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1.
Nat Commun ; 14(1): 108, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609505

RESUMO

Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics in mitigating such processes and their impact on muscle fitness remain unaddressed. Here we report that opposite mitochondrial morphologies induce distinct inflammatory signatures, caused by differential activation of DNA sensors TLR9 or cGAS. In the context of mitochondrial fragmentation, we demonstrate that mitochondria-endosome contacts mediated by the endosomal protein Rab5C are required in TLR9 activation in cells. Skeletal muscle mitochondrial fragmentation promotes TLR9-dependent inflammation, muscle atrophy, reduced physical performance and enhanced IL6 response to exercise, which improved upon chronic anti-inflammatory treatment. Taken together, our data demonstrate that mitochondrial dynamics is key in preventing sterile inflammatory responses, which precede the development of muscle atrophy and impaired physical performance. Thus, we propose the targeting of mitochondrial dynamics as an approach to treating disorders characterized by chronic inflammation and mitochondrial dysfunction.


Assuntos
DNA Mitocondrial , Miosite , Humanos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Receptor Toll-Like 9/metabolismo , Dinâmica Mitocondrial/genética , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Inflamação/patologia
2.
Clin Med (Lond) ; 23(1): 85-87, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36697016

RESUMO

A previously fit and well 38-year-old man presented during the COVID-19 pandemic with dyspnoea, cough and palpitations. C-reactive protein was elevated and chest X-ray demonstrated bilateral lower zone consolidation. SARS CoV-2 swab was negative. He was diagnosed with community-acquired pneumonia and treated with oral antibiotics. He developed severe type 1 respiratory failure and was admitted to the high-dependency unit for non-invasive ventilation. CTPA was negative for pulmonary embolism, instead demonstrating bilateral organising pneumonia. Empirical treatment for swab-negative COVID-19 pneumonitis was started; however, further deterioration ensued and prompted intubation and ventilation. Microbiological testing did not yield any positive results, thereby raising suspicion for the presence of an autoimmune disease. Pulsed intravenous methylprednisolone was administered with good effect. ENA screen was positive for anti-Jo1 and myositis-specific autoantibodies were positive for Ro-52, Ku and PL-12. The patient was extubated and did not exhibit any muscle weakness on clinical examination. Creatine kinase was only mildly elevated. He was diagnosed with amyopathic antisynthetase syndrome - frequently considered as a form of idiopathic inflammatory myopathy (IIM) - and treated with further intravenous methylprednisolone and cyclophosphamide. Oxygen therapy was gradually weaned and the patient discharged on mycophenolate mofetil and a weaning course of oral steroids.


Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Miosite , Pneumonia , Masculino , Humanos , Adulto , Pandemias , Miosite/complicações , Miosite/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Autoanticorpos , Metilprednisolona/uso terapêutico
3.
J Investig Med High Impact Case Rep ; 11: 23247096221150636, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36661254

RESUMO

Immune-mediated necrotizing myopathy (IMNM) is a subtype of inflammatory myopathy that is characterized by proximal muscle weakness, markedly elevated serum creatine kinase, myopathic electromyographic findings, and muscle biopsies revealing necrosis or regeneration with sparse inflammatory infiltrate. IMNM tends to be idiopathic but has been associated with certain medications. This supports the possibility for other pharmacotherapies to induce IMNM-particularly leflunomide. Leflunomide is used in the treatment for rheumatoid arthritis and has been shown to induce autoimmune diseases-including autoimmune hepatitis and polymyositis. After an extensive review of history and workup of muscle weakness, we conclude that leflunomide induced an IMNM in our patient. As this is the first case of leflunomide-induced IMNM, it is important for clinicians to suspect an inflammatory myopathy in the setting of myositis while on leflunomide.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Miosite , Humanos , Leflunomida/efeitos adversos , Músculo Esquelético/patologia , Miosite/induzido quimicamente , Miosite/complicações , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/complicações , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Debilidade Muscular
5.
RMD Open ; 9(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36635001

RESUMO

BACKGROUND: Pain is considered a priority for research by adult patients with autoimmune inflammatory myopathy (AIM) and their families. Our aim was to review the literature for studies reporting on pain in adult AIM and to summarise their findings. METHODS: A scoping review was conducted searching for studies in PubMed and MEDLINE including more than five adult patients with AIM and assessing pain using a patient-reported outcome measure. Study population characteristics, pain measurement and clinical correlates of pain were extracted using a standardised protocol. RESULTS: The search strategy identified 2831 studies with 33 meeting inclusion criteria. Most studies used visual analogue scales (n=14) and/or the Medical Outcomes Study 36-Item Short Form Bodily Pain Scale (n=17). Frequency of pain and/or myalgias ranged from 64% to 100%. Subjects with AIM had significantly more pain than the general population and comparable pain to other chronic rheumatic diseases. Insufficient results were available to identify significant clinical correlates of pain in AIM. CONCLUSION: This review suggests that the burden of pain in AIM is considerable. Still, due to the heterogeneity and low quality of the evidence, significant knowledge gaps persist. Studies are needed to characterise pain trajectories of patients with AIM.


Assuntos
Doenças Autoimunes , Miosite , Adulto , Humanos , Dor/etiologia , Miosite/complicações
6.
Nutrients ; 15(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615906

RESUMO

Eccentric contraction can easily cause muscle damage and an inflammatory response, which reduces the efficiency of muscle contraction. Resveratrol causes anti-inflammatory effects in muscles, accelerates muscle repair, and promotes exercise performance after contusion recovery. However, whether resveratrol provides the same benefits for sports injuries caused by eccentric contraction is unknown. Thus, we explored the effects of resveratrol on inflammation and energy metabolism. In this study, mice were divided into four groups: a control group, an exercise group (EX), an exercise with low-dose resveratrol group (EX + RES25), and an exercise with high-dose resveratrol group (EX + RES150). The results of an exhaustion test showed that the time before exhaustion of the EX + RES150 group was greater than that of the EX group. Tumour necrosis factor-α (Tnfα) mRNA expression was lower in the EX + RES150 group than in the EX group. The energy utilisation of the EX + RES150 group was greater than that of the EX + RES25 group in different muscles. High-dose resveratrol intervention decreased Tnfα mRNA expression and enhanced the mRNA expressions of sirtuin 1, glucose transporter 4, AMP-activated protein kinase α1, and AMP-activated protein kinase α2 in muscles. These results revealed that high-dose resveratrol supplementation can reduce inflammation and oxidation and improve energy utilisation during short-duration high-intensity exercise.


Assuntos
Músculo Esquelético , Miosite , Camundongos , Animais , Resveratrol/farmacologia , Resveratrol/metabolismo , Músculo Esquelético/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Miosite/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Contração Muscular/fisiologia , RNA Mensageiro/metabolismo
7.
Med. clín (Ed. impr.) ; 160(1): 10-16, enero 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-213902

RESUMO

Objectives: Idiopathic inflammatory myopathies (IIMs) are systemic, heterogeneous diseases, which mainly affect skeletal muscle. Myositis with cancer is often referred to as cancer-associated myositis (CAM), which is associated with poor prognosis. This study aimed to determine the cancer associated myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with IIMs.MethodsThis retrospective study enrolled 312 patients with IIMs who were treated at Tianjin Medical University General Hospital, China, from January 2015 to December 2020. Clinical data were collected. Serum MSAs, including anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ and anti-HMGCR antibodies were detected. Cancer-associated MSAs, their phenotypic and survival features were estimated through SPSS 20.0.ResultsThe results revealed that anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies with odds ratios (95% CI) of 8.70 (3.35–22.64) and 22.31 (4.32–115.05), respectively. Skin lesions, proximal weakness, dysphagia and dysarthria were observed more frequently in patients carrying anti-TIF1-γ antibody. By contrast, patients with anti-TIF1-γ antibody had a lower frequencies of fever, arthritis/arthralgia and interstitial lung disease (ILD). Anti-TIF1-γ antibody positive CAM comprised about half of CAM entities and had the characteristic of close temporal association with cancer detection/recurrence. Female-dominant, common reproductive system tumors were other clinical features of this subset. Besides, patients with anti-TIF1-γ antibody positive had significantly lower survival rates than the anti-TIF1-γ antibody negative group. (AU)


Objetivo: La miopatía inflamatoria idiopática (IIM, por sus siglas en inglés) es una enfermedad sistémica y heterogénea que afecta principalmente al músculo esquelético. La miositis asociada al cáncer se denomina a menudo miositis relacionada con el cáncer, y está relacionada con un mal pronóstico. El objetivo de este estudio fue identificar autoanticuerpos específicos de miositis relacionados con el cáncer en pacientes chinos, y dilucidar su correlación con las características clínicas.MétodosEl estudio retrospectivo incluyó a 312 pacientes con IIM tratados en el hospital general de la Universidad Médica de Tianjin, China, de enero de 2015 a diciembre de 2020. Recoger datos clínicos. Se detectaron autoanticuerpos específicos de miositis sérica, incluyendo anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ, anti-HMGCR. Los autoanticuerpos relacionados con el cáncer, sus fenotipos y sus características de supervivencia fueron evaluados por SPSS® 20.0.ResultadosLos resultados mostraron que el anticuerpo anti-TIF1-γ y el anticuerpo anti-SAE eran autoanticuerpos relacionados con el cáncer con una relación de predominio (IC 95%) de 8,70 (3,35–22,64) y 22,31 (4,32–115,05), respectivamente. La frecuencia de lesiones cutáneas, debilidad proximal, disfagia y disartria fue mayor en los pacientes portadores de anticuerpos anti-TIF1-γ. En comparación, la incidencia de fiebre, artritis/artralgia y enfermedad pulmonar intersticial (ILD) en pacientes con anticuerpos anti-TIF1-γ fue menor. La miositis relacionada con el cáncer con anticuerpos anti-TIF1-γ positivos representa aproximadamente la mitad de la miositis relacionada con el cáncer y tiene características temporales estrechamente relacionadas con la detección/recidiva del cáncer. (AU)


Assuntos
Humanos , Autoanticorpos , Miosite , Neoplasias/complicações , China/epidemiologia , Estudos Retrospectivos
8.
Rev Neurol ; 76(1): 31-34, 2023 01 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36544374

RESUMO

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. CONCLUSION: In this case, exclusion of inflammatory myopathies, metabolic muscle disorders and other neurological diseases is necessary for establishing a reliable diagnosis. In SINAM, simply discontinuing statin is often insufficient and aggressive immunosuppression or immunomodulation therapy is needed to achieve disease remission. This case aims to demonstrate that statins can induce serious muscular diseases that require aggressive immunosuppression.


TITLE: Debilidad muscular proximal progresiva de inicio subagudo en un paciente anciano: descripción de un caso.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. Conclusiones. En este caso, la exclusión de miopatías inflamatorias, trastornos musculares metabólicos y otras enfermedades neurológicas es necesaria para establecer un diagnóstico fidedigno. En la SINAM, la simple suspensión de las estatinas a menudo es insuficiente, y es necesaria una terapia de inmunosupresión o inmunomodulación agresiva para lograr la remisión de la enfermedad. Este caso tiene como objetivo demostrar que las estatinas pueden inducir enfermedades musculares graves que requieren una inmunosupresión agresiva.


Assuntos
Doenças Autoimunes , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Musculares , Miosite , Humanos , Feminino , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Autoanticorpos , Doenças Musculares/induzido quimicamente , Debilidade Muscular/induzido quimicamente , Creatina Quinase
10.
Rev Med Inst Mex Seguro Soc ; 61(1): 99-105, 2023 Jan 02.
Artigo em Espanhol | MEDLINE | ID: mdl-36542793

RESUMO

Dermatomyositis positive anti-melanoma differentiation-associated gene 5 (anti-MDA5 DM) is a rare disease that represents less than 2%. The prevalence of anti-MDA5 DM ranges from 7 to 60%, with higher prevalence in Asian (11-60%) and women. The clinical picture may be variable and is accompanied by the typical features of dermatomyositis, such as periorbital heliotrope (blue-purple) rash with edema, erythematous rash on the face, or the anterior chest (in a V-sign), and back and shoulders (in a shawl sign), violaceous papules or plaques located on the dorsal part of the metacarpophalangeal or interphalangeal joints, which are pathognomonic by definition; yet, one of the most striking signs is the painful ulceration skin that is found in 82% of cases, which is deep and in punching holes or showing hyperkeratotic crusts. For diagnosis is necessary the typical DM rashes (Gottron's papules or Gottron's sign and heliotrope rash), along with either an "interface dermatitis" skin pathology or evidence of myositis or a MSA (myositis-specific autoantibodies). Immunoprecipitation is the gold standard method to detect MSA. Combinations of glucocorticoids and immunosuppressants are used for treatment; besides, it is necessary the detection of rapidly progressive interstitial disease (RP-ILD) with a high-resolution CT because of its high association with fatal prognosis.


La dermatomiositis positiva contra el gen 5 asociado a la diferenciación de melanoma (DM anti-MDA5) es una enfermedad rara que representa menos del 2%. La prevalencia de DM anti-MDA5 varía de 7 a 60%, con mayor prevalencia en asiáticos (11-60%) y mujeres. El cuadro clínico es muy variado y se acompaña por las características típicas de dermatomiositis, como la eritema en heliotropo, con edema, exantema eritematoso en la cara o la parte anterior del tórax (signo de V) y en la espalda y los hombros (signo del chal), las pápulas de Gottron en la parte dorsal de las articulaciones metacarpofalángicas o interfalángicas, que son patognomónicas por definición, pero uno de los signos más llamativos es la ulceración cutánea dolorosa que se encuentra hasta en un 82% de los casos, es profunda y en sacabocados muestran costras hiperqueratósicas. Para el diagnóstico son necesarias las erupciones típicas de la DM (pápulas de Gottron o signo de Gottron y erupción de heliotropo), junto con una patología cutánea de "dermatitis de interfase" o evidencia de miositis o un MSA (autoanticuerpos específicos de miositis). La inmunoprecipitación es el método de referencia para detectar MSA. Para su tratamiento se usan combinaciones de glucocorticoides e inmunosupresores; ademas, es necesaria la detección de enfermedad intersticial rápidamente progresiva (RP-ILD) con tomografía computarizada de alta resolución por su alta asociación con un pronóstico fatal.


Assuntos
Dermatomiosite , Exantema , Miosite , Humanos , Feminino , Dermatomiosite/diagnóstico , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Prognóstico , Exantema/complicações , Autoanticorpos/uso terapêutico
11.
Autoimmun Rev ; 22(2): 103264, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36549353

RESUMO

Idiopathic inflammatory myopathies (IIM) are a group of different conditions typically affecting striate muscle, lung, joints, skin and gastrointestinal tract. Treatment typically relies on glucocorticoids and synthetic immunosuppressants, but the occurrence of refractory, difficult to treat, manifestations, may require more aggressive treatment, borrowed from other autoimmune diseases, including biologic disease modifying drugs (bDMARDs). In this regard, we conducted a systemic literature review in order to depict the current evidence about the use of bDMARDs in IIM. A total of 78 papers, published during the last 21 years, were retrieved. The majority of patients was treated with TNF-α inhibitors, whose effectiveness was assessed particularly in recalcitrant striate muscle, skin and joints involvement. Rituximab, whose evidence is supported by a large number of real-life studies and trials, seems to be an excellent option in case of ILD and anti-synthetase syndrome, while Tocilizumab, despite not meeting primary and secondary endpoints in a recently published clinical trial, proved its effectiveness in rapidly progressing ILD. Similarly, Abatacept, studied in a phase IIb clinical trial with conflicting evidence, was reported to be effective in some case reports of refractory dermatomyositis. Less data exist for anti-IL1 and anti-IL23 agents, which were employed particularly for inclusion body myositis and severe skin disease, respectively. This study provides an organ-focused assessment of bDMARDs in IIM, which display encouraging results in the treatment of refractory subsets of disease.


Assuntos
Produtos Biológicos , Doenças Pulmonares Intersticiais , Miosite , Humanos , Produtos Biológicos/uso terapêutico , Miosite/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico
12.
Rheumatology (Oxford) ; 61(6): 2504-2511, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34617994

RESUMO

OBJECTIVE: To determine whether histopathological, electromyographic and laboratory markers correlate with clinical measures in inclusion body myositis (IBM). METHODS: We reviewed our electronic medical records to identify patients with IBM according to European Neuromuscular Center (ENMC) 2011 criteria, seen between 2015 and 2020. We only included patients who had a muscle biopsy and needle electromyography (EMG) performed on the same muscle (opposite or same side). We used a detailed grading system [0 (normal) to 4 (severe)] to score histopathological and EMG findings. Clinical severity was assessed by the modified Rankin scale (mRS), muscle strength sum score (SSS), quadriceps strength and severity of dysphagia on swallow evaluation. Serum markers of interest were creatine kinase level and cN-1A antibodies. RESULTS: We included 50 IBM patients, with a median age of 69 years; 64% were males. Median disease duration at diagnosis was 51 months. On muscle biopsy, endomysial inflammation mainly correlated with dysphagia, and inversely correlated with mRS. Vacuoles and congophilic inclusions did not correlate with any of the clinical measures. On EMG, the shortness of motor un it potential (MUP) duration correlated with all clinical measures. Myotonic discharges, and not fibrillation potentials, correlated with the severity of inflammation. Serum markers did not have a statistically significant correlation with any of the clinical measures. CONCLUSIONS: Dysphagia was the main clinical feature of IBM correlating with endomysial inflammation. Otherwise, inclusion body myositis clinical measures had limited correlation with histopathological features in this study. The shortness of MUP duration correlated with all clinical measures.


Assuntos
Transtornos de Deglutição , Miosite de Corpos de Inclusão , Miosite , Idoso , Transtornos de Deglutição/etiologia , Eletromiografia , Feminino , Humanos , Inflamação/patologia , Masculino , Músculos/patologia , Miosite/complicações , Miosite/patologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/patologia
13.
Indian J Tuberc ; 69(4): 699-701, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460411

RESUMO

Disseminated tuberculosis is a life-threatening form of tuberculosis resulting from haematogenous spread of M. tuberculosis. It is most commonly seen in an immunocompromised patient. Here we report a case of Pulmonary tuberculosis with Tubercular myositis of forearm flexors and carpal tunnel syndrome presenting as a discharging sinus in an immunocompetent patient.


Assuntos
Mycobacterium tuberculosis , Miosite , Tuberculose Miliar , Tuberculose Pulmonar , Humanos , Antebraço , Miosite/diagnóstico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico
14.
J Med Case Rep ; 16(1): 488, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575546

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis; however, the exact underlying pathogenesis of severe acute respiratory syndrome coronavirus 2-induced myositis is still unclear. CASE PRESENTATION: Herein, we report a rare case of necrotizing autoimmune myositis in a 67-year-old middle eastern male following coronavirus disease 2019 infection, who presented with muscle weakness. The patient had positive anti-NXP2. The diagnosis of necrotizing autoimmune myositis was made according to muscle weakness, increased liver enzymes, electromyography and nerve conduction velocity results, and muscle biopsy. The patient underwent a full malignancy evaluation, which was unremarkable, and was discharged in relatively well condition with a daily dose of 1 mg/kg prednisolone and azathioprine 150 mg (2 mg/kg). CONCLUSION: Our report highlights the already known possible protracted sequence of coronavirus disease 2019 infection and the potential for delayed-onset necrotizing myositis.


Assuntos
Doenças Autoimunes , COVID-19 , Miosite , Masculino , Humanos , Idoso , COVID-19/complicações , Miosite/diagnóstico , Miosite/tratamento farmacológico , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Debilidade Muscular , Prednisolona , SARS-CoV-2
15.
Int J Mol Sci ; 23(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36498905

RESUMO

Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the positivity of autoantibodies against different aminoacyl transfer RNA (tRNA) synthetases. Morbidity and mortality of this disease are highly affected by interstitial lung disease (ILD) which is present in about 80% of patients. In this study, we investigated possible differences in 84 immune-related circulating miRNAs between ASSD patients with and without ILD; we enrolled 15 ASSD patients, 11 with ILD (ILD+) and 4 without ILD (ILD-), and 5 patients with idiopathic pulmonary fibrosis (IPF) as an additional control group. All patients were at disease onset and not on therapy at the time of inclusion. Differentially expressed miRNAs were identified in plasma-derived exosomes, using an miRNA PCR array (MIHS-111ZG, Qiagen, Hilden, Germany); miR-30a-5p and miR-29c-3p were upregulated in ASSD-ILD patients compared to patients without lung involvement (adjusted p-value < 0.05). IPF patients showed higher miR-29c-3p expression levels with respect to both ASSD and ASSD-ILD (p = 0.0005), whereas levels of miR-30a-5p were not different. miR-29c-3p and miR-30a-5p are overexpressed in ASSD-ILD+ patients compared with ILD-. These miRNAs are involved in the regulation of inflammation and fibrosis through their action on NF-κB and TGF-ß1. Although the mechanistic role of these miRNAs in ASSD-ILD development has to be elucidated, we suggest that their exosome levels could be useful in identifying patients at risk of ILD.


Assuntos
Exossomos , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , MicroRNAs , Miosite , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças Pulmonares Intersticiais/genética , Exossomos/genética , Exossomos/metabolismo , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/genética
16.
Continuum (Minneap Minn) ; 28(6): 1643-1662, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36537973

RESUMO

PURPOSE OF REVIEW: This article outlines the salient clinical, serologic, electrophysiologic, imaging, and histopathologic findings and treatment options for the idiopathic inflammatory myopathies, including those related to immune checkpoint inhibitors and SARS-CoV-2. RECENT FINDINGS: The classification of idiopathic inflammatory myopathies has improved with the integration of myositis-specific antibodies and histopathologic findings. Characteristic features of immune checkpoint inhibitor-related myositis have been identified, allowing early recognition and treatment of the syndrome. The COVID-19 pandemic has had a profound impact on the care of patients with idiopathic inflammatory myopathies, and several mechanisms of virus-related muscle injury have been proposed. SUMMARY: A comprehensive evaluation including clinical examination, EMG, imaging, antibody testing, muscle biopsy, and cancer screening, when appropriate, can lead to an earlier accurate diagnosis and an individualized treatment approach for patients with idiopathic inflammatory myopathies.


Assuntos
COVID-19 , Doenças Musculares , Miosite , Humanos , Pandemias , SARS-CoV-2 , Miosite/diagnóstico , Miosite/tratamento farmacológico , Autoanticorpos
17.
Continuum (Minneap Minn) ; 28(6): 1663-1677, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36537974

RESUMO

PURPOSE OF REVIEW: This article highlights the clinical and diagnostic features of inclusion body myositis (IBM) and provides recent insights into the pathomechanisms and therapeutic strategies of the disease. RECENT FINDINGS: IBM is an often-misdiagnosed myopathy subtype. Due to the insidious onset and slow progression of muscle weakness, it can often be dismissed as a sign of aging as it commonly presents in older adults. While challenging to recognize upon initial clinical evaluation, the recent recognition of specialized stains highlighting features seen on muscle pathology, the use of diagnostic tools such as the anti-cytosolic 5'-nucleotidase 1A antibody biomarker, and the ability of muscle imaging to detect patterns of preferential muscle involvement seen in IBM has allowed for earlier diagnosis of the disease than was previously possible. While the pathogenesis of IBM has historically been poorly understood, several ongoing studies point toward mechanisms of autophagy and highly differentiated cytotoxic T cells that are postulated to be pathogenic in IBM. SUMMARY: Overall advancements in our understanding of IBM have resulted in improvements in the management of the disease and are the foundation of several strategies for current and upcoming novel therapeutic drug trials in IBM.


Assuntos
Miosite de Corpos de Inclusão , Miosite , Humanos , Idoso , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/terapia , Autoanticorpos/uso terapêutico , 5'-Nucleotidase/uso terapêutico , Debilidade Muscular , Biomarcadores
18.
Artigo em Inglês | MEDLINE | ID: mdl-36554566

RESUMO

Delayed-onset muscle soreness (DOMS) is associated with exercise-induced muscle damage and inflammation, which is mainly caused by prolonged eccentric exercise in humans. Triptolide, an extract from the Chinese herb Tripterygium wilfordii Hook F, has been used for treating autoimmune and inflammatory diseases in clinical practice. However, whether triptolide attenuates acute muscle damage is still unclear. Here, we examined the effect of triptolide on carrageenan-induced DOMS in rats. Rats were injected with 3% of carrageenan into their muscles to induce acute left gastrocnemius muscular damage, and triptolide treatment attenuated carrageenan-induced acute muscular damage without affecting hepatic function. Triptolide can significantly decrease lipid hydroperoxide and nitric oxide (NO) levels, proinflammatory cytokine production, and the activation of nuclear factor (NF)-ĸB, as well as increase a reduced form of glutathione levels in carrageenan-treated rat muscles. At the enzyme levels, triptolide reduced the inducible nitric oxide synthase (iNOS) expression and muscular myeloperoxidase (MPO) activity in carrageenan-treated DOMS rats. In conclusion, we show that triptolide can attenuate muscular damage by inhibiting muscular oxidative stress and inflammation in a carrageenan-induced rat DOMS model.


Assuntos
Miosite , Fenantrenos , Humanos , Ratos , Animais , Mialgia/tratamento farmacológico , Carragenina/farmacologia , Estresse Oxidativo , Modelos Animais , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Inflamação/tratamento farmacológico
19.
Int J Immunopathol Pharmacol ; 36: 3946320221145784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36541856

RESUMO

OBJECTIVES: Pericardial effusion is a rare clinical manifestation in idiopathic inflammatory myopathies (IIMs). It has been described in a small number of literature studies worldwide. We describe the clinical and laboratory characteristics of 19 IIM patients combined with pericardial effusion, and compare them with previously reported cases. The single-center observational-study-inspired collected of 156 IIM patients with complete data from January 1, 2016 to January 1, 2021 in the First Affiliated Hospital of Xinjiang Medical University, of which 19 patients had pericardial effusion. METHODS: The clinical characteristics of 19 IIM patients complicated with pericardial effusion were investigated by descriptive analysis and compared with previously reported cases. RESULTS: 19 cases of IIM patients had pericardial effusion (12.2%), patients without a large amount of pericardial effusion or pericardial tamponade. There was a predominance of women in the patients with 78.9% pericardial effusion . In the clinical examination, 10 cases showed chest tightness (52.6%), pulmonary fibrosis (47.4%), and the frequency of muscle nuclear magnetic, which suggested that muscle lymphocyte infiltration rate was 63.2%. Anti-Ro-52 antibody and anti-Jo-1 antibody were positive (26.3%, 42.1%). IIM patients with pericardial effusion were accompanied by decreased serum albumin levels and elevated ESR. In the literature review, the most common clinical characteristics of IIM patients with pericardial effusion were female, pulmonary fibrosis, shortness of breath, positive anti-Ro-52 pulmonary fibrosis, and anti-Jo-1 antibody. CONCLUSION: In the study, 19 patients of IIMs with pericardial effusion present with chest tightness, and are accompanied by pulmonary fibrosis, positive anti-Jo-1 antibody, and anti-Ro-52 antibody. It is suggested that pericardial effusion in IIM patients may be related to anti-synthetase antibody.


Assuntos
Miosite , Derrame Pericárdico , Fibrose Pulmonar , Humanos , Feminino , Masculino , Estudos Transversais , Derrame Pericárdico/complicações , Miosite/complicações , Miosite/diagnóstico
20.
Front Immunol ; 13: 1051609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578492

RESUMO

Objective: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases with various subtypes, myositis-specific antibodies, and affect multiple systems. The treatment of IIMs remains challenging, especially for refractory myositis. In addition to steroids and traditional immunosuppressants, rituximab (RTX), a B cell-depleting monoclonal antibody, is emerging as an alternative treatment for refractory myositis. However, the therapeutic response to RTX remains controversial. This meta-analysis aimed to systematically evaluate the efficacy and safety of RTX in patients with IIMs, excluding sporadic inclusion body myositis. Methods: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang Data were searched for relevant studies. The overall effective rate, complete response rate, and partial response rate were calculated to assess the efficacy of RTX. The incidences of adverse events, infection, severe adverse events, severe infection, and infusion reactions were collected to evaluate the safety of RTX. Subgroup analyses were performed using IIM subtypes, affected organs, continents, and countries. We also performed a sensitivity analysis to identify the sources of heterogeneity. Results: A total of 26 studies were included in the quantitative analysis, which showed that 65% (95% confidence interval [CI]: 54%, 75%) of patients with IIMs responded to RTX, 45% (95% CI: 22%, 70%) of patients achieved a complete response, and 39% (95% CI: 26%, 53%) achieved a partial response. Subgroup analyses indicated that the overall efficacy rates in patients with refractory IIMs, dermatomyositis and polymyositis, as well as anti-synthetase syndrome were 62%, 68%, and 62%, respectively. The overall efficacy rates for muscle, lungs, and skin involvement were 59%, 65%, and 81%, respectively. In addition, studies conducted in Germany and the United States showed that patients with IIMs had an excellent response to RTX, with an effective rate of 90% and 77%, respectively. The incidence of severe adverse events and infections was 8% and 2%, respectively. Conclusion: RTX may be an effective and relatively safe treatment choice in patients with IIMs, especially for refractory cases. However, further verification via randomized controlled trials is warranted.


Assuntos
Doenças Autoimunes , Miosite , Polimiosite , Humanos , Rituximab/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Autoimunes/tratamento farmacológico
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