The Radiographic Appearance of Pulmonary Tuberculosis

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Note: Mycobacterium tuberculosis is an aerobic, acid-fast Gram positive rod ..... Pulmonary tuberculosis: presentation, diagnosis, and treatment. In: Friedman LN  ...
David A. Walton Gillian Lieberman, M. D.

The Radiographic Appearance of Pulmonary Tuberculosis

David Walton, Harvard Medical School, Year IV Gillian Lieberman, M.D.

David A. Walton

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Gillian Lieberman, M. D.

Patients History A clinic in rural Haiti

• CM, a 34-year-old male Haitian peasant farmer p/w 2 months of fever, night sweats, fatigue, weight loss, and 2 episodes of hemoptysis • CXR was obtained

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CXR

CXR revealed a RUL infiltrate with three right perihilar cavitary lesions

Source: Clinic Bon Sauveur, Cange, Haiti

David A. Walton Gillian Lieberman, M. D.

• • • • • • • • • •

DDx of upper lobe infiltrates and cavitation:

Tuberculosis Atypical mycobacteria Sarcoidosis Silicosis Wegner’s granulomatosis Collagen vascular disease Adenosquamous cancer Lymphoma (esp. Hodgskins) Actinomycosis Histoplasmosis

Source: Clinic Bon Sauveur, Cange, Haiti

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David A. Walton Gillian Lieberman, M. D.

Sputum microscopy revealed numerous acid-fast bacilli Pt started on a four drug anti-tuberculous regimen (INH, RIF, PZA, ETH)

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Symptoms of Pulmonary TB Respiratory

Constitutional

Cough (initially dry, later productive)

Malaise

Chest pain

Lassitude

Hemoptysis (sparse early, heavy

Fever

w/ cavitation)

Sweats

Shortness of breath

Anorexia

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Diagnosis • Smear microscopy • • •

Ziehl-Neelsen Kinyoun Rhodamine auramine

• Culture – Can take up to six weeks to identify positive cultures (TB doubling time is 15-24 hours)

• Chest radiography – Suggestive, not diagnostic

• Bronchoscopy • Tuberculin skin testing – Does not differentiate latent infection or BCG vaccination from active disease

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Histopathology

Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 191.

Ziehl Neelsen smear of acid fast Mycobacterium tuberculosis

Source: http://www.mssm.edu/medicine/infectious-disease/consultative/case_11.html

Culture of Mycobacterium tuberculosis on LowensteinJensen medium

Note: Mycobacterium tuberculosis is an aerobic, acid-fast Gram positive rod

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Epidemiology • One third of the world’s population—two billion people—is infected with the tubercle bacillus • Eight million people per year develop active disease • Two million deaths per year are attributable to M. tuberculosis • Tuberculosis remains the world’s leading infectious cause of adult mortality • Estimates for the next 20 years include one billion new infections, 200 million with active disease, and 35 million deaths

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Global Incidence of Tuberculosis, 1997

World Health Organization. WHO report on the tuberculosis epidemic, 2000

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Reported TB Cases United States, 1953 - 1998 100,000

Cases (Log Scale)

70,000 *

50,000

*

30,000 20,000

10,000 53

60

70

80

90

Year *Change in case definition Source: http://www.cdc.gov/nchstp/tb/pubs/slidesets/core/html/trans3_slides.htm

98

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Transmission and Pathogenesis •







Tuberculosis is an airborne infection spread by droplet nuclei (5-10µm) When inhaled, droplet nuclei are deposited in terminal airspaces of the lung Macrophages ingest the bacilli and transport them to regional lymph nodes Further dissemination occurs via lymphohematogenous routes to other parts of the lungs and extrapulmonary sites

Source: Centers for Disease Control and Prevention. Core Curriculum on Tuberculosis, 4th ed. 2000.

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Transmission and Pathogenesis in the lungs Inhalation and deposition of the tubercle bacillus leads to one of three possible outcomes: • Immediate clearance of the organism Source: http://telpath2.med.utah.edu/

• Primary disease • Active disease many years after initial infection (post-primary disease)

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Transmission of Tuberculosis and Progression of Latent Infection

Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 192.

