Spectrum Of Idiopathic Inflammatory Myopathies Research Articles

The spectrum of idiopathic inflammatory myopathies: a Tunisian cohort

Background Inflammatory idiopathic myopathies (IIM) are a heterogeneous group of complex connective tissue diseases (CTD), primarily characterized by inflammatory involvement of skeletal muscles. Several other organs may also be affected, including lungs, heart, skin, gastrointestinal tract, and joints. Objective Describe the clinical and immunological characteristics of IIM among Tunisian patients. Method A retrospective study conducted in the internal medicine department at the Rabta Hospital over 22 years, including adult patients with IIM according to the ACR/EULAR classification criteria, and anti-synthetase syndrome (ASS) according to Connors’ criteria. Inclusion body myositis was excluded. Demographic, clinical, and immunological characteristics were analyzed. Results Ninety-seven patients were included (Male/female ratio= 0.36, mean age = 48.4 +- 13.8 years). The ACR/EULAR criteria enabled the inclusion of 88% of the patients. Dermatomyositis (DM) was the most frequent entity (47%), followed by Polymyositis (PM) (36%) and Amyotrophic dermatomyositis (ADM) (4%). Connors criteria allowed the inclusion and classification with ASS of 33 patients, including those excluded by the ACR/EULAR criteria (12%). Muscular involvement was present in 88% of patients, affecting locomotor (88%), gastrointestinal (43%), laryngeal (10%), cardiac (8%), and respiratory (1%) muscles. Myolysis was observed in 77% of patients, and histological evidence of myositis in 73%. ILD was reported across all subgroup: ASS (85%), PM (57%), DM (17%), and ADM (100%). NSIP was the most common radiologic pattern (59%). Skin involvement (85%), consistently present in DM and ADM, affected 91% of ASS patients. Joint involvement (48%) was predominantly polyarticular (68%). Myositis-specific antibodies (MSAs) were detected in 52% of patients, with a predominance of anti-synthetase antibodies (ASAs). Another CTD was noted in 24% of patients and cancer in 17% of patients. Conclusion Our study underscored the clinical diversity among IIM patients and the systemic nature of these diseases, where muscular involvement is not always uniform.

The spectrum of idiopathic inflammatory myopathies: a Tunisian cohort

Background Idiopathic inflammatory myopathies (IIM) encompass a heterogenous group of auto-immune diseases. The identification of myositis specific antibodies (MSA) and their associations with distinct phenotypes has improved the categorization of these conditions. Objective The aim of this study was to describe and report the clinical and immunological characteristics of IIM among Tunisian patients. Method A retrospective study conducted in the internal medicine department at the Rabta University Hospital Center over 22 years, including adult patients with IIM according to the American college of rheumatology/European league against rheumatism (ACR/EULAR) classification criteria and Connors’ criteria for anti-synthetase syndrome (ASS). Inclusion body myositis and myositis associated with other conditions were excluded. Demographic, clinical, and immunological characteristics were analyzed and compared. Results Ninety-seven patients were included (Male/female ratio= 0.36, mean age = 48.4 +- 13.8 years). Muscular involvement was present in 88% of patients, affecting locomotor muscles (88%), gastrointestinal (43%), laryngeal (10%), cardiac (8%), and respiratory (1%) systems. Muscle weakness was primarily noted in the pelvic girdle (81%), scapular region (74%), axial muscles (20%), and distal muscles (5%). Myolysis was observed in 77% of patients, and histological evidence of myositis in 73%. Diffuse interstitial pneumonia (DIP) was present in 45% of patients, cutaneous involvement in 85%, and articular involvement in 48%. MSAs were detected in 52% of patients. Analysis revealed significantly higher frequencies of amyopathic forms, DIP, palmar hyperkeratosis, and articular involvement in the ASS group. The DM group exhibited higher frequencies of gastrointestinal signs, Gottron’s papules, heliotrope rash, photosensitive rashes, ulcerations, and skin necrosis. The NAM group had higher frequencies of gastrointestinal signs, myolysis, and lower frequencies of DIP and cutaneous involvement. Conclusion Our findings corroborate previously established clinico-immunological associations reported in the literature underscoring the need for a combined clinico-serological approach in classifying IIM.

Comparison of rituximab efficacy in treatment-naive and refractory inflammatory myopathies: experiences from a tertiary care centre.

