特发性炎性肌病的免疫病理及诊断

特发性炎性肌病（idiopathic inflammatory myopathy，IIM）是一组获得性的、与自身免疫有关的骨骼肌疾病.临床主要有3个亚型：多发性肌炎（polymyositis，PM）、皮肌炎（dermatomyositis，DM）和包涵体肌炎（inclusion-body myositis，IBM）.由于PM和DM应用皮质醇和免疫抑制剂治疗有效，其诊断和鉴别诊断一直备受临床医生关注.1975年Bohan和Peter提出了PM和DM的诊断标准，在世界范围内得到广泛采用.但这一诊断标准主要是以临床表现和普通组织病理为基础，在临床实践中容易造成误诊和漏诊.例如，根据这一标准不能对PM和IBM进行鉴别;无法将肌活检未发现炎症浸润的PM与其他坏死性肌病进行鉴别;也不能区别一些伴有继发性炎症反应的肌营养不良与PM.近年来，随着组织病理、免疫病理和分子病理方面的研究进展，以免疫病理和免疫组织化学为基础的IIM诊断标准和临床分型逐渐得到了确立。     

他汀类药物相关抗HMGCR抗体介导坏死性肌病的研究进展

抗3-羟基3-甲基戊二酰辅酶A还原酶(HMGCR)抗体介导的坏死性肌病是近年逐渐被认识的一类疾病,该病与他汀类药物的使用密切相关。患者具有坏死性肌病的一般特点,通过抗HMGCR抗体阳性与其他类型的坏死性肌病相鉴别。多数患者可通过激素联合其他免疫抑制剂治疗可控制病情。文中回顾了该病的发病机制、流行病学、临床特点、诊断及鉴别诊断、治疗等研究现状,以加强临床医生对该病的认识。     

11例多发性肌炎合并周围神经损伤的临床分析

目的：探讨多发性肌炎（PM）合并周围神经损伤临床特点，实验室检查，诊断及治疗。方法：对11例PM合并周围神经损伤患者的临床表现及实验室检查资料进行分析。结果：本组11例患者均有不同程度的肌无力、肌痛，血清酶升高，并均有肌电图异常，表现神经肌肉混合损伤；本组患者占同期PM住院病人的13.1％（11/84），应用皮质激素及免疫抑制剂治疗有效。结论：结合临床表现、实验室及肌电图检查，可早期诊断PM合并周围神经损伤，激素仍为本病的有效治疗药物。     

坏死性肌病

坏死性肌病是一种与炎症性肌病、特别是多发性肌炎（PM）相类似的肌病,其病因大多是肿瘤。主要表现为近端肢体对称性无力、肌肉疼痛;血清肌酶、尤其是肌酸磷酸激酶（CK）升高;病理学上有肌细胞的变性、坏死、再生,部分肌纤维有吞噬现象,但无或极少炎性细胞浸润,部分患者毛细血管壁增厚,呈杆状,上皮细胞内可出现包涵体;肌电图呈肌源性损害;大部分患者对类固醇激素反应良好。目前为止,本病个案报告已有10余篇,40余例。现结合文献综述如下。     

重症肌无力合并多发性肌炎两例临床分析并文献复习

目的观察重症肌无力(MG)合并多发性肌炎(PM)的临床特征及疗效,并探讨其共病机制及治疗方法,提高临床识别度。方法报道作者医院收治的两例MG合并PM患者的临床资料,结合文献分析其发病特点、实验室检查、疗效及预后等。结果两例患者临床症状以四肢无力、球肌麻痹、肌肉疼痛为主要表现,疲劳现象不明显,实验室检查可见肌酶升高,偶有心肌受累,肌电图提示肌源性损害;单用溴吡斯的明治疗效果不佳,联合激素和免疫制剂治疗反应良好。结论 MG合并PM的病例少见;MG患者在规范化治疗过程中若出现肌肉疼痛、肌酶谱升高,或疲劳现象消失、眼肌症状不明显等表现时,需行肌电图、肌活检等明确有无合并肌肉疾病的可能;治疗上以免疫治疗为主,急重症者建议使用丙种球蛋白或血浆置换等方法。     

神经性肌炎7例分析

目的:通过对7例多发性肌炎合并周围神经损害(神经性肌炎)患者临床资料的分析以探讨其临床特点。方法:采用回顾性研究方法。结果:神经性肌炎患者血清肌酶水平增高不明显,肌电图有神经性损害,肌肉病理为不典型炎症改变,激素及免疫抑制剂治疗效果不佳。结论:多发性肌炎合并周围神经损害(神经性肌炎)有特殊的临床特点,肌电图和肌活检对诊断有重要意义。     

60例多发性肌炎和皮肌炎治疗体会

多发性肌炎(PM)是一组以许多骨骼肌的间质性炎变和肌纤维变性为特征的综合征,如同时累及皮肤则称为皮肌炎(DM).现已明确本病是具有遗传易感性的个体被各种环境因素触发后产生的免疫介导过程.皮质激素及免疫抑制剂常作为本病的首选药物,但由于用药方法不同对其远期疗效影响颇大,至今尚无公认或普遍适用的治疗方案.本文总结自1990年以来收治的60例PM和DM,着重对首发和复发患者的治疗进行讨论.     

