Neutrophil extracellular traps are involved in the occurrence of interstitial lung disease in a murine experimental autoimmune myositis model.

The excessive formation of neutrophil extracellular traps (NETs) has been demonstrated to be a pathogenic mechanism of idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD). This study aimed to answer whether an experimental autoimmune myositis (EAM) model can be used to study IIM-ILD and whether NETs participate in the development of EAM-ILD. An EAM mouse model was established using skeletal muscle homogenate and pertussis toxin (PTX). The relationship between NETs and the ILD phenotype was determined via histopathological analysis. As NETs markers, serum cell-free DNA (cfDNA) and serum citrullinated histone 3 (Cit-H3)-DNA were tested. The healthy mouse was injected with PTX intraperitoneally to determine whether PTX intervention could induce NETs formation in vivo. Neutrophils isolated from the peripheral blood of healthy individuals were given different interventions to determine whether PTX and skeletal muscle homogenate can induce neutrophils to form NETs in vitro. EAM-ILD had three pathological phenotypes similar to IIM-ILD. Cit-H3, neutrophil myeloperoxidase, and neutrophil elastase were overexpressed in the lungs of EAM model mice. The serum cfDNA level and Cit-H3-DNA complex level were significantly increased in EAM model mice. Serum cfDNA levels were increased significantly in vivo intervention with PTX in mice. Both PTX and skeletal muscle homogenate-induced neutrophils to form NETs in vitro. EAM-ILD pathological phenotypes are similar to IIM-ILD, and NETs are involved in the development of ILD in a murine model of EAM. Thus, the EAM mouse model can be used as an ideal model targeting NETs to prevent and treat IIM-ILD.

Inflammatory Myositis Following Statin Use in a Patient With Untreated Hypothyroidism.

Inflammatory myositis (IM) presents a diagnostic challenge due to its multifaceted etiology and varying clinical presentations. This case involves a 55-year-old male with asymptomatic hypothyroidism, recent statin use, and rapidly progressing proximal muscle weakness. He presented with profound weakness in the upper and lower extremities, severely impairing his daily activities. The patient's medical history included recent hospitalizations for idiopathic interstitial lung disease, myopericarditis, and pneumonia, adding complexity to his condition. Laboratory findings revealed elevated serum muscle enzymes, notably creatine kinase, indicating muscle damage and rhabdomyolysis. Serological testing confirmed the absence of myositis-specific antibodies and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. The patient was eventually diagnosed with IM and rhabdomyolysis, likely secondary to statin use or hypothyroidism. Treatment with methylprednisolone, levothyroxine, and discontinuation of atorvastatin led to rapid improvements in AST levels and overall muscle strength. This case highlights the challenges of managing IM and emphasizes the importance of assessing thyroid function before initiating lipid-lowering therapy.

Dysphagia: A Case Report of an Atypical Presentation of Statin-Induced Necrotizing Myositis.

Statin medications act by inhibiting the enzyme hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR), thus decreasing hepatic cholesterol synthesis. They are considered the mainstay treatment of hypercholesterolemia due to their tremendous efficacy and mortality benefit. Although generally well tolerated, statins may adversely affect skeletal muscle resulting in side effects ranging from mild myalgia to life-threatening necrotizing myositis. Statin-induced necrotizing autoimmune myositis is a rare yet devastating adverse effect that may occur shortly after initiation of therapy or after several years of use. Unfortunately, medication discontinuation has shown no impact on prevention or alleviation of symptoms. Though there is currently no definitive guidance for the treatment of this condition, corticosteroids are generally considered to be first line, via high-dose oral prednisone or intravenous methylprednisolone. In this case report, we discuss the case of a 72-year-old male with an unusual presentation of statin-induced necrotizing autoimmune myositis: dysphagia, weakness, and weight loss. His diagnosis was confirmed by muscle biopsy indicating necrotizing myositis and his serum was found to be strongly positive for anti-HMG-CoA reductase antibodies. This patient had a very brief history of statin use, but his primary care provider discontinued the medication a couple of months prior to symptom onset due to elevated liver function tests. He was treated with aggressive intravenous fluid hydration and intravenous corticosteroids during an extended inpatient hospital stay. He was discharged to a rehabilitation facility. This report demonstrates the importance of creating a wide differential for patients who present with fatigue, generalized weakness, and dysphagia. It is essential to always consider statin-induced necrotizing myositis if a patient has a history of statin use, even if the statin has been discontinued. Necrotizing myositis demands timely diagnosis and management to improve mortality.

