de inicio del proceso. Los casos incidentes serán todos los pacientes que al inicio del estudio en cada centro estén diagnosticados desde hace menos de 12 meses y casos prevalentes desde hace más de 12 meses. Se construirá un registro en el que se incluirán los datos de la visita basal, del año y dos años. Se recogerán variables sociodemográficas, clínicas, analíticas, complicaciones, comorbilidad, asociación con otras enfermedades reumáticas, ingresos hospitalarios, mortalidad y tratamientos. Además, se determinarán índices, escalas y cuestionarios de actividad, afectación muscular, daño, discapacidad y calidad de vida. El periodo de reclutamiento será de 23 meses. El propósito es conseguir una cohorte de 400 pacientes con MII. Conclusiones El estudio Myo-Spain constituye la oportunidad para desarrollar una cohorte de pacientes incidentes y prevalentes con MII en España. Myo-Spain permitirá evaluar en detalle, las características clínicas de la enfermedad en diferentes momentos. Se espera que la información exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros análisis. Objectives: To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. Methods: Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. Conclusions: Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis. Sin financiación No data JCR 2021 0.311 SJR (2021) Q3, 44/61 Rheumatology No data IDR 2021 UEM

Necrotizing myopathy is a broad term. It includes patients with the recently described immune-mediated necrotizing myopathies (IMNM) who have specific antibodies, such as anti-hydroxy-3-methylglutaryl-CoA reductase or anti-signal recognition particle, seronegative phenotypes that can be associated with cancer, and other types of myositis and connective tissue diseases involving necrotic muscle fibers as a characteristic pathologic feature. Necrotizing myopathies that are not immune-mediated, such as those caused by drugs, dystrophies, infections, or even hypothyroidism are also included. The purpose of this review is to address the differential diagnosis of these disorders.New IMNM have been described over the last few years, some of them related with checkpoint inhibitors, drugs that are being increasingly used in cancer treatment. Necrotizing myopathy has also been reported in association with specific phenotypes and autoantibodies (e.g. anti-Mi2 dermatomyositis, antisynthetase syndrome, and myositis associated with antimitochondrial antibodies). Rarer cases associated with graft-versus-host disease and severe acute respiratory syndrome coronavirus 2 infection are also emerging.Differentiation between patients with IMNM and those without the superimposed autoimmune phenomena helps clinicians determine the best individualized approach to use and the appropriate immunosuppressive therapy, whenever needed.

Purpose of the review Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders. The presence of different autoantibodies allows clinicians to define distinct phenotypes. Antibodies against the melanoma differentiation-associated protein 5 gene, also called anti-MDA5 antibodies, are associated with a characteristic phenotype, the clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. This review aims to analyze the different pharmacological options for the treatment of rapidly progressive interstitial lung disease in patients with anti-MDA5 antibodies. Recent findings Evidence-based therapeutic recommendations suggest that the best initial approach to treat these patients is an early combination of immunosuppressive drugs including either glucocorticoids and calcineurin inhibitors or a triple therapy adding intravenous cyclophosphamide. Tofacitinib, a Janus kinase inhibitor, could be useful according to recent reports. High ferritin plasma levels, generalized worsening of pulmonary infiltrates, and ground-glass opacities should be considered predictive factors of a bad outcome. In this scenario, clinicians should consider rescue therapies such as therapeutic plasma exchange, polymyxin-B hemoperfusion, veno-venous extracorporeal membrane oxygenation, or even lung transplantation. Summary Combined immunosuppressive treatment should be considered the first-line therapy for patients with anti-MDA5 rapidly progressive interstitial lung disease. Aggressive rescue therapies may be useful in refractory patients.

There is a well-recognized association between cancer and myositis, so cancer screening at diagnosis is recommended. We aim to report the results of our cancer screening strategy and to ascertain the reliability of using PET/CT to identify cancer-associated myositis (CAM) in a large cohort of patients with myositis from a single center over 10 years.This retrospective observational study included all patients diagnosed with any type of myositis except for inclusion body myositis. Cancer screening strategy was individualized according to clinical and serological data, including PET/CT as the main test to detect occult cancer (OC). Procedures derived from a positive PET/CT were registered. Qualitative data expressed as percentages, and quantitative data as the median with the interquartile range were analyzed. A ROC curve was used to estimate the reliability of PET/CT for CAM diagnosis.Seventy-seven out of 131 patients underwent a PET/CT for OC screening. The performance of the PET/CT in patients with myositis at disease onset yielded an area under the curve ROC of 0.87 (0.73-0.97) for CAM diagnosis. Invasive procedures in 7 (9%) patients without a final diagnosis of cancer did not cause derived complications. Patients not evaluated for OC did not develop cancer after a median follow-up of 3.3 years (1.7-6.7).Cancer screening strategy should be individualized. PET/CT at myositis onset seems to be an efficient approach to rule out CAM. This practice does not seem to significantly increase harm to patients related to the additional tests needed to clarify inconclusive results.

Objective To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions Our results support the association of the HLA complex with the susceptibility to ASSD.

Objectives To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. Methods Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. Conclusions Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.

