Myositis Subtypes Research Articles

Distinct Transcript-Level Expression Profiles and Unique Alternative Splicing in Inflammatory Myopathies.

The pathogenesis of inflammatory myopathies is poorly understood and there is a need to dissect the transcriptome in more granular ways beyond gene expression. We used a set of muscle RNA-sequencing data from different myositis subtypes grouped by their specific autoantibodies (n = 152). We quantified annotated RNA transcripts for each myositis subtype and identified uniquely expressed RNA as well as transcriptional similarities among myositis types. In addition, we quantified event-based alternative splicing with predicted protein changes. And finally, we searched for cryptic exons. We saw considerable overlap in RNA expression among subtypes. In addition, MADCAM1 was previously shown to be uniquely expressed in Mi-2 myositis; we discovered it was two noncanonical transcripts that predominantly contributed to the observed increased expression. At the transcriptional level, dermatomyositis subtypes were least similar to inclusion body myositis (IBM) or Jo1, followed by HMGCR, then SRP and other dermatomyositis subtype. Additionally, we discovered many alternative splicing events that were unique by myositis subgroup, including events in muscle dystrophy genes and one event in SRP72, which was seen uniquely in SRP myositis. Finally, we looked for previously reported cryptic exons in IBM and did not find them. The large degree of transcriptional overlap among myositis subtypes reinforces the need to use disease (in addition to healthy) controls to find unique features of autoimmune disease. Unique alterations in the transcriptome that are seen in one myositis subtype and not others advance our understanding of distinct disease pathology.

The impact of pain on daily activities in patients with idiopathic inflammatory myopathies: Report from the OMERACT myositis working group

BackgroundInternational focus groups with patients with idiopathic inflammatory myopathies (IIM) conducted by the OMERACT Myositis Working Group over the years demonstrated the pain as an important symptom experienced by these patients. In this study, we aimed to examine the frequency and degree of pain interference, the aspects of daily life impacted by pain, and the factors associated with pain interference in adults with IIM. MethodsThis was a prospective observational study with two visits. The patients who fulfilled the probable/definite IIM (ACR/EULAR Myositis Classification Criteria) were enrolled. Pain interference was assessed with PROMIS pain interference form (6a). Myositis core set measures and PROMIS fatigue (7a) and physical function (8b) were obtained at both visits. Logistic regression and linear mixed models were performed to assess the association between pain interference and other parameters. ResultsA total of 129 patients with IIM (60 % females) were recruited from U.S., South Korea, Netherlands, Sweden, and Australia. Approximately 71 % reported pain interference. The patients in the greater pain interference group were more likely to be female, had significantly worse patient/physician global disease activity, fatigue, and physical function than those in the lower pain interference group. The most commonly impacted life aspect was household chores. Manual muscle testing, patient/physician global disease activity, fatigue, and physical function were all significantly associated with pain interference score >60. ConclusionThe majority of the patients with IIM experience the impact of pain on their daily activities, particularly household chores. Myositis disease activity, duration, and subtype could be associated with greater pain interference.

Inflammasome in Skeletal Muscle: NLRP3 Is an Inflammatory Cell Stress Component in Inclusion Body Myositis

Inclusion body myositis (IBM) is a chronic, mostly treatment-resistant, inflammatory myopathy with a pathology that centers around specific interactions between inflammation and protein accumulation. The study aimed to identify the inflammasome as a key event in the complex network of pathomechanisms. Regulation of the inflammasome was assessed in a well-established pro-inflammatory cell culture model using human myoblasts and primary human myotubes. By quantitative PCR, western blot and immunocytochemistry, inflammasome markers including NLRP3 were assessed in muscle cells exposed to the cytokines IL-1β and IFN-γ. The data were corroborated by analysis of muscle biopsies from patients with IBM compared to other myositis subtypes. In the cell culture model of IBM, the NLRP3 inflammasome was significantly overexpressed, as evidenced by western blot (p = 0.03) and quantitative PCR (p < 0.01). Target genes that play a role in inflammasome assembly, T-cell migration, and MHC-I expression (p = 0.009) were highly co-upregulated. NLRP3 was significantly overexpressed in muscle biopsies from IBM samples compared to disease controls (p = 0.049), including other inflammatory myopathies. Due to the extraordinary features of the pathogenesis and the pronounced upregulation of NLRP3 in IBM, the inflammasome could serve as a key molecule that drives the inflammatory cascade as well as protein accumulation in the muscle. These data can be useful for future therapeutic developments.

