mdr tb journal

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834 AJR:191, September 2008

trol measures as well as or ensuring the ap-

propriate therapy or inected patients. Un-

ortunately, acid-ast bacilli are ound in the

sputum in a limited number o patients with

active pulmonary TB [6]. Thereore, the im-

aging diagnosis would provide an appropri-

ate therapy or inected patients beore the

denitive diagnosis by the bacteriology. The

aim o this article is to elaborate new con-

cepts in the diagnosis and treatment o pul-

monary TB in the 21st century, to review the

characteristic imaging ndings o various

orms o pulmonary TB, and to assess the

role o CT in the diagnosis and management

o pulmonary TB.

Development of Infection and

PathogenesisM. tuberculosis is an aerobic, nonmotile,

non-spore-orming rod that is highly resis-

tant to drying, acid, and alcohol. It is trans-

mitted rom person to person via droplet nu-

clei containing the organism and is spread

mainly by coughing. A person with active

but untreated TB inects approximately

1015 other people per year. The probability

o transmission rom one person to another

depends on the number o inectious droplets

Pulmonary Tuberculosis: Up-to-Date Imaging and Management

Yeon Joo Jeong1

Kyung Soo Lee2

Jeong YJ, Lee KS

1Department o Diagnostic Radiology, Pusan National

University Hospital, Pusan National University School o

Medicine and Medical Research Institute, Pusan, Korea.

2Department o Radiology and Center or Imaging

Science, Samsung Medical Center, Sungkyunkwan

University School o Medicine, 50, Ilwon-Dong,Kangnam-Ku, Seoul 135-710, Korea. Address correspon-

dence to K. S. Lee ([email protected]).

Chest Imaging Review

CME

This article is available or CME credit.

See www.arrs.org or more inormation.

AJR2008; 191:834844

0361803X/08/1913834

American Roentgen Ray Society

Tuberculosis (TB) is an airborne

inectious disease caused byMy-

cobacterium tuberculosis and is

a major cause o morbidity and

mortality, particularly in developing coun-

tries [13]. In 2005, 8.8 million people devel-

oped active TB and 1.6 million died o the

disease [4]. Most cases occur in Southeast

Asia and Arica.

Patients with active pulmonary TB may be

asymptomatic, have mild or progressive dry

cough, or present with multiple symptoms,

including ever, atigue, weight loss, night

sweats, and a cough that produces bloody

sputum. I TB is detected early and ully

treated, people with the disease quickly be-

come noninectious and eventually cured.

However, multidrug-resistant (MDR) and ex-tensively drug-resistant TB, HIV-associated

TB, and weak health systems are major chal-

lenges. The World Health Organization is

making an eort to dramatically reduce the

burden o TB and to halve TB deaths and

prevalence by 2015, through its Stop TB

Strategy and supporting the Global Plan to

Stop TB [5].

The prompt diagnosis o TB is essential

or community public health inection con-

Keywords: lung CT, lung disease, lung inection,

tuberculosis , pulmonary

DOI:10.2214/AJR.07.3896

Received February 24, 2008 ; accepted ater revision

April 11, 200 8.

Supported by the SRC/ERC program o MOST/KOSEF

(grant no. R11-2002-103).

OBJECTIVE. Pulmonary tuberculosis (TB) is a common worldwide inection and a med-

ical and social problem causing high mortality and morbidity, especially in developing coun-

tries. The traditional imaging concept o primary and reactivation TB has been recently chal-

lenged, and radiologic eatures depend on the level o host immunity rather than the elapsed

time ater the inection. We aimed to elaborate the new concept o the diagnosis and treatment

o pulmonary TB, to review the characteristic imaging ndings o various orms o pulmo-

nary TB, and to assess the role o CT in the diagnosis and management o pulmonary TB.CONCLUSION.Fast and more accurate TB testing such as bacterial DNA ngerprint-

ing and whole-blood intereron- assay has been developed. Miliary or disseminated primary

pattern or atypical maniestations o pulmonary TB are common in patients with impaired

immunity. CT plays an important role in the detection o TB in patients in whom the chest

radiograph is normal or inconclusive, in the determination o disease activity, in the detection

o complication, and in the management o TB by providing a roadmap or surgical treatment

planning. PET scans using 18F-FDG or 11C-choline can sometimes help dierentiate tubercu-

lous granuloma rom lung malignancy.

