非結(jié)核分支桿菌病影像學(xué)(NTM)-修改版

1、非結(jié)核分支桿菌病影像學(xué)（修改版）中國石油中心醫(yī)院 影像科 楊景震2016-2月修改版非結(jié)核分枝桿菌肺病的發(fā)病率逐年上升。因臨床、影像表現(xiàn)與其他疾病相似，極易誤診為其他疾病。 非結(jié)核分枝桿菌（nontuberculous mycobacteria ，NTM）指除結(jié)核分枝桿菌（MTB）復(fù)合群和麻風(fēng)分枝桿菌以外的一大類分枝桿菌。 NTM感染 指感染了NTM，但未發(fā)病。 NTM病指感染了NTM，并引起相關(guān)組織、臟器的病變。一、什么是非結(jié)核分支桿菌二、細(xì)菌學(xué)分類1.伯杰細(xì)菌分類系統(tǒng)（生長速度） .快速生長型 .緩慢生長型2.Runyon分類 .光產(chǎn)色菌（eg.堪薩斯分枝桿菌、海分枝桿菌） .暗產(chǎn)色菌（e

2、g.瘰疬分枝桿菌） .不產(chǎn)色菌（eg.鳥-胞內(nèi)分枝桿菌復(fù)合菌組（MAC）、嗜血分枝桿菌） .快速生長分枝桿菌（eg.膿腫分枝桿菌、龜分枝桿菌、偶發(fā)分枝桿菌）三、NTM 流行病學(xué)傳播途徑：自然環(huán)境（主要為水和土壤），潮熱地帶為主，尚未發(fā)現(xiàn)動(dòng)物人及人人間傳播證據(jù)。臺灣地區(qū) MAC（30%）、膿腫分枝桿菌（17.5%）、偶發(fā)分枝桿菌（13.0%)上海 龜分枝桿菌（26.7%）、偶發(fā)分枝桿菌（15.4%）、堪薩斯分枝桿菌（14.2%）、MAC（13.1%）東亞地區(qū) MAC（67%）、快速生長分枝桿菌（16%）我國NTM發(fā)病率呈上升 趨勢 1990年（4.9%） 2010年（22.9%）四、發(fā)病機(jī)制（與

3、MTB類似）1. 感染途徑：呼吸道、消化道、皮膚等，為條件致病菌。2. 致病過程：中性粒滅殺巨噬細(xì)胞吞噬、溶酶體酶溶解抗原及菌體成分轉(zhuǎn)運(yùn)至局部淋巴結(jié)激活效應(yīng)細(xì)胞、釋放細(xì)胞因子 CD+T細(xì)胞（釋放-干擾素和IL-12等）等介導(dǎo)免疫反應(yīng)和遲發(fā)型變態(tài)反應(yīng)。3. 腫瘤壞死因子-（TNF-）：激活其他細(xì)胞因子、上調(diào)黏附分子表達(dá)、促進(jìn)巨噬細(xì)胞活化、參與肉芽腫形成、導(dǎo)致組織壞死和空洞形成，TNF-拮抗劑英夫利昔和可溶性受體依那西普可能使NTM感染發(fā)展為活動(dòng)性NTM病。4. NTM肺病常發(fā)生于結(jié)構(gòu)性肺部疾病基礎(chǔ)上（如COPD、支擴(kuò)、肺TB、囊性纖維化、塵肺等）。5. 具有某些表型特征，如絕經(jīng)期、脊柱側(cè)彎、漏斗

4、胸、二尖瓣脫垂和關(guān)節(jié)伸展過度等，可對NTM易感。五、病理變化菌體成分及抗原與MTB有共性，毒力較MTB弱，干酪樣壞死較少，機(jī)體組織反應(yīng)較弱1.NTM肺病病理反應(yīng)：滲出性反應(yīng)：淋巴細(xì)胞、巨噬細(xì)胞浸潤、干酪樣壞死；增殖性反應(yīng)：類上皮細(xì)胞、朗漢斯巨細(xì)胞肉芽腫形成；硬化性反應(yīng)：細(xì)胞萎縮、膠原纖維增生。組織學(xué)分型：纖維空洞或類結(jié)核型、支氣管擴(kuò)張型、結(jié)節(jié)型及其他（肺纖維化、肺氣腫和肺不張等）。壞死和空洞形成，常多發(fā)或多房性，侵及雙肺，位于胸膜下，薄壁為主，空洞壞死層較厚且稀軟。2.NTM淋巴結(jié)病 早期：肉芽腫形成，淋巴結(jié)粘連、質(zhì)韌；晚期：纖維化、鈣化，或迅速干酪樣壞死及軟化、破潰形成慢性竇道。3.皮膚NT

