炎性肌病和系統(tǒng)性血管炎課件

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.插入電位：肌病急性期或活動(dòng)期插入電位活動(dòng)性增強(qiáng)，慢性期減弱纖顫電位和正銳波：異常的自發(fā)放電自發(fā)奇異高頻放電：提示炎性肌病低波幅，短時(shí)限，多相運(yùn)動(dòng)單位電位鑒別是肌源性的？還是神經(jīng)源性的？Imagingthe symmetric inflammation in the affected muscle多為對(duì)稱(chēng)性病變。T1等信號(hào)，T2高信號(hào)，提示肌肉炎性水腫部位。 Bohan and Peter Criteria for Polymyositis and Dermatomyositis, 1975DIAGNOSIS 6PM確診：符合所有14條；DM確診：第5條及

9、14條中任3條。2022/8/7DM皮疹PM發(fā)病機(jī)制不同病理不同2022/8/7PolymyositisDermatomyositis周?chē)罨疶細(xì)胞明顯增多，但功能下降活化B細(xì)胞明顯增多肌細(xì)胞和肌內(nèi)膜CD8+T細(xì)胞（內(nèi)有穿孔素、顆粒酶）浸潤(rùn)C(jī)D8+T細(xì)胞少肌束膜和血管周?chē)鷧^(qū)B細(xì)胞少CD4+T細(xì)胞，B細(xì)胞，血管壁膜攻擊復(fù)合物（MAC）沉積肌細(xì)胞表面表達(dá)抗原類(lèi)型MHC-IMHC-II免疫異常細(xì)胞免疫為主體液免疫為主損傷組織肌纖維小血管損傷為先，繼發(fā)肌肉損傷PM：發(fā)病起于CD8+T細(xì)胞識(shí)別肌細(xì)胞表面MHC-1，分泌穿孔素和顆粒酶，損傷肌細(xì)胞。束周萎縮血管周?chē)酌黠@DM：發(fā)病起于MAC在血管壁沉積及

10、對(duì)血管內(nèi)皮細(xì)胞直接損傷，有CD4+T細(xì)胞和B細(xì)胞參與，繼而肌肉損傷。2022/8/7分類(lèi)標(biāo)準(zhǔn)敏感性（95%CI）特異性（95%CI）B&P（1975）94%（77-99）23%（6.0-54）ENMC（2004）68%（49-83）85%（54-97）分類(lèi)診斷標(biāo)準(zhǔn)的演進(jìn)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抗體抗PL-7抗體抗PL-12抗體抗EJ抗體抗KS抗體抗OJ抗體抗Ha抗體抗Zo抗體抗合成酶抗體綜合征肌炎肺間質(zhì)病變關(guān)節(jié)炎發(fā)熱雷諾現(xiàn)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老年男性多見(jiàn)，起病隱匿，近端肌群和遠(yuǎn)端肌群均可受累，不對(duì)稱(chēng)，肌細(xì)胞胞漿中或胞核內(nèi)有

25、管狀或絲狀包涵體肌細(xì)胞內(nèi)可見(jiàn)嗜酸性包涵體，包涵體旁充滿了堿性顆粒的帶邊空泡TREATMENT82022/8/7 Systemic VasculitisVasculitis is a heterogeneous group of disorders linked by the primary finding of inflammation within blood vessel walls.以血管的炎癥與壞死為主要病理改變，常累及全身多個(gè)系統(tǒng)，也可局限在某一臟器。臨床表現(xiàn)各異，最常累及的部位是皮膚、腎臟、肺、神經(jīng)系統(tǒng)等。44動(dòng)脈的種類(lèi)：1）大動(dòng)脈是近心的動(dòng)脈，包括主動(dòng)脈、肺動(dòng)脈、無(wú)名動(dòng)脈、頸總動(dòng)

26、脈、鎖骨下動(dòng)脈等等2）中動(dòng)脈除主動(dòng)脈、肺動(dòng)脈等大動(dòng)脈外，在解剖學(xué)中有名稱(chēng)的動(dòng)脈大多屬于中動(dòng)脈。3）小動(dòng)脈管徑在0.31mm的動(dòng)脈4）微動(dòng)脈管徑在0.3mm以下的動(dòng)脈45血管炎的分類(lèi)大血管性血管炎小血管性血管炎 巨細(xì)胞（顳）動(dòng)脈炎 韋格納肉芽腫 大動(dòng)脈炎 Churg-Strauss綜合征中等 血管性血管炎 顯微鏡下多血管炎 結(jié)節(jié)性多動(dòng)脈炎 Henoch-Schonlein 紫癜 川崎病 冷球蛋白血癥性血管炎 皮膚白細(xì)胞破碎性血管炎1993 Chapel Hill 共識(shí)會(huì)議2022/8/7Chapel Hill 1993 分類(lèi)優(yōu)缺點(diǎn)優(yōu)點(diǎn)缺點(diǎn)簡(jiǎn)單未說(shuō)明同一血管炎可能累及不同大小的血管（BD，Coga

27、n）宜于臨床工作未提及發(fā)病機(jī)制 ANCA繼發(fā)性血管炎等未歸入2022/8/7Chapel Hill 2012 Classification舊血管炎分類(lèi) Large Vessel vasculitis Medium Vessel vasculitis Small Vessel vasculitis新增加的血管炎分類(lèi) Variable Vessel vasculitis Single Organ vasculitis Vasculitis Associated with Systemic Disease Vasculitis with Probable Etiology 2022/8/72022/

28、8/7新增加的血管炎分類(lèi)ACR classification criteria for Takayasus Arteritis左鎖骨動(dòng)脈閉塞右腎動(dòng)脈狹窄 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 （睪丸炎）the most characteristic symptom of PAN.睪丸炎，腓腸肌痛，垂腕、垂足（單神經(jīng)炎）、腎功不全和腎性高血壓活檢部位：皮膚（深達(dá)皮下脂肪層）、腓腸肌、腓淺神經(jīng)等。Antineutrophil Cytoplasm AntibodyAssociated Vasculitis顯微鏡下多動(dòng)脈炎（MPA），肉芽腫性多動(dòng)脈炎（GPA）和嗜酸性肉芽腫性多動(dòng)脈

31、炎（EGPA）髓過(guò)氧化物酶（MPO）和蛋白酶3（PCR3）是ANCA的主要靶抗原ANCA相關(guān)性血管炎是一種常見(jiàn)的累及多系統(tǒng)的自身免疫性疾病，多累及肺、腎和神經(jīng)系統(tǒng)。c - ANCAp - ANCA 蛋白酶-3（PR3）髓過(guò)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