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肺结核是最常见的全身性传染病之一，也是全球主要公共卫生问题之一。该病症有多种表现形式和临床表现，仍是引起成人死亡的重要原因之一。肺结核的一种罕见表现形式是支气管内膜结核，约占肺结核病例的10-40%。该病症可能并发气管支气管狭窄，瘘管是一种少见的并发症，多数形成于胸膜区，少数形成于食道（BEF）。这种罕见并发症多发于免疫功能受损的患者（如艾滋病患者、恶性肿瘤患者和接受免疫抑制治疗的患者），且诱发风险更高。在这些病例中，往往会发生诊断失误或延误。

结核性淋巴结炎通过酪状碎屑坏死及支气管和食管之间的瘘管开放的过程同样会导致支气管食管瘘的形成。

这篇文章旨在探讨一例有罕见临床表现的胸椎结核病例，并强调早期诊断对于降低死亡率及预防群体感染的重要性。

病例报告

病例报道了一例73岁，免疫功能正常的白人男性患者，有42年吸烟史，已戒烟。在过去6个月里，患者在饮食过程中伴有干咳，在食用液体食物时尤其明显。同时在一年内患者暴瘦了10公斤。患者无发热、呼吸困难、盗汗、胸痛和咯血症状。患者家族没有结核病史，本人也从未接触过结核患者。既往无任何与该病症有关的用药史或手术史，干咳症状出现之前无明显呼吸系统症状。

前6个月内怀疑为胃食管反流，全科医生给予标准剂量的质子泵抑制剂（PPI）进行治疗。由于治疗效果不佳，2013年6月，他接受了钡餐造影检查。钡剂造影胸部X线检查的结果表明患者存在一个从食管下道延伸到右侧主支气管的瘘道（图1），无肺部软组织浸润或胸膜受累的迹象。

Figure1.Fistulademonstratedbybariumcontrastswallowfrom

themiddlethirdandlowerthirdoftheesophagustotherightmainbronchus.

图1.钡餐造影法可见从食管中下1/3到右主支气管的瘘道。

随后患者行内镜食管瘘金属圈夹闭。第一阶段的诊断未进行胸部CT扫描。

2013年7月，患者因持续性咳嗽再次入院，在经胸部CT扫描后，在门诊部进行了支气管镜检查。

患者血常规检测正常；仅PCR（3.45毫克/升）检测结果偏高。血清QuantiFERON结果呈阳性（2.41IU/毫升），其他全身检查未见异常。

胸部CT对比扫描表明纵隔淋巴结肿大（图2A），进而造成气管右侧受压迫，管腔空间缩小，引发腔内增殖病变。右侧锁骨和腋窝区也发现了淋巴结肿大，但无并发性软组织浸润。

Figure2.(A)CTscanofchest(coronalview)pre-antitubercolosistreatmentshowingamediastinallesions.

(B)CTscanofchest(coronalview)duringantitubercolosistreatmentshowingregressionofmediastinallesions.

图2.(A)CT扫描（冠状面）显示为抗结核治疗前纵膈内淋巴结肿大。

(B)CT扫描（冠状面）显示抗结核治疗后纵膈淋巴结缩小。

支气管镜检查结果显示支气管粘膜有轻度炎症，同时隆突、主支气管内壁和中间支气管侧壁均有不同程度的增殖性病变(图3)。

Figure3.Bronchoscopicviewshowingavegetatinglesions.

图3.支气管镜下视图显示增殖性病变。

组织病理学检查提示中度慢性肉芽肿性炎症，该病症以存在淋巴细胞、组织细胞和朗格汉斯型巨细胞为特征。常规培养，真菌和AFB（抗酸杆菌）的支气管抽吸试验结果均为阴性。

一周后，由于病情恶化同时为了再评价瘘道的状况，患者进行了食管镜和支气管镜检查，对病情做出再评估。首次确定患者患有持久性食管支气管瘘，并安置了深度内镜夹。支气管镜对比检查显示增殖性病变区扩大，固以激光治疗法疏通管腔。支气管抽吸检查证实存在伴随巨细胞的显著性淋巴细胞和组织细胞炎症渗透和无中央坏死的肉芽肿性成分。科赫氏芽孢杆菌的显微镜检查和分子检测(PCR)结果均为阴性。