To find out if Rituximab (RTX) is effective in "treatment naive" idiopathic inflammatory myopathies (IIM), and whether there could be differential treatment responses between the "treatment naive" and treatment "refractory" IIM. Data obtained from a prospectively maintained database comprising patients with IIM treated with rituximab. Patient details were obtained at baseline, 3-months, 6-months intervals, and subsequent follow up visits. Treatment response was categorised as improved, worsening, or stable based on manual muscle testing (MMT8) scores, patient global and physician global improvement (PtGA and PGA) for skin and joint symptoms improvement and spirometry at 6 months. The time to clinical improvement and remission were noted and survival analysis curves were constructed. 60 patients with IIM (including 18 with anti-SRP myopathy) were included, out of which 33 who received RTX were treatment naïve. The remaining 27 were started on rituximab for refractory myopathy. Mean age was 39 years (SD12.58) in "treatment-naive" group and 43 years (SD 12.12) in "refractory" group. At 6 months of follow up, 48/55 (87%) patients showed response, 31/31 (100%) in "treatment-naive" and 17/24 (70%) in "refractory" cases, p 0.006*. In refractory group, 7 (29%) had stable disease. The mean changes in MMT8 were significantly more in the "treatment-naive" treatment group (13.41(SD 7.31) compared with "refractory" IIM 8.33 (SD 7.92) (p= 0.017*). Majority of patients were able to reduce dose below 5 mg/day before 6 months. No major adverse events were reported over the median follow-up of 24 (IQR 36) months. Rituximab is effective and safe across the spectrum of IIM. Early use in disease is associated with better outcomes.

Review of Pulmonary Manifestations in Antisynthetase Syndrome.

Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be diverse. Additional common symptoms experienced by patients with ASyS include Raynaud's phenomenon, mechanic's hand, and fever. Although there is a significant overlap with polymyositis and dermatomyositis, the key distinction lies in the presence of antisynthetase antibodies (ASAs). Up to 10 ASAs have been identified to correlate with a presentation of ASyS, each having manifestations that may slightly differ from others. Despite the proposal of three classification criteria to aid diagnosis, the heterogeneous nature of patient presentations poses challenges. ILD confers a significant burden in patients with ASyS, sometimes manifesting in isolation. Notably, ILD is also often the initial presentation of ASyS, requiring pulmonologists to remain vigilant for an accurate diagnosis. This article will comprehensively review the various aspects of ASyS, including disease presentation, diagnosis, management, and clinical course, with a primary focus on its pulmonary manifestations.

Hidden in Plain Sight: Pitfalls of a Case of Amyopathic Anti-Synthetase Syndrome Associated with Grawitz Tumor

Abstract Anti-synthetase syndrome (ASS) is a rare autoimmune disease whose hallmark consists of the presence of autoantibodies directed against aminoacyl transfer RNA (tRNA) synthetases thus making it a distinctive pathology of the broad spectrum of idiopathic inflammatory myopathies (IIM). Clinically, lung involvement in the form of interstitial lung disease (ILD) and myositis are typical findings. Inflammatory myopathies should always raise the suspicion of an adjancent tumoral process and therefore prompt the clinician to perform a thorough screening. We present the case of a 55 year old caucasian male who was diagnosed with amyopathic ASS and a clear cell renal carcinoma (Grawitz tumor), along with the consequent therapeutic challenges.

The spectrum of idiopathic inflammatory myopathies in Western Australia: epidemiological characteristics and mortality over time

To determine long term overall and subgroup specific incidence rates and associated mortality for idiopathic inflammatory myopathies (IIM) in a population wide study. We included patients hospitalised between 1980 and 2015 with incident IIM as defined by relevant diagnostic codes for dermatomyositis (DM) polymyositis (PM), inclusion body myositis (IBM), other IIM and overlap myositis (OM) in the Western Australia Health Hospital Morbidity Data Collection (n = 846). Trends over time for annual incidence rate per million population (AIR) were analysed by least square regression and Kaplan–Meier survival and mortality rates (MR)/100 person years compared with a matched control group (n = 3681). The averaged AIR for all IIM was 19 (CI 10.4–27.5) and stable over time with point prevalence reaching 205.3 (CI 185.6–226.6) per million in 2015. Over time, the AIR for DM 5.0 (CI 0.6–9.4) and IBM 3.3 (CI 0.7–9.6) was stable, while AIR decreased for PM (p < 0.01) and increased for other IIM (p < 0.01) and OM (p < 0.01). IBM patients were eldest at diagnosis (68 years, CI 59–77) with male preponderance in IBM (53.4%) and other IIM (55.8%) groups. Crude mortality (54.5 vs 41.3%), MR ratio (6.65 vs 5.91) and 5 (65.8% vs 71.6%) and 10-year (52.5% vs 58.7%) survival were all worse for IIM patients (all p < 0.05). IBM patients had highest MR (10.1; CI 8.38–12.14) and lowest 10-year survival (39.2%). While cardiovascular disease and cancer were predominant causes of death, they were proportionally lower in IIM patients, where respiratory and rheumatic disease were more frequent causes of death. While the overall incidence of IIM in WA was stable over 35 years, the spectrum of IIM has changed significantly with increases especially in other IIM and OM. The overall prognosis with IIM remains guarded with 10-year survival just over 50%.

