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Clinical manifestations and complications of pulmonary

tuberculosis
Author: Anton Pozniak, MD, FRCP
Section Editor: John Bernardo, MD
Deputy Editor: Elinor L Baron, MD, DTMH

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2020. | This topic last updated: Oct 25, 2019.

INTRODUCTION

The lungs are the major site for Mycobacterium tuberculosis primary infection and tuberculosis (TB)
disease. Clinical manifestations of TB include primary TB, reactivation TB, laryngeal TB, endobronchial
TB, lower lung field TB infection, and tuberculoma. Pulmonary complications of TB can include
hemoptysis, pneumothorax, bronchiectasis, extensive pulmonary destruction, malignancy, and chronic
pulmonary aspergillosis.

The clinical manifestations and evaluation of pulmonary TB will be reviewed here. The clinical
manifestations of pulmonary TB in children and HIV-infected patients are discussed separately, as are
the epidemiology, pathogenesis, laboratory diagnosis, and treatment of pulmonary TB. Extrapulmonary
and miliary TB are also discussed separately. (See related topics.)

CLINICAL MANIFESTATIONS

Natural history — The natural history of tuberculosis infection is described in detail separately. (See
"Tuberculosis: Natural history, microbiology, and pathogenesis", section on 'Natural history of infection'.)

After primary infection, 90 percent of individuals with intact immunity control further replication of the
bacilli, which may then be cleared or enter a "latent" phase. The person remains asymptomatic, but
latent disease has the potential to become active at any time.

The remaining 10 percent of individuals develop progressive primary disease with TB pneumonia and
expansion of infiltrates at the site of the initial seeding or near the hilum. They also may have hilar
lymphadenopathy or present with disease at more distant sites, commonly with cervical
lymphadenopathy, meningitis, pericarditis, or miliary dissemination. Progression to local pulmonary
disease or dissemination occurs more frequently in those with poor immune responses, such as in those
with HIV infection, chronic kidney failure, poorly controlled diabetes mellitus, and in those receiving
immunosuppressive medications (including transplant recipients), young children (before the age of
five), and older adults.

Individuals with latent TB have bacilli that can "reactivate" and progress to symptomatic disease.
Approximately two to three billion people in the world are latently infected with M. tuberculosis, and 5 to
15 percent of these people will suffer from reactivation of TB during their lifetime. Factors including HIV
infection, organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts, and
kidney dialysis contribute to a significantly increased TB reactivation risk.

Primary tuberculosis — Primary TB is a term that describes new TB infection or active disease in a

previously naïve host. Primary TB was considered to be mainly a disease of childhood until the
introduction of effective chemotherapy with isoniazid in the 1950s. Many studies since that time have
shown an increased frequency in the acquisition of TB in adolescents and adults [1,2].

Asymptomatic primary infection — Individuals with asymptomatic primary infection have no

symptoms or signs suggesting TB disease. Individuals at risk of new TB infection and individuals at
increased risk of reactivation warrant testing and treatment for latent tuberculosis infection, as
discussed separately. (See "Approach to diagnosis of latent tuberculosis infection (tuberculosis
screening) in adults" and "Treatment of latent tuberculosis infection in HIV-uninfected nonpregnant
adults".)

Symptomatic primary disease

Symptoms and signs — The natural history of primary TB was well described in a prospective
study of 517 new tuberculin converters living on the Faroe Islands off the coast of Norway from 1932 to
1946 [3]. The study included 331 adults and 186 children; all were followed for more than five years. The
clinical manifestations of primary TB varied substantially in this population, and symptoms and signs
referable to the lungs were present in approximately one-third of patients. Fever was the most common
symptom, occurring in 70 percent of 232 patients in whom fever was not a condition for enrollment in
the study. The fever onset was generally gradual and low grade but could be as high as 39°C (102.2°F)
and lasted for an average of 14 to 21 days. Fever resolved in 98 percent of patients by 10 weeks.

Fever was not usually accompanied by other symptoms, although approximately 25 percent of patients
developed pleuritic or retrosternal pain. One-half of patients with pleuritic chest pain had evidence of a
pleural effusion. Retrosternal and dull interscapular pain were ascribed to enlarged bronchial lymph
nodes and sometimes worsened with swallowing. Rarer symptoms included fatigue, cough, arthralgia,
and pharyngitis. (See "Tuberculous pleural effusion".)

Radiographic findings — In primary pulmonary TB, the chest radiograph is often normal.
Common radiographic changes include Hilar adenopathy, pleural effusion, and pulmonary infiltrates. In
one series including 517 patents with recent skin test conversion, chest radiograph findings were
notable for the following [3]:
 ● Hilar adenopathy was the most common finding, occurring in 65 percent of cases. Hilar changes
were visible early as one week after skin test conversion, and within two months in all cases.

● Pleural effusions developed in approximately one-third of patients, typically within the first three to
four months after infection but occasionally as late as one year.

● Pulmonary infiltrates were observed in 27 percent of patients; in general, they resolved slowly, over
months to years.

• Perihilar and right-sided infiltrates were the most common, and ipsilateral hilar enlargement
was the rule.

• Contralateral hilar changes sometimes were present; only 2 percent of patients had bilateral
infiltrates.

• Lower and upper lobe infiltrates were observed in 33 and 13 percent of patients, respectively; 43
percent of adults with infiltrates also had effusions.

• The infiltrates progressed within the first year after skin test conversion in 20 patients (15
percent of cases), reflecting progressive primary TB. The majority of these patients had
progression of disease at the original site; four developed cavitation.

Other studies that provide insight into the clinical manifestations of TB have focused retrospectively
upon patients with culture-proven TB [4-6]. In one series from Canada, 188 patients were assessed, all of
whom were culture positive and had abnormal chest radiographs [5]. Thirty patients (18 percent) were
classified clinically as having primary TB. The most common finding was hilar lymphadenopathy, present
in 67 percent. Right middle lobe collapse may complicate the adenopathy but usually resolves with
therapy.

