Clinical Manifestations and Complications of Pulmonary Tuberculosis

4/3/2016
Clinicalmanifestationsandcomplicationsofpulmonarytuberculosis
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Author
AntonPozniak,MD,FRCP
SectionEditor
CFordhamvonReyn,MD
DeputyEditor
ElinorLBaron,MD,DTMH
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Mar2016.|Thistopiclastupdated:Jan12,2016.
INTRODUCTIONThelungsarethemajorsiteforMycobacteriumtuberculosisprimaryinfectionanddisease.
Clinicalmanifestationsoftuberculosis(TB)includeprimaryTB,reactivationTB,laryngealTB,endobronchialTB,
lowerlungfieldTBinfection,andtuberculoma.PulmonarycomplicationsofTBcanincludehemoptysis,
pneumothorax,bronchiectasis,extensivepulmonarydestruction,malignancy,andchronicpulmonaryaspergillosis.
TheclinicalmanifestationsandevaluationofpulmonaryTBwillbereviewedhere.Theclinicalmanifestationsof
pulmonaryTBinchildrenandHIVinfectedpatientsarediscussedseparately,asaretheepidemiology,
pathogenesis,laboratorydiagnosis,andtreatmentofpulmonaryTB.ExtrapulmonaryandmiliaryTBarealso
discussedseparately.(Seerelatedtopics.)
CLINICALMANIFESTATIONS
PrimarytuberculosisPrimarytuberculosis(TB)isatermthatdescribesnewtuberculosisinfectionoractive
diseaseinapreviouslynavehost.PrimaryTBwasconsideredtobemainlyadiseaseofchildhooduntilthe
introductionofeffectivechemotherapywithisoniazidinthe1950s.Manystudiessincethattimehaveshownan
increasedfrequencyintheacquisitionofTBinadolescentsandadults[1,2].
SymptomsandsignsThenaturalhistoryofprimaryTBwaswelldescribedinaprospectivestudyof517
newtuberculinconverterslivingontheFaroeIslandsoffthecoastofNorwayfrom1932to1946[3].Thestudy
included331adultsand186childrenallwerefollowedformorethanfiveyears.Theclinicalmanifestationsof
primaryTBvariedsubstantiallyinthispopulation,andsymptomsandsignsreferabletothelungswerepresentin
approximatelyonethirdofpatients.Feverwasthemostcommonsymptom,occurringin70percentof232patients
inwhomfeverwasnotaconditionforenrollmentinthestudy.Thefeveronsetwasgenerallygradualandlow
gradebutcouldbeashighas39C(102.2F)andlastedforanaverageof14to21days.Feverresolvedin98
percentofpatientsby10weeks.
Feverwasnotusuallyaccompaniedbyothersymptoms,althoughapproximately25percentofpatientsdeveloped
pleuriticorretrosternalpain.Onehalfofpatientswithpleuriticchestpainhadevidenceofapleuraleffusion.
Retrosternalanddullinterscapularpainwereascribedtoenlargedbronchiallymphnodesandsometimesworsened
withswallowing.Rarersymptomsincludedfatigue,cough,arthralgias,andpharyngitis.(See"Tuberculouspleural
effusionsinHIVuninfectedpatients"and"TuberculouspleuraleffusionsinHIVinfectedpatients".)
RadiographicabnormalitiesInprimarypulmonaryTB,thechestradiographisoftennormal.Inoneseries
including517patentswithrecentskintestconversion,chestradiographfindingswerenotableforthefollowing[3]:
Hilaradenopathywasthemostcommonfinding,occurringin65percentofcases.Hilarchangeswerevisible
earlyasoneweekafterskintestconversion,andwithintwomonthsinallcases.
Pleuraleffusionsdevelopedinapproximatelyonethirdofpatients,typicallywithinthefirstthreetofour
monthsafterinfectionbutoccasionallyaslateasoneyear.
Pulmonaryinfiltrateswereobservedin27percentofpatientsingeneral,theyresolvedslowly,overmonths
toyears.
Perihilarandrightsidedinfiltrateswerethemostcommon,andipsilateralhilarenlargementwasthe
rule.
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Contralateralhilarchangessometimeswerepresentonly2percentofpatientshadbilateralinfiltrates.
Lowerandupperlobeinfiltrateswereobservedin33and13percentofpatients,respectively43
percentofadultswithinfiltratesalsohadeffusions.
Theinfiltratesprogressedwithinthefirstyearafterskintestconversionin20patients(15percentof
cases),reflectingprogressiveprimaryTB.Themajorityofthesepatientshadprogressionofdiseaseat
theoriginalsitefourdevelopedcavitation.
OtherstudiesthatprovideinsightintotheclinicalmanifestationsofTBhavefocusedretrospectivelyuponpatients
withcultureprovenTB[46].InoneseriesfromCanada,188patientswereassessed,allofwhomwereculture
positiveandhadabnormalchestradiographs[5].Thirtypatients(18percent)wereclassifiedclinicallyashaving
primaryTB.Themostcommonfindingwashilarlymphadenopathy,presentin67percent.Rightmiddlelobe
collapsemaycomplicatetheadenopathybutusuallyresolveswiththerapy.
Severalfactorsprobablyfavorinvolvementoftherightmiddlelobe:itismoredenselysurroundedbylymphnodes,
ithasarelativelylongerlengthandsmallerinternalcaliber,andithasasharperbranchingangle.
