Tuberc Respir Dis.  2015 Apr;78(2):47-55. 10.4046/trd.2015.78.2.47.

Diagnosis and Treatment of Extrapulmonary Tuberculosis

• Lee JY

• KMID: 2320594
• DOI: http://doi.org/10.4046/trd.2015.78.2.47

Abstract

Extrapulmonary tuberculosis (EPTB) constitutes about 20% of all cases of tuberculosis (TB) in Korea. Diagnosing EPTB remains challenging because clinical samples obtained from relatively inaccessible sites may be paucibacillary, thus decreasing the sensitivity of diagnostic tests. Whenever practical, every effort should be made to obtain appropriate specimens for both mycobacteriologic and histopathologic examinations. The measurement of biochemical markers in TB-affected serosal fluids (adenosine deaminase or gamma interferon) and molecular biology techniques such as polymerase chain reaction may be useful adjuncts in the diagnosis of EPTB. Although the disease usually responds to standard anti-TB drug therapy, the ideal regimen and duration of treatment have not yet been established. A paradoxical response frequently occurs during anti-TB therapy. It should be distinguished from other causes of clinical deterioration. Surgery is required mainly to obtain valid diagnostic specimens and to manage complications. Because smear microscopy or culture is not available to monitor patients with EPTB, clinical monitoring is the usual way to assess the response to treatment.

Keyword

Tuberculosis; Diagnosis; Therapeutics; Surgical Procedures, Operative

MeSH Terms

Biomarkers
Diagnosis*
Diagnostic Tests, Routine
Drug Therapy
Humans
Korea
Microscopy
Molecular Biology
Polymerase Chain Reaction
Surgical Procedures, Operative
Tuberculosis*

Reference

1. World Health Organization. Definitions and reporting framework for tuberculosis: 2013 revision (updated December 2014). Geneva: World Health Organization;2013.

2. Korea Centers for Disease Control and Prevention. Annual report on the notified tuberculosis in Korea. Cheongwon: Korea Centers for Disease Control and Prevention;2014. p. 2013.

3. Kruijshaar ME, Abubakar I. Increase in extrapulmonary tuberculosis in England and Wales 1999-2006. Thorax. 2009; 64:1090–1095.

4. Canadian Thoracic Society and The Public Health Agency of Canada and Licensors. Canadian tuberculosis standards. 7th ed. Ottawa: Public Health Agency of Canada;2013.

5. Parimon T, Spitters CE, Muangman N, Euathrongchit J, Oren E, Narita M. Unexpected pulmonary involvement in extrapulmonary tuberculosis patients. Chest. 2008; 134:589–594.

6. Lee J, Lee SY, Choi KJ, Lim JK, Yoo SS, Lee SY, et al. Clinical Utility of CT-based bronchial aspirate TB-PCR for the rapid diagnosis of pleural tuberculosis. Tuberc Respir Dis. 2013; 75:150–156.

7. Conde MB, Loivos AC, Rezende VM, Soares SL, Mello FC, Reingold AL, et al. Yield of sputum induction in the diagnosis of pleural tuberculosis. Am J Respir Crit Care Med. 2003; 167:723–725.

8. Kennedy DH, Fallon RJ. Tuberculous meningitis. JAMA. 1979; 241:264–268.

9. Marshall JB. Tuberculosis of the gastrointestinal tract and peritoneum. Am J Gastroenterol. 1993; 88:989–999.

10. de Noronha AL, Bafica A, Nogueira L, Barral A, Barral-Netto M. Lung granulomas from Mycobacterium tuberculosis/HIV-1 co-infected patients display decreased in situ TNF production. Pathol Res Pract. 2008; 204:155–161.

11. Zumla A, James DG. Granulomatous infections: etiology and classification. Clin Infect Dis. 1996; 23:146–158.

12. Valdes L, Alvarez D, San Jose E, Penela P, Valle JM, Garcia-Pazos JM, et al. Tuberculous pleurisy: a study of 254 patients. Arch Intern Med. 1998; 158:2017–2021.

13. Kim DW, Jung SJ, Ha TK, Park HK. Individual and combined diagnostic accuracy of ultrasound diagnosis, ultrasoundguided fine-needle aspiration and polymerase chain reaction in identifying tuberculous lymph nodes in the neck. Ultrasound Med Biol. 2013; 39:2308–2314.

