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Mohammed, Abdel Gaffar A., Ayanda Gcelu, Farzana Moosajee, Stella Botha, and Asgar Ali Kalla. "Immune Mediated Necrotizing Myopathy: Where do we Stand?" Current Rheumatology Reviews 15, no. 1 (December 12, 2018): 23–26. http://dx.doi.org/10.2174/1573397114666180406101850.
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Immune-mediated necrotizing myopathies (IMNMs) are a group of acquired autoimmune muscle disorders which are characterized by proximal muscle weakness, high levels of creatinine kinase, and myopathic findings on electromyogram (EMG). Muscle biopsy in IMNM differentiates it from the other subgroups of Idiopathic Inflammatory Myositis (IIM) by the presence of myofibre necrosis and prominent regeneration without substantial lymphocytic inflammatory infiltrates. Anti-signal recognition particle (SRP) and anti-3hydroxy-3 methylglutarylcoenzyme A reductase (HMGCR) autoantibodies were found in two-thirds of IMNM patients. In terms of treatment, IMNM is more resistant to conventional immunosuppressive treatment, therefore, other modalities of treatment such as Intravenous Immunoglobulin (IVIG) and rituximab are often required.
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Allenbach, Yves, and Olivier Benveniste. "Peculiar clinicopathological features of immune-mediated necrotizing myopathies." Current Opinion in Rheumatology 30, no. 6 (November 2018): 655–63. http://dx.doi.org/10.1097/bor.0000000000000547.
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Pinal-Fernandez, Iago, and Andrew L. Mammen. "Spectrum of immune-mediated necrotizing myopathies and their treatments." Current Opinion in Rheumatology 28, no. 6 (November 2016): 619–24. http://dx.doi.org/10.1097/bor.0000000000000335.
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Knauss, Samuel, Corinna Preusse, Yves Allenbach, Sarah Leonard-Louis, Mehdi Touat, Norina Fischer, Helena Radbruch, et al. "PD1 pathway in immune-mediated myopathies." Neurology - Neuroimmunology Neuroinflammation 6, no. 3 (April 10, 2019): e558. http://dx.doi.org/10.1212/nxi.0000000000000558.
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ObjectiveTo investigate the relevance of dysfunctional T cells in immune-mediated myopathies. We analyzed T-cell exhaustion and senescence, in the context of programmed cell death protein 1 (PD1)-related immunity in skeletal muscle biopsies from patients with immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), and myositis induced by immune checkpoint inhibitors (irMyositis).MethodsSkeletal muscle biopsies from 12 patients with IMNM, 7 patients with sIBM, and 8 patients with irMyositis were analyzed by immunostaining and immunofluorescence as well as by quantitative PCR. Eight biopsies from nondisease participants served as controls.ResultsCD3+CD8+ T cells in biopsies from IMNM, sIBM, and irMyositis were largely PD1-positive, while CD68+ macrophages were sparsely positive to the ligand of programmed cell death protein 1 (PD-L1). The sarcolemma of myofibers was PD-L2+ and was colocalized with major histocompatibility complex (MHC) class I. CD68+ macrophages were colocalized with PD-L2. Senescent T cells were strongly enriched in skeletal muscle of sIBM, revealing a distinct immunologic signature. Biopsies from patients with irMyositis showed mild signs of senescence and exhaustion.ConclusionPersistent exposure to antigens in IMNMs and sIBM may lead to T-cell exhaustion, a process controlled by the PD1 receptor and its cognate ligands PD-L1/PD-L2. To our knowledge, these data are the first evidence of presence of dysfunctional T cells and relevance of the PD1 pathway in IMNM, sIBM, and irMyositis. These findings may guide the way to a novel understanding of the immune pathogenesis of immune-mediated myopathies.
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Lee, Jong-Mok. "Immune-Mediated Necrotizing Myopathy: A Review for Clinicians." Journal of Electrodiagnosis and Neuromuscular Diseases 24, no. 3 (December 31, 2022): 57–61. http://dx.doi.org/10.18214/jend.2022.00087.
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Immune-mediated necrotizing myopathy (IMNM) is a group of inflammatory myopathies showing necrotic and regenerating fibers without noteworthy inflammatory cell infiltration on pathology. The pathologic findings are different from those of dermatomyositis or sporadic inclusion body myositis. Furthermore, the discovery of myositis-specific antibodies in patients with IMNM, such as anti-signal recognition particle or anti-3-hydroxy-3-methylglutaryl-CoA reductase antibodies, has enabled us to expand our knowledge of IMNM. However, the phenotype and pathological findings of IMNM are unremarkable; therefore, it is difficult to diagnose, and IMNM has been relatively unrecognized. In this review, we introduce the clinical features, diagnosis, pathomechanism, and treatment of IMNM for clinicians.
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Akbar, Shalla, Sandhya Dasaraju, and Osama Elkadi. "A Case of Immune-Mediated Necrotizing Myopathy With Associated Skeletal Muscle Involvement by Sarcoid Granulomata: A Rare Association." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S69. http://dx.doi.org/10.1093/ajcp/aqz113.078.
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Abstract Skeletal muscle involvement by noncaseating granulomata occurs in a variety of conditions, including sarcoidosis, infections, and rarely in association with primary inflammatory myopathies such as inclusion body myositis (IBM) and dermatomyositis (DM). Sarcoid myopathy is typically asymptomatic; however, a picture of acute myositis with proximal muscle weakness has been described. Immune-mediated necrotizing myopathy (IMNM) is a subgroup of inflammatory myopathies typically presenting with proximal muscle weakness and markedly elevated muscle enzymes, mostly occurring in the setting of statin treatment. IMNM is associated with positive autoantibodies, but a subset of cases is antibody negative. Here we describe a case of myopathy occurring in association with sarcoidosis with combined features of granulomatous and necrotizing myopathy. The patient was a 54-year-old African American male with medical history significant for statin use 3 years ago, which was discontinued due to myalgia and elevated muscle enzymes and biopsy-proven sarcoidosis diagnosed on a pulmonary lymph node biopsy. He presented with progressive worsening of bilateral proximal weakness involving the upper and lower extremities. Electromyogram showed features of active myopathy with no evidence of peripheral neuropathy. Myositis panel was negative for the following antibodies: anti-Jo1, Mi-2, anti-Ku, PL-7, PL-12, OJ, EJ, and SRP. However, there was elevation of aldolase, CRP, and CK-MB. Biopsy of thigh and deltoid muscle showed necrotic muscle fibers, myophagocytosis with associated minimal inflammation, and multiple well-formed nonnecrotizing granulomas with multinucleated giant cells. Myopathic features include increased internalized nuclei, round atrophic fibers, and scattered split fibers. Specific features of IBM or DM were not present. Conclusion Myopathies developing or worsening after discontinuation of statin are rare. The association of necrotizing myopathy with sarcoidosis is not well described in the literature. Additional studies are warranted to elucidate this association.
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Swafford, Collin, and E. Steve Roach. "Juvenile Dermatomyositis and the Inflammatory Myopathies." Seminars in Neurology 40, no. 03 (April 6, 2020): 342–48. http://dx.doi.org/10.1055/s-0040-1705120.
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AbstractThe inflammatory myopathies comprise disorders of immune-mediated muscle injury. The histopathology and clinical features help distinguish them. Juvenile dermatomyositis (JDM) is the most common form of myositis in children and adolescents. Children with JDM present with proximal muscle weakness and characteristic rashes. The presentation is similar in children and adults, but JDM is a primary disorder and the adult form often is concerning for a paraneoplastic syndrome. Proximal muscle weakness occurs with dermatomyositis, polymyositis, and immune-mediated necrotizing myopathy, but the latter two conditions have no dermatologic findings or distinct tissue changes which set them apart from dermatomyositis. Inclusion body myositis, also included in the inflammatory myopathies, presents with more distal involvement, and microscopically exhibits identifiable rimmed vacuoles. We review key features of these disorders, focusing in more detail on JDM because it is more often encountered by the child neurologist.
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Mecoli, Christopher A., Arash H. Lahouti, Robert A. Brodsky, Andrew L. Mammen, and Lisa Christopher-Stine. "High-dose cyclophosphamide without stem cell rescue in immune-mediated necrotizing myopathies." Neurology - Neuroimmunology Neuroinflammation 4, no. 5 (July 11, 2017): e381. http://dx.doi.org/10.1212/nxi.0000000000000381.
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Objective:To describe the experience managing treatment-refractory immune-mediated necrotizing myopathies (IMNM) with high-dose cyclophosphamide (HiCy) therapy.Methods:Five patients with severe refractory IMNM who were treated with HiCy without stem cell rescue were identified. Their medical records were reviewed to assess demographic, clinical, and histologic characteristics as well as response to therapy.Results:Three patients with anti–signal recognition particle (SRP) and 2 patients with anti-HMG-CoA reductase autoantibodies were included. The mean follow-up time after HiCy therapy was 37 ± 28 months. Two patients demonstrated substantial response, evidenced by improved muscle strength and decreased muscle enzymes after HiCy therapy; both of these patients were anti-SRP positive. Four patients experienced febrile neutropenia after HiCy therapy, one of which required a prolonged intensive care unit stay for infectious complications, from which they eventually recovered.Conclusions:These data suggest that HiCy therapy without stem cell rescue may be considered as an alternative for the treatment of refractory IMNM.
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Park, Sunha, Dae-Hyun Jang, Jae-Min Kim, and Nara Yoon. "Prominent Asymmetric Muscle Weakness and Atrophy in Seronegative Immune-Mediated Necrotizing Myopathy." Diagnostics 11, no. 11 (November 8, 2021): 2064. http://dx.doi.org/10.3390/diagnostics11112064.
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Immune-mediated necrotizing myopathy, a new subgroup of inflammatory myopathies, usually begins with subacute onset of symmetrical proximal muscle weakness. A 35-year-old male presented with severe asymmetric iliopsoas atrophy and low back pain with a previous history of left lower extremity weakness. Although his first left lower extremity weakness occurred 12 years ago, he did not receive a clear diagnosis. Magnetic resonance imaging of both thigh muscles showed muscle edema and contrast enhancement in patch patterns, and the left buttock and thigh muscles were more atrophied compared to the right side. Serum creatine kinase levels were elevated, and serologic testings were all negative. Genetic testing using a targeted gene-sequencing panel for neuromuscular disease including myopathy identified no pathogenic variants. Muscle biopsy on the right vastus lateralis showed scattered myofiber necrosis with phagocytosis and an absence of prominent inflammatory cells, consistent with seronegative necrotizing myopathy. Thus, unusual asymmetric muscle weakness and atrophy can be a manifestation of inflammatory myopathy.
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Chiapparoli, Ilaria, Claudio Galluzzo, Carlo Salvarani, and Nicolò Pipitone. "A glance into the future of myositis therapy." Therapeutic Advances in Musculoskeletal Disease 14 (January 2022): 1759720X2211002. http://dx.doi.org/10.1177/1759720x221100299.
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The idiopathic inflammatory myopathies are chronic diseases of the skeletal muscle that comprise various conditions, including dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and the antisynthetase syndrome. Although there are a number of distinguishing features, all these disorders are characterized by an immune and inflammatory response mainly directed against the muscle. Hence, therapy is geared toward curbing the autoimmune and inflammatory response. A quite wide range of medications are currently available to treat these disorders, but despite all therapeutic progress still a number of patients are unable to maintain a sustained remission. In this review article, we have marshaled a variety of potential therapeutic agents that may hold promise for the future treatment of the idiopathic inflammatory myopathies. It is to be expected that by increasing the therapeutic armamentarium with agents that have different mechanisms of action even challenging cases could be successfully managed, thus reducing disease burden and disability.
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Kamperman, Renske G., Anneke J. van der Kooi, Marianne de Visser, Eleonora Aronica, and Joost Raaphorst. "Pathophysiological Mechanisms and Treatment of Dermatomyositis and Immune Mediated Necrotizing Myopathies: A Focused Review." International Journal of Molecular Sciences 23, no. 8 (April 13, 2022): 4301. http://dx.doi.org/10.3390/ijms23084301.
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Idiopathic inflammatory myopathies (IIM), collectively known as myositis, are a composite group of rare autoimmune diseases affecting mostly skeletal muscle, although other organs or tissues may also be involved. The main clinical feature of myositis is subacute, progressive, symmetrical muscle weakness in the proximal arms and legs, whereas subtypes of myositis may also present with extramuscular features, such as skin involvement, arthritis or interstitial lung disease (ILD). Established subgroups of IIM include dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), overlap myositis (OM) and inclusion body myositis (IBM). Although these subgroups have overlapping clinical features, the widespread variation in the clinical manifestations of IIM suggests different pathophysiological mechanisms. Various components of the immune system are known to be important immunopathogenic pathways in IIM, although the exact pathophysiological mechanisms causing the muscle damage remain unknown. Current treatment, which consists of glucocorticoids and other immunosuppressive or immunomodulating agents, often fails to achieve a sustained beneficial response and is associated with various adverse effects. New therapeutic targets have been identified that may improve outcomes in patients with IIM. A better understanding of the overlapping and diverging pathophysiological mechanisms of the major subgroups of myositis is needed to optimize treatment. The aim of this review is to report on recent advancements regarding DM and IMNM.