Senescent fibro-adipogenic progenitors are potential drivers of pathology in inclusion body myositis

Inclusion body myositis (IBM) is unique across the spectrum of idiopathic inflammatory myopathies (IIM) due to its distinct clinical presentation and refractoriness to current treatment approaches. One explanation for this resistance may be the engagement of cell-autonomous mechanisms that sustain or promote disease progression of IBM independent of inflammatory activity. In this study, we focused on senescence of tissue-resident cells as potential driver of disease. For this purpose, we compared IBM patients to non-diseased controls and immune-mediated necrotizing myopathy patients. Histopathological analysis suggested that cellular senescence is a prominent feature of IBM, primarily affecting non-myogenic cells. In-depth analysis by single nuclei RNA sequencing allowed for the deconvolution and study of muscle-resident cell populations. Among these, we identified a specific cluster of fibro-adipogenic progenitors (FAPs) that demonstrated key hallmarks of senescence, including a pro-inflammatory secretome, expression of p21, increased β-galactosidase activity, and engagement of senescence pathways. FAP function is required for muscle cell health with changes to their phenotype potentially proving detrimental. In this respect, the transcriptomic landscape of IBM was also characterized by changes to the myogenic compartment demonstrating a pronounced loss of type 2A myofibers and a rarefication of acetylcholine receptor expressing myofibers. IBM muscle cells also engaged a specific pro-inflammatory phenotype defined by intracellular complement activity and the expression of immunogenic surface molecules. Skeletal muscle cell dysfunction may be linked to FAP senescence by a change in the collagen composition of the latter. Senescent FAPs lose collagen type XV expression, which is required to support myofibers’ structural integrity and neuromuscular junction formation in vitro. Taken together, this study demonstrates an altered phenotypical landscape of muscle-resident cells and that FAPs, and not myofibers, are the primary senescent cell type in IBM.

Idiopathic inflammatory myopathies: Not nearly the end of the road

The clinical spectrum of idiopathic inflammatory myopathies (IIM) has broadened over the past half century from a simple disease characterised primarily by muscle and skin manifestations, to a potentially life-threatening complex condition of multiple organ involvement. In the recent decade, the discovery and addition of novel autoantibody profiles including the myositis-specific autoantibodies (MSAs) and myositis-associated

VP.43 Immune-mediated necrotizing myopathies: clinical-serological features of a large Italian cohort of patients

Immune-mediated necrotizing myopathies (IMNMs) represent a heterogeneous group of muscle disorders recently identified within the spectrum of idiopathic inflammatory myopathies (IIMs) by distinctive clinical, pathological, serological, and therapeutic features. Currently, three different IMNM entities have been defined: 1) anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy; 2) anti-signal recognition particle (SRP) myopathy; 3) antibody negative IMNM. An accurate diagnosis of IMNMs is relevant for prognostic purposes and to provide the best chance of treatment for patient subtypes and prevent long-term disability. We aimed to investigate clinical and histological features of different serological subgroups within an Italian cohort of IMNM patients. We included 128 patients diagnosed with IMNM in 12 neuromuscular referral centers in Italy, relying on the 2017 European Neuromuscular Centre criteria. The study population was composed by 57 males and 71 females, with an overlapping median age at disease onset equal to 65 years old for men and 64 for women. Forty-five patients (35,2%) were positive for HMGCR autoantibodies (Abs), of whom 30 had a history of statin exposure (13 males, 17 females). Among anti-HMGCR Ab–positive IMNM patients naïve to statin therapy, females were more represented (61,5%). Furthermore, 35 patients (27,3%) had anti-signal recognition particle (SRP) Abs, 27 patients (21,1%) resulted seronegative, and 21 patients (16,4%) did not have a complete Ab assessment. Malignancies were reported in 17 patients. Onset muscle weakness distribution, muscle biopsy pathological features, clinical outcome after therapy, CPK levels and extra-muscular manifestations according to serological type were evaluated. This study provides new insights about IMNM characteristics in a large Italian cohort.

