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1、非结核分枝杆菌肺病的发病率逐年上升。因临床、影像表现与其他疾病相似，极易误诊为其他疾病。,非结核分枝杆菌（nontuberculous mycobacteria，NTM）指除结核分枝杆菌（MTB）复合群和麻风分枝杆菌以外的一大类分枝杆菌。NTM感染 指感染了NTM，但未发病。NTM病指感染了NTM，并引起相关组织、脏器的病变。,一、什么是非结核分支杆菌,二、细菌学分类,1.伯杰细菌分类系统（生长速度）.快速生长型.缓慢生长型2.Runyon分类.光产色菌（eg.堪萨斯分枝杆菌、海分枝杆菌）.暗产色菌（eg.瘰疬分枝杆菌）.不产色菌（eg.鸟-胞内分枝杆菌复合菌组（MAC）、嗜血分枝杆菌）.快速
2、生长分枝杆菌（eg.脓肿分枝杆菌、龟分枝杆菌、偶发分枝杆菌）,三、NTM 流行病学,传播途径：自然环境（主要为水和土壤），潮热地带为主，尚未发现动物人及人人间传播证据。台湾地区 MAC（30%）、脓肿分枝杆菌（17.5%）、偶发分枝杆菌（13.0%)上海 龟分枝杆菌（26.7%）、偶发分枝杆菌（15.4%）、堪萨斯分枝杆菌（14.2%）、MAC（13.1%）东亚地区 MAC（67%）、快速生长分枝杆菌（16%）我国NTM发病率呈上升 趋势 1990年（4.9%）2010年（22.9%）,四、发病机制（与MTB类似）,感染途径：呼吸道、消化道、皮肤等，为条件致病菌。致病过程：中性粒灭杀巨噬细胞吞
3、噬、溶酶体酶溶解抗原及菌体成分转运至局部淋巴结激活效应细胞、释放细胞因子 CD+T细胞（释放-干扰素和IL-12等）等介导免疫反应和迟发型变态反应。肿瘤坏死因子-（TNF-）：激活其他细胞因子、上调黏附分子表达、促进巨噬细胞活化、参与肉芽肿形成、导致组织坏死和空洞形成，TNF-拮抗剂英夫利昔和可溶性受体依那西普可能使NTM感染发展为活动性NTM病。NTM肺病常发生于结构性肺部疾病基础上（如COPD、支扩、肺TB、囊性纤维化、尘肺等）。具有某些表型特征，如绝经期、脊柱侧弯、漏斗胸、二尖瓣脱垂和关节伸展过度等，可对NTM易感。,五、病理变化,菌体成分及抗原与MTB有共性，毒力较MTB弱，干酪样坏死
4、较少，机体组织反应较弱1.NTM肺病病理反应：渗出性反应：淋巴细胞、巨噬细胞浸润、干酪样坏死；增殖性反应：类上皮细胞、朗汉斯巨细胞肉芽肿形成；硬化性反应：细胞萎缩、胶原纤维增生。组织学分型：纤维空洞或类结核型、支气管扩张型、结节型及其他（肺纤维化、肺气肿和肺不张等）。坏死和空洞形成，常多发或多房性，侵及双肺，位于胸膜下，薄壁为主，空洞坏死层较厚且稀软。2.NTM淋巴结病 早期：肉芽肿形成，淋巴结粘连、质韧；晚期：纤维化、钙化，或迅速干酪样坏死及软化、破溃形成慢性窦道。3.皮肤NTM病最易侵犯真皮和皮下脂肪组织，其次为深层肌肉组织；主要病理表现：肉芽肿性病变，非特异性慢性化脓性炎症 早期：急性炎
5、症反应、渗出 晚期：硬结、脓肿、窦道形成4.播散性NTM病 最常侵犯肝脏、淋巴结和胃肠道，亦可累及肺、骨髓、心和肾 肉眼观：肝、脾、淋巴结肿大，可见柠檬色肉芽肿镜下：弥漫性肉芽肿，由特征性纹状组织细胞组成，仅少数为典型肉芽肿。,六、临床及影像学表现,1.NTM 肺病（最为常见）-影像上需要鉴别！主要致病菌种：MAC、脓肿分枝杆菌、偶发分枝杆菌。女性患病率高于男性，老年人居多，尤其是绝经期妇女最为常见，大多已有基础肺部疾病。大多为缓慢起病，临床症状表现差别较大。症状和体征：与肺结核相似，全身中毒症状较轻。影像学：胸片：多为炎性病灶及单发或多发薄壁空洞，多累及上叶尖段和前段；胸部CT:通常以多种形
6、态病变混杂存在，如：结节影、斑片及小斑片样实变影、空洞影、支扩、树芽征、磨玻璃影、线状及纤维条索影、胸膜肥厚粘连等。肺功能：通气功能减退较肺结核更为明显。,2.NTM 淋巴结病（儿童中最常见）-影像上需要鉴别！主要致病菌种：MAC、嗜血分枝杆菌。多见于儿童，1-5岁最常见，10岁以上少见，男：女为1：1.3-2.0。最常累及上颈部和下颌下淋巴结，其次为耳部、腹股沟和腋下淋巴结，单侧多见。多无全身症状体征，仅有局部表现，无或轻度压痛，迅速软化、破溃形成慢性窦道。PPD试验多呈弱阳性，NTM抗原皮试为强阳性。超声或CT：非对称性淋巴结肿大，周围炎症反应较轻，对此可酌情选择MRI检查评价。,3.NT
7、M 皮肤病-临床上易忽视的！主要致病菌种：偶发分枝杆菌、脓肿分枝杆菌等。可引起皮肤及皮下软组织病变。局部脓肿常见，多位于针刺伤口、开放性伤口或骨折处，往往迁延不愈。亦可为皮肤感染（Buruli溃疡）、游泳池肉芽肿、类孢子丝菌病、皮肤播散性和多中心结节灶。4.播散性NTM病-临床上易忽视！主要致病菌种：MAC、堪萨斯分枝杆菌、脓肿分枝杆菌等。见于免疫功能受损者，多见于HIV感染，亦可见于脏器移植、长期应用皮质激素和白血病等。可有淋巴结病、骨病、肝病、胃肠道疾病、心内膜炎、心包炎和脑膜炎等。临床表现多种多样，最常见为不明原因持续性或间歇性发热，多有进行性体重减轻、夜间盗汗 可有轻度腹痛甚至持续性腹
