, 187:263 | Cite as

Tuberculous Pleural Effusion

  • José M. Porcel


Tuberculous pleural effusion is one of the most common forms of extrapulmonary tuberculosis (TB). The immediate cause of the effusion is a delayed hypersensitivity response to mycobacterial antigens in the pleural space. For this reason microbiological analyses are often negative and limited by the lengthy delay in obtaining results. In areas with high TB prevalence, pleural fluid adenosine deaminase (ADA) levels greater than 40 U/l argue strongly for TB; in contrast, low levels of pleural ADA have high negative predictive value in low-prevalence countries. The specificity of this enzyme increases if only lymphocytic exudates are considered. The shortcoming of the ADA test is its inability to provide culture and drug sensitivity information, which is paramount in countries with a high degree of resistance to anti-TB drugs. Sputum induction (in addition to pleural fluid) for acid-fast bacilli and culture is a recommended procedure in all patients with TB pleurisy. The microscopic-observation drug-susceptibility assay performed on pleural fluid or pleural tissue increases by two to three times the detection of TB over conventional cultures, and it allows for the identification of multidrug-resistant TB. A reasonable management strategy for pleural TB would be to initiate a four-drug regimen and perform a therapeutic thoracentesis in patients with large, symptomatic effusions.


Pleural effusion Tuberculosis Adenosine deaminase 


  1. 1.
    World Health Organization (2008) Global tuberculosis control: surveillance, planning, financing. WHO, GenevaGoogle Scholar
  2. 2.
    Baumann MH, Nolan R, Petrini M, Lee YC, Light RW, Schneider E (2007) Pleural tuberculosis in the United States: incidence and drug resistance. Chest 131:1125–1132PubMedCrossRefGoogle Scholar
  3. 3.
    Situació epidemiològica i tendència de l’èndèmia tuberculosa a Catalunya [Epidemiology and trend of tuberculous endemia in Catalonia]. Departament de Salut, Generalitat de Catalunya, Informe Anual, Barcelona (2006)Google Scholar
  4. 4.
    Valdés L, Alvarez D, Valle JM, Pose A, San José E (1996) The etiology of pleural effusions in an area with high incidence of tuberculosis. Chest 109:158–162PubMedCrossRefGoogle Scholar
  5. 5.
    Light RW (2007) Pleural diseases, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 211–224Google Scholar
  6. 6.
    Valdés L, Alvarez D, San José E, Penela P, Valle JM, García-Pazos JM, Suárez J, Pose A (1998) Tuberculous pleurisy: a study of 254 patients. Arch Intern Med 158:2017–2021PubMedCrossRefGoogle Scholar
  7. 7.
    Ibrahim WH, Ghadban W, Khinji A, Yasin R, Soub H, Al-Khal AL, Bener A (2005) Does pleural tuberculosis disease pattern differ among developed and developing countries? Respir Med 99:1038–1045PubMedCrossRefGoogle Scholar
  8. 8.
    Porcel JM, Alemán C, Bielsa S, Sarrapio J, Fernández de Sevilla T, Esquerda A (2008) A decision tree for differentiating tuberculous from malignant pleural effusions. Respir Med 102:1159–1164PubMedCrossRefGoogle Scholar
  9. 9.
    Pérez-Rodriguez E, Light RW (2008) Effusions from infections: tuberculosis. In: Light RW, Gary Lee YC (eds) Textbook of pleural diseases, 2nd edn. Hodder Arnold, London, pp 367–378Google Scholar
  10. 10.
    Cases Viedma E, Lorenzo Dus MJ, González-Molina A, Sanchis Aldás JL (2006) A study of loculated tuberculous pleural effusions treated with intrapleural urokinase. Respir Med 100:2037–2042PubMedCrossRefGoogle Scholar
  11. 11.
    Porcel JM, Vives M (2003) Etiology and pleural fluid characteristics of large and massive effusions. Chest 124:978–983PubMedCrossRefGoogle Scholar
  12. 12.