Autoimmune inflammatory myopathies.

The autoimmune inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation and moderate to severe muscle weakness. Based on currently evolved distinct clinical, histologic, immunopathologic, and autoantibody features, these disorders can be best classified as dermatomyositis, necrotizing autoimmune myositis, antisynthetase syndrome-overlap myositis, and inclusion body myositis. Although polymyositis is no longer considered a distinct subset but rather an extinct entity, it is herein described because its clinicopathologic information has provided over many years fundamental information on T-cell-mediated myocytotoxicity, especially in reference to inclusion body myositis. Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis, and response to immunotherapies, necessitating the need to correctly diagnose each subtype from the outset and avoid disease mimics. The paper describes the main clinical characteristics that aid in the diagnosis of each myositis subtype, highlights the distinct features on muscle morphology and immunopathology, elaborates on the potential role of autoantibodies in pathogenesis or diagnosis , and clarifies common uncertainties in reference to putative triggering factors such as statins and viruses including the 2019-coronavirus-2 pandemic. It extensively describes the main autoimmune markers related to autoinvasive myocytotoxic T-cells, activated B-cells, complement, cytokines, and the possible role of innate immunity. The concomitant myodegenerative features seen in inclusion body myositis along with their interrelationship between inflammation and degeneration are specifically emphasized. Finally, practical guidelines on the best therapeutic approaches are summarized based on up-to-date knowledge and controlled studies, highlighting the prospects of future immunotherapies and ongoing controversies.

An undifferentiated cause of rhabdomyolysis: a case report.

BACKGROUND: Rhabdomyolysis can occur secondary to infections, trauma, or myotoxic substances. Rhabdomyolysis secondary to autoimmune myositis occurs rarely. Distinguishing autoimmune rhabdomyolysis from rhabdomyolysis secondary to other causes is paramount in considering the long-term management of autoimmune rhabdomyolysis. It is further important to continue close follow-up and further testing to completely understand the extent of this disease as diagnoses may be ever-changing. CASE PRESENTATION: A previously healthy female presented to the hospital with myalgias and myoglobinuria following a respiratory infection treated with azithromycin and promethazine. Labs demonstrating elevated creatine kinase (CK) prompted treatment for rhabdomyolysis and rheumatology consultation. The patient was given 3 l of intravenous (IV) 0.9% sodium chloride in the Emergency Department. Upon admission, the patient was placed on a continuous IV drip of 0.9% sodium chloride running at 300 cc/hour for all 8 days of her hospital admission. The rheumatology autoantibody panel pointed towards autoimmune myositis as a potential cause of her rhabdomyolysis. The patient was discharged to follow up with rheumatology for further testing. CONCLUSION: Autoimmune myositis, although less common than other etiologies of rhabdomyolysis, is important to consider as the long-term management of autoimmune myositis includes the use of immunosuppressants, antimalarials, or IV immunoglobulins, which may be inappropriate for other etiologies of rhabdomyolysis.

Statin-induced autoimmune myositis: a proposal of an "experience-based" diagnostic algorithm from the analysis of 69 patients.

Statin-induced autoimmune myositis (SIAM) represents a rare clinical entity that can be triggered by prolonged statin treatment. Its pathogenetic substrate consists of an autoimmune-mediated mechanism, evidenced by the detection of antibodies directed against the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR Ab), the target enzyme of statin therapies. To facilitate the diagnosis of nuanced SIAM clinical cases, the present study proposes an "experience-based" diagnostic algorithm for SIAM. We have analyzed the clinical data of 69 patients diagnosed with SIAM. Sixty-seven patients have been collected from the 55 available and complete case records regarding SIAM in the literature; the other 2 patients represent our direct clinical experience and their case records have been detailed. From the analysis of the clinical features of 69 patients, we have constructed the diagnostic algorithm, which starts from the recognition of suggestive symptoms of SIAM. Further steps provide for CK values dosage, musculoskeletal MR, EMG/ENG of upper-lower limbs and, Anti-HMGCR Ab testing and, where possible, the muscle biopsy. A global evaluation of the collected clinical features may suggest a more severe disease in female patients. Atorvastatin proved to be the most used hypolipidemic therapy.