P154 Real-world audit of patients with idiopathic inflammatory myositis-related interstitial lung disease in a European population

Abstract Background/Aims The British Society for Rheumatology (BSR) has released guidelines for managing idiopathic inflammatory myositis (IIM). Our centre operates specialist clinics for scleroderma and lupus, but to date, IIM patients are seen in a general CTD clinic. As part of work to establish a dedicated myositis clinic, we collated data on 71 patients under active follow-up with myositis spectrum disease deemed appropriate for follow-up within a specialist clinic. We aimed to review patients diagnosed with IIM-ILD and review serological immune profile, screening practices for pulmonary involvement, findings on CT/pulmonary function tests (PFTs) and pharmacological management. Methods We performed a detailed retrospective review of the notes of suitable patients, identified using diagnostic codes attached to clinic letters. Results 71 patients were identified: 14 with anti-synthetase syndrome (ARS), 21 with dermatomyositis (DM), 13 with polymyositis (PM), 3 with immune-mediated necrotising myopathy (IMNM) and 17 with overlap syndrome. 65% (46/70) of adult IIM patients were screened for pulmonary involvement. Screening practices of patients based on antibody profile and myositis subtype are further described in the table. 31% of patients (22/70) had IIM-ILD, of which 12 had ARS, 4 had PM, 1 had DM and 5 had overlap disease (2 PM/scleroderma, 1 DM/ARS, 1 DM/scleroderma and 1 scleroderma/ARS). 21/22 underwent PFTs; 53% of patients had active ILD over an average of 51.8 months. On imaging, 76.2% (16/22) had changes consistent with ILD. Ground glass change and reticulation were demonstrated in 50% of scans. In comparison, honeycombing and traction bronchiectasis was found in 22% and 44% of scans, respectively. A non-specific interstitial pneumonia (NSIP) pattern was described in 44% of scans, organising pneumonia (OP) pattern in 22%, and 17% had a mixed OP and NSIP pattern. 20/22 patients were prescribed high-dose steroids, csDMARD therapy or aggressive immunosuppression (cyclophosphamide or rituximab). Conclusion Our review demonstrates that 65% of patients with adult IIM were screened for ILD. NSIP and OP were the most common radiological appearances. Half of our cohort required aggressive immunosuppression, cyclophosphamide being the most commonly prescribed agent and mycophenolate being preferred for maintenance therapy. No patients were prescribed tacrolimus or ciclosporin. Despite treatment, 52% of patients had evidence of progressive disease on serial PFTs. Disclosure A. Loganathan: Grants/research support; Arthritis Australia. S. Sturney: None. N. Foley: None. T. Hartley: None. S. Tansley: None.

The value of metagenomic next-generation sequencing in bronchoalveolar lavage fluid samples of anti-MDA5-positive dermatomyositis patients.

Dear Editor, Anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5-positive DM) is a special subtype of myositis often combined with rapidly progressive interstitial lung disease, which has received increasing attention due to its poor prognosis and high mortality. A recent study reported a close relationship between anti-MDA5-positive DM and infection [1]. However, real-world clinical information is limited in those patients. Metagenomic next-generation sequencing (mNGS) is a sensitive detection technology that combines high-throughput sequencing with bioinformatic analysis for investigating an entire pathogen genome through RNA or DNA gene sequencing in a given sample. We retrospectively collected the data on 22 anti-MDA5-positive DM patients who completed mNGS testing with bronchoalveolar lavage fluid (BALF). Demographic data, including sex, age, detected pathogens, CD4 T cell counts and treatments, are shown in Table 1. Twenty-two patients were divided into two groups. In group 1, 10 patients underwent BALF mNGS testing prior to any treatment. Of these, four patients had bacterial infection, six had Pneumocystis jirovecii infection, four had viral infection and one had parasitic infection. In group 2, 12 patients showed aggravated dyspnoea symptoms after received glucocorticoids and immunosuppressants, underwent chest CT examination, and showed newly appearing pulmonary infiltrates compared with baseline. The BALF mNGS testing demonstrated six patients with bacterial infection. Of the seven patients with fungal infection, five were infected with P. jirovecii (71.4%). Eight patients had viral infection, with human betaherpesvirus 5 (cytomegalovirus, CMV) and human gammaherpesvirus 4 (Epstein–Barr virus; EBV) showing the highest detection rate (CMV: 87.5% and EBV: 50%). Finally, 11 patients had P. jirovecii infection, and for them the level of CD4 T cells was 283.1 (50.1) cells/µl, which was significantly lower than the level (452.5 (140.6) cells/µl) in patients without the P. jirovecii infection (P < 0.01, independent-sample t-test).