14. Fontanilla JM, Barnes A, von Reyn CF. Current diagnosis and management of peripheral tuberculous lymphadenitis. Clin Infect Dis. 2011; 53:555–562.

15. Chow KM, Chow VC, Hung LC, Wong SM, Szeto CC. Tuberculous peritonitis-associated mortality is high among patients waiting for the results of mycobacterial cultures of ascitic fluid samples. Clin Infect Dis. 2002; 35:409–413.

16. Jeon D. Tuberculous pleurisy: an update. Tuberc Respir Dis. 2014; 76:153–159.

17. Ruan SY, Chuang YC, Wang JY, Lin JW, Chien JY, Huang CT, et al. Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area. Thorax. 2012; 67:822–827.

18. Bielsa S, Palma R, Pardina M, Esquerda A, Light RW, Porcel JM. Comparison of polymorphonuclear- and lymphocyterich tuberculous pleural effusions. Int J Tuberc Lung Dis. 2013; 17:85–89.

19. Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J, et al. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009; 59:167–187.

20. Greco S, Girardi E, Masciangelo R, Capoccetta GB, Saltini C. Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis. Int J Tuberc Lung Dis. 2003; 7:777–786.

21. Lee SJ, Kim HS, Lee SH, Lee TW, Lee HR, Cho YJ, et al. Factors influencing pleural adenosine deaminase level in patients with tuberculous pleurisy. Am J Med Sci. 2014; 348:362–365.

22. Abrao FC, de Abreu IR, Miyake DH, Busico MA, Younes RN. Role of adenosine deaminase and the influence of age on the diagnosis of pleural tuberculosis. Int J Tuberc Lung Dis. 2014; 18:1363–1369.

23. Liao YJ, Wu CY, Lee SW, Lee CL, Yang SS, Chang CS, et al. Adenosine deaminase activity in tuberculous peritonitis among patients with underlying liver cirrhosis. World J Gastroenterol. 2012; 18:5260–5265.

24. Cho BH, Kim BC, Yoon GJ, Choi SM, Chang J, Lee SH, et al. Adenosine deaminase activity in cerebrospinal fluid and serum for the diagnosis of tuberculous meningitis. Clin Neurol Neurosurg. 2013; 115:1831–1836.

25. Tuon FF, Higashino HR, Lopes MI, Litvoc MN, Atomiya AN, Antonangelo L, et al. Adenosine deaminase and tuberculous meningitis: a systematic review with meta-analysis. Scand J Infect Dis. 2010; 42:198–207.

26. Riquelme A, Calvo M, Salech F, Valderrama S, Pattillo A, Arellano M, et al. Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: a metaanalysis. J Clin Gastroenterol. 2006; 40:705–710.

27. Tuon FF, Litvoc MN, Lopes MI. Adenosine deaminase and tuberculous pericarditis: a systematic review with metaanalysis. Acta Trop. 2006; 99:67–74.

28. Jiang J, Shi HZ, Liang QL, Qin SM, Qin XJ. Diagnostic value of interferon-gamma in tuberculous pleurisy: a metaanalysis. Chest. 2007; 131:1133–1141.

29. Burgess LJ, Reuter H, Carstens ME, Taljaard JJ, Doubell AF. The use of adenosine deaminase and interferon-gamma as diagnostic tools for tuberculous pericarditis. Chest. 2002; 122:900–905.

30. Manjunath N, Shankar P, Rajan L, Bhargava A, Saluja S, Shriniwas . Evaluation of a polymerase chain reaction for the diagnosis of tuberculosis. Tubercle. 1991; 72:21–27.

31. Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, et al. A systematic review of rapid diagnostic tests for the detection of tuberculosis infection. Health Technol Assess. 2007; 11:1–196.

32. Linasmita P, Srisangkaew S, Wongsuk T, Bhongmakapat T, Watcharananan SP. Evaluation of real-time polymerase chain reaction for detection of the 16S ribosomal RNA gene of Mycobacterium tuberculosis and the diagnosis of cervical tuberculous lymphadenitis in a country with a high tuberculosis incidence. Clin Infect Dis. 2012; 55:313–321.

33. Trajman A, da Silva Santos Kleiz de Oliveira EF, Bastos ML, Belo Neto E, Silva EM, da Silva Lourenco MC, et al. Accuracy of polimerase chain reaction for the diagnosis of pleural tuberculosis. Respir Med. 2014; 108:918–923.

