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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 1 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 David A. Walton Gillian Lieberman, M. D. 2 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 3 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) 4 David A. Walton 5 Gillian Lieberman, M. D. 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 David A. Walton 6 Gillian Lieberman, M. D. 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 David A. Walton 7 Gillian Lieberman, M. D. 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 David A. Walton 8 Gillian Lieberman, M. D. 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 David A. Walton 9 Gillian Lieberman, M. D. Global Incidence of Tuberculosis, 1997 World Health Organization. WHO report on the tuberculosis epidemic, 2000 David A. Walton 10 Gillian Lieberman, M. D. 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 David A. Walton 11 Gillian Lieberman, M. D. 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. David A. Walton 12 Gillian Lieberman, M. D. 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) David A. Walton 13 Gillian Lieberman, M. D. Transmission of Tuberculosis and Progression of Latent Infection Small PM, Fujiwara PI. NEJM 2001; 189-200, p. 192. David A. Walton 14 Gillian Lieberman, M. D. 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 David A. Walton 15 Gillian Lieberman, M. D. 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 David A. Walton 16 Gillian Lieberman, M. D. 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 David A. Walton 17 Gillian Lieberman, M. D. Radiographic Residuals of Primary Infection Source: Iseman MD. A clinical guide to tuberculosis, 1999, p. 137. David A. Walton 18 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 David A. Walton 19 Gillian Lieberman, M. D. 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 David A. Walton 20 Gillian Lieberman, M. D. 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 David A. Walton 21 Gillian Lieberman, M. D. Post-Primary Tuberculosis Source: Cotran, et al. Robbins Pathologic Basis of Disease, 1999, p. 724. David A. Walton 22 Gillian Lieberman, M. D. 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 David A. Walton 23 Gillian Lieberman, M. D. 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 David A. Walton 24 Gillian Lieberman, M. D. Cavitary Disease Source: Socios en Salud, Lima, Peru David A. Walton 25 Gillian Lieberman, M. D. 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 David A. Walton 26 Gillian Lieberman, M. D. Cavitary Disease Source: Dr. Seymor Shalek, BIDMC Source: Socios en Salud, Lima, Peru David A. Walton 27 Gillian Lieberman, M. D. 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. David A. Walton 28 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 29 David A. Walton 30 Gillian Lieberman, M. D. 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 31 David A. Walton 32 Gillian Lieberman, M. D. Tuberculous effusion Pre-thoracentesis Source: Clinic Bon Sauveur, Cange, Haitit Post-thoracentesis Source: Clninc Bon Sauveur, Cange, Haiti David A. Walton 33 Gillian Lieberman, M. D. Spontaneous pneumothorax End-inspiration End-expiration Source: Dr. Seymor Shalek, BIDMC Source: Dr. Seymor Shalek, BIDMC David A. Walton 34 Gillian Lieberman, M. D. 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 David A. Walton 35 Gillian Lieberman, M. D. 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 36 David A. Walton 37 Gillian Lieberman, M. D. 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 David A. Walton 38 Gillian Lieberman, M. D. 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 David A. Walton 39 Gillian Lieberman, M. D. There is a differential: DDX: Miliary TB Sarcoidosis Metastatic Disease Diffuse fungal infection Source: Clinic Bon Sauveur, Cange, Haiti David A. Walton 40 Gillian Lieberman, M. D. 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 David A. Walton 41 Gillian Lieberman, M. D. 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 David A. Walton 42 Gillian Lieberman, M. D. 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. David A. Walton 43 Gillian Lieberman, M. D. 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%) David A. Walton 44 Gillian Lieberman, M. D. 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 David A. Walton 45 Gillian Lieberman, M. D. 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. David A. Walton 46 Gillian Lieberman, M. D. 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. David A. Walton 47 Gillian Lieberman, M. D. 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