炎性肌病和系统性血管炎课件

1、The idiopathic inflammatory myopathies (IIMs) are a group of rare, systemic autoimmune diseases characterizedclinically by progressive proximal muscle weakness histopathologically by the presence of inflammatory cells in muscle tissueDefinition1Polymyositis (PM) Dermatomyositis (DM)Juvenile DMNecrot

2、izing myopathy (IMNM)Sporadic inclusion body myositis (sIBM)separate IIM subtypes:DMIBMPMusually in the late teens or older;the mean age at onset being 40 to 60 years;F:M ratio 2:1)two peaks5 to 15 years 45 to 65 yearsF:M ratio 2:1)in individualsolder than 50 years;rare in younger adults5Muscle weak

3、nessslow onset of muscle fatigue, pain and atrophyprogressive weakness of proximal limb musclesCLINICAL FEATURES3Skin symptomsGottron s signsHeliotrope rashV-signShawl signPeriorbital oedemaMechanics hand8Raynaud s phenomenonCalcinosis cutisUlcerationArthritisJoint pain and arthritis are commonarthr

4、itis is typically nonerosiveMost frequently, arthritis is seen in patients with antiJo-1 Ab and other antisynthetase Abs.LungDyspnea and cough are common.weakness of the respiratory musclesinflammation of the lung tissue (interstitial lung disease)Lung involvement is frequent in PM and DM and is a m

5、ajor risk factor for mortality. HeartCardiac involvement may be overlooked conduction abnormalities and arrhythmiasMyocarditis, result in sudden deathCK-MB/total CK ratio may be greater than 3%increased serum levels of cardiac isoform troponin I12Gastrointestinal TractDifficulty swallowingReflux, we

6、akness in the lower esophagusMuscle strengthThe skin should also be examined to detect changes including those in nail folds and the scalp. Joints can be affected by arthritis, heart and lung changes should be carefully looked for.PHYSICAL EXAMINATION4BiochemicalMeasuring serum levels of muscle enzy

7、mesImmunologicANAs are found in approximately 60% to 70% of myositis patients.LABORATORY EVALUATION5Myositis-specific autoantibodies 2022/8/7Myositis associated autoantibodies Anti- RNPAnti- SSAAnti- SSBElectromyographyElectromyogram (EMG) changes are usually nonspecific but are a useful indicator o

8、f myopathic changes.插入电位：肌病急性期或活动期插入电位活动性增强，慢性期减弱纤颤电位和正锐波：异常的自发放电自发奇异高频放电：提示炎性肌病低波幅，短时限，多相运动单位电位鉴别是肌源性的？还是神经源性的？Imagingthe symmetric inflammation in the affected muscle多为对称性病变。T1等信号，T2高信号，提示肌肉炎性水肿部位。 Bohan and Peter Criteria for Polymyositis and Dermatomyositis, 1975DIAGNOSIS 6PM确诊：符合所有14条；DM确诊：第5条及

9、14条中任3条。2022/8/7DM皮疹PM发病机制不同病理不同2022/8/7PolymyositisDermatomyositis周围血活化T细胞明显增多，但功能下降活化B细胞明显增多肌细胞和肌内膜CD8+T细胞（内有穿孔素、颗粒酶）浸润CD8+T细胞少肌束膜和血管周围区B细胞少CD4+T细胞，B细胞，血管壁膜攻击复合物（MAC）沉积肌细胞表面表达抗原类型MHC-IMHC-II免疫异常细胞免疫为主体液免疫为主损伤组织肌纤维小血管损伤为先，继发肌肉损伤PM：发病起于CD8+T细胞识别肌细胞表面MHC-1，分泌穿孔素和颗粒酶，损伤肌细胞。束周萎缩血管周围炎明显DM：发病起于MAC在血管壁沉积及

10、对血管内皮细胞直接损伤，有CD4+T细胞和B细胞参与，继而肌肉损伤。2022/8/7分类标准敏感性（95%CI）特异性（95%CI）B&P（1975）94%（77-99）23%（6.0-54）ENMC（2004）68%（49-83）85%（54-97）分类诊断标准的演进2022/8/7Classification criteria for IIM (except IBM), proposed by ENMC, 2004Clinical criteriaserum creatine kinase levelOther laboratory criteria: MSAs and MRI of mu