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Fischer, Norina, Corinna Preuße, Josefine Radke, Debora Pehl, Yves Allenbach, Udo Schneider, Eugen Feist, et al. "Sequestosome‐1 (p62) expression reveals chaperone‐assisted selective autophagy in immune‐mediated necrotizing myopathies." Brain Pathology 30, no. 2 (August 27, 2019): 261–71. http://dx.doi.org/10.1111/bpa.12772.
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Stenzel, W., H. H. Goebel, and E. Aronica. "Review: Immune-mediated necrotizing myopathies - a heterogeneous group of diseases with specific myopathological features." Neuropathology and Applied Neurobiology 38, no. 7 (November 14, 2012): 632–46. http://dx.doi.org/10.1111/j.1365-2990.2012.01302.x.
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Bondarenko, Inna B., Liubov A. Ponomareva, and Elena N. Popova. "Clinical types of lung disease in polymyositis and dermatomyositis." Clinical review for general practice 2, no. 4 (May 16, 2021): 34–39. http://dx.doi.org/10.47407/kr2021.2.4.00058.
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The idiopathic inflammatory myopathies are a group of rare, heterogeneous connective tissue disorders characterized by skeletal muscle inflammation. The four main forms of idiopathic inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and necrotizing immune-mediated myopathy. Each form of myositis, other than inclusion body myositis, can be associated with damage to many organs, including the lungs, heart, joints, and skin. The most often observed damage to the lung tissue with the development of interstitial lung disease, which occurs with or without myositis. The severity of the course varies from mild to severe, with rapid development of respiratory failure. Interstitial lung disease can be fatal in patients with myositis, therefore, it is necessary to assess the damage to the lung tissue in the early stages of the disease.
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Petreski, Tadej, Nejc Piko, Timotej Petrijan, Benjamin Dvoršak, Radovan Hojs, and Sebastjan Bevc. "Statin-Associated Necrotizing Myopathy Leading to Acute Kidney Injury: A Case Report." Case Reports in Nephrology and Dialysis 11, no. 2 (June 17, 2021): 129–35. http://dx.doi.org/10.1159/000515584.
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Statins or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are a mainstay of cardiovascular disease therapy. In addition to their lipid-lowering capabilities, they exhibit several pleiotropic effects. Their adverse reactions such as myalgias are not uncommon, but in rare cases, the resulting rhabdomyolysis can be fatal. Recently, more insight has been brought into the pathogenesis of statin-induced rhabdomyolysis, and immune-mediated necrotizing myopathies are diagnosed more frequently. We present a case of a female patient who was on chronic rosuvastatin therapy and developed necrotizing myopathy. The disease progressed to acute kidney and liver injury. We discontinued the drug, started supportive measures, and initiated renal replacement therapy with a high cutoff dialysis membrane once. Her recovery was prompt, with a normal control electromyography 2 weeks after discharge.
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Allenbach, Yves, Louiza Arouche-Delaperche, Corinna Preusse, Helena Radbruch, Gillian Butler-Browne, Nicolas Champtiaux, Kuberaka Mariampillai, et al. "Necrosis in anti-SRP+ and anti-HMGCR+myopathies." Neurology 90, no. 6 (January 12, 2018): e507-e517. http://dx.doi.org/10.1212/wnl.0000000000004923.
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ObjectiveTo characterize muscle fiber necrosis in immune-mediated necrotizing myopathies (IMNM) with anti–signal recognition particle (SRP) or anti–3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) antibodies and to explore its underlying molecular immune mechanisms.MethodsMuscle biopsies from patients with IMNM were analyzed and compared to biopsies from control patients with myositis. In addition to immunostaining and reverse transcription PCR on muscle samples, in vitro immunostaining on primary muscle cells was performed.ResultsCreatine kinase levels and muscle regeneration correlated with the proportion of necrotic fibers (r = 0.6, p < 0.001). CD68+iNOS+ macrophages and a Th-1 immune environment were chiefly involved in ongoing myophagocytosis of necrotic fibers. T-cell densities correlated with necrosis but no signs of cytotoxicity were detected. Activation of the classical pathway of the complement cascade, accompanied by deposition of sarcolemmal immunoglobulins, featured involvement of humoral immunity. Presence of SRP and HMGCR proteins on altered myofibers was reproduced on myotubes exposed to purified patient-derived autoantibodies. Finally, a correlation between sarcolemmal complement deposits and fiber necrosis was observed (r = 0.4 and p = 0.004). Based on these observations, we propose to update the pathologic criteria of IMNM.ConclusionThese data further corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in IMNM, highlighting humoral mechanisms as key players in immunity and myofiber necrosis.
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Trandafir, Andreea, Violeta Claudia Bonjincă, Delia Tulba, and Gelu Onose. "An odd case of immune-mediated necrotizing myopathy, complicated with sagittal, transverse and sigmoid sinus thrombosis." Balneo and PRM Research Journal 14, Vol.14, no. 4 (December 20, 2023): 630. http://dx.doi.org/10.12680/balneo.2023.630.
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INTRODUCTION: Immune-mediated necrotizing myopathy (IMNM) is a rare variant of immune-mediated inflammatory myopathy (IMIM) that exhibits a severe prognosis and is unresponsive to conventional treatment. (1,2)Notably, the incidence of immune-mediated inflammatory myopathies (IMIMs) is low, estimated at 1.16 to 19/million/year and only 3-6% of IMIMs are diagnosed as IMNM. (1,3–5). Systemic inflammation has been found to play a crucial role in promoting the onset of cerebral venous thrombosis. (6,7) MATERIAL AND METHODS: We present the case of a 46-years-old Chinese woman, without any known prior pathology, who was referred to the Rheumatology Department for symmetrical, proximal muscle weakness of the limbs, dysphagia for solid food, and weight loss (5 kg within 2 months). The pathologic clinical examination revealed itchy erythematous plaques on the posterior thoracolumbar region and signs of muscle weakness. Laboratory workup showed significant inflammatory syndrome, severe muscle and hepatic cytolysis syndrome, and positivity for thyroid-specific autoantibodies but with normal thyroid function, positivity for antinuclear antibodies (more precisely: SS-A, Ro-52, SS-B), and myositis antibodies (SRP, Ro-52, SAE1, PM-Scl, MDA5). The CT scan of the thoracic, abdominal, and pelvis showed fibrosis of the lungs, hepatic hypertrophy, and an enlarged uterus, further diagnosed by transvaginal ultrasound as adenomyosis. The positive diagnosis is immune-mediated necrotizing myopathy. Differential diagnoses included dermatomyositis, toxic/infectious myositis, hypothyroidism, and neuro-muscular diseases (5,8). The initial treatment was made with glucocorticoids (pulse therapy followed by oral therapy) and immunosuppressants (Mycophenolate Mofetil – stopped because of severe dyspepsia and myelosuppression). After five days of pulse therapy, the patient developed muscle weakness and paresthesia on the left side of the body, and the cerebral CT scan revealed sagittal, transverse, and sigmoid sinus thrombosis. Thrombophilia screening uncovered the positivity of the lupus anticoagulant. (9) RESULTS: The patient was treated with anticoagulants (low molecular weight heparin, and afterward Vitamin K antagonist), low doses of oral glucocorticoids, and immunosuppressant (Methotrexate), without any other adverse event. CONCLUSION: In the presence of the lupus anticoagulant, even though the antiphospholipid syndrome is not confirmed, the only anticoagulant therapy that has proven its efficacy is the Vitamin K antagonist. Immune inflammatory myopathies, like IMNMs, create a significant inflammatory status that leads to hypercoagulability and endothelial injury, which exposes collagen and tissue factors, promoting further platelet aggregation, and can even lead to cerebral thrombosis. (2,6)
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Silva, André Macedo Serafim, Eliene Dutra Campos, and Edmar Zanoteli. "Inflammatory myopathies: an update for neurologists." Arquivos de Neuro-Psiquiatria 80, no. 5 suppl 1 (May 2022): 238–48. http://dx.doi.org/10.1590/0004-282x-anp-2022-s131.
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ABSTRACT Idiopathic inflammatory myopathies (IIM) are a heterogenous group of treatable myopathies. Patients present mainly to the rheumatologist and neurologists, complaining of acute or subacute onset of proximal weakness. Extramuscular manifestations may occur, including involvement of the lungs, skin, and joints. Classically, the diagnosis used to be made based on the creatine kinase level increase, abnormalities in electroneuromyography and presence of inflammatory infiltrates in the muscle biopsy. Recently, the importance of autoantibodies has increased, and now they may be identified in more than half of IIM patients. The continuous clinicoseropathological improvement in IIM knowledge has changed the way we see these patients and how we classify them. In the past, only polymyositis, dermatomyositis and inclusion body myopathy were described. Currently, immune-mediated necrotizing myopathy, overlap myositis and antisynthetase syndrome have been considered the most common forms of IIM in clinical practice, increasing the spectrum of classification. Patients previously considered to have polymyositis, in fact have these other forms of seropositive IIM. In this article, we reviewed the new concepts of classification, a practical way to make the diagnosis and how to plan the treatment of patients suffering from IIM.
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Bonanno, S., and L. Maggi. "VP.43 Immune-mediated necrotizing myopathies: clinical-serological features of a large Italian cohort of patients." Neuromuscular Disorders 32 (October 2022): S83. http://dx.doi.org/10.1016/j.nmd.2022.07.174.
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San, Pyae Phyo, Nicholas Davies, Venkataramanan Srinivasan, Amrit Samra, Srinivasa Paluri, Simon Ubben, Prateek Kumar, Konstantinos Kiolachidis, Saikat Dhar, and Carl-Christian Moor. "175 A case series of anti-HMGCR immune mediated necrotizing myopathy: the West Midlands data." Journal of Neurology, Neurosurgery & Psychiatry 93, no. 9 (August 12, 2022): e2.134. http://dx.doi.org/10.1136/jnnp-2022-abn2.219.
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BackgroundAmong immune mediated myopathies, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) immune mediated necrotizing myopathy (IMNM) has been increasingly rec- ognised over the last two decades.Majority are associated with statin exposure and typically present with hovering high creatinine kinase (CK) and/or progressive proximal myopathy despite discontinuation of statin.MethodWe analysed the data of 18 cases of anti-HMGCR IMNM from West Midlands region from 2016 to 2022.Results16 had statin exposure. Only 1 was asymptomatic but the rest experienced progressive proximal myopathy. Strikingly, two-thirds reported dysphagia and 3 required Intensive Unit admissions.Anti-HMGCR antibody was positive in all cases. CK levels remained high (mean=9053IU/l) despite dis- continuation of statin. A trend of persistently high ALT, lowering creatinine and weight loss reflected smouldering muscle loss.The asymptomatic patient did not need treatment. Significant improvement/remission was achieved spontaneously in 1, with steroids or IVIG alone in 10 and with combined immunotherapies in the rest. 1 patient died despite improvement in CK level.ConclusionAnti-HMGCR IMNM, especially when associated with statin, responds well to immunotherapy. We suggest having a low threshold for checking anti-HMGCR antibody in patients with persistently high CK levels and/or proximal limb/pharyngeal muscle weakness, especially in the presence of statin exposure.
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Kolomeychuk, A. A. "Capabilities of magnetic resonance imaging in the diagnosis of idiopathic inflammatory myopathies." Rheumatology Science and Practice 61, no. 6 (January 1, 2024): 689–99. http://dx.doi.org/10.47360/1995-4484-2023-689-699.
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Idiopathic inflammatory myopathies (IIM) are a group of chronic autoimmune conditions characterized by proximal muscle weakness and potentially accompanied by a range of extramuscular clinical manifestations. There are subtypes of IIM including dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), overlap myositis (OM) with subgroup of anti-synthetase syndrome (ASS) and cancer-associated myositis. Taking into account rarity of the disease, heterogeneity of clinical presentation, difficulties in detection methods and interpretation of myositis associated autoantibodies (MAAs) and myositis specific autoantibodies (MSAs), search for objective imaging methods of muscle damage continues. This is important to definitive diagnosis, predicting subtypes of IIM and case follow-up. One of the most promising methods is magnetic resonance imaging (MRI). The aim of the review was to examine the role of MRI in assessment muscle damage, in particular, most typical MRI-findings and there features in different types of IIM with further clinical cases.
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Zerlotin, Roberta, Marco Fornaro, Mariella Errede, Patrizia Pignataro, Clelia Suriano, Maddalena Ruggieri, Silvia Colucci, Florenzo Iannone, Maria Grano, and Graziana Colaianni. "Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance." International Journal of Molecular Sciences 24, no. 3 (January 27, 2023): 2469. http://dx.doi.org/10.3390/ijms24032469.