Jeong and LeePulmonary Tuberculosis

Chest ImagingReview


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AJR:191, September 200 8 835

Pulmonary Tuberculosis

expelled by a carrier, the duration o exposure,

and the virulence o theM. tuberculosis. The

risk o developing active TB is greatest in pa-

tients with altered host cellular immunity,

including extremes o age, malnutrition, can-

cer, immunosuppressive therapy, HIV inec-

tion, end-stage renal disease, and diabetes.

TB inection begins when the mycobacte-ria reach the pulmonary alveoli, where they

invade and replicate within alveolar macro-

phages. Inhaled mycobacteria are phagocy-

tized by alveolar macrophages, which interact

with T lymphocytes, resulting in dierentia-

tion o macrophages into epithelioid histio-

cytes [7]. Epithelioid histiocytes and lympho-

cytes aggregate into small clusters, resulting

in granulomas. In the granuloma, CD4 T

lymphocytes (eector T cell) secrete cyto-

kines, such as intereron-, which activate

macrophages to destroy the bacteria with

which they are inected. CD8 T lymphocytes

(cytotoxic T cell) can also directly kill in-

ected cells [8]. Importantly, bacteria are not

always eliminated rom the granuloma, but

can become dormant, resulting in a latent in-

ection. Another eature o human TB granu-

lomas is the development o necrosis in the

center o the tubercles.

The primary site o inection in the lungs is

called the Ghon ocus [9]. It either enlarges

as disease progresses or, much more com-

monly, undergoes healing. Healing may re-

sult in a visible scar that may be dense and

contain oci o calcication. During the early

stage o inection, organisms commonlyspread via lymphatic channels to regional hi-

lar and mediastinal lymph nodes and via the

bloodstream to more distant sites in the body.

The combination o the Ghon ocus and a-

ected lymph nodes is known as the Ranke

complex. The initial inection is usually clini-

cally silent. In approximately 5% o inected

individuals, immunity is inadequate and clin-

ically active disease develops within 1 year o

inection, a condition known as progressive

primary inection [10]. For most inected in-

dividuals, however, TB remains clinically

and microbiologically latent or many years.

In approximately 5% o the inected popu-lation, endogenous reactivation o latent in-

ection develops many years ater the initial

inection (this has also been called postpri-

mary TB) [10]. The reactivation TB tends to

involve predominantly the apical and posteri-

or segments o the upper lobes and the supe-

rior segments o the lower lobes. This location

is likely due to a combination o relatively

higher oxygen tension and impaired lymphat-

ic drainage in these regions [11]. As distinct

rom primary inection site, in which healing

is the rule, reactivation TB tends to prog-

ress. The main abnormalities are progressive

extension o infammation and necrosis, re-

quently with development o communication

with the airways and cavity ormation. The

endobronchial spread o necrotic materialrom a cavity may result in TB inection in

the same or in other lobes. Hematogenous

dissemination may result in miliary TB.

Diagnosis

A denitive diagnosis o TB can only be

made by culturingM. tuberculosis organisms

rom a specimen taken rom the patient.

However, TB can be a dicult disease to di-

agnose, mainly because o the diculty in

culturing this slow-growing organism in the

laboratory. A complete evaluation or TB

must include a medical history, a chest radio-

graph, a physical examination, and microbio-

logic smears and cultures. It may also include

a tuberculin skin test and a serologic test.

The treatment o latent TB inection to pre-

vent progression to active disease has been an

essential component o public health eorts

to eliminate TB [12]. Currently, latent inec-

tion is diagnosed in a nonimmunized person

by a tuberculin skin test (TST), which yields

a delayed-hypersensitivity-type response to

puried protein derivatives oM. tuberculo-

sis. However, the TST, which has been used

or years or the diagnosis o latent TB inec-

tion, has many limitations, including alse-positive test results in individuals who were

vaccinated with bacille Calmette-Gurin

(BCG) and in individuals who have inec-

tions not related toM. tuberculosis [13, 14].

Discovery o the role o T lymphocytes

and intereron- in the immune process has

led to the development o an in vitro assay or

cell-mediated immune reactivity to M. tu-

berculosis [15]. Recently, this whole-blood

intereron- assay has been introduced or

the diagnosis o latent TB inection and has

shown a higher diagnostic accuracy than the

TST [13, 16]. These new TB tests are being

developed with the hope o cheap, ast, andmore accurate TB testing. These new tests

use polymerase chain reaction detection o

bacterial DNA and whole-blood intereron-

assay [17]. Individuals with a positive TST or

whole-blood intereron- assay, especially

HIV-inected persons or those who have

chest radiographic or CT ndings consistent

with TB, should be considered or treatment

o a latent inection [18].