Several factors probably favor involvement of the right middle lobe (RML). The RML bronchus is more
densely surrounded by lymph nodes, it has a relatively longer length and smaller internal caliber, and it
has a sharper branching angle.

In this retrospective series, pleural effusions were present in 33 percent and were the sole abnormality
in 23 percent of cases [5]. Pulmonary infiltrates were present in 63 percent of patients, and 85 percent of
infiltrates were in the mid- to lower lung fields. Two patients had cavitation and two others had evidence
of endobronchial spread.

Reactivation tuberculosis — Multiple terms have been used to describe reactivation TB: chronic TB,
postprimary disease, recrudescent TB, endogenous reinfection, and adult-type progressive TB.
Reactivation TB represents 90 percent of adult cases among HIV-uninfected individuals and results from
reactivation of a previous focus of mycobacterial containment that was seeded at the time of the
primary infection. The apical posterior segments of the upper lobes or the superior segment of the
lower lobe of the lung are frequently involved ( image 1). The reason for this is uncertain; relatively
poor lymphatic flow in the apices may be associated with poor organism clearance. It has also been
suggested that M. tuberculosis organisms prefer the higher oxygen tensions in the apical area of the
lungs, although TB may not be an obligate aerobe [7,8]. The original site of infection may have been
previously visible as a small scar called a Simon focus.

Symptoms

General principles — Reactivation TB may remain undiagnosed and potentially infectious for two
to three years or longer, with development of symptoms only late in the course of the disease. The
symptoms of reactivation TB have been described retrospectively, mainly in case series of hospitalized
patients in single institutions [9-11]. In these series, symptoms typically began insidiously and were
present for weeks or months before the diagnosis was made. One-half to two-thirds of patients
developed cough, weight loss, and fatigue. Fever and night sweats or night sweats alone were present in
approximately one-half. Chest pain and dyspnea each were reported in approximately one-third of
patients and hemoptysis in approximately one-quarter. Many patients had vague or nonspecific
symptoms; almost one-third of patients had pulmonary TB diagnosed after an admission for unrelated
complaints [9].

● Fever is usually low grade at onset but becomes marked with progression of disease. It is classically
diurnal, with an afebrile period early in the morning and a gradually rising temperature throughout
the day, reaching a peak in the late afternoon or evening. Fever subsides during sleep, but night
sweats may occur. Fever and night sweats are more common among patients with advanced
pulmonary TB [12].

● Cough may be absent or mild initially and may be nonproductive or productive of only scant
sputum. Initially, it may be present only in the morning, when accumulated secretions during sleep
are expectorated. As the disease progresses, cough becomes more continuous throughout the day
and productive of yellow or yellow-green and occasionally blood-streaked sputum, which is rarely
foul smelling. Symptomatic individuals are more likely to have smear-positive sputum [13]. Frank
hemoptysis, due to caseous sloughing or endobronchial erosion, typically occurs later in the disease
and is rarely massive. Nocturnal coughing is associated with advanced disease, often with
cavitation.

● Dyspnea can occur in the setting of extensive parenchymal involvement, pleural effusions, or a
pneumothorax. Pleuritic chest pain is not common but, when present, signifies inflammation
abutting or invading the pleura, with or without an effusion. Rarely, this can progress to frank
empyema.

● In the absence of treatment, patients may present with painful ulcers of the mouth, tongue, larynx,
or gastrointestinal tract due to chronic expectoration and swallowing of highly infectious secretions;
these findings are rare in the setting of antituberculous therapy.

● Anorexia, wasting (consumption), and malaise are common features of advanced disease and may
be the only presenting features in some patients.
Ambulatory patients with active TB typically have milder and less specific symptoms than hospitalized
patients. In a study including 313 TB cases identified among ambulatory patients, cough >2 weeks was
observed among 52 percent of patients with pulmonary disease; fever >2 weeks was observed among
29 percent of patients [14]. In addition, clinical symptoms were observed less frequently among patients
of Asian ethnicity than among other patients.

Other comorbidities may affect the presentation of reactivation TB; these include diabetes,
administration of tumor necrosis factor (TNF)-alpha inhibitors and advanced HIV infection. Such patients
present with more symptoms and a higher proportion of smear positivity, cavitation, treatment failure,
and non-TB deaths [15]. (See "Tumor necrosis factor-alpha inhibitors and mycobacterial infections" and
"Diagnosis of pulmonary tuberculosis in adults".)

Presentation in older adults — In nonendemic countries, the incidence of pulmonary TB is two to

three times higher among older adults, especially those in old age homes, and the risk of death is higher
compared with younger patients [16,17].

Comparative studies have suggested some differences in the manifestations of pulmonary TB between
older and younger patients. A meta-analysis including 12 studies noted no significant differences
between patients >60 years and patients <60 years with respect to time to diagnosis, prevalence of
cough, sputum production, weight loss, or fatigue/malaise [18]. Findings observed less commonly
among older adults included fever, sweats, hemoptysis, cavitary disease, and a positive tuberculin skin
test, but they were likely to present with the nonspecific symptoms of dyspnea and fatigue. Findings
observed more frequently among older adults included hypoalbuminemia, leukopenia, and underlying
disorders such as cardiovascular disease, chronic obstructive pulmonary disease (COPD), diabetes,
malignancy, and gastrectomy. Cavitary disease is less common, and multilobar and lower lobe
involvement more common. Because of comorbidities such as COPD and the nonspecificity of
symptoms, the diagnosis in older adults can be delayed or missed [19,20].