基于病理学特点，我们决定给予患者标准抗结核治疗：异烟肼300毫克/天，利福平600毫克/天、吡嗪酰胺1500毫克/天和乙胺丁醇1200毫克/天。病人被安排住在负压隔离监护病房。

40天后，首次支气管镜检培养证实结核分枝杆菌的生长（Lowenstei-Jensen培养基和分枝杆菌生长指示管（MGIT）960TB系统）。药敏试验未表现出对一线药物的任何耐药性。患者进行了持续2个月的抗结核治疗，而后接受了4个月的利福平和异烟肼治疗。

抗结核治疗过程中症状逐渐减轻。2个月后行CT和支气管镜检查显示淋巴结缩小（图2B）和支气管腔内病变消失。支气管镜也显示支气管食管瘘闭合（图4）。

Figure4.Bronchoscopicview:scartissueofthefistula.

图4.支气管镜下视图：肛瘘的疤痕组织。

在6个月和1年的随访中，身体检查和支气管镜检查均未发现复发迹象，1年后胸部CT扫描未显示纵隔淋巴结肿大，病人的症状得以解除。最终诊断为“支气管内膜结核和纵隔淋巴结肿大的食管支气管瘘”。

支气管食管或气管食管瘘极少发生于成人。该病症多为先天性疾病；若后天形成，则通常继发于原发性肿瘤（良性，恶性，或转移性）、传染性疾病（结核病、组织胞浆菌病、放线菌病、梅毒），创伤性（手术后遗症）和结缔组织疾病。成年支气管食管瘘（BEF）的发生通常是由于恶性肿瘤，主因为食管癌，少数为淋巴瘤、肺部或气管肿瘤。临床少见良性BEF。瘘道具有病程短、可透过胃中的空气和气道中的液体的特点。进食时出现的临床症状及体征与瘘口的大小密切相关，表现为胸痛、呼吸困难、犬吠样咳嗽，发绀，咯血和咳痰；在某些病例中出现的肺炎和其他呼吸道感染是通过一种“吸入”机制所致。

支气管内膜结核（EBTB）是指“伴随有微生物和组织病变的支气管树的结核感染”，是结核病的一种特殊形式。1698年，Mortem首次描述了支气管内膜结核，提出此疾病约占活动性肺结核的10~40%。年轻人更易出现支气管内膜结核病，其中以女性居多，老年人仅占所有患者的15%。该病引起的危险性后果（气管和支气管狭窄、复发性肺炎、肺不张、呼吸衰竭）可能是群体性感染的重要传染源。其发病机制目前尚不清楚；但研究人员已经提出了许多不同的机制，其中较合理的几个观点为：直接吸入结核分枝杆菌（Mt）至支气管，或实质性病变的感染扩大，或从相邻纵隔淋巴结到支气管的侵蚀和浸润。

结核性纵隔淋巴结炎极少发生于免疫功能正常且未有肺部病症的成年人，多发于HIV阳性患者以及肺结核发病率较高的发展中国家例如撒哈拉以南非洲地区。

在原发性肺结核中，结核杆菌感染纵隔或肺门淋巴结，引发淋巴结肿大，但实质浸润的患者如果免疫功能正常，那么在未行常规X线摄影的情况下该症状也可能消除。结核分枝杆菌可能在淋巴结内以不活跃状态（休眠）潜伏多年，在免疫状态下降时，例如在老年人身上会再次激活。

我们的临床案例指出了如下几个观点：

患者治疗耽误主要在胸部CT扫描及支气管镜检查。一旦有瘘管的可疑症状，就应及时进行支气管镜检查。就餐时咳嗽暗示存在支气管食管瘘，也能用于评估疾病病因。

通常认为有EBTB类分枝杆菌结核病患者的支气管抽吸和支气管肺泡灌洗液的微生物检查呈阳性，而这项检查有利于得到好的诊断率。由Ozkaya等人进行的研究强调了支气管内膜结核基于支气管肺泡灌洗液分析，支气管抽吸或痰液分析的细菌学诊断面临的困境，同时本临床病例证实，较高的诊断率是通过支气管活检的组织病理学检查获得的。

