Postprimary Tuberculosis Lung Imaging

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Postprimary Tuberculosis Lung Imaging

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Tuberculosis (TB) has existed for millennia, and despite initial declines in its incidence during the middle of the 20th century, the disease has been reemerging across the world. [1] The radiologic diagnosis of TB started only about a century ago, after Roentgen’s discovery of x-rays. [2] Fluoroscopy was used in the early part of the 20th century to detect cavitary TB, because experienced fluoroscopists could easily detect cavities. Over the years, improvements in technology, coupled with extensive investigation into the radiologic patterns of pulmonary TB, have resulted in diagnostic imaging being an essential adjunct to the clinical and microbiologic diagnosis of this disease. These events contributed to the routine practice of documenting cavitary disease and following up the disease on film. [3, 4, 5, 6, 7]

Images related to postprimary tuberculosis are provided below.

Tuberculosis results from infection by any of the TB complex mycobacteria, including Mycobacterium tuberculosis, M bovis, M africanum, M microti, and M canetti. [8]

TB can be divided into primary, progressive-primary, and postprimary forms on the basis of the natural history of the disease. Postprimary TB results from either reactivation of a latent primary infection or, less commonly, from the repeat infection of a previously sensitized host. The term “postprimary” is preferred to “reactivation” when referring to the clinical diagnosis, because firmly distinguishing recurrence from an antecedent infection is impossible in most cases. Approximately 10% of all infected patients are likely to develop reactivation, and the risk is highest within the first 2 years or during periods of immunosuppression. [9, 10, 11, 12]

No radiologic study shows findings that are specific for tuberculosis. A cavitary process that is demonstrated on chest radiographs or computed tomography (CT) scans in the apical and posterior segments of the upper pulmonary lobe or in the superior segments of the lower lobes is likely to be TB; however, differential considerations include other diseases, such as histoplasmosis and other fungal infections, bacterial abscesses, and necrotic neoplasms, especially lung neoplasms. [13, 14, 15]

In immunocompromised patients, postprimary TB may mimic primary TB, and the condition can appear with pleural effusion, lymphadenopathy, or miliary spread. The usual pattern of cavitary upper-lobe disease is less common in immunocompromised hosts than in immunocompetent hosts. [16]

Although the findings of currently active TB can often be differentiated from previous scarring on radiologic images, the possibility of latent or temporarily quiescent infection exists, and healed or inactive TB should not be diagnosed without adequate clinical information and/or the finding of calcified lesions. Radiographic follow-up is recommended in all cases of TB because it provides valuable information regarding the extent of the disease and its progression.

Stout et al reviewed 241 radiographs from 99 patients with pulmonary tuberculosis to determine reliability in predicting tuberculosis relapse. Agreement among 3 independent readers was very good for the findings of bilateral disease and cavitation, but substituting a consensus interpretation for the original interpretation increased the odds ratio for the association between cavitation on early chest radiograph and subsequent tuberculosis relapse from 4.97 to 8.97. According to the authors, improving the reliability of these findings could improve the utility of chest radiographs for predicting tuberculosis relapse. [17]

Sant’Anna et al, in a Brazilian study, observed the radiographic features of young patients with pulmonary TB and found cavitary lesions in 67 of 243 patients (27.6%) between the ages of newborn and 15 years and in 116 of 321 patients (36.1%) in adolescents aged 16 to 19 years. The most common radiographic lesions were postprimary tuberculosis (53.3%), tuberculous expansile pneumonia (27%), and primary complex with adenomegaly (1.8%). [18]

In a Japanese study, Nakanishi et al concluded that even in cases of negative sputum smears, high-resolution computed tomography (HRCT) scanning can be used to predict the risk of pulmonary TB with good reproducibility and to indicate which patients have a high probability of pulmonary TB. The authors examined findings in 116 patients with suspected pulmonary TB who had negative sputum smears for acid-fast bacilli. They found that large nodules, tree-in-bud appearance, lobular consolidation, and the main lesion being located in S1, S2, and S6 were significantly associated with an increased risk of pulmonary TB. [19]

For excellent patient education resources, visit eMedicineHealth’s Infections Center. Also, see eMedicineHealth’s patient education article Tuberculosis.

Pulmonary tuberculosis, especially postprimary disease, nearly always causes abnormalities on chest radiographs. Typically, the disease is parenchymal without nodal enlargement, and it manifests as cavitary lesions. Upper-lobe involvement with cavitation and the absence of lymphadenopathy are helpful in distinguishing postprimary TB from primary TB. In addition to the usually involved pulmonary segments—namely, the apical or posterior segments of the upper lobe or the superior segment of a lower lobe—anterior or basal segments may be involved in as many as 75% of cases. See the image below. [20]

Cavitation is a distinguishing feature of postprimary TB; this finding is seen on chest radiographs in about half of the cases and is discernible on chest CT scans in most cases. Typical cavities are thick walled and irregular. Air-fluid levels are uncommon and usually indicate superinfection; however, in 9% of cases, air-fluid levels can be seen in other circumstances. The persistence of cavitation without healing is unusual and should be investigated to exclude mycetomas, particularly in patients with persisting hemoptysis. Cavitation can lead to endobronchial spread to the remaining lung or rupture into the pleural space, where it can cause an empyema or bronchopleural fistula. Cavitation can also cause pseudoaneurysms of the pulmonary artery, which are called Rasmussen aneurysms. See the image below.