5、M病最易侵犯真皮和皮下脂肪組織，其次為深層肌肉組織；主要病理表現(xiàn)：肉芽腫性病變，非特異性慢性化膿性炎癥 早期：急性炎癥反應(yīng)、滲出 晚期：硬結(jié)、膿腫、竇道形成4.播散性NTM病 最常侵犯肝臟、淋巴結(jié)和胃腸道，亦可累及肺、骨髓、心和腎 肉眼觀：肝、脾、淋巴結(jié)腫大，可見檸檬色肉芽腫鏡下：彌漫性肉芽腫，由特征性紋狀組織細(xì)胞組成，僅少數(shù)為典型肉芽腫。六、臨床及影像學(xué)表現(xiàn)1.NTM 肺?。ㄗ顬槌Ｒ姡?影像上需要鑒別！ 主要致病菌種：MAC、膿腫分枝桿菌、偶發(fā)分枝桿菌。 女性患病率高于男性，老年人居多，尤其是絕經(jīng)期婦女最為常見，大多已有基礎(chǔ)肺部疾病。 大多為緩慢起病，臨床癥狀表現(xiàn)差別較大。 癥狀和體征：與肺

6、結(jié)核相似，全身中毒癥狀較輕。 影像學(xué)：胸片：多為炎性病灶及單發(fā)或多發(fā)薄壁空洞，多累及上葉尖段和前段；胸部CT:通常以多種形態(tài)病變混雜存在，如：結(jié)節(jié)影、斑片及小斑片樣實(shí)變影、空洞影、支擴(kuò)、樹芽征、磨玻璃影、線狀及纖維條索影、胸膜肥厚粘連等。 肺功能：通氣功能減退較肺結(jié)核更為明顯。2.NTM 淋巴結(jié)?。▋和凶畛Ｒ姡?影像上需要鑒別！ 主要致病菌種：MAC、嗜血分枝桿菌。 多見于兒童，1-5歲最常見，10歲以上少見，男：女為1：1.3-2.0。 最常累及上頸部和下頜下淋巴結(jié)，其次為耳部、腹股溝和腋下淋巴結(jié)，單側(cè)多見。 多無全身癥狀體征，僅有局部表現(xiàn)，無或輕度壓痛，迅速軟化、破潰形成慢性竇道。 PP

7、D試驗(yàn)多呈弱陽性，NTM抗原皮試為強(qiáng)陽性。 超聲或CT：非對稱性淋巴結(jié)腫大，周圍炎癥反應(yīng)較輕，對此可酌情選擇MRI檢查評價(jià)。3.NTM 皮膚病- 臨床上易忽視的！ 主要致病菌種：偶發(fā)分枝桿菌、膿腫分枝桿菌等。 可引起皮膚及皮下軟組織病變。 局部膿腫常見，多位于針刺傷口、開放性傷口或骨折處，往往遷延不愈。 亦可為皮膚感染（Buruli潰瘍）、游泳池肉芽腫、類孢子絲菌病、皮膚播散性和多中心結(jié)節(jié)灶。4.播散性NTM病- 臨床上易忽視！ 主要致病菌種：MAC、堪薩斯分枝桿菌、膿腫分枝桿菌等。 見于免疫功能受損者，多見于HIV感染，亦可見于臟器移植、長期應(yīng)用皮質(zhì)激素和白血病等。 可有淋巴結(jié)病、骨病、肝病