Inthisretrospectiveseries,pleuraleffusionswerepresentin33percentandwerethesoleabnormalityin23
percentofcases[5].Pulmonaryinfiltrateswerepresentin63percentofpatients,and85percentofinfiltrateswere
inthemidtolowerlungfields.Twopatientshadcavitationandtwoothershadevidenceofendobronchialspread.
NaturalhistoryAfterprimaryinfection,90percentofindividualswithintactimmunitycontrolfurther
replicationofthebacilli,whichmaythenentera"latent"phase.Theremaining10percentofindividualsdevelopa
TBpneumoniawithexpansionofinfiltratesatthesiteoftheinitialseedingornearthehilumandmayhavehilar
lymphadenopathyorpresentwithdiseaseatmoredistantsites,commonlywithcervicallymphadenopathy,
meningitis,pericarditis,ormiliarydissemination.Progressiontolocaldiseaseordisseminationoccursmore
frequentlyinthosewithpoorimmuneresponses,suchasinthosewithHIVinfection,chronickidneyfailure,poorly
controlleddiabetesmellitus,andinthosereceivingimmunosuppressivemedications(includingtransplant
recipients)andolderadults.(See"Naturalhistory,microbiology,andpathogenesisoftuberculosis",sectionon
'Naturalhistoryofinfection'.)
ReactivationtuberculosisMultipletermshavebeenusedtodescribereactivationTB:chronicTB,postprimary
disease,recrudescentTB,endogenousreinfection,andadulttypeprogressiveTB.ReactivationTBrepresents90
percentofadultcasesamongHIVuninfectedindividualsandresultsfromreactivationofapreviousfocusof
mycobacterialcontainmentthatwasseededatthetimeoftheprimaryinfection.Theapicalposteriorsegmentsof
theupperlobesorthesuperiorsegmentofthelowerlobeofthelungarefrequentlyinvolved(image1).Thereason
forthisisuncertainrelativelypoorlymphaticflowintheapicesmaybeassociatedwithpoororganismclearance.
IthasalsobeensuggestedthatM.tuberculosisorganismspreferthehigheroxygentensionsintheapicalareaof
thelungs,althoughTBmaynotbeanobligateaerobe[7,8].Theoriginalsiteofinfectionmayhavebeenpreviously
visibleasasmallscarcalledaSimonfocus.
SymptomsReactivationTBmayremainundiagnosedandpotentiallyinfectiousfortwotothreeyearsor
longer,withdevelopmentofsymptomsonlylateinthecourseofthedisease.ThesymptomsofreactivationTB
havebeendescribedretrospectively,mainlyincaseseriesofhospitalizedpatientsinsingleinstitutions[911].In
theseseries,symptomstypicallybeganinsidiouslyandwerepresentforweeksormonthsbeforethediagnosis
wasmade.Onehalftotwothirdsofpatientsdevelopedcough,weightloss,andfatigue.Feverandnightsweatsor
nightsweatsalonewerepresentinapproximatelyonehalf.Chestpainanddyspneaeachwerereportedin
approximatelyonethirdofpatientsandhemoptysisinapproximatelyonequarter.Manypatientshadvagueor
nonspecificsymptomsalmostonethirdofpatientshadpulmonaryTBdiagnosedafteranadmissionforunrelated
complaints[9].
Feverisusuallylowgradeatonsetbutbecomesmarkedwithprogressionofdisease.Itisclassicallydiurnal,
withanafebrileperiodearlyinthemorningandagraduallyrisingtemperaturethroughouttheday,reachinga
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peakinthelateafternoonorevening.Feversubsidesduringsleep,butnightsweatsmayoccur.Feverand
nightsweatsaremorecommonamongpatientswithadvancedpulmonaryTB[12].
Coughmaybeabsentormildinitiallyandmaybenonproductiveorproductiveofonlyscantsputum.Initially,
itmaybepresentonlyinthemorning,whenaccumulatedsecretionsduringsleepareexpectorated.Asthe
diseaseprogresses,coughbecomesmorecontinuousthroughoutthedayandproductiveofyelloworyellow
greenandoccasionallybloodstreakedsputum,whichisrarelyfoulsmelling.Symptomaticindividualsare
morelikelytohavesmearpositivesputum[13].Frankhemoptysis,duetocaseoussloughingor
endobronchialerosion,typicallyoccurslaterinthediseaseandisrarelymassive.Nocturnalcoughingis
associatedwithadvanceddisease,oftenwithcavitation.
Dyspneacanoccurinthesettingofextensiveparenchymalinvolvement,pleuraleffusions,ora
pneumothorax.Pleuriticchestpainisnotcommonbut,whenpresent,signifiesinflammationabuttingor
invadingthepleura,withorwithoutaneffusion.Rarely,thiscanprogresstofrankempyema.
Intheabsenceoftreatment,patientsmaypresentwithpainfululcersofthemouth,tongue,larynx,or
gastrointestinaltractduetochronicexpectorationandswallowingofhighlyinfectioussecretionsthese
findingsarerareinthesettingofantituberculoustherapy.
Anorexia,wasting(consumption),andmalaisearecommonfeaturesofadvanceddiseaseandmaybethe
onlypresentingfeaturesinsomepatients.
AmbulatorypatientswithactiveTBtypicallyhavemilderandlessspecificsymptomsthanhospitalizedpatients.In
astudyincluding313TBcasesidentifiedamongambulatorypatients,cough>2weekswasobservedamong52
percentofpatientswithpulmonarydiseasefever>2weekswasobservedamong29percentofpatients[14].In
addition,clinicalsymptomswereobservedlessfrequentlyamongpatientsofAsianethnicitythanamongother
patients.