8、痛、腹泻、消化不良、肝脾肿大、皮下多发性结节或脓肿等。实验室检查：全血细胞减少，CD4+T细胞降低，血清碱性磷酸酶和乳酸脱氢酶升高，肝功能异常，体液或分泌物涂片、培养抗酸染色多为阳性。5.其他NTM病-临床上易忽视！主要致病菌种：海分枝杆菌、MAC。可引起手或腕部滑膜慢性病变、化脓性关节病、牙龈病变、泌尿生殖系、眼、胃肠道疾病等。,八、诊断,1.NTM感染的诊断：皮肤试验阳性，缺乏组织、器官侵犯证据。2.疑似NTM病（具备上述7项之一即可考虑为疑似NTM病）痰抗酸染色阳性，临床表现与肺结核不相符；痰液显微镜发现异常分枝杆菌；痰或其他标本分枝杆菌培养阳性，菌落形态及生长与MTB不相符；正规抗结核
9、无效而且反复排菌，肺部病灶以支扩、多发性小结节及薄壁空洞为主；支气管卫生净化处理后痰分枝杆菌未能转阴；有免疫功能缺陷，但已除外肺结核者；医源性或非医源性软组织损伤，或外科术后伤口长期不愈而不明原因者。3.NTM病（无论NTM肺病还是肺外NTM病，或是播散性NTM病，均需进行NTM菌种鉴定）NTM肺病：呼吸和（或）全身症状+胸部影像+排除其他疾病+NTM培养和（或）病理学特征改变；肺外NTM病：局部和（或）全身症状+排除其他疾病+NTM培养；播散性NTM病：相关症状+肺或肺外病变+血培养NTM阳性和（或）骨髓、肝脏等穿刺物NTM培养。,九、治疗,1.治疗原则 治疗前药敏试验；根据药敏试验结果和用
10、药史，5-6种药物联合治疗，强化期6-12个月，巩固期12-18个月，NTM 培阳阴转后继续治疗12个月以上；不同 NTM 病用药种类、疗程不同；不建议对疑似 NTM 病患者行经验性治疗；NTM 肺病慎用外科手术治疗。,2.治疗药物 新型大环内酯类：克拉霉素（巨噬细胞和组织内浓度较高）、阿奇霉素；利福霉素类:利福平、利福他汀（肝代谢酶诱导作用较弱）；乙胺丁醇：最常用的基本药物；氨基糖苷类：链霉素、阿米卡星（主要针对MAC）、妥布霉素（主要针对龟分枝杆菌）；氟喹诺酮类：DC-159a、氧氟沙星、环丙沙星、左氧氟沙星、加替沙星和莫西沙星（主要针对MAC、偶发分枝杆菌）；头孢西丁：主要针对快速生长分
11、枝杆菌（对99%脓肿分枝杆菌敏感）；其他：主要为针对快速生长分枝杆菌的药物，如四环素类（多西环素、米诺环素、替加环素）、磺胺类（磺胺甲恶唑、复方磺胺甲恶唑）、碳青霉烯类（伊米培南/西司他丁）、利奈唑胺。,NTM感染肺部影像解读,NTM影像表现：小叶中心结节,NTM 影像学表现：树芽征,NTM 影像学表现：肺实变,NTM 影像学表现：多中心肺实变,NTM 影像学表现：多灶性磨玻璃影,鸟胞内分枝杆菌（MAC）感染肺部空洞及空腔,Jong Woon Song，et al,AJR 2008;191:W160W166,鸟胞内分枝杆菌（MAC）感染肺部结节影,Jong Woon Song，et al,AJ
12、R 2008;191:W160W166,鸟胞内分枝杆菌（MAC）支气管扩张,Jong Woon Song，et al,AJR 2008;191:W160W166,鸟胞内分枝杆菌复合体（MAC）支气管扩张,Jong Woon Song，et al,AJR 2008;191:W160W166,Pulmonary Nontuber-culous Mycobacterial Infection:Radiologic Manifestations Jeremy J et al RadioGraphics 1999;19:14871503,Pulmonary M avium-intracellulare
13、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 to antimycobacterial therapy and underwent right upper lobe resection.(b)Posteroanterior ches
14、t 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 aviumintracellulare infection was confirmed with transbronchial lung biopsy.The infection responded poorly to anti
15、mycobacterial 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 air in the right pleural space,a finding consistent with a bronchopleural fistula from chronic M avi
16、um-intracellulare infection.Note the scattered heterogeneous areas of increased opacity in the left lung.,鸟胞内分枝杆菌（MAC）感染,女，50岁。慢性咳嗽。A)右上肺高密度伴体积缩小。对抗分支杆菌治疗不敏感。B）3年后，右上叶实变，左侧肺出现病灶。活检证实MAC感染，药物治疗不敏感，行右上肺切除术。右侧胸腔持续感染而导致脓胸。C）一年后，支气管胸膜瘘。,Pulmonary M avium-intracellulare infection in a 72-year-old woman wi
