Necrotizing Autoimmune Myositis Research Articles

Immune-mediated necrotizing myopathy (NAM) related to SARS-Cov-2 infection: a case report

BackgroundThere is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies.Case presentationWe described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline.ConclusionSARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

Complement in autoimmune inflammatory myopathies, the role of myositis-associated antibodies, COVID-19 associations and muscle amyloid deposits

Introduction The inflammatory myopathies (IM) have now evolved into distinct subsets requiring clarification about their immunopathogenesis to guide applications of targeted therapies Areas covered Immunohistopathologic criteria of IM with focus on complement, anti-complement therapeutics and other biologic immunotherapies. The COVID19-triggered muscle autoimmunity along with the correct interpretation of muscle amyloid deposits are discussed. Expert opinion The IM, unjustifiably referred as idiopathic, comprise Dermatomyositis (DM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). In DM, complement activation with MAC-mediated endomysial microvascular destruction and perifascicular atrophy is the fundamental process, while innate immunity activation factors, INF1 and MxA, sense and secondarily enhance inflammation. Complement participates in muscle fiber necrosis from any cause and may facilitate muscle-fiber necrosis in NAM but seems unlikely that myositis-associated antibodies participate in complement-fixing. Accordingly, anti-complement therapeutics should be prioritized for DM. SARS-CoV-2 can potentially trigger muscle autoimmunity but systematic studies are needed as the reported autopsy findings are not clinically relevant. In IBM, tiny amyloid deposits within muscle fibers are enhanced by inflammatory mediators contributing to myodegeneration; in contrast, spotty amyloid deposits in the endomysial connective tissue do not represent “amyloid myopathy” but only have diagnostic value for amyloidosis due to any cause.

Inflammatory myopathies: update on diagnosis, pathogenesis and therapies, and COVID-19-related implications.

The inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation. Based on steadily evolved clinical, histological and immunopathological features and some autoantibody associations, these disorders can now be classified in five characteristic subsets: Dermatomyositis (DM) Polymyositis (PM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis and response to immunotherapies, necessitating the need to correctly identify each subtype from the outset to avoid disease mimics and proceed to early therapy initiation. The review presents the main clinicopathologic characteristics of each subset highlighting the importance of combining expertise in clinical neurological examination with muscle morphology and immunopathology to avoid erroneous diagnoses and therapeutic schemes. The main autoimmune markers related to autoreactive T cells, B cells, autoantibodies and cytokines are presented and the concomitant myodegenerative features seen in IBM muscles are pointed out. Most importantly, unsettled issues related to a role of autoantibodies and controversies with reference to possible triggering factors related to statins are clarified. The emerging effect SARS-CoV-2 as the cause of hyperCKemia and potentially NAM is addressed and practical guidelines on the best therapeutic approaches and concerns regarding immunotherapies during COVID-19 pandemic are summarized.

Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis.

Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune muscle diseases with significant morbidity and mortality. This review details and updates the pathogenesis and emerging importance of myositis-specific antibodies in the development of IIMs. An increase in the understanding of how these myositis-specific antibodies play a role in IIMs has led to the further categorization of IIMs from the traditional polymyositis versus dermatomyositis, to additional subcategories of IIMs such as necrotizing autoimmune myositis (NAM). The diagnosis of IIMs, including manual muscle testing, laboratory studies, and non-invasive imaging have become important in classifying IIM subtypes and for identifying disease severity. Treatment has evolved from an era where glucocorticoid therapy was the only option to a time now that includes traditional steroid-sparing agents along with immunoglobulin therapy and biologics, such as rituximab.

Atorvastatin-induced necrotizing autoimmune myositis: An emerging dominant entity in patients with autoimmune myositis presenting with a pure polymyositis phenotype.