OthercomorbiditiesmayaffectthepresentationofreactivationTBtheseincludediabetes,administrationoftumor
necrosisfactor(TNF)alphainhibitorsandadvancedHIVinfection.Suchpatientspresentwithmoresymptomsand
ahigherproportionofsmearpositivity,cavitation,treatmentfailure,andnonTBdeaths[15].(See"Epidemiology,
clinicalmanifestations,anddiagnosisoftuberculosisinHIVinfectedpatients"and"Tumornecrosisfactoralpha
inhibitorsandmycobacterialinfections".)
PresentationinolderadultsInnonendemiccountries,theincidenceofpulmonaryTBistwotothree
timeshigheramongolderadults,especiallythoseinoldagehomes,andtheriskofdeathishighercomparedwith
youngerpatients[16,17].
ComparativestudieshavesuggestedsomedifferencesinthemanifestationsofpulmonaryTBbetweenolderand
youngerpatients.Ametaanalysisincluding12studiesnotednosignificantdifferencesbetweenpatients>60
yearsandpatients<60yearswithrespecttotimetodiagnosis,prevalenceofcough,sputumproduction,weight
loss,orfatigue/malaise[18].Findingsobservedlesscommonlyamongolderadultsincludedfever,sweats,
hemoptysis,cavitarydisease,andapositivetuberculinskintest,buttheywerelikelytopresentwiththe
nonspecificsymptomsofdyspneaandfatigue.Findingsobservedmorefrequentlyamongolderadultsincluded
hypoalbuminemia,leukopenia,andunderlyingdisorderssuchascardiovasculardisease,chronicobstructive
pulmonarydisease(COPD),diabetes,malignancy,andgastrectomy.Cavitarydiseaseislesscommon,and
multilobarandlowerlobeinvolvementmorecommon.BecauseofcomorbiditiessuchasCOPDandthe
nonspecificityofsymptoms,thediagnosisinolderadultscanbedelayedormissed[19,20].
PhysicalfindingsPhysicalfindingsofpulmonaryTBarenotspecificandusuallyareabsentinmildor
moderatedisease.Dullnesswithdecreasedfremitusmayindicatepleuralthickeningoreffusion.Cracklesmaybe
presentthroughoutinspirationormaybeheardonlyafterashortcough(posttussivecrackles).Whenlargeareas
ofthelungareinvolved,signsofconsolidationassociatedwithopenbronchi,suchaswhisperedpectoriloquyor
tubularbreathsounds,maybeheard.Distanthollowbreathsoundsovercavitiesarecalledamphoric,afterthe
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soundmadebyblowingacrossthemouthofjarsusedinantiquity(amphorae).Extrapulmonarysignsinclude
clubbingandfindingslocalizedtoothersitesofinvolvement.(See"Clinicalmanifestations,diagnosis,and
treatmentofextrapulmonaryandmiliarytuberculosis".)
LaboratoryfindingsTheapproachtodiagnosisoftuberculosisisdiscussedseparately.(See"Diagnosisof
pulmonarytuberculosisinHIVuninfectedpatients"and"Epidemiology,clinicalmanifestations,anddiagnosisof
tuberculosisinHIVinfectedpatients".)
RoutinehematologyandbiochemistrylaboratorystudiesarefrequentlynormalinthesettingofpulmonaryTB.The
Creactiveprotein(CRP)canbeelevatedinupto85percentofpatients[21].Lateinthedisease,hematologic
changesmayincludenormocyticanemia,leukocytosis,or,morerarely,monocytosis.Hyponatremiamaybe
associatedwiththesyndromeofinappropriateantidiuretichormonesecretion(SIADH)[22]orrarelywithadrenal
insufficiency.Hypoalbuminemiaandhypergammaglobulinemiaalsocanoccuraslatefindings.
RadiographicfindingsMostpatientswithreactivationTBhaveabnormalitiesonchestradiography,evenin
theabsenceofrespiratorysymptoms[9,23].ReactivationTBtypicallyinvolvestheapicalposteriorsegmentsof
theupperlobes(80to90percentofpatients),followedinfrequencybythesuperiorsegmentofthelowerlobes
andtheanteriorsegmentoftheupperlobes(image1andimage2)[9,2426].InmultiplelargeseriesofTBamong
adults,70to87percenthadupperlobeinfiltratestypicalofreactivation19to40percentalsohadcavities,with
visibleairfluidlevelsinasmanyas20percentofcases[9,2426].
Adultswithoutupperlobeinfiltrateshave"atypical"radiographicpatterns(13to30percentofpulmonaryTBcases)
[4,27,28].Thesefindingsincludehilaradenopathy(sometimesassociatedwithrightmiddlelobecollapse),
infiltratesorcavitiesinthemiddleorlowerlungzones,pleuraleffusions,andsolitarynodules.These"atypical"
findingsaremorecommoninthesettingofprimaryTBandprobablyrepresentincreasingincidenceofprimaryTB
ratherthan"atypical"formsofreactivationTB.(See'Primarytuberculosis'above.)
Upto5percentofpatientswithactiveTBpresentwithupperlobefibrocalcificchangesthoughttobeindicativeof
healedprimaryTB.However,suchpatientsshouldbeevaluatedforactiveTBinthesettingofpulmonary
symptomsorabsenceofserialfilmsdocumentingstabilityofthelesion.