OBJECTIVESTo investigate the incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases receiving targeted biologic and synthetic disease modifying anti-rheumatic drugs (tDMARDs) and to explore the possible effect of these treatments in the clinical expression of COVID-19.METHODSA cross-sectional study comprising of a telephone survey and electronic health records review was performed including all adult and paediatric patients with rheumatic diseases treated with tDMARDs in a large rheumatology tertiary centre in Barcelona, Spain. Demographics, disease activity, COVID-19 related symptoms and contact history data were obtained from the start of the 2020 pandemic. Cumulative incidence of confirmed cases (SARS-CoV-2 positive PCR test) was compared to the population estimates for the same city districts from a governmental COVID-19 health database. Suspected cases were defined following WHO criteria and compared to those without compatible symptoms.RESULTS959 patients with rheumatic diseases treated with tDMARDs were included. We identified 11 confirmed SARS-CoV-2 positive cases in the adult cohort and no confirmed positive cases in the paediatric cohort. All patients had a successful recovery and only one patient required admission in the intensive care unit. When using the same classification criteria (only COVID-19 positive cases with pneumonia), COVID-19 incidence rates of the rheumatic patient cohort were very similar to that of the general population [(0.48% (95% CI 0.09 to 8.65%)] and [0.58% (95% CI 5.62 to 5.99%)], respectively. We found significant differences in tDMARDs proportions between the suspected and non-suspected cases (p=0.002).CONCLUSIONAdult and paediatric patients with rheumatic diseases on tDMARDs do not seem to present a higher risk of COVID-19 or a more severe disease outcome when compared to general population. Our exploratory analysis suggests that the proportion of COVID-19 suspected cases differs between tDMARDs.

Objectives: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. Methods: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. Results: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. Conclusions: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion. This project was supported by Spanish Rheumatology Society and Spanish Society of Internal Medicine (GEAS, Study Group on Autoimmune Diseases).

MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD, This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ‘Instituto de Salud Carlos III’ (ISCIII), cofunded by the European Social Fund (ESF, ‘Investing in your future’) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ESF). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG,is member of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG (PI17/00409), was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

Despite the well-recognized association between malignancy and myositis, definite data indicating the best strategy for diagnosing cancer in myositis patients is lacking. In this article, we review the data on cancer screening in patients with myositis, and propose an algorithm for this purpose based on recently published data.Evidence has recently emerged supporting blind screening in patients with certain myositis phenotypes. In addition to the clinical examination, imaging techniques such as PET/computed tomography scanning and whole-body MRI, and determination of the autoantibody profile beyond anti-TIF1γ antibody, the well known cancer biomarker in dermatomyositis, will help the clinician face this complex clinical situation. Molecules related to the checkpoint inhibitor pathway, specifically soluble programmed death 1, may also have a role in the diagnostic work-up of cancer in myositis. In the future, blood tests analysing circulating DNA will certainly help in detecting patients with cancer-associated myositis (CAM).A step forward has been achieved in the pathway to establish optimal cancer screening for myositis patients. International consensus guidelines for an effective diagnostic work-up of CAM are in progress and will be of paramount importance to improving the outcome in these patients.

It is well established that myositis is associated with cancer, although it took decades to consistently recognize this relationship because of the low incidence of inflammatory myopathies in the population. This association can be a challenge for clinicians who must decide when and how to implement screening for occult cancer in their myositis patients and the best therapeutic options for those with cancer-associated myositis. In this chapter, we will review the current knowledge regarding the epidemiology, risk factors, association with specific autoantibodies, diagnosis, and management of cancer-associated myositis (CAM).

Objectives. To analyse the influence of genetic alterations and differential expression of transcription intermediary factor 1 (TIF1) genes in the pathophysiology of cancer-associated myositis (CAM). Methods. Paired blood and tumour DNA samples from patients with anti-TIF1 gamma-positive CAM and from controls were analysed by whole-exome sequencing for the presence of somatic mutations and loss of heterozygosity (LOH) in their TIF1 genes. The genesis and maintenance of the autoimmune process were investigated immunohistochemically by studying TIF1 gamma expression in the different tissues involved in CAM (skin, muscle and tumour) based on the immunohistochemical H-score. Results. From seven patients with anti-TIF1 gamma-positive CAM, we detected one somatic mutation and five cases of LOH in one or more of the four TIF1 genes compared with just one case of LOH in tumours from TIF1 gamma-negative myositis patients (86% vs 17%; P = 0.03). Compared with type-matched control tumours from non-myositis patients, TIF1 gamma staining was more intense in tumours from anti-TIF1 gamma-positive patients (H-score 255 vs 196;P = 0.01). Also, TIF1 gamma staining in muscle was slightly more intense in anti-TIF1 gamma-positive than in anti-TIF1 gamma-negative myositis (H-score 22 vs 5; P = 0.03). In contrast, intense TIF1 gamma staining was detected in the skin of both myositis and control patients. Conclusion. Tumours from paraneoplastic anti-TIF1 gamma-positive patients showed an increased number of genetic alterations, such as mutations and LOH, in TIF1 genes. These genetic alterations, in the context of a high expression of TIF1 gamma in the tumour, muscle and skin of these patients may be key to understanding the genesis of paraneoplastic myositis.