The Significance of Autoantibodies in Juvenile Dermatomyositis.

Juvenile dermatomyositis is a chronic and rare autoimmune disorder classified into the spectrum of idiopathic inflammatory myopathies. Although this entity is mainly characterized by the presence of pathognomonic cutaneous lesions and proximal muscle weakness, the clinical manifestation can be highly heterogeneous; thus, diagnosis might be challenging. Current treatment recommendations for juvenile dermatomyositis, based mainly upon case series, include the use of corticosteroids, immunomodulatory, and immunosuppressive agents. Recently, several specific autoantibodies have been shown to be associated with distinct clinical phenotypes of classic dermatomyositis. There is a need to further evaluate their relevance in the formation of various clinical features. Furthermore, while providing more personalized treatment strategies, one should consider diversity of autoantibody-related subgroups of juvenile dermatomyositis.

P35 Dermatomyositis with retinal involvement: a case series

P35 Dermatomyositis with retinal involvement: a case series

Importance of collaboration of dermatology and rheumatology to advance the field for lupus and dermatomyositis.

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

Contribución del panel de miositis en el estudio de pacientes con enfermedades pulmonares intersticiales y sospecha de enfermedad del tejido conectivo

Introduction: The most common extramuscular manifestation of the idiopathic inflammatory myopathies (IIM) is interstitial lung disease (ILD) and the diagnosis is based on serum autoantibodies. The new specific and associated antibodies to IIM have helped to identify new clinical entities in the spectrum of IIM. The objective of this study is to evaluate the diagnostic contribution of a myositis antibodies panel (MP) in a cohort of Chilean patients with ILD without a definitive connective tissue disease (CTD). Materials and Methods: Starting on January 2017 we performed a MP to 111 consecutive patients with ILD and suspected CTD but without a definitive diagnosis through another diagnostic tools in the Lung-Rheumatological Program at the “Instituto Nacional del Torax”, Santiago, Chile. The clinical and serological baseline characteristics of the patients that were most frequently associated with the probability of having a positive panel were compared. Results: The MP was positive in 56 of 111 patients. Anti synthetase syndrome (ASS) was the most prevalent diagnosis. The most frequent antibodies were Ro-52, PM/Scl-75 and Ku. The most frequent variables in the positive MP group were the presence of Raynaud’s phenomenon, myositis, mechanic’s hands, positive Ro and La antibodies and the presence of combined pattern of nonspecific interstitial pneumonia and organizing pneumonia in chest computed tomography scan. Conclusions: The incorporation of the MP has helped us to improve our diagnostic precision of patients with CTD/ILD. We present clinical and serological elements that refine the performance of the test.

The spectrum of idiopathic inflammatory myopathies in South Africa.

There are many reports on idiopathic inflammatory myopathies (IIM) but little information from sub-Saharan Africa. We conducted a retrospective study of IIM in a multi-ethnic cohort seen at a single centre in Durban, South Africa. The study included patients who fulfilled the Bohan and Peter or European League Against Rheumatism/American College of Rheumatology criteria for IIM. The information recorded included demographic data, clinical findings, results of investigations, treatment and outcome. Patients with overlap myositis (OM) had myositis and criteria for another connective tissue disease. There were 104 patients with IIM; 82.7% female and 70.2% African blacks. They included 41 (39.4%) with OM, 26 (25%) polymyositis (PM), 26 (25%) dermatomyositis (DM), six (5.8%) juvenile dermatomyositis and five (4.8%) cancer-associated myositis. Our patients had a younger mean age at diagnosis (36.8 ± 14.7years) compared with 45-55years in most other studies. Scleroderma-myositis overlap accounted for 26 (63.4%) of the patients with OM. Patients with OM were significantly younger than PM (p = 0.004) and DM (p = 0.044) and had lower, but not statistically significant, creatine kinase levels at diagnosis compared with PM (p = 0.052) and DM (p = 0.073). Interstitial lung disease was more common in OM (p = 0.001) and PM (p = 0.024) than DM. Oropharyngeal weakness was more common in DM than OM (p = 0.001) and PM (p = 0.032). African blacks were younger (p = 0.028) at diagnosis and had more cardiac abnormalities (p = 0.034) than Indians. The spectrum of IIM in our cohort of mainly African blacks is similar to other studies, with OM being the most frequent subtype. Key Points • As there is limited information on idiopathic inflammatory myopathies (IIM) in sub-Saharan Africa, this study reports the spectrum of IIM in a South African cohort of predominantly African blacks. • Our patients were younger at diagnosis, and overlap myositis was the most common phenotype. • Comparisons with other studies show similarities in the manifestations of IIM.