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Primary Tuberculosis • Most often a childhood infection in endemic settings • Few clinical symptoms in immunocompetent hosts • Lymphangitic spread to hilar and paratracheal nodes result in enlargement of these structures • Often the only residua of primary infection is a positive skin test and the Ranke complex • Primary progressive tuberculosis occurs in a minority of cases

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The natural history of primary tuberculosis in adults Event

Time

Alveolar deposition of tubercle bacilli

0

Bacilli proliferate and disseminate

3-8 weeks

Some patients develop pleurisy; A minority develop miliary disease

8-26 weeks

High-risk period for pulmonary and Extrapulmonary disesase

26-156 weeks

Iseman MD. A clinical guide to tuberculosis, 1999, p. 130

Comments Bacilli engulfed by alveolar macrophage Tuberculin skin test becomes reactive; chest x-ray may become abnormal

10% infected will develop TB

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Primary Tuberculosis •

• • •

• •



Lymphadenopathy is the hallmark of primary disease in childhood, seen in up to 90% of cases Usually affects the hilum and right paratracheal regions Bilateral adenopathy occurs in one third of cases Adenopathy usually seen in association with parenchymal consolidation or atelectasis Lymphadenopathy can be the only manifestation of TB in young children Adenopathy resolves slowly, and nodal calcification may occur six months after the initial infection Pleural effusion may occur in a minority of cases

Source: Dr. Seymor Shalek, BIDMC

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Radiographic Residuals of Primary Infection

Source: Iseman MD. A clinical guide to tuberculosis, 1999, p. 137.

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Gillian Lieberman, M. D.

Primary Tuberculosis Ranke’s Complex

Simon Foci

Source:Cotran et al. Robbins Pathologic Basis of Disease, 1999, p. 723.

Source: Clinic Bon Sauveur, Cange, Haiti

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Post-Primary Tuberculosis • Post-primary TB represents 90 percent of adult cases in the non-HIV-infected population • Results from reactivation of a previously dormant focus seeded at the time of primary infection • 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 • The original site of spread is occasionally associated with Simon foci—residual uni- or bilateral apical fibronodular shadows from primary infection • Post-primary disease also known as reactivation TB, recrudescent TB, chronic TB, endogenous reinfection, and adult type progressive TB

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Post-Primary Tuberculosis The radiographic appearance of post-primary disease can include:: • • • • •

Upper lobe infiltrates Cavitary lesions Tuberculomas Absence of lymphadenopathy Complete lobar or lung opacification and lobar collapse in severe cases • Complications, including effusion, empyema, bronchiectasis, mililary pattern, and spontaneous pneumothorax

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Post-Primary Tuberculosis

Source: Cotran, et al. Robbins Pathologic Basis of Disease, 1999, p. 724.

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Post-Primary Tuberculosis

Bilateral upper lobe involvement seen in this patient with postprimary disease Source: Dr. Seymor Shalek, BIDMC

Advanced post-primary tuberculosis in an immunocompetent host Source: Clinic Bon Sauveur, Cange, Haiti

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Cavitary Disease • A characteristic finding of post-primary disease • Cavitation implies a high bacillary burden and high infectivity • Cavity size ranges from a few mm to several cm • Variable wall thickness • Air fluid levels rare, and may be an indication of bacterial or fungal superinfection Source: Clinic Bon Sauveur, Cange, Haiti

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Cavitary Disease

Source: Socios en Salud, Lima, Peru

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Pathology • Gross specimen of upper lobe cavitary disease and endobronchial spread to both upper and lower lobes • Infected bronchi appear as small, pale nodules with a hyperemic border

Source: http://pathhsw5m54.ucsf.edu/case32/image327.html

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Cavitary Disease

Source: Dr. Seymor Shalek, BIDMC

Source: Socios en Salud, Lima, Peru

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Tuberculoma • Single or multiple rounded, wellcircumscribed, focal lesions • Manifestation of primary or postprimary disease • Easily mistaken for coin lesions or metastatic disease on chest radiograph • Vary in size from a few millimeters to 5 or 6 cm in diameter but usually range from 1 to 3 cm. • They may or may not contain calcium

Source: Juhl JH, et al. Paul and Juhl's Essentials of Radiologic Imaging, 7th ed., 1998, p. 872.

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Gillian Lieberman, M. D.

Post-Primary Tuberculosis

Interval improvement of 4 x 2 cm cavitary mass abutting right hilum after 4 months of effective therapy

Source: BiDMC

David A. Walton Gillian Lieberman, M. D.