Purpose of Review Positron emission tomography (PET) combined with computed tomography (CT) has proven useful as a cancer screening technique in patients with inflammatory myopathy, mainly dermatomyositis. In this review, we focus on advances in this direction and other potential applications of PET/CT in patients with inflammatory myopathy. Recent Findings Cancer screening by PET/CT seems suitable and cost-effective in patients with myositis. It has also shown value as a hybrid technique for diagnosing myositis versus controls and could be of interest for differentiating between polymyositis and sporadic inclusion body myositis. Quantification of muscle activity by PET/CT seems reliable. Preliminary data suggest that it could also be used to diagnose and measure the activity of the disease in the lung. Summary PET/CT should be in the toolbox of physicians managing patients with myositis. The multiple applications of PET/CT include its value for cancer screening, measuring the activity of the disease in muscle, and helping to differentiate between myositis phenotypes. The possibility to diagnose and monitor inflammatory lung activity remains to be demonstrated in welldesigned studies.

Cancer-associated dermatomyositis provides a unique opportunity to explore the relationship between autoimmunity and cancer. In this review, we describe the related epidemiological issues, considering the various currently accepted myositis phenotypes, their link with cancer, and the possible mechanisms leading to this relationship. We discuss current evidence regarding the role of molecular mimicry, somatic DNA tumor mutations, and the PD-1/PD-L1 pathway in the association between cancer and myositis. We also review tumor-infiltrating lymphocytes as a relevant factor to be evaluated in cancer-associated myositis, their interaction with tumor neoantigens, and the tumor mutational burden, all of which have implications for the treatment of these patients with immunotherapy. Finally, we discuss clinical scenarios related to the relationship between cancer and myositis, delineating a comprehensive theory linking autoimmunity and cancer.

Background:There is a well-recognized association between cancer and myositis, so cancer screening at diagnosis is recommended.Objectives:We aim to report the results of our cancer screening strategy and to ascertain the reliability of using PET/CT to identify cancer-associated myositis (CAM) in a large cohort of patients with myositis from a single center over 10 years.Methods:This retrospective observational study included all patients diagnosed with any type of myositis except for inclusion body myositis. Cancer screening strategy was individualized according to clinical and serological data, including PET/CT as the main test to detect occult cancer (OC). Procedures derived from a positive PET/CT were registered. Qualitative data expressed as percentages, and quantitative data as the median with the interquartile range were analyzed. A ROC curve was used to estimate the reliability of PET/CT for CAM diagnosis.Results:Seventy-seven out of 131 patients underwent a PET/CT for OC screening. The performance of the PET/CT in patients with myositis at disease onset yielded an area under the curve ROC of 0.87 (0.73-0.97) for CAM diagnosis. Invasive procedures in 7 (9%) patients without a final diagnosis of cancer did not cause derived complications. Patients not evaluated for OC did not develop cancer after a median follow-up of 3.3 years (1.7-6.7).Conclusion:Cancer screening strategy should be individualized. PET/CT at myositis onset seems to be an efficient approach to rule out CAM. This practice does not seem to significantly increase harm to patients related to the additional tests needed to clarify inconclusive results.Disclosure of Interests:None declared

Background:Several reports have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a vigorous immune response that could lead to the appearance of various autoantibodies such as antinuclear antibodies, antiphospholipid antibodies or anti-neutrophil cytoplasmic antibodies, among others. Moreover, the pulmonary involvement in SARS-CoV-2 may resemble that of patients with anti-MDA5 positive syndrome or acute form of antisynthetase syndrome.Objectives:Our aim was to analyse the presence of anti-MDA5 and other myositis-specific autoantibodies such as the antisynthetase antibodies in patients diagnosed with severe acute respiratory syndrome caused by SARS-CoV-2.Methods:Retrospective observational study performed in a tertiary care center. We included 28 patients admitted to the intensive care unit with severe acute respiratory syndrome, 14 at the onset of the disease (group A) and 14 after 30 days of being treated in an intensive care unit (group B). Chest CT was performed at the admission. We analyzed the presence of anti-MDA5 and antisynthetase antibodies by immunoblot (Euroimmune®) and in those who were positive we performed a confirmatory test by immunoprecipitation.Results:All chest CT showed bilateral ground glass pattern. Three out of 14 patients of group A (12 males, 86%, mean ± SD age 67.1 ± 12.2) were positive for antisynthetase antibodies (2 anti-PL7, 1 anti-Jo1), and 6 out of 14 patients of the group B (6 males, 48%, mean ± SD age 68.7 ± 8.1) were positive to antisynthetase antibodies (2 anti-PL7, 2 anti-PL-12, 1 anti-EJ, 1 anti-OJ+PL7). Immunoblots also show positivity for other myositis-specific or associated antibodies, such as anti-TIF1g, anti-PM75, anti-SAE and anti-SRP. All of these results found by immunoblotting were negative by immunoprecipitation. None of the 28 patients were positive for anti-MDA5 antibodies.Conclusion:Severe SARS-CoV-2 pneumonia is characterized by ground glass pattern in chest CT, as it is found in anti-MDA5 or antisynthetase syndrome. The positivity of several myositis related autoantibodies showed in immunoblot appears to be more related to the vigorous immune response producing polyclonal immunoglobulins than triggering a real myositis-associated interstitial lung disease. Clinicians must be aware about these false positive results in patients with severe COVID-19 acute respiratory syndrome.References:[1]Xu Q. MDA5 should be detected in severe COVID-19 patients. Med Hypotheses. 2020; 143:109890.[2]Giannini M, Ohana M, Nespola B, Zanframundo G, Geny B, Meyer A. Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care? Eur Respir J. 2020; 56:2001618.[3]Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, Tzioufas AG. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis. 2020 Dec;79(12):1661-1663Disclosure of Interests:None declared