New Concept of Radiologic

Manifestations of Tuberculosis

Patients who develop disease ater initial

exposure are considered to have primary TB,

whereas patients who develop disease as a

result o reactivation o a previous ocus o

TB are considered to have reactivation TB.

Traditionally, it was believed that the clini-cal, pathologic, and radiologic maniesta-

tions o reactivation TB were quite distinct

rom those o primary TB. This concept has

been recently challenged on the basis o

DNA ngerprinting.

DNA ngerprint pattern with restriction

ragment length polymorphism (RFLP) anal-

ysis oM. tuberculosis isolates can give clini-

cians an insight into the transmission o TB

[19]. Isolates rom patients inected with epi-

demiologically unrelated strains o TB have

dierent RFLP patterns, whereas those rom

patients with epidemiologically linked strains

generally have identical RFLP patterns.

Thereore, clustered cases o TB, dened as

those in which the isolates have identical or

closely related genotypes, have usually been

transmitted recently. In contrast, cases in

which the isolates have distinctive genotypes

generally are a reactivation o inection ac-

quired in the distant past [20, 21].

A recent study based on genotyping M.

tuberculosis isolates with RFLP showed that

the radiographic eatures are oten similar in

patients who apparently have a primary dis-

ease and those who have a reactivation TB

[22, 23]. Thereore, time rom acquisition oinection to the development o clinical dis-

ease does not reliably predict the radiograph-

ic appearance o TB. The only independent

predictor o radiographic appearance may be

integrity o the host immune response;

namely, severely immunocompromised pa-

tients show a tendency to have the primary

orm o TB, whereas immunocompetent pa-

tients tend to have the reactivation orm [22,

23]. Because this result is preliminary and

most published data are based on the tradi-

tional concept o primary and reactivation

disease, we ollow the traditional outline in

this ar ticle.

Radiologic Manifestations in

Immunocompetent Hosts

Primary Tuberculosis

The initial parenchymal ocus o TB may

enlarge and result in an area o airspace con-

solidation or, more commonly, undergo heal-

ing by transormation o the granulomatous

tissue into mature brous tissue. Primary TB


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836 AJR:191, September 200 8

Jeong and Lee

occurs most commonly in children but is be-

ing seen with increasing requency in adults

[24]. The most common abnormality in chil-

dren is lymph node enlargement, which is

seen in 9095% o cases [25, 26]. The

lymphadenopathy is usually unilateral and

located in the hilum or the paratracheal re-

gion. On CT, the enlarged nodes typicallyshow central low attenuation, which repre-

sents caseous necrosis, and peripheral rim

enhancement, which represents the vascular

rim o the granulomatous infammatory tis-

sue [27, 28] (Fig. 1).

Airspace consolidation, related to paren-

chymal granulomatous infammation and

usually unilateral, is evident radiographical-

ly in approximately 70% o children with

primary TB [26]. It shows no predilection

or any particular lung zone [26]. On CT, the

parenchymal consolidation in primary TB is

most commonly dense and homogeneous but

may also be patchy, linear, nodular, or mass-

like [29] (Fig. 2).

Pleural eusion is usually unilateral and

on the same side as the primary ocus o TB.

The eusion may be large and occur in pa-

tients without evidence o parenchymal dis-

ease on chest radiographs [30].

Reactivation Tuberculosis

The most common radiographic manies-

tation o reactivation pulmonary TB is ocal

or patchy heterogeneous consolidation in-

volving the apical and posterior segments o

the upper lobes and the superior segments othe lower lobes [29, 31]. Another common

nding is the presence o poorly dened nod-

ules and linear opacities, which are seen in

approximately 25% o patients [31]. Cavities,

the radiologic hallmark o reactivation TB,

are evident radiographically in 2045% o

patients [2931]. In approximately 5% o pa-

tients with reactivation TB, the main mani-

estation is a tuberculoma, dened as a sharp-

ly marginated round or oval lesion measuring

0.54.0 cm in diameter [29, 31]. Histologi-

cally, the central part o the tuberculoma con-

sists o caseous material and the periphery, o

epithelioid histiocytes and multinucleated gi-ant cells and a variable amount o collagen.

