TB pleural effusion

1. TB pleural effusion 林倬睿醫師

2. Outlines • Introduction • Etiology & pathogenesis • Symptoms, laboratory & radiologic findings • Diagnosis • Treatment & management • Complications

3. Introduction • 是由結核菌感染肋膜所引起 • 通常為exudate, 可以同時合併肺部病灶 • 為最常見的肺外結核表現 • HIV患者若CD4數目較高,則TB pleural effusion發生率較高,可見TB pleural effusion的形成不只是感染,更是一種免疫反應(immunological response)

4. Etiology & pathogenesis • Mycobacterial protein access pleural cavity through a rupture of a subpleural focus • TB protein  mesothelial/endothelial cells  cytokines neutrophils, lymphocytes, monocytes, etc • Pleural fluid: neutrophil in the early phase, highly suggestive of TB if lymphocyte > 85%

5. Mycobacteria liposaccharides Mesothelial / endothelial cells IL-1, IL-6, TNF- α chemokines-α chemokines- MIP-1, MCP-1, TNF- α IL-8, NAP2 ADA1 Neutrophil, lymphocyte ADA2-ADA1 Activated lymphocyte Th1 Monocyte- macrophage Mycobacteria IL-1, TNF- α Mesothelial cell IL-12, IFN-ɤ

6. Etiology & pathogenesis • HIV pt 因免疫反應差,在effusion中較常發現TB菌,biopsy中則較少見granuloma • Effusion的形成雖與免疫反應有關,但得到TB pleurisy不表示就因此產生抵抗力,若未治療,即使自然痊癒,將來仍有超過65%會發生active pulmonary TB • TB可以躲在macrophage中

7. Symptoms • Male : female = 3 : 1 • Mostly < 35y/o or > 70y/o • Acute or subacute onset • S/S to diagnosis: < 1month • Cough, fever, chest pain, dyspnea • HIV pt: hepatosplenomegaly, LAP, less PPD (+)

8. Laboratory findings • Non-specific (ESR , normal WBC) • Pleural effusion: • color : serofibrinous, serosanguinous • exudate • lymphocyte predominant • exclude TB, if : eosinophil > 10% mesothelial cell > 5%

9. Radiological findings • Usually unilateral, small to moderate in size • 30% 的病人在同側肺實質有radiological disease • HIV pt 的effusion量較多,雙側有水的機會也比一般人高 • Primary: lower lobe involvement & LAP

12. Diagnosis • Presumption: prevalence, HIV co-infection, pleural effusion, clinical symptoms • Definite diagnosis: • M. TB in sputum or effusion • caseous granulomas in the pleura

14. P.E. with atelectasis • anechoic (C) complex nonseptated • (D) complex septated • (E) homogenously echogenic • (F) parapneumonic effusion • (G) malignant effusion

15. Granuloma of Tuberculosis

20. Diagnosis • Positive sputum culture rate: • 30–50% in pleural + lung involvement • only 4% in pleural involvement alone • Diagnostic methods: • pleural effusion culture: 23-86% • biopsy culture: 39-71% • presence of necrotizing caseous granuloma in biopsy: most efficient, 51-87% • all combined: 82-98%

21. Diagnosis • Among HIV pt: • more positive sputum culture • more AFB (+) in pleural effusion • more positive biopsy culture • less granuloma formation

22. Diagnosis • Conventional method: pleural biopsy • New methods: • finding TB: radiometric culture system, PCR • measure parameters caused by immunological-metabolic mechanism: adenosine deaminase (ADA), IFN-ɤ, etc

23. Diagnosis • Radiometric culture system: • accelerate diagnosis by 2-3 weeks • PCR • rapid • identify the type of mycobacteria • determine susceptibility to drugs • not that reliable, requires QC procedure

24. Diagnosis • ADA (adenosine deaminase) • Pleural TB infection  increased metabolic activity of the monocytes & macrophages  increased production of ADA • High levels of ADA: TB pleurisy, empyema, malignant lymphoma, collagen-vascular disease • Sensitivity: 77-100%, specificity: 81-97%

25. Diagnosis • ADA (adenosine deaminase) • Association with L/N ratio > 0.75 or < 35y/o greatly improves the specificity • No differences with regard to HIV status • May be a better negative predictive parameter • ADA1: ubiquitous • ADA2: only in monocytes, macrophages

26. Diagnosis • IFN-ɤ • relative good sensitivity & specificity • False positive: parapneumonic effusion, lymphoma, malignancy • Disadvantage: expensive, slow • Others • Lysozyme, tuberculostearic acid, monoclonal antibody, cytokines

27. Treatment • Spontaneous resolution in 2-4 months in healthy individuals • 65% will develop pulmonary tuberculosis in 5 years • So, it is important to treat pleural tuberculosis

28. Treatment • Should be monitored by official public health center • Ensure correct treatment • Prevent the emergence of resistant strain • Evaluation of contacts • Monitor the pattern of resistances • Provide education to the patients • Identify possible outbreaks

29. Treatment • As pulmonary TB, combination therapy is preferred • Reducing the population of mycobacteria • Without creating resistance • Sterilizing the lesions during prolonged treatment phase

30. Treatment • Duration: 6 month is recommended • Number of drugs: HRZ for 2 months, then HR for 4 months. • Add EMB if • Local resistance to INAH > 4% • High levels of resistance are reported • Received anti-TB drug previously • Exposed to MDR-TB patients

31. Treatment • Some may show an increase of pleural effusion during the initial phase • Standard treatment is recommended for HIV patients. • If the clinical or bacteriological response is slow or less than optimal  prolong treatment

32. Treatment • Use of steroid • Insufficient evidence to prove that steroid can reduce inflammation and subsequent residual pachypleuritis • 不如在診斷性抽水時把水抽乾一點

33. Complications • Residual pleural thickening • Most frequent • Incidence varies according to the time of evaluation and the degree of thickness • No variable idetified • Minimal impact on lung functions

34. Complications • Tuberculous empyema • Unusual, normally related to BP fistula • Response to medical treatment is limited • Frequently requires thoracotomy and/or decortication • May consider repeated thoracentesis with prolonged medical treatment • Thoracic wall infection • Rare, 1/106

35. Thanks for your attention!