Background:Idiopathic inflammatory myopathies are a heterogenous group of systemic autoimmune diseases. Several phenotypes have been linked to specific autoantibodies. Clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease, the most severe form of ILD, is associated with the anti-MDA5 antibodies. However not all the patients with dermatomyositis and anti-MDA5 positive antibodies develop this severe condition.Objectives:We aim to define different phenotypes from a large cohort of patients diagnosed with dermatomyositis who were positive to anti-MDA5 antibodies.Methods:We retrospective analyzed the clinical and immunological data of 90 anti-MDA5 patients [50 female, 55.6%, mean (SD) age at diagnosis 47 (15.4) yrs.] with dermatomyositis recruited from a multicenter register in Spain (MEDRA5) including 30 hospitals. All the patients fulfill de International Myositis Classification Criteria (EULAR/ACR) for dermatomyositis (score >90%). Anti-MDA5 were detected by means of commercial immunoblot (EUROIMMUN©). The chi-square test was used to assess the relationships between qualitative variables. The Kruskal-Wallis test was used to compared medians between groups.Results:Sixty-six patients (73.3%) were diagnosed with clinically amyopathic dermatomyositis. Three different phenotypes linked with the anti-MDA5 antibody were identified. Group 1: patients with rapidly-ILD phenotype (28 patients, 31.1%), group 2: antisynthetase-like phenotype (23 patients, 25.5%), and group 3: non-ILD phenotype (39 patients, 43.3%). Clinical and immunological comparison between the groups disclosed that age at disease onset was higher (median, IQR) in patients from group 1 [53 (43-60)] vs. group 2 [46 (40-56)] or group 3 [42(41-51)] (p=0.01); disease onset was more frequent in spring in patients from group 1 (46.5%) than in the rest of the groups (21.7% and 28.9%) (pConclusion:Three different phenotypes of patients positive to anti-MDA5 were identified. The presence or not of ILD, or the different type (rapidly progressive or not) of ILD were the main feature that allow to differentiate these phenotypes, which are relevant in clinical practice.References:[1]Allenbach Y, Uzunhan Y, Toquet S, et al; French Myositis Network. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases. Neurology. 2020;95: e70-e78.Acknowledgements:List of contributors of MEDRA5 group: Aguilar-García J (Internal Medicine, Hospital Costa del Sol, Marbella), Carrión-Barberá I (Rheumatology, Hospital del Mar, Barcelona), Cobo-Ibañez T (Rheumatology, Hospital Infanta Sofía, San Sebastián de los Reyes), de Escalante-Yangüela B (Internal Medicine, Hospital Clínico Lozano Blesa, Zaragoza), Fonseca-Aizpuru EM (Internal Medicine, Hospital de Cabueñes, Gijón), González-Cubillo L (Intensive Medicine, Hospital Universitario de Cruces, Barakaldo), González-Gay MA (Rheumatology, Hospital Marqués de Valdecilla, Santander), Prieto-González S (Internal Medicine, Hospital Clinic, Barcelona), Ruiz-Román A (Rheumatology, Hospital Universitario Virgen del Rocío, Sevilla), Calero-Paniagua I (Internal Medicine, Hospital Virgen de la Luz, Cuenca), Callejas-Rubio JL (Internal Medicine, Hospital Clínico San Cecilio, Granada), Gil-Vila A (Internal Medicine, Hospital Vall d’Hebron, Barcelona), de Miguel-Campo B (Internal Medicine, Hospital Doce de Octubre, Madrid), García-Sevilla R (Pneumology, Hospital General Universitario de Alicante, Alicante), Iriarte-Fuster A (Internal Medicine, Hospital de Bellvitge, Hospitalet de Llobregat), Jovani-Casano V (Rheumatology, Hospital General Universitario de Alicante, Alicante), Lozano-Rivas N (Rheumatology, Hospital Virgen de la Arritxaca, Murcia), Martín-Gascón M (Internal Medicine, Hospital Morales Meseguer, Murcia), Martinez-González O (Rheumatology, Hospital Universitario de Salamanca, Salamanca), Monteagudo-Jiménez M (Internal Medicine, Hospital Parc Taulí, Sabadell), Mora-Ortega GM (Pneumology, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes), Moral-Moral Pedro (Internal Medicine, Hospital Universitari i Politecnic La Fe, Valencia), Pérez-De Pedro I (Interna Medicine, Hospital Regional Universitario de Málaga, Málaga), Picazo-Talavera MR (Rheumatology, Hospital del Sureste, Madrid), Rubio-Rivas M (Internal Medicine, Hospital de Bellvitge, Hospitalet de Llobregat)Disclosure of Interests:None declared