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

BACKGROUND: There 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 PRESENTATION: We 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. CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

Debilidad muscular proximal progresiva de inicio subagudo en un paciente anciano: descripción de un caso / Progressive proximal muscle weakness with subacute onset in an elderly patient: a case report

Introducción: Las estatinas son de los medicamentos más recetados. Aunque las estatinas generalmente se toleran bien, pueden provocar efectos secundarios musculoesqueléticos. La miopatía autoinmune necrotizante inducida por estatinas (SINAM) es una afección rara y la prevalencia sólo es de 1 de cada 100.000 personas. Este trastorno se caracteriza por debilidad muscular simétrica progresiva y grave, elevación marcada de la creatincinasa y síntomas persistentes a pesar de la interrupción de la estatina. La electromiografía suele mostrar un patrón de miopatía irritable inespecífico, indistinguible de otras miopatías inflamatorias. La biopsia muscular muestra la presencia de fibras necróticas, fibras en regeneración sin células inflamatorias significativas y una regulación positiva difusa o focal de la expresión del complejo mayor de histocompatibilidad de clase I. Los anticuerpos anti-3-hidroxi-3-metilglutaril-coenzima A (anti-HMG-CoA) reductasa representan un rasgo serológico característico de la SINAM.Caso clínico: Presentamos a un paciente que desarrolló debilidad muscular progresiva después de tomar simvastatina durante los últimos siete años. En la presentación inicial, su nivel de creatincinasa fue de 2.954 U/L y los anticuerpos anti-HMG-CoA reductasa fueron positivos. La biopsia mostró rasgos miopáticos profundos con numerosas fibras necróticas, algunas fibras en regeneración e infiltrado de células inflamatorias perimisial, combinado con una sobreexpresión difusa del complejo mayor de histocompatibilidad de clase I. Se le diagnosticó SINAM, se suspendió la estatina y se inició una dosis alta de corticoides sistémicos, inmunoglobulina intravenosa y metotrexato. Después de tres meses de seguimiento, tuvo una mejora significativa en la fuerza muscular y el nivel de creatincinasa volvió a la normalidad.(AU)

Introduction: Statins are some of the most widely prescribed medications. Although statins are generally well tolerated, they can lead to musculoskeletal side effects. Statin-induced necrotizing autoimmune myositis (SINAM) is a rare condition and the prevalence is only 1 per 100,000 people. This disorder is characterized by progressive and severe symmetric muscle weakness, marked elevation of creatine kinase and persistent symptoms despite statin discontinuation. Electromyography commonly shows a nonspecific irritable myopathy pattern indistinguishable from other inflammatory myopathies. Muscle biopsy shows the presence of necrotic fibers, regenerating fibers without significant inflammatory cells and diffuse or focal upregulation of major histocompatibility complex class I expression. The anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies represent a characteristic serological feature of SINAM. Case report: We present a patient who developed progressive muscle weakness after taking simvastatin for the last seven years. At initial presentation, her creatine kinase level was 2,954 U/L and anti-HMGCR antibodies were positive. The biopsy showed a profound myopathic features with numerous necrotic fibers, some regenerating fibers and perimysial inflammatory cell infiltrate, combined with a diffuse overexpression of major histocompatibility complex class I products. She was diagnosed with SINAM, statin was suspended and a high dose of systemic corticosteroids, intravenous immunoglobulin therapy and methotrexate was started. At three-month follow-up, she had significant improvement in muscle strength and creatine kinase level returned to normal...(AU)

Statin-Induced Necrotizing Autoimmune Myositis.

Statins are the most frequently prescribed medications for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The United States Preventative Services Task Force recommends that clinicians selectively offer a statin for the primary prevention of ASCVD for adults aged 40 - 75 years with one or more cardiovascular disease risk factors and an estimated 10-year risk of a cardiovascular event of 10% or greater. Despite their ubiquity, it is estimated that approximately 6-10% of patients remain intolerant due to muscle aches. Here, we present a case of a 71-year-old female that was taking atorvastatin for a year and presented to the emergency room with proximal muscle aches and weakness. Laboratory values were significant for an elevated creatinine kinase of 4,166 U/L (reference range, 20 - 180). Her magnetic resonance imaging was significant for edema in bilateral lower extremity proximal muscles. Serology revealed a high anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody, confirming the diagnosis of statin-induced necrotizing autoimmune myositis. A muscle biopsy of the right vastus lateralis revealed necrotic muscle fibers. During her hospital course, she was treated with intravenous methylprednisolone, mycophenolate mofetil, and tacrolimus. Her symptoms gradually improved, and she was discharged after 14 days with a rheumatology follow-up. This is an exceedingly rare complication of statin use and has only recently received increasing attention. Here we present our experience with this disease.