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Dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necrosis with scarce inflammatory infiltrates. Muscle biopsies and laboratory tests are helpful in diagnosis, but currently, few biomarkers of disease activity and progression are available. In this context, we conducted a cohort study of forty-one DM and IMNM patients, aged 40–70 years. In comparison with control subjects, in the muscle biopsies of these patients, there was a lower expression of FNDC5, the precursor of irisin, a myokine playing a key role in musculoskeletal metabolism. Expectedly, the muscle cross-sectional areas of these patients were reduced, while, surprisingly, serum irisin levels were higher than in CTRL, as were mRNA levels of ADAM10, a metalloproteinase recently shown to be the cleavage agent for FNDC5. We hypothesize that elevated expression of ADAM10 in the skeletal muscle of DM and IMNM patients might be responsible for the discrepancy between irisin levels and FNDC5 expression. Future studies will be needed to understand the mechanisms underlying exacerbated FNDC5 cleavage and muscle irisin resistance in these inflammatory myopathies.
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Xiong, Anji, Guancui Yang, Zhuoyao Song, Chen Xiong, Deng Liu, Yu Shuai, Linqian He, Liangwen Zhang, Zepeng Guo, and Shiquan Shuai. "Rituximab in the treatment of immune-mediated necrotizing myopathy: a review of case reports and case series." Therapeutic Advances in Neurological Disorders 14 (January 2021): 175628642199891. http://dx.doi.org/10.1177/1756286421998918.
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Immune-mediated necrotizing myopathy (IMNM) is a group of immune-related myopathies characterized by progressive proximal muscle weakness, extremely high serum creatine kinase (CK) levels, and necrotic muscle fibers with a relative lack of inflammation. Treatment of IMNM is challenging, with most cases refractory to high-dose steroids in combination with multiple immunotherapies. The role of rituximab (RTX) for IMNM has been explored in isolated case reports and small series. The aim of this article was to perform a literature review of patients with IMNM treated with RTX and to evaluate RTX efficacy and safety. A total of 34 patients with IMNM were reviewed: 52.9% (18/34) with anti-signal recognition particle (SRP) antibodies and 47.1% (16/34) with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies. Patient age at onset varied from 11 years to 81 years (mean 41 years). The majority of patients presented as a severe proximal muscle weakness and the peak level of CK varied from 3900 IU/L to 56,000 IU/L (mean 18,440 IU/L). Prior to RTX administration, all patients were treated with high-dose steroids and most were treated with multiple immunotherapies. The reason for initiating RTX was that 64.7% (22/34) of patients showed no improvement after previous treatments, and 35.3% (12/34) of patients relapsed when attempting to wean steroids or other immunosuppressive agents. With regard to RTX efficacy, 61.8% (21/34) of patients presented a response to RTX. Our data may support the use of RTX as an effective treatment strategy against IMNM resistant to steroids and multiple immunotherapies. Meanwhile, RTX as a first-line therapy could be a choice in IMNM, particularly in African Americans with anti-SRP antibody-positive subsets. ANA, antinuclear antibody; CK, creatine kinase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; IMNM, immune-mediated necrotizing myopathy; MAC, membrane attack complex; MHC-I, major histocompatibility complex-I; RTX, rituximab; SRP, signal recognition particle.
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de Souza, Jean Marcos, Leonardo Santos Hoff, and Samuel Katsuyuki Shinjo. "Intravenous human immunoglobulin and/or methylprednisolone pulse therapies as a possible treat-to-target strategy in immune-mediated necrotizing myopathies." Rheumatology International 39, no. 7 (February 18, 2019): 1201–12. http://dx.doi.org/10.1007/s00296-019-04254-3.
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de Oliveira, Diego Sales, Isabela Bruna Pires Borges, Suely Kazue Nagahashi Marie, Antonio Marcondes Lerario, Sueli Mieko Oba-Shinjo, and Samuel Katsuyuki Shinjo. "Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis." Archives of Rheumatology 38, no. 2 (October 21, 2022): 189–99. http://dx.doi.org/10.46497/archrheumatol.2023.9257.
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Objectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs). Patients and methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8±2.3 years; range, 43 to 54 years), six with immune mediated necrotizing myopathy (IMNM; 3 males, 3 females; mean age: 58.5±10.6 years; range, 46 to 74 years), and 10 control individuals (CTRL group; 4 males, 6 females; mean age: 48.7±3.9 years; range, 41 to 56 years) were included. The muscle biopsy before and after the intervention was performed to evaluate the intramuscular lipid content. Patients underwent a combined exercise training program for 12 weeks. Skeletal muscle gene expression was analyzed and the DM versus CTRL group, DM pre- and post-, and IMNM pre- and post-intervention were compared. Results: The DM group had a higher intramuscular lipid content in type II muscle fibers compared to the CTRL group. After the intervention, there was a reduction of lipid content in type I and II fibers in DM and IMNM group. The CTRL group showed a significantly higher expression of genes related to insulin and lipid oxidation pathways (AMPKβ2, AS160, INSR, PGC1-α, PI3K, and RAB14) compared to the DM group. After exercise training, there was an increase gene expression related to insulin pathway and lipid oxidation in DM group (AMPKβ2, AS160, INSR, PGC1-α, PI3K, and RAB14) and in IMNM group (AKT2, AMPKβ2, RAB10, RAB14, and PGC1-α). Conclusion: Exercise training attenuated the amount of fat in type I and II muscle fibers in patients with DM and IMNM and increased gene expression related to insulin pathways and lipid oxidation in DM and IMNM. These results suggest that exercise training can improve the quality and metabolic functions of skeletal muscle in these diseases.
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Kurashige, Takashi, Tomomi Murao, Naoko Mine, Tomohito Sugiura, Yukiko Inazuka, Kazuya Kuraoka, Tetsuya Takahashi, Hirofumi Maruyama, and Tsuyoshi Torii. "Anti-HMGCR Antibody-Positive Myopathy Shows Bcl-2-Positive Inflammation and Lymphocytic Accumulations." Journal of Neuropathology & Experimental Neurology 79, no. 4 (February 25, 2020): 448–57. http://dx.doi.org/10.1093/jnen/nlaa006.
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Abstract Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p < 0.001). In 5 patients with anti-HMGCR antibodies, Bcl-2-positive lymphocytes formed lymphocytic accumulations, which were not observed in other IIMs. Low-density lipoprotein cholesterol levels were not increased except for patients with Bcl-2-positive lymphocytic accumulations (p = 0.010). Bcl-2 and CCR4 lymphocyte infiltrations could be a pathological characteristic of anti-HMGCR antibody-positive IMNM.
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Matsuda, Nozomu, Shunsuke Kobayashi, Osamu Hasegawa, Kenji Yoshida, Hitoshi Kubo, Yoshikazu Ugawa, and Kazuaki Kanai. "Subclinical involvement of the trunk muscles in idiopathic inflammatory myopathies." Acta Radiologica Open 11, no. 2 (February 2022): 205846012210757. http://dx.doi.org/10.1177/20584601221075796.
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Background Whole-body magnetic resonance imaging (WB-MRI) is a useful tool for revealing the disease-specific distribution of affected muscles and clinically asymptomatic muscle involvements in idiopathic inflammatory myopathies (IIMs). Purpose To examine inflammatory changes in the systemic skeletal muscles, including the thoracoabdominal trunk, in IIMs using WB-MRI. Material and Methods We prospectively obtained WB-MRI axial images from 10 patients with IIMs, including antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis, and myopathy associated with antimitochondrial antibody. We evaluated 108 systemic skeletal muscles in short-tau inversion recovery (STIR) images and rated changes in signal intensity using a semiquantitative scale. Correlations between STIR sum score, peak creatine kinase (CK) and muscle strength were examined. We also investigated the correlation between STIR sum score within the thoracoabdominal trunk and forced vital capacity. Results High STIR signal changes were frequently identified in asymptomatic and routinely unexamined muscles. Thoracoabdominal trunk muscles were frequently involved in ASS and IMNM. Peak CK was positively correlated with the STIR sum score ( R2 = 0.62, p < .01). There was no significant correlation between the STIR sum score within the thoracoabdominal trunk and forced vital capacity. Conclusion WB-MRI can detect subclinical muscle inflammation in the systemic muscles including the trunk muscles. STIR sum score is positively correlated with serum peak CK level; therefore, it could be a biomarker of overall muscle inflammation.
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Lee, Seung-Ah, Hyun Joon Lee, Bum Chun Suh, Ha Young Shin, Seung Woo Kim, Byeol-A. Yoon, Young-Chul Choi, and Hyung Jun Park. "Clinical significance of anti-NT5c1A autoantibody in Korean patients with inflammatory myopathies." PLOS ONE 18, no. 4 (April 14, 2023): e0284409. http://dx.doi.org/10.1371/journal.pone.0284409.
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To explore the clinical significance of anti-cytosolic 5’-nucleoditase 1A (NT5c1A) antibody seropositivity in inflammatory myopathies, we measured anti-NT5c1A antibodies and analyzed their clinical features. Anti-NT5c1A antibodies were measured in the sera of 103 patients with inflammatory myopathies using an enzyme-linked immunosorbent assay. Positivity for anti-NT5c1A antibody was found in 13 (12.6%) of 103 patients with inflammatory myopathy. Anti-NT5c1A antibody was most frequently identified in patients with inclusion body myositis (IBM) (8/20, 40%), followed by dermatomyositis (2/13, 15.4%), immune-mediated necrotizing myopathy (2/28, 7.1%), and polymyositis (1/42, 2.4%). In eight patients with the anti-NT5c1A antibody-seropositive IBM, the median age at symptom onset was 54 years (interquartile range [IQR]: 48–57 years), and the median disease duration was 34 months (IQR: 24–50 months]. Knee extension weakness was greater than or equal to hip flexion weakness in eight (100%) patients, and finger flexion strength was less than shoulder abduction in three (38%) patients. Dysphagia symptoms were found in three (38%) patients. The median serum CK level was 581 IU/l (IQR: 434–868 IU/L]. Clinically significant differences were not found between anti-NT5c1A antibody-seropositive and seronegative IBM groups with respect to gender, age at symptom onset, age at diagnosis, disease duration, serum CK values, presence of other autoantibodies, dysphagia, and the pattern of muscle impairment. Although anti-NT5c1A antibody is known to be associated with IBM, seropositivity has also been noted in non-IBM inflammatory myopathies, and is insufficient to have clinical significance by itself. These findings have important implications for interpreting anti-NT5c1A antibody test results as the first study in Korea.
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Meyer, A., L. Messer, J. Goetz, B. Lannes, J.-C. Weber, B. Geny, JE Gottenberg, and J. Sibilia. "Immune-mediated necrotizing myopathies are serologically heterogeneous and autoantibodies may predict their clinical phenotype: two cases associated with anti-Pl7 antibodies." Scandinavian Journal of Rheumatology 43, no. 1 (January 2014): 81–83. http://dx.doi.org/10.3109/03009742.2013.864421.
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Danielsson, Olof, Björn Lindvall, Istvan Gati, and Jan Ernerudh. "Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients." Journal of Rheumatology 40, no. 7 (May 1, 2013): 1173–82. http://dx.doi.org/10.3899/jrheum.120804.
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Objective.Insights into the pathogenesis of inflammatory myopathies have led to new diagnostic methods. The aims of our study were (1) to evaluate the consequences of using the classification of Amato/European Neuromuscular Centre Workshop (ENMC) compared to that of Bohan and Peter; and (2) to evaluate any diagnostic benefit in using an extended pathological investigation.Methods.From a consecutive retrospective database, we evaluated 99 patients for classification. Patients with inclusion body myositis (IBM) were classified according to Griggs,et al. In addition to routine stainings and immunohistochemistry, a multilevel serial sectioning procedure was performed on paraffin-embedded material, to identify scarce pathological findings.Results.Classification according to Bohan and Peter could be performed for 83 of the 99 patients, whereas only 60 patients met the Amato/ENMC criteria, the latter resulting in the following diagnostic groups: IBM (n = 18), nonspecific myositis (n = 14), polymyositis (n = 12), dermatomyositis (n = 10), dermatomyositis sine dermatitis (n = 5), and immune-mediated necrotizing myopathy (n = 1). Most of the Amato/ENMC diagnostic groups harbored patients from several of the Bohan and Peter groups, which included a substantial group lacking proximal muscle weakness. The serial sectioning procedure was essential for classification of 9 patients (15%), and led to a more specific diagnosis for 13 patients (22%) according to Amato/ENMC.Conclusion.The classification of Amato/ENMC was more restrictive, forming groups based on clinical criteria and specified myopathological findings, which clearly differed from the groups of the Bohan and Peter classification. An extended pathological investigation increased the diagnostic yield of a muscle biopsy and highlights the quantity and specificity of certain pathological findings.
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Khelkovskaia-Sergeeva, A., O. Desinova, M. Starovoytova, L. P. Ananyeva, M. Cherkasova, and R. Shayakhmetova. "AB0444 СLINICAL-IMMUNOLOGICAL CHARACTERISTICS OF PATIENTS WITH INFLAMMATORY MYOPATHIES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1249.3–1250. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3101.