Background:Antisynthetase syndrome (ASS) is characterized by inflammatory myopathy, interstitial lung disease, arthritis, mechanical hands and Raynaud phenomenon, among other features. Recent studies have shown that idiopathic inflammatory myopathies (IIM) may develop cardiac involvement, either ischemic (coronary artery disease) or inflammatory (myocarditis). We wonder if characteristic lung interstitial involvement (interstitial lung disease) that appears in patients with the ASS may also affect the myocardial interstitial tissue. New magnetic resonance mapping techniques could detect subclinical myocardial involvement, mainly as edema (increase extracellular volume in interstitium and extracellular matrix), even in the absence of visible late Gadolinium enhancement (LGE).Objectives:Our aim was to describe the presence of interstitial myocarditis in a group of patients with ASS.Methods:Cross-sectional, observational study performed in a tertiary care center. We included 13 patients diagnosed with ASS (7 male, 53%, mean (SD) age at diagnosis 56,8 years (±11,8)). The patients were consecutively selected from our outpatient myositis clinic. Myositis specific and associated antibodies were performed by means of line immunoblot (EUROIMMUN©). Cardiac magnetic resonance (CMR) was performed on all patients. The study protocol includes functional cine magnetic resonance and standard late gadolinium enhancement (LGE), as well as novel parametric T1 and T2 mapping sequences (modified look locker inversion recovery sequences - MOLLI) with extracellular volume (ECV) calculation 20 minutes after the injection of a gadolinium-based contrast material.Results:CMR could not be performed in one patient due to anxiety. All patients studied (12) had a normal biventricular function, without alteration of segmental contraction. A third (4 out of 12, 33%) of the studied patients showed elevated T2 myocardial values without focal LGE, half of them (2/4) with an elevated ECV, consistent with myocardial edema. Two patients with normal T2 values showed unspecific LGE focal patterns, one in the right ventricle union points and another with mild interventricular septum enhancement (Figure 1). None of the patients studied refer any cardiac symptomatology. All the four patients with T2 mapping alterations (100%) had interstitial lung involvement, but only 4 out of 8 (50%) of the rest ASS patients without T2 mapping positivity. The autoimmune profile was as follows: 10 anti-Jo1/Ro52, 1 anti-EJ/Ro52, 2 anti-PL12.Conclusion:Myocarditis, although subclinical, appears to be a feature in ASS patients. T1 and T2 mapping sequences might be valuable to detect and monitor subclinical cardiac involvement in these patients. The possibility that the same etiopathogenic mechanism may be involved in the interstitial tissue in lung and myocardium is raised. More studies must be done in order to assert the prevalence of myocarditis in ASS.References:[1]Dieval C et al. Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes. Medicine (Baltimore). 2015 Jul;94(26):e798.[2]Myhr KA, Pecini R. Management of Myocarditis in Myositis: Diagnosis and Treatment. Curr Rheumatol Rep. 2020 Jul 22; 22:49.[3]Sharma K, Orbai AM, Desai D, Cingolani OH, Halushka MK, Christopher-Stine L, Mammen AL, Wu KC, Zakaria S. Brief report: antisynthetase syndrome-associated myocarditis. J Card Fail. 2014 Dec;20(12):939-45.Figure 1.Cardiac magnetic resonance images from ASS patients.Disclosure of Interests:None declared

To evaluate the clinical manifestations, long-term clinical outcome and longitudinal pulmonary function in a large cohort of Spanish patients with anti-Jo1 antibodies.We retrospectively analyzed the clinical data and lung function parameters of 148 anti-Jo1 patients recruited from a multicentre registry including 18 Spanish hospitals. A composite endpoint was defined, comprising death due to respiratory failure directly related to antisynthetase syndrome (ASS), the need for long-term oxygen therapy or lung transplantation.Median follow-up was 78.3 months. Clinical presentation patterns at onset are as follows: isolated interstitial lung disease (ILD) (32.4%), isolated myositis (26.9%), concomitant myositis and ILD (22.8%), and isolated polyarthritis (17.9%). Myositis with ILD was the most frequent final clinical phenotype (67.6%). In most ASS patients, ILD was a non-progressive disease, tending to stabilize with therapy. The endpoint was reached in a significantly larger number of ILD patients with dyspnea at onset than those with paucisymptomatic or asymptomatic forms (p = 0.01). A steady FVC decrease was the hallmark of patients with end-stage lung disease. Estimated survival rates were 87.7% and 75.4% at 5 and 10 years, respectively. Cancer (p = 0.02) and advanced age at ASS diagnosis (p0.0001) were related to poorer survival. Mortality was significantly higher than in the general Spanish population, with a standardised mortality ratio (95% CI) of 4.03 (2.79-5.64).Anti-Jo1 ASS is a heterogeneous syndrome. ILD in ASS under immunosuppressive therapy is mainly a non-progressive disease. Dyspnea at ILD onset and a steady FVC decrease over time were related to a poorer respiratory prognosis.

