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TUBERCULOSIS PLEURAL
EFFUSION - MANAGEMENT
Introduction : ETB – 15-20%
Pleural effusion – 20% in non HIV
Under reporting because of AFB negative in
fluid
In HIV patients: EPTB – 20%
                   PTB + EPTB – 50%
                   Pleural Effusion – 20%
It is more common in young populations.
Now tendency to affect aged patients.
(IndianJMedical Res )
PATHOGENESIS
 Typically 4-7 months following initial
 infection with TB.
 Rupture of small subpleural focus
 Delayed hypersensitivity reaction
 Possibility the intense inflammation
 obstructs the lymphatic pores in the
 parietal     pleura    which      causes
 accumulation of protein in pleural
 cavity.
CLINICAL
MANIFESTATION
 Most commonly manifests as an acute
 illness
 Cough 70% , usually non productive
 Chest pain 75%
 Usually unilateral
 Bil – Occurs in 10%
NATURAL HISTORY OF
 UNTREATED EFFUSION
90% usually subside spontaneously
Effusion usually resolve and all other
symptoms disappear within 2-4 months
Follow up over time – 40-60% develop
tuberculosis
Size of original effusion and the presence or
absence of small radiologic residual pleural
disease do not correlate with subsequent
tuberculosis
Residual     pleural    thickening   common
sequelae ~ 50%.
DIAGNOSIS
 Diagnosis depends on the
 demonstration of tubercle bacilli –
 In sputum
 Pleural fluid
 Pleural biopsy specimen
 Granuloma in pleura
 The diagnosis can also be established
 with reasonable certaintly by ADA ↑
TUBERCULIN TEST
Positive in 60-75% patients, many of negative
patients will become tuberculin positive in 6-8
week
Negative tuberculin – HIV patients &
malnutrition
There may sequestration of PPD reactive
lymphocytes in the pleural space.
A circulating adherent cell suppresses the
sensitized T- lymphocytes
Sputum Examination
 Even in absence of underlying infiltrate
 Sputum AFB & culture – 55%
RADIOLOGY
Parenchymal infiltrates – 20%
The classic patterns of primary tuberculosis
in the form of non cavitary, lower lobe
parenchymal infiltrates.
CT Scan – 40% parenchyma involvement
Encysted effusion usually occurs during ATT
treatment
Most often encystment occurs in the
costoparietal regions ( Post aspects)
PLEURAL FLUID – ANALYSIS
Often protein > 5.0 gm/ dl
Usually more than 50% lymphocytes
If symptoms less than 2 weeks then pleural
fluid may reveal poly.
Eosinophil > 10% usually excludes the
diagnosis of tuberculosis pleuritis.
Mesothelial cells < 3% .
HIV infected patients with tuberculosis
pleuritis may have significant number of
mesothelial cells in the pleural fluids.
ADA
Enzyme that catalyzes the conversion of
adenosinie to inosine.
1978 – Pirus et al
ADA-1 – All cells
ADA -2 – Only in monocytes
Majority of ADA in tuberculosis pleural fluid
is ADA -2
Higher the pleural fluid ADA level, the more
likely patient is to have tuberculosis.
ADA (contd.)
 Level of cut-off value
   High Specificity – 83%
   Sensitivity – 77-100%
 L: N > 0.75 – Specificity ↑
 High ADA – empyema
 - Rheumatoid arthritis
 But do not have pleural fluid
 lymphocytosis
 Cut off value < 40
        40-60
ADA ( contd.)
Although the use of a ratio of the ADA -1
to ADA -2 less than 0: 42 will slightly
increase the sensitivity and specificity of
ADA, the separation of ADA into its
isoenzyme is not necessary.
ADA     level   maintained    at   ambient
temperature. It decreases with time. But
addition of glycerol, sodium sulfate–Stable
at room temperature for 3 months.
INTERFERON – GAMMA
Produced by CD4
Sensitivity & specificity > 94%
It retains diagnostic efficacy in HIV patients
IFN - γ is more specific than ADA chiefly
due to low levels of IFN in lymphoma and
empyma.
Expensive not used routinely.