8、、胃腸道疾病、心內(nèi)膜炎、心包炎和腦膜炎等。 臨床表現(xiàn)多種多樣，最常見為不明原因持續(xù)性或間歇性發(fā)熱，多有進(jìn)行性體重減輕、夜間盜汗 可有輕度腹痛甚至持續(xù)性腹痛、腹瀉、消化不良、肝脾腫大、皮下多發(fā)性結(jié)節(jié)或膿腫等。 實(shí)驗(yàn)室檢查：全血細(xì)胞減少，CD4+T細(xì)胞降低，血清堿性磷酸酶和乳酸脫氫酶升高，肝功能異常，體液或分泌物涂片、培養(yǎng)抗酸染色多為陽性。5.其他NTM病- 臨床上易忽視！ 主要致病菌種：海分枝桿菌、MAC。 可引起手或腕部滑膜慢性病變、化膿性關(guān)節(jié)病、牙齦病變、泌尿生殖系、眼、胃腸道疾病等。八、診斷1.NTM感染的診斷：皮膚試驗(yàn)陽性，缺乏組織、器官侵犯證據(jù)。2.疑似NTM病 （具備上述7項(xiàng)之一即可

9、考慮為疑似NTM病） 痰抗酸染色陽性，臨床表現(xiàn)與肺結(jié)核不相符； 痰液顯微鏡發(fā)現(xiàn)異常分枝桿菌； 痰或其他標(biāo)本分枝桿菌培養(yǎng)陽性，菌落形態(tài)及生長與MTB不相符； 正規(guī)抗結(jié)核無效而且反復(fù)排菌，肺部病灶以支擴(kuò)、多發(fā)性小結(jié)節(jié)及薄壁空洞為主； 支氣管衛(wèi)生凈化處理后痰分枝桿菌未能轉(zhuǎn)陰； 有免疫功能缺陷，但已除外肺結(jié)核者； 醫(yī)源性或非醫(yī)源性軟組織損傷，或外科術(shù)后傷口長期不愈而不明原因者。3.NTM病 （無論NTM肺病還是肺外NTM病，或是播散性NTM病，均需進(jìn)行NTM菌種鑒定） NTM肺?。汉粑停ɑ颍┤戆Y狀+胸部影像+排除其他疾病+NTM培養(yǎng)和（或）病理學(xué)特征改變； 肺外NTM病：局部和（或）全身癥狀+排除

10、其他疾病+NTM培養(yǎng)； 播散性NTM?。合嚓P(guān)癥狀+肺或肺外病變+血培養(yǎng)NTM陽性和（或）骨髓、肝臟等穿刺物NTM培養(yǎng)。九、治療1.治療原則 治療前藥敏試驗(yàn)； 根據(jù)藥敏試驗(yàn)結(jié)果和用藥史，5-6種藥物聯(lián)合治療，強(qiáng)化期6-12個(gè)月，鞏固期12-18個(gè)月，NTM 培陽陰轉(zhuǎn)后繼續(xù)治療12個(gè)月以上； 不同 NTM 病用藥種類、療程不同； 不建議對疑似 NTM 病患者行經(jīng)驗(yàn)性治療； NTM 肺病慎用外科手術(shù)治療。2.治療藥物 新型大環(huán)內(nèi)酯類：克拉霉素（巨噬細(xì)胞和組織內(nèi)濃度較高）、阿奇霉素； 利福霉素類:利福平、利福他?。ǜ未x酶誘導(dǎo)作用較弱）； 乙胺丁醇：最常用的基本藥物； 氨基糖苷類：鏈霉素、阿米卡星（主

11、要針對MAC）、妥布霉素（主要針對龜分枝桿菌）； 氟喹諾酮類：DC-159a、氧氟沙星、環(huán)丙沙星、左氧氟沙星、加替沙星和莫西沙星（主要針對MAC、偶發(fā)分枝桿菌）； 頭孢西丁：主要針對快速生長分枝桿菌（對99%膿腫分枝桿菌敏感）； 其他：主要為針對快速生長分枝桿菌的藥物，如四環(huán)素類（多西環(huán)素、米諾環(huán)素、替加環(huán)素）、磺胺類（磺胺甲惡唑、復(fù)方磺胺甲惡唑）、碳青霉烯類（伊米培南/西司他丁）、利奈唑胺。NTM感染肺部影像解讀NTM影像表現(xiàn)：小葉中心結(jié)節(jié)NTM 影像學(xué)表現(xiàn)：樹芽征NTM 影像學(xué)表現(xiàn)：肺實(shí)變NTM 影像學(xué)表現(xiàn)：多中心肺實(shí)變NTM 影像學(xué)表現(xiàn)：多灶性磨玻璃影鳥胞內(nèi)分枝桿菌（MAC）感染肺部空洞