Background Patients with clinically amyopathyc dermatomyositis (CADM) with MDA5 positive autoantibodies may develop a severe pulmonary syndrome with rapidly progressive interstitial lung disease (RP-ILD) with a bad prognosis and high mortality. Objectives To analyse the efficacy of a therapeutic protocol that includes hemoperfusion with polymyxin B (PMX-HP) in addition to immunosuppressive treatment with tacrolimus and glucocorticoids, plasmapheresis and intravenous immunoglobulin (IVIG). Methods We retrospectively analysed 12 (10 male) patients diagnosed with anti-MDA5 (+) CADM associated RP-ILD between 1983 and 2018. Anti-MDA5 antibodies were determined by ELISA and confirmed by blot. RP-ILD was defined as a worsening of radiologic interstitial changes with progressive dyspnoea and hypoxemia within 1 month after the onset of respiratory symptoms. From 2014 to 2018, patients (Group 1) were treated with the following protocol: pulses of methylprednisolone (500 mg/day for 3 consecutive days), tacrolimus 2 mg/12 hour, PMX-HP (Toraymyxin 20R, Toray Medical Co., Tokyo, Japan) at a flow of 100 ml/h for 3 hour once daily on two successive days, and a plasmapheresis scheme with replacement of 3.5 l of seroalbumin 5% followed by IVIG infusion (0.4 mg/kg) during 3 consecutive days and then in alternate days for 7 days more. A comparison was performed with anti-MDA5 (+) CADM associated RP-ILD patients from a historical group (Group 2). PaO2/FiO2 (P/F) ratio was measured before and after PMX therapy. A composite endpoint that included mortality due to respiratory failure or lung transplantation was defined. Differences between pre- and post-PMX P/F values were evaluated using paired sample t-test. Results Mean (SD) age at diagnosis was 49 (3.5) yrs, with a mean (SD) follow-up of 13 (3.9) months. Comparison between both Groups showed that 3 out of 6 (50%) patients from the Group 1 in comparison with 5 out of 6 (83.3%) from the historical group (Group 2) reached the composite end point. Mean (CI 95%) values of P/F after PMX treatment showed a significantly improvement when compared with the pre-PMX values (240 [85–396] vs. 125,60–189 p=0.038) Conclusions Our protocol seems to be useful at some extent in anti-MDA5 (+) CADM associated RP-ILD patients. A transient but significant improvement can be attributed to PMX-HP. Adsorption and elimination of inflammatory cytokines, mediators and activated leukocytes, as well as anti-MDA5 antibodies could be the rationale of its efficacy. Disclosure of Interest None declared

AIM To describe the prevalence, clinical characteristics and risk factors of opportunistic infection (OI) in a cohort of patients with inflammatory myopathies, and compare mortality rates between those with and without OIs. METHODS In total, 204 patients from our myositis cohort were reviewed to identify patients who had experienced an OI during the period 1986-2014. The patients' clinical characteristics, treatments received, and outcomes were systematically recorded. Disease activity at the OI diagnosis and the cumulative doses of immunosuppressive drugs were analyzed, as well as the specific pathogens involved and affected organs. RESULTS The prevalence of OI in the total cohort was 6.4%: viruses, 44.4% (varicella-zoster virus, cytomegalovirus); bacteria, 22.2% (Salmonella sp., Mycobacterium tuberculosis, M. chelonae); fungi, 16.7% (Candida albicans, Pneumocystis jirovecii); and parasites, 16.7% (Toxoplasmosis gondii, Leishmania spp.). Lung and skin/soft tissues were the organs most commonly affected (27.8%). Overall, 55.6% of OIs developed during the first year after the myositis diagnosis and OI was significantly associated with administration of high-dose glucocorticoids (P = 0.0148). Fever at onset of myositis (P = 0.0317), biological therapy (P

Introduction: Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy.Areas covered: Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms myositis', statin-induced autoimmune myopathy', immune-mediate necrotizing myopathy', statins', muscular manifestations', and anti-HMGCR antibodies' were used.Expert commentary: Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.

Nearly one-third of adult myositis patients additionally have some type of associated cancer, observed most commonly in dermatomyositis patients. The relationship between cancer and myositis is generally considered a paraneoplastic phenomenon; that is, in one way or another, the two conditions are related. A parallel course of the diseases—myositis improves after cancer is cured and when cancer recurs, myositis worsens—is considered a classical paraneoplastic criterion. Nevertheless, this parallel clinical course does not always occur in true cancer-associated myositis, or perhaps it cannot be seen because of the interference of therapy. Based on epidemiologic studies, the current gold standard for the diagnosis of cancer-associated myositis is a temporal criterion: diagnosis of the two diseases within a 3-year period, although to a certain extent, this is an arbitrary standard.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune diseases characterized by symmetric proximal muscle weakness and inflammatory infiltrates on muscle biopsy. A meticulously collected combination of clinical, serological, and pathological data is essential to correctly diagnose and classify myositis patients, often a considerable challenge for clinicians. This article provides a comprehensive overview of the most useful tools for the diagnosis and follow-up of patients with myositis. Capillaroscopy, serological biomarkers (particularly the autoantibody profile) and imaging techniques, such as muscle magnetic resonance and chest ultrasound, are of great aid in diagnosing, classifying and managing these patients. Relevant clinical scenarios, such as interstitial lung disease, associated cancer and pregnancy are also addressed in this review. Myositis registries, identification of new autoantibodies, and genetic studies will enhance our understanding of the pathogenesis of these conditions and help to define new diagnostic and therapeutic approaches.