34. Kim YW, Kwak N, Seong MW, Kim EC, Yoo CG, Kim YW, et al. Accuracy of the Xpert(R) MTB/RIF assay for the diagnosis of extra-pulmonary tuberculosis in South Korea. Int J Tuberc Lung Dis. 2015; 19:81–86.

35. Denkinger CM, Schumacher SG, Boehme CC, Dendukuri N, Pai M, Steingart KR. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and metaanalysis. Eur Respir J. 2014; 44:435–446.

36. World Health Organization. Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children: policy update. Geneva: World Health Organization;2013.

37. Fan L, Chen Z, Hao XH, Hu ZY, Xiao HP. Interferon-gamma release assays for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. FEMS Immunol Med Microbiol. 2012; 65:456–466.

38. Cho OH, Park KH, Kim SM, Park SJ, Moon SM, Chong YP, et al. Diagnostic performance of T-SPOT.TB for extrapulmonary tuberculosis according to the site of infection. J Infect. 2011; 63:362–369.

39. Shin JA, Chang YS, Kim HJ, Ahn CM, Byun MK. Diagnostic utility of interferon-gamma release assay in extrapulmonary tuberculosis. Diagn Microbiol Infect Dis. 2015; 02. 14. [Epub]. http://dx.doi.org/10.1016/j.diagmicrobio.2015.02.002.

40. Zhang L, Zhang Y, Shi X, Zhang Y, Deng G, Lalvani A, et al. Utility of T-cell interferon-gamma release assays for diagnosing tuberculous serositis: a prospective study in Beijing, China. PLoS One. 2014; 9:e85030.

41. Zhou Q, Chen YQ, Qin SM, Tao XN, Xin JB, Shi HZ. Diagnostic accuracy of T-cell interferon-gamma release assays in tuberculous pleurisy: a meta-analysis. Respirology. 2011; 16:473–480.

42. Park KH, Cho OH, Lee EM, Lee SO, Choi SH, Kim YS, et al. Tcell-based assays on cerebrospinal fluid and PBMCs for rapid diagnosis of TB meningitis in non-HIV patients. Eur Respir J. 2012; 39:768–770.

43. Kim SH, Cho OH, Park SJ, Lee EM, Kim MN, Lee SO, et al. Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells. Clin Infect Dis. 2010; 50:1349–1358.

44. Thwaites GE, van Toorn R, Schoeman J. Tuberculous meningitis: more questions, still too few answers. Lancet Neurol. 2013; 12:999–1010.

45. Lee JY, Kim SM, Park SJ, Lee SO, Choi SH, Kim YS, et al. A rapid and non-invasive 2-step algorithm for diagnosing tuberculous peritonitis using a T cell-based assay on peripheral blood and peritoneal fluid mononuclear cells together with peritoneal fluid adenosine deaminase. J Infect. 2015; 70:356–366.

46. Biglino A, Crivelli P, Concialdi E, Bolla C, Montrucchio G. Clinical usefulness of ELISPOT assay on pericardial fluid in a case of suspected tuberculous pericarditis. Infection. 2008; 36:601–604.

47. Bathoorn E, Limburg A, Bouwman JJ, Bossink AW, Thijsen SF. Diagnostic potential of an enzyme-linked immunospot assay in tuberculous pericarditis. Clin Vaccine Immunol. 2011; 18:874–877.

48. World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization;2008.

49. Ruslami R, Ganiem AR, Dian S, Apriani L, Achmad TH, van der Ven AJ, et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013; 13:27–35.

50. Joint Committee for the Revision of Korean Guidelines for Tuberculosis, Korea Centers for Disease Control and Prevention. Korean guidelines for tuberculosis. 2nd ed. Seoul and Cheongwon: Joint Committee for the Revision of Korean Guidelines for Tuberculosis, Korea Centers for Disease Control and Prevention;2014.

51. Campbell IA, Ormerod LP, Friend JA, Jenkins PA, Prescott RJ. Six months versus nine months chemotherapy for tuberculosis of lymph nodes: final results. Respir Med. 1993; 87:621–623.