AnormalchestradiographisalsopossibleeveninactivepulmonaryTB.Asanexample,inoneCanadianstudyof
518patientswithcultureprovenpulmonaryTB,25patients(5percent)hadnormalchestradiographs23ofthese
patientshadpulmonarysymptomsatthetimeofthenormalradiograph[29].Inthisseriesconductedovera10
yearperiod,normalchestradiographsrepresentedlessthan1percentoftheradiographsin1988to1989but
increasedto10percentfrom1996to1997.
Computedtomographic(CT)scanningismoresensitivethanplainchestradiographyfordiagnosis,particularlyfor
smallerlesionslocatedintheapexofthelung[30].CTscanningmaydemonstrateacavityorapicoposterior
infiltrates,cavities,pleuraleffusions,fibroticlesionscausingdistortionoflungparenchyma,elevationoffissures
andhila,pleuraladhesions,andformationoftractionbronchiectasis.HighresolutionCTistheimagingtechnique
ofchoicetodetectearlybronchogenicspread.Themostcommonfindingsconsistofcentrilobular2to4mm
nodulesorbranchinglinearlesionsrepresentingintrabronchiolarandperibronchiolarcaseationnecrosis[31].
Radiographicfindingsinthesettingofpulmonarytuberculosisarediscussedfurtherseparately.(See"Diagnosisof
pulmonarytuberculosisinHIVuninfectedpatients",sectionon'Radiographicimaging'.)
EndobronchialtuberculosisEndobronchialTBisdefinedastuberculousinfectionofthetracheobronchialtree.
Itmaydevelopviadirectextensiontothebronchifromanadjacentparenchymalfocus(usuallyacavity)orvia
spreadoforganismstothebronchiviainfectedsputum.Lesionsaremorelikelytobeobservedinthemainand
upperbronchiin5percentofpatients,thelowertracheaisinvolved[32].
Priortotheavailabilityofantituberculoustherapy,endobronchialTBwasrelativelycommoninthesettingof
primaryinfectionandreactivationTB[3336].Ina1943studyinaTBsanatoriuminWestVirginia,lesionsinthe
tracheobronchialtreewereobservedin15percentofcasesviarigidbronchoscopyandin40percentofcasesat
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autopsy[33].EndobronchialdiseasewasobservedmorefrequentlyamongpatientswithextensivepulmonaryTB,
particularlycavitarylesions.Upperlungparenchymalorcavitarydiseasewithbronchogenicspreadtothelower
lungfieldswascommonlyobserved,presumablyfrompooledinfectedsecretions.
Sincetheavailabilityofantituberculoustherapy,endobronchialTBhasbeendescribedin10to40percentof
patientswithactivepulmonaryTB[37,38].Somedegreeofbronchialstenosisisobservedin90percentofcases
ofendobronchialTBearlydiagnosisandprompttreatmentpriortodevelopmentoffibrosisareimportanttoreduce
thelikelihoodofthiscomplication.Endobronchialdiseaseinpatientswithprimaryinfectionhasalsobeen
associatedwithimpingementofenlargedlymphnodesonthebronchi[3942].Associatedinflammationcanleadto
endobronchialulcerationorperforation.OthercomplicationsofendobronchialTBincludeobstruction,atelectasis
(withorwithoutsecondaryinfection),bronchiectasis,andtrachealstenosis[43].
SymptomsSymptomsmaybeacuteinonsetandbeconfusedwithbacterialpneumonia,asthma[44],or
foreignbodyaspiration[45].Theclinicalmanifestationscanalsobesubacuteorchronic,resemblingbronchogenic
carcinoma[45].
Abarkingcoughhasbeendescribedinapproximatelytwothirdsofpatientswithendobronchialdisease,often
accompaniedbysputumproduction[4143,46,47].Rarely,patientsdevelopsocalledbronchorrhea,whichis
productionofmorethan500mL/dayofsputum[48].Insomecases,caseousmaterialfromendobronchiallesions
orcalcificmaterialfromextensionofcalcificnodesintothebronchiisexpectorated,whichisknownaslithoptysis.
Wheezingandhemoptysismayalsobeobserved.Lymphnoderupturecanbeassociatedwithchestpain.The
presenceofdyspneamaysignalobstructionoratelectasis.
PhysicalfindingsDiminishedbreathsounds,rhonchi,orwheezingmaybeheard.Thewheezeislow
pitched,monophonic,constant,andisauscultatedconsistentlyoverthesameareaonthechestwall.
RadiographicabnormalitiesBecauseendobronchiallesionscanexistwithoutextensiveparenchymal
abnormalities,anormalchestradiographisobservedin10to20percentofcases.Insuchcases,CTscanning
maydemonstrateendobronchiallesionsorstenosis.ThemostcommonradiographicfindingofendobronchialTBin
adultsisanupperlobeinfiltrateandcavitywithipsilateralspreadtothelowerlobeandpossiblytothesuperior
segmentofthecontralaterallowerlobe(image3).Patchy,smalllowerlobeinfiltratesmayprogresstoconfluence
orevencavitation.ExtensiveendobronchialTBcanalsobeassociatedwithbronchiectasisonCTscan.
WhenendobronchialTBoccursinpatientswithprimarydisease,segmentalatelectasismaybetheonlyfinding
atelectasisismorefrequentintherightmiddlelobeandtheanteriorsegmentoftherightupperlobe.