17、th 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 in the lingula.There is right paratracheal adenopathy(arrows).(b)Posteroanterior chest radiograph obtaine
18、d 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 increased opacity in the right upper lobe and lingula.New areas of increased opacity have developed in the middle lo
19、be(arrowhead).,女，72岁，肺MAC感染，慢性咳嗽。MAC痰培养阳性。胸片可见双侧肺散在局灶高密度影，右侧纵隔淋巴结增大。经长期抗结核治疗，5年后胸片显示上叶气管旁淋巴结体积渐缩小，右上叶和左侧舌叶密度增高影改善。右侧肺中叶新增病灶。,Pulmonary M avium-intracellulare infection in a 58-year-old woman with a history of chronic cough and recent onset of shortness of breath and fatigue.Posteroanterior chest rad
20、iograph 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 opacity bilaterally,女性，58岁。肺MAC感染，慢性咳嗽、近来呼吸短促、疲乏。胸片显示右上叶薄壁空洞，左上叶边界清楚的结节灶。双侧肺多发性高密度结节灶。,Pulmonary MAC infection in
21、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 heterogeneous linear and nodular areas of increased opacity in the left lung.There is marked destruction of the right lung with a
22、rchitectural 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 later with progressive weight loss and hemoptysis.(b)Chest radiograph shows progressive destruction of the upper lobes
23、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 and traction bronchiectasis(arrowheads).(c)Left bronchial arteriogram shows a bronchial arterypulmonary artery fistula(arrow
24、s).The patient died after massive hemoptysis.,男，43岁，慢阻肺，肺MAC感染，杵状指、慢性咳嗽；支气管灌洗液MAC阳性。a)胸片：左肺不均匀线样、结节样高密度影，右肺结构显著破坏，并右下叶背段可见气液平；20个月期间抗痨治疗不规则，伴进行性体重减轻及咯血。b)胸片：右上叶进行性破坏伴右上叶肺大泡；左肺上叶不均匀密度增高灶（箭），伴肺结构破坏及牵拉性支扩（箭头）。C)左肺支气管动脉造影显示支气管动脉-肺动脉瘘（箭）。病人大咯血后死亡。,Pulmonary M avium-intracellulare infection in a 50-year-o
25、ld 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 admission shows sutures(arrow)and scarring in the right upper lobe from partial pulmonary resection.(b)Posteroanterior chest radiogra
26、ph obtained at admission shows progressive volume loss,more areas of increased opacity around the sutures,and adjacent pleural thickening.M avium-intracellulare was cultured from bronchial washings.No malignant cells were found,and the patients condition improved with appropriate antimycobacterial t