在第一次就诊时，患者进行的胸部X光检查未显示结核病的可疑症状。没有如实质合并，肺炎和/或食道和气道之间过度的胃肠道气化，活动性结核或非活性疤痕的特异性病变等直接迹象；也没有支气管内膜结核并发症（复发性肺炎或肺不张）或纵隔淋巴结肿大。事实上，超过20%的EBTB患者胸片检查正常。

一些非特异性症状，如进食时咳嗽，会误判为胃食管反流病。事实上，尽管患者支气管受阻，仍不会表现任何支气管内膜结核的症状。支气管内膜结核有时会呈现较长的潜伏期，在某些情况下，它也可能表现为其他疾病如肺癌或支气管哮喘。这种症状可以掩盖许多疾病，进而误导医生的准确诊断。此外，一些研究表明，老年人较年轻人更不会表现出经典的结核病体征和症状，如发热、消瘦、盗汗、咯血、咳痰。

这个具体的病例报告中食管支气管瘘的发病机制目前尚难以解释。可能是继发于支气管内膜结核，通过对支气管壁的侵蚀作用、累及纵隔淋巴结，而后在食管形成瘘。然而，这一作用过程不能缺少实质的参与。更可能的机制是气管和支气管周围淋巴结的感染复发，而后产生免疫抑制应答，继而淋巴结侵蚀食管，支气管和食瘘，在支气管粘膜产生结核分枝杆菌和二次支气管结核。类似的研究表明，这两种机制都是少见或罕见的胸椎结核并发症。据我们所知，文献中尚未报道并发支气管食管瘘，无实质性累及的支气管内膜结核和纵隔淋巴结核的老年患者。

尽管治疗受到拖延且处理失当，给予患者标准剂量治疗还是得到了最佳疗效，其治疗方式为服用异烟肼，利福平、吡嗪酰胺和乙胺丁醇2个月，而后进一步服用异烟肼和利福平4个月。随访1年的结果显示，肺结核已愈合且无复发迹象。

支气管食管瘘是肺结核等常见疾病的罕见临床表现。

众所周知，早期诊断和合理治疗可以改变这种疾病的自然病程，提高治愈率。因此，如果不及时治疗，患者可能会出现严重的并发症，并危及其生命。

对该疾病及其严重并发症知识的欠缺造成了本病例报告中的困境，耽误了诊断，也拖延了抗结核治疗的开展。

附英文原文

Background

Tuberculosisisoneofthemostcommonsystemicinfectiousdisease,andamajorpublichealthproblemallovertheworld.Ithasseveralformsofpresentationandclinicalmanifestationsandremainsanimportantcauseofpreventabledeathintheadultpopulation.Anuncommonformofpulmonarytuberculosisisendobronchialtuberculosis,whichaccountsforabout10–40%ofthecasesofactivetuberculosis.Itmaybecomplicatedbytracheobronchialstenosis,andfistulaformationisanunusualcomplication,mainlyintheregionofthepleuraandlessfrequentlyintheoesophagus(BEF).Increasedriskofacquiringtheserarecomplicationsoccurslargelyinimmunocompromisedpeople(e.g.,HIV,malignancies,andpatientsundergoingimmunesuppressi

vetherapy).Inthesecases,thediagnosisisoftenmissedordelayed.

Tubercularlymphadenitiscanalsoleadtofistulaformationthroughaprocessofcaseumnecrosisandopeningofafistulabetweenthebronchusandoesophagus.

Thepurposeofthisarticleistodiscussacasereportofthoracictuberculosisthatshowedanunusualpresentation,emphasizingtheimportanceofanearlydiagnosisinordertoreduceboththeriskofmortalityandpreventthespreadofinfectiontothecommunity.