EvaluationandapproachThediagnosisofendobronchialTBmaybeestablishedbybronchoscopy,which
maydemonstrateerythematous,vascular,and/orulceratedtissues.Granulationtissuemaybebulkyorpolypoid.
Hilarnoderupturemaybevisibleasamassprotrudingintothebronchiallumenwithperforationofthenodeinto
thebronchus,caseousorcalcificmaterialmaybeseenextrudingintothelumen.Bronchialstenosisalsomaybe
visible[43,49].Thelikelihoodofdevelopingstenosisisincreasedinthesettingofadistortedairwayoramass
occludingtheairway.
Brushingsofthelesionsorlavageofthedistalairwayscanincreasethefrequencyofpositivesmearstheyieldfor
culturesofthismaterialis>90percent[32,37].(See"DiagnosisofpulmonarytuberculosisinHIVuninfected
patients",sectionon'Laboratorystudies'.)
TreatmentregimensforendobronchialdiseasearethesameasforotherformsofpulmonaryTB.(See"Treatment
ofpulmonarytuberculosisinHIVuninfectedadults"and"TreatmentofpulmonarytuberculosisinHIVinfected
adults".)
Othermanifestations
LaryngealtuberculosisPriortotheavailabilityofantituberculoustherapy,laryngealTBwasconsidereda
terminalcondition,asitusuallyoccurredduringprogressionofpulmonarydisease,developingsoonbeforedeath.
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Sincetheavailabilityofantituberculoustherapy,laryngealTBhasbecomerare(<1percentofTBcases).Itcan
alsooccurintheabsenceofpulmonarydiseaseasanextrapulmonarymanifestation.Symptomsinclude
dysphonia,cough,dysphagia,odynophagia,stridor,andhemoptysis[50].Thetruevocalcords,epiglottis,and
falsevocalcordsarethemostcommonsitesinvolved,andareasofhyperemia,nodules,ulcerations,orexophytic
massescanbeseenonlaryngoscopy.
ThesimilarityoflaryngealTBtochroniclaryngitiswarrantsconsiderationofTBinthedifferentialdiagnosisof
inflammatorylaryngealdiseaseinpatientswithepidemiologicriskfactors[51].(See"Hoarsenessinadults".)
LowerlungfieldtuberculosisLowerlungfieldTBreferstodiseaseinvolvementbelowthehila(including
theperihilarregions)onchestimaging[52].Theincidenceinadultsis2to9percent[9,52].Consolidationinlower
lungfieldTBtendstobemoreextensiveandhomogeneousthanupperlobeTB[5355].Cavitationmayoccur,and
largecavitieshavebeendescribed.SymptomsinlowerlobeTBaregenerallyeithersubacuteinonset(meanof12
weeks)orchronic(upto6months).LowerlobeTBisfrequentlymisdiagnosedinitiallyasviralorbacterial
pneumonia,bronchiectasis,orcarcinoma.
LowerlobeinvolvementcanbeamanifestationofprimaryTB(withinvolvementofadjacentlymphnodes),
reactivationTB(involvingthesuperiorsegmentsofthelowerlobes),orendobronchialTB[53,54,56].
EndobronchialTBcanaffectlowerlungfieldsinbothprimaryinfection(especiallywhenadjacentlymphnodesare
involved)andreactivation(spreadfromupperlobediseasecansecondarilyinfectthelowerlungfields).
OlderadultpatientsandthosewithHIV,diabetes,renalorhepaticdisease,thosereceivingcorticosteroids,and
thosewithunderlyingsilicosisappearathighestriskforlowerlobeTB.However,manypatientshaveno
underlyingmedicalillnesses.StudiesinnursinghomessuggestthatlowerlobeTBmaybeamanifestationof
activetuberculosisinanolder,tuberculinnegativepopulationwithsignificantunderlyingdiseasesoranergy[56].In
somecases,thepatientsaresuspectedorknowntohavehadpreviousTBbutdevelopexogenousreinfection,
perhapsduetoalossofdemonstrabletissuehypersensitivity.
TuberculomaRoundedmasslesionscandevelopduringprimaryinfectionorwhenafocusofreactivation
TBbecomesencapsulated[55].Cavitationisrare.Thedifferentialdiagnosisofpulmonarycoinlesionsis
extensive,andthediagnosisoftuberculomacanbedifficultsinceairwayculturesareoftennegative.Fineneedle
aspirationorlungbiopsymaybenecessaryfordiagnosis.(See"Diagnosticevaluationandmanagementofthe
solitarypulmonarynodule".)
COMPLICATIONSOFTUBERCULOSISPulmonarycomplicationsoftuberculosis(TB)includehemoptysis,
pneumothorax,bronchiectasis,extensivepulmonarydestruction(includingpulmonarygangrene),malignancy,and
chronicpulmonaryaspergillosis.
HemoptysisHemoptysisoccursmostfrequentlyinthesettingofactivetuberculosisbutmayalsooccurafter
completionoftreatment[5759].Manypatientswithhemoptysisareacidfastbacilli(AFB)smearpositiveand
usuallyhavecavitarydisease.Bleedingusuallyisofsmallvolume,appearingasbloodstreakedsputum.Massive
hemoptysisisararecomplicationsincetheadventofchemotherapy.Priortoeffectivechemotherapy,massive
hemoptysisaccountedforapproximately5percentofdeathsfromTB.