27、herapy.,男，50岁，肺MAC感染，既往有非小细胞癌病史，进来消瘦、咯血。a)入院前4年胸片显示右上叶切除后的缝合（箭）和瘢痕。b)入院时胸片显示病变肺体积缩小加重、更致密，邻近胸膜增厚。支气管灌洗液培养MAC阳性，没有恶性细胞，经抗分支杆菌治疗后，症状改善。,Pulmonary M avium-intracellulare infection in a 64-year-old man with a historyof chronic weight loss,cough,and occasional hemoptysis.(a)Posteroanterior chest radiogra
28、ph 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 biapical pleural thickening.(b)Coronal(FDG)positron emission tomographic scan shows marked increased FDG uptake in the upper lobes and in the
29、wall of the right upper lobe cavity.Although increased FDG uptake is usually indicative of malignancy,false-positive studies can occur with NTMB infection.C=normal cardiac activity,H=hepatic activity,M=mediastinal activity.,男，64岁，肺MAC感染。咳嗽、体重减轻、偶有咯血。a)胸片：双上肺体积缩小、其中见散在分布的结节样高密度区；右上空洞气液面及胸膜增厚.b)PET冠状图
30、示双上叶病变、右上叶空洞壁明显高摄取。这种易误认为恶性肿瘤的高摄取同样可见于NTMB感染。,Pulmonary M kansasii infectionin a 28-year-old woman with a history of surgically treated tricuspid atresia who presented with weight loss,fever,and a cough.(a)Posteroanterior chest radiograph shows heterogeneous areas of increased opacity in the right u
31、pper 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 portion of the right lung,which are due to endobronchial spread of infection.,女，28岁，肺堪萨斯分支杆菌感染。外科治疗三尖瓣闭锁术后，消瘦、咳嗽、发热。a)、胸片示右上叶密度不均匀病灶。b、c)、CT示右上叶大的空洞（b）和由于支气管播散所致的高密度小结
32、节、“树芽征”（c）,Pulmonary M avium-intracellulare infection in a 67-year-old woman.The infection was proved with resection of the lingula.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岁，舌叶切除标本证实肺MAC感染。
33、CT扫描图：右肺中叶轻度柱状支扩（箭）；小叶中心结节（a图箭头）,Pulmonary M avium-intracellulare infection in a 70-year-old white woman with a chronic cough,malaise,and weight loss.M avium-intracellulare was cultured from bronchial washings.Thin-section CT scans(1-mm collimation)show atelectasis and bronchiectasis bilaterally,mor
34、e severe in the middle lobe and lingula.Note the small,peripheral,tree-in-bud areas of increased opacity(arrow in a)and the 1.5-cm-diameter nodule in the left lower lobe(arrow in b).,女，70岁，慢性咳嗽、不适及体重减轻，支气管灌洗液培养证实肺MAC感染。薄层CT扫描示双侧肺散在不张及支扩，以右肺中叶及左肺舌叶著。注：外周区树芽征（a图箭）、左下叶1.5cm结节（b图箭）。,Pulmonary M avium-in
35、tracellulare infection in a 60-year-old asymptomatic woman.(a)Close-up posteroanterior chest radiograph of the right 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 show