Mechanic's Hand Heralding Relapse in an Indian Adolescent with Anti-MDA5 Positive Juvenile Dermatomyositis.

Anti-MDA5 antibodies characterise a distinct phenotype of dermatomyositis in adults as well as children, with ethnic disparity in clinical presentation and severity. They often present as a diagnostic conundrum with rash, ulceration, and polyarthritis, but minimal muscle disease. Mechanic's hands are typically associated with anti-synthetase syndrome, but their presence in anti-MDA5 antibody positive patients, although reported, is not well known. We present the case of a boy in whom mechanic's hand heralded a relapse of juvenile dermatomyositis which was suspected based on remotely assessed patient-reported outcome measures on teleconsultation. This report suggests that mechanic's hands should also prompt testing for myositis antibodies including anti-MDA5 in Indian children with JDM. Diligent awareness of the condition, and timely use of patient reported outcome measures of muscle power and skin assessment may guide management while delivering remote care in challenging situations such as a global pandemic.

Statin-Related Necrotizing Autoimmune Myositis: More Than Myalgia.

Statins are widely prescribed for cardiovascular disease, and, in general, are well tolerated by most people. Most side effects related to statins are mild, with some side effects also considered a nocebo effect. Occasionally, statins can be associated with severe side effects. One of the more severe adverse events is immune-mediated necrotizing myositis, which is both difficult to diagnose and treat. The symptoms can be debilitating, and aggressive immunosuppressive therapy is the best-recognized method of treatment of this complication. In this case report, we discuss the clinical features, diagnosis, and treatment of this disease entity with an emphasis on the need for rapid diagnosis and aggressive treatment to help reduce morbidity.

Activation of TLR4 induces inflammatory muscle injury via mTOR and NF-κB pathways in experimental autoimmune myositis mice.

Idiopathic inflammatory myopathy (IIM) is an autoimmune disease that invades skeletal muscle; however, the etiology of IIM is still poorly understood. Toll-like receptor (TLR) 4 has been widely reported to take part in the autoimmune inflammation of IIMs. The mammalian target of rapamycin, mTOR, is a key central substance which mediates immune responses and metabolic changes, and also has been confirmed to be involved in the pathogenesis of IIMs. However, the interconnectedness between TLR4 and mTOR in IIM inflammation has not been fully elucidated. We hypothesized that TLR4 may play an important role in IIM inflammatory muscle injury by regulating mTOR. Mice were divided into four groups: a normal control group, IIM animal model (experimental autoimmune myositis, EAM) group, TAK242 intervention group and rapamycin (RAPA) intervention group. The results of EAM mice showed that TLR4, mTOR, nuclear factor-kappa B (NF-κB) and inflammatory factors interleukin-17A (IL-17A) and interferon γ (IFN-γ) mRNA levels were significantly upregulated. These factors were positively correlated with the degree of muscle inflammatory injury. When EAM mice were given the antagonist TAK242 to inhibit the TLR4 pathway, the results demonstrated that both mTOR and NF-κB were downregulated in the muscle of the mice. Muscle staining showed that the inflammatory injury was alleviated and the EAM mouse muscle strength was improved. Then, RAPA was used to inhibit the mTOR pathway, and the inflammatory factors IL-17A and IFN-γ were downregulated in EAM mouse muscle and serum. Consistently, muscle inflammatory injury was significantly reduced, and muscle strength was significantly improved. Our results suggest that TLR4 may regulate inflammatory muscle injury in EAM by activating the mTOR and NF-κB pathways, which provides both an experimental complement for the pathological mechanism of IIM and an encouraging target for the selection of effective treatments.

An exploratory study of circulating cytokines and chemokines in patients with muscle disorders proposes CD40L and CCL5 represent general disease markers while CXCL10 differentiates between patients with an autoimmune myositis.

Discriminating an autoimmune myositis from other disorders and subtyping of patient groups within this heterogeneous group of conditions remain diagnostic challenges. In our study we explored the potential of cytokine and chemokine typing in patient sera as an addition to the expanding set of blood-accessible diagnostic biomarkers available today. We selected sets of ten patients within well-characterized disease groups representing healthy controls, and patients with hereditary muscular dystrophies, immune-mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis (IBM). Prescreening using proteome arrays singled out three biomarker candidates, being the cytokine CD40L, and chemokines CXCL10 and CCL5. Enzyme-linked immunosorbent assays showed all three markers to be elevated in muscle disease irrespective of patient subgroup. CXCL10 levels on the other hand were higher in autoimmune myositis only, and levels were significantly higher in IBM compared to IMNM. The strong CXCL10 expression observed in the auto-aggressive inflammatory cells within IBM muscle tissues possibly represents a major source of circulating CXCL10. We conclude that CXCL10 levels could represent a convenient marker for autoimmune myositis indicative of patient subgroups.