多发性肌炎合并周围神经病（附5例临床及随访）

目的 :探讨多发性肌炎 (PM )合并周围神经病的临床及预后。方法 :对临床和实验室检查证实的PM合并周围神经病 5例进行了分析及 3个月～ 2年的随访。结果 :5例病人经免疫抑制剂治疗预后良好。结论 :PM合并周围神经病的周围神经损害及表现可轻可重 ,但预后并不比单纯多发性肌炎的预后差     

抗信号识别颗粒抗体阳性坏死性肌病研究进展

以抗信号识别颗粒（SRP）抗体阳性为标志的坏死性肌病,因其起病急、病情重、进展快,单用类固醇激素疗效差,成为近年特发性炎性肌病领域中备受关注的热点。本综述回顾了近年来国内外坏死性肌病相关文献,分析SRP＋NM与IMNM临床表现及病理改变的异同,阐述SRP抗原免疫原性改变和线粒体能量代谢异常两因素在坏死性肌病致病机制中的作用,认为抗SRP抗体的早期检测有益于SRP＋NM的针对性治疗及预后。     

特发性炎性肌病分型诊断标准研究进展

特发性炎性肌病分型诊断以Bohan和Peter标准应用最广泛,随着免疫发病机制的研究进展,Dalakas标准提出CD8/MHC-I复合体是诊断PM特征性免疫病理标志.ENMC标准纳入了核磁共振、肌炎特异性抗体、必备的组织化学与免疫组织化学病理诊断标准,单克隆抗体免疫组织化学染色可显示浸润炎细胞的类型及MHC-I、MAC免疫标志物的表达,使特发性炎性肌病分型诊断更具准确性,临床应积极推广应用,有助提高诊断治疗水平.     

Immune‐mediated necrotizing myopathy associated with statins

We report patients from two neuromuscular centers who were evaluated between the years 2000 and 2008 and met the following criteria: (1) proximal muscle weakness occurring during or after treatment with statins; (2) elevated serum creatine kinase (CK); (3) persistence of weakness and elevated CK despite discontinuation of the statin; (4) improvement with immunosuppressive agents; and (5) muscle biopsy showing necrotizing myopathy without significant inflammation. Twenty‐five patients fulfilled our inclusion criteria. Twenty‐four patients required multiple immunosuppressive agents. Fifteen patients relapsed after being tapered off immunosuppressive therapy. Exposure to statins prior to onset was significantly higher in patients with necrotizing myopathy (82%) as compared to those with dermatomyositis (18%), polymyositis (24%), and inclusion‐body myositis (38%) seen in the same time period. The lack of improvement following discontinuation of statins, the need for immunosuppressive therapy, and frequent relapse when treatment was tapered suggest an immune‐mediated etiology for this rare, statin‐associated necrotizing myopathy. Muscle Nerve, 2010     

Myopathy associated with anti-signal recognition peptide antibodies: clinical heterogeneity contrasts with stereotyped histopathology

We report three patients with anti-signal recognition particle antibodies who had different presenting clinical pictures, mimicking acute polymyositis, limb-girdle muscular dystrophy, and acute rhabdomyolysis. Muscle biopsies typically showed necrotizing myopathy with little or no inflammation and deposits of membrane attack complex (C5b-9) in endomysial capillaries. The clinical course was severe in two patients and mild in one. The combination of corticosteroid with either an immunosuppressive agent or intravenous immunoglobulins was required to improve the condition of these patients.     

Treatment of idiopathic inflammatory myopathies

PURPOSE OF REVIEW: This article reviews the results of recent therapeutic trials in dermatomyositis, polymyositis, and inclusion body myositis and suggests an approach to treating patients with inflammatory myopathy. RECENT FINDINGS: We reviewed 10 double-blind, placebo-controlled therapeutic trials in patients with inflammatory myopathy. Only one, using intravenous immunoglobulin in refractory dermatomyositis, indicated benefit. A brief trial of azathioprine in polymyositis and eight studies using various treatments in inclusion body myositis did not show benefit. SUMMARY: There have been no adequate double-blind, placebo-controlled therapeutic trials of dermatomyositis and polymyositis. It is generally accepted, however, that these disorders respond to immunosuppressive agents. Prednisone is usually the initial treatment. There is no agreement on how prednisone should be administered and even less agreement about other agents. Inclusion body myositis, which now appears to be the most common (in adults), is unresponsive to immunosuppressive and immunomodulating therapies. There are candidate treatments for inclusion body myositis and a need for additional double-blind, placebo-controlled therapeutic trials in all patients with inflammatory myopathy.     