    Haro M, Ruiz-Manzano J, Gallego M, Abad J, Manterola JM, Morera J (1996) Pleural tuberculosis: analysis of 105 cases. Enferm Infecc Microbiol Clin 14:285–289PubMedGoogle Scholar
  13. 13.
    Yilmaz MU, Kumcuoglu Z, Utkaner G, Yalniz O, Erkmen G (1998) Computed tomography findings of tuberculous pleurisy. Int J Tuberc Lung Dis 2:164–167PubMedGoogle Scholar
  14. 14.
    Kim HJ, Lee HJ, Kwon SY, Yoon HI, Chung HS, Lee CT, Han SK, Shim YS, Yim JJ (2006) The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis. Chest 129:1253–1258PubMedCrossRefGoogle Scholar
  15. 15.
    Porcel JM, Vives M (2003) Differentiating tuberculous from malignant pleural effusions: a scoring model. Med Sci Monit 9:CR175–CR180PubMedGoogle Scholar
  16. 16.
    Gopi A, Madhavan SM, Sharma SK, Sahn SA (2007) Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest 131:880–889PubMedCrossRefGoogle Scholar
  17. 17.
    Lin MT, Wang JY, Yu CJ, Lee LN, Yang PC, The TAMI Group (2009) Mycobacterium tuberculosis and polymorphonuclear pleural effusion: incidence and clinical pointers. Respir Med 103:820–826PubMedCrossRefGoogle Scholar
  18. 18.
    Porcel-Pérez JM, Vives Soto M, Esquerda Serrano A, Jover Sáenz A (2004) Cuttoff values of biochemical tests on pleural fluid: their usefulness in differential diagnosis of 1,040 patients with pleural effusion. An Med Interna 21:113–117PubMedGoogle Scholar
  19. 19.
    Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ (2008) Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med 102:744–754PubMedCrossRefGoogle Scholar
  20. 20.
    Baba K, Hoosen AA, Langeland N, Dyrhol-Riise AM (2008) Adenosine deaminase activity is a sensitive marker for the diagnosis of tuberculous pleuritis in patients with very low CD4 counts. PLoS ONE 3(7):e2788PubMedCrossRefGoogle Scholar
  21. 21.
    Porcel JM, Vives M, Esquerda A, Ruiz A (2006) Usefulness of the British Thoracic Society and the American College of Chest Physicians guidelines in predicting pleural drainage of non-purulent parapneumonic effusions. Respir Med 100:933–937CrossRefGoogle Scholar
  22. 22.
    Lee YC, Rogers JT, Rodriguez RM, Miller KD, Light RW (2001) Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions. Chest 120:356–361PubMedCrossRefGoogle Scholar
  23. 23.
    Porcel JM, Vives M (2002) Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions. Chest 121:1379–1380PubMedCrossRefGoogle Scholar
  24. 24.
    Jiménez Castro D, Díaz Nuevo G, Pérez-Rodríguez E, Light RW (2003) Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions. Eur Respir J 21:220–224PubMedCrossRefGoogle Scholar
  25. 25.
    Zemlin AE, Burgess LJ, Carstens ME (2009) The diagnostic utility of adenosine deaminase isoenzymes in tuberculous pleural effusions. Int J Tuberc Lung Dis 13:214–220PubMedGoogle Scholar
  26. 26.
    Trajman A, Pai M, Dheda K, van Zyl Smit R, Zwerling AA, Joshi R, Kalantri S, Daley P, Menzies D (2008) Novel tests for diagnosing tuberculous pleural effusion: what works and what does not? Eur Respir J 31:1098–1106PubMedCrossRefGoogle Scholar
  27. 27.
    Jiang J, Shi HZ, Liang QL, Qin SM, Qin XJ (2007) Diagnostic value of interferon-gamma in tuberculous pleurisy: a meta-analysis. Chest 131:1133–1141PubMedCrossRefGoogle Scholar
  28. 28.
