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Tuberculous pleural effusions in HIV-uninfected patients

Michael D Frye, MD
John T Huggins, MD
Section Editor
C Fordham von Reyn, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Tuberculous pleural effusion accounts for approximately 5 percent of disease due to Mycobacterium tuberculosis and is the second most common form of extrapulmonary tuberculosis (TB) after lymphatic involvement [1,2]. Tuberculous pleural effusion is synonymous with the term tuberculous pleurisy.

Tuberculous pleural effusion is an exudative, lymphocyte-predominant pleural effusion that occurs as a result of a delayed hypersensitivity reaction to mycobacteria or mycobacterial antigens in the pleural space. Acid-fast bacilli (AFB) stains and AFB cultures are of low yield in the setting of tuberculous pleural effusions, and often pleural biopsy is needed to confirm the diagnosis. In contrast, tuberculous empyema is a chronic, suppurative infection due to the presence of a high Mycobacterium burden in the pleural space (image 1). When pleural fluid is aspirated in tuberculous empyema, it is grossly purulent and is always AFB smear and culture positive.

Issues related to the diagnosis and treatment of tuberculous pleural effusions in HIV-uninfected patients will be reviewed here. Issues related to tuberculous pleural effusions in HIV-infected patients are discussed separately. (See "Tuberculous pleural effusions in HIV-infected patients".)


Tuberculous pleural effusions are thought to result from a delayed hypersensitivity reaction to mycobacteria and mycobacterial antigens in the pleural space [3]. These organisms and/or their antigens probably enter the pleural space due to leakage or rupture of a subpleural focus of disease. In one study of 24 patients with tuberculous pleural effusions who underwent thoracotomy, for example, a caseous focus in the lung contiguous with the diseased pleura was found in half of cases [4]. Development of pleural effusion occurs largely as a result of hypersensitivity reaction, but tuberculous pleurisy must be considered to be due to active disease since culture of the fluid grows mycobacteria in some cases and culture of the pleural tissue usually grows mycobacteria. Tuberculous pleural effusions are usually self-limited and resolve spontaneously with or without treatment in most cases. However, the condition can potentially progress and worsen and become a tuberculous empyema.

A tuberculous empyema represents chronic active disease involving the pleural space and can occur in the setting of a large pleural effusion that progresses, usually leading to an unexpandable lung [5]. Simple tuberculous pleural effusion and tuberculous empyema can be considered a continuum of the same process. Tuberculous empyema can also develop via extension of infection from thoracic lymph nodes or subdiaphragmatic focus, via hematogenous spread, or in the setting of therapeutic pneumothorax therapy leading to an unexpandable lung.