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Background:Inflammatory disorders of the skeletal muscle include polymyositis (PM), dermatomyositis (DM), amyopathic dermatomyositis ADM, (immune mediated) necrotizing myopathy (NM), overlap syndrome with myositis (overlap myositis, OM) and including anti-synthetase syndrome (ASS).The detection of myositis-specific antibodies, the clinical effect of which remains to be determined, may be of great importance for diagnosis.Objectives:To study clinical-immunological characteristics of patients with inflammatory myopathies.Methods:57 pts were enrolled in this study: 28 (47%) pts were diagnosed with DM, 14 (23%) pts – OM, 5(8%) pts – PM, 5 (8%) pts-NM, 4 (7%) pts-ADM, 1 (2%)- ACC. Duration of disease in average 11,29 (2-48) month. Standard clinical examination and laboratory immunological evaluation including myositis-specific autoantibodies were performed.Results:There were 3 age groups: 18-39 years old – 16 (28%) pts, 40-49 yo – 28 (49%) pts and > 60 yo – 13 (33%) pts. Symptoms of myositis were muscle weakness 57 (100%) pts, dysphagia 29 (51%) pts, arthritis -12 (21%) pts, Raynaud’s phenomenon 21 (37%) pts, skin lesions- 37 (65%) pts (Gottron signs- 7 (12%) pts, digital ulcers -11 (19) pts, panniculitis – 6(11%) pts, hand of mechanic 16(28%) pts). MMT 8 was 55,57 (SD 18,49) (20-80) score. Clinical features of myositis were myocarditis 8 (14%) pts and arrhythmia 9 (16%) pts, interstitial lung disease 20 (35%) pts, esophageal involvement 29 (51%) pts of them 5 (9%) pts needed enteral feeding. 2 (4%) pts had oncopathology. СК was increased in 49 (86%) pts: < 10 N -15 (26%) pts, >10 N – 28 (49%) pts, > 50 N – 6 (11%). ANA positive - in 39 (70%) pts. Antibodies identified in 25(44%) pts: Pm-Scl 7 (12%) pts, PL-7 1 (2%), Mi-2 10 (17,5%), Ku 2 (3,5%) pts, AMA-M2 2 (2%)pts, a-SRP 4 (7%) and SS-A/Ro-52 13 (23%), SS-A/Ro-60 2 (3%) pts.Conclusion:The group of inflammatory myopathies is characterized by clinical and immunological heterogeneity. Finding antibodies specific for myositis can help diagnose the disease.Disclosure of Interests:None declared.
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Turner, Richard Myles, and Munir Pirmohamed. "Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components." Journal of Clinical Medicine 9, no. 1 (December 20, 2019): 22. http://dx.doi.org/10.3390/jcm9010022.
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Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy and pro-apoptotic signalling. Rare variants in several metabolic myopathy genes including CACNA1S, CPT2, LPIN1, PYGM and RYR1 increase myopathy/rhabdomyolysis risk following statin exposure. The immune system is implicated in both conventional statin intolerance/myotoxicity via LILRB5 rs12975366, and a strong association exists between HLA-DRB1*11:01 and anti-HMGCR positive myopathy. Epigenetic factors (miR-499-5p, miR-145) have also been implicated in statin myotoxicity. SRM remains a challenge to the safe and effective use of statins, although consensus strategies to manage SRM have been proposed. Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.
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Musset, Lucile, Yves Allenbach, Olivier Benveniste, Olivier Boyer, Xavier Bossuyt, Chelsea Bentow, Joe Phillips, et al. "Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study." Autoimmunity Reviews 15, no. 10 (October 2016): 983–93. http://dx.doi.org/10.1016/j.autrev.2016.07.023.
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Pepper, Elizabeth, Lilian Vilar, and Ian M. Ward. "Clinical Characteristics and Prognostic Value of Ro52/SSA Antibodies in Idiopathic Inflammatory Myopathies." JCR: Journal of Clinical Rheumatology 29, no. 7 (October 2023): 347–53. http://dx.doi.org/10.1097/rhu.0000000000002015.
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Background/Purpose Anti-Ro52 are myositis-associated antibodies found in idiopathic inflammatory myopathies (IIMs). This chart review aims to evaluate the frequency, significance, and associated clinical characteristics of Ro52/SSA positivity in IIM patients. Methods We performed a chart review of IIM patients diagnosed between January 2006 and December 2020. All patients met either the 1975 Bohan and Peter or the European League Against Rheumatism/American College of Rheumatology classification criteria for probable or definite myositis. Demographics, clinical and serologic parameters, treatments, and outcomes were compared in patients with anti-Ro52/SSA antibodies and patients without anti-Ro52/SSA antibodies. Results One hundred eighty-nine patients with IIM were tested for either Ro52 or SSA, with 45 positive for Ro52/SSA (23.8%). Patients with IIM and Ro52/SSA+ were younger at age at onset of disease (44.8 vs. 51.2 years, p = 0.008). Ro52/SSA+ was more common in antisynthetase syndrome (p < 0.001; odds ratio [OR], 4.44; 95% confidence interval [CI], 2.11–9.33) and not frequently identified in clinically amyopathic dermatomyositis (CADM) (p = 0.02; OR, 0.13; 95% CI, 0.02–0.96) or immune-mediated necrotizing myopathy (p = 0.003; OR, 0.14; 95% CI, 0.03–0.63). Of the extraskeletal muscle manifestations, interstitial lung disease (ILD) was strongly associated with Ro52/SSA+ (p < 0.001; OR, 6.61; 95% CI, 3.15–13.86), as was dysphagia (p = 0.006; OR, 2.73; 95% CI, 1.31–5.71). Interstitial lung disease pattern and pulmonary function testing impairment did not differ based on antibody status. There was no significant difference in outcomes between groups. Conclusion In this myositis cohort, Ro52/SSA+ was present in nearly one-fourth of the population and had a strong association with the antisynthetase syndrome subtype, ILD, and dysphagia. Although these disease manifestations are associated with significant morbidity, in our cohort, they were not associated with increased mortality or more severe ILD.
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Corrales-Selaya, C., D. Martínez-López, D. Prieto-Peña, J. L. Martín-Varillas, and R. Blanco. "AB0874 EPIDEMIOLOGY AND CLINICAL FEATURES OF IDIOPATHIC INFLAMMATORY MYOPATHIES IN SINGLE REGION IN NORTHERN SPAIN." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1651–52. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2852.
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BackgroundIdiopathic inflammatory myopathies (IIM) are a heterogeneous group of disorders characterized by proximal muscle weakness and inflammation. The main subtypes of IIM are dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), immune-mediated necrotizing myopathy (IMNM) and antisynthetase syndrome (ASS). Prevalence and incidence vary depending on the geographic location.ObjectivesTo describe the epidemiological and clinical features of IIM in a single region in northern Spain.MethodsWe included all consecutive patients diagnosed with IIM in the region of Cantabria, excluding IBM, from January 2000 to December 2022.IIM was diagnosed by expert rheumatologists according toa) EULAR/ACR 2017 classification criteria of IIM in PM and DM,b) Definition of the European Neuromuscular International Workshop 2016 in IMNM andc) Connor’s criteria in ASS.Data regarding demographics features, clinical findings, laboratory tests and treatments were extracted from the patients’ clinical records.ResultsWe included a total of 63 patients, mean age at diagnosis 52.1±19.3 years. Most of the patients were women (n=44, 69.8%). Main features are shown inTABLE 1.Prevalence of IIM was 10.8/100.000 population. The incidence rate was 4.9 cases per million persons per year. An upward trend in annual incidence was observed from 1.7 in 2000 to 15.4 per million in 2018(FIGURE 1).The most common IIM subtype was DM (n=34, 54%).Gottron papules, muscle weakness and Interstitial lung disease were the most frequent manifestations in DM, IMNM and ASS group, respectively.The most frequent autoantibody was anti-Ro 52 (n=12, 19%), however in 28 patients (44.4%) none was detected.Most used treatments were glucocorticoids (n=61, 96.8%), azathioprine (n=30, 47.6%), intravenous immunoglobulins (n=29, 46%) and rituximab (n=29, 46%).ConclusionWe describe the prevalence, incidence rate, clinical features and main treatments used in IIM in our area. An upward trend in annual incidence was observed in our study.Table 1.Main demographic, clinical features, laboratory findings and treatments in 63 patients diagnosed with IIM.Dermatomyositis (n=34)Polymyositis (n=5)Immune-mediated Necrotizing Myopathy (n=9)Antisynthetase Syndrome (n=15)DM (n=34)PM (n=5)IMNM (n=9)ASS (n=15)Age at diagnosis (years), mean ± SD53.9 ± 18.6. (*) DMJ 5.5 ± 1.754.8 ± 11.664.5 ± 752.7 ± 11.7LDH mg/dl, mean ± SD489.5 ± 223.71360 ± 992.7654 ± 258343.6 ± 151.2Sex (women), n (%)26 (76.5)3 (60)6 (66.7)9 (60)AntiJo1/Mi2/MDA5, n (%)1 (2.9)/1 (2.9)/3 (8.8)2 (40)/0/ 004 (26.7)/ 0/ 0Dyslipidemia, n (%)10 (29.4)2 (40)9 (100)4 (26.7)PL7/PL12/EJ, n (%)0/0/1 (2.9)007 (46.7)/ 4 (26.7)/ 0Hypertension, n (%)9 (26.5)1 (20)7 (77.8)1 (6.66)HMGCR/ Ro52, n (%)0/3 (8.8)09 (100)/ 00/ 8 (53.3)Diabetes Mellitus, n (%)4 (11.8).7 (77.8).Edema/Atrophy RMI, n (%)12 (100)/ 2 (16.7)2 (100)/ 05 (55.6)/ 3 (33.3)1(11.1)/ 0Cancer, n (%)6 (17.7)...Oral/ Intravenous Corticosteroids, n (%)34 (100)/ 18 (52.9)5 (100)/ 1 (20)7 (77.8)/ 3 (33.3)15 (100)/ 5 (33.3)Muscle weakness, n (%)26 (76.5)3 (60)9 (100)3 (20)Methotrexate/ Azathioprine, n (%)15 (44.1)/ 15 (44.1)2 (40)/ 4 (80)3 (33.3)/ 3 (33.3)2 (13.3)/ 8 (53.3)Myalgia, n (%)11 (32.4)2 (40)4 (44.4)4 (26.7)Mycophenolate/ Cyclophosphamide n (%)4 (11.8)// 4 (11.8)0/ 1 (20).9 (60)/ 4 (26.7)Gottron papule/Sign/Heliothrope rash, n (%)27 (79.4)/25 (73.5)/11(32.3)..1 (6.7)/./.Calcineurin Inhibitors, n (%)5 (14.7)/ 4 (11.8)..2 (13.3)Arthritis/ Raynaud, n (%)9 (26.5)/ 3 (8.8)1 (20)/ 1 (20).4 (26.7)/ 9 (60)Hydroxychloroquine, n (%)15 (44.1)..3 (20)Interstitial Lung Disease, n (%)5 (14.7)2 (40).14 (93,3)Intravenous Immunoglobulins, n (%)21 (61.8)1 (20)6 (66.7)1 (6.7)Dysphagia/ Calcinosis, n (%)15 (44.1)/ 6 (17.6).3 (33.3)/.2 (13.3)/.Rituximab, n (%)13 (38.2)1 (20)3 (33.3)12 (80)Creatin-Kinase (UI/L), median [IQR]533 [226.5-1325.5]3360 [3158-4100]4977 [3273-9271]57 [35-550]Figure 1.Annual incidence of IIM from 2000 to 2022.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsCristina Corrales-Selaya: None declared, David Martínez-López: None declared, Diana Prieto-Peña Grant/research support from: UCB Pharma, Roche, Sanofi, Pfizer, Jansen, Amgen, AbbVie, Novartis,and Lilly., José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Celgene, Janssen, and UCB Pharma., Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, lilly, Bristol-Myers, Janssen, Galapagos and MSD., Consultant of: Abbvie, Pfizer, Roche, lilly, Bristol-Myers, Janssen and MSD., Grant/research support from: Abbvie, MSD, novartis and Roche.
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Rosa, C., K. Chaudhuri, T. Blake, T. Potter, and S. Banerjee. "AB0888 CLINICAL CHARACTERISTICS OF ANTI HMGCOA REDUCTASE ANTIBODY POSITIVE IMMUNE MEDIATED NECROTIZING MYOPATHY: CASE SERIES OF 5 PATIENTS FROM A TERTIARY CENTRE." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1659.1–1659. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5438.