Anti-Ro52 Autoantibody Is Common in Systemic Autoimmune Rheumatic Diseases and Correlating with Worse Outcome when Associated with interstitial lung disease in Systemic Sclerosis and Autoimmune Myositis.

This review highlights the 30 plus years research progress since the discovery of autoantibody to Ro52/TRIM21 in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). After the initial expression cloning of the Ro52 cDNA, it has taken many years to the current understanding in the interesting biological function of Ro52 as an E3 ubiquitin ligase and its role in innate immune clearance of intracellular IgG-bound complex. Early observations show that anti-Ro52, mostly associated with anti-SS-A/Ro60 and/or anti-SS-B/La, is commonly found in SLE (40-70%), SjS (70-90%), neonatal lupus erythematosus (NLE, 75-90%), and subacute cutaneous lupus erythematosus (50-60%). Anti-Ro52 has long been postulated to play a direct pathogenic role in congenital heart block in NLE as well as in the QT interval prolongation in some adults. The widespread availability of the anti-Ro52 assay has led to the detection of anti-Ro52 in other diseases including autoimmune hepatitis (20-40%), systemic sclerosis (10-30%), and autoimmune myositis (20-40%). More than ten studies have pointed to an association of anti-Ro52 with interstitial lung disease and, more importantly, correlating with poor outcome and worse survival. Other studies are implicating an interesting role for anti-Ro52 in the diagnosis of certain cancers. Future studies are needed to examine the mechanism in the pathogenesis of anti-Ro52 and carefully documenting its causal relationships in different disease conditions.

The prevalence and clinical characteristics of anti-HMGCR (anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) antibodies in idiopathic inflammatory myopathy: an analysis from the MyoCite registry.

This study aimed to determine the prevalence and clinical characteristics of anti-HMGCR antibodies in idiopathic inflammatory myositis (IIM) at a tertiary care centre in northern India. Data (adult and children) were retrieved from the MyoCite dataset, identifying patients with polymyositis, dermatomyositis, and antibody-negative IIM whilst fulfilling the ACR/EULAR criteria. SLE, sarcoidosis, and systemic sclerosis were included for comparison as disease controls. The baseline clinical profile, laboratory tests, and muscle biopsies were retrieved and analysed. Descriptive statistics and non-parametric statistics were used for comparison. Among 128 IIM (112 adults, 16 children, M:F 1:2.8) of age 37 (24-47) years and 6 (3-17) months disease duration, 4 (3.6%) young adults tested positive for anti-HMGCR antibodies. All children and disease control tested negative for the antibody. Anti-HMGCR + IIM exhibited higher muscle enzymes [AST (367 vs 104 IU/L, p = 0.045), ALT (502 vs 78 IU/L, p = 0.004), and CPK (12,242 vs 699 IU/L, p = 0.001] except lactate dehydrogenase with less frequent systemic features such as fatigue than antibody-negative IIM. One young girl presented with a Limb-girdle muscular dystrophy (LGMD) with chronic pattern. None of the patients exhibited rashes, statin exposure, or cancer, though one had anti-Ro52 and mild disease. Our observations depict a younger population while affirming previous literature, including NM-like presentation, and chronic LGMD-like pattern of weakness in one case. Although a small number of children were included, ours is one of the few paediatric studies that evaluated HMGCR antibodies thus far. Further investigations in a larger Indian cohort are warranted to substantiate our findings.

A Rapidly Debilitating Myopathy: A Rare Case of Statin-Induced Necrotizing Myositis.

Statins are well tolerated in general but can be associated with myopathies. Statin-induced myopathies can range widely from mild myalgias to necrotizing autoimmune myopathies. We present a case of an 81-year-old man on statins for five years with no complications, who developed progressive muscle weakness, rhabdomyolysis, and dysphagia. His laboratory workup revealed elevated inflammatory markers with creatine kinase (CK) levels above 2000 U/L. The myositis panel was negative, and the anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody was positive. His muscle biopsy showed randomly scattered necrotic fibers with minimal perivascular inflammation confirming statin-induced necrotizing autoimmune myopathy (SINAM). Statins were discontinued immediately after initial suspicion. The patient was started on intravenous immunoglobulin followed by hydrocortisone and mycophenolate mofetil. The patient continued to have muscle weakness and progressive dysphagia to the point that he could not handle his secretions. His disease course was complicated by recurrent aspiration pneumonia. Percutaneous endoscopic gastrostomy tube placement was considered, but his family decided on hospice care given his overall comorbidities. Physicians should note that SINAM can occur after a few months to several years of statin use. This disease can be rapidly debilitating and progress even after discontinuation of statins, and treatment requires immunosuppressants, including steroids and steroid-sparing agents.