Role of CT in Pulmonary Tuberculosis • Chest radiography remains the first choice of initial evaluation of patients with tuberculosis • CT may be helpful in the patients who initially present with a normal chest radiograph and high suspicion of active disease • Various patterns of primary and post-primary disease may necessitate CT as a diagnostic tool in pulmonary tuberculosis • CT facilitates differentiation of pulmonary tuberculosis from lung cancer or other granulomatous lung disease

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Role of CT in Pulmonary Tuberculosis CT reveals 4 x 3 cm right hilar cavitary mass poorly seen on chest X-ray

Source: BIDMC

Source: BIDMC

David A. Walton Gillian Lieberman, M. D.

Complications of Post-Primary Tuberculosis

• • • • • •

Tuberculous effusion Tuberculous empyema Bronchostenosis Broncholithiasis Spontaneous pneumothorax Dissemination to other organs

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Tuberculous effusion Pre-thoracentesis

Source: Clinic Bon Sauveur, Cange, Haitit

Post-thoracentesis

Source: Clninc Bon Sauveur, Cange, Haiti

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Spontaneous pneumothorax End-inspiration

End-expiration

Source: Dr. Seymor Shalek, BIDMC

Source: Dr. Seymor Shalek, BIDMC

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Miliary Tuberculosis

• Results from hematogenous dissemination of tubercle bacilli • Seen in both primary and post-primary disease • Occurs more frequently in young children and immunocompromised patients

Source: Brigham and Women’s Hospital, Boston, Massachusetts

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Miliary Tuberculosis

• Characteristic radiographic appearance is a faint reticulonodular pattern consisting of widespread nodular opacities measuring 2-3 mm in diameter scattered diffusely throughout both lungs • Associated lymphadenopathy seen in 95% of children, 12% of adults

Source: Dr. Seymor Shalek, BIDMC

David A. Walton Gillian Lieberman, M. D.

• • • • • • • • • •

Differential of a miliary pattern on chest radiograph or CT:

Miliary tuberculosis Atypical mycobateria Disseminated fungal infection (blastomycosis, histoplasmosis, etc.) Metastatic neoplastic disease Disseminated viral infection (varicella, CMV, etc.) Bacterial (nocardia, tuleremia, brucellosis, staphylococcus, streptococcus, etc.) Schistosomiasis Pneumoconioses Sarcoidosis Hypersensitivity pneumonitis Source: Brigham and Women’s Hospital, Boston, Massachusetts

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Miliary Tuberculosis

Source: http://www.UpToDate.com

Millet seeds, after which the disease was named. The size of the seeds correspond to the size of the lesions seen on chest radiograph

Source: http://www-medlib.med.utah.edu/WebPath/LUNGHTML/LUNG039.html

Gross specimen of lung demonstrating the diffuse nature of miliary disease

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Challenge Patient 61-year-old female Haitian peasant with cough, SOB, and significant weight loss over 4 months

What is the cause for the miliary pattern?

Source: Clinic Bon Sauveur, Cange, Haiti

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There is a differential:

DDX: Miliary TB Sarcoidosis Metastatic Disease Diffuse fungal infection

Source: Clinic Bon Sauveur, Cange, Haiti

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Miliary Metastases

**S/p left mastectomy for breast CA**

DDX: Miliary TB Sarcoidosis Metastatic Disease Diffuse fungal infection Absent left breast shadow

Source: Clinic Bon Sauveur, Cange, Haiti

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Other causes of Miliary patterns:

Source: Brigham and Women’s Hospital, Boston, MAssachusetts Source: Dr. Seymor Shalek, BIDMC

Varicella pneumonia is also part of the differential for a miliary pattern on chest radiograph

In immunocompromised patients, one must rule out Pneumocystis carinii pneumonia as a potential etiology of a miliary pattern on chest radiograph

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Radiographic findings for patients with pulmonary TB, according to HIV status Finding

HIV-positive (n=72)

HIV-negative (n=52)

Focal infiltrate

38 (53%)

46 (89%)

Upper-lobe infiltrate

19 (26%)

32 (62%)

One or more cavities

5 (7%)

23 (44%)

Hilar or mediastinal lymphadenopathy

28 (39%)

6 (12%)

Normal

8 (11%)

3 (6%)

Alpert, et al. Clinical Infectious Diseases 1997; 24:661-8.

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Radiological features of pulmonary TB in 963 HIV-infected adults compared to 1000 HIV-negative adults with TB HIV-positive (n=963)

HIV-negative (n=1000)

Cavitation

319 (33%)

784 (78%)

Lymphadenopathy

253 (26%)

131 (13%)

Pleural effusions

159 (16%)

68

(7%)

Miliary pattern

94

52

(5%)

Atelectasis

112 (12%)

237 (24%)

Consolidation

94

(10%)

32

(3%)

Interstitial changes

120 (12%)

68

(7%)

Radiological feature

Tshibwabwa-Tumba, et al. Clinical Radiology 1997; 52:837-841.

