Background: Tuberculosis is an infectious disease that has been known for centuries. Traditionally, the term tuberculosis has been used to indicate infections caused by Mycobacterium tuberculosis and Mycobacterium bovis; however, a multitude of mycobacteria are recognized.

Tuberculosis may involve multiple organs such as the lung, liver, spleen, kidney, brain, and bone. In endemic regions, the normal host immune response may be sufficient to contain the infection and prevent clinical presentation. Uncontrolled or uncontained infection may result in great morbidity and mortality.

Pathophysiology: Mycobacteria are non–spore-forming bacilli that are obligate aerobes. They are recognized microscopically by an intense staining with aniline dyes (notably carbol-fuchsin) and resistance to decoloration with acid washing; therefore, the term acid-fast bacilli is used to describe them. Unlike other bacteria, mycobacteria require enriched culture media and extended incubation (usually 2-8 wk). Therefore, bacteriologic recognition of a mycobacterial infection is a protracted process that may delay appropriate medical therapy. The advent of polymerase chain reaction (PCR) techniques has increased the rapidity with which tuberculous infection is diagnosed.

Tuberculous infection occurs as a consequence of the inhalation of bacillus-laden droplets expelled from an infected host. Given the stringent growth requirements of the organism, the development of an infection depends on prolonged exposure (on the order of weeks) to an individual with active pulmonary tuberculosis. Once the organism is inhaled, it travels via the airways to the pulmonary parenchyma where it is deposited. Although the organism may be deposited in any lobe, a predilection for the lower lobes exists.

The organism is ingested by alveolar macrophages, which then attempt to phagocytize the bacilli. As a result of the natural defenses of the tubercle bacillus, alveolar macrophages may be unsuccessful in attempting to completely destroy the bacilli, which then lie dormant within the macrophage. As a consequence, bacilli often remain viable within the macrophages in immunocompetent individuals. Subsequently, bacilli may travel via the pulmonary lymphatics, or they may enter the vascular system and seed distant sites such as the liver, spleen, or bone marrow.

In most immunocompetent individuals, macrophages are successful in containing the bacilli, and the infection is self-limited and often subclinical. The contained infection in immunocompetent hosts is called primary tuberculosis. Primary tuberculosis is seen most often in children in endemic regions. Since the advent of the AIDS era, adults may present with radiographic findings similar to those of primary tuberculosis.

In some patients, pulmonary macrophages are unable to contain the bacilli and are overwhelmed, leading to a clinically apparent infection. This is more common in patients who are immunocompromised, notably the population with HIV/AIDS. This form of tuberculosis is called progressive primary tuberculosis. Patients with progressive primary tuberculosis may present with pulmonary manifestations (often with miliary tuberculosis) or with manifestations of systemic or disseminated disease.

Postprimary (reactivation) tuberculosis is seen in patients in whom the initial infection was contained successfully by the pulmonary macrophages, with bacilli remaining viable within the macrophages. Infection results when the host's immune status (T cells) is compromised. This form may appear in the elderly population, for example.

Frequency:

• In the US: The incidence of tuberculosis markedly declined in the United States from the 1950s to the 1980s, largely as a result of improvements in public health programs, the development of effective chemotherapeutic agents, and improved living conditions. Subsequently, the incidence increased in 1985-1992, with an overall incidence of 10.5 cases per 100,000 population in 1992. The change has been attributed to the emergence of the HIV/AIDS epidemic during this decade. The incidence of tuberculosis again declined in the 1990s, with an incidence of 6.8 cases per 100,000 population in 1998.

• Internationally: In 1997, the World Health Organization conducted a study to determine worldwide incidence and prevalence of tuberculosis. The total number of new cases in 1997 was estimated to be 7.96 million. This figure includes an estimated 3.52 million cases of infectious pulmonary tuberculosis. The death rate attributed to tuberculosis in 1997 was approximately 1.87 million.

Mortality/Morbidity: In immunocompetent patients in endemic regions, the primary infection is contained, and the patients remain asymptomatic. In some patients with relative immune compromise, primary infection may lead to fulminant pulmonary infection, with pulmonary necrosis leading to death. This is called progressive primary tuberculosis. Pulmonary manifestations of progressive pulmonary tuberculosis may be radiographically indistinguishable from manifestations of postprimary tuberculosis.