Background Idiopathic inflammatory myopathies, also known as myositis, are a heterogeneous group of acquired diseases of probable autoimmune origin, characterized by the presence of inflammatory muscle infiltrates.Infectious complications are not uncommon in myositis, and some predisposing factors, such as upper esophageal involvement, calcinosis cutis, ventilatory insufficiency due to diaphragm involvement, and immunosuppressive drug therapies, seem to be implicated. Objectives To describe the prevalence, clinical characteristics, and risk factors for opportunistic infection (OI) in a cohort of patients with inflammatory myopathies, and compare mortality rates between those with and without OIs. Methods In total, 204 patients from our myositis cohort were reviewed to identify patients who had experienced an OI during the period 1986–2014. The patients9 clinical characteristics, treatment received, and outcome were systematically recorded. Disease activity at the OI diagnosis and cumulative doses of immunosuppressive drugs were analyzed, as well as the specific pathogens involved and affected organs. Results The prevalence of OI in the total cohort, was 6.4%: viruses, 44.4% (varicella-zoster virus, cytomegalovirus); bacteria, 22.2% ( Salmonella sp. , Mycobacterium tuberculosis , M. chelonae); fungi, 16.7% ( Candida albicans , Pneumocystis jirovecii); and parasites, 16.7% ( Toxoplamosis gondii , Leishmania spp. ) were the pathogens detected. Lung and skin/soft tissues were the organs most commonly affected (27.8%). Overall, 55.6% of OIs developed during the first year after the myositis diagnosis and were significantly associated with administration of high-dose glucocorticoids (p=0.0148). Fever at onset of myositis (p=0.0317), biological therapy (p Conclusions The prevalence of OI was 6.4% in our myositis cohort. High-dose glucocorticoids at disease onset and severe immunosuppression are implicated in the development of these complications. Mortality did not differ from the remainder of the cohort. Disclosure of Interest None declared

Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome.

Purpose of review Currently available data support the idea that inflammatory myopathies, particularly dermatomyositis, are paraneoplastic diseases. Cancer screening is usually recommended in patients with these conditions, but there is no consensus regarding how and how often screening should be performed. This review will address recent advances in our understanding of the relationship between cancer and myositis and describe new data regarding the best approach for cancer screening in myositis patients. Recent findings A newly described autoantibody to a 155-kDa nuclear protein, identified as transcription intermediary factor 1-gamma (TIF1-γ), has proven useful for cancer screening in patients with dermatomyositis. Occult tumor detection by PET/computed tomography (PET/CT) seems to be a good alternative to broad conventional screening. A combination of both methods, detection of autoantibodies against p155 and PET/CT study, may be the best approach to ascertain the presence of occult malignancy in patients with dermatomyositis. Summary Advances in immunology and imaging techniques are increasing the accuracy of occult malignant cancer detection in dermatomyositis patients. Nevertheless, the diagnosis of cancer in this population remains elusive in some cases. Further investigation is needed to improve our knowledge of the link between myositis and cancer.

Objective To determine the value of whole-body [ 18 F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for diagnosing occult malignant disease in patients with myositis compared with broad conventional cancer screening. Methods We prospectively studied 55 consecutive patients with a recent diagnosis of myositis in 3 teaching hospitals over a 3-year period by whole-body FDG-PET/CT and compared the results with those of conventional cancer screening, which included thoracoabdominal CT, mammography, gynecologic examination, ultrasonography, and tumor marker analysis. Comparisons were made using predictive values and their 95% confidence intervals. Results A total of 9 of 55 patients were diagnosed with paraneoplastic myositis. FDG uptake was positive in 7 patients (1 false-positive), negative in 44 patients (3 false-negative), and inconclusive in 4 patients. Positive and negative predictive values of FDG-PET/CT for the diagnosis of cancer were 85.7% and 93.8%, respectively. Conventional screening was cancer-positive in 9 patients (2 false-positive) and negative in the remaining 46 patients (2 false-negative). Positive and negative predictive values were 77.8% and 95.7%, respectively. The overall predictive value of broad conventional screening was the same as that of FDG-PET/CT (92.7 vs 92.7). Conclusion The performance of FDG-PET/CT, a single imaging study, for diagnosing occult malignant disease in patients with myositis was comparable to that of broad conventional screening, which includes multiple tests.

To study the presence and characteristics of nailfold capillary changes in a cohort of adult patients with inflammatory myopathies, determine correlations with disease activity and severity, and investigate any relationship between capillary findings and the immunological or clinical characteristics of the groups.Fifty-three consecutive adult patients followed in our outpatient clinic were evaluated using a Wild M3 stereomicroscope with an Intralux 5000 Volpi cold light lamp. A semiquantitative rating scale was used to score capillaroscopy changes. Disease activity and severity were assessed with the Myositis Disease Activity Assessment Tool and Myositis Damage Index, respectively. Associations between capillaroscopy findings and other factors were calculated with the chi(2) and Mann-Whitney U tests. Serum autoantibody profile was determined in all patients.Twenty-three patients (43%) showed relevant capillaroscopy changes. No significant association was observed between the number of capillaroscopy alterations and the clinical or immunological groups, or disease duration. Disease activity and severity were both significantly associated with a larger number of capillaroscopy findings (P0.05). The combination of microhemorrhages and capillary enlargement was significantly more frequent in patients with dermatomyositis (OR, 8.9; 95% CI, 1.8-45.2), and a characteristic capillaroscopy pattern was associated with paraneoplastic myositis (OR, 14.7; 95% CI, 2.0-106.4). Interstitial lung disease significantly correlated with higher capillary score (OR, 3.7; 95% CI, 1.1-13.0).Nailfold microcirculation as determined by semiquantitative simple capillaroscopy appears to provide useful information in patients with idiopathic inflammatory myopathy, contributing to an early diagnosis and identifying patients with a poor prognosis.