11、scle tissues were includedMuscle biopsyMuscle biopsy is the “gold standard” for the diagnosis of inflammatory myopathies and a critical component of the definitive diagnosis of IIMs.26Classification criteria for IIM (except IBM), proposed by ENMC, 2004Components:Clinical criteriaInclusion criteria:(

12、a) Onset usually over 18 years (post-puberty), onset may be in childhood in DM and non-specific myositis(b) Subacute or insidious onset(c) Pattern of weakness: symmetric, proximal distal, neck flexor neck extensor(d) Rash typical of DM: heliotrope (purple); periorbital oedema; Gottrons sign; V-sign

13、and shawl signExclusion criteria:(a) Clinical features of IBM (see Griggs et al. (Ann Neurol 1995;38:705 13): asymmetric weakness, wrist/finger flexors same or worse that deltoids; knee extensors and/or ankle dorsiflexors same or worse than hip flexors)(b) Ocular weakness, isolated dysarthria, neck

14、extensor neck flexor weakness(c) Toxic myopathy (e.g. recent exposure to myotoxic drugs), active endocrinopathy (hyper-or hypothyroid, hyperparathyroid), amyloidosis, family history of muscular dystrophy or proximal motor neuropathies (e.g. SMA)Elevated serum creatine kinase levelOther laboratory cr

15、iteria:ElectromyographyMRI: diffuse or patchy increased signal (oedema) within muscle tissue on STIR images (c) Myositis-specific antibodies detected in serum29Muscle biopsy:(a) Endomysial inflammatory cell infiltrate (T-Cells) surrounding and invading non-necrotic muscle fibres PM(b) Endomysial CD8

16、 +T-cells surrounding, but not definitely invading non-necrotic muscle fibres, or ubiquitous MHC-1 expression PM(c) Perifascicular atrophy DM(d) MAC depositions on small blood vessels, or reduced capillary density, or tubuloreticular inclusions in endothelial cells on EM, or MHC-1 expression of peri

17、fascicular fibres DM(e) Perivascular, perimysial inflammatory cell infiltrate DM(f) Scattered endomysial CD8 + T-cells infiltrate that does not clearly surround or invade muscle fibres(g) Many necrotic muscle fibres as the predominant abnormal histological feature. Inflammatory cells are sparce or o

18、nly slight perivascular; perimysial infiltrate is not evident. MAC deposition on small blood vessels or pipestem capillaries on EM may be seen, but tubuloreticular inclusions in endothelial cells are uncommon or not evident. Immune-mediated necrotizing myopathy(h) Rimmed vacuoles, ragged red fibres,

19、 cytochrome oxidase-negative fibres that would suggest IBM(i) MAC deposition on the sarcolemma of non-necrotic fibres and other indications of muscular dystrophies with immunopathologyClassification criteria for IIMPolymyositis Definite polymyositis:1. All clinical criteria with the exception of ras

20、h2. Elevated serum CK3. Muscle biopsy criteria include a; and exclude c; d ; h; iEndomysial inflammatory cell infiltrate (T-Cells) surrounding and invading non-necrotic muscle fibres PMEndomysial CD8+ T-cells surrounding, but not definitely invading non-necrotic muscle fibres, or ubiquitous MHC-1 ex

21、pression DermatomyositisDefinite dermatomyositis:1. All clinical criteria2. Muscle biopsy criteria include c;Perifascicular atrophy DMMAC depositions on small blood vessels, or reduced capillary density, or tubuloreticular inclusions in endothelial cells on EM, or MHC-1 expression of perifascicular

22、fibres 2022/8/7DIFFERENTIAL DIAGNOSIS72022/8/7DIFFERENTIAL DIAGNOSIS2022/8/7DIFFERENTIAL DIAGNOSIS2022/8/7抗Jo-1抗体抗PL-7抗体抗PL-12抗体抗EJ抗体抗KS抗体抗OJ抗体抗Ha抗体抗Zo抗体抗合成酶抗体综合征肌炎肺间质病变关节炎发热雷诺现象技工手Antisynthetase SyndromeNecrotizing myopathy (NM)immune-mediated necrotizing myopathy or necrotizing autoimmune myopathy

23、,This group of NM is heterogeneous and includes: autoimmune inflammatory mechanisms, paraneoplastic conditions, exposure to toxins or drugs38The major findings are scattered necrotic muscle fibres. Sparse inflammatory cells may surround the necrosis. Macrophages are predominant and few lymphocytes a