Primary Gougerot-Sj?gren syndrome with necrotizing polymyositis: favorable effect of hydroxychloroquine

A 61-year-old woman was admitted for acute arthralgias and proximal weakness in all four limbs. Clinical examination found xerostomia, xerophthalmia, enlarged parotid glands. The Schirmer test was positive and the salivary gland biopsy showed a mononuclear, lymphoid, sometimes nodular infiltrate. A muscle biopsy showed necrotizing myopathy with perifascicular atrophy. The patient refused steroids and was given hydroxychloroquine (600 mg daily). She improved gradually, and one year later there were no further complications. The favorable course both of Sj?gren's syndrome and polymyositis with hydroxychloroquine treatment is unexpected. This led us to suppose that both could have had a common cause.     

误诊为多发性肌炎的脂质沉积性肌病——附3例报告

目的探讨脂质沉积性肌病(lipid storage myopathy,LSM)的临床特征、病理改变、代谢异常及治疗。方法回顾性分析我院确诊的3例LSM患者的临床表现、肌肉病理所见及血、尿代谢检查结果 ,结合文献报道总结LSM的临床特点和发病机制,并对多发性肌炎的诊断标准进行讨论。结果 3例患者均有对称性肌无力和/或肌痛,肌酶谱增高,最初均诊断为多发性肌炎,经激素治疗可好转,但病情反复。肌肉病理显示肌纤维大小不等,大量肌纤维内可见类圆形空泡,油红O染色见肌纤维内大量红染的脂滴沉积。经调整饮食、口服维生素B2、左卡尼汀等药物治疗后,症状改善明显。结论应用Bohan/Peter标准可能导致对多发性肌炎的过度诊断。对临床表现为肌无力、肌痛的患者,不要盲目应用激素治疗,应积极进行骨骼肌活检,明确诊断。     

Progressive myopathy with up-regulation of MHC-I associated with statin therapy

Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.     

Inclusion body myositis: Clinical and pathological boundaries

Inclusion body myositis, polymyositis, and dermatomyositis are three distinct categories of inflammatory myopathy. Some authorities commented on the selective early weakness of the volar forearm muscles, quadriceps, and ankle dorsiflexors in inclusion body myositis. The most important feature distinguishing inclusion body myositis from the other two inflammatory myopathies is the lack of responsiveness to immunosuppressive treatment. Although most patients with inclusion body myosities have characteristic muscle biopsy findings, some cannot be distinguished histologically early from polymyositis. Presdicting responsiveness to mmunosuppressive medications, independent of muscle histology, would be valuable to clinicians. We retrospectively reviewed the pattern of weakness and other clinical features of 46 patients newly diagnosed with either inclusion body myositis, polymyositis, or dermatomyosities. Asymmetrical muscle weakness with prominent wrist flexor, finger flexor, and knee extensor involvement was specific for inclusion body myositis and unresponsive polymyositis. Male sex, lower creatine kinase levels, slower rate of progression, and peripheral neuropathy were also more common in inclusion body myositis and unresponsive polymyositis than in responsive polymyositis and dermatomyositis patients. Repeat muscle biopsy in 2 patients in teh unresponsive polymyositis group demonstrated histological features of inclusion body myositis. We suspect that patients with clinical features of inclusion body myositis but lacking histological confirmation may nonetheless have inclusion body myositis. Our study supports the recently proposed criteria for defintie and possible inclusion body myositis.     

Immunosuppressive therapy in polymyositis

Immunosuppressive drugs were given to seven patients with polymyositis. The in-vitro activity of peripheral blood lymphocytes had previously been studied in five of these patients with findings suggestive of disturbed immunological processes. Some improvement occurred in five cases, but only in two was the improvement marked and sustained. In this small series of cases, the response to treatment was best in a patient with polymyositis who showed no evidence of involvement of tissues or organs other than muscle and in a second case with subacute polymyositis occurring in association with an unidentified connective tissue disorder. The response was less satisfactory in two patients with dermatomyositis, in two with polymyositis associated with systemic sclerosis, and in one in whom the muscle disorder complicated rheumatoid arthritis. At present such treatment is usually given only in cases which are resistant to, or intolerant of, steroids. The relative values of steroid and immunosuppressive therapy are discussed; a combination of the two in moderate doses may eventually prove to be the best initial treatment for the disorder.