Idiopathic inflammatory myopathy: From muscle biopsy to serology

Idiopathic inflammatory myopathies (IIMs) are heterogeneous group of muscle disorders characterized by variable degree of muscle weakness and muscle inflammation. Various classification systems have been proposed for myositis. However, there remains a diagnostic uncertainty due to the presence of overlapping clinical and pathological features. Similar treatment outcomes to immunosuppressant drugs further add to diagnostic confusion. Introduction of myositis-specific and myositis-associated autoantibodies has widened the disease spectrum of IIMs. Despite being very crucial for the diagnosis and classification of myositis, these autoantibodies are not always present. Therefore, histopathological features and immunohistochemical markers are considered gold standard for the diagnosis of myositis. A correct diagnosis has important clinical and therapeutic implications. In this review, we have focused on salient clinicopathological features and newly developed serological markers in major subtypes of IIMs.

Disease Specific Autoantibodies in Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies represent still a diagnostic and therapeutic challenge in different disciplines including neurology, rheumatology, and dermatology. In recent years, the spectrum of idiopathic inflammatory myopathies has been significantly extended and the different manifestations were described in more detail leading to new classification criteria. A major breakthrough has also occurred with respect to new biomarkers especially with the characterization of new autoantibody-antigen systems, which can be separated in myositis specific antibodies and myositis associated antibodies. These markers are detectable in approximately 80% of patients and facilitate not only the diagnostic procedures, but provide also important information on stratification of patients with respect to organ involvement, risk of cancer and overall prognosis of disease. Therefore, it is not only of importance to know the significance of these markers and to be familiar with the optimal diagnostic tests, but also with potential limitations in detection. This article focuses mainly on antibodies which are specific for myositis providing an overview on the targeted antigens, the available detection procedures and clinical association. As major tasks for the near future, the need of an international standardization is discussed for detection methods of autoantibodies in idiopathic inflammatory myopathies. Furthermore, additional investigations are required to improve stratification of patients with idiopathic inflammatory myopathies according to their antibody profile with respect to response to different treatment options.

Necrotizing Autoimmune Myopathy: Clinicopathologic Study from a Single Tertiary Care Centre.

Background:Idiopathic inflammatory myopathies (IIMs) are a group of chronic, autoimmune disorders which include a new entity, necrotizing autoimmune myopathy (NAM). NAM lacks inflammation and presents with markedly elevated creatinine phosphokinase (CPK) levels. It is associated with connective tissue diseases (CTDs), statin use, malignancies, and most cases are idiopathic.Objectives:The objectives of this study are to describe the clinicopathologic features in muscle biopsy-proven cases of NAM. To emphasize the role of laboratory parameters such as CPK levels and myositis profile in the diagnosis of NAM.Materials and Methods:This is a retrospective study including 15 patients of NAM diagnosed on muscle biopsy over a period of 2 years. The slides of the biopsies were reviewed, and clinical data, electromyography findings, and CPK levels were obtained. Myositis profile was done.Results:Necrotizing myopathy accounted for 13.63% (15 cases) of total inflammatory myopathies (110 cases) in the study. These were grouped into CTD-associated NAM, statin-associated NAM, paraneoplastic NAM and idiopathic NAM which was the common type. All cases presented with progressive proximal muscle weakness and had markedly elevated CPK levels. Anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and antisignal recognition particle antibodies were seen to be positive in six patients. Muscle biopsies showed predominant fiber necrosis with significant fiber degeneration and regeneration in the absence of inflammation. All patients received immunotherapy with significant improvement was seen in six patients with two mortalities.Conclusion:Necrotizing myopathy is a new addition to the spectrum of IIM. Clinicopathologic correlation is important for appropriate diagnosis. It is found to be refractory to corticosteroids monotherapy. The course of illness is not uniform, and in some patients, there can be rapid worsening with mortality.