Physical findings — Physical findings of pulmonary TB are not specific and usually are absent in mild
or moderate disease. Dullness with decreased fremitus may indicate pleural thickening or effusion.
Crackles may be present throughout inspiration or may be heard only after a short cough (posttussive
crackles). When large areas of the lung are involved, signs of consolidation associated with open
bronchi, such as whispered pectoriloquy or tubular breath sounds, may be heard. Distant hollow breath
sounds over cavities are called amphoric, after the sound made by blowing across the mouth of jars
used in antiquity (amphorae). Extrapulmonary signs include clubbing and findings localized to other
sites of involvement. (See "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

Laboratory findings — The approach to diagnosis of TB is discussed separately. (See "Diagnosis of

pulmonary tuberculosis in adults".)

Routine hematology and biochemistry laboratory studies are frequently normal in the setting of
pulmonary TB. The C-reactive protein (CRP) can be elevated in up to 85 percent of patients [21]. Late in
the disease, hematologic changes may include normocytic anemia, leukocytosis, or, more rarely,
monocytosis. Hyponatremia may be associated with the syndrome of inappropriate antidiuretic
hormone secretion (SIADH) [22] or rarely with adrenal insufficiency. Hypoalbuminemia and
hypergammaglobulinemia also can occur as late findings.

Radiographic findings — Most patients with reactivation TB have abnormalities on chest

radiography, even in the absence of respiratory symptoms [9,23]. Reactivation TB typically involves the
apical-posterior segments of the upper lobes (80 to 90 percent of patients), followed in frequency by the
superior segment of the lower lobes and the anterior segment of the upper lobes ( image 1 and
image 2) [9,24-26]. In multiple large series of TB among adults, 70 to 87 percent had upper lobe
infiltrates typical of reactivation; 19 to 40 percent also had cavities, with visible air-fluid levels in as many
as 20 percent of cases [9,24-26].

Adults without upper lobe infiltrates have "atypical" radiographic patterns (13 to 30 percent of
pulmonary TB cases) [4,27,28]. These findings include hilar adenopathy (sometimes associated with right
middle lobe collapse), infiltrates or cavities in the middle or lower lung zones, pleural effusions, and
solitary nodules. These "atypical" findings are more common in the setting of primary TB and probably
represent increasing incidence of primary TB rather than "atypical" forms of reactivation TB. (See
'Primary tuberculosis' above.)

Up to 5 percent of patients with active TB present with upper lobe fibrocalcific changes thought to be
indicative of healed primary TB. However, such patients should be evaluated for active TB in the setting
of pulmonary symptoms or absence of serial films documenting stability of the lesion.

A normal chest radiograph is also possible even in active pulmonary TB. As an example, in one Canadian
study of 518 patients with culture-proven pulmonary TB, 25 patients (5 percent) had normal chest
radiographs; 23 of these patients had pulmonary symptoms at the time of the normal radiograph [29].
In this series conducted over a 10-year period, normal chest radiographs represented less than 1
percent of the radiographs in 1988 to 1989 but increased to 10 percent from 1996 to 1997.

Computed tomographic (CT) scanning is more sensitive than plain chest radiography for diagnosis,
particularly for smaller lesions located in the apex of the lung [30]. Chest CT is useful in patients with
suspected pulmonary TB and normal or nonspecific abnormalities on chest radiograph. CT scans
typically demonstrate more lesions than are visible on chest radiograph and are particularly helpful in
detecting hilar or mediastinal lymphadenopathy.

Chest CT may also demonstrate a cavity or apicoposterior infiltrates, cavities, pleural effusions, fibrotic
lesions causing distortion of lung parenchyma, elevation of fissures and hila, pleural adhesions, and
formation of traction bronchiectasis. High-resolution CT is the imaging technique of choice to detect
early bronchogenic spread. The most common findings consist of centrilobular 2 to 4 mm nodules or
branching linear lesions representing intrabronchiolar and peribronchiolar caseation necrosis [31].

Radiographic findings in the setting of pulmonary TB are discussed further separately. (See "Diagnosis of
pulmonary tuberculosis in adults".)
Other manifestations

Endobronchial tuberculosis — Endobronchial TB is defined as tuberculous disease that involves the

tracheobronchial tree. It may develop via direct extension to the bronchi from an adjacent parenchymal
focus (usually a cavity) or via spread of organisms to the bronchi via infected sputum. Lesions are more
likely to be observed in the main and upper bronchi; in 5 percent of patients, the lower trachea is
involved [32].

Prior to the availability of antituberculous therapy, endobronchial TB was relatively common in the
setting of primary infection and reactivation TB [33-36]. In a 1943 study in a TB sanatorium in West
Virginia, lesions in the tracheobronchial tree were observed in 15 percent of cases via rigid
bronchoscopy and in 40 percent of cases at autopsy [33]. Endobronchial disease was observed more
frequently among patients with extensive pulmonary TB, particularly cavitary lesions. Upper lung
parenchymal or cavitary disease with bronchogenic spread to the lower lung fields was commonly
observed, presumably from pooled infected secretions. Endobronchial TB appears to have a
preponderance in females in their second and third decades of life [3,4] and in the older adult
population (mean age 70 years) [5,37].

Since the availability of antituberculous therapy, endobronchial TB has been described in 10 to 40

percent of patients with active pulmonary TB [38,39]. Some degree of bronchial stenosis is observed in
90 percent of cases of endobronchial TB; early diagnosis and prompt treatment prior to development of
fibrosis are important to reduce the likelihood of this complication. Endobronchial disease in patients
with primary infection has also been associated with impingement of enlarged lymph nodes on the
bronchi [40-43]. Associated inflammation can lead to endobronchial ulceration or perforation. Other
complications of endobronchial TB include obstruction, atelectasis (with or without secondary infection),
bronchiectasis, and tracheal stenosis [44].

