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-
IL-8, NAP2
MIP-1, MCP-1, TNF- α
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: PCR
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: %, 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 Others relative good sensitivity & specificity
False positive: parapneumonic effusion, lymphoma, malignancy
Disadvantage: expensive, slow
Others
Lysozyme, tuberculostearic acid, monoclonal antibody, cytokines

27. So, it is important to treat pleural tuberculosis
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 Thoracic wall infection
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!