Pain profile and opioid medication use in patients with idiopathic inflammatory myopathies.

Pain is commonly reported in people living with myositis. This study assesses the presence of pain in the subtypes of myositis as well as the frequency of opioid and non-opioid pain medication use. A survey was developed and distributed by Myositis Support and Understanding, a patient-led advocacy organization, to members of its group. Multivariate logistic regression analysis and chi-squared tests were performed. A total of 468 participants completed the survey. A total of 423 participants (DM n = 183, PM n = 109 and IBM n = 131) were included, based on reported diagnosis, for final analysis. Some 91.5% of myositis participants reported current or past pain, with 99% attributing their pain to myositis. There was a lower likelihood of pain in participants aged >60 years [odds ratio (OR) 0.2, 95% confidence interval (CI)0.1, 0.6, P = 0.003]. The percentage of participants reporting pain was statistically different based on myositis type (DM 97.2%, IBM 80.9% and PM 94.5%, P < 0.001), with a higher likelihood of pain in DM compared with IBM (OR 3.7, 95% CI 1.3, 10.2, P = 0.011). There was a lower likelihood of pain in participants aged >60 years (OR 0.2, 95% CI 0.1, 0.6, P = 0.003). Of the 387 participants reporting pain, 335 reported using pain medications (69% prescribed opioids). Male sex, age >60 years and myositis subtype were not associated with likelihood of non-opioid use. Pain is a commonly reported symptom in myositis with variable treatment strategies, including opioid medications. This study highlights the importance of addressing pain as part of myositis treatment as well as the need for future studies understanding treatment effectiveness.

Performance of ENMC and EULAR/ACR classification systems applied to a single tertiary center cohort of dermatomyositis patients

BackgroundThere have been numerous classification systems to diagnose corresponding myositis subtypes and select appropriate therapeutic measures. However, the lack of a broad consensus on diagnostic criteria has led to clinical uncertainties. The objective of this study was to compare two commonly used dermatomyositis-classification systems regarding their clinical practicability and to point out their specific advantages and disadvantages.MethodsThis study included 30 patients diagnosed with dermatomyositis at the Charité university hospital, Berlin, Germany from 2010 to 2017. Patient files with complete data and defined historical classifications were enrolled and ENMC (2003) and EULAR/ACR (2017) criteria retrospectively applied.ResultsAccording to the ENMC approach, 14 patients were classified as "definite" and 12 as "probable" dermatomyositis. One patient exhibited an "amyopathic dermatomyositis" and three a "DM without dermatitis". Regarding the criteria probability of the EULAR/ACR set, 16 patients had a "high", 13 a "medium" and one a "low probability". There was a significant difference (p = 0.004) between the subclasses of the ENMC in relation to the EULAR/ACR score. The agreement between the classification probabilities of "definite/high" (κ = 0.400) and "possible/medium" (κ = 0.324) was fair.ConclusionsIt is important to find a consensus among the medical disciplines involved and to establish a structured procedure. Future studies with newer approaches are warranted to conclusively decide which system to use for the physician.

Role of Intravenous Immunoglobulin in Necrotizing Autoimmune Myopathy.