Symptoms — Symptoms include a productive cough, chest pain, hemoptysis, lethargy, fever, and
dyspnea. Symptoms may be acute in onset and be confused with bacterial pneumonia, asthma [45], or
foreign body aspiration [46]. The clinical manifestations can also be subacute or chronic, resembling
bronchogenic carcinoma [46].

A barking cough has been described in approximately two-thirds of patients with endobronchial disease,
often accompanied by sputum production [42-44,47,48]. Rarely, patients develop so-called
bronchorrhea, which is production of more than 500 mL/day of sputum [49]. In some cases, caseous
material from endobronchial lesions or calcific material from extension of calcific nodes into the bronchi
is expectorated (known as lithoptysis). Wheezing and hemoptysis may also be observed. Lymph node
rupture can be associated with chest pain. The presence of dyspnea may signal obstruction or
atelectasis.

Physical findings — Physical findings can include diminished breath sounds, rhonchi, or

wheezing. The wheeze typically is low pitched, monophonic, constant, and is auscultated consistently
over the same area on the chest wall.
 Radiographic findings — Because endobronchial lesions can exist without extensive parenchymal
abnormalities, a normal chest radiograph is observed in 10 to 20 percent of cases. In such cases, CT
scanning may demonstrate endobronchial lesions or stenosis and rarely fistulas. The most common
radiographic finding of endobronchial TB in adults is an upper lobe infiltrate and cavity with ipsilateral
spread to the lower lobe and possibly to the superior segment of the contralateral lower lobe (
image 3). Patchy, small lower lobe infiltrates may progress to confluence or even cavitation. Extensive
endobronchial TB can also be associated with bronchiectasis on CT scan.

When endobronchial TB occurs in patients with primary disease, segmental atelectasis may be the only
finding; atelectasis is more frequent in the right middle lobe and the anterior segment of the right upper
lobe.

Evaluation and approach — The diagnosis of endobronchial TB may be suspected based on the

history and physical findings and chest radiography; it can be established by bronchoscopy. Findings
may include edematous-hyperemic lesions (with or without ulceration or fibrosis) or nonspecific
bronchitis [50]. Hilar node rupture may be visible as a mass protruding into the bronchial lumen; with
perforation of the node into the bronchus, caseous or calcific material may be seen extruding into the
lumen. Bronchial stenosis also may be visible [44,51]. The tendency to develop bronchial stenosis can be
predicted from bronchoscopic appearances of the mucosa. Edematous-hyperemic, fibrostenotic, and
tumorous lesions tend to progress to eventual bronchial stenosis and/or obstruction within three
months even with appropriate antituberculous therapy.

Brushings of the lesions or lavage of the distal airways can increase the frequency of positive smears;
the yield for cultures of this material is >90 percent [32,38]. (See "Diagnosis of pulmonary tuberculosis in
adults".)

Treatment regimens for endobronchial disease are the same as for other forms of pulmonary TB. (See
"Treatment of drug-susceptible pulmonary tuberculosis in HIV-uninfected adults" and "Treatment of
pulmonary tuberculosis in adults with HIV infection: Initiation of therapy".)

Lower lung field tuberculosis — In reactivation TB, the upper lobes are the most common site of
disease. Sometimes only the lower lobes are affected; this can lead to misdiagnosis as viral or bacterial
pneumonia, bronchiectasis, or carcinoma.

Lower lung field TB refers to disease involvement below the hila (including the perihilar regions) on
chest imaging [52]. The incidence in adults is 2 to 9 percent [9,52]. Consolidation in lower lung field TB
tends to be more extensive and homogeneous than upper lobe TB [53-55]. Cavitation may occur, and
large cavities have been described. Symptoms in lower lobe TB are generally either subacute in onset
(mean of 12 weeks) or chronic (up to 6 months).

Lower lobe involvement can be a manifestation of primary TB (with involvement of adjacent lymph
nodes), reactivation TB (involving the superior segments of the lower lobes), or endobronchial TB
[53,54,56]. Endobronchial TB can affect lower lung fields in both primary infection (especially when
adjacent lymph nodes are involved) and reactivation (spread from upper lobe disease can secondarily
infect the lower lung fields).

Older adult patients and those with HIV, diabetes, renal or hepatic disease, those receiving
corticosteroids, and those with underlying silicosis appear at highest risk for lower lobe TB. However,
many patients have no underlying medical illnesses. Studies in nursing homes suggest that lower lobe
TB may be a manifestation of active TB in an older, tuberculin-negative population with significant
underlying diseases or anergy [56]. In some cases, the patients are suspected or known to have had
previous TB but develop exogenous reinfection, perhaps due to a loss of demonstrable tissue
hypersensitivity.

Tuberculoma — A pulmonary tuberculoma is a well-circumscribed nodule or a mass. Pulmonary

tuberculomas can occur in both primary and postprimary TB and have been described in 6 to 9 percent
of reactivation TB. The proposed mechanism consists of repeated extension of bronchopneumonic foci,
subsequent necrosis, and re-encapsulation. They are usually found in the upper lobes. Tuberculomas are
usually as a single nodule; multiple nodules can occur. The size ranges from <1 cm to >10 cm in
diameter. The margins are usually smooth and sharp; uncommonly, cavitation or calcification may be
observed.

In one series, including 45 patients, symptoms were present in nearly half of cases. The most frequent
symptoms were sputum, cough, general weakness, and fatigue [57]. The diagnosis of tuberculoma can
be difficult since airway cultures are often negative [55]. Fine needle aspiration or lung biopsy may be
necessary for diagnosis. (See "Diagnostic evaluation of the incidental pulmonary nodule".)

Laryngeal tuberculosis — Laryngeal TB is divided into two forms based upon its pathogenesis:
primary disease, which develops via direct invasion of bacilli into the larynx, and secondary disease,
which develops via bronchogenic spread from advanced pulmonary TB or via hematogenous or
lymphatic spread [58]. The most common sites of involvement include the true vocal cords, epiglottis,
and false vocal cords. On laryngoscopy, areas of hyperemia, nodules, ulcerations, or exophytic masses
can be seen.