Miliary spread is less common in postprimary TB and is caused by erosion of bronchial vessels or pulmonary veins. See the image below.

Most cases of TB in patients with human immunodeficiency virus (HIV) infection or other immunosuppressive diseases are secondary to reactivation of a latent infection. However, a hypersensitive response or the absence of adequate immunity results in disease that behaves like primary TB. Miliary spread with systemic dissemination is more common in these immunocompromised individuals than in the healthy population. In these patients, radiographic findings are atypical, and the images often show diffuse dissemination, with striking lymphadenopathy and/or pleural effusions. Parenchymal involvement can range from consolidation to the absence of any lung opacities. Pleural effusion and parenchymal involvement are seen in the image below.

In the developed world, cavitation is uncommon in HIV-infected patients who have TB. In endemic areas, a more typical response, including upper-lobe disease and cavitation, is frequently seen in affected patients. This variance may be related to differences in the immune status of the patients.

TB and lung cancer coexist in as many as 5% of cases, but whether TB independently increases the likelihood of cancer remains unclear.

TB cannot be confidently diagnosed on the basis of chest radiographic findings alone because the imaging results can often be normal in primary TB. Normal findings are unusual in postprimary lung disease, but they cannot be used to exclude extrapulmonary TB. However, the combined positive predictive value is high for the typical symptoms of the disease and the finding of cavitary upper-lobe infiltrates on chest radiographs.

Sarcoidosis, granulomatous fungal infections, Nocardia infections, and atypical mycobacterioses are the conditions that most commonly mimic pulmonary TB.

Because typical postprimary TB is readily seen on conventional chest radiographs, the major utility of CT scanning is for assessment of the extent and nature of the disease. As mentioned above in Radiograph, CT scanning is more sensitive than chest radiography in depicting cavitation. The associated complications of postprimary TB, such as the erosion of vessels, rupture into the pleural space, and miliary and bronchogenic spread, are also better defined with CT scanning than with radiography. See the images below. [21, 22, 23]

A tree-in-bud pattern of 5- to 10-mm centrilobular nodules has been associated with endobronchial spread on HRCT scans, which helps in identifying active disease. Also, postprimary TB disease in immunocompromised patients may not be seen on chest radiographs. Mediastinal adenopathy, subtle pleural changes, and miliary lung parenchymal involvement are best detected with CT scanning.

Although no single radiologic feature is diagnostic of postprimary TB, a combination of upper-lobe opacities with a dominant cavitary process increases confidence in the diagnosis of TB. A tree-in-bud pattern is associated with endobronchial spread and suggests active disease.

Regarding false-positive findings, nontuberculous mycobacterial (NTM) infections can mimic all radiologic findings that are associated with postprimary TB. Typically, these findings are seen in elderly men with chronic obstructive pulmonary disease (COPD); in such patients, NTM infections should always be considered. Fungal infections, particularly histoplasmosis, may also result in similar findings. Cavitary lung disease that resembles TB has also been reported in cases of pyogenic infections, sarcoidosis, vasculitis, parasitic infections, bronchiolitis obliterans and organizing pneumonia (BOOP), and malignancies.

Regarding false-negative findings, postprimary TB resembles primary TB in immunocompromised patients, and it can be radiologically misclassified. CT and/or HRCT scan results are unlikely to be completely normal in postprimary TB.

Positron emission tomography (PET) scans may be positive in cases of active tuberculosis. Positive results are usually found when malignancy is suspected during the workup of a lung abnormality.

Current nuclear medicine tests are not specific for tuberculosis. There is increasing research on tagging nuclear medicine labels to molecular ligands for Mtb. While such molecular imaging is likely to be useful, it is yet to reach clinical practice. In one small study, [24] Technetium Tc-99m ciprofloxacin single-photon emission computed tomography (SPECT) was found to have 89% positive predictive value and 83% negative predictive value for the diagnosis of active pulmonary tuberculosis. This approach is particularly promising in differentiating active tuberculosis from prior scarring.

Cegielski JP, Chin DP, Espinal MA, et al. The global tuberculosis situation. Progress and problems in the 20th century, prospects for the 21st century. Infect Dis Clin North Am. 2002 Mar. 16(1):1-58. [Medline].

Rubin SA. Tuberculosis. Captain of all these men of death. Radiol Clin North Am. 1995 Jul. 33(4):619-39. [Medline].

Hopewell PC. A clinical view of tuberculosis. Radiol Clin North Am. 1995 Jul. 33(4):641-53. [Medline].

Ellis SM. The spectrum of tuberculosis and non-tuberculous mycobacterial infection. Eur Radiol. 2004 Mar. 14 (suppl 3):E34-42. [Medline]. [Full Text].

Fujita J, Higa F, Tateyama M. Radiological findings of mycobacterial diseases. J Infect Chemother. 2007 Feb. 13(1):8-17. [Medline].