Satellite nodules around the tuberculoma

may be present in as many as 80% o cases

[32]. Because o active glucose metabolism

caused by active granulomatous infamma-

tion, tuberculomas sometimes have been re-

ported to accumulate 18F-FDG and to cause

PET scans to be interpreted as alse-positive

or malignancy [33] (Fig. 3). Unlike 18F-FDG

A

Fig. 1Primary tuberculosis maniesting primarily as lymphadenopathy in 26-year-old woman.A, Posteroanterior chest radiograph shows right hilar mass (arrow). Note smaller nodule (arrowhead) in rightupper lung zone.B, Contrast-enhanced transverse CT scan (5.0-mm section thickness) obtained at level o basal trunk usingmediastinal window setting shows enlarged right hilar and subcarinal lymph nodes (arrows), central necroticlow attenuation, and peripheral rim enhancement.

B

A

Fig. 2Primary tuberculosis presenting with consolidation and lymphadenopathy in 21-year-old woman.A, Posteroanterior chest radiograph shows airspace consolidation in right middle lung zone.B, Contrast-enhanced transverse CT scan (5.0-mm section thickness) obtained at level o right middle lobarbronchus using mediastinal window setting shows airspace consolidation in right middle lobe. Note enlargedright hilar and subcarinal lymph nodes (arrows). Hilar node has necrotic low attenuation.

B

Fig. 3Tuberculous granulomas in 58-year-old man.18F-FDG PET/CT scan shows increased FDG uptakein noduleswell-dened predominant nodule(arrow) and surrounding smaller satellite nodules(arrowheads)in right upper lobe with maximumstandard uptake value o 6.1.


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PET scans, 11C-choline PET scans can help

dierentiate between lung cancer and tuber-

culoma [34]. The standard uptake value o

tuberculoma is low in 11C-choline PET scans.

Hilar or mediastinal lymphadenopathy is

uncommon in reactivation TB, being seen in

approximately 510% o patients [30, 31].

Pleural eusion, typically unilateral, occursin 1520% o patients [35].

The most common CT ndings o reacti-

vation pulmonary TB are centrilobular small

nodules, branching linear and nodular opaci-

ties (tree-in-bud sign), patchy or lobular ar-

eas o consolidation, and cavitation [24, 36,

37]. The centrilobular small nodules and

tree-in-bud sign refect the presence o endo-

bronchial spread and are due to the presence

o caseous necrosis and granulomatous in-

fammation lling and surrounding terminal

and respiratory bronchioles and alveolar

ducts [36, 38] (Fig. 4). These tree-in-bud

signs are considered a reliable marker o the

activity o the process [6]. Cavitation is also

a sign o an active disease process and usu-

ally heals as a linear or brotic lesion.

Although it is usually accompanied by pa-

renchymal abnormalities, pleural eusion

may be the sole imaging maniestation o

TB. In this particular situation, the determi-

nation o pleural fuid adenosine deaminase

(ADA) level (elevated in TB pleurisy) can be

helpul or the characterization o the pleural

fuid; the ADA assay has a sensitivity o 92%

(95% CI, 9093%) and a specicity o 90%

(8991%) or diagnosing TB pleurisy [39].New subpleural lung nodules may develop

during medication or TB pleural eusion. It

should not be regarded as treatment ailure.

These paradoxical subpleural nodules will

eventually show improvement with contin-

ued medication [40].

Miliary Tuberculosis

Miliary TB reers to widespread dissemi-

nation o TB by hematogenous spread. It oc-

curs in 26% o primary TB and also occurs

somewhat more requently in reactivation TB

[41]. In the latter situation, miliary TB may be

seen in association with typical parenchymalchanges or may be the only pulmonary abnor-

mality. Each ocus o miliary inection results

in local granulomas that, when well devel-

oped, consist o a region o central necrosis

surrounded by a relatively well-delimited rim

o epithelioid histiocytes and brous tissue.