Postprimary tuberculosis is a significant cause of worldwide morbidity and mortality. Morbidity may result in any affected organ system. Pulmonary morbidity may result from a chronic cough, hemoptysis (which may be fatal), fibrosis, superinfection (eg, mycetoma), bronchial stenosis, repeated pulmonary infections from tuberculous bronchiectasis, or empyema. Significant morbidity also may arise from chronic tuberculous osteomyelitis, chronic renal insufficiency, or neurologic changes related to central nervous system (CNS) tuberculosis.

Race: Tuberculosis is a worldwide infection. Endemic areas include India, Southeast Asia, and sub-Saharan Africa.

Sex: No sex predilection exists for tuberculosis.

Age: Infection may occur at any age and is most significant at the extremes of age. Primary tuberculosis is usually seen in young children in endemic regions. The incidence is increasing in individuals in nonendemic regions who are immunocompromised.

Anatomy: Tuberculosis is transmitted via the spread of bacilli in aerosolized droplets. Infected droplets pass from the nasopharynx into the tracheobronchial tree and continue to the lung. As a result of gravity, droplets tend to be deposited in the lower lobes; therefore, primary tuberculosis is more common in the lower lobes. The oxygen tension is higher in the upper lobes, where reactivation tuberculosis usually occurs.

The intrapulmonary lymphatics and blood vessels play an important role in the manifestations of tuberculosis. The lymphatics and vasculature lie within the interstitium of the lung, and they drain (veins and lymphatics) and supply (arteries) the adjacent region of lung. This anatomy accounts for ipsilateral lymphadenopathy because infected lymph is drained along the interstitium to the hilar and mediastinal lymph nodes. Venous drainage allows hematogenous dissemination of the infection.

Clinical Details: Primary tuberculosis is usually a self-limited infection seen in children in endemic regions. As many as 60% of children and 5% of adults with primary tuberculosis are asymptomatic. Patients with primary pulmonary tuberculosis may be minimally symptomatic, with minimal constitutional symptoms. Children may present with fever, malaise, weight loss, cough, and occasional hemoptysis.

Progressive primary tuberculosis occurs in the setting of acute infection in patients with minimal or marked immune compromise. Patients with progressive primary tuberculosis become acutely ill, and they may have extensive lung parenchymal opacities and cavitation. Hypoxia and death may occur.

Patients with postprimary tuberculosis often manifest disease within 2 years of the initial infection or many years later, often as a result of comorbid states: old age, malnutrition, and/or neoplasm. These patients experience indolent clinical symptoms that include lethargy, anorexia, weight loss, low-grade fever, cough, hoarseness, and hemoptysis.

Preferred Examination: Diagnosis is based on a combination of tuberculin skin testing (purified protein derivative testing), sputum cultures, and radiography. Bronchoscopy may be required to obtain specimens.

Patients with primary tuberculosis may not undergo imaging; however, if imaging is performed, a conventional chest radiograph may be sufficient for diagnosis in the appropriate clinical setting.

In patients with progressive primary or postprimary tuberculosis, computed tomography (CT) is often performed, in addition to chest radiography. Magnetic resonance imaging (MRI) may be used to evaluate complications of thoracic disease. Patients with postprimary tuberculosis may also undergo bronchoscopy to evaluate endobronchial disease and to obtain sputum specimens for microbacteriologic cultures.

Limitations of Techniques: With the purified protein derivative skin test, false-positive results may be seen in individuals who have been inoculated with bacillus Calmette-Guérin vaccine. False-negative results may occur in patients who are anergic, such as patients with HIV infection and decreased CD4 counts. These patients require an anergy panel.

As a result of the stringent growth requirements of the bacillus, culturing of the organisms is often a lengthy and difficult process. False-negative results may be seen if insufficient organisms are present in the specimen.

Conventional radiography is limited in its sensitivity and specificity. As many as 15% of patients with primary tuberculosis have normal chest radiographic findings. Clinical suspicion must remain high for prompt diagnosis in these individuals. Chest radiographic results are not specific for tuberculosis, and other entities must remain in the differential diagnosis.

DIFFERENTIALS

Aspergillosis, Thoracic
Aspiration Pneumonia
Atelectasis, Lobar
Bronchiectasis
Histoplasmosis, Thoracic
Hodgkin Disease, Thoracic
Lung, Metastases
Lung, Nontuberculous Mycobacterial Infections
Non-Hodgkin Lymphoma, Thoracic
Pneumonia, Atypical Bacterial
Pneumonia, Typical Bacterial
Pneumonia, Viral
Sarcoidosis, Thoracic
Solitary Pulmonary Nodule
Trachea, Stenosis

X-RAY

Findings:

Primary tuberculosis

Pulmonary imaging findings in individuals with primary tuberculosis are nonspecific.