Griffith-Richards SB, Goussard P, Andronikou S, et al. Cavitating pulmonary tuberculosis in children: correlating radiology with pathogenesis. Pediatr Radiol. 2007 Aug. 37(8):798-804. [Medline].

McAdams HP, Erasmus J, Winter JA. Radiologic manifestations of pulmonary tuberculosis. Radiol Clin North Am. 1995 Jul. 33(4):655-78. [Medline].

Dunlap NE, Bass J, Fujiwara P, et al. Diagnostic standards and classification of tuberculosis in adults and children. Ad-hoc committee of the Scientific Assembly on Microbiology, Tuberculosis, and Pulmonary Infections. Am J Respir Crit Care Med. 2000 Apr. 161 (4 pt 1):1376-95. [Medline]. [Full Text].

American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. Controlling tuberculosis in the United States. Am J Respir Crit Care Med. 2005 Nov 1. 172(9):1169-227. [Medline]. [Full Text].

Barnes PF, Lakey DL, Burman WJ. Tuberculosis in patients with HIV infection. Infect Dis Clin North Am. 2002 Mar. 16(1):107-26. [Medline].

Washington L, Miller WT Jr. Mycobacterial infection in immunocompromised patients. J Thorac Imaging. 1998 Oct. 13(4):271-81. [Medline].

Hunter RL, Actor JK, Hwang SA, Karev V, Jagannath C. Pathogenesis of post primary tuberculosis: immunity and hypersensitivity in the development of cavities. Ann Clin Lab Sci. 2014 Fall. 44 (4):365-87. [Medline].

Pitman AG, Hicks RJ, Binns DS, et al. Performance of sodium iodide based (18)F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses. Br J Radiol. 2002 Feb. 75(890):114-21. [Medline]. [Full Text].

Skoura E, Zumla A, Bomanji J. Imaging in tuberculosis. Int J Infect Dis. 2015 Mar. 32:87-93. [Medline].

Bolursaz MR, Mehrian P, Aghahosseini F, Lotfian F, Khalilzadeh S, Baghaie N, et al. Evaluation of the relationship between smear positivity and high-resolution CT findings in children with pulmonary tuberculosis. Pol J Radiol. 2014. 79:120-5. [Medline].

Washington L, Palacio D. Imaging of bacterial pulmonary infection in the immunocompetent patient. Semin Roentgenol. 2007 Apr. 42(2):122-45. [Medline].

Stout JE, Kosinski AS, Hamilton CD, Goodman PC, Mosher A, Menzies D, et al. Effect of improving the quality of radiographic interpretation on the ability to predict pulmonary tuberculosis relapse. Acad Radiol. 2010 Feb. 17(2):157-62. [Medline].

Sant’Anna C, March MF, Barreto M, Pereira S, Schmidt C. Pulmonary tuberculosis in adolescents: radiographic features. Int J Tuberc Lung Dis. 2009 Dec. 13(12):1566-8. [Medline].

Nakanishi M, Demura Y, Ameshima S, Kosaka N, Chiba Y, Nishikawa S, et al. Utility of high-resolution computed tomography for predicting risk of sputum smear-negative pulmonary tuberculosis. Eur J Radiol. 2010 Mar. 73(3):545-50. [Medline].

Kim WS, Choi JI, Cheon JE, et al. Pulmonary tuberculosis in infants: radiographic and CT findings. AJR Am J Roentgenol. 2006 Oct. 187(4):1024-33. [Medline].

Amorosa JK. Essentials of Radiology [CD-ROM]. Moraga, Calif: Medical Interactive; 1999.

Goo JM, Im JG. CT of tuberculosis and nontuberculous mycobacterial infections. Radiol Clin North Am. 2002 Jan. 40(1):73-87, viii. [Medline].

Poey C, Verhaegen F, Giron J, et al. High resolution chest CT in tuberculosis: evolutive patterns and signs of activity. J Comput Assist Tomogr. 1997 Jul-Aug. 21(4):601-7. [Medline].

Lee M, Yoon M, Hwang KY, Choe W. Tc-99m ciprofloxacin SPECT of pulmonary tuberculosis. Nucl Med Molecular Imag. June 2010. 44:116-22.

Anjali Agrawal, MD Adjunct Assistant Professor of Radiology, Baylor College of Medicine; Consultant Radiologist, Teleradiology Solutions, India

Anjali Agrawal, MD is a member of the following medical societies: American Roentgen Ray Society, Indian Radiological and Imaging Association, American Society of Emergency Radiology, Radiological Society of North America

Disclosure: Nothing to disclose.

Anurag Agrawal, MBBS, PhD Principal Scientist, CSIR Institute of Genomics and Integrative Biology; Associate Professor, Academy of Scientific and Innovative Research, New Delhi, India

Anurag Agrawal, MBBS, PhD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine

Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging

Disclosure: Nothing to disclose.

Judith K Amorosa, MD, FACR Clinical Professor of Radiology and Vice Chair for Faculty Development and Medical Education, Rutgers Robert Wood Johnson Medical School

Judith K Amorosa, MD, FACR is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America, Society of Thoracic Radiology

Disclosure: Nothing to disclose.

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