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BackgroundImmune Mediated Necrotizing Myopathy is a type of autoimmune myopathy which is commonly associated with the use of statins. Common antibody detected in these patients would be HMGCoA reductase antibodies. Significant muscle necrosis with paucity of cellular infiltration is the characteristic histological feature.ObjectivesTo describe clinical and therapeutic characteristics of anti HMGCoA reductase antibody positive necrotizing myopathy.MethodsCohort of patients with myositis were selected. The myositis antibody panel was assessed and patients with HMGCoA reductase antibody were selected. Diagnosis was made based on the 2017 EULAR/ ACR criteria[1]. Clinical manifestations, statin use, investigations, treatment offered, and outcome were described.ResultsOf the selected 5 cases, all the patients were middle aged with 3 males and 2 female patients. All 5 patients were on statins and 3 of them were on statins for many years prior to development of myopathy. None of the cases had other systemic involvement including dermatological or cardiac involvement.All 5 patients were positive for HMGCOA reductase antibodies. One patient had CLL which never required any specific treatment and another was incidentally found to have an atypical lipoma which was managed conversatively. All patients required steroids with either Methotrexate and Mycophenolate mofetil. Three of the patients received intravenous immunoglobulin therapy with good response. All of the patients had made a complete recovery though 2 of them required prolonged rehabilitation.Case12345GenderFemaleMaleMaleFemaleMaleAge (Years)5463665754Statin useSimvastatin and then Atorvastatin (10 years of statin use)Simvastatin changed to Atorvastatin/ Pravastatin(6 years of statins prior to myopathy)Atorvastatin 20mg daily (for 2 years) and dose increased 8 months prior to onset of myopathyAtorvastatin 10 mg stopped 6 months before IMNM due to myalgiaAtorvastatin for 4 yearsMuscles involvedProximal muscle weaknessNo proximal muscle weaknessProximal muscle weaknessProximal muscle weaknessIncluding neck flexors, dysphagia and respiratory failureProximal muscle weakness in lower limbsOther Manifestations - skin, myocarditisNoneNoneNoneNoneNoneCK on presentation4341104919383316668009Inflammatory markersESR 66CRP <3ESR 24CRP 13ESR 113CRP 60ESR 62CRP 100ESR 20CRP 140ANANegativeNegativeNegativeNegativeNegativeAnti HMGCoA reductase antibodies>200359.5>200Positive>200Associated conditionsCLLNoneNoneNoneAtypical lipomaEMG patternMyopathicNo myopathy/ myositisMyositisMyositisMyopathicBiopsyNecrosis with minimal inflammationRecovery phase of necrotising myopathyNecrotising features with foci of sparse inflammatory cellsNecrotic and regenerative fibres, paucity of cellular infiltratesNot doneMRIMuscle oedema of thighsNot doneProximal muscle oedemaMuscle oedema of thighsMuscle oedema in thighsTreatmentSteroidsOralOralIV followed by oralIV followed by oralOralDMARDNone – patient declinedMMF & IvIGMethotrexateIvIGCyclophosphomideIvIGMaintenance with Mycophenolate mofetilCombination of Mycophenolate mofetil and methotrexateOutcomeCK441906464124Muscle powerThighs - +4/5Shoulders 5/5NormalNormalHip flexors – 4/5NormalConclusionStatin induced necrotising myopathy patients could develop the disease after many years of statin therapy. It is possible that changes in the drug or the dose could act as a precipitant. This cohort of patients tend to be treated with intravenous immunoglobulin in addition to other conventional treatments. In spite of having very severe disease at the onset, with timely and appropriate immunosuppression and rehabilitation patients appeared to have a good outcome.Reference[1]Lundberg IE, Tjärnlund A, Bottai M. 2017 EULAR/ ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.Ann Rheum Dis. 2017;76(12):1955-1964. doi:10.1136/annrheumdis-2017-211468Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Robert, M., L. Gallay, P. Petiot, T. Fenouil, L. Lessard, L. Perard, J. Svahn, et al. "POS0862 INAUGURAL DROPPED HEAD SYNDROME AND CAMPTOCORMIA IN INFLAMMATORY MYOPATHIES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 725.1–725. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1605.
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BackgroundThe idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases that can affect the muscles, skin, lungs, heart, and joints. Increase knowledge about histopathological findings, clinical manifestations and auto-antibodies have allowed further novel classification of IIMs. Today, the main IMs subgroups are: dermatomyositis (DM), inclusion body myositis (IBM), immune-mediated necrotizing myopathies (IMNM), overlap myositis (OM) and immune-checkpoint inhibitor-related myositis (ICIrm). Axial muscle involvement results either in a “Dropped Head Syndrome (DHS)”, with a marked weakness of the neck extensors, or in a camptocormia (CC), with a weakness of the thoracolumbar paraspinal muscles. This atypical presentation is poorly described in the course of IMs while it may results in a major disability, and may lead to myositis diagnosis delay.ObjectivesThis study aimed to describe IMs revealed by DHS and/or CC. Secondary outcomes were to define subgroups of patients according to clinical, biological and histopathological characteristics. Then, the effects of treatments used were analyzed.MethodsA historical cohort was designed using the register MYOLYON which includes all IMs followed at the University Hospital of Lyon (France) between 2000 and 2021. All patients with IM revealed by DHS and/or CC and having an histologically proven IMs were included, after exclusion of alternative (e.g., myasthenia gravis, motoneuron disease). Clinical, biological, immunological, histopathological data as well as outcome and care were collected through a standardized form. Agreement for the study was obtained from the French Ministry of the Research and the study was approved by the Local Research Ethics Committee.ResultsTwenty-two patients were fully characterized: DM (n=4), IBM (n=7), OM (n=8), ICIrm (n=2) and one myositis with anti-Hu antibodies. Two groups of patients were identified according to the age at first symptoms and to the type of muscle axial involvement (e.g, DHS and/or CC). Before the age of 70 (n=13/22), the two most common diagnoses (n=11/13) were DM (n=4/4) and OM (n=7/8). Axial muscle involvement was diffuse (DHS and CC) in 10/13 patients. After 70 years old (n=9/22), there were a majority of IBM (n=6/9) and all cases of ICIrm (n=2). Axial involvement was restricted to one group of muscles (DHS or CC) in 5/9 patients. Finally, 77% (17/22) of patients had refractory disease and required a second line treatment (e.g, immunoglobulins). All of these results are summarized in the Figure 1.Figure 1.ConclusionWhile IM diagnosis is challenging in the presence of inaugural axial involvement, these results highlight the subset of IM to be considered according to the age at first symptoms and the type of axial involvement (e.g., DHS and/or CC).References[1]Mariampillai, K. et al. Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies. JAMA Neurol75, 1528-1537 (2018).[2]Landon-Cardinal, O. et al. Recognising the spectrum of scleromyositis: HEp-2 ANA patterns allow identification of a novel clinical subset with anti-SMN autoantibodies. RMD Open6 (2020).[3]Suarez, G.A. & Kelly, J.J., Jr. The dropped head syndrome. Neurology42, 1625-1627 (1992).[4]Oerlemans, W.G. & de Visser, M. Dropped head syndrome and bent spine syndrome: two separate clinical entities or different manifestations of axial myopathy? J Neurol Neurosurg Psychiatry65, 258-259 (1998).Disclosure of InterestsNone declared
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Lopez, B., C. Fuego-Varela, J. Galloway, and P. Gordon. "THU0335 IS CARDIOVASCULAR RISK IN INFLAMMATORY MYOPATHIES UNDERESTIMATED?" Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 398.2–399. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4926.
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Background:Inflammatory myopathies (IIM) comprise a heterogeneous group of rare connective tissue diseases (CTD) which can occur in any age group and in association with other autoimmune CTD. Extramuscular manifestations, including cardiac involvement, are common and may occur in the absence of muscle symptoms.The link between inflammation and atherosclerosis has been well established in other immune-mediated diseases suggesting that atherosclerosis in these conditions is driven by disease activity rather than traditional cardiovascular (CV) risk factors. Large observational studies have identified atherosclerotic cardiovascular events (CVE) as one of the leading causes in mortality in IIM but to date there are no specific recommendations for patients with IIM beyond the general guidelines for management of CV risk in the general population.A systematic review of the literature available was carried out, identifying six observational studies based on data collected from local or national healthcare databases. All six studies showed an increased incidence of MI and/or stroke compared to the general population, with a suggestion in some of them that this incidence was particularly high in the first few years after disease onset.Objectives:To establish if the incidence of atherosclerotic CVE in an IIM cohort is higher than expected when compared to QRISK2 predicted risk, and if so to determine if this risk is influenced by disease duration, gender, disease phenotype or ethnicity.Methods:Patients referred to the Myositis clinic at King’s College Hospital (KCH) were identified, excluding patients with Inclusion Body Myositis, overlap diagnoses with other CTD or prior atherosclerotic CVE. Only patients fulfilling ACR/EULAR criteria for IIM and under follow up at KCH (Denmark Hill site) were included in the study. Retrospective data was gathered by reviewing electronic patient records.Results:327 patients were identified through the Myositis Departmental database. After applying exclusion criteria the final dataset consisted of 159 patients (114 female, 71.7%), including dermatomyositis (82 patients), polymyositis (49 patients), Clinically Amyopathic Dermatomyositis (7 patients), anti-synthetase syndrome (12 patients) and necrotizing myopathy (9 patients). 81 patients were white (50.9%). Mean age of entry in the study was 49.1 years (SD 15.2) for women and 49.7 years (SD 12.2) for men. The mean follow up time was 2.61 years with a median time of 2.78 years (IQR 1.64-2.85). The mean disease duration was 6.77 years for the whole cohort with a median time of 4.61 years (IQR 2.43-9.07).The incidence rate of atherosclerotic CVE was 16.3/1000 patient-years (95% CI: 8.8-30.3), twice as high as expected by QRISK2. Analysis showed statistical difference with males (RR=6.49, p=0.002) and white patients (RR=5.04, p=0.02) although the statistical significance for white ethnicity was lost after adjusting for age and gender. Statistical analysis showed association between disease duration and higher incidence of atherosclerotic CVE, with a rate reduction of 0.7 per year from disease onset (p=0.01) after adjusting for age and gender.Fig. 1.Atherosclerotic risk by disease durationFig. 2.Kaplan-Meier survival plot to atherosclerotic eventConclusion:Our results suggest that atherosclerotic cardiovascular risk in inflammatory myopathies is underestimated, particularly early on the disease. Based on our results we would recommend a low threshold for primary prevention of atherosclerosis including the use of statins particularly for the first year after diagnosis.Disclosure of Interests:None declared
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Uruha, Akinori, Atsuko Nishikawa, Rie S. Tsuburaya, Kohei Hamanaka, Masataka Kuwana, Yurika Watanabe, Shigeaki Suzuki, Norihiro Suzuki, and Ichizo Nishino. "Sarcoplasmic MxA expression." Neurology 88, no. 5 (December 30, 2016): 493–500. http://dx.doi.org/10.1212/wnl.0000000000003568.
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Objective:To evaluate the diagnostic value of myxovirus resistance A (MxA) expression in the cytoplasm of myofibers in the diagnosis of dermatomyositis (DM).Methods:We assessed the sensitivity and specificity of the sarcoplasmic expression of MxA in muscles with DM by immunohistochemistry in consecutive cases of DM (n = 34) and other idiopathic inflammatory myopathies (n = 120: 8 with polymyositis, 16 with anti–tRNA-synthetase antibody–associated myositis, 46 with immune-mediated necrotizing myopathy, and 50 with inclusion body myositis) and compared them with conventional pathologic hallmarks of DM, including perifascicular atrophy (PFA) and membrane attack complex (MAC) deposition on endomysial capillaries.Results:The sensitivity and specificity of sarcoplasmic MxA expression were 71% and 98%, respectively. While the specificity was almost comparable to that of PFA and capillary MAC deposition, the sensitivity was higher, with PFA showing 47% sensitivity and 98% specificity and capillary MAC deposition showing 35% sensitivity and 93% specificity. Of note, in patients with DM with typical skin rash but no PFA, 44% of the samples showed sarcoplasmic MxA expression, which was higher than the 17% sensitivity of capillary MAC deposition in the population.Conclusions:Sarcoplasmic MxA expression detected by immunohistochemistry is a more sensitive marker of DM than the conventional hallmarks, indicating its practical utility in the diagnosis of DM. It may well be included in the routine immunohistochemistry panel for myositis.Classification of evidence:This study provides Class II evidence that immunohistochemistry-detected sarcoplasmic MxA expression accurately identifies patients with dermatomyositis.
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Suzuki, K., Y. Kondo, S. Ishigaki, S. Takanashi, and Y. Kaneko. "AB1630 RISK FACTORS FOR CARDIAC INVOLVEMENT IN IDIOPATHIC INFLAMMATORY MYOPATHIES." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 2049.1–2049. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1969.