(9.8%)

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Summary • • • • • • • •

Pulmonary tuberculosis is a disease with protean, non-specific symptoms, but often associated with fever, weight loss, cough, night sweats, and hemoptysis M. Tuberculosis is the world’s leading infectious cause of adult mortality, with two billion infected worldwide Tuberculosis is an airborne infection After initial infection, one can develop primary TB, latent TB, or post-primary TB Primary TB characterized radiographically by lymphadenopathy Post-primary TB characterized radiographically by upper lobe infiltrates, cavitary lesions, and tuberculomas Although chest radiograhy is indicated when TB is suspected, CT can aid in the diagnosis Miliary TB, which can be secondary to primary or post-primary disease, is characterized by faint reticulonodular pattern consisting of widespread nodular opacities measuring 2-3 mm in diameter scattered diffusely throughout both lungs

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References • • • • • • • • •

McAdams HP, Erasmus J, Winter JA. Radiologic manifestations of pulmonary tuberculosis. Radiologic Clinics of North America 1995; 33(4):655-676. Friedman LN, Selwyn PA. Pulmonary tuberculosis: presentation, diagnosis, and treatment. In: Friedman LN (ed.). Tuberculosis: Current concepts and treatment. New York, CRC Press, 2001. Farmer PE, Walton DA, Becerra MC. International tuberculosis control in the 21st century. In: Friedman LN (ed.). Tuberculosis: current concepts and treatment. New York, CRC Press, 2001. Iseman MD. A clinician’s guide to tuberculosis. Lippincott Williams and Wilkins, Philadelphia, 2000. Cotran RS, Kumar V, Collins T. Robbins pathologic basis of disease. WB Saunders Company, Philadelphia, 1999. Juhl JH, Crummy AB, Kuhlman, JE. Paul and Juhl's essentials of radiologic imaging, 7th edition. Lippincott, Williams and Wilkins, New York, 1998. Small PM, Fujiwara PI. Management of tuberculosis in the United States. New England Journal of Medicine 2001; 345(3): 189-200. Rottenberg, GT, Shaw P. Radiology of pulmonary tuberculosis. British Journal of Hospital Medicine 1996; 56(5): 195-199. Kwong JS, Carignan S, Kang EY, Muller NL, FitzGerald JM. Miliary tuberculosis: diagnostic accuracy of chest radiography. Chest; 110(2): 339-42.

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References • • • • • • • •



• •

www.mssm.edu/medicine/infectious-disease/consultative/case_11.html www.cdc.gov/nchstp/tb/pubs/slidesets/core/html/trans3_slides.htm World Health Organization. WHO report on the tuberculosis epidemic. Geneva: World Health Organization; 2000. Centers for Disease Control and Prevention. Core Curriculum on Tuberculosis, 4th ed. Centers for Disease Control and Prevention, Atlanta, 2000. http://telpath2.med.utah.edu/ http://pathhsw5m54.ucsf.edu/case32/image327.html www.UpToDate.com Alpert PL, Munsiff SS, Gourevitch MN, Greenberg B, Klein R. A prospective study of tuberculosis and human immunodeficiency virus infection clinical manifestations and factors associated with survival. Clinical Infectious Diseases 1997; 24:661-668. Tshibwabwa-Tumba E, Mwinga A, Pobee J, Zumla A. Radiological features of pulmonary tuberculosis in 963 HIV-infected adults at three central African hospitals. Clinical Radiology 1997; 52: 837-841. Lee KS, Im JG. CT in adults with tuberculosis of the chest: characteristic findings and role in management. American Journal of Roentgenology 1995; 164: 1361-1367. Lee KS, Hwang JW, Chung MP, Kim H, Kwon OJ. Utility of CT in the evaluation of pulmonary tuberculosis in patients without AIDS. Chest 1996; 110(4): 977-984.

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Acknowledgements I would like to thank: • Dr. Seymor Shalek for his dedication to teaching and sharing his wonderful radiographic collection with me • Paul Farmer for his kindness, support, and mentorship • The staff of Zanmi Lasante • Dr. Fernet Leandre for helping me find cases in Haiti • The patients of Clinic Bon Sauveur • Dr. Phillip Boiselle for his assistance • Our webmasters, Larry Barbaras and Cara Lyn D’amour • Beverlee Turner and Pamela Lepkowski