• Common findings include segmental or lobar airspace consolidation, ipsilateral hilar and mediastinal lymphadenopathy, and/or pleural effusion.

   

• Atelectasis may occur in primary pulmonary tuberculosis, often as a consequence of tuberculous airway involvement.

   

• Note that chest radiographic findings may be normal in as many as 15% of patients with primary pulmonary tuberculosis.

   

• Parenchymal consolidation may be observed.

   

  • Although consolidation may occur in any segment or lobe or in multiple segments or lobes, the disease has a predilection for the lower lobes, for the middle lobe and lingula, and for the anterior segments of the upper lobes.

     

  • Airspace consolidation tends to be homogeneous, with ill-defined margins. If the consolidation abuts a fissure, a well-defined margin may be identified.

     

  • Cavitation within parenchymal opacity is distinctly uncommon in primary infection. As the host immune response continues, healing begins.

     

  • Caseous necrosis occurs centrally within the lung parenchymal opacity, decreasing its size.

     

  • The lung opacity tends to become rounded with healing, and it continues to shrink until only a small nodule remains. Subsequently, the nodule may become calcified or ossified, resulting in a calcified granuloma. Note that although a granuloma may calcify, this does not necessarily reflect an absence of bacilli. The organisms may remain quiescent within this nodule, serving as a possible source for reactivated of disease.

   

• Lymphadenopathy is a common manifestation of primary pulmonary tuberculosis.

   

  • The presence of hilar and mediastinal lymphadenopathy may distinguish primary from postprimary tuberculosis, because lymphadenopathy is conspicuously absent in postprimary tuberculosis.

     

  • Lymphadenopathy without a parenchymal opacity may occur as the only manifestation of primary pulmonary tuberculosis. Most commonly, this is seen in the population with HIV infection.

     

  • As expected, adenopathy is most common in the ipsilateral hilar region. Hilar lymphadenopathy is seen in approximately 60% of children with primary tuberculosis, paratracheal adenopathy is seen in 40%, and subcarinal lymphadenopathy is seen in 80%.

     

  • In adults, lymphadenopathy is unusual in an immunocompetent host but it does occur, particularly in blacks and Asians. In adults with HIV infection, adenopathy is common.

     

  • The pattern of lymphadenopathy is indistinguishable from that of sarcoid or lymphoma.

     

  • Lymphadenopathy may be symptomatic if it secondarily involves the airways.

     

  • With an appropriate immune response or with adequate chemotherapy, enlarged necrotic lymph nodes may diminish in size and commonly calcify. The presence of calcified lymph node and a granuloma represents the Ranke complex.

   

• Airway involvement is frequently present in primary tuberculosis.

   

  • The airway may be involved in one of the following ways:

     

    • Airway compression by adjacent lymphadenopathy with resultant atelectasis

       

    • Mucosal infection with resultant ulceration and long-term stricture formation

       

    • Broncholithiasis, ie, extrinsic erosion of a bronchus by adjacent lymphadenopathy with extrusion of calcified material into the bronchus

       

    • Endobronchial spread of infection

       

    • Bronchiectasis

     

  • Atelectasis is most notable within the anterior segments of the upper lobes and the medial segment of the middle lobe. Atelectasis may resolve as lymphadenopathy regresses with host response. A sudden resolution of atelectasis may represent perforation of an infected lymph node into the airway, which relieves the bronchial obstruction.

     

  • A possible long-term sequela of infection is tracheobronchial stenosis. The airways may be involved by tuberculosis in a variety of ways, including direct mucosal involvement from infected sputum, direct extension from perforating lymphadenopathy or adjacent parenchymal infection, and hematogenous or lymphatic drainage.

     

  • The endobronchial spread of infection may be seen with tuberculous tracheobronchial disease. Bacilli from the infected airways disseminate into more distal bronchi and bronchioles and subsequently enter the alveoli, where they become deposited. The resultant radiographic appearance is one of small ill-defined acinar shadows and small nodules.

     

  • Endobronchial tuberculosis may lead to bronchiectasis, either from bronchial stenosis or secondary to traction from fibrosis. Bronchiectasis is more frequently seen in postprimary tuberculosis (see Postprimary tuberculosis below).