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BackgroundIdiopathic inflammatory myopathies (IIMs) are heterogenous systemic autoimmune disorders that mainly affect the skin, muscles, and lungs. Whereas cardiac involvement is considered to be rare, it causes cardiac inflammation and fibrosis leading to severe morbidity and mortality. However, little is known about clinical characteristics and risk factors for cardiac involvement in patients with IIMs.ObjectivesThe aim of this study was to clarify the frequency and clinical characteristics of cardiac involvement and its risk factors in patients with IIMs.MethodsWe retrospectively reviewed consecutive patients with IIMs who visited Keio University Hospital from 2002 to 2022. We divided patients into two groups according to the presence or absence of symptomatic cardiac involvement and compared their clinical characteristics and autoantibodies between the two groups. We defined symptomatic cardiac involvement as the presence of chest pain, palpitation, cardiogenic leg edema, or respiratory distress accompanied by abnormal findings of cardiac examinations such as electrocardiography, echocardiography, and/or cardiac magnetic resonance imaging (MRI).ResultsWe included 145 patients with IIMs in the analysis. The mean age at IIMs diagnosis was 55 years old, and 71.7% were female. Forty patients (27.6%) were polymyositis, 53 (36.6%) were dermatomyositis, 44 (30.3%) were amyopathic dermatomyositis, and 8 (5.5%) were immune-mediated necrotizing myopathy. Among them, 52 patients (35.9%) had abnormal findings on electrocardiography, echocardiography, and/or cardiac MRI, and 17 (11.7%) were diagnosed with symptomatic cardiac involvement at the mean age of 65 years during the mean observation period of 20.0 years. Comparison of clinical characteristics identified no difference in the mean age, sex distribution, and duration from IIM diagnosis to symptomatic cardiac involvement between the two groups. Also, no significant difference was found in the positivity of anti-amynoacyl tRNA synthetase antibody, anti-MDA5 antibody, and anti-SS-A antibody, IIMs subtypes, presence of skin rash, malignancy, interstitial lung disease, history of cyclophosphamide use, and maximum levels of CK, aldolase, CK-MB, troponin T, and CRP. However, the presence of Raynaud’s phenomenon and neutrophil/lymphocyte ratio at diagnosis were significantly higher in the cardiac involved group compared to the non-cardiac involved group (53.85% vs 15.24%, p=0.0009; 56.25% vs 18.25%, p=0.0006). Multivariable analysis identified Raynaud’s phenomenon (odds ratio [OR] 8.42, 95% confidence interval [CI] 2.10-33.8, p=0.0026) and elevated neutrophil/lymphocyte ratio (OR 6.92, 95% CI 1.73-27.6, p=0.0061) as independent risk factors for symptomatic cardiac involvement. One patient in the cardiac involved group died of cardiac failure during the observation period.ConclusionAbnormal findings in cardiac examinations and symptomatic cardiac involvement are frequent in patients with IIMs. Evaluating cardiac involvement is important, especially in patients with Raynaud’s phenomenon and elevated neutrophil/lymphocyte ratio at diagnosis.Reference[1]Lilleker JB, Vencovsky J, Wang G, et al. The EuroMyositis registry: an international collaborative tool to facilitate myositis research. Ann Rheum Dis. 2018;77: 30–39.Figure 1.Risk factors for cardiac involvement in inflammatory myopathiesAcknowledgements:NIL.Disclosure of InterestsNone Declared.
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Larco Rojas, X. E., S. Sáez-Álvarez, P. Pérez-García, C. Sieiro Santos, I. González Fernández, C. Moriano, A. López Robles, M. Martín Martín, C. Álvarez Castro, and E. Diez Alvarez. "AB0706 Demographic, clinical and serological characteristics in Idiopathic Inflammatory Myopathies. The role of specific antibodies." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1479.3–1480. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3657.
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BackgroundIdiopathic Inflammatory myopathies are a heterogenous group of diseases which main common characteristic is muscle injury. Specific autoantibodies related with different phenotypes have become an important diagnostic and prognostic tool. These antibodies may be associated with different histopathological features in muscle biopsies.ObjectivesTo describe the demographic, clinical and serological characteristics of Idiopathic Inflammatory Myopathies (IIM); the most frequent corticoid sparing agents used and the frequency of associated neoplasms in a sample of patients with a compatible biopsy result. To compare these characteristics in patients with positive and negative ANA and the association of different biopsy patterns with specific myositis antibodies.MethodsMuscle biopsies results that were compatible with inflammatory myopathy were collected from the Pathology Unit database of Leon´s hospital between January 2010 and March 2021.Demographic, clinical and serological characteristics, associated malignancies and treatments used were collected from clinical records.ResultsWe included 30 patients in the study. Patient`s characteristics are shown in Table 1. Median age of diagnosis was 59 years. Arthritis and lung disease were found in 20% of patients. The patterns of lung involvement found in HRCT were NSIP in 2, UIP in 1, and bronchiectasis in 3 patients. Associated collagenopathies were found in 26,7%, being vasculitis the most frequent (2 patients). Associated Malignancies were found in 13,3%: lung carcinoma in 1, Urothelial carcinoma in 1, cervix carcinoma in 1 and prostate carcinoma 1 patient. Specific myositis antibodies were negative in 56,7%; positive ANA was found in 60%.Table 1.Demographic, clinical, serological characteristics and treatment in the sample studiedCharacteristicsPatients (n=30)Median; IQR or n(%)Age at diagnosis (years)59; 18,5Sex F/M17(56,7)/13(43,3)Artralgias11(36,7)Arthritis6(20)Raynaud3(10)Lung disease6 (20)Skin disease7 (23,3)Autoimmunity biomarkers (+/-/ not done)ACPA2(6,7) /3 (10) /25(83,3)Positive Rheumatoid Factor4(13,3) /13 (43,3) /13(43,3)ANA18 (60%) /12(40%)Specific Myositis AntibodiesAnti SRP1(3,3)Anti-HMG CoA reductase5 (16,7)Anti Jo12(6,7)Negative17 (56,7)Not done5 (16,4)Biopsy patternnecrotizing8 (26,7)inflammatory15(50)Inclusion Bodies4 (13,3)dermatomyositis3 (10)DiagnosisDermatomyositis3 (10)Statin Myopathy5(16,7)Inclusion body myopathy3(10)Polymyositis8(26,7)Immune-mediated necrotizing myopathy2 (6,7)Antisynthetase syndrome1(3,3)Other collagenopathies8(26,7)TreatmentMethotrexate11(36,7)Azathioprine3(10)immunoglobulins5(16,7)Rituximab5(16,7)Mycophenolate4(13,3)Cyclophosphamide2 (6,7)None11 (36,7)2 or more treatments8(26,7)Associated malignancies4 (13,3)The median of levels at diagnosis of CK was: 1181; IQR:6252,5; aldolase 14,4; IQR: 34,65; AST 62; IQR:181,25; ALT 55,5; IQR:119,25; CRP 7,6; IQR 13,55.When compared, CK and ALT levels in patients with negative and positive ANA, this were higher in negative patients (6365; IQR:9592vs888;3045; P=0.044) and (182; IQR:287vs43; 85; P=0,035) respectively. Anti HMGCoA reductase antibodies were more frequently found in patients with necrotizing pattern in biopsies 5/8 patients; (62,5%); p=0.002.Methotrexate was the corticoid sparing agent most frequently used (36,7% of patients), 36,7% of patients were treated only with corticoids and 26,7% needed more than one treatment.ConclusionSpecific myositis antibodies are helpful tools in the diagnosis when present, meanwhile biopsy can be an important tool when antibodies are negative. ANA positivity seems to be associated with milder disease at the muscular domain.References[1]Zanframundo G,Tripoli A, Cometi L, et al. One year in review 2020: idiopathic inflammatory myopathies. Clin Exp Rheumatol 2021; 39: 1-12.Disclosure of InterestsNone declared
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Galindo-Feria, A. S., B. Horuluoglu, J. Day, C. Cerqueira, S. Proudman, I. E. Lundberg, and V. Limaye. "POS0883 DETECTION OF AUTOANTIBODIES AGAINST MUSCLE-SPECIFIC FOUR-AND-A-HALF-LIM DOMAIN 1 (FHL1) IN INFLAMMATORY MYOPATHIES: RESULTS FROM A SINGLE-CENTER COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 697.3–698. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3640.
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Background:Autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), have been previously identified in patients with idiopathic inflammatory myopathies (IIM) (1).Objectives:The aim of this project was to determine the prevalence and associations of anti-FHL antibody in South Australian patients with histologically-confirmed IIM and in an autoimmune disease control (systemic sclerosis (SSc)).Methods:Sera from patients with IIM (n=267) from the South Australian Myositis Database (SAMD), and SSc (n=174) from the Australian Scleroderma Cohort Study (ASCS) followed at the Royal Adelaide Hospital, and healthy controls (HC, n=100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Clinical, serological and histological details were retrieved from the SAMD and the ASCS.Results:Autoantibodies to FHL1 were more frequent in patients with IIM (55/267, 20.5%) compared with SSc (18/174, 10%) (p<0.001) and HC (4/100, 4%) (p<0.001). Muscular vessel inflammation and atrophy were seen more frequently in IIM anti-FHL1+ patients compared with anti-FHL1- (p<0.01 and p<0.05). Dysphagia, marked muscle atrophy, and high CK levels were frequent in anti-FHL1+ patients with inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). In 35/54 anti-FHL1+ patients, there were no other myositis-specific autoantibodies present. Anti-FHL1 autoantibodies in patients with SSc were associated with gastric antral vascular ectasia.Conclusion:Anti-FHL1 autoantibodies were detected in 20.5% of IIM patients. In IBM and IMNM, the presence of anti-FHL1-autoantibodies was associated with a severe myopathy as suggested by presence of dysphagia and muscle atrophy.References:[1]Albrecht I, Wick C, Hallgren A, Tjarnlund A, Nagaraju K, Andrade F, et al. Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. J Clin Invest. 2015;125(12):4612-24.Disclosure of Interests:Angeles Shunashy Galindo-Feria: None declared, Begum Horuluoglu: None declared, Jessica Day: None declared, Catia Cerqueira: None declared, Susanna Proudman: None declared, Ingrid E. Lundberg Consultant of: Consulting fees from Corbus Pharmaceuticals, Inc, Grant/research support from: Research grants from Bristol Myers Squibb and Astra Zeneca, Vidya Limaye Consultant of: Scientific adviser for Actelion and Boehringer-Ingelheim, Grant/research support from: PI for clinical trials for Bayer, Boehringer-Ingelheim, Corbus, and CSL
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De Lorenzo, R., S. Cavalli, F. Bonomi, S. Tronci, S. L. Calvisi, S. Previtali, and P. Rovere-Querini. "AB0567 CHARACTERIZATION OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY AND MYOCARDIAL INVOLVEMENT: A MONO-CENTRIC EXPERIENCE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1580.3–1580. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6248.
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Background:Idiopathic inflammatory myopathies (IIM) are immune-mediated disorders of the skeletal muscle, with dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM) representing major subtypes. Beyond skeletal muscle, other organs may be affected and myocardial involvement may lead to severe life-threatening complications. The exact prevalence of myocardial involvement among IIM patients and its impact on other disease characteristics remain unclear.Objectives:To investigate the prevalence of myocarditis in patients affected by IIM in and to determine whether the presence and extent of myocardial involvement identify a distinct disease phenotype.Methods:42 longitudinally followed IIM patients were routinely screened for myocardial involvement during a median [IQR] follow-up time of 4.2 [2-8.5] years. Patients with secondary causes of myocardial dysfunction were not included. Patients were considered to have myocarditis in case of:i) abnormal elevation of both circulating troponin T and troponin I,ii) signs of myocardial inflammation or necrosis/fibrosis at cardiac MRI, oriii) positive myocardial tissue histology. Demographic, clinical and serologic features of patients with myocarditis were compared to those with no sign of myocardial involvement. Moreover, we determined whether the extent of myocardial involvement based on troponin levels predicts skeletal muscle disease severity.Results:57.1% (24 of 42) of patients had myocarditis. The frequency of myocardial dysfunction was similar among patients with DM, PM, IBM or IMNM and was not related to autoantibody positivity. Myocarditis was not associated with sex or ethnicity. Patients with or without myocarditis were similar in terms of age at disease onset and extra-muscular manifestations including dysphonia, dysphagia, arthralgias or arthritis, Raynaud phenomenon or interstitial lung disease. Independent of the IIM subtype, the presence of perimysial macrophages at skeletal muscle biopsy seems to protect from myocarditis development (p=0.04). Patients with myocarditis had higher median [IQR] levels of aldolase (10.9 [7.8-15.8] vs. 5.6 [4.9-8.6], p=0.014) and creatine kinase (1785 [966-5852] vs. 685 [168-2255], p=0.04) compared to patients with no myocardial dysfunction. Among patients with myocarditis, levels of troponin I negatively correlated with manual muscle testing 8 (MMT8) score (r=-1, p=0.01), strength in biceps (r=-0.95, p=0.014) and wrist extensors (r=-0.95, p=0.014) at last visit. Troponin T and troponin I titers were similar among patients with different IIM subtypes. C-reactive protein (p<0.04) but not erythrocyte sedimentation rate was found to predict myocardial involvement.Conclusion:Our findings suggest that myocarditis is a frequent occurrence among patients with IIM and should be routinely ruled out. A more severe skeletal muscle disease is associated with an increased likelihood of myocarditis development, presumably due to higher systemic disease activity or inefficient disease control. The extent of myocardial damage faithfully reflects the severity of skeletal muscle dysfunction.References:[1]Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015 Apr 30;372(18):1734-47. doi: 10.1056/NEJMra1402225.[2]Schwartz T, Diederichsen LP, Lundberg IE, et al. Cardiac involvement in adult and juvenile idiopathic inflammatory myopathies. RMD Open 2016;2:e000291. doi:10.1136/rmdopen-2016- 000291.Disclosure of Interests:None declared
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Li, Wenli, Chuiwen Deng, Hanbo Yang, Xiaolan Tian, Lida Chen, Qingyan Liu, Chang Gao, Xin Lu, Guochun Wang, and Qinglin Peng. "Upregulation of the CD155-CD226 Axis Is Associated With Muscle Inflammation and Disease Severity in Idiopathic Inflammatory Myopathies." Neurology - Neuroimmunology Neuroinflammation 10, no. 5 (July 25, 2023): e200143. http://dx.doi.org/10.1212/nxi.0000000000200143.
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Background and ObjectivesThe CD155-CD226/T-cell Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) pathway plays a critical role in regulating T-cell responses and is being targeted clinically. However, research on the role of this pathway in autoimmune diseases is limited. This study aimed to investigate the expression and tissue-specific roles of CD155-CD226/TIGIT pathway molecules in the inflamed muscles of patients with idiopathic inflammatory myopathies (IIMs).MethodsImmunohistochemistry, Western blot analysis, and polychromatic immunofluorescence staining were performed to examine the expression of CD155, CD226, and TIGIT in skeletal muscle biopsies from 30 patients with dermatomyositis (DM), 10 patients with amyopathic DM (ADM), 20 patients with immune-mediated necrotizing myopathy (IMNM), 5 patients with dysferlinopathy, and 4 healthy controls. Flow cytometry analysis was used to analyze the functions of T cells with different phenotypes.ResultsStrong expression of CD155 was observed in patients with DM and IMNM, while its expression was largely negative in those with ADM and dysferlinopathy and healthy controls. The costimulatory receptor CD226 was highly expressed on muscle-infiltrating cells, while the coinhibitory receptor TIGIT was expressed at low levels. These infiltrating CD226+ cells were mainly activated effector T cells that localized adjacent to CD155-expressing myofibers, but were faintly detectable within the muscle fascicles lacking CD155. A strong positive correlation between CD155 and CD226 expression scores was also observed. Polychromatic immunofluorescence staining revealed that CD155+ muscle cells coexpressed major histocompatibility complex classes I and II, and tumor necrosis factor alpha expression was detected in CD226+ T cells at their close sites with the myofibers. Furthermore, the expression levels of CD155 and CD226 showed a positive correlation with creatine kinase, lactate dehydrogenase, and the muscle histopathology damage scores and an inverse correlation with the Manual Muscle Testing-8 scores. In addition, CD155 and CD226 expressions were significantly decreased in representative patients who achieved remission posttreatment.DiscussionThese findings demonstrate that the CD155-CD226 axis is highly activated in inflamed muscle tissues of patients with IIM and is associated with muscle disease severity. Our data uncover the immunopathogenic role of the axis in the pathology of IIMs.
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Zhao, Bing, Tingjun Dai, Dandan Zhao, Xiaotian Ma, Cuiping Zhao, Ling Li, Yuan Sun, et al. "Clinicopathologic Profiles of Sporadic Late-Onset Nemaline Myopathy." Neurology - Neuroimmunology Neuroinflammation 9, no. 4 (May 17, 2022): e1184. http://dx.doi.org/10.1212/nxi.0000000000001184.
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Background and ObjectivesSporadic late-onset nemaline myopathy (SLONM) is a treatable or otherwise fatal myopathy. Diagnosis of SLONM is still challenging, and no therapeutic consensus has been achieved. Here, we reported the clinicopathologic features and long-term follow-up data of SLONM in a Chinese cohort.MethodsWe performed a retrospective evaluation of clinical, pathologic, and treatment outcomes of 17 patients with SLONM diagnosed between March 1986 and April 2021 at our neuromuscular center. Immunohistochemistry (IHC) with antibodies against 5 Z-disc–associated proteins was performed in the muscle biopsies of SLONM to identify a potential pathologic marker in aid of diagnosis. In comparison, we also performed muscle IHC in patients with selective type II fiber atrophy (n = 22), neurogenic atrophy (n = 22), mitochondrial myopathy (n = 5), immune-mediated necrotizing myopathy (n = 5), and normal controls (n = 5).ResultsMost of the patients exhibited asymmetric limb muscles weakness (71%, 12/17) and neck extensor weakness (53%, 9/17). Immunofixation electrophoresis was performed in 11 patients, and 4 of them were identified with monoclonal gammopathy of undetermined significance (MGUS). EMG from 16 patients demonstrated a myopathic pattern with spontaneous activities in 69% (11/16) of them. Muscle MRI showed preferential involvement of paraspinal, gluteus minimus and medius, semimembranosus, and soleus muscles. Suspected nemaline bodies on modified Gomori trichrome were confirmed by IHC using anti–α-actinin antibody (100%, 17/17), anti-myotilin antibody (94%, 16/17), anti-desmin antibody (94%, 16/17), anti–α-B crystallin antibody (65%, 11/17), and anti-telethonin antibody (18%, 3/17) with various positive rates. Notably, anti–α-actinin IHC showed the highest percentage of strongly positive staining (77%, 13/17), being the only one without negative results. Moderate improvement following autologous stem cell transplantation (ASCT) was noted in 3/4 patients with MGUS; favorable outcomes were also achieved in 6/7 patients without MGUS, including 3 patients with complete recovery who were given a combined treatment of prednisone and another immunosuppressant.DiscussionSLONM is a treatable myopathy with ASCT or traditional immunotherapy, especially when combined with steroids and immunosuppressants. Anti–α-actinin immunostaining is the most reliable pathologic marker to identify rod-bearing fibers, and it should be performed routinely in adult patients with undiagnosed nonnecrotic myopathies.
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Robert, M., L. Lessard, T. Fenouil, A. Hot, T. Laumonier, A. Bouche, B. Chazaud, N. Streichenberger, and L. Gallay. "POS0490 USEFULNESS OF MHC-II IMMUNO-STAINING ON MUSCLE BIOPSIES IN IDIOPATHIC INFLAMMATORY MYOPATHIES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 499.2–500. http://dx.doi.org/10.1136/annrheumdis-2022-eular.5186.
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BackgroundIdiopathic inflammatory myopathies (IIMs) constitute a group of acquired muscular diseases that occur during childhood and adulthood, exhibit a variety of phenotypes and are potentially life-threatening. IIM diagnosis considers clinical, serological, and histological data. Muscle pathological analysis of IIM patients gives relevant elements for the diagnosis (immune cell infiltrate, vascular and connective tissues, as well as myofiber morphology). Immunochemistry (IHC) labeling for major histocompatibility complex class I (MHC-I), and C5b9, that are negative in normal muscle, appeared of interest in IIM diagnosis and the understanding of IIM pathogenesis. In normal muscle, myofibers are negative for MHC-II IHC. Its interest in the neuropathological exam of IIM muscle remains to be better characterized.ObjectivesThis study aims to analyze the pattern of MHC-II expression in various IIMs.MethodsA historical cohort was designed using the MYOLYON register (IIM patients diagnosed between 2016 and 2020 at the University Hospital of Lyon, France). Inclusion criteria were IIM diagnosis that was established histologically and available frozen muscle samples for additional analyses. Exclusion criterium was any treatment before muscle biopsy. Demographical data and final diagnosis were collected retrospectively from medical records. A centralized, standardized, and blind analysis of muscle MHC-II immuno-staining was conducted to define the various patterns of MHC-II by myofibers and by capillaries. The study complied with ethical requirements.ResultsSeventy-three patients were included: 23 dermatomyositis (DM), 13 anti-synthetase syndrome (ASS), 13 immune-mediated necrotizing myopathies (IMNM), 13 inclusion body myositis (IBM), and 11 overlap myositis (OM). MHC-II immuno-staining of myofibers or capillaries was abnormal for 91.8% of the analyzed biopsies (Figure 1). The analysis of MHC-II myofiber immuno-staining revealed distinguishable patterns according to IIM subtype: the labeling was diffuse in IBM (69.2%, n=9/13), perifascicular in ASS (61.5%, n=8/13), and variable in OM (patchy for 27.3% n=3/11 or clustered for 36.4%, n=4/11). MHC-II immuno-staining was negative in IMNM (84.6%, n=11/13) and in DM (47.8%, n=11/23). DM exhibiting positive MHC-II myofibers (n=12) were associated with the presence of anti-TIF1γ, anti-NXP2 and anti-SAE auto antibodies (n=5, n=3 and n=2, respectively). Among the 12 patients, there were juvenile cases (n=5, 41.7%) or DM associated with ongoing neoplasia (n=4, 33.3%). Three main architectures were described for capillaries: giant, leaky and capillary dropout. Patterns of MHC-II positive capillaries were the following: DM was characterized by capillary dropout (68.2%), IMNM showed leaky capillaries (75.0%), IBM giant capillaries (66.7%), ASS exhibited both giant (61.5%) and/or leaky (58.3%) capillaries, while OM showed giant (63.6%) or/and leaky (80.0%) capillaries and capillaries dropout (60.0%).ConclusionThe present work establishes the usefulness of MHC-II immuno-staining for IIM diagnosis, and gives additional elements on the impairment of myofibers and capillaries in the various IIM subgroups. MHC-II expression is known to be induced by inflammatory cytokine such as interferon type II. This could be linked to myofiber and/or capillary impairment in some IIMs, such as IBM, ASS and OM. These results also support the implication of vasculopathy in IIM pathogenesis, with various structural and cellular consequences regarding the different subgroups. Finally, MHC-II immuno-staining in IIM muscle biopsies enables a foremost analysis of myofibers and capillaries, and represents an additional biomarker to distinguish IIM subgroups.References[1]De Bleecker, J.L. et al. 205th ENMC International Workshop: Pathology diagnosis of idiopathic inflammatory myopathies part II 28-30 March 2014, Naarden, The Netherlands. Neuromuscul Disord 2015, 25, 268-272.Disclosure of InterestsNone declared.
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Dourado, E., A. T. Melo, P. Martins, M. J. Sousa Bandeira, V. Fraga, J. L. Ferraro, A. Saraiva, et al. "POS0891 REUMA.pt/MYOSITIS – THE PORTUGUESE REGISTRY OF INFLAMMATORY MYOPATHIES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 742. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3259.
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BackgroundThe idiopathic inflammatory myopathies (IMM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/Myositis) is a tool used to systematically evaluate IIM patients.ObjectivesTo clinically characterise the Reuma.pt/Myositis cohort.MethodsMulticentre open cohort study, including IIM patients registered in Reuma.pt up to January 2022. Data collected included demographic, clinical, and treatment data and patient-reported outcomes. Data were presented as frequencies and median (interquartile range) for categorical and continuous variables, respectively.Results280 patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years, respectively. Patients were classified as having definite (N=57/118, 48.3%; N=35/224, 15.6%), likely (N=23/118, 19.5%; N=50/224, 22.3%), or possible (N=2/118, 1.7%; N=46/224, 20.5%) IIM by 2017 EULAR/ACR and Bohan-Peter criteria, respectively. Disease subtypes included dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), myositis in overlap syndromes (N=41/280, 14.6%), clinically amyopathic DM (N=17/280, 6.1%), nonspecific myositis (N=13/280, 4.6%), mixed connective tissue disease (N=12/280, 4.3%), immune-mediated necrotizing myositis (N=9/280, 3.2%), and inclusion bodies myopathy (N=7/280, 2.5%). Over the course of the disease, the most common symptoms were proximal muscle weakness (N=180/215, 83.7%), arthralgia (N=127/249, 52.9%), erythema (N=63/166, 38.0%), fatigue (N=47/127, 37.0%), Raynaud’s phenomenon (N=76/234, 32.5%), and dysphagia (N=33/121, 27.3%), and the most common clinical signs were Gottron’s sign (N=75/184, 40.8%), heliotrope rash (N=101/252, 40.1%), Gottron’s papules (N=93/237, 39.2%), and arthritis (N=38/98, 38.8%). Organ involvement included lung (N=78/230, 33.9%), oesophageal (N=40/221, 18.1%), and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) and/or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent antibodies were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%) at diagnosis, with median highest CK levels of 1308 (518-3172) and aldolase of 42 (12-121) mg/dL. Neoplasia was found in 11/127 patients (8.7%), most commonly breast (N=3/11, 27.3%), non-melanoma skin (N=2/11, 18.2%), and colorectal (N=2/11, 18.2%) cancer (Table 1). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs over the course of disease were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), mycophenolate mofetil (N=56/280, 20.0%), intravenous immunoglobulin (N=55/280, 19.6%), and rituximab (N=45/280, 16.1%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125).Table 1.Autoantibodies in cancer-associated myositisCancerIIMAutoantibodiesBreastDM (3)Mi2, SRP (+ SSA/SSB), Pm/SclSkin (non-melanoma)Clinically amyopathic DM, PMJo1, SAE1 (+SSA/SSB)ColorectalDM (2)Mi2 (2)KidneyDM-LungDM-LymphomaInclusion bodies myopathy-UnknownDM-ConclusionReuma.pt/Myositis adequately captures the main features of inflammatory myopathies’ patients, depicting in this first report a heterogeneous population, with frequent muscle, joint, skin and lung involvements. Of interest, most patients reached low disease activity at the last follow-up appointment.Disclosure of InterestsNone declared
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Adsuara de Sousa, L. F., R. G. Misse, L. De Macedo Dos Santos, A. Fontes Baptista, C. Tanaka, J. M. D’andréa Greve, and S. Katsuyuki Shinjo. "POS0887 TRANSCRANIAL ELECTRICAL STIMULATION IS SAFE AND EFFICIENT IN PATIENTS WITH SYSTEMIC AUTOIMMUNE MYOPATHIES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 699.2–700. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3723.
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Background:There is currently few information regarding rehabilitation in patients with systemic autoimmune myopathies (SAMs). Transcranial direct current stimulation (tDCS) has shown promising results for the motor performance of healthy individuals as for patients with, e.g., post-stroke hemiparetic limbs.Objectives:The present study was aimed to assessing the safety and efficiency of tDCS in patients with SAMs.Methods:This study is a prospective, randomized, sham controlled, double blind, and clinical trial with ethical approval. Eighteen adult patients with dermatomyositis, polymyositis, antisynthetase syndrome or immune-mediated necrotizing myopathies in remission or with minimal disease activity were enrolled from 2018 to 2019. Patients were allocated randomly in two groups to receive sham or active tDCS with 2mA amplitude submitted for 20 minutes for three consecutive days. The 5x7cm sponge-electrodes were positioned with the anode over the left (C1) or right (C2) - contralateral to the dominant limb, whereas the cathode over the FP2 or FP3, respectively (10-10 EEG electrodes placement). The groups were evaluated in four moments: pre-stimulation, and 30 minutes, 3 weeks and 8 weeks post-tDCS. They were evaluated in the different moments with International Myositis Assessment and Clinical Studies Group set scores, Short-Form health survey (SF-36), state-trait anxiety inventory (STAI), Beck depression inventory (BDI), timed up-and-go test (TUG), time-stands test (TST), isokinetic extension and flexion testing of bilateral knee and elbow. A specific security questionnaire for tDCS was used after the active or sham stimulation in all patients.Results:The demographic data, kind of myositis, disease duration, and disease status (all with low disease activity) were comparable between both active and sham tDCS groups. After interventions, there was improvement of values of patient’s VAS (P=0.042) and serum levels of creatine phosphokinase (P=0.005), independent of the group. Moreover, in active tDCS group, the physical aspects of SF-36 in week 8 (P<0.001), mean and better TST at each evaluation (P<0.001), absolute peak tork (P<0.001) and peak tork adjusted for body weight values (P<0.001) of stimulated inferior limb extension also improved. No differences were observed in the STAI, BDI, or TUG in both groups. The patients’ adherence to the protocol was 100% and no adverse event was reported, including disease relapsing.Conclusion:This unprecedented study evidences the safety of tDCS, besides the potential efficiency in improving rehabilitation of tDCS in SAMs. More studies with a large samples and period of tDCS sessions are necessaries to corroborate with the present study.References:[1]Lundberg IE, et al. 2017 European league against rheumatism/ American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Arthritis Rheum. 2017;69:2271-82.[2]Tanaka S, et al. Single session of transcranial direct current stimulation transiently increases knee extensor force in patients with hemiparetic stroke. Neurorehabil Neural Repair. 2011;25:565-9.Acknowledgements:This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 303.379/2018-9, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 2019/11776-6, Faculdade de Medicina da USP/SP to SKS.Disclosure of Interests:None declared
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Graf, M., A. S. L. Von Stuckrad, A. Uruha, J. Klotsche, L. Zorn-Pauly, N. Unterwalder, T. Buttgereit, et al. "POS0183 SIGLEC1 AS A TYPE I INTERFERON BIOMARKER IN IDIOPATHIC INFLAMMATORY MYOPATHIES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 305.1–305. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2816.
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Background:Idiopathic inflammatory myopathies (IIM) are autoimmune diseases that mainly affect skeletal muscle, lung, skin and joints. IIM can be separated into dermatomyositis (DM), inclusion body myositis (IBM), antisynthetase syndrome (AS) and immune-mediated necrotizing myopathy (IMNM). Type I interferons (IFN) are known to play a crucial role in the etiopathogenesis of some of these entities such as DM.[1] Sialic acid binding Ig-like lectin 1 (SIGLEC1, CD169) is part of the type I IFN signature found in SLE and DM and is expressed on the cell surface of monocytes. Thus, analysis of SIGLEC1 expression by flow cytometry enables a straightforward assessment of the type I IFN signature. Its utility has been shown for juvenile and adult SLE and other rheumatic diseases but not in IIM.[2,3] The assessment of the type I IFN system in clinical practice is an unmet need and, in this context, SIGLEC1 might be useful.Objectives:To assess SIGLEC1 expression on monocytes by flow cytometry as a type I IFN biomarker in IIMMethods:Pediatric and adult patients with a clinical diagnosis of DM, AS, IMNM and IBM and at least one measurement of SIGLEC1 who have been treated at the Department of Rheumatology, Charité - Universitätsmedizin Berlin between 2015 and 2020 were included in this retrospective study. Control groups of healthy individuals (n=19) and SLE patients (n=30) were included. Disease activity was assessed by Physician Global Assessment (PGA) and Childhood Myositis Assessment Scale (CMAS). SIGLEC1 expression on monocytes was analyzed by flow cytometry. Cross-sectional analyses (n=74) were performed using Mann Whitney-U test (MWU) and two-level mixed-effects linear regression model was used for longitudinal analyses (n=26, 110 visits). This study was approved by the local ethics committee of the Charité - Universitätsmedizin Berlin.Results:74 patients (adult/juvenile DM: n=21/n=17; AS: n=19; IMNM: n=8; IBM: n=9) were included. In cross-sectional analysis, SIGLEC1 expression was significantly upregulated in adult and juvenile DM patients with moderate to severe disease activity (PGA≥5) compared with adult/juvenile DM patients with no to moderate disease activity (PGA<5) (both p<0.001). In longitudinal analyses, SIGLEC1 correlated with disease activity in juvenile DM (SIGLEC1 vs. CMAS: betaST=-0.65; p<0.001) and adult DM (SIGLEC1 vs. PGA: betaST=0.52; p<0.001), better than Creatine Kinase (CK) (juvenile DM, CK vs. CMAS: betaST=-0.50; p<0.001; adult DM, CK vs PGA: betaST=0.17; p=0.149). In AS 42,1% of the patients showed elevated SIGLEC1 expression, while it was not upregulated in IMNM and only in two patients with IBM, who were concurrently positive for autoantibodies that affect the type I IFN system (see Figure 1).Conclusion:SIGLEC1 is a useful biomarker to identify an activated type I IFN system in IIM. Flow cytometry is used widely in laboratory medicine, which could facilitate the implementation of SIGLEC1 into clinical routine.References:[1]Gallay L, Mouchiroud G, Chazaud B. Interferon-signature in idiopathic inflammatory myopathies: Current Opinion in Rheumatology 2019;31:634–42. doi:10.1097/BOR.0000000000000653[2]Rose T, Grutzkau A, Hirseland H, et al. IFNalpha and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus. Ann Rheum Dis 2013;72:1639–45. doi:10.1136/annrheumdis-2012-201586[3]Stuckrad SL von, Klotsche J, Biesen R, et al. SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus. Lupus 2020;:961203320965699. doi:10.1177/0961203320965699Figure 1.SIGLEC1 expression on monocytes in IIM subgroups and control groups; in IIM subgroups, patients with low disease activity (PGA<5) are marked in blue, patients with high disease activity (PGA≥5) are marked in red; mAb/cell, monoclonal antibodies bound per cellDisclosure of Interests:None declared
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Kastrati, K., T. Nakuz, I. Gessl, E. Simader, D. Mrak, M. Bonelli, H. Kiener, et al. "POS0889 ASSESSMENT OF MYOSITIS-RELATED INTERSTITIAL LUNG DISEASE BY68GA-DATA.SA.FAPI PET-CT." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 752.1–752. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2974.
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BackgroundIdiopathic inflammatory myopathies (IIM) are a group of heterogeneous autoimmune disorders marked by skeletal muscle inflammation and extra-muscular complications including pulmonary involvement. Interstitial lung disease (ILD) is a common manifestation affecting up to 78% in IIM patients. Methods and means for in-vivo visualization of ongoing tissue remodeling in affected organs are scarce.ObjectivesTo quantify and compare fibroblast activation in the lungs between IIM-patients and control subjects using68Ga-labelled inhibitor of Fibroblast-Activation-Protein based positronic emission tomography-computed tomography (68Ga-DATA.SA.FAPI PET-CT) imaging.MethodsPatients with IIM recruited prospectively from the rheumatology outpatient clinic, and control subjects without rheumatic conditions or ILD recruited from the cardiology outpatient clinic underwent68Ga-FAPI PET-CT imaging. Pulmonary FAPI accumulation was assessed by measuring the maximal standardized uptake value (SUVmax) and mean SUV (SUVmean) over the whole lung (wl), respectively. Values of SUV were compared across IIM patients with and without ILD and controls using analysis of variance (ANOVA) test and displayed as mean ±standard deviation (SD).ResultsThe clinical characteristics of patients with IIM (15 patients with ILD confirmed by CT and 4 non-ILD patients with primary muscular affection) and control subjects (n=17) are displayed in the Table 1. Subtypes of IIM included antisynthetase syndrome (57.9%), dermatomyositis (15.8%), overlap myositis (15.8%), and immune-mediated-necrotizing-myositis (10.5%). In individuals with IIM-related ILD, whole-lung68Ga-DATA.SA.FAPi uptake was significantly increased as compared to both, the non-ILD IIM patients and the control group: wlSUVmax (6.63 [±2.05] vs. 3.74 [±0.71] and 4.74 [±1.24] respectively, both p<0.001) (Figure 1A) and wlSUVmean (1.50 [±0.48] vs. 0.94 [±0.22] and 1.11 [±0.34] respectively, both p<0.05) (Figure 1B). No differences of wlSUVmax or wlSUVmean were observed between non-ILD IIM patients and the control group.ConclusionThis study demonstrates enhanced tracer uptake in68Ga-DATA.SA.FAPi PET-CT in patients with IIM. Thus, FAPi PET-CT may provide a useful tool for the assessment of lung disease in IIM. Further discriminatory and diagnostic testing approaches are needed to integrate this novel imaging method into clinical decision making.Table 1.Demographic and clinical characteristics of participants at baseline.IIM patientsControlsNo. (n)1917Sex (female)11 (57.9%)13 (76.5%)Mean age (years ± SD)49.0 ± 16.779.0 ± 3.8Ethnicity (Caucasian)18 (94.7%)19 (100%)Disease subtype Antisynthetase Syndrome11 (57.9%)- Dermatomyositis3 (15.8%)- Overlap Myositis3 (15.8%)- Immune-mediated necrotizing myopathy2 (10.5%)-Interstitial lung disease (ILD) Yes15 (78.9%)-ILD-Subtype NSIP8 (53.3%)- UIP1 (6.7%)- OP3 (20%)- NSIP and OP3 (20%)-Autoantibodies Aminoacyl-tRNA synthetase11 (57.9%)- Ro-523 (15.8%)- MDA52 (10.5%)- Mi-21 (5.3%)- Seronegative2 (10.5%)-Pulmonary function tests FVC % (mean ± SD)81.9 ± 21.4- DLCO % (mean ± SD)66.1 ± 21.3-Abbreviations: No./n, number; SD, standard deviation; NSIP, nonspecific interstitial pneumonia; UIP, usual interstitial pneumonia; OP, organizing pneumonia; FVC, forced vital capacity; DLCO, diffusion capacity of the lungs for carbon monoxide.Figure 1.68Ga-FAPI-04 uptake in the lungs of IIM-patients and controls.A) whole lung maximal standardized uptake value; B) whole lung mean standardized uptake value in myositis patients with or without interstitial lung disease and control subjects. P values <0.05 were considered statistically significant. Abbreviations: wlSUVmax, whole-lung maximal standardized uptake value; wlSUVmean, whole-lung mean standardized uptake value; ILD, interstitial lung disease; ns, not significant. P values <0.05 are marked with one asterisk; p values <0.001 are marked with two asterisks.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.