Immune-mediated necrotizing myopathy (IMNM) is a subtype of myositis that is associated with a refractory phenotype and poorer prognosis. The aim of the study was to provide single large center experience of outcomes of intravenous immunoglobulin (IVIg) for patients with IMNM using longitudinally collected data. This case series longitudinally evaluated 4 of the 6 myositis core set measures at baseline and at 3 and 6 months after IVIg on 20 adult IMNM patients from 2014 to 2019 at the University of Pittsburgh. We assessed patients for improvement in core set measures, prednisone dose, adverse effects, and by the "limited" ACR/EULAR 2016 myositis response criteria. The mean differences in CK and manual muscle testing (MMT-8) were compared using a paired t test. A clinically significant response was defined as a >10% absolute improvement in the MMT-8 and a >50% absolute reduction in serum CK at 6 months of IVIg. Intravenous immunoglobulin treatment was associated with marked improvement in IMNM patients, with 85% of patient meeting clinically significant response. The median (interquartile range) relative percent improvement in CK level was 96% (85%-98%) and in MMT was 29% (14%-36%) at 6 months.There was a significant reduction in the mean (SD) dose of prednisone at 6 months and had minimal adverse effects. In addition, with IVIg, most (13/14) patients had at least minimal improvement as per ACR/EULAR 2016 myositis response criteria. Based on objective, meaningful improvement in MMT-8 and CK as well as marked reduction in prednisone doses with acceptable tolerability, early implementation of IVIg should be considered in adult IMNM.

AUTOIMMUNE & INFLAMMATORY NMD: EP.06 Granulomatous myositis, perimysial pathology and immune-mediated necrotizing myopathy in anti-PL7 antisynthetase syndrome

A 72-year-old woman presented with a 6-month history of anorexia, weight loss (-14kg) and myalgia in upper limbs. Clinical examination showed moderate proximal muscle weakness in upper limbs and crepitation at lung auscultation, but no skin rash nor joint involvement. Biological assessment disclosed increased C-reactive protein (68µM) and creatine-kinase (3800 U/l) serum levels and anti-nuclear and -PL7 autoantibodies at immunological screening. Thoracic CT-scan showed abnormalities consistent with interstitial pneumonia. Search for cancer was negative. Deltoid muscle biopsy revealed an unusual myositis combining (i) randomly distributed myonecrosis with complement activation and membrane attack complex deposition at the surface of non-necrotic myofibers, (ii) perimysial inflammation with collagenolysis, and (iii) non-caseous granulomas. Immunohistochemical techniques revealed ubiquitous myofiber expression of major histocompatibility complex (MHC)-class I and multifocal MHC-II myofiber expression witnessing interferon-gamma signature. The peculiar histopathological features found in this patient was strikingly similar to that previously reported in anti-PL7 myositis, suggesting that anti-PL7 could be the marker of a specific subtype of overlap myositis.

AUTOIMMUNE & INFLAMMATORY NMD: EP.03 Clinicopathological findings of anti-mitochondrial antibody associated myositis

Anti-mitochondrial M2 antibody (AM2A) has been associated with myositis although it is unknown whether it is an independent subtype of myositis. To characterize the clinicopathological features, we reviewed the clinical information and muscle pathology slides of 226 patients (160 women) with AM2A whose pathological diagnosis was made at National Center of Neurology and Psychiatry. The age at muscle biopsy was 58.6±12.9 years and disease duration before biopsy was 52.4±75.3 months. Serum CK level was 1,585±2,319 U/L.

Dermatomyositis-related interstitial lung disease mimicking COVID-19 pneumonia.

A subtype of myositis with characteristic skin rashes and ulcers, amyopathic or hypomyopathic symptoms, and rapidly progressive ILD.

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry.