    Greco S, Girardi E, Masciangelo R, Capoccetta GB, Saltini C (2003) Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis. Int J Tuberc Lung Dis 7:777–786PubMedGoogle Scholar
  29. 29.
    Villena V, López-Encuentra A, Pozo F, Echave-Sustaeta J, Ortuño-de-Solo B, Estenoz-Alfaro J, Martín-Escribano P (2003) Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis. Am J Med 115:365–370PubMedCrossRefGoogle Scholar
  30. 30.
    Hooper CE, Lee YC, Maskell NA (2009) Interferon-gamma release assays for the diagnosis of TB pleural effusions: hype or real hope? Curr Opin Pulm Med 15:358–365PubMedCrossRefGoogle Scholar
  31. 31.
    Kim SH, Song KH, Choi SJ, Kim HB, Kim NJ, Oh MD, Choe KW (2009) Diagnostic usefulness of a T-cell-based assay for extrapulmonary tuberculosis in immunocompromised patients. Am J Med 122:189–195PubMedCrossRefGoogle Scholar
  32. 32.
    Baba K, Sørnes S, Hoosen AA, Lekabe JM, Mpe MJ, Langeland N, Dyrhol-Riise AM (2008) Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON TB-Gold interferon-gamma assay. BMC Infect Dis 8:35PubMedCrossRefGoogle Scholar
  33. 33.
    Ariga H, Kawabe Y, Nagai H, Kurashima A, Masuda K, Matsui H, Tamura A, Nagayama N, Akagawa S, Machida K, Hebisawa A, Nakajima Y, Yotsumoto H, Mori T (2007) Diagnosis of active tuberculous serositis by antigen-specific interferon-gamma response of cavity fluid cells. Clin Infect Dis 45:1559–1567PubMedCrossRefGoogle Scholar
  34. 34.
    Losi M, Bossink A, Codecasa L, Jafari C, Ernst M, Thijsen S, Cirillo D, Ferrarese M, Greinert U, Fabbri LM, Richeldi L, Lange C, TBNET European Tuberculosis Network (2007) Use of a T-cell interferon-gamma release assay for the diagnosis of tuberculous pleurisy. Eur Respir J 30:1173–1179PubMedCrossRefGoogle Scholar
  35. 35.
    Joshi R, Pai M (2008) Can pleural tuberculosis be diagnosed using interferon-gamma release assays? Respiration 76:128–130PubMedCrossRefGoogle Scholar
  36. 36.
    Conde MB, Loivos AC, Rezende VM, Soares SL, Mello FC, Reingold AL, Daley CL, Kritski AL (2003) Yield of sputum induction in the diagnosis of pleural tuberculosis. Am J Respir Crit Care Med 167:723–725PubMedCrossRefGoogle Scholar
  37. 37.
    Luzze H, Elliott AM, Joloba ML, Odida M, Oweka-Onyee J, Nakiyingi J, Quigley M, Hirsch C, Mugerwa RD, Okwera A, Johnson JL (2001) Evaluation of suspected tuberculous pleurisy: clinical and diagnostic findings in HIV-1-positive and HIV-negative adults in Uganda. Int J Tuberc Lung Dis 5:746–753PubMedGoogle Scholar
  38. 38.
    Hasaneen NA, Zaki ME, Shalaby HM, El-Morsi AS (2003) Polymerase chain reaction of pleural biopsy is a rapid and sensitive method for the diagnosis of tuberculous pleural effusion. Chest 124:2105–2111PubMedCrossRefGoogle Scholar
  39. 39.
    Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, Sanchez E, Piñedo Y, Saravia JC, Salazar C, Oberhelman R, Hollm-Delgado MG, LaChira D, Escombe AR, Friedland JS (2006) Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 355:1539–1550PubMedCrossRefGoogle Scholar
  40. 40.
    Tovar M, Siedner MJ, Gilman RH, Santillan C, Caviedes L, Valencia T, Jave O, Escombe AR, Moore DA, Evans CA (2008) Improved diagnosis of pleural tuberculosis using the microscopic-observation drug-susceptibility technique. Clin Infect Dis 46:909–912PubMedCrossRefGoogle Scholar
  41. 41.
    Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A (2007) A systematic review of rapid diagnostic tests for the detection of tuberculosis infection. Health Technol Assess 11:1–196PubMedGoogle Scholar
  42. 42.
    Pai M, Flores LL, Hubbard A, Riley LW, Colford JM Jr (2004) Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis. BMC Infect Dis 4:6PubMedCrossRefGoogle Scholar
  43. 43.
    Diacon AH, Van de Wal BW, Wyser C, Smedema JP, Bezuidenhout J, Bolliger CT, Walzl G (2003) Diagnostic tools in tuberculous pleurisy: a direct comparative study. Eur Respir J 22:589–591PubMedCrossRefGoogle Scholar
  44. 44.
    Daniil ZD, Zintzaras E, Kiropoulos T, Papaioannou AI, Koutsokera A, Kastanis A, Gourgoulianis KI (2007) Discrimination of exudative pleural effusions based on multiple biological parameters. Eur Respir J 30:957–964PubMedCrossRefGoogle Scholar
  45. 45.
    Zarić B, Kuruc V, Milovancev A, Markovic M, Sarcev T, Canak V, Pavlović S (2008) Differential diagnosis of tuberculous and malignant pleural effusions: what is the role of adenosine deaminase? Lung 186:233–240PubMedCrossRefGoogle Scholar
  46. 46.
    Ruiz-Manzano J, Blanquer R, Calpe JL, Caminero JA, Caylà J, Domínguez JA, García JM, Vidal R (2008) Diagnosis and treatment of tuberculosis. Arch Bronconeumol 44:551–566PubMedCrossRefGoogle Scholar
  47. 47.
    La tuberculosi a Catalunya [Tuberculosis in Catalonia] (2007) Programa de prevenció i control de la tuberculosi [Program of prevention and control of tuberculosis]. Departament de Salut, Generalitat de Catalunya, BarcelonaGoogle Scholar
  48. 48.
    Mitnick CD, Appleton SC, Shin SS (2008) Epidemiology and treatment of multidrug resistant tuberculosis. Semin Respir Crit Care Med 29:499–524PubMedCrossRefGoogle Scholar
  49. 49.
    Onyebujoh PC, Ribeiro I, Whalen CC (2007) Treatment options for HIV-associated tuberculosis. J Infect Dis 196(Suppl 1):S35–S45PubMedCrossRefGoogle Scholar
  50. 50.
    Lawn SD, Myer L, Bekker LG, Wood R (2007) Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS 21:335–341PubMedCrossRefGoogle Scholar
  51. 51.
    Cohen M, Sahn SA (2001) Resolution of pleural effusions. Chest 119:1547–1562PubMedCrossRefGoogle Scholar
  52. 52.
    Lai YF, Chao TY, Wang YH, Lin AS (2003) Pigtail drainage in the treatment of tuberculous pleural effusions: a randomized study. Thorax 58:149–151PubMedCrossRefGoogle Scholar
  53. 53.
    Chung CL, Chen CH, Yeh CY, Sheu JR, Chang SC (2008) Early effective drainage in the treatment of loculated tuberculous pleurisy. Eur Respir J 31:1261–1267PubMedCrossRefGoogle Scholar
  54. 54.
    Porcel JM, Rubio-Caballero M (2005) Sequelae of tuberculous pleural effusion. Med Clin (Barc) 124:494–496CrossRefGoogle Scholar
  55. 55.
    Engel ME, Matchaba PT, Volmink J (2007) Corticosteroids for tuberculous pleurisy. Cochrane Database Syst Rev 4:CD001876PubMedGoogle Scholar
  56. 56.
    Sahn SA, Iseman MD (1999) Tuberculous empyema. Semin Respir Infect 14:82–87PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Internal Medicine, Pleural Diseases Unit, Arnau de Vilanova University HospitalInstitut de Recerca Biomèdica de Lleida (IRBLLEIDA)LleidaSpain

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