Estudio descriptivo y retrospectivo de una serie de 35 pacientes con miopatia inflamatoria idiopatica, que a partir de la recogida de variables clinicas, de laboratorio y patologicas, se propone los siguientes objetivos: caracterizar a este grupo de enfermedades, clasificar a los pacientes en subgrupos en funcion de criterios histopatologicos y caracterizar los distintos subgrupos analizando que variables permiten diferenciar mejor cada categoria.

Las miopatias inflamatorias idiopaticas son un grupo heterogeneo de enfermedades cuya principal caracteristica es la debilidad muscular y la identificacion de una inflamacion subyacente en la biopsia muscular. Se incluyen en este grupo la dermatomiositis, la polimiositis y recientemente la miositis con cuerpos de inclusion, con toda probabilidad la menos inflamatoria y tambien la miopatia adquirida mas frecuentemente a partir de los 50 anos. Aunque el principal organo diana es el musculo, la piel y el pulmon, entre otros organos internos, se afectan con frecuencia, por lo que las miopatias inflamatorias se consideran enfermedades sistemicas. En ocasiones pueden asociarse a cancer y la presencia de autoanticuerpos especificos y asociados a estas enfermedades sustenta la etiologia autoinmune del proceso y ayuda a categorizar a los pacientes. El tratamiento incluye la administracion de glucocorticoides, inmunodepresores y puntualmente terapias biologicas, sin descuidar la rehabilitacion incluso en la fase aguda de la enfermedad

Idiopathic inflammatory myopathies are a group of heterogeneous, acquired systemic diseases characterized by progressive symmetrical muscle weakness, elevated serum levels of muscle enzymes, electromyographic abnormalities, and inflammatory infiltrates on muscle biopsy. Characteristic histopathologic features allow classification of idiopathic inflammatory myopathies into polymyositis, dermatomyositis, and sporadic inclusion-body myositis. These are commonly regarded as autoimmune disorders, and various autoantibodies directed to specific nuclear and cytoplasmic antigens are found. Other organs besides the muscle can be involved being the skin and lung the most frequent. Occasionally dermatomyositis and polymyositis can be associated with cancer in a paraneoplastic manner. Corticosteroids and immunosuppressive agents are the mainstay therapy, although in refractory cases biologic therapy can be used. Physical therapy can not be forgotten.

Procalcitonin (PCT), the precursor of the hormone calcitonin, is a new parameter of inflammation. This acutephase hormokine seems to be more accurate for differentiating between bacterial infections and viral or non-infective causes of inflammation than other serological markers. PCT, which is induced in invasive bacterial infections, is routinely assayed in some intensive care, surgery, haematological units and emergency rooms to help determine the cause of a systemic inflammatory response syndrome (SIRS). Patients with systemic autoimmune diseases have a higher risk of developing severe systemic bacterial infections due to the disease itself and to the immunosuppressive therapy received. Distinguishing between infection and a disease flare is sometimes difficult. Strategies to reach a precise diagnosis are decisive to establish early, adequate patient management. Studies in febrile patients with systemic autoimmune diseases (systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated systemic vasculitis, and rheumatoid arthritis) suggest that elevated PCT concentrations offer good sensitivity and specificity for diagnosing systemic bacterial infection. Nevertheless, there is little published information on PCT levels in other autoimmune diseases and inflammatory processes. In this review we summarise the current evidence regarding the pathophysiological basis of systemic PCT production in sepsis and the results from current case series on the response of this peptide to infectious and non-infectious SIRS in systemic autoimmune diseases.

BACKGROUND AND OBJECTIVE: Eosinophilic fasciitis is an uncommon scleroderma-like syndrome with unknown etiology and pathogenesis. We report the clinical manifestations and response to therapy in a series of patients diagnosed with eosinophilic fasciitis. PATIENTS AND METHOD: The records of 10 eosinophilic fasciitis patients seen at our hospital between 1996-2004 were reviewed. RESULTS: Five patients were males, ages ranged from 20 years to 67 years, with a mean of 59 years. Patients were followed for 33.4 (27.1) months (SD). Nailfold capillaroscopy was near normal in all patients. Only one patient had antinuclear antibody positivity, and another had an autoimmune thyroiditis. No significant relationship was detected between the eosinophil count and the extent of skin induration. The clinical course was inadequate and the treatment response poor in patients with spreading cutaneous induration (p = 0.008). These patients had more often ventilatory restriction and perimyositis. CONCLUSIONS: Eosinophilic fasciitis does not always have a good prognosis. Ventilatory restriction, perimyositis and poor treatment response are not infrequent in a series of patients attended in a general hospital.