SourcesofmassivehemoptysisduetoTBincludethepulmonaryartery,bronchialarteries,intercostalarteries,and
othervesselssupplyingthelung."Rasmussen'saneurysm"isarelativelyuncommoncauseofhemoptysisit
referstotheformationofananeurysminthesettingofcavitaryinfectionthatextendsintotheadventitiaandmedia
ofbronchialarteries,resultingininflammationandthinningofthevesselwall[60,61].Thisaneurysmsubsequently
rupturesintothecavity,producingmassivehemoptysis.
HemoptysisafterthecompletionoftherapyforTBonlyoccasionallyrepresentsTBrecurrence.Othercauses
includeresidualbronchiectasis,anaspergillomaorotherfungusballinvadingorcolonizinganoldhealedcavity,a
rupturedbroncholiththaterodesthroughabronchialartery,acarcinoma,oranotherinfectiousorinflammatory
process.
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Patientswithsignificanthemoptysisshouldbeevaluatedpromptlytodefinethesourceofbleedingandtofacilitate
immediateintervention.Apartfromimpendingexsanguination(whichrequiresimmediatesurgicalcare),bronchial
arteryembolizationisthepreferredmanagementapproachiffeasible[62,63].Inonestudyincluding140patients
withTBandmassivehemoptysis(morethan300mLofbloodin24hours)whounderwentbronchialartery
embolization,nearlycompletecontrolofhemoptysiswasachievedin73percentofcases[62].Intheabsenceof
accesstoappropriatefacilitiesforbronchialarteryembolization,othertreatmentsincludesbedrest,postural
management,volumereplacement,coughsuppression,andintravenousvasopressin[64].(See"Massive
hemoptysis:Initialmanagement".)
Ifembolizationandmedicalmanagementfail,surgicaloptionsincludeligationofarteries,resectionofalunglobe,
andendobronchialtamponade.Bothligationandembolizationcanbecomplexbecauseofthefrequentpresenceof
multiplefeederarteriesoftenconnectingsystemicwithbronchialcirculation[65].Olderstudiessuggestthatafter
anepisodeofmassivehemoptysisorrepeatedepisodesofseverehemoptysis,surgicalinterventionimproves
survival[6668]andshouldbeconsideredifembolizationfails.
PneumothoraxPriortotheavailabilityofantituberculoustherapy,spontaneouspneumothoraxwasafrequent
anddangerouscomplicationofpulmonaryTB[69].Sincetheavailabilityofantituberculoustherapy,spontaneous
pneumothoraxassociatedwithTBhasbeenreportedinabout1percentofhospitalizedpatients[7072].Acase
seriesfromTurkeyreportedpneumothoraxin1.5percentofcasesofpulmonaryTB[72].InregionswhereTBis
endemic,itmaybethemostcommoncauseofspontaneouspneumothorax[73].
Pneumothoraxappearstoresultfromtheruptureofaperipheralcavityorasubpleuralcaseousfocuswith
liquefactionintothepleuralspace[70,71].Inflammationcanleadtodevelopmentofabronchopleuralfistula,which
canpersistorsealoffspontaneously.Thelungmayreexpandifthebronchopleuralfistulasealsspontaneously,but
morecommonlychesttubedrainageisrequired.
Factorspreventingsuccessfulchesttubedrainageandexpansionincludeextensivepulmonaryparenchymal
diseasewithlargefistulas,alongintervalbetweenpneumothoraxandchesttubeinsertion,andthedevelopmentof
anempyemaduetoTBand/orbacterialsuperinfection.However,successfulclosureofevenextensiveairleaks
hasbeenreportedafterasmuchassixweeksofchesttubedrainageaccompaniedbyappropriateantituberculous
chemotherapy[74].(See"Secondaryspontaneouspneumothoraxinadults".)
BronchiectasisBronchiectasismaydevelopfollowingprimaryorreactivationTBandcanbeassociatedwith
hemoptysis[7580].(See"Clinicalmanifestationsanddiagnosisofbronchiectasisinadults".)
FollowingprimaryTBinfection,extrinsiccompressionofabronchusbyenlargednodesmaycausebronchial
dilationdistaltotheobstruction.TheremaybenoevidenceofparenchymalTB.
InthesettingofreactivationTB,progressivedestructionandfibrosisoflungparenchymamayleadtolocalized
bronchialdilation.Ifendobronchialdiseaseispresent,bronchialstenosismayresultindistalbronchiectasis.
BronchiectasisismorefrequentinthecommonsitesofreactivationTB(apicalandposteriorsegmentsofthe
upperlobe)butmaybefoundinotherareasofthelung.
ExtensivepulmonarydestructionRarely,untreatedorinadequatelytreatedTBcancauseprogressive,
extensivedestructionofareasofoneorbothlungs[81,82].InprimaryTB,occasionallylymphnodeobstructionof
thebronchitogetherwithdistalcollapse,necrosis,andbacterialsuperinfectioncanproduceparenchymal
destruction[82].Morecommonly,destructionresultsfromchronicreactivationTB,typicallyintheabsenceof
effectivechemotherapy.Symptomsincludeprogressivedyspnea,hemoptysis,andweightloss.
Inoneseriesof18patientswithextensivedestructionofoneorbothlungs,eightdied[81].Causesofdeathwere
massivehemoptysisandrespiratoryfailure,sometimesinthepresenceofactiveTBorsuperinfection.