In one series including 127 US cases between 1970 and 2012, the mean duration of symptoms was 19
weeks (range 1 to 104 weeks) and mean age was 40.5 years [59]. The most common symptoms were
dysphonia (96 percent), weight loss (46 percent), cough (38 percent), dysphagia (26 percent),
odynophagia (25 percent), and stridor (9 percent). Radiographic evidence of pulmonary TB was reported
in 86 percent of cases; however, laryngeal TB can occur in the absence of pulmonary disease.

In another series including 36 Brazilian patients with laryngeal TB, the main presenting symptoms were
dysphagia and cough; the true vocal folds the most frequently affected site [60]. Smoking was
associated with the development of more extensive lesions.

Laryngeal TB may be complicated by vocal cord paralysis. This can occur as a result of enlarged
mediastinal lymph nodes compressing the recurrent laryngeal nerve along the intrathoracic
course/aortopulmonary window or via stretching or entrapment of the recurrent laryngeal nerve due to
mediastinal or lung fibrosis [61].

Prior to the availability of antituberculous therapy, laryngeal TB was considered a terminal condition, as
it usually occurred during progression of pulmonary disease, developing soon before death. Since the
availability of antituberculous therapy, laryngeal TB has become relatively rare (<1 percent of United
States TB cases).

HIV-infected patients

Clinical manifestations

General principles — The clinical manifestations of TB in HIV-infected patients are influenced by

the degree of immunosuppression [62,63]. Early in the course of HIV disease, the clinical presentation of
TB is similar to that of HIV-uninfected patients; symptoms include fever, cough, weight loss, fatigue, loss
of appetite, night sweats, and hemoptysis.

As immunity declines, the frequency of pulmonary cavitation and hemoptysis also declines [62,63]. HIV-
infected patients with advanced immunosuppression are at increased risk of extrapulmonary TB and
disseminated TB [64-69]. Virtually any site can be involved; the most common presentations are
lymphadenitis and pleural involvement [63,64,69-73]. Septicemic-like illness with hypotension can occur,
with high mortality rate unless diagnosed and treated rapidly. In contrast, active TB may be subclinical in
some patients with advanced immunosuppression, with no symptoms and a normal chest radiograph
[74]. (See "Tuberculous lymphadenitis" and "Tuberculous pleural effusion".)

Effect of antiretroviral therapy — In patients who develop active TB while on antiretroviral

therapy (ART), the clinical presentation depends on the level of immunosuppression. In one study from
South Africa, the World Health Organization symptom screen (presence of any: active cough of any
duration, fever, night sweats, or weight loss) had lower sensitivity among patients on ART than among
patients not on ART (24 vs 47 percent), but higher specificity (94 vs 80 percent) [75].

Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory disorder that can occur in
association with initiation of ART in some HIV-infected individuals; it is typically associated with
paradoxical worsening of pre-existing infectious processes, including TB. Issues related to IRIS are
discussed separately. (See "Immune reconstitution inflammatory syndrome", section on 'Tuberculosis'.)

Radiographic findings — Early in the course of HIV disease, radiographic findings of TB are similar to
that of HIV-uninfected patients, as described in the preceding sections. (See 'Radiographic findings'
above and 'Radiographic findings' above.)

As immunity declines (eg, in patients not treated with antiretroviral therapy), radiographic findings are
more likely to be atypical, including noncavitary pulmonary infiltrates with no particular preference for
the upper lung fields ( image 4 and image 5) [62,63]. HIV-infected patients with CD4 count <200
cells/mm3 are more likely to have mediastinal or hilar lymphadenopathy and extrapulmonary
involvement and are less likely to have cavitation (compared with HIV-infected patients with CD4 count
≥200 cells/mm3). Miliary or disseminated disease has also been associated with severe
immunosuppression [76].

In one study including 133 patients with HIV/AIDS and TB in New York City prior to the availability of
antiretroviral therapy, chest radiograph findings were as follows [62]:

● Pattern typical for primary TB: 36 percent. These findings included pleural effusion, intrathoracic
lymphadenopathy (mediastinum and hilum), or middle or lower lobe consolidation without
cavitation.

● Pattern compatible with reactivation TB: 29 percent. These findings included apical/posterior
consolidation of the upper lobes or consolidation of the superior segments of the lower lobes
(without adenopathy or effusion), endobronchial spread (acinar or 3 to 4 mm shadows, remote from
a cavity or upper lobe consolidation), or bronchiectasis.

● Miliary pattern: 4 percent.

● Atypical findings for TB, such as diffuse infiltrates: 13 percent.

● Minimal changes: 5 percent.

● Normal chest radiographs: 14 percent.

Most patients with CD4 count ≥200 cells/mm3 had typical patterns of reactivation disease (ie, cavitation
and upper lobe infiltrates), while patients with CD4 count <200 cells/mm3 were nearly as likely to have
normal chest radiographs as they were to have patterns of reactivation disease (21 versus 23 percent). A
number of other studies have also reported that normal chest radiographs are common in patients with
CD4 counts <200 cells/mm3 [64,77-80].

Similarly, in a study from South India including 200 HIV-infected patients with CD4 <200 cells/mm3,
noncavitary infiltration and consolidation was the predominant finding [81]. Radiographic findings
consisted of diffuse or mid and lower lung zone involvement, rather than classic upper lobe
involvement. With restoration of cellular immunity on antiretroviral therapy, radiographic findings are
more likely to resemble those in patients with CD4 counts >200 cells/mm3.

Chest CT is useful in patients with suspected pulmonary TB and normal or nonspecific abnormalities on
chest radiograph. Even if there is no parenchymal disease, lymphadenopathy or pleural effusions may
be observed.