   

• Pleural involvement is uncommon in children with primary tuberculosis, occurring in approximately 10% of children. Pleural involvement is seen more frequently in adults with primary pulmonary tuberculosis, and it is even more frequently identified in postprimary tuberculosis.

Postprimary tuberculosis

The findings of reactivation tuberculosis typically become radiographically apparent within 2 years of the initial infection. Pleural effusions develop if the infection remains untreated. Tuberculous empyema is a much less common finding.

• Postprimary tuberculosis may have any of a number of parenchymal manifestations including the following:

   

  • Patchy or confluent airspace opacities are opacities that involve the apical and posterior segments of the upper lobes and the superior segments of the lower lobes.

     

  • In postprimary tuberculosis, cavitary disease is secondary to caseous necrosis within the opacity. The debris from the lesion is expelled via the tracheobronchial tree with which the cavity is in communication. The cavities, similar to airspace opacities in reactivation tuberculosis are commonly within the upper lung zones. The cavities demonstrate a thick outer wall with a smooth inner contour. Air-fluid levels may be present. Superinfection by Aspergillus organisms may occur, leading to a mycetoma.

     

  • Tuberculomas are rounded discrete nodules that are known to harbor bacilli. They may be present in primary or postprimary tuberculosis and radiographically appear as discrete nodules, typically within the upper lobes. Tuberculomas may calcify. Satellite lesions (ie, small discrete nodules in the vicinity of the tuberculoma) are present in as many as 90% of patients.

     

  • Endobronchial spread of infection with acinar opacities occurs as a consequence of infected material passing into the tracheobronchial tree from an infected portion of the lung. The organisms pass via the airways into previously uninvolved portions of the lung. The radiographic appearance is one of widespread ill-defined acinar shadows. Foci may become confluent and mimic bacterial pneumonia. Spread from the upper lobes to the lower lobes is common and called the upstairs-downstairs pattern.

     

  • Pulmonary miliary tuberculosis is a consequence of hematogenous spread of organisms to the pulmonary parenchyma. Radiographically, miliary spread can be recognized by circumscribed nodules less than 1-2 mm in diameter located diffusely throughout both lungs.

   

• In contrast to primary tuberculosis, lymphadenopathy is notably absent in patients with postprimary tuberculosis, with the exception of patients with HIV/AIDS infection.

   

• Airway involvement in postprimary tuberculosis may be observed.

   

  • Tracheobronchial stenosis may not be directly visualized on conventional chest radiographs. Airway stenosis may result in atelectasis in the segments of the lung supplied by that bronchus.

     

  • Bronchiectasis may be visualized on radiographs as dilated air-containing structures, with a tram-track appearance representing the parallel walls of the dilated airway. Dilated bronchi may be irregular in caliber and varicoid in appearance or may be cystic. Traction bronchiectasis may occur as well, as a consequence of fibrosis.

   

• Pleural involvement is seen more commonly in postprimary tuberculosis than in primary infection.

   

  • Pleural effusions may occur and may progress to empyema. An empyema may require emergent surgical intervention because the infection is maintained within a closed space and because it may result in rapid destruction of surrounding structures (eg, lung parenchyma, osseous structures of the thorax).

     

  • If infection extends from the pleural space to involve the chest wall, it is called empyema necessitans.

     

  • Osseous destruction and, possibly, air within subcutaneous tissues may be identified radiographically, or the empyema may present as a palpable soft-tissue mass.

Degree of Confidence: The imaging features of primary tuberculosis are nonspecific, and they may mimic those of other infectious processes. A finding that differentiates primary tuberculosis from other infectious processes is lymphadenopathy, which is typically absent in bacterial pneumonia.

Postprimary tuberculosis may be recognized more readily with the presence of fibrocavitary disease and a history of prior tuberculosis exposure or infection. Radiologic findings of postprimary tuberculosis are highly suggestive of, but not pathognomonic for, the disease. Inactive disease cannot be established without prior radiographs, regardless of the pattern.

False Positives/Negatives: As many as 15% of conventional chest radiographs may be normal in primary tuberculosis.

In the immunocompromised population, lymphadenopathy occasionally may occur in isolation, and it may not be detected on conventional radiographs. Additional imaging with CT is often required because CT is more sensitive in depicting lymphadenopathy.