CaseReport

Animmunocompetent73-year-oldCaucasianmanwhoisanex-smokerof42pack-years,presentedinthepast6monthswithahistoryofaccessionalnonproductivecoughthatappearedduringmeals,especiallyafteringestionofliquids,andasignificantweightlossof10kginayear.Hehadnofever,dyspnea,nightsweats,chestpain,orhemoptysis.TherewasnofamilyhistoryoftuberculosisorpreviouscontactwithaTBpatient.Hehadnosignificantpastmedicalorsurgicalhistoryandpriortotheonsetofcoughingduringmeals,remarkablerespiratorysymptomswerenotreported.

Duringthefirst6months,onthebasisofaclinicalsuspicionofgastroesophagealreflux,hewasinitially,treatedbyageneralpractitioner,withastandarddoseofprotonpumpinhibitors(PPI)therapy.Duetothelackofatreatmentresponse,inJune2013,heunderwentabariumcontrastswallowtest.ThechestX-rayexaminationperformedwithabariumcontrastshowedthepresenceofafistulaextendingfromthelowertractoftheesophagustotherightmainbronchus(Figure1),withoutevidenceofactiveparenchymallunginfiltratesorpleuralinvolvement.

Hewasthenendoscopicallytreatedbyapplicationofmetalclipsintheesophagusforfistulaclosure.NochestCTscanwasperformedinthisfirstphaseofthediagnosticprocess.

Forpersistenceofcough,onJuly2013thepatientwassenttoourClinicwhere,afterchestCTscan,heunderwentaflexiblefiberopticbronchoscopyinanoutpatientsetting.

Routinebloodinvestigationresultswerenormal;onlyanincreaseofPCR(3.45mg/dl)wasfound.SerumQuantiFERONtestingwaspositive(2.41IU/mL).Theremainingsystemicexaminationrevealednoabnormality.

ThechestCTscan“withcontrast”showedasignificantenlargementofmediastinallymphnodes(Figure2A)thatcausedtrachealcompressionwithdeflectiontotherightsideandreductionofitslumenforpresenceofanendoluminalvegetatinglesion.Severalotherenlargedlymphnodeswereseenintherightsupraclavicularandaxillaryarea,buttherewasnoassociatedparenchymalinfiltrates.

Bronchoscopyrevealedamildinflammationofthebronchialmucosaandthepresenceofdifferentvegetatinglesionsinthecarina,onthemedialwallofthemainbronchi,andonthelateralwalloftheintermediusbronchus(Figure3).

Histopathologyrevealedmoderatechronicgranulomatousinflammationcharacterizedbythepresenceoflymphocytes,histiocytes,andLanghans-typegiantcells.Bronchialaspiratetestresultsforroutineculture,fungal,andAFB(acid-fastbacilli)werenegative.

Thepatientwasre-evaluatedafteraweekbyesophagoscopyandbronchoscopy,mainlyforworseningsymptomsandforthereevaluationofthefistula.Thefirstreconfirmedthepersistenceofbronchoesophagealfistula,sofurtherendo-clipswereplaced.Thebronchoscopycontrolshowedthatthevegetatinglesionshadincreasedinsize,soalasertreatmentwasperformedwithlumendesobstruction.Bronchialaspiratetestingconfirmedthepresenceofamarkedlymphocyticandhistiocyticinflammatoryinfiltratewithgiantcellsandgranulomatouscomponentwithoutcentralnecrosis.Resultsofamicroscopicexaminationandmoleculartest(PCR)forKoch’sbacilluswerenegative.

Basedonthepathologicalpattern,wedecidedtostartastandardantituberculartreatmentwithisoniazid300mgdaily,rifampin600mgdaily,pyrazinamide1500daily,andethambutol1200mgdaily.Thepatientwasplacedinisolationwithnegativepressureinsidetheroom.

After40days,thecultureofthefirstbronchoscopicbiopsydemonstratedthegrowthofMycobacteriumtuberculosis(Lowenstei-JensenmediumandBactecMycobacteriaGrowthIndicatorTube(MGIT)960TBSystem).Thedrugsusceptibilitytestdidnotshowanyresistancetothefirst-linedrugs.Ourpatientcontinuedanti-tuberculoustreatmentfor2months,followedbyrifampicinandisoniazidtreatmentforthefollowing4months.