Study of the correlation between the noncanonical pathway of pyroptosis and idiopathic inflammatory myopathy.

BACKGROUND: The pathogenesis of idiopathic inflammatory myopathy (IIM) is complex and unclear. The purpose of this study was to investigate whether the noncanonical pathway of pyroptosis is involved in the pathogenesis of IIM, and the intervention effect of drugs glyburide and bright blue G (BBG). METHODS: After the drug intervention, we detected the expression of the caspase-4, caspase-5, caspase-11, GSDMD, pannexin-1, NLRP3 and P2X7R proteins in skeletal muscle tissues from the six groups using Western blotting. We detected the expression of the caspase-11, GSDMD, pannexin-1, NLRP3 and P2X7R mRNAs in skeletal muscle tissues from the six groups using RT-qPCR and detected the serum IL-18 and IL-1ß levels in the six groups using ELISAs. RESULT: Lower expression levels of the P2X7R and NLRP3 proteins were observed in the EAM + BBG group than in the EAM1 group (P < 0.05). The expression of NLRP3 in the EAM + glyburide group was lower than in the EAM2 group (P < 0.05). Lower expression levels of the P2X7R and NLRP3 mRNAs were detected in the EAM + BBG group than in the EAM1 group (P < 0.05). NLRP3 was expressed at lower levels in the EAM + glyburide group than in the EAM2 group (P < 0.05). Lower serum IL-1ß levels were detected in the EAM + BBG group than in the EAM1 group (P < 0.05), and serum IL-1ß and IL-18 levels in the EAM + glyburide group were lower than those in the EAM2 group (P < 0.05). CONCLUSION: Our results suggest that the noncanonical pathway of pyroptosis may be involved in the pathogenesis of IIM, and glyburide and BBG exert certain intervention effects on its pathogenesis.

Delayed-onset Necrotizing Myositis following COVID-19 Infection.

As the numbers of cases of COVID-19 continue to rise, the heterogeneity of its clinical manifestation continues to increase. Here, we describe a case of delayed-onset, biopsy-proven necrotizing myositis following infection with SARS-CoV-2. LEARNING POINTS: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.We need more studies to understand the underlying pathogenesis of SARS-CoV-2-induced myositis.

The Diagnostic Value of MR IVIM and T2 Mapping in Differentiating Autoimmune Myositis From Muscular Dystrophy.

RATIONALE AND OBJECTIVES: To confirm the feasibility and compare the accuracy of magnetic resonance imaging intravoxel incoherent motion (IVIM) and T2 mapping models for the differentiation of autoimmune myositis from muscular dystrophy. MATERIALS AND METHODS: Fourty-two autoimmune myositis and 11 muscular dystrophy patients proven by diagnostic criteria were enrolled in the study. Conventional MR sequences, IVIM, and T2 mapping through the bilateral thighs were obtained as well as blood samples for all patients. IVIM and T2 mapping parameters as well as serum markers were compared between the autoimmune myositis and muscular dystrophy groups. Mann-Whitney U tests were performed for statistical analysis along with receiver operating characteristic curves. Spearman correlation coefficient models were constructed to analyze the correlation between IVIM and T2 mapping with serological parameters. RESULTS: The intramuscular apparent diffusion coefficient, tissue diffusivity (D), perfusion fraction (fp), and T2 relaxation time values were statistically significantly different between the autoimmune myositis and muscular dystrophy groups (p < 0.05). Pseudo diffusivity (Dp) values showed no statistical difference between the groups (p > 0.05). D parameter of IVIM sequences differentiated autoimmune and muscular dystrophy with a higher specificity of 75.60%. T2 values within the thighs were correlated with serum creatine kinase and lactate dehydrogenase levels (p < 0.05). CONCLUSION: Thigh muscle IVIM and T2 mapping parameters are useful in differentiating autoimmune myositis from muscular dystrophy, particularly the IVIM parameters.

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients.

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.