COMPLICATIONS

Pulmonary complications of TB include hemoptysis, pneumothorax, bronchiectasis, extensive pulmonary

destruction (including pulmonary gangrene), fistula, tracheobronchial stenosis, malignancy, and chronic
pulmonary aspergillosis. These complications occur more commonly in the setting of reactivation
disease.
Tuberculous effusions and empyema are discussed separately (See "Tuberculous pleural effusion".).

Hemoptysis — Hemoptysis occurs most frequently in the setting of active TB but may also occur after
completion of treatment [82-84]. Many patients with hemoptysis are acid-fast bacilli (AFB) smear positive
and usually have cavitary disease. Bleeding usually is of small volume, appearing as blood-streaked
sputum. Massive hemoptysis is a rare complication since the advent of chemotherapy. Prior to effective
chemotherapy, massive hemoptysis accounted for approximately 5 percent of deaths from TB.

Sources of massive hemoptysis due to TB include the pulmonary artery, bronchial arteries, intercostal
arteries, and other vessels supplying the lung. Tuberculous vascular lesions include pulmonary or
bronchial arteritis and thrombosis, bronchial artery dilatation, and Rasmussen aneurysm. "Rasmussen's
aneurysm" is a relatively uncommon cause of hemoptysis; it refers to the formation of an aneurysm in
the setting of cavitary infection that extends into the adventitia and media of bronchial arteries,
resulting in inflammation and thinning of the vessel wall [85,86]. This aneurysm subsequently ruptures
into the cavity, producing massive hemoptysis.

Hemoptysis after the completion of therapy for TB only occasionally represents TB recurrence. Other
causes include residual bronchiectasis, an aspergilloma or other fungus ball invading or colonizing an
old healed cavity, a ruptured broncholith that erodes through a bronchial artery, a carcinoma, or another
infectious or inflammatory process.

Patients with significant hemoptysis should be evaluated promptly to define the source of bleeding and
to facilitate immediate intervention. Apart from impending exsanguination (which requires immediate
surgical care), bronchial artery embolization is the preferred management approach if feasible [87,88].
In one study including 140 patients with TB and massive hemoptysis (more than 300 mL of blood in 24
hours) who underwent bronchial artery embolization, nearly complete control of hemoptysis was
achieved in 73 percent of cases [87]. In the absence of access to appropriate facilities for bronchial artery
embolization, other treatments includes bed rest, postural management, volume replacement, cough
suppression, and intravenous vasopressin [89]. (See "Evaluation and management of life-threatening
hemoptysis".)

If embolization and medical management fail, surgical options include ligation of arteries, resection of a
lung lobe, and endobronchial tamponade. Both ligation and embolization can be complex because of
the frequent presence of multiple feeder arteries often connecting systemic with bronchial circulation
[90]. Older studies suggest that after an episode of massive hemoptysis or repeated episodes of severe
hemoptysis, surgical intervention improves survival [91-93] and should be considered if embolization
fails.

Pneumothorax — Prior to the availability of antituberculous therapy, spontaneous pneumothorax was a

frequent and dangerous complication of pulmonary TB [94]. Since the availability of antituberculous
therapy, spontaneous pneumothorax associated with TB has been reported in about 1 percent of
hospitalized patients [95-97]. A case series from Turkey reported pneumothorax in 1.5 percent of cases
of pulmonary TB [97]. In regions where TB is endemic, it may be the most common cause of
spontaneous pneumothorax [98].

Pneumothorax appears to result from the rupture of a peripheral cavity or a subpleural caseous focus
with liquefaction into the pleural space [95,96]. Inflammation can lead to development of a
bronchopleural fistula, which can persist or seal off spontaneously. The lung may reexpand if the
bronchopleural fistula seals spontaneously, but more commonly chest tube drainage is required.

Factors preventing successful chest tube drainage and expansion include extensive pulmonary
parenchymal disease with large fistulas, a long interval between pneumothorax and chest tube
insertion, and the development of an empyema due to TB and/or bacterial superinfection. However,
successful closure of even extensive air leaks has been reported after as much as six weeks of chest tube
drainage accompanied by appropriate antituberculous chemotherapy [99]. (See "Treatment of secondary
spontaneous pneumothorax in adults".)

Bronchiectasis — Bronchiectasis may develop following primary or reactivation TB and can be

associated with hemoptysis [100-105]. (See "Clinical manifestations and diagnosis of bronchiectasis in
adults".)

Following primary TB infection, extrinsic compression of a bronchus by enlarged nodes may cause
bronchial dilation distal to the obstruction. There may be no evidence of parenchymal TB.

In the setting of reactivation TB, progressive destruction and fibrosis of lung parenchyma may lead to
localized bronchial dilation. If endobronchial disease is present, bronchial stenosis may result in distal
bronchiectasis. Bronchiectasis is more frequent in the common sites of reactivation TB (apical and
posterior segments of the upper lobe) but may be found in other areas of the lung.

Broncholithiasis — Broncholithiasis is defined as the presence of calcified or ossified material within

the lumen of the tracheobronchial tree; it is an uncommon complication of pulmonary TB. The calcific
nidus in a tuberculous lymph node erodes into the bronchial wall and may occlude the bronchus [33].
Presenting symptoms may include cough, hemoptysis, wheezing, or evidence of recurrent pneumonia
[106].

Extensive pulmonary destruction — Rarely, untreated or inadequately treated TB can cause

progressive, extensive destruction of areas of one or both lungs [107,108]. In primary TB, occasionally
lymph node obstruction of the bronchi together with distal collapse, necrosis, and bacterial
superinfection can produce parenchymal destruction [108]. More commonly, destruction results from
chronic reactivation TB, typically in the absence of effective chemotherapy. Symptoms include
progressive dyspnea, hemoptysis, and weight loss.