24、re present, which were identified as CD4+ and CD8+T cells Muscle biopsy:Most patients with SRP autoantibodies fulfill the criteria for NM;Two-thirds of myositis patients with HMGCR autoantibodies have previously been exposed to statins.Inclusion body myositis老年男性多见，起病隐匿，近端肌群和远端肌群均可受累，不对称，肌细胞胞浆中或胞核内有

25、管状或丝状包涵体肌细胞内可见嗜酸性包涵体，包涵体旁充满了碱性颗粒的带边空泡TREATMENT82022/8/7 Systemic VasculitisVasculitis is a heterogeneous group of disorders linked by the primary finding of inflammation within blood vessel walls.以血管的炎症与坏死为主要病理改变，常累及全身多个系统，也可局限在某一脏器。临床表现各异，最常累及的部位是皮肤、肾脏、肺、神经系统等。44动脉的种类：1）大动脉是近心的动脉，包括主动脉、肺动脉、无名动脉、颈总动

26、脉、锁骨下动脉等等2）中动脉除主动脉、肺动脉等大动脉外，在解剖学中有名称的动脉大多属于中动脉。3）小动脉管径在0.31mm的动脉4）微动脉管径在0.3mm以下的动脉45血管炎的分类大血管性血管炎小血管性血管炎 巨细胞（颞）动脉炎 韦格纳肉芽肿 大动脉炎 Churg-Strauss综合征中等 血管性血管炎 显微镜下多血管炎 结节性多动脉炎 Henoch-Schonlein 紫癜 川崎病 冷球蛋白血症性血管炎 皮肤白细胞破碎性血管炎1993 Chapel Hill 共识会议2022/8/7Chapel Hill 1993 分类优缺点优点缺点简单未说明同一血管炎可能累及不同大小的血管（BD，Coga

27、n）宜于临床工作未提及发病机制 ANCA继发性血管炎等未归入2022/8/7Chapel Hill 2012 Classification旧血管炎分类 Large Vessel vasculitis Medium Vessel vasculitis Small Vessel vasculitis新增加的血管炎分类 Variable Vessel vasculitis Single Organ vasculitis Vasculitis Associated with Systemic Disease Vasculitis with Probable Etiology 2022/8/72022/

28、8/7新增加的血管炎分类ACR classification criteria for Takayasus Arteritis左锁骨动脉闭塞右肾动脉狭窄 ACR classification criteria for Giant cell arteritisPolyarteritis Nodosa Polyarteritis nodosa (PAN), characterized by necrotizing vasculitis of medium-sized arteries with few or no immune deposits.Small arteries may also be

29、 involved, but small vessels, including arterioles, capillaries, and venules, are not.2022/8/7Clinical manifestation:The occlusion or rupture of inflamd arteries might produce tissue ischemia or hemorrhage in a variety of organs and systemsNot affect lung, not cause glomerulonephritis, and no ANCA p

30、ositive The peripheral nervous system and the skin are the most frequently involved territoriesOrchitisis （睾丸炎）the most characteristic symptom of PAN.睾丸炎，腓肠肌痛，垂腕、垂足（单神经炎）、肾功不全和肾性高血压活检部位：皮肤（深达皮下脂肪层）、腓肠肌、腓浅神经等。Antineutrophil Cytoplasm AntibodyAssociated Vasculitis显微镜下多动脉炎（MPA），肉芽肿性多动脉炎（GPA）和嗜酸性肉芽肿性多动脉

31、炎（EGPA）髓过氧化物酶（MPO）和蛋白酶3（PCR3）是ANCA的主要靶抗原ANCA相关性血管炎是一种常见的累及多系统的自身免疫性疾病，多累及肺、肾和神经系统。c - ANCAp - ANCA 蛋白酶-3（PR3）髓过氧化物酶（MPO)56Granulomatosis with polyangiitis （GPA）Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels (capillaries,

32、venules, arterioles, arteries)Criteria for classification of GPA58Eosinophilic granulomatosis with polyangiitisEosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels, associated with asthma and blood eosinophi

33、liaCriteria for classification of EGPA60Microscopic polyangiitis （MPA）Necrotizing vasculitis with few or no immune deposits affecting small vessels (capillaries, venules, arterioles)Differential diagnostic Features of the ANCA-Associated VasculitidesImmune ComplexMediated Small Vessel VasculitisCutaneous involvemen