12、及空腔Jong Woon Song，et al, AJR 2008; 191:W160W166鳥胞內(nèi)分枝桿菌（MAC）感染肺部結(jié)節(jié)影Jong Woon Song，et al, AJR 2008; 191:W160W166鳥胞內(nèi)分枝桿菌（MAC）支氣管擴(kuò)張Jong Woon Song，et al, AJR 2008; 191:W160W166鳥胞內(nèi)分枝桿菌復(fù)合體（MAC）支氣管擴(kuò)張Jong Woon Song，et al, AJR 2008; 191:W160W166Pulmonary Nontuber-culous Mycobacterial Infection: Radiologic Man

13、ifestations Jeremy J et al RadioGraphics 1999; 19:14871503Pulmonary M avium-intracellulare infection in a 50-year-old woman with a chronic cough. (a) Posteroanterior chest radiograph shows heterogeneous areas of increased opacity in the right upper lobe with volume loss. The patient responded poorly

14、 to antimycobacterial therapy and underwent right upper lobe resection. (b) Posteroanterior chest radio-graph obtained 3 years after resection shows consolidation in the upper aspect of the right lung and new areas of increased opacity in the left lung. The diagnosis of recurrent M aviumintracellula

15、re infection was confirmed with transbronchial lung biopsy. The infection responded poorly to antimycobacterial therapy, and right pneumonectomy was performed.Persistent infection resulted in chronic empyema in the right pleural space. (c) Posteroanterior chest radiograph obtained 1 year later shows

16、 air in the right pleural space, a finding consistent with a bronchopleural fistula from chronic M avium-intracellulare infection. Note the scattered heterogeneous areas of increased opacity in the left lung.鳥胞內(nèi)分枝桿菌（MAC）感染女，50歲。慢性咳嗽。A)右上肺高密度伴體積縮小。對抗分支桿菌治療不敏感。B）3年后，右上葉實(shí)變，左側(cè)肺出現(xiàn)病灶?；顧z證實(shí)MAC感染，藥物治療不敏感，行右上

17、肺切除術(shù)。右側(cè)胸腔持續(xù)感染而導(dǎo)致膿胸。C）一年后，支氣管胸膜瘺。Pulmonary M avium-intracellulare infection in a 72-year-old woman with a chronic cough. M avium-intracellulare was cultured from the sputum. (a) Posteroanterior chest radiograph shows scattered, bilateral, pulmonary areas of increased opacity with focal consolidation

18、in the lingula. There is right paratracheal adenopathy (arrows). (b) Posteroanterior chest radiograph obtained 5 years later after long-term antituberculous drug therapy shows progressive volume loss in the upper lobes, in-creased paratracheal adenopathy (arrow), and improvement in the areas of incr

19、eased opacity in the right upper lobe and lingula. New areas of increased opacity have developed in the middle lobe (arrowhead).女，72歲，肺MAC感染，慢性咳嗽。MAC痰培養(yǎng)陽性。胸片可見雙側(cè)肺散在局灶高密度影，右側(cè)縱隔淋巴結(jié)增大。經(jīng)長期抗結(jié)核治療，5年后胸片顯示上葉氣管旁淋巴結(jié)體積漸縮小，右上葉和左側(cè)舌葉密度增高影改善。右側(cè)肺中葉新增病灶。Pulmonary M avium-intracellulare infection in a 58-year-old wom

20、an with a history of chronic cough and recent onset of shortness of breath and fatigue. Posteroanterior chest radiograph shows thin-walled cavities in the right upper lobe and a well-defined nodule in the left upper lobe (arrow). There are scattered heterogeneous and small nodular areas of increased