The characteristic radiographic and high-

resolution CT ndings consist o innumera-

ble, 1- to 3-mm diameter nodules randomly

A

B C

D E

Fig. 4Reactivation tuberculosis in 55-year-old man.A, Anteroposterior chest radiograph shows cavitaryconsolidation in right upper lung zone and mul tiple ill-dened nodules in both lungs.BandC, High-resolution CT scans (1.0-mm section

thickness) obtained at levels o aortic arch (B) andproximal ascending aorta (C) show consolidation andacinus-sized nodules containing several cavities inboth upper lobes. Note branching nodular and linearopacities (tree-in-bud signs) (arrows) and centri-lobular small nodules (arrowheads, C) in both lungs.D, Photograph o gross specimen obtained atlobectomy rom dierent patient shows multiple ocio nodules and consolidation that are distinctly white,consistent with caseous necrosis. Most have nodularappearance and some appear to be branching (arrows),suggestive o airway-centered nature o lesions.E, Photomicrograph o surgical specimendisclosesmultiple granulomas, each related to small membra-nous bronchiole (arrows). Some granulomas showcentral caseous necrosis (arrowhead). (H and E, 40)

distributed throughout both lungs [4144]

(Fig. 5). Thickening o interlobular septa

and ne intralobular networks are requently

evident [37]. Diuse or localized ground-

glass opacity is sometimes seen, which may

herald acute respiratory distress syndrome

[4345] (Fig. 6).

Airway Tuberculos is

The most common cause o infammatory

stricture o the bronchus is TB. Tracheobron-

chial TB has been reported in 1020% o all

patients with pulmonary TB [24, 46]. The prin-

cipal CT ndings o airway TB are circumer-

ential wall thickening and luminal narrowing,

with involvement o a long segment o the

bronchi [46, 47]. In active disease, the airways

are irregularly narrowed in their lumina and

have thick walls, whereas in brotic disease,

the airways are smoothly narrowed and have

thin walls [46, 47]. The let main bronchus is

involved more requently in brotic disease,

whereas both main bronchi are equally in-volved in active disease [46] (Fig. 7).

Radiologic Manifestations in

Immunocompromised Hosts

Impaired host immunity has been regard-

ed as a predisposing actor in TB. Known

risk actors or development o active TB


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Jeong and Lee

A

Fig. 5Miliary tuberculosis in 70-year-old man.A, Posteroanterior chest radiograph shows evenlydistributed, discrete, uniormly sized, millet-sizednodular opacities in both lungs.B, High-resolution CT image (1.0-mm section

thickness) at level o right upper lobar bronchusshows uniorm-sized small nodules randomlydistributed throughout both lungs. Note subpleuraland subssural nodules (arrows).

B

Fig. 6Miliary tuberculosis presenting as acute respiratory distress syndrome in 47-year-old man.A, Posteroanterior chest radiograph shows innumerable millet-sized nodular opacities and ground-glass opacities in both lungs.B, High-resolution CT image (1.0-mm section thickness) obtained at ventricular level shows randomly distributed small nodules and extensive bilateral ground-glassopacity. Note interlobular septal (arrows) and intralobular interstitial thickenings in both lungs.C, Photomicrograph o pathologic specimen obtained with transbronchial lung biopsy discloses granuloma (arrows) in alveolar wall. Diuse alveolar wall thickening andintraalveolar brin deposition (not shown) suggesting early stage o diuse alveolar damage were also observed. (H and E, 400)

CA B

A

Fig. 7Actively caseating bronchial tuberculosis in 42-year-old woman.A andB, Contrast-enhanced transverse CT scans (5.0-mm section thickness) using mediastinal window setting obtained at levels o thoracic inlet (A) and main bronchi(B) show luminal narrowing o trachea and proximal le t main bronchus and irregular wall thickening. Note lymph nodes (arrows, A) in mediastinum.C, Bronchoscopy shows narrowed let main bronchial lumen with its mucosa swollen and covered diusely with whitish cheeselike substance ( arrow).

CB

include conditions that are associated with

deects in cell-mediated immunity, such as

HIV inection; malnutrition; drug and alco-

hol abuse; malignancy; end-stage renal dis-

ease; diabetes mellitus; and corticosteroid

or other immunosuppressive therapy [48].

Infiximab and etanercept (used in the treat-

ment o Crohns disease and rheumatoid ar-

thritis) are human antibodies against tumor

necrosis actor- (TNF-), which is in-

volved in the host deense against TB

killing oM. tuberculosis by macrophage,

granuloma ormation, or apoptosis and pre-

vention o dissemination o inection to

other sites. Active TB may develop soon ater


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the initiation o treatment with such drugs.

Thereore, beore prescribing these drugs,assessment o TB inection risk actors and

a TST or intereron- assay are strongly rec-

ommended to determine the patients latent

TB inection status and the risk o active

disease [49, 50].