Duringantituberculartreatment,symptomsprogressivelyimproved.CTandbronchoscopyperformed2monthslatershowedregressionoflymphnodeenlargement(Figure2B)andthedisappearanceofintraluminallesionsinthetracheobronchialtree.Bronchoscopyalsoshowedthebronchoesophagealfistulaclosure(Figure4).

At6-monthand1-yearfollow-up,physicalandbronchoscopyexaminationsdidnotshowevidenceofrecurrence,achestCTscanat1yeardemonstratednoevidenceofmediastinallymphadenopathy,andsymptomsofpatientwereresolved.Thefinaldiagnosiswas“bronchoesophagealfistulainendobronchialtuberculosisandmediastinallymphadenopathy”.

Discussion

Bronchoesophagealortracheoesophagealfistulaisextremelyrareinadults.Itismorefrequentlyacongenitalcondition;otherwise,theacquiredforms,areusuallysecondarytoprimaryneoplasm(benign,malignant,ormetastatic),infectiousdiseases(tuberculosis,histoplasmosis,actinomycosis,andsyphilis),traumaticevents(sequelsofsurgicalprocedures),andconnectivetissuediseases.Broncho-esophagealfistula(BEF)inadultsiscommonlyduetomalignancy,mainlyoesophaguscarcinomaand,lessfrequently,lymphoma,carcinomaofthelungsortrachea.BenignBEFisararecondition.Thefistulahasashortcourseandusuallythecommunicationispervious,permittingthepassageofairinthestomachandliquidsintheairways.Theclinicalsymptomsandsignsthatoccurasaresultofattemptedoralfeedingarecloselyrelatedtothesizeofthefistulaandarecharacterizedbychestpain,dyspnea,barkingcough,cyanosis,hemoptysis,andsputumproduction;insomecasesepisodesofpneumoniaandotherrespiratoryinfectionscanoccurthroughamechanismof“aspiration”.

Endobronchialtuberculosis(EBTB),definedas“tuberculousinfectionofthetracheobronchialtreewithmicrobialandhistopathologicalevidence”,isaparticularformofTB.DescribedforthefirsttimebyMortemin1698,representsabout10–40%ofcasesofactiveTB.It’smorecommoninyoungadults,withafemalepredominance,andonly15%inelderlypatients.Oftendangerousforitsconsequences(tracheaandbronchostenosis,recurrentpneumonia,atelectasisandrespiratoryfailure)ispotentiallyanimportantsourceofinfectionspreadinthecommunity.Itspathogenesisremainsunclear;however,differentmechanismshavebeensuggestedandthemoreplausibleare:directimplantationofMycobacteriumtuberculosis(Mt)inthebronchusaftertheirinhalation,ordirectextensionofinfectionfromparenchymallesionsorerosionandinfiltrationfromadjacentmediastinallymphnodesintothebronchus.

Themediastinaltuberculouslymphadenitisisrareintheabsenceofsimultaneouslunginvolvementinimmunocompetentadults，whileitmaybeobservedmorefrequentlyinHIV-positivepatientsandindevelopingcountrieswithhighratesofTBjustasitisinsub-SaharanAfrica.

DuringprimaryTB,tuberclebacillusreachesthemediastinalorhilarlymphnodescausinglymphnodeenlargementbuttheparenchymalinfiltrateinanimmunocompetentsubjectmayresolvewithoutsequelsatconventionalradiography.Mycobacteriumtuberculosismaystayinactive(dormant)formanyyearsinsidethelymphnodesandbecomesactiveagainduringdecreasedimmunestatus,asforexampleintheelderly.

Ourclinicalcasewascharacterizedbyseveralcriticisms:

•TheconsiderabledelaywithwhichthepatienthasbeensubjecttoachestCTscanandbronchoscopy.Bronchoscopyshouldbedonepromptlyinthecaseofafistulasuspicion.Thecoughduringmealswouldsuggestthepresenceofabronchoesophagealfistulaandthissuspicioninvolvestheassessmentofthecause.