The Clinical and Histological Spectrum of Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of myositis, characterised by chronic muscle weakness, cutaneous features, different extra-muscular manifestations and circulating autoantibodies. IIMs included classical polymyositis (PM), dermatomyositis (DM) and other different types of myositis with a wide range of muscle involvement. A complete autoantibody profile and a muscle biopsy are mandatory to correctly diagnose different clinical entities and to define their different prognosis. Bohan and Peter's criteria included five items to diagnose adult onset PM and DM. The sensitivity was 74-100%, while the specificity is low, due to a poor ability to differentiate PM from neuromuscular diseases. Other criteria included a more accurate histological definition of PM, DM or amyopathic DM, obtaining a higher specificity. Autoantibodies' association, interstitial lung disease and clinical cardiac involvement represent the main items that could define the prognosis of these patients. On the other hand, inclusion body myositis is a different myopathy characterised by a peculiar muscle mass involvement, muscle atrophy and progressive loss of function, due to complete failure to all immunosuppressive drugs used. Treatment of IIMs is based on corticosteroids (CS), which show rapid clinical response and functional improvement. Different immunosuppressant drugs are given to obtain a better control of the disease during CS tapering dose. No controlled double blind trials demonstrated the superiority of one immunesuppressant on another. The occurrence of interstitial lung involvement requires the immediate introduction of immunosuppressants in addiction to CS. Severe dysphagia seems to improve with intravenous immunoglobulins (Ig). Physical therapy could be started after the acute phase of diseases and seems to have a beneficial role in muscle strength recovery.

Nuclear actin aggregation is a hallmark of anti-synthetase syndrome-induced dysimmune myopathy.

To analyze antisynthetase syndrome-associated myositis by modern myopathologic methods and to define its place in the spectrum of idiopathic inflammatory myopathies (IIMs). Skeletal muscle biopsies from antisynthetase syndrome-associated myositis and other IIMs from different institutions worldwide were analyzed by histopathology, quantitative PCR, and electron microscopy. Myonuclear actin filament inclusions were identified as a unique morphologic hallmark of antisynthetase syndrome-associated myositis. Nuclear actin inclusions were never found in dermatomyositis, polymyositis, sporadic inclusion body myositis, autoimmune necrotizing myopathy associated with signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies, or nonspecific myositis associated with other systemic diseases, harboring myositis-associated autoantibodies, and presenting myofiber necrosis. We show that molecules involved in actin filament formation and actin shuttling mechanisms are altered in antisynthetase syndrome, and may thus be involved in pathologic myonuclear actin aggregation. In addition, we have identified a typical topographic distribution of necrotic myofibers predominantly located at the periphery of muscle fascicles accompanied by inflammation and destruction of the perimysial connective tissue. Antisynthetase syndrome-associated myositis is characterized by distinctive myonuclear actin filament inclusions, including rod formations and a typical necrotizing perimysial myositis. This supports the hypothesis that antisynthetase syndrome-associated myositis is unique and should not be grouped among dermatomyositis, polymyositis, sporadic inclusion body myositis, necrotizing autoimmune myositis, or nonspecific myositis. This study provides Class II evidence that for patients with IIMs, the presence of myonuclear actin filament inclusions accurately identifies patients with antisynthetase syndrome-associated myositis (sensitivity 81%, specificity 100%).

Cardiological features in idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIMs) represent a heterogeneous group of autoimmune systemic diseases characterized by chronic muscle weakness and inflammatory cell infiltrates in skeletal muscle. The most frequent IIMs, such as adult-onset polymyositis and dermatomyositis, display a wide range of clinical manifestations other than myositis, including skin changes, Raynaud's phenomenon and interstitial lung disease. Cardiac involvement is now well recognized as a clinically important manifestation in patients with polymyositis or dermatomyositis, although its actual frequency is still uncertain. Cardiovascular complications represent one of the most frequent causes of death in myositis, apart from cancer and lung involvement. Despite the fact that clinical manifestations are relatively rare, asymptomatic cardiovascular features are frequently reported in patients with polydermatomyositis and dermatomyositis. They are characterized by isolated electrocardiographic changes, valve disease, coronary vasculitis, ischemic abnormalities, heart failure and myocarditis. Chronic inflammation producing myocyte degeneration, tissues fibrosis and vascular alterations can explain the majority of reported cardiac features in myositic patients. Although previous works reported an association between heart involvement and some myositis-specific autoantibodies (namely anti-signal recognition particle), electrocardiography, echocardiography and, where necessary, heart magnetic resonance remain the mainstay for diagnosing and monitoring myocardial inflammation in these diseases. Anyway, a complete multiorgan assessment and a careful analysis of autoantibodies should be performed in every patient in order to define any possible distinct disease entities with different prognosis within the spectrum of IIMs.