The general aim of this study was to evaluate the disease spectrum in patients presenting with a pure polymyositis (pPM) phenotype. Specific objectives were to characterize clinical features, autoantibodies (aAbs), and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing autoimmune myositis (NAM). Patients from the Centre hospitalier de l’Université de Montréal autoimmune myositis (AIM) Cohort with a pPM phenotype, response to immunosuppression, and follow-up ≥3 years were included. Of 17 consecutive patients with pPM, 14 patients had a NAM, of whom 12 were previously exposed to atorvastatin (mean 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. All had aAbs to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and none had overlap aAbs, aAbs to signal recognition particle, or cancer. Three stages of myopathy were recognized: stage 1 (isolated serum creatine kinase [CK] elevation), stage 2 (CK elevation, normal strength, and abnormal electromyogram [EMG]), and stage 3 (CK elevation, proximal weakness, and abnormal EMG). At diagnosis, 10/12 (83%) patients had stage 3 myopathy (mean CK elevation: 7247 U/L). The presenting mode was stage 1 in 6 patients (50%) (mean CK elevation: 1540 U/L), all of whom progressed to stage 3 (mean delay: 37 months) despite atorvastatin discontinuation. MAC deposition was observed in all muscle biopsies (isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries, or mixed pattern). Oral corticosteroids alone failed to normalize CKs and induce remission. Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with ≥1 year remission on stable maintenance therapy, IVIG was needed in 50%, either with methotrexate (MTX) monotherapy or combination immunosuppression. In the remaining patients, MTX monotherapy or combination therapy maintained remission without IVIG. AtorAIM emerged as the dominant entity in patients with a pPM phenotype and treatment-responsive myopathy. Isolated CK elevation was the mode of presentation of atorAIM. The new onset of isolated CK elevation on atorvastatin and persistent CK elevation on statin discontinuation should raise early suspicion for atorAIM. Statin-induced AIM should be included in the differential diagnosis of asymptomatic hyperCKemia. Three patterns of MAC deposition, while nonpathognomonic, were pathological clues to atorAIM. AtorAIM was uniformly corticosteroid resistant but responsive to IVIG as induction and maintenance therapy.

Atypical Myositis Presenting with Peripheral Neuropathy

Necrotizing Autoimmune Myositis (NAM) is an Acute autoimmune disease of the proximal skeletal muscle. The increased rate of morbidity and mortality in NAM is related to the severety and extant of muscle weakness. Patients with NAM develop antibodies to a specific signal recognition particle (anti-SRP ab). Peripheral neuropathy is extremely rare during the course of the disease. We report the case of a 35 y old male, hospitalized for severe proximal and distal muscle weakness with positive anti-SRB ab and concomitant peripheral neuropathy. The outcome was severe respiratory failure and death.

Case Report of Necrotizing Autoimmune Myositis With Slightly High Creatinine Phosphokinase

The idiopathic inflammatory myopathy consists of dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). The specific etiologies of these muscle diseases are not well known and are thought to involve components of the humoral and cellular immune system as well as other nonimmune factors. A case of NAM who was HIV-positive was reported. His muscle biopsy was highly suggestive of NAM but creatinine phosphokinase (CPK) was not favoring the diagnosis. After receiving IVIG pulse therapy, his weakness improved up to that much that he returned back to his work of auto rickshaw driving. J Neurol Res. 2014;4(4):117-120 doi: http://dx.doi.org/10.14740/jnr288w

Anti-synthetase syndrome associated with anti PL-12 and anti-Signal recognition particle antibodies and a necrotizing auto-immune myositis

We report a 37-year-old woman with a 2month history of proximal muscle weakness and extremely high creatine kinase (21,808U/L) due to necrotizing auto-immune myositis (NAM) in association with anti-synthetase syndrome. Myositis-specific auto-immune antibody panel was positive for anti-Signal recognition particle and anti-PL-12. CT scan of the chest confirmed interstitial lung disease. Prednisolone, intravenous immunoglobulin and cyclophosphamide therapy was given with gradual improvement. This patient is notable for the unusual combination of NAM and anti-synthetase syndrome with the rare finding of two myositis-specific autoantibodies, which directed testing for associated extramuscular features and management with more aggressive immunotherapy.

10. Anti-synthetase syndrome associated with necrotizing myositis – Utility of myositis specific autoantibodies in predicting prognosis and choice of treatment

The anti-synthetase syndrome is a rare, autoimmune multi-system disorder of unclear etiology characterized by a variable combination of inflammatory myositis, interstitial lung disease, Raynaud’s phenomenon and arthritis. Serum autoantibodies to aminoacyl-tRNA synthetase (Anti-PL-12) are often present. The prognosis of the disease is largely determined by the pulmonary involvement. Prednisone with or without azathioprine and methotrexate have been used for myositis, while cyclophosphamide should be considered for severe pulmonary involvement. Anti SRP associated necrotizing autoimmune myositis is part of the spectrum of autoimmune inflammatory myopathies. It is characterized by the presence of signal recognizing particle antibodies which may occur in isolation or in some cases, in conjunction with other serum auto-antibodies. We describe a rare and interesting case of a 37 year old female who presented with a progressive proximal muscle weakness involving the upper and lower limbs in association with lethargy. She also displayed Raynaud’s phenomenon and complained of exertional shortness of breath. She had extremely high creatine kinase levels (22,000) U/L and electrophysiological confirmation of an active myositis. She had positive anti SRP antibodies and muscle biopsy findings of a necrotizing autoimmune myositis. In addition, she had anti-PL-12 antibodies and evidence of interstitial lung disease on pulmonary function tests and CT lung imaging. Her constellation of symptoms, signs and investigative findings were consistent with an anti-synthetase syndrome. She was treated initially with methylprednisone, azathioprine and IVIG without significant improvement. Her myositis and ILD partially responded to IV cyclophosphamide therapy. This case demonstrates a unique patient with anti-synthetase syndrome in association with anti-SRP and anti-PL-12 myositis specific antibodies. It highlights the use of myositis-specific antibody testing in assisting the diagnosis and choice of therapy. Further studies are required to determine the occurrence of multiple myositis specific antibodies in necrotizing myopathies and if their presence correlates with prognosis and treatment response.