•Usually,itisthoughtthatmicrobiologicalexaminationofbronchialaspirateandBALarepositiveforMycobacteriumtuberculosisinpatientswithEBTB,andthatexaminationprovidesagooddiagnosticyield.AstudyconductedbyOzkayaetal.highlightsthedifficultyofthebacteriologicaldiagnosisofEBTBbasedonBALanalysis,bronchialaspirate,orsputumanalysis,andshowedthatahighdiagnosticyieldwasobtainedthroughthehistopathologicexaminationsofbronchialbiopsies,confirmedinourclinicalcase.

•Chestx-ray,performedonourpatientinthefirstinstance,didnotposeasuspicionofTB.Therewerenodirectsignssuchasparenchymalconsolidation,orpneumoniaand/orexcessivegastricandintestinalgasificationasexpressionofcommunicationbetweentheoesophagusandairway,specificlesionsofactiveTBorinactiveasscarring;complicationsofendobronchialTB(recurrentpneumoniaoratelectasis)ormediastinumlymphnodeenlargement.Infact,upto20%ofpatientswithEBTBhaveanormalchestradiograph.

•Thepresenceofnon-specificsymptomssuchascough,onlypresentduringmeals,simulatedagastro-esophagealrefluxdisease.Infact,despitethebronchialobstruction,thepatientdidn’thaveanysymptomsofendobronchialtuberculosis.EBTB,maysometimespresentwithaveryinsidiousonsetand,insomecases,itmaysimulateotherpathologicalconditionssuchasbronchogeniccarcinomaorbronchialasthma.Thissymptomcanmimicmanydiseases,misleadingthedoctorforaproperdiagnosis.Moreover,severalstudiesshowedthat,intheelderly,theclassicsignsandsymptomsofTB,suchasfever,weightloss,nightsweats,andhemoptysisandsputumproductionaresometimesabsentcomparedtoyoungadult.

•Pathogenesisofbronchoesophagealfistulainthisspecificcasereportremainsdifficulttointerpret.Itmaybesecondarytoendobronchialtuberculosis,throughamechanismoferosionofthebronchialwall,involvementofmediastinallymphnodesandthenfistulaformationintotheesophagus.However,theabsenceofparenchymalinvolvement,makesunlikelythismechanism.Muchmoreprobable,wasareactivationofaprimaryinfectioninperitrachealandperibronchiallymphnodes,asaconsequenceofanimmunodepressionstate,subsequentlymphnodeerosionintooesophagusandbronchusandfistulizationwithaconsequentimplantationofMtinthebronchialmucosaandsecondaryendobronchialTBonset.Similarstudiesshowthatbothmechanismsareuncommonorrarecomplicationsofthoracictuberculosis.Asfarasweknow,nocaseshavebeenreportedintheliteraturewithsimultaneouscombinationofbronchoesophagealfistula,endobronchialtuberculosiswithoutparenchymalinvolvement,mediastinaltuberculouslymphadenitisintheelderly.

Despitethedelayandthemismanagement,thepatienthasrespondedoptimallytoastandardtreatmentwithisoniazid,rifampicin,pyrazinamideandethambutolfor2months,followedbyisoniazidandrifampicinforafurther4months.The1-yearfollow-upshowedhealingoftuberculosis,withoutevidenceofrecurrence.

Conclusions

Bronchoesophagealfistulaisararemanifestationofacommondiseasesuchastuberculosis.

Weknowthatearlydiagnosisandpropertreatmentmaymodifythenaturalcourseofthisdiseaseandincreasetherateofhealing.Therefore,ifnottreated,severecomplicationsmayoccur,endangeringthepatient’slife.

Thedifficultyofthiscasereport,associatedwiththelowlevelofknowledgeoftheillnessanditsseriouscomplications,causedadiagnosticdelay,deferringthestartofaneffectiveantituberculartreatment.

Wecannotforgetthatanormalchestradiographandthepresenceofnonspecificsymptomsdonotexcludethediagnosisoftuberculosis,buteventhebestearlydetectionisofnouseifsubsequenttreatmentisinadequate,ordownrightwrong.

由MediCool医库软件王露黔赵美凤编译

原文来自：

UnusualClinicalPresentationofThoracicTuberculosis:TheNeedforaBetterKnowledgeofIllness

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