Radiographically,patientshadlargecavitiesandfibrosisofremaininglunginsomecases,airfluidlevelsatthe
baseofthedestroyedlungwereobserved[81,82].
Pulmonarygangrenereferstoacutepulmonarydestruction[83].ThisformofTBprogressesrapidlyfroma
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homogeneous,extensiveinfiltratetodenseconsolidation.Airfilledcystsdevelopandcoalesceintocavities.
Necroticlungtissueattachedtothewallofthecavitymaybeobserved.Pulmonarygangrenemayresemblean
intracavitaryclot,fungusball,orRasmussen'saneurysm.Pathologydemonstratesarteritisandthrombosisofthe
vesselssupplyingthenecroticlung.Mortalityusuallyishighinonesmallseries,75percentofpatientsdied[83].
Resolutionwitheffectivetherapyhasalsobeenreported[84].
SepticshockTBcancausesepticshockthemanifestationsaresimilartobacterialsepticshock.Compared
withpatientswithsepticshockduetootherpathogens,patientswithsepticshockduetoTBhavelowermean
bodymassindices(22versus27),lowermeanwhitebloodcounts(10.4versus16.2),andaremoreoftenHIV
infected(15versus3percent)[85].TheprobabilityofsurvivalinpatientswithM.tuberculosissepticshockis
extremelypoor,withaninhospitalmortalityrateof79percentdelayedinitiationofappropriatetherapylikely
playedanimportantroleinclinicaloutcome[85].Extrapulmonarydiseasemaybeobservedinmorethan50
percentofcases.(See"Sepsissyndromesinadults:Epidemiology,definitions,clinicalpresentation,diagnosis,
andprognosis".)
MalignancyAstudyconductedbytheNationalCancerInstitutefoundthatpulmonarytuberculosiswas
associatedwithanincreasedriskoflungcancer,afteradjustmentforactivesmokingandsocioeconomicstatus
(oddsratio[OR]2.1,95%CI1.43.1)[86].Thecausalrelationshipisnotclearbutmycobacterialcellwall
componentsmayinduceproductionofnitricoxideandreactiveoxygenspecies,whichhavebeenimplicatedin
DNAdamageleadingtocarcinogenesis[87].Chronicinflammationmayalsoenhancemutagenesis.Inaddition,
immunesuppressionandradiationtherapyforlungcancermaybeassociatedwithanincreasedriskof
tuberculosis.ClinicalandradiographicsimilaritiesbetweenTBandmalignancymayleadtoadelayinestablishing
thecorrectdiagnosis.
VenousthromboembolismTuberculosis,bothpulmonaryandextrapulmonary,hasbeensuggestedasan
independentriskfactorforvenousthromboembolism(VTE),perhapsduetoahypercoagulablestate.Inone
retrospectivestudyincluding3485casesofactiveTB,theprevalenceofVTEwasapproximately2percent[88],
whichissimilartotherateassociatedwithmalignancyandapproximately100timeshigherthantheincidenceof
VTEamonghospitalizedpatientsingeneral[89].TheclinicalapproachtoVTEisdiscussedfurtherseparately.
(See"Overviewofacutepulmonaryembolisminadults".)
ChronicpulmonaryaspergillosisChronicpulmonaryaspergillosiscanbeasequelaofpulmonary
tuberculosis,especiallyinthosewithcavitarydisease.Thisisdiscussedfurtherseparately.(See"Clinical
manifestationsanddiagnosisofchronicpulmonaryaspergillosis",sectionon'Underlyingdiseases'.)
DIFFERENTIALDIAGNOSISThefollowingconditionscancausecavitarypulmonarylesionsandsymptoms
suggestiveoftuberculosis(TB)includingfever,cough,andweightloss:
Nontuberculousmycobacterialinfection(NTM)SymptomsofNTMincludefatigue,dyspnea,and
occasionalhemoptysisfeverandweightlossoccurlessfrequentlythaninpatientswithtuberculosis.
ClinicalfeaturesofMycobacteriumkansasiiareoftenverysimilartothoseofTB.NTMisdistinguishedfrom
TBbycultureresultsand/ormoleculardiagnostictesting.(See"Overviewofnontuberculousmycobacterial
infectionsinHIVnegativepatients".)
FungalinfectionFungalpneumoniacanpresentwitharangeofmanifestationsincludingpneumonia,
pulmonarynodule,andcavitarylungdisease.ItisdistinguishedfromTBbyepidemiologicexposureand
cultureresults.(See"Diagnosisandtreatmentofpulmonaryhistoplasmosis"and"Diagnosisofinvasive
aspergillosis"and"Mucormycosis(zygomycosis)"and"Clinicalmanifestationsanddiagnosisof
blastomycosis"and"Epidemiology,clinicalmanifestations,anddiagnosisofCryptococcusneoformans
meningoencephalitisinHIVinfectedpatients".)
SarcoidosisSarcoidosismostcommonlypresentswithdiffuseinterstitiallungdisease.Itrarelyforms
cavitiesandisdistinguishedfromTBbyhistopathologicdetectionofnoncaseatinggranulomas.(See
"Clinicalmanifestationsanddiagnosisofpulmonarysarcoidosis".)
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LungabscessLungabscessgenerallypresentswithfever,cough,andsputumproductionbutwithout
shakingchillsortruerigors.Chestimagingusuallyshowsinfiltrateswithacavity.Thediagnosisis
establishedbasedoncultureresults.(See"Lungabscess".)