52. Park SH, Yang SK, Yang DH, Kim KJ, Yoon SM, Choe JW, et al. Prospective randomized trial of six-month versus ninemonth therapy for intestinal tuberculosis. Antimicrob Agents Chemother. 2009; 53:4167–4171.

53. Cho OH, Park KH, Park SY, Moon SM, Chong YP, Kim MN, et al. Drug-resistant extrapulmonary tuberculosis. Infect Chemother. 2011; 43:258–261.

54. Cheng VC, Ho PL, Lee RA, Chan KS, Chan KK, Woo PC, et al. Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients. Eur J Clin Microbiol Infect Dis. 2002; 21:803–809.

55. Geri G, Passeron A, Heym B, Arlet JB, Pouchot J, Capron L, et al. Paradoxical reactions during treatment of tuberculosis with extrapulmonary manifestations in HIV-negative patients. Infection. 2013; 41:537–543.

56. American Thoracic Society. CDC. Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003; 52:1–77.

57. Jeon K, Choi WI, An JS, Lim SY, Kim WJ, Park GM, et al. Paradoxical response in HIV-negative patients with pleural tuber culosis: a retrospective multicentre study. Int J Tuberc Lung Dis. 2012; 16:846–851.

58. Garg RK, Malhotra HS, Kumar N. Paradoxical reaction in HIV negative tuberculous meningitis. J Neurol Sci. 2014; 340:26–36.

59. Cho OH, Park KH, Kim T, Song EH, Jang EY, Lee EJ, et al. Paradoxical responses in non-HIV-infected patients with peripheral lymph node tuberculosis. J Infect. 2009; 59:56–61.

60. Park KH, Lee MS, Lee SO, Choi SH, Kim YS, Woo JH, et al. Incidence and outcomes of paradoxical lymph node enlargement after anti-tuberculosis therapy in non-HIV patients. J Infect. 2013; 67:408–415.

61. Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT, Nguyen TC, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004; 351:1741–1751.

62. Prasad K, Singh MB. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 2008; (1):CD002244.

63. Mayosi BM, Ntsekhe M, Volmink JA, Commerford PJ. Interventions for treating tuberculous pericarditis. Cochrane Database Syst Rev. 2002; (4):CD000526.

64. Mayosi BM, Ntsekhe M, Bosch J, Pandie S, Jung H, Gumedze F, et al. Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis. N Engl J Med. 2014; 371:1121–1130.

65. Engel ME, Matchaba PT, Volmink J. Corticosteroids for tuberculous pleurisy. Cochrane Database Syst Rev. 2007; (4):CD001876.

66. Lai YF, Chao TY, Wang YH, Lin AS. Pigtail drainage in the treatment of tuberculous pleural effusions: a randomised study. Thorax. 2003; 58:149–151.

67. Chung CL, Chen CH, Yeh CY, Sheu JR, Chang SC. Early effective drainage in the treatment of loculated tuberculous pleurisy. Eur Respir J. 2008; 31:1261–1267.

68. Mayosi BM, Burgess LJ, Doubell AF. Tuberculous pericarditis. Circulation. 2005; 112:3608–3616.

69. Cek M, Lenk S, Naber KG, Bishop MC, Johansen TE, Botto H, et al. EAU guidelines for the management of genitourinary tuberculosis. Eur Urol. 2005; 48:353–362.

70. van Loenhout-Rooyackers JH, Laheij RJ, Richter C, Verbeek AL. Shortening the duration of treatment for cervical tuberculous lymphadenitis. Eur Respir J. 2000; 15:192–195.

71. Jain AK, Sreenivasan R, Saini NS, Kumar S, Jain S, Dhammi IK. Magnetic resonance evaluation of tubercular lesion in spine. Int Orthop. 2012; 36:261–269.

72. Joseffer SS, Cooper PR. Modern imaging of spinal tuberculosis. J Neurosurg Spine. 2005; 2:145–150.

73. Youn JE, Park IB, Kwon SY, Kim JS, Byun KS, Bak YT, et al. Follow-up colonoscopy at 3 months of therapy in patients with tentative diagnosis of intestinal tuberculosis. Korean J Med. 1996; 50:227–233.

74. Kim YS, Kim YH, Lee KM, Kim JS, Park YS. IBD Study Group of the Korean Association of the Study of Intestinal Diseases. Diagnostic guideline of intestinal tuberculosis. Korean J Gastroenterol. 2009; 53:177–186.