Pulmonary gangrene refers to acute pulmonary destruction which occurs as a rare complication of
severe pulmonary infection. It has been described most frequently in the setting of pulmonary infection
due to Klebsiella pneumonia or Streptococcus pneumonia; pulmonary gangrene due to TB has also been
described [109,110]. Pulmonary gangrene occurs as a consequence of arteritis and thrombosis of distal
pulmonary vessels, leading to an inflammatory pyogenic process and massive necrosis of lung
parenchyma.

This form of TB progresses rapidly from a homogeneous, extensive infiltrate to dense consolidation. Air-
filled cysts develop and coalesce into cavities. Necrotic lung tissue attached to the wall of the cavity may
be observed. Pulmonary gangrene may resemble an intracavitary clot, fungus ball, or Rasmussen's
aneurysm. The presence of a mobile mass that contains pulmonary tissue within a pulmonary cavity is
characteristic on computed tomography scanning.

Resolution with effective antimicrobial therapy has been described [110]. In many cases, urgent surgical
intervention is needed because of life-threatening complications such as acute respiratory failure and
shock that persist despite appropriate antimicrobial therapy [110].

Mortality usually is high; in one series including four patients, three died [109]. In another series
including 18 patients with extensive destruction of one or both lungs, eight died [107]. Causes of death
were massive hemoptysis and respiratory failure, sometimes in the presence of active TB or
superinfection. Radiographically, patients had large cavities and fibrosis of remaining lung; in some
cases, air-fluid levels at the base of the destroyed lung were observed [107,108].

Septic shock — TB can cause septic shock; the manifestations are similar to bacterial septic shock.
Compared with patients with septic shock due to other pathogens, patients with septic shock due to TB
have lower mean body mass indices (22 versus 27), lower mean white blood counts (10.4 versus 16.2),
and are more often HIV infected (15 versus 3 percent) [111]. The probability of survival in patients with
M. tuberculosis septic shock is extremely poor, with an in hospital mortality rate of 79 percent; delayed
initiation of appropriate therapy likely played an important role in clinical outcome [111].
Extrapulmonary disease may be observed in more than 50 percent of cases. (See "Sepsis syndromes in
adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis".)

Malignancy — A study conducted by the National Cancer Institute found that pulmonary TB was
associated with an increased risk of lung cancer, after adjustment for active smoking and socioeconomic
status (odds ratio 2.1, 95% CI 1.4-3.1) [112]. Similarly, in a meta-analysis from China, TB was associated
with a 1.78-fold increase in the risk of lung cancer among nonsmokers and an association with
adenocarcinoma (relative risk 1.6; 95% CI 1.2-2.1) [113].

TB is thought to increase lung cancer risk via chronic pulmonary inflammation and fibrosis, but no
causal relationship has been established. TB infection may cause a profound and extended host immune
response, with inflammatory cells in the lung producing extensive cytokine signaling cascades, reactive
nitrogen and oxygen species, prostaglandins, and tissue-destructive proteases. Mycobacterial cell wall
components may induce production of nitric oxide and reactive oxygen species, which have been
implicated in DNA damage leading to carcinogenesis [114]. Chronic inflammation may also enhance
mutagenesis. In addition, immunosuppression and radiation therapy administered for treatment of lung
cancer may be associated with an increased risk of TB.
Venous thromboembolism — TB, both pulmonary and extrapulmonary, has been suggested as an
independent risk factor for venous thromboembolism (VTE), perhaps due to a hypercoagulable state. In
one retrospective study including 3485 cases of active TB, the prevalence of VTE was approximately 2
percent [115], which is similar to the rate associated with malignancy and approximately 100 times
higher than the incidence of VTE among hospitalized patients in general [116]. The clinical approach to
VTE is discussed further separately. (See "Overview of acute pulmonary embolism in adults".)

Chronic pulmonary aspergillosis — Chronic pulmonary aspergillosis can be a sequela of pulmonary TB,

especially in those with cavitary disease. This is discussed further separately. (See "Clinical
manifestations and diagnosis of chronic pulmonary aspergillosis", section on 'Underlying diseases'.)

DIFFERENTIAL DIAGNOSIS

The following conditions can cause cavitary pulmonary lesions and symptoms suggestive of TB including
fever, cough, and weight loss:

● Nontuberculous mycobacterial infection (NTM) – Symptoms of NTM include fatigue, dyspnea, and
occasional hemoptysis; fever and weight loss occur less frequently than in patients with TB. Clinical
features of Mycobacterium kansasii are often very similar to those of TB. NTM is distinguished from
TB by culture results and/or molecular diagnostic testing. (See "Overview of nontuberculous
mycobacterial infections".)

● Fungal infection – Fungal pneumonia can present with a range of manifestations including
pneumonia, pulmonary nodule, and cavitary lung disease. It is distinguished from TB by
epidemiologic exposure and culture results. (See "Diagnosis and treatment of pulmonary
histoplasmosis" and "Diagnosis of invasive aspergillosis" and "Mucormycosis (zygomycosis)" and
"Clinical manifestations and diagnosis of blastomycosis" and "Epidemiology, clinical manifestations,
and diagnosis of Cryptococcus neoformans meningoencephalitis in patients with HIV".)

● Sarcoidosis – Sarcoidosis most commonly presents with diffuse interstitial lung disease. It rarely
forms cavities and is distinguished from TB by histopathologic detection of noncaseating
granulomas. (See "Clinical manifestations and diagnosis of pulmonary sarcoidosis".)

● Lung abscess – Lung abscess generally presents with fever, cough, and sputum production but
without shaking chills or true rigors. Chest imaging usually shows infiltrates with a cavity. The
diagnosis is established based on culture results. (See "Lung abscess".)

● Septic emboli – Septic emboli to the lung from an extrapulmonary nidus are distinguished from TB
by blood culture results and echocardiography. (See "Complications and outcome of infective
endocarditis", section on 'Septic embolization'.)