21、 opacity bilaterally女性，58歲。肺MAC感染，慢性咳嗽、近來呼吸短促、疲乏。胸片顯示右上葉薄壁空洞，左上葉邊界清楚的結(jié)節(jié)灶。雙側(cè)肺多發(fā)性高密度結(jié)節(jié)灶。Pulmonary MAC infection in a 43-year-old man with chronic obstructive lung disease, digital clubbing, and a chronic productive cough. Bronchial washings were positive for MAC. (a) Chest radiograph shows heterogeneo

22、us linear and nodular areas of increased opacity in the left lung. There is marked destruction of the right lung with architectural distortion and an air-fluid level in the superior segment of the right lower lobe. The patient was poorly compliant with antituberculous therapy and presented 20 months

23、 later with progressive weight loss and hemoptysis. (b) Chest radiograph shows progressive destruction of the upper lobes with a large bulla in the right upper lobe. Heterogeneous areas of increased opacity are present in the left upper lobe (arrows), and there is associated architectural distortion

24、 and traction bronchiectasis (arrowheads). (c) Left bronchial arteriogram shows a bronchial arterypulmonary artery fistula (arrows). The patient died after massive hemoptysis.男，43歲，慢阻肺，肺MAC感染，杵狀指、慢性咳嗽；支氣管灌洗液MAC陽性。a)胸片：左肺不均勻線樣、結(jié)節(jié)樣高密度影，右肺結(jié)構(gòu)顯著破壞，并右下葉背段可見氣液平；20個(gè)月期間抗癆治療不規(guī)則，伴進(jìn)行性體重減輕及咯血。b)胸片：右上葉進(jìn)行性破壞伴右上葉肺大

25、泡；左肺上葉不均勻密度增高灶（箭），伴肺結(jié)構(gòu)破壞及牽拉性支擴(kuò)（箭頭）。C)左肺支氣管動(dòng)脈造影顯示支氣管動(dòng)脈-肺動(dòng)脈瘺（箭）。病人大咯血后死亡。Pulmonary M avium-intracellulare infection in a 50-year-old man with a history of resected nonsmall cell lung cancer and recent onset of weight loss and hemoptysis. (a) Posteroanterior chest radiograph obtained 4 years before adm

26、ission shows sutures (arrow) and scarring in the right upper lobe from partial pulmonary resection. (b) Posteroanterior chest radiograph obtained at admission shows progressive volume loss, more areas of increased opacity around the sutures, and adjacent pleural thickening. M avium-intracellulare wa

27、s cultured from bronchial washings. No malignant cells were found, and the patients condition improved with appropriate antimycobacterial therapy.男，50歲，肺MAC感染，既往有非小細(xì)胞癌病史，進(jìn)來消瘦、咯血。a)入院前4年胸片顯示右上葉切除后的縫合（箭）和瘢痕。b)入院時(shí)胸片顯示病變肺體積縮小加重、更致密，鄰近胸膜增厚。支氣管灌洗液培養(yǎng)MAC陽性，沒有惡性細(xì)胞，經(jīng)抗分支桿菌治療后，癥狀改善。Pulmonary M avium-intracellul

28、are infection in a 64-year-old man with a historyof chronic weight loss, cough, and occasional hemoptysis. (a) Posteroanterior chest radiograph shows scattered nodular areas of increased opacity and volume loss in both upper lobes. Note the cavity in the right upper lobe with an air-fluid level and

29、biapical pleural thickening. (b) Coronal (FDG) positron emission tomographic scan shows marked increased FDG uptake in the upper lobes and in the wall of the right upper lobe cavity. Although increased FDG uptake is usually indicative of malignancy, false-positive studies can occur with NTMB infecti

30、on. C = normal cardiac activity, H = hepatic activity, M = mediastinal activity.男，64歲，肺MAC感染。咳嗽、體重減輕、偶有咯血。a)胸片：雙上肺體積縮小、其中見散在分布的結(jié)節(jié)樣高密度區(qū)；右上空洞氣液面及胸膜增厚.b)PET冠狀圖示雙上葉病變、右上葉空洞壁明顯高攝取。這種易誤認(rèn)為惡性腫瘤的高攝取同樣可見于NTMB感染。Pulmonary M kansasii infectionin a 28-year-old woman with a history of surgically treated tricuspid

31、 atresia who presented with weight loss, fever, and a cough. (a) Posteroanterior chest radiograph shows heterogeneous areas of increased opacity in the right upper lobe. (b, c) CT scans show a large upper lobe cavity (b) and small, nodular, tree-in-bud areas of increased opacity (c) in the dependent

32、 portion of the right lung, which are due to endobronchial spread of infection. 女，28歲，肺堪薩斯分支桿菌感染。外科治療三尖瓣閉鎖術(shù)后，消瘦、咳嗽、發(fā)熱。 a)、胸片示右上葉密度不均勻病灶。b、c)、CT示右上葉大的空洞（b）和由于支氣管播散所致的高密度小結(jié)節(jié)、“樹芽征”（c）Pulmonary M avium-intracellulare infection in a 67-year-old woman. The infection was proved with resection of the lingul

33、a. Close-up CT scans of the right lung show mild cylindrical bronchiectasis (arrow) and small centrilobular nodules in the middle lobe (arrowhead in a).女，67歲，舌葉切除標(biāo)本證實(shí)肺MAC感染。CT掃描圖：右肺中葉輕度柱狀支擴(kuò)（箭）；小葉中心結(jié)節(jié)（a圖箭頭）Pulmonary M avium-intracellulare infection in a 70-year-old white woman with a chronic cough, m

34、alaise, and weight loss. M avium-intracellulare was cultured from bronchial washings. Thin-section CT scans (1-mm collimation) show atelectasis and bronchiectasis bilaterally, more severe in the middle lobe and lingula. Note the small, peripheral, tree-in-bud areas of increased opacity (arrow in a)

35、and the 1.5-cm-diameter nodule in the left lower lobe (arrow in b).女，70歲，慢性咳嗽、不適及體重減輕，支氣管灌洗液培養(yǎng)證實(shí)肺MAC感染。薄層CT掃描示雙側(cè)肺散在不張及支擴(kuò)，以右肺中葉及左肺舌葉著。注：外周區(qū)樹芽征（a圖箭）、左下葉1.5cm結(jié)節(jié)（b圖箭）。Pulmonary M avium-intracellulare infection in a 60-year-old asymptomatic woman. (a) Close-up posteroanterior chest radiograph of the righ

36、t lung shows scattered, small, heterogeneous areas of increased opacity and a thin-walled cavityin the right upper lobe (arrowheads). (b) Close-up thin-section CT scan of the right lung shows the thin-walled cavity in the right upper lobe, as well as a communicating bronchus (arrowheads) and small c

37、entrilobular nodules (arrows).60歲，女。肺MAC感染，無癥狀。胸片示右上肺片狀高密度影伴薄壁空洞。薄層CT顯示薄壁空洞及引流支氣管（箭頭）；小葉中心結(jié)節(jié)（箭）Pulmonary M aviumintracellulare infection in a 42-yeold woman with a chronic cough. Sputum cultures were negative. M avium-intracellulare infection was diagnosed with transbronchial lung biopsy. Thin-secti

38、on CT scan (1-mm collimation) shows cylindrical bronchiectasis, bronchial wall thickening, and tree-in-bud areas of increased opacity女，42歲。慢性咳嗽，痰培養(yǎng)陰性，內(nèi)鏡活檢證實(shí)MAC感染。薄層CT顯示柱狀支擴(kuò)、支氣管壁增厚、樹芽征。Pulmonary M chelonae infection in a 45-year-old asymptomatic woman. Close up posteroanterior chest radiograph of the

39、right lower lobe shows a well-defined, noncalcified, 1-cm-diameter nodule (arrow). M chelonae infection was diagnosed at resection.Pulmonary M avium-intracellulare infection in a 29-year-old man with AIDS.(a) Close-up posteroanterior chest radiograph of the upper right lung shows a mass in the apex of the lung (arrows) without hilar or paratracheal adenopathy. (b) CT scan shows a heterogeneous soft-tissue mass (M) in the right upper lobe abutting the mediastinum and chest wall. Biopsy revealed granul