Case Report of Necrotizing Autoimmune Myositis With Slightly High Creatinine Phosphokinase

The idiopathic inflammatory myopathy consists of dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). The specific etiologies of these muscle diseases are not well known and are thought to involve components of the humoral and cellular immune system as well as other nonimmune factors. A case of NAM who was HIV-positive was reported. His muscle biopsy was highly suggestive of NAM but creatinine phosphokinase (CPK) was not favoring the diagnosis. After receiving IVIG pulse therapy, his weakness improved up to that much that he returned back to his work of auto rickshaw driving. J Neurol Res. 2014;4(4):117-120 doi: http://dx.doi.org/10.14740/jnr288w

Autoantibodies in Polymyositis and Dermatomyositis

Inflammatory myopathies are a group of acquired diseases, characterized by immunoflogistic processes primarily involving the skeletal muscle. According to recent classification criteria, four major diseases have been identified: polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myositis (NAM). Autoantibodies can be found in the sera of most patients with myositis. Myositis-specific autoantibodies (MSAs) are markers of very specific disease entities within the spectrum of myositis, and target proteins involved in key processes of protein synthesis. Myositis autoantigens comprise the well-defined aminoacyl-tRNA synthetases, the Mi-2 helicase/histone deacetylase protein complex, and the signal recognition particle (SRP) ribonucleoprotein, together with novel targets such as TIF1-γ, MDA5, NXP2, SAE, and HMGCR. Recent studies suggest that autoantigens drive a B cell antigen-specific immune response in muscles. Interestingly, an increased expression of Jo-1 and Mi-2 in regenerating fibers in muscle biopsies from PM and DM patients compared to normal was demonstrated. Myositis autoantigen up-regulation was observed in neoplastic tissues, thus representing a potential link between cancer and autoimmunity in myositis. Non-immunological mechanisms seem to participate to the pathogenesis of inflammatory myopathies; induction of endoplasmic reticulum stress response in response to abnormal muscle regeneration and inflammation has recently been reported in patients with myositis. This review article provides an update of new emerging insights about the clinical and pathophysiologic role of principal autoantibodies in myositis.

Pathophysiology of inflammatory and autoimmune myopathies

The main subtypes of inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion-body myositis (sIBM). The review provides an update on the main clinical characteristics unique to each subset, including fundamental aspects on muscle pathology helpful to assure accurate diagnosis, underlying immunopathomechanisms and therapeutic strategies. DM is a complement-mediated microangiopathy leading to destruction of capillaries, distal hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmunity with macrophages as the final effector cells mediating fiber injury. PM and IBM are characterized by cytotoxic CD8-positive T cells which clonally expand in situ and invade MHC-I-expressing muscle fibers. In IBM, in addition to autoimmunity, there is vacuolization and intrafiber accumulation of degenerative and stressor molecules. Pro-inflammatory mediators, such as gamma interferon and interleukin IL1-β, seem to enhance the accumulation of stressor and amyloid-related misfolded proteins. Current therapies using various immunosuppressive and immunomodulating drugs are discussed for PM, DM and NAM, and the principles for effective treatment strategies in IBM are outlined.

Review: An update on inflammatory and autoimmune myopathies

The review provides an update on the diagnosis of the main subtypes of inflammatory myopathies including dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). The fundamental aspects on muscle pathology and the unique pathomechanisms of each subset are outlined and the diagnostic dilemmas concerning the distinction of PM from sIBM and NAM are addressed. Dermatomyositis is a complement-mediated microangiopathy leading to destruction of capillaries, hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM, is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmuity with macrophages as the final effector cells causing fibre injury. In PM and sIBM cytotoxic CD8-positive T cells clonally expand in situ and invade major histocompatibility-I-expressing muscle fibres. The pathology of sporadic inclusion body myositis is complex because, in addition to the inflammatory mechanisms, there are degenerative features characterized by vacuolization and the accumulation of stressor and amyloid-related misfolded proteins. Inducible pro-inflammatory molecules, such as interleukin 1-β, may enhance the accumulation of stressor proteins. The principles for more effective treatment strategies are discussed.