TB is a major cause o death among peo-

ple living with HIV inection or AIDS. In

2005, the World Health Organization (WHO)

estimated that 12% o HIV deaths globally

were due to TB and that there were 630,000

new coinections with TB and HIV [51]. Im-mune restoration induced by highly active

anti-retroviral therapy (HAART) in devel-

oped countries has considerably improved

the outcome o HIV-positive patients and re-

duced the prevalence o opportunistic inec-

tion and TB in these patients. However, HIV-

associated TB still continues to occur in

countries where HAART is widely used [52].

Furthermore, HAART may result in para-

doxical worsening or TB maniestations in

patients with immune reconstitution infam-matory syndrome [53, 54] (Fig. 8).

The radiographic maniestations o HIV-

associated pulmonary TB are thought to be

dependent on the level o immunosuppression

at the time o overt disease [5557]. On CT,

HIV-seropositive patients with a CD4 T lym-

phocyte count < 200/mm3 have a higher prev-

alence o mediastinal or hilar lymphadenopa-

thy, a lower prevalence o cavitation, and oten

A

Fig. 8Paradoxical worsening o tuberculouslymphadenitis associated with immune reconstitutioninfammatory syndrome in 40-year-old woman withAIDS.A, Contrast-enhanced transverse CT scan (5.0-mmsection thickness) using mediastinal window settingobtained at level o aortic arch just beore highly activeantiretroviral therapy, shows multiple enlarged lymphnodes (arrows) with central necrotic low attenuation in

prevascular and right paratracheal areas. Patients HIVRNA viral load and CD4 counts were more than 1 millioncopies/mL and 35 cells/L, respectively.B, Follow-up CT image obtained 3 months ater Ashows increased extent o necrotic lymph nodes(arrows). Patients HIV RNA viral load and CD4 countsat this time were 433 copies/mL and 142 cells/L,respectively.

B

A B

C D

Fig. 9Pulmonary tuberculosis withlymphadenopathy and extrapulmonary involvementin 42-year-old man with AIDS. His CD4 count was 64cells/L.

A, Posteroanterior chest radiograph shows multiplesmall nodular opacities in both lungs, especially inupper lung zones.B, High-resolution CT scan (1.0-mm section

thickness) obtained at level o aortic arch showsrandomly distributed small nodules and interlobularseptal thickenings in both lungs.CandD, Contrast-enhanced transverse CT scans(5.0-mm section thickness) using mediastinal windowsetting obtained at levels o mandible (C) and thoracicinlet (D) show enlarged lymph nodes (arrows),central necrotic low attenuation, and peripheral rimenhancement in right neck and let axilla.


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Jeong and Lee

extrapulmonary involvement as compared

with HIV-seropositive patients with a CD4 T

lymphocyte count equal to or 200/mm3 [58]

(Figs. 9 and 10). Miliary or disseminated dis-

ease has also been reported to be associated

with severe immunosuppression [58] (Fig. 9).

Unusual or atypical maniestations o pul-

monary TB are common in patients with im-

paired host immunity. In cases o active pulmo-

nary TB, diabetic and immunocompromised

patients have a higher prevalence o multiple

cavities in a tuberculous lesion and o nonseg-

mental distribution than do patients without

underlying disease [48]. The incidence o TBin patients with idiopathic pulmonary brosis

(IPF) is more than our times higher than that

o the general population. Atypical maniesta-

tions such as subpleural nodules or a lobar or

segmental airspace consolidation are com-

mon in patients with IPF, which may mimic

lung cancer or bacterial pneumonia [59]. Pul-

monary TB in patients with systemic lupus

erythematosus (SLE) has a higher incidence

and prevalence because o abnormal unction

o alveolar macrophages and exposure to cor-

ticosteroid and cytotoxic drugs. TB in patients

with SLE tends to show radiologic ndings o

miliary dissemination, diuse consolidation,

or primary TB [60].

Radiologic Manifestations of

Multidrug-Resistant Tuberculosis

Anti-TB drug resistance is a major public

health problem that threatens the success o

global TB control. The major concerns o

drug resistance are ear regarding the spread

o drug-resistant organisms and the ineec-tiveness o chemotherapy in patients inected

with the resistant organisms. In addition,

MDR TB is a atal disease because o the

high mortality rate, depending on the under-

lying diseases, particularly in HIV-inected

patients [61, 62].

Imaging ndings o MDR TB do not basi-

cally dier rom those o drug-sensitive TB.