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Literature review current through: Jan 2017. | This topic last updated: Wed Feb 10 00:00:00 GMT+00:00 2016.
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  1. Seibert AF, Haynes J Jr, Middleton R, Bass JB Jr. Tuberculous pleural effusion. Twenty-year experience. Chest 1991; 99:883.
  2. Baumann MH, Nolan R, Petrini M, et al. Pleural tuberculosis in the United States: incidence and drug resistance. Chest 2007; 131:1125.
  3. Leibowitz S, Kennedy L, Lessof MH. The tuberculin reaction in the pleural cavity and its suppression by antilymphocyte serum. Br J Exp Pathol 1973; 54:152.
  4. STEAD WW, EICHENHOLZ A, STAUSS HK. Operative and pathologic findings in twenty-four patients with syndrome of idiopathic pleurisy with effusion, presumably tuberculous. Am Rev Tuberc 1955; 71:473.
  5. Sahn SA, Iseman MD. Tuberculous empyema. Semin Respir Infect 1999; 14:82.
  6. Antony VB, Repine JE, Harada RN, et al. Inflammatory responses in experimental tuberculosis pleurisy. Acta Cytol 1983; 27:355.
  7. Antony VB, Sahn SA, Antony AC, Repine JE. Bacillus Calmette-Guérin-stimulated neutrophils release chemotaxins for monocytes in rabbit pleural spaces and in vitro. J Clin Invest 1985; 76:1514.
  8. Ellner JJ, Barnes PF, Wallis RS, Modlin RL. The immunology of tuberculous pleurisy. Semin Respir Infect 1988; 3:335.
  9. Gopi A, Madhavan SM, Sharma SK, Sahn SA. Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest 2007; 131:880.
  10. Torgersen J, Dorman SE, Baruch N, et al. Molecular epidemiology of pleural and other extrapulmonary tuberculosis: a Maryland state review. Clin Infect Dis 2006; 42:1375.
  11. Kim HJ, Lee HJ, Kwon SY, et al. The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis. Chest 2006; 129:1253.
  12. Merino JM, Carpintero I, Alvarez T, et al. Tuberculous pleural effusion in children. Chest 1999; 115:26.
  13. Berger HW, Mejia E. Tuberculous pleurisy. Chest 1973; 63:88.
  14. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med 2000; 161:1376.
  15. Valdés L, Alvarez D, San José E, et al. Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 1998; 158:2017.
  16. Frye MD, Pozsik CJ, Sahn SA. Tuberculous pleurisy is more common in AIDS than in non-AIDS patients with tuberculosis. Chest 1997; 112:393.
  17. SIBLEY JC. A study of 200 cases of tuberculous pleurisy with effusion. Am Rev Tuberc 1950; 62:314.
  18. Hulnick DH, Naidich DP, McCauley DI. Pleural tuberculosis evaluated by computed tomography. Radiology 1983; 149:759.
  19. Levine H, Metzger W, Lacera D, Kay L. Diagnosis of tuberculous pleurisy by culture of pleural biopsy specimen. Arch Intern Med 1970; 126:269.
  20. Epstein DM, Kline LR, Albelda SM, Miller WT. Tuberculous pleural effusions. Chest 1987; 91:106.
  21. Light RW. Chapter 10. In: Pleural Diseases, 2d ed, Lea & Febiger, Philadelphia 1990.
  22. Trajman A, da Silva Santos Kleiz de Oliveira EF, Bastos ML, et al. Accuracy of polimerase chain reaction for the diagnosis of pleural tuberculosis. Respir Med 2014; 108:918.
  23. Denkinger CM, Schumacher SG, Boehme CC, et al. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. Eur Respir J 2014; 44:435.
  24. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis 2017; 64:e1.
  25. Piras MA, Gakis C, Budroni M, Andreoni G. Adenosine deaminase activity in pleural effusions: an aid to differential diagnosis. Br Med J 1978; 2:1751.
  26. Riantawan P, Chaowalit P, Wongsangiem M, Rojanaraweewong P. Diagnostic value of pleural fluid adenosine deaminase in tuberculous pleuritis with reference to HIV coinfection and a Bayesian analysis. Chest 1999; 116:97.
  27. Ocaña I, Martinez-Vazquez JM, Segura RM, et al. Adenosine deaminase in pleural fluids. Test for diagnosis of tuberculous pleural effusion. Chest 1983; 84:51.
  28. Valdés L, San José E, Alvarez D, et al. Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma. Chest 1993; 103:458.
  29. Orriols R, Coloma R, Ferrer J, et al. Adenosine deaminase in tuberculous pleural effusion. Chest 1994; 106:1633.
  30. Bañales JL, Pineda PR, Fitzgerald JM, et al. Adenosine deaminase in the diagnosis of tuberculous pleural effusions. A report of 218 patients and review of the literature. Chest 1991; 99:355.
  31. Villegas MV, Labrada LA, Saravia NG. Evaluation of polymerase chain reaction, adenosine deaminase, and interferon-gamma in pleural fluid for the differential diagnosis of pleural tuberculosis. Chest 2000; 118:1355.
  32. Jiménez Castro D, Díaz Nuevo G, Pérez-Rodríguez E, Light RW. Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions. Eur Respir J 2003; 21:220.
  33. Gakis C. Adenosine deaminase in pleural effusions. Chest 1995; 107:1772.
  34. Verea Hernando HR, Masa Jimenez JF, Dominguez Juncal L, et al. Meaning and diagnostic value of determining the lysozyme level of pleural fluid. Chest 1987; 91:342.
  35. Hiraki A, Aoe K, Eda R, et al. Comparison of six biological markers for the diagnosis of tuberculous pleuritis. Chest 2004; 125:987.
  36. Aoe K, Hiraki A, Murakami T, et al. Diagnostic significance of interferon-gamma in tuberculous pleural effusions. Chest 2003; 123:740.
  37. Wongtim S, Silachamroon U, Ruxrungtham K, et al. Interferon gamma for diagnosing tuberculous pleural effusions. Thorax 1999; 54:921.
  38. Jiang J, Shi HZ, Liang QL, et al. Diagnostic value of interferon-gamma in tuberculous pleurisy: a metaanalysis. Chest 2007; 131:1133.
  39. Sahn SA, Huggins JT, San José ME, et al. Can tuberculous pleural effusions be diagnosed by pleural fluid analysis alone? Int J Tuberc Lung Dis 2013; 17:787.
  40. Kirsch CM, Kroe DM, Azzi RL, et al. The optimal number of pleural biopsy specimens for a diagnosis of tuberculous pleurisy. Chest 1997; 112:702.
  41. Sahn SA. State of the art. The pleura. Am Rev Respir Dis 1988; 138:184.
  42. Diacon AH, Van de Wal BW, Wyser C, et al. Diagnostic tools in tuberculous pleurisy: a direct comparative study. Eur Respir J 2003; 22:589.
  43. Emad A, Rezaian GR. Diagnostic value of closed percutaneous pleural biopsy vs pleuroscopy in suspected malignant pleural effusion or tuberculous pleurisy in a region with a high incidence of tuberculosis: a comparative, age-dependent study. Respir Med 1998; 92:488.
  44. Conde MB, Loivos AC, Rezende VM, et al. Yield of sputum induction in the diagnosis of pleural tuberculosis. Am J Respir Crit Care Med 2003; 167:723.
  45. Aggarwal AN, Agarwal R, Gupta D, et al. Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis. J Clin Microbiol 2015; 53:2451.
  46. Losi M, Bossink A, Codecasa L, et al. Use of a T-cell interferon-gamma release assay for the diagnosis of tuberculous pleurisy. Eur Respir J 2007; 30:1173.
  47. ROPER WH, WARING JJ. Primary serofibrinous pleural effusion in military personnel. Am Rev Tuberc 1955; 71:616.
  48. Lai YF, Chao TY, Wang YH, Lin AS. Pigtail drainage in the treatment of tuberculous pleural effusions: a randomised study. Thorax 2003; 58:149.
  49. Lee CH, Wang WJ, Lan RS, et al. Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study. Chest 1988; 94:1256.
  50. Matchaba PT, Volmink J. Steroids for treating tuberculous pleurisy. Cochrane Database Syst Rev 2000; :CD001876.
  51. Light RW. Update on tuberculous pleural effusion. Respirology 2010; 15:451.
  52. Engel ME, Matchaba PT, Volmink J. Corticosteroids for tuberculous pleurisy. Cochrane Database Syst Rev 2007; :CD001876.
  53. Barbas CS, Cukier A, de Varvalho CR, et al. The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis. Chest 1991; 100:1264.
  54. de Pablo A, Villena V, Echave-Sustaeta J, Encuentra AL. Are pleural fluid parameters related to the development of residual pleural thickening in tuberculosis? Chest 1997; 112:1293.