Anti-Melanoma Differentiation-Associated gene 5 (MDA-5) Dermatomyositis (MDA5, DM) is a recently identified subtype of myositis characteristically associated with Rapidly Progressive Interstitial Lung Disease (RP-ILD) and unique cutaneous features. We reviewed PubMed, SCOPUS and Web of Science databases and selected 87 relevant articles after screening 1485 search results, aiming to gain a better understanding of the pathophysiology, clinical features, diagnosis, and treatment approaches of anti-MDA-5 DM described in the literature. The etiopathogenesis is speculatively linked to an unidentified viral trigger on the background of genetic predisposition culminating in an acquired type I interferonopathy. The clinical phenotype is highly varied in different ethnicities, with new clinical features having been recently described, expanding the spectrum of cases that should raise the suspicion of anti-MDA-5 DM. Unfortunately, the diagnosis is frequently missed despite excessive mortality, calling for wider awareness of suspect symptoms. RP ILD is the major determinant of survival, treatment being largely based on observational studies with recent insights into aggressive combined immunosuppression at the outset.

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission. Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Gene expression profiles in muscle differ in myositis subtypes.

Gene expression profiles in muscle differ in myositis subtypes.

Aberrant Expression of High Mobility Group Box Protein 1 in the Idiopathic Inflammatory Myopathies.

IntroductionHigh Mobility Group Box Protein 1 (HMGB1) is a DNA-binding protein that exerts inflammatory or pro-repair effects upon translocation from the nucleus. We postulate aberrant HMGB1 expression in immune-mediated necrotising myopathy (IMNM).MethodsHerein, we compare HMGB1 expression (serological and sarcoplasmic) in patients with IMNM with that of other myositis subtypes using immunohistochemistry and ELISA.ResultsIMNM (n = 62) and inclusion body myositis (IBM, n = 14) patients had increased sarcoplasmic HMGB1 compared with other myositis patients (n = 46). Sarcoplasmic HMGB1 expression correlated with muscle weakness and histological myonecrosis, inflammation, regeneration and autophagy. Serum HMGB1 levels were elevated in patients with IMNM, dermatomyositis and polymositis, and those myositis patients with extramuscular inflammatory features.DiscussionAberrant HMGB1 expression occurs in myositis patients and correlates with weakness. A unique expression profile of elevated sarcoplasmic and serum HMGB1 was detected in IMNM.

The Value of Intravenous Immunoglobulin Therapy in Idiopathic Inflammatory Myositis in the Current Transformed Era of Biologics.

The understanding of etiology and pathogenesis of idiopathic immune myositis is fast evolving, and so is the classification of myositis subtypes. The diversity in genetics, major histocompatibility complex expressions, immunohistochemical, and specific and associated autoantibodies not only explains the individual variability in response to therapies but also begs for subtype-specific treatments. With the evolution of the new biological therapies, the treatment of idiopathic immune myositis (IIM) has greatly transformed in recent years. This article appraises the current therapeutic value of intravenous immunoglobulin (IVIg) in idiopathic immune myopathy patients in the era of transformed treatment options. This article argues why the IVIg therapy still retains its value as an unreplaceable treatment option in certain specific subtypes of idiopathic immune myositis patients as well as in certain specific clinical idiopathic immune myositis scenarios.

A Clinically and Biologically Based Subclassification of the Idiopathic Inflammatory Myopathies Using Machine Learning.

ObjectivePublished predictive models of disease outcomes in idiopathic inflammatory myopathies (IIMs) are sparse and of limited accuracy due to disease heterogeneity. Computational methods may address this heterogeneity by partitioning patients based on clinical and biological phenotype.MethodsTo identify new patient groups, we applied similarity network fusion (SNF) to clinical and biological data from 168 patients with myositis (64 adult polymyositis [PM], 65 adult dermatomyositis [DM], and 39 juvenile DM [JDM]) in the Rituximab in Myositis trial. We generated a sparse proof‐of‐concept bedside classifier using multinomial regression and identified characteristics that distinguished these groups. We conducted χ2 tests to link new patient groups with the myositis subtypes.Results SNF identified five patient groups in the discovery cohort that subdivided the myositis subtypes. The sparse multinomial regressor to predict patient group assignments (areas under the receiver operating characteristic curve = [0.78, 0.97]; areas under the precision‐recall curve = [0.55, 0.96]) found that autoantibody enrichment defined four of these groups: anti–Mi‐2, anti–signal recognition peptide (SRP), anti–nuclear matrix protein 2 (NXP2), and anti‐synthetase (Syn). Depletion of immunoglobulin M (IgM) defined the fifth group. Each group was associated with one subtype, with adult DM being associated with anti–Mi‐2 and anti‐Syn autoantibodies, JDM being associated with anti‐NXP2 autoantibodies, and adult PM being associated with IgM depletion and anti‐SRP autoantibodies. These associations enabled us to further resolve the current myositis subtypes.ConclusionUsing unsupervised machine learning, we identified clinically and biologically homogeneous groups of patients with IIMs, forming the basis of an integrated disease classification based on both clinical and biological phenotype, thus validating other approaches and what has been previously described.