However, multiple cavities and ndings o

chronicity, such as bronchiectasis and calcied

granulomas, are more common in patients

with MDR TB [63, 64] (Fig. 11). A strong cor-

relation seems to exist between the radiologic

eatures o MDR TB and the mode o acquisi-

tion o drug-resistance. Patients with primary

drug resistance, who develop MDR TB with-

out a history o anti-TB chemotherapy or a

therapy history o less than 1 month, were

ound to present with noncavitary consolida-

tion, pleural eusion, and a primary tubercu-

losis pattern o disease [65]. On the other hand,

those who acquired MDR TB with a chemo-

therapy history o longer than 1 month otenshow cavitary consolidations and in general

show a reactivation pattern o the disease.

Extensively-drug-resistant TB is dened

as TB that has evolved resistance to riampin

and isoniazid, as well as to any member o

the quinolone amily and at least one o the

ollowing second-line TB treatments: kana-

mycin, capreomycin, or amikacin [66]. Ex-

tensively-drug-resistant TB is associated

A

Fig. 10Pulmonary tuberculosis in 51-year-old man with AIDS. His CD4 count was 4 cells/L.A, Posteroanterior chest radiograph shows multiocal masslike airspace consolidation in bilateral upper lung zones.B andC, High-resolution CT scans (1.0-mm section thickness) obtained at levels o let innominate vein ( B) and azygos arch (C) show masslike airspace consolidationwith air bronchograms, centrilobular small nodules (arrows, C), and ground-glass opacity in both upper lobes.

CB

A

Fig. 11Multidrug-resistant tuberculosis in 36-year-old man.A, Posteroanterior chest radiograph shows multiplesmall nodules, patchy consolidation containingseveral cavities, and linear opacities in both lungs.Note decreased volume in right lung and apicalpleural thickening.B, High-resolution CT scan (1.0-mm section

thickness) obtained at level o let basal trunk showsconsolidation containing several cavities in rightmiddle lobe and right lower lobe. Note small cavitarynodule and centrilobular nodules in let upper lobe.

B


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with a much higher mortality rate than MDR

TB because o a reduced number o eective

treatment options. The epidemiology and

imaging ndings o extensively-drug-resis-

tant TB have not been well studied, but it is

believed that the spread o extensively-drug-

resistant TB is closely associated with a high

prevalence o HIV and poor inection control

[67]. There has been no report on radiologic

ndings o extensively-drug-resistant pulmo-

nary TB; but in our experience, the disease

maniests an advanced pattern o primaryTB (extensive consolidation with or without

lymphadenopathy) in AIDS patients and an

advanced pattern o MDR TB (multiple cavi-

tary lesions in consolidative or nodular le-

sions) in non-AIDS patients.

Complications and Sequelae

of Tuberculosis

A variety o thoracic sequelae and compli-

cations rom pulmonary TB may occur and

may involve the lungs, airways, vessels, me-

diastinum, pleura, or chest wall [47, 6871]

(Appendix 1, Figs. 12 and 13).

The radiologic maniestations o acute re-spiratory distress syndrome secondary to TB

include extensive bilateral areas o ground-

glass opacity or consolidation superimposed

on ndings o miliary or endobronchial

spread o TB. Multiple cystic lesions may de-

velop in patients recovering rom acute re-

spiratory distress syndrome or in patients

with extensive consolidation due to TB [71].

The cystic lesions may resemble pneumato-

celes or bullae, which may resolve over sev-

eral months or persist [71].

Rasmussen aneurysm is a pseudoaneurysm

that results rom weakening o the pulmonary

artery wall by adjacent cavitary TB (Fig. 12).

Empyema necessitatis (Fig. 13) results rom

leakage o tuberculous empyema through the

parietal pleura and discharge o its contents

into the subcutaneous tissues o the chest wall

or, less commonly, into the pericardium, ver-

tebral column, or esophagus [69].

CT in Tuberculosis

Chest radiographs play a major role in the

screening, diagnosis, and response to treat-

ment o patients with TB. However, the ra-

diographs may be normal or show only mild

or nonspecic ndings in patients with active

disease [30]. Common causes o a missed

diagnosis o TB are ailure to recognize hilar

and mediastinal lymphadenopathy as a man-

iestation o primary disease in adults, over-

looking o mild parenchymal abnormalities

in patients with reactivation disease, and

ailure to recognize that an upper lobe nod-

ule or mass surrounded by small nodularopacities or scarring may represent TB [30].