36、s the thin-walled cavity in the right upper lobe,as well as a communicating bronchus(arrowheads)and small centrilobular nodules(arrows).,60岁，女。肺MAC感染，无症状。胸片示右上肺片状高密度影伴薄壁空洞。薄层CT显示薄壁空洞及引流支气管（箭头）；小叶中心结节（箭）,Pulmonary M aviumintracellulare infection in a 42-yeold woman with a chronic cough.Sputum culture
37、s were negative.M avium-intracellulare infection was diagnosed with transbronchial lung biopsy.Thin-section CT scan(1-mm collimation)shows cylindrical bronchiectasis,bronchial wall thickening,and tree-in-bud areas of increased opacity,女，42岁。慢性咳嗽，痰培养阴性，内镜活检证实MAC感染。薄层CT显示柱状支扩、支气管壁增厚、树芽征。,Pulmonary M c
38、helonae infection in a 45-year-old asymptomatic woman.Close up posteroanterior chest radiograph of theright 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 A
39、IDS.(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 granulomat
40、ous inflammation,and a culture was positive for M aviumintracellulare.,女，45岁，龟分枝杆菌感染，无症状。非钙化性结节灶,29岁，男性，艾滋病人。右肺尖肿块，不伴肺门和纵隔淋巴结增大。活检为炎性肉芽肿，细菌培养：MAC阳性,Disseminated M avium-intracellulare infection in a 35-year-old man with AIDS who presented with a cough and fever.Sputum cultures were negative.M avium-
41、intracellulare infection was diagnosed with bronchoscopy and transbronchial biopsy.Posteroanterior chest radiograph shows masslike areas of increased opacity and smaller,scattered,nodular areas of increased opacity in the upper lobes.There is no hilar or mediastinal adenopathy.,男，35岁。艾滋病，咳嗽、发热。痰培养阴性
42、，内镜活检为MAC。胸片双上肺块状高密度影，呈结节状分布。没有肺门、纵隔淋巴结增大。,Disseminated M avium intracellulare infection in a 33-year-old man with AIDS who presented with weight loss,pyrexia,and back pain.(a)Posteroanterior chest radiograph shows diffuse small nodules with basal predominance.There isno hilar or mediastinal adenopa
43、thy.(b)Chest CT scan also shows small,discrete nodules.Transbronchial biopsy was positive for M avium-intracellulare.(c)CT scan of the abdomen shows a right psoas abscess(arrow).Needle aspiration was positive for M avium-intracellulare.,男，33岁，艾滋病人。胸片弥漫性小结节，CT见散在结节；右侧腰大肌脓肿，活检均为非结核分支杆菌感染（MAC）。,女，36岁。体检发现肺部病变，体温低热，咳嗽，有痰，既往年幼时即发生过肺感染，以后间断发生并抗感染治疗后缓解。,2016年网络会诊病例,抗痨治疗后症状缓解,该病例10年前的CT检查,此例显然符合在原肺部疾病基础上感染NTM,E N D,