Granulomatosis-associated myositis: High prevalence of sporadic inclusion body myositis.

To refine the predictive significance of muscle granuloma in patients with myositis. A group of 23 patients with myositis and granuloma on muscle biopsy (granuloma-myositis) from 8 French and Belgian centers was analyzed and compared with (1) a group of 23 patients with myositis without identified granuloma (control-myositis) randomly sampled in each center and (2) a group of 20 patients with sporadic inclusion body myositis (sIBM) without identified granuloma (control-sIBM). All but 2 patients with granuloma-myositis had extramuscular involvement, including signs common in sarcoidosis that were systematically absent in the control-myositis and the control-sIBM groups. Almost half of patients with granuloma-myositis matched the diagnostic criteria for sIBM. In these patients, other than the granuloma, the characteristics of the myopathy and its nonresponse to treatment were similar to the control-sIBM patients. Aside from 1 patient with myositis overlapping with systemic sclerosis, the remaining patients with granuloma-myositis did not match the criteria for a well-defined myositis subtype, suggesting pure sarcoidosis. Matching criteria for sIBM was the sole feature independently associated with nonresponse to myopathy treatment in patients with granuloma-myositis. Patients with granuloma-myositis should be carefully screened for sIBM associated with sarcoidosis in order to best tailor their care.

Polymyositis, Dermatomyositis, and Statins: A Review

BACKGROUND: Statins are a well-recognized cause of a variety of skeletal myopathic effects, which generally resolve when discontinuing the treatment. Among autoimmune manifestations associated with statins, there are typical polymyositis (PM) and typical dermatomyositis (DM).OBJECTIVE: To perform a review on published case reports and case series about statin-associated PM and DM.METHODS: This literature comprehensive search was conducted mainly on PubMed, but also congress abstracts and university websites were considered. Given the paucity of cases, the search was extended to include articles in all languages with English abstract.RESULTS: Twenty-eight PM and 30 DM cases have been described with prevalence in female (64%) and senile age. The drugs most frequently involved were atorvastatin and simvastatin. The differential diagnosis should be made among the main myositis subtypes: immuno-mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM), and overlap syndrome with myositis (OM), including anti-synthetase syndrome (ASS).CONCLUSIONS: Even though the onset of polymyositis or dermatomyositis is a rare phenomenon, it is advisable to consider their presence in patients taking statins and with a non-reversible elevation of creatine phosphokinase.

Dermatomyositis etiopathogenesis: a rebel soldier in the muscle.

The purpose of this article is to review the etiopathogenesis of dermatomyositis, including the predisposing factors, triggers, inflammatory cells, pathways and target antigens associated with dermatomyositis. During the last few years, we have made considerable progress in unveiling the etiopathogenesis of dermatomyositis. In the first place, we have defined genes within the major histocompatibility complex locus as the greatest genetic risk factor for the disease. Second, we have demonstrated that certain environmental factors, as well as tumors, may trigger certain dermatomyositis subtypes. Moreover, we have established the importance of the interferon pathway in dermatomyositis pathogenesis compared with other myositis subtypes. But probably, the most remarkable advance has been the discovery of multiple autoantibodies that define groups of patients with characteristic clinical features, prognosis and response to treatment. Dermatomyositis cause and pathogenesis have proven to be a complex and fascinating task for the scientific community and the last decade has been full of new findings on how the disease starts and how it causes damage to different organ systems. However, we have still more questions than answers in this topic, answers that will be critical to understanding autoimmunity and finding effective therapies to dermatomyositis.