CT is more sensitive than chest radiography

in the detection and characterization o both

subtle localized or disseminated parenchymal

disease and mediastinal lymphadenopathy [37,

42, 72, 73]. The radiographic diagnosis o TB

is initially correct in only 49% o all cas-

es34% or the diagnosis o primary TB and

59% or the diagnosis o reactivation TB [30].

With CT, the diagnosis o pulmonary TB is

correct in 91% o patients and TB is correctly

excluded in 76% o patients [74]. CT and high-

resolution CT are particularly helpul in the

detection o small oci o cavitation in areas o

confuent pneumonia and in areas o dense

nodularity and scarring [37]. In one study o 41

patients with active TB [37], high-resolution

CT showed cavities in 58%, whereas chest ra-

diographs showed cavities in only 22%.

In addition to the diagnosis o TB, high-

resolution CT is useul in determining diseaseactivity. A tentative diagnosis o active TB on

CT could be based on the pattern o parenchy-

mal abnormalities and the presence o cavita-

tion or evidence o endobronchial spread, such

as the presence o centrilobular nodules or a

tree-in-bud pattern. In the series by Lee et al.

[74], 80% o patients with active disease and

89% o those with inactive disease were cor-

rectly dierentiated on high-resolution CT.

CT is also helpul in the evaluation o

pleural complications, including tuberculous

eusion, empyema, and bronchopleural s-

tula, and may show pleural disease that is not

evident on chest radiography [75].In addition to its major role in the diagno-

sis o TB, CT plays an important role in the

management o TB, especially in complicat-

ed or MDR TB. MDR TB oten shows mul-

tiple cavities, which lead to the expectoration

o a large number o bacilli and endobron-

chial spread to previously unaected areas

o the lung. Limited drug penetration into the

cavities that harbor large numbers o myco-

A

Fig. 12Rasmussen aneurysm in chronic destructive pulmonary tuberculosis in 62-year-old man.A, Contrast-enhanced transverse CT scan (2.5-mm section thickness) obtained at level o main bronchi using mediastinal window setting shows cavitary consolidationwith air-crescent sign (low-attenuation lesion and surrounding air) (arrow) in let upper lobe.

B, CT scan obtained 15 mm inerior to A shows contrast-enhancing round vascular structure (arrow) in consolidative lesion.C, Let pulmonary angiogram shows contrast material lling aneurysm (arrow).

CB


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Jeong and Lee

bacteria is believed to contribute to the drug

resistance. Thereore, surgery may be an ad-

juvant treatment or MDR TB, although

present-day TB treatment relies on chemo-

therapy [76]. CT can locate the site o cavita-

tion and the extent o active disease and

thereore can be a roadmap or the planningo surgical treatment.

Conclusion

Although the slow reduction o the inci-

dence o TB has been seen in developed

countries, TB is still a major challenge

among inectious diseases, even in the 21st

century. Fast and accurate TB testing, such

as bacterial DNA analysis and whole-blood

intereron- assay, has been developed or

detecting latent inection. The traditional

imaging concept o primary and reactivation

TB has recently been challenged on the basis

o DNA ngerprinting, and radiologic ea-tures depend on the level o host immunity

rather than the elapsed time ater the inec-

tion. PET scans using 18F-FDG or 11C-cho-

line can sometimes help dierentiate a tu-

berculous nodule rom lung malignancy. CT

is an eective diagnostic method when chest

radiographs are normal or inconclusive, and

it provides valuable inormation or the diag-

nosis and management o TB.

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APPENDIX 1: Complications and Sequelae of Thoracic Tuberculosis

Parenchymal complications

Acute respiratory distress syndrome

Extensive lung destruction and cicatrization

Multiple cystic lung lesions

Aspergilloma

Airway complicationsBronchiectasis

Bronchiolitis obliterans

Tracheobronchial stenosis

Broncholithiasis

Vascular complications

Pulmonary and bronchial ar teritis and thrombosis

Bronchial artery pseudoaneurysm

Pulmonary artery pseudoaneurysm (Rasmussen aneurysm)

Mediastinal complications

Esophagomediastinal stula

Esophagobronchial stula

Fibrosing mediastinitisConstrictive pericarditis

Pleural complications

Pleurisy

Empyema

Fibrothorax

Pneumothorax

Bronchopleural stula

Chest wall complications

Osteomyelitis

Chondritis

Spondylitis

Empyema necessitatis

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