PCR
PCR is certainly not superior to either the
pleural fluid ADA or interferon gamma
levels
Sensitivity ~ 80%
Specificity is not 100%
False positive may occur due to DNA
contamination
  Nonviable organism
  Latent infection
  Reactivation due to imunosuppression caused
  by primary malignant involvement of pleura.
Lysozyme

Released from lysozyme containing cells –
granulocytes, monocytes, macrophages.
The value of lysozyme levels in the
diagnosis of tuberculosis effusion, however,
is controversial
ADA : Lysozyme , has been found to
be useful in differentiating tuberculosis
from empyema. A thresholds value
above 3.3 has been shown to be highly
specific for tuberculosis pleural effusion.
PLEURAL FLUIDS STAINS
AND CULTURE
 In immunocompetent patients AFB
 smear – rarely positive.
 In HIV patients AFB smear is positive –
 20%
 Pleural fluid culture is positive ~ 40%
 Use of BACTEC system with bedside
 inoculation provides higher yield and
 faster results than do conventional
 methods.
PLEURAL BIOPSY
 The demonstration of granuloma in the
 parietal pleura suggests TB
 Other common causes of granuloma
               fungal disease
               RA
               Sarcoidosis
 Acid fast stain is positive in 25%.
 Culture for AFB positive – 60% .
 Combination of three test. Positive in
 91%.
Standard recommendation for biopsy
If ADA > 70        L:N > 0.75 – No biopsy
If ADA – 40-70 : L:N > 0.75
    Presumptive diagnosis of tuberculosis
    Biopsy if clinical picture is not
supportive of tuberculosis
ADA < 40- Clinical picture suggestive of
tuberculosis – Pleural biopsy
USG guided ( Tru cut ) biopsy of pleura
Involvement of pleura is not uniform, so
 closed biopsy may miss actual site of
 lesions.
 Closed biopsy with cope or an abrams
 needle can obtain adequate specimen and
 achieve 57-80% diagnostic rate in
 tuberculosis pleuritis.
DISADVANTAGES
Air leakage
Needle breakage
May not be diagnostic
Abrams needle wide bore, needs skin
incision
Nonspecific changes upto as high as
68% have been reported in the closed
biopsy.
USG GUIDED TRU CUT
BIOPSY
Advantages
 It can localize the minimal or loculated
 effusion
 it can demonstrate focal pleural
 thickening
 sensitivity for pleural tuberclosis – 86%
TREATMENTS
Goals
 To prevent the subsequent
 development of active tuberculsosis
 To relieve symptoms
 to prevent development of a fibrothorax
ATT
 Average patient becomes afebrile
 without 2 week
 Complete resorption of fluid 6-12 weeks
 The incidence of pleural thickening at 6-
 12 months -50%
CORTICOSTEROIDS
 No role of systemic steroids
 If more than mildly symptomatic
   A therapeutic thoracentesis is
   recommended
 Severe symptoms & diagnosis has been
 established – Steroids
Surgical procedure
 Large pleural effusion – thoracentesis,
 Decortication rarely necessary
Tuberculosis Empyema
 ICTD + ATT
HIV & TUBERCULOSIS
PLEURAL EFFUSION

 Incidence – CD4 < 200- 0 ↓
 CD> 200 - ↑
 Overall incidence - ±↑↓
 Duration of illness longer
 Chest pain less common
Systemic      manifestation   –    Fever,   anemia,
lymphadenopathy, organomegaly – common
Mantoux test often negative (40%)
AFB smear in pleural fluid -25%
If CD4 count < 100. 50% positive fluid AFB smear
positive
Significant number of mesothelial cells in their
pleural fluid
Biopsy – Granuloma on pleural biopsy are less well
formed
In pleural fluid ,the level of albumin are relatively
low
The level of ADA in patients without AIDS are
comparable.
THANK YOU

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  • 1. TUBERCULOSIS PLEURAL EFFUSION - MANAGEMENT Introduction : ETB – 15-20% Pleural effusion – 20% in non HIV Under reporting because of AFB negative in fluid In HIV patients: EPTB – 20% PTB + EPTB – 50% Pleural Effusion – 20% It is more common in young populations. Now tendency to affect aged patients. (IndianJMedical Res )
  • 2. PATHOGENESIS Typically 4-7 months following initial infection with TB. Rupture of small subpleural focus Delayed hypersensitivity reaction Possibility the intense inflammation obstructs the lymphatic pores in the parietal pleura which causes accumulation of protein in pleural cavity.