SepticemboliSepticembolitothelungfromanextrapulmonarynidusaredistinguishedfromTBbyblood
cultureresultsandechocardiography.(See"Complicationsandoutcomeofinfectiveendocarditis",sectionon
'Septicembolization'.)
LungcancerLungcancermostcommonlypresentswithcough,hemoptysis,chestpain,anddyspnea.Itis
distinguishedfromTBbyhistopathology.(See"Overviewoftheriskfactors,pathology,andclinical
manifestationsoflungcancer".)
LymphomaLymphomatypicallypresentswitharapidlygrowingmasstogetherwithfever,nightsweats,
andweightloss.ItisdistinguishedfromTBbyhistopathology.(Seerelatedtopics.)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopic(see"Patientinformation:Tuberculosis(TheBasics)")
BeyondtheBasicstopic(see"Patientinformation:Tuberculosis(BeyondtheBasics)")
SUMMARY
Clinicalmanifestationsofpulmonarytuberculosis(TB)includeprimaryTB,reactivationTB,endobronchial
TB,lowerlungfieldTBinfection,andtuberculoma.(See'Introduction'above.)
Amongpatientswithprimarytuberculosis,clinicalmanifestationshavebeenobservedinapproximatelyone
thirdofcases.Symptomsincludefeverandchestpain.Retrosternalpainanddullinterscapularpainhave
beenascribedtoenlargedbronchiallymphnodes.Thephysicalexamisgenerallynormal.Themostcommon
chestradiographabnormalityinonelargeserieswashilaradenopathy.Othermanifestationsincludepleural
effusionsandpulmonaryinfiltrates.(See'Primarytuberculosis'above.)
ReactivationTBreferstoreactivationofapreviouslydormantfocusseededatthetimeoftheprimary
infection.Theapicalposteriorsegmentsofthelungarefrequentlyinvolved(image1).Typically,symptoms
areinsidiousandmayincludecough,weightloss,fatigue,fever,nightsweats,chestpain,dyspnea,and/or
hemoptysisthesefindingsareobservedlessfrequentlyamongpatients>60years.(See'Reactivation
tuberculosis'above.)
EndobronchialTBmaydevelopviadirectextensiontothebronchifromanadjacentparenchymalfocus
(usuallyacavity)orviaspreadoforganismstothebronchiviainfectedsputum.Itcanoccurinpatientswith
primaryTBorreactivationTBandwasobservedmorefrequentlypriortotheantituberculoustherapyera.
Symptomsmaybeacuteorchronicabarkingcoughhasbeendescribedinapproximatelytwothirdsof
patients.(See'Endobronchialtuberculosis'above.)
PulmonarycomplicationsofTBincludehemoptysis,pneumothorax,bronchiectasis,extensivepulmonary
destruction(includingpulmonarygangrene),malignancy,venousthromboembolism,andchronicpulmonary
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aspergillosis.(See'Complicationsoftuberculosis'above.)
Thedifferentialdiagnosisforpulmonarytuberculosisisbroadandincludesothercausesofchronicinfection,
inflammatorydiseases,andmalignancy.(See'Differentialdiagnosis'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
Topic7026Version21.0
http://www.uptodate.com.etechconricyt.idm.oclc.org/contents/clinicalmanifestationsandcomplicationsofpulmonarytuberculosis?topicKey=ID%2F7026&el 10/14
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GRAPHICS
Chestradiographsoftuberculosis
Chestradiographs(posteroanteriorandlateralviews)demonstratingcavitary
reactivationoflatenttuberculosisinfectionintheposteriorapicalsegmentof
therightupperlobe.
Reproducedwithpermissionfrom:CrapoJD,GlassrothJ,KarlinskyJB,KingTE.Baum's
TextbookofPulmonaryDiseases,7thEdition.Philadelphia:LippincottWilliams&Wilkins,
2004.Copyright2004LippincottWilliams&Wilkins.
Graphic54832Version3.0
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Chestradiographsofdifferentpresentationsoftuberculosis
(A)Primarytuberculosisinachild(notetherightsidedhilaradenopathy,rightsided
lowerlobeinfiltrates,andvolumeloss).
(B)Lowerlungfieldtuberculosisinfiltrationandcavitywithairfluidlevelinlingula.
(C)Reactivatedtuberculosis,faradvanceddiseasewithbronchogenicspread.
(D)Miliarytuberculosis.
Reproducedwithpermissionfrom:GorbachSL,BartlettJG,etal.InfectiousDiseases.
Philadelphia:LippincottWilliams&Wilkins,2004.Copyright2004LippincottWilliams&
Wilkins.
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Imagingofcavitarylesionsintuberculosis
Chestradiograph(A)andcomputedtomography(CT)scan(B),thelatterof
whichmoreclearlydemonstratestwocavitarylesions.ArepeatedCTscan(C)
showedimprovementafteronemonthoftreatmentinayoungwomanwith
primarymultidrugresistanttuberculosis.
Reproducedwithpermissionfrom:GorbachSL,BartlettJG,etal.InfectiousDiseases.
Philadelphia:LippincottWilliams&Wilkins,2004.Copyright2004LippincottWilliams&
Wilkins.
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ContributorDisclosures
AntonPozniak,MD,FRCPNothingtodisclose.CFordhamvonReyn,MDNothingtodisclose.ElinorL
Baron,MD,DTMHNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovided
tosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDate
standardsofevidence.
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