● Lung cancer – Lung cancer most commonly presents with cough, hemoptysis, chest pain, and
dyspnea. It is distinguished from TB by histopathology. (See "Overview of the risk factors, pathology,
 and clinical manifestations of lung cancer".)

● Lymphoma – Lymphoma typically presents with a rapidly growing mass together with fever, night
sweats, and weight loss. It is distinguished from TB by histopathology. (See related topics.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the
world are provided separately. (See "Society guideline links: Hemoptysis".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and “Beyond the Basics.” The
Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are
written at the 10th to 12th grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Tuberculosis (The Basics)")

● Beyond the Basics topic (see "Patient education: Tuberculosis (Beyond the Basics)")

SUMMARY

● Clinical manifestations of pulmonary tuberculosis (TB) include primary TB, reactivation TB,
endobronchial TB, lower lung field TB, and tuberculoma. (See 'Introduction' above.)

● Among patients with primary TB, clinical manifestations have been observed in approximately one-
third of cases. Symptoms include fever and chest pain. Retrosternal pain and dull interscapular pain
have been ascribed to enlarged bronchial lymph nodes. The physical exam is generally normal. The
most common chest radiograph abnormality in one large series was hilar adenopathy. Other
manifestations include pleural effusions and pulmonary infiltrates. (See 'Primary tuberculosis'
above.)

● Reactivation TB refers to reactivation of a previously dormant focus seeded at the time of the
primary infection. The apical posterior segments of the lung are frequently involved ( image 1).
 Typically, symptoms are insidious and may include cough, weight loss, fatigue, fever, night sweats,
chest pain, dyspnea, and/or hemoptysis; these findings are observed less frequently among patients
>60 years. (See 'Reactivation tuberculosis' above.)

● Endobronchial TB may develop via direct extension to the bronchi from an adjacent parenchymal
focus (usually a cavity) or via spread of organisms to the bronchi via infected sputum. It can occur in
patients with primary TB or reactivation TB and was observed more frequently prior to the
antituberculous therapy era. Symptoms may be acute or chronic; a barking cough has been
described in approximately two-thirds of patients. (See 'Endobronchial tuberculosis' above.)

● Pulmonary complications of TB include hemoptysis, pneumothorax, bronchiectasis, extensive

pulmonary destruction (including pulmonary gangrene), malignancy, venous thromboembolism,
and chronic pulmonary aspergillosis. (See 'Complications' above.)

● The differential diagnosis for pulmonary TB is broad and includes other causes of chronic infection,
inflammatory diseases, and malignancy. (See 'Differential diagnosis' above.)

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Topic 7026 Version 30.0
GRAPHICS

Chest radiographs of tuberculosis

Chest radiographs (posteroanterior and lateral views) demonstrating cavitary reactivation of latent
tuberculosis infection in the posterior apical segment of the right upper lobe.

Reproduced with permission from: Crapo JD, Glassroth J, Karlinsky JB, King TE. Baum's Textbook of Pulmonary
Diseases, 7th Edition. Philadelphia: Lippincott Williams & Wilkins, 2004. Copyright © 2004 Lippincott Williams &
Wilkins.

Graphic 54832 Version 3.0

Chest radiographs of different presentations of tuberculosis

(A) Primary tuberculosis in a child (note the right-sided hilar adenopathy, right-sided lower lobe
infiltrates, and volume loss).
(B) Lower lung field tuberculosis infiltration and cavity with air-fluid level in lingula.
(C) Reactivated tuberculosis, far-advanced disease with bronchogenic spread.
(D) Miliary tuberculosis.

Reproduced with permission from: Gorbach SL, Bartlett JG, et al. Infectious Diseases. Philadelphia: Lippincott Williams
& Wilkins, 2004. Copyright © 2004 Lippincott Williams & Wilkins.

Graphic 62501 Version 3.0

Imaging of cavitary lesions in tuberculosis

Chest radiograph (A) and computed tomography (CT) scan (B), the latter of which more clearly
demonstrates two cavitary lesions. A repeated CT scan (C) showed improvement after one month
of treatment in a young woman with primary multidrug-resistant tuberculosis.

Reproduced with permission from: Gorbach SL, Bartlett JG, et al. Infectious Diseases. Philadelphia: Lippincott
Williams & Wilkins, 2004. Copyright © 2004 Lippincott Williams & Wilkins.

Graphic 76337 Version 3.0

Chest radiograph - Tuberculosis and HIV

Chest radiograph showing asymmetric hilar and mediastinal adenopathy and non-
confluent opacification left mid and lower zones. Typical appearance of tuberculosis in
patients with CD4 counts <200 cells/microL.

HIV: human immunodeficiency virus.

Courtesy of Gary Maartens, MBChB, MMed.

Graphic 79587 Version 6.0

Pulmonary tuberculosis in a man with AIDS (CD4 count 4 cells/mm 3)

(A) Posteroanterior chest radiograph shows multifocal mass-like airspace consolidation in bilateral upper lung zones. (B and C) High-resolution
computed tomography scans (1.0-mm section thickness) obtained at levels of left innominate vein (B) and azygos arch (C) show mass-like
airspace consolidation with air bronchograms, centrilobular small nodules (arrows) (C), and ground-glass opacity in both upper lobes.

Reprinted with permission from the American Journal of Roentgenology. Jeong YJ, Lee KS. Pulmonary tuberculosis: Up-to-date imaging and management. Am J
Roentgenol 2008; 191:834. Copyright © 2008 American Roentgen Ray Society.

Graphic 116255 Version 1.0

Contributor Disclosures
Anton Pozniak, MD, FRCP Consultant/Advisory Boards: Cepheid [Sexually transmitted infections]. John Bernardo,
MD Nothing to disclose Elinor L Baron, MD, DTMH Nothing to disclose

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