  • 3. CLINICAL MANIFESTATION Most commonly manifests as an acute illness Cough 70% , usually non productive Chest pain 75% Usually unilateral Bil – Occurs in 10%
  • 4. NATURAL HISTORY OF UNTREATED EFFUSION 90% usually subside spontaneously Effusion usually resolve and all other symptoms disappear within 2-4 months Follow up over time – 40-60% develop tuberculosis Size of original effusion and the presence or absence of small radiologic residual pleural disease do not correlate with subsequent tuberculosis Residual pleural thickening common sequelae ~ 50%.
  • 5. DIAGNOSIS Diagnosis depends on the demonstration of tubercle bacilli – In sputum Pleural fluid Pleural biopsy specimen Granuloma in pleura The diagnosis can also be established with reasonable certaintly by ADA ↑
  • 6. TUBERCULIN TEST Positive in 60-75% patients, many of negative patients will become tuberculin positive in 6-8 week Negative tuberculin – HIV patients & malnutrition There may sequestration of PPD reactive lymphocytes in the pleural space. A circulating adherent cell suppresses the sensitized T- lymphocytes
  • 7. Sputum Examination Even in absence of underlying infiltrate Sputum AFB & culture – 55%
  • 8. RADIOLOGY Parenchymal infiltrates – 20% The classic patterns of primary tuberculosis in the form of non cavitary, lower lobe parenchymal infiltrates. CT Scan – 40% parenchyma involvement Encysted effusion usually occurs during ATT treatment Most often encystment occurs in the costoparietal regions ( Post aspects)
  • 9. PLEURAL FLUID – ANALYSIS Often protein > 5.0 gm/ dl Usually more than 50% lymphocytes If symptoms less than 2 weeks then pleural fluid may reveal poly. Eosinophil > 10% usually excludes the diagnosis of tuberculosis pleuritis. Mesothelial cells < 3% . HIV infected patients with tuberculosis pleuritis may have significant number of mesothelial cells in the pleural fluids.
  • 10. ADA Enzyme that catalyzes the conversion of adenosinie to inosine. 1978 – Pirus et al ADA-1 – All cells ADA -2 – Only in monocytes Majority of ADA in tuberculosis pleural fluid is ADA -2 Higher the pleural fluid ADA level, the more likely patient is to have tuberculosis.
  • 11. ADA (contd.) Level of cut-off value High Specificity – 83% Sensitivity – 77-100% L: N > 0.75 – Specificity ↑ High ADA – empyema - Rheumatoid arthritis But do not have pleural fluid lymphocytosis Cut off value < 40 40-60
  • 12. ADA ( contd.) Although the use of a ratio of the ADA -1 to ADA -2 less than 0: 42 will slightly increase the sensitivity and specificity of ADA, the separation of ADA into its isoenzyme is not necessary. ADA level maintained at ambient temperature. It decreases with time. But addition of glycerol, sodium sulfate–Stable at room temperature for 3 months.
  • 13. INTERFERON – GAMMA Produced by CD4 Sensitivity & specificity > 94% It retains diagnostic efficacy in HIV patients IFN - γ is more specific than ADA chiefly due to low levels of IFN in lymphoma and empyma. Expensive not used routinely.
  • 14. PCR PCR is certainly not superior to either the pleural fluid ADA or interferon gamma levels Sensitivity ~ 80% Specificity is not 100% False positive may occur due to DNA contamination Nonviable organism Latent infection Reactivation due to imunosuppression caused by primary malignant involvement of pleura.
  • 15. Lysozyme Released from lysozyme containing cells – granulocytes, monocytes, macrophages. The value of lysozyme levels in the diagnosis of tuberculosis effusion, however, is controversial
  • 16. ADA : Lysozyme , has been found to be useful in differentiating tuberculosis from empyema. A thresholds value above 3.3 has been shown to be highly specific for tