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Immune-mediated necrotizing myopathy (IMNM) is a rare and severe disease that corresponds to a specific entity of idiopathic inflammatory myopathy. Patients with IMNM suffer from proximal muscle weakness, and present high levels of creatine kinase and necrotic myofibers. Anti-Signal Recognition Particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (HMGCR) have recently been identified in two thirds of patients with IMNM and are used as a hallmark of the disease. In this review, we provide a detailed description of these antibodies and the tests used to detect them in the serum of patients. Based on in vitro studies and mouse models of IMNM, we discuss the role of autoantibodies in the pathogenesis of the disease. Finally, in the light of the latest knowledge, we conclude with a review of recent therapeutic approaches in IMNM. [ABSTRACT FROM AUTHOR]

Background: Immune-mediated necrotizing myopathies (IMNM) is a rare disease that was first described in 2004. Due to the lack of large case series, there are no formal treatment recommendations for IMNM. Methods: We presented a case of a 47-year-old woman who experienced progressive limb weakness, starting from the lower limbs and gradually affecting the upper limbs. She also reported experiencing dyspnea after engaging in daily activities. When she was admitted to the hospital, her upper limbs were almost unable to move and she could not stand even with support. Her Creatine kinase (CK) level significantly increased (> 3500 u/l). Electromyography showed myogenic damage, anti-Signal recognition particle (anti-SRP) and anti-Ro52 antibodies were highly positive. Pathological biopsy of the right biceps muscle showed necrotizing myopathy in the skeletal muscle. She was ultimately diagnosed with anti-SRP IMNN, and was given monotherapy with methylprednisolone and combination therapy with immunoglobulin, but her symptoms continued to worsen. The patient refused to bear the possible further liver dysfunction and blood system damage caused by Cyclophosphamide and Rituximab, and she chose to try to use Ofatumumab (OFA). Results: After receiving three doses of OFA treatment without any adverse reactions, she reported that her muscle strength had basically recovered and she was able to walk independently. The B cells in the circulatory system have been depleted, and blood markers such as liver function have consistently remained within normal range. During the follow up, her activity tolerance continued to improve. Discussion: We have presented a severe case of SRP-IMNM in which the patient showed poor response to conventional immunotherapy. However, rapid symptom relief was achieved with early sequential use of OFA treatment. This provides a new option for the treatment of SRP-IMNM, and more large-scale studies will be needed in the future to verify our results. [ABSTRACT FROM AUTHOR]

Necrotizing myopathies are a subtype of autoimmune myopathies characterized by muscle fiber necrosis with minimal infiltration by inflammatory cells on muscle biopsy. This group of myopathies is defined by flaccid palsies due to prima‑ ry skeletal muscle damage as well as extramuscular manifestations such as fever, rash, arthritis, Raynaud’s syndrome and interstitial lung disease. The presence of anti-SRP antibodies is associated with rapidly progressive refractory myositis predominantly affecting limb muscles and axial muscles.Objective of the work is to analyze the course of severe, refractory to several lines of immunosuppressive therapies anti-SRP associated necrotizing myopathy and to highlight an adequate treatment regime.Necrotizing myopathy was suspected in patients aged 39 and 56 years with rapidly progressive flaccid tetraparesis on the basis of clinical and anamnestic data, the results of needle electromyography and muscle magnetic resonance imaging, as well as the analysis of myositis-specific and myositis-associated autoantibodies. In both cases, a rapid development of atrophies, marked muscle weakness in the limbs, without involvement of the bulbar musculature, was observed. To achieve effective control of the disease progression, several lines of therapy were required: glucocorticosteroids, intravenous immunoglobulins, methotrexate and rituximab. Our observations are consistent with those in the literature.Our observations illustrate the clinical course of severe myopathy associated with anti-SRP antibodies. Early initiation of aggressive immunosuppression is crucial to control the disease progression. Treatment and rehabilitation allow achieving significant improvement of the patient’s condition.

BackgroundImmune-mediated necrotizing myopathies (IMNM) is a rare disease that was first described in 2004. Due to the lack of large case series, there are no formal treatment recommendations for IMNM.MethodsWe presented a case of a 47-year-old woman who experienced progressive limb weakness, starting from the lower limbs and gradually affecting the upper limbs. She also reported experiencing dyspnea after engaging in daily activities. When she was admitted to the hospital, her upper limbs were almost unable to move and she could not stand even with support. Her Creatine kinase (CK) level significantly increased (> 3500 u/l). Electromyography showed myogenic damage, anti-Signal recognition particle (anti-SRP) and anti-Ro52 antibodies were highly positive. Pathological biopsy of the right biceps muscle showed necrotizing myopathy in the skeletal muscle. She was ultimately diagnosed with anti-SRP IMNN, and was given monotherapy with methylprednisolone and combination therapy with immunoglobulin, but her symptoms continued to worsen. The patient refused to bear the possible further liver dysfunction and blood system damage caused by Cyclophosphamide and Rituximab, and she chose to try to use Ofatumumab (OFA).ResultsAfter receiving three doses of OFA treatment without any adverse reactions, she reported that her muscle strength had basically recovered and she was able to walk independently. The B cells in the circulatory system have been depleted, and blood markers such as liver function have consistently remained within normal range. During the follow up, her activity tolerance continued to improve.DiscussionWe have presented a severe case of SRP-IMNM in which the patient showed poor response to conventional immunotherapy. However, rapid symptom relief was achieved with early sequential use of OFA treatment. This provides a new option for the treatment of SRP-IMNM, and more large-scale studies will be needed in the future to verify our results.

Immune-mediated necrotizing myopathy (IMNM) is a rare and severe disease that corresponds to a specific entity of idiopathic inflammatory myopathy. Patients with IMNM suffer from proximal muscle weakness, and present high levels of creatine kinase and necrotic myofibers. Anti-Signal Recognition Particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (HMGCR) have recently been identified in two thirds of patients with IMNM and are used as a hallmark of the disease. In this review, we provide a detailed description of these antibodies and the tests used to detect them in the serum of patients. Based on in vitro studies and mouse models of IMNM, we discuss the role of autoantibodies in the pathogenesis of the disease. Finally, in the light of the latest knowledge, we conclude with a review of recent therapeutic approaches in IMNM.

Introduction: Necrotizing autoimmune myopathy (NAM) is strongly associated with pathognomonic autoantibodies targeting 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) or signal recognition particle (SRP), whose levels in turn are correlated with serum creatine kinase (CK) and necrosis. Thus, NAM may be amenable to therapeutic plasma exchange (TPE) to remove pathogenic antibodies and improve patient symptoms. Methods: A retrospective case series and literature review of patients presenting with NAM and undergoing treatment with TPE was performed. Clinical data including patient demographics, symptoms, physical exam findings, muscle biopsy, lower extremity imaging, prior therapy, and duration from diagnosis to TPE initiation were collected retrospectively for adult patients with NAM treated with TPE after failing to respond to immunomodulatory therapy. Laboratory data including change in CK levels and myositis‐specific antibody titers from baseline were measured in some patients. Results: Six patients (median age at diagnosis 52.5 years, interquartile range [IQR] 35.8‐64.5 years, four male/two female) underwent a median of 7.5 (IQR: 5‐10) TPE procedures with 5% albumin as replacement. All patients exhibited a statistically significant reduction in CK level from pre‐TPE baseline (range: 43.0%‐58.7% reduction). Responses in this cohort were best in patients with antibodies targeting HMGCR and SRP, which are most strongly associated with NAM. These results compare favorably to a literature review of NAM patients (n = 19) treated with TPE, who also exhibited positive clinical and laboratory responses across varying treatment lengths. Conclusion: TPE can play a role in the management of NAM, particularly in patients with HMGCR or SRP antibodies who are refractory to pharmacologic immunosuppression. [ABSTRACT FROM AUTHOR]

Necrotizing autoimmune myopathy (NAM) is a rare inflammatory process characterized by bilateral proximal muscle weakness and elevated creatinine kinase levels. It is one of the idiopathic inflammatory myopathies. It can be associated with anti-signal recognition particle (SRP) antibody which is commonly seen in middle-aged females. Classic findings on muscle biopsy include muscle fiber necrosis without inflammation. Pulmonary manifestations associated with anti-SRP NAM is rare, and often a challenging correlation to make as our understanding of inflammatory myopathies and interstitial lung disease is still evolving. There have been some associations of Anti SRP NAM with NSIP which responds to corticosteroids. We present a 29 year old male with asymptomatic NAM who presented with a combination of NSIP and pulmonary arterial hypertension (PAH). His PAH was responsive to oral vasodilator therapy however his interstitial lung disease (ILD) rapidly progressed to usual interstitial pneumonia (UIP) requiring lung transplantation. This case highlights 1) an extremely rare presentation of rapidly progressive NAM associated ILD in a young man, in which pulmonary manifestations occurred in the absence of myopathy, 2) The importance of doing a complete work up for interstitial lung disease, including diligent examination for myopathic features and obtaining CK levels, 3) Identifying that interstitial lung diseases can progress despite control of the underlying etiology with corticosteroids and immunosuppressives, 4) Recognition of pre capillary PAH in patients with disproportionally elevated pressures relative to their pulmonary findings, 5) The first report of treatment responsive pulmonary vascular disease associated with NAM, and 6) The importance of early lung transplantation evaluation.

Aim: Juvenile idiopathic inflammatory myopathies have been recently reclassified into clinico‐serological subgroups. Myopathological correlates of the subgroups are incompletely understood. Methods: We studied muscle biopsies from 101 children with clinically and serologically defined juvenile idiopathic inflammatory myopathies from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review and C5b‐9 complement analysis. Results: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti‐TIF1γ, 15/90 anti‐NXP2, 11/90 anti‐MDA5, 5/90 anti‐Mi2 and 6/90 anti‐PmScl. JDM biopsy severity scores were consistently low in the anti‐MDA5 group, high in the anti‐Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage‐rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101) and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b‐9‐deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b‐9 deposition. Conclusion: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes. [ABSTRACT FROM AUTHOR]

The objective of this study is to determine autoantibody profile in children with juvenile dermatomyositis (JDM). Children who were diagnosed with JDM (either recently diagnosed during the study period or follow-up patients) were included in the study. Autoantibodies were detected with commercially available Immunodot kit. Thirty patients were included in the study. Nine out of thirty patients (30%) were positive for one of the 12 autoantibodies tested. Anti-SRP antibody was most common antibody detected in 3 patients followed by anti-MDA-5 antibody in 2 patients; while anti-Jo1 antibody, anti-TIF1-γ antibody, anti-Mi-2 antibody, and anti-PM-Scl antibody were positive in 1 patient each. A different disease phenotype was observed with each autoantibody. The patient with anti-Jo1 antibody had a severe systemic disease in the form of interstitial lung disease; patients with anti-MDA-5 antibody and anti-Mi2 antibody had more severe skin disease with mild muscle disease and patients with anti-SRP antibody had significant skin and muscle disease. Anti-TIF1-γ and anti-PM-Scl antibodies were seen in patients with features of overlap syndrome (myositis-scleroderma). Estimation of autoantibodies may serve as an adjunct tool in delineating and defining distinct clinical phenotypes in children diagnosed with juvenile dermatomyositis. They may also help in prognostication. [ABSTRACT FROM AUTHOR]

Las miopatías inflamatorias idiopáticas son un grupo heterogéneo de miopatías potencialmente tratables. Se clasifican en 4 subtipos: dermatomiositis, polimiositis, miositis autoinmune necrosante y miositis por cuerpos de inclusión, en función de las características clínicas e histológicas. Los anticuerpos asociados a miositis y los autoanticuerpos específicos de miositis se encuentran frecuentemente en pacientes con miopatías inflamatorias, siendo útiles en el diagnóstico y clasificación. El anticuerpo anti-histidil tRNA sintetasa es el más prevalente y el más específico para polimiositis. El anticuerpo de partícula de reconocimiento de señal es también un autoanticuerpo especıfico para polimiositis, pero más infrecuente, y raramente se encuentra en pacientes que presentan otros autoanticuerpos específicos para miositis. En este trabajo se presenta un paciente con polimiositis en el que coexisten los 2 autoanticuerpos en el suero, lo que se considera una situación clínica extremadamente rara. Aquí analizamos la evolución clínica y hallazgos para examinar el efecto de la coexistencia y la posible interacción sobre el pronóstico. Idiopathic inflammatory myopathies are a heterogeneous group of potentially treatable myopathies. They are classified, on the basis of clinical and histopathological features, into four subtypes: dermatomyositis, polymyositis, necrotizing autoimmune myositis and inclusion-body myositis. Myositis-associated antibodies and myositis-specific autoantibodies are frequently found in patients with idiopathic inflammatory myopathies, and are useful in the diagnosis and classification. Anti-histidyl transfer RNA synthetase antibody is the most widely prevalent and is highly specific for polymyositis. Signal recognition particle antibody is also a specific autoantibody for polymyositis, but it is infrequent and rarely found in patients having other myositis-specific autoantibodies. We present a man with polymyositis who had both antibodies in serum, which is considered an extremely rare clinical situation. Here we analyze the clinical course and findings, and examine the effect of the coexistence and possible interaction on prognosis. [ABSTRACT FROM AUTHOR]

Objectives. To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs). Methods. Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated auto-antibodies levels and CSM were estimated using linear mixed models. Results. Following rituximab, anti-Jo-1 levels decreased over time (P < 0.001) and strongly correlated with all CSMs (P< 0.008). Anti-TIF1-γ levels also decreased over time (P< 0.001) and were only associated with HAQ, MMT and physician and patient global disease activity. Anti-SRP levels did not change significantly over time, but were significantly associated with serum muscle enzymes. Anti-Mi-2 levels significantly decreased over time and were associated with muscle enzymes, MMT and the physician global score. Conclusion. Anti-Jo-1, anti-TIF1-γ and anti-Mi-2 levels in myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti-Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity. [ABSTRACT FROM AUTHOR]

The idiopathic inflammatory myopathies (IIMs) comprise a group of autoimmune disorders that target skeletal muscle. They are characterized by typical laboratory and clinical features including muscle weakness, elevated muscle enzymes, characteristic histopathology of muscle biopsies, as well as electromyography abnormalities. The IIMs are divided into polymyositis, dermatomyositis, inclusion body myositis, nonspecific myositis, and immune-mediated necrotizing myopathy (IMNM). IMNM is distinguished by the absence of primary inflammation on muscle biopsy. IMNM may be associated with myositis-specific autoantibodies (i.e., anti- SRP and anti-HMGCR) and malignancy, in association with viral infections (HIV or hepatitis C), or in relation to other connective tissue diseases (i.e., scleroderma). Typical clinical findings such as severe muscle weakness, highly elevated creatine kinase (CK) levels, as well as resistance to conventional immunosuppressive therapy are associated with this subtype of IIM. This review provides an overview of this disease entity and focuses on its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Only few reports exist regarding the coexistence of multiple sclerosis (MS) and autoimmune myopathies. We describe the case of a man with a long history of undiagnosed left lower limb motor impairment who was hospitalized for subacute onset of a myopathic syndrome. In addition, neurological examination revealed sensory impairment and pyramidal signs in the left limbs. Muscle biopsy revealed a necrotizing myopathy and serum anti-signal recognition particle (SRP) antibodies were found. Brain and spinal cord MRI displayed several non-enhancing demyelinating lesions, and CSF-restricted oligoclonal bands were detected. Multimodal evoked potentials showed increased latency of central conduction. Total body PET-CT did not reveal malignancies. A final diagnosis of anti-SRP necrotizing autoimmune myopathy (NAM) and MS was made, and subsequent therapy with azathioprine resulted in a complete stability for both diseases during the follow up. To the best of our knowledge this is the first reported case of concomitant NAM and MS. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies are systemic, chronic autoimmune diseases characterized by symmetrical, proximal muscle weakness. Homogeneous groups present with similar symptoms. The response to therapy and prognosis could be facilitated by myositis-specific autoantibodies, and in this way, give rise to immunoserological classification. The myositis-specific autoantibodies are directed against specific proteins found in the cytoplasm or in the nucleus of the cells. To date, literature suggests the rarity of the co-existence of two myositis-specific autoantibodies. In this study the authors highlight rare associations of myositis-specific autoantibodies. Three hundred and thirty-seven Hungarian patients with polymyositis or dermato-myositis were studied. Their clinical findings were noted retrospectively. Specific blood tests identified six patients with the rare co-existence of myositis-specific autoantibodies, anti-Jo-1 and antiSRP, anti-Jo-1 and anti-Mi-2, anti-Mi-2 and anti-PL-12, anti-Mi-2 and anti-SRP, and anti-SRP and anti-PL-7, respectively. This case review aims to identify the clinical importance of these rare associations and their place within the immunoserological classification. [ABSTRACT FROM AUTHOR]

Résumé: La définition de myopathie nécrosante (MN) est histologique montrant des lésions de nécrose-régénération associées à peu ou pas d’infiltrat inflammatoire. Les causes de MN sont variées, pouvant se rencontrer aussi bien dans des affections musculaires acquises que dans certaines dystrophies musculaires de formule histologique inhabituelle. Parmi les formes acquises, les myopathies nécrosantes auto-immunes (MNAI) constituent une entité récemment individualisée au sein des myopathies dites inflammatoires (MI). Elles présentent une grande hétérogénéité sur le plan clinique, sérologique et évolutif. Initialement, elles étaient considérées comme des myopathies sévères, de début subaigu, associées à une hyperCKémie supérieure à 10 fois la normale. Cependant, des formes plus insidieuses ont été rapportées. Plusieurs tableaux clinico-sérologiques de MNAI sont distingués : les MNAI associées aux auto-anticorps anti-SRP, les MNAI associées aux anticorps anti-HMG-CoA réductase, les MNAI associées à des maladies de système et les MNAI paranéoplasiques. Pour porter le diagnostic de MNAI, il est nécessaire d’exclure les diagnostics différentiels que sont les MN toxiques, certaines affections musculaires héréditaires et les autres myopathies inflammatoires pour lesquelles l’histologie peut être trompeuse. Actuellement, les MNAI sont rares mais probablement sous-diagnostiquées. L’enjeu d’un diagnostic précoce est majeur. Bien que ces formes soient fréquemment cortico-résistantes, le recours à plusieurs thérapeutiques peut permettre une bonne réponse thérapeutique. Le développement de nouvelles classifications des MI prenant en compte à la fois les critères clinico-sérologiques et anatomopathologiques devrait permettre d’améliorer leur diagnostic. Nous proposons à la fin de cette revue un arbre décisionnel diagnostique des MNAI en fonction du mode évolutif. [Copyright &y& Elsevier]

The idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by chronic inflammation, resulting in the progressive weakness of the proximal muscles. Myositis-specific or myositis-associated autoantibodies can often be found in serum of polymyositis and dermatomyositis patients. This autoantibody presence may play a significant role in patient diagnosis and classification. We present a female polymyositis patient characterized with serious muscle weakness and lung involvement. Anti-Jo1 antibodies were detected in the patient’s serum at the time of diagnosis. After 5 years of treatment and surveillance, recent laboratory analysis showed the presence anti-SRP antibody in her serum. [ABSTRACT FROM AUTHOR]

Abstract: Necrotizing myopathy is an unusual and severe form of paraneoplastic myopathy in which inflammation is minimal or absent. We report two cases of necrotizing myopathy which demonstrated significant response to intravenous immunoglobulin (IVIG) (one in spite of tumor progression). A third case represents the first association of anti-signal recognition particle (anti-SRP) syndrome with large-cell lung cancer. These cases highlight the role of histopathologic diagnosis in directing the treatment of paraneoplastic myopathy, and the role for IVIG in treatment of the syndrome. [Copyright &y& Elsevier]

Necrotizing autoimmune myopathy (NAM) is a rare inflammatory process characterized by bilateral proximal muscle weakness and elevated creatinine kinase levels. It is one of the idiopathic inflammatory myopathies. It can be associated with anti-signal recognition particle (SRP) antibody which is commonly seen in middle-aged females. Classic findings on muscle biopsy include muscle fiber necrosis without inflammation. Pulmonary manifestations associated with anti-SRP NAM is rare, and often a challenging correlation to make as our understanding of inflammatory myopathies and interstitial lung disease is still evolving. There have been some associations of Anti SRP NAM with NSIP which responds to corticosteroids. We present a 29 year old male with asymptomatic NAM who presented with a combination of NSIP and pulmonary arterial hypertension (PAH). His PAH was responsive to oral vasodilator therapy however his interstitial lung disease (ILD) rapidly progressed to usual interstitial pneumonia (UIP) requiring lung transplantation. This case highlights 1) an extremely rare presentation of rapidly progressive NAM associated ILD in a young man, in which pulmonary manifestations occurred in the absence of myopathy, 2) The importance of doing a complete work up for interstitial lung disease, including diligent examination for myopathic features and obtaining CK levels, 3) Identifying that interstitial lung diseases can progress despite control of the underlying etiology with corticosteroids and immunosuppressives, 4) Recognition of pre capillary PAH in patients with disproportionally elevated pressures relative to their pulmonary findings, 5) The first report of treatment responsive pulmonary vascular disease associated with NAM, and 6) The importance of early lung transplantation evaluation. - Creatinine kinase should be checked in all interstitial lung disease evaluation. - Pulmonary involvement with anti-SRP necrotizing autoimmune myopathy is rare. - Pulmonary involvement and severity does not correlate with myositis activity. - Lung transplantation evaluation should be performed early on with rare diseases. [ABSTRACT FROM AUTHOR]

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Amaç: Nekrotizan otoimmün miyopati (NOM), akut veya su-bakut proksimal kas güçsüzlüğü ile karakterize olan idiyopatik üıflamatuvar miyopatinin nadir bir şeklidir. Hastalık, histopato-lojik olarak belirgin inflamasyonun eşlik etmediği miyozit, nekroz ve rejenerasyon ile karakterizedir. Hastalık, anti-SRP ve/ve-ya anti-HMGCoAR otoantikorları ile ilişkili olup %20-30 vakada antikorlar bulunmayabilir. Bazı hastalarda intersisyel akciğer hastalığı ve nadiren de kardiyomiyopati olabilir. Biz, burada inflamatuvar miyopatinin nadir bir formu olan nekrotizan otoimmün miyopati vakasını sunduk. Olgu: 65 yaşında kadın hasta 4 haftadan beri devam eden efor dispnesi, yutma zorluğu ve proksimalde kas güçsüzlüğü nedeni ile tarafımıza başvurdu. Hastanın fizik muayenesinde tansiyon arteriyel: 95/60 mmHg, nabız: 100/dk, solunum sayısı: 22/dk olup proksimal kas güeü 1/5 idi. Laboratuvannda AST: 446 U/L, ALT: 296 U/L, LDH: 1994 U/L, kreatin kinaz: 4267 U/L, troponin: 49.7 pg/mL, CRP: <2 mg/L, sedimantasyon: 22 mm/saat, ANA: 1/320 titrede nükleolar ve 1/100 titrede granü-ler paternde, Ro-52 +3 pozitif ve anti-SRP +3 pozitifti. EMG'de primer kas lifi tutulumu ile uyumlu bulgular vardı. Yapılan kas biyopsisinde kas liflerinin %50-60'ı nekrotik ve arada rejenere/atrofik kas lifleri saptandı. Takiplerde göğüste baskı hissi ve troponin yüksekliği olması nedeni ile koroner arter hastalığına yönelik olarak anjiyografi yapıldı. Koroner arter anjiyo-grafisinde anlamk darlık saptanmadı. Hastaya mevcut bulgular ile NOM tanısı konuldu. Hastaya 1 mg/kg dozda metilpredni-solon ve 10-15 mg/hafta dozda metotreksat haşlandı. Sonuç: inflamatuvar belirteçlerin yükselmediği, anti-SRP ve/veya anti-HMGCoAR otoantikorları pozitif olan miyopatili hastalarda inflamatuvar miyopatinin nadir bir formu olan nek-rotizan otoimmün miyopati alala gelmelidir. [ABSTRACT FROM AUTHOR]

Necrotizing myopathies (NM) are defined by histological features. Muscle biopsy demonstrates marked muscle necrosis with regeneration, with little or an absence of inflammatory infiltrate. Histological pattern of NM is unspecific and can be encountered in diverse conditions as acquired myopathies and muscular dystrophies. Among acquired forms of NM, necrotizing autoimmune myopathy (NAM) is a recently recognized sub-group of the idiopathic inflammatory myopathies. Classically, patients present with a subacute severe proximal myopathy, associated with a markedly elevated creatine kinase level, usually greater than 10 times the upper limit of normal. Nevertheless, the clinical presentation can be misleading, with chronic course mimicking muscular dystrophy. Different forms of NAM can be distinguished with various underlying inciting conditions, including autoantibodies to the SRP, autoantibodies to the HMG-CoA reductase, association to connective tissue disease or underlying malignancy. Other associated conditions need yet to be identified. To confirm a diagnosis of NAM, other causes of NM should be excluded as toxic myopathies, muscular dystrophies and other inflammatory myopathies with a misleading histological pattern. NAM is a rare condition but is probably underdiagnosed. Both clinicoserologic and pathologic data must be taken into account to improve this diagnosis. We propose guidelines for diagnosis of NAM according to clinical course, to be used in clinical practice., (Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)