静脉注射免疫球蛋白治疗特发性炎性肌病的研究进展

特发性炎性肌病(idiopathic inflammatory myopathies，IIM)是一组以免疫病理为基础的肌肉慢性炎性疾病。临床上以多发性肌炎(polymyositis，PM)、皮肌炎(dermatomyositis，DM)、包涵体肌炎(inclusion body myositis，IBM)三种类型最常见。糖皮质激素是目前IIM治疗的首选药物，但绝大多数患者需同时加用免疫抑制剂。近年来一种较为安全有效的疗法——静脉注射免疫球蛋白(intravenous immunoglobulin，IVIg)疗法日益受到重视，临床应用逐渐增多。本文就近年来有关IVIg治疗IIM的基础及临床研究进展作一综述。     

特发性炎性肌病的分子病理研究进展

特发性炎性肌病(IIM)是一组临床特点、病理表现和治疗预后各异的自身免疫性疾病。主要临床表现为肌无力,也可影响包括皮肤、关节、肺脏、心脏和消化道等多个骨骼肌外系统和器官,有些IIM的亚型甚至以肌外系统损害为主要表现。近年来发现了多种肌炎特异性抗体与IIM密切相关,不同抗体相关的临床表型、病理改变和对治疗的反应均各不相同,提示存在不同的病理生理机制。目前比较公认基于临床-病理-血清学特点,将IIM进一步分为皮肌炎、抗合成酶抗体综合征、免疫介导坏死性肌病、包涵体肌炎和多发性肌炎这几种亚型。本文介绍了IIM各亚型的分子病理研究的最新进展,以期为临床和病理医生提供参考。     

特发性炎性肌病的评估与监测

特发性炎性肌病(IIM)是一种慢性近端肌肉炎症，并以肌无力为主要特征的全身性自身免疫性疾病，可累及多个系统及器官。由于疾病活动，IIM患者日常生活质量和工作均受到不同程度的影响，临床缓解是患者追求的现实目标，对IIM的疾病全面评估和监测可准确反映患者疾病变化的全貌。本文结合国际肌炎评估和临床研究小组(IMACS)开发的肌炎疾病活动和器官损害的评估工具及其他临床常用评估工具，为临床IIM的疾病活动度评估和监测提供新思路。     

特发性炎性肌病诊治进展

特发性炎性肌病（IIM）是一组以骨骼肌炎性病变为主要表现的获得性异质性疾病。IIM有多种分类方法，较被广泛接受的是1975年Bohan和Peter提出的分类诊断方法。随着近年来对IIM免疫病理机制研究的不断深入，对IIM的诊断与治疗有了更全面而深入的认识，现综述如下。     

特发性炎性肌病合并肺间质病变的生物标志物研究进展

特发性炎性肌病(IIM)是一组以骨骼肌炎症为特征的自身免疫性疾病。肺间质病变(ILD)是IIM最常见的并发症,也是IIM患者死亡的主要原因。IIM-ILD的治疗反应及预后差异大,其治疗取决于ILD的严重与进展程度。因此了解IIM-ILD的危险因素,对于预测ILD的发展、预后及选择治疗方案非常重要。IIM患者可检出多种自身抗体,其中抗合成酶抗体(ASA)、抗黑色素瘤分化相关基因(MDA5)抗体与ILD密切相关,涎液化糖链抗原(KL-6)、铁蛋白、肺表面活性蛋白D(SP-D)、B淋巴细胞刺激因子(BAFF)等生物标志物对预测ILD、监测疾病活动、评估疗效及预后等方面有重要作用。本文对近年来IIM-ILD相关生物标志物的研究进展进行综述。     

特发性炎性肌病合并间质性肺病相关生物学标志物的研究进展

<正>特发性炎性肌病(idiopathic inflammatory myopathy,IIM,以下简称肌炎)是一种系统性的自身免疫性疾病,受累靶器官众多,其中以肺脏较为常见,肌炎合并间质性肺病(interstitial lung disease,ILD)是IIM死亡的主要原因之一~([1,2]),因此早期诊断ILD对于改善肌炎患者的预后是重要的。对于拟诊或确诊为IIM-ILD的患者,寻找可以早期预测ILD发生发展、监测疾病活动度和判断预后的特异性     

B细胞刺激因子在特发性炎性肌病相关肺间质病变的临床意义

目的 探究B细胞刺激因子(BAFF)在特发性炎性肌病(IIM)相关肺间质病变(ILD)中的临床意义。方法 纳入122例IIM患者,其中86例并发ILD,按性别、年龄匹配40例正常人作为对照,采用酶联免疫吸附试验检测BAFF,分析其临床意义。结果 与non-ILD组相比,IIM-ILD组BAFF水平显著升高[2.19(1.07～4.54) ng/mL vs.1.14(0.61～2.30) ng/mL,P=0.005],是IIM-ILD的独立危险因素。抗MDA5抗体及抗合成酶抗体(ASA)阳性的IIM患者BAFF水平显著高于双阴性患者(P<0.05)。BAFF>3.74 ng/mL时,对于诊断IIM-ILD的敏感性为36.0%,特异性为97.2%(AUC=0.681,P=0.002);联合KL-6时,对于诊断IIM-ILD的敏感性为82.6%,特异性为80.6%(AUC=0.868,P<0.001)。BAFF与铁蛋白呈正相关(r=0.368,P<0.001),与KL-6、肺部HRCT评分、肺功能无明显相关性。结论 BAFF在IIM-ILD患者中显著升高,可作为IIM...     

特发性炎性肌病肌炎特异性抗体谱的临床意义

目的研究特发性炎性肌病(IIM)患者血清肌炎特异性抗体(MSAs)水平与其临床特征、实验室指标及预后的相关性。方法收集178例IIM患者的临床资料,免疫印迹法检测患者血清中12种MSAs的水平,并分析其与患者临床特征、实验室指标和预后的相关性。进一步建立Logistic回归模型,分析MSAs亚型是否为患者临床症状的独立危险因素。结果12种MSAs中,抗氨基酰tRNA合成酶[ARS,包括组氨酰-tRNA合成酶(Jo-1)、PL-7、PL-12、EJ、OJ]抗体(34.8%)最常见,其次为抗黑色素瘤分化相关基因5(MDA5)抗体(32.6%)、抗转录中介因子γ(TIF1γ)抗体(11.8%)和抗信号识别颗粒(SRP)抗体(11.8%)。抗ARS抗体阳性组肺间质性病变和技工手的发生率高于阴性组(90.3%比66.4%,P<0.001;16.1%比4.3%,P=0.007);抗MDA5抗体阳性组较阴性组更易出现肺间质性病变、Gottron疹、面部红斑和关节炎(均P<0.05),肌无力和吞咽障碍发生率更低(55.2%比78.3%,P=0.001;8.6%比23.3%,P=0.018);抗TIF1γ抗体在≥65岁患者中的阳性率高于<65岁患者(25.9%比9.3%,P=0.032),该抗体阳性组肿瘤发生率比阴性组高(19.0%比3.2%,P=0.01);抗SRP抗体阳性患者肌无力发生率、肌酸激酶(CK)值、乳酸脱氢酶(LDH)值和谷草转氨酶(AST)值高于阴性组(均P<0.05)。抗Mi-2β抗体阳性组肺间质病变发生率低于阴性组(40.0%比77.9%,P=0.003)。Logistics回归分析显示,抗MDA5抗体和抗Jo-1抗体是肺间质性病变(ILD)发生的独立危险因素,抗TIF1γ抗体是吞咽障碍发生的独立危险因素。生存分析结果表明,抗MDA5抗体阳性患者比阴性患者生存时间更短(5.0月比14.0月,P=0.001)。结论抗ARS抗体是最常见的MSAs亚型,不同的MSAs亚型与特定的临床特征有关。检测MSAs水平有利于对不同患者进行分型,指导治疗并判断预后。     

重视肌炎诊疗中的感染及其对策

特发性炎性肌病(IIM)尤其是MDA5抗体皮肌炎(DM)与包括新型冠状病毒感染(COVID-19)在内的各种感染关系密切。感染不仅诱发IIM起病，且在免疫治疗过程中，IIM易合并感染，导致预后不佳。本文从IIM发病前及治疗中的感染情况、感染发生的危险因素及对感染的管理等多个角度进行阐述。     

特发性炎性肌病分型诊断标准的比较分析

目的 评价Bohan/Peter标准(B/P标准)与欧洲神经肌肉疾病中心(ENMC)标准对特发性炎性肌病分型诊断皮肌炎和多发性肌炎的准确性.方法 回顾性收集86例初诊为特发性炎性肌病患者的临床、实验室及骨骼肌病理资料,分别用B/P标准与ENMC标准进行分型诊断,比较两个标准诊断皮肌炎和多发性肌炎的异同性.数据分析采用SPSS 13.0软件系统进行非参数检验(Mann Whitney U检验)和一致性检验(Kappa分析)方法.结果 B/P标准诊断皮肌炎37例,多发性肌炎49例;ENMC标准诊断皮肌炎46例,多发性肌炎仅14例,其余为嗜酸细胞性肌炎1例、疑诊散发性包涵体肌炎9例,未能分型者5例,肢带型肌营养不良2B型11例.Kappa分析检验两个标准诊断皮肌炎一致性较好(κ=0.79),诊断多发性肌炎一致性差(κ=0.26).结论 B/P标准对多发性肌炎存在过度诊断、误诊风险.ENMC标准纳入免疫病理,增加了临床与病理诊断的排除标准,其分型诊断准确性优于B/P标准.     

Idiopathic Inflammatory Myopathy with Diffuse Alveolar Damage

Interstitial lung disease (ILD) in patients with myositis is defined by the presence of interstitial changes on radiographic examination. The reported prevalence of ILD varies from 0% to nearly 50%. However, only rarely has the pathological pattern of diffuse alveolar damage (DAD) associated with idiopathic inflammatory myopathy (IIM) been reported. We report five patients with IIM (one with dermatomyositis, one with polymyositis, and three with amyopathic dermatomyositis) and respiratory failure. Four underwent open lung biopsy with pathological proof of diffuse alveolar damage (DAD). Despite intensive immunosuppressive therapy, all of them died. In addition to the case reports, we discuss DAD in patients with IIM. Received: 18 June 2001 / Accepted: 6 March 2002     

特发性炎症性肌病的心血管表现

心脏损害是特发性炎症性肌病死亡和致残的重要原因。然而,心力衰竭、传导异常及冠心病等临床心血管表现相对少见,非特异性的心电图显示的传导异常及心律失常却很常见。事实上,这些心血管表现或多或少与心肌纤维化及小血管平滑肌增生相关,可致特发性炎症性肌病患者的死亡。因此,有必要推荐特发性炎症性肌病患者进行常规而全面的心脏评估。     

Inflammatory Myopathy Associated with Anti-mitochondrial Antibody Presenting Only with Respiratory Failure

A 56-year-old woman presenting with type II respiratory failure was transferred to our hospital. She did not exhibit muscle weakness or elevated serum myogenic enzymes, but needle electromyography revealed myogenic changes in the limb muscles, and her blood tests were positive for anti-mitochondrial antibodies (AMA). Muscle histopathological findings included immune-mediated necrotizing myopathy, so she was diagnosed with inflammatory myopathy associated with AMA. After treatment with corticosteroids and noninvasive positive pressure ventilation, her symptoms improved. If a diagnosis of type II respiratory failure is difficult, inflammatory myopathy associated with AMA should be considered as a differential diagnosis.     

心肌标志物在评估特发性炎症性肌病心脏损伤中的价值

心脏损伤作为特发性炎症性肌病的严重并发症,其检出率不断增加,早期诊断和干预有助于改善患者的临床结局。心肌标志物(肌钙蛋白和传统的肌酸激酶)作为一种便捷和无创的心肌损伤敏感的生物学指标,在评估特发性炎症性肌病患者心脏损伤中的价值尚不明确。现就心肌标志物在特发性炎症性肌病评估中的作用做一综述。     

Interstitial Lung Disease in Idiopathic Inflammatory Myopathy

The lung is one of the most common extra-muscular targets in idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD) contributes to nearly 80% of the mortality in IIM with a reported prevalence of 65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical and laboratory findings of myositis, overt signs of muscle disease may be absent in the setting of significant lung disease. Understanding the varied scope of presentation of these diseases is essential to providing optimal patient care. This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention.     

Idiopathic inflammatory myositis

Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose.A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings.There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting.     

Inflammatory myopathy associated with statins: report of three cases

Abstract

Statins are well-established lipid-lowering drugs that reduce morbidity and mortality due to cardiovascular disease and cause adverse effects relatively rarely. It is still unclear whether statins are capable of inducing an immune-mediated response directed against skeletal muscle. Here, we present the cases of three patients who developed inflammatory myopathy in the course of statin treatment. Moreover, multiple mitochondrial DNA deletions were found in two of them. The ability of statins to induce an immune-mediated response and their interactions with mitochondrial metabolism pathways are discussed.     

High Bone Mass and Hypocalcaemic Myopathy in a Patient with Idiopathic Hypoparathyroidism

The clinical manifestations of hypoparathyroidism are mainly characterised by increased neuromuscular irritability as a consequence of hypocalcaemia. Occasionally, elevation of the muscle enzymes may mimic polymyositis. Reduced parathyroid hormone production, but also vitamin D treatment and calcium supplementation, may contribute to the increased bone mass found in patients with postsurgical hypoparathyroidism. We report the case of a 36-year-old woman with untreated idiopathic hypoparathyroidism and a high bone mass despite severe muscle impairment due to hypocalcaemic myopathy. Received: 20 April 1999 / Accepted: 17 June 1999     

Skeletal Muscle Myopathy in Heart Failure: the Role of Ejection Fraction

Purpose of Review

This review summarizes: (1) the structural and functional features coupled with pathophysiological factors responsible of skeletal muscle myopathy (SMM) in both heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction and (2) the role of exercise as treatment of SMM in these HF-related phenotypes.

Recent Findings

The recent literature showed two main phenotypes of heart failure (HF): (1) HFrEF primarily due to a systolic dysfunction of the left ventricle and (2) HFpEF, mainly related to a diastolic dysfunction. Exercise intolerance is one of most disabling symptoms of HF and it is shown that persists after the normalization of the central hemodynamic impairments by therapy and/or cardiac surgery including heart transplant. A specific skeletal muscle myopathy (SMM) has been defined as one of the main causes of exercise intolerance in HF.

Summary

The SMM has been well described in the last 20 years in the HFrEF; on the contrary, few studies are available in HFpEF. Recent evidences have revealed that exercise training counteracts HF-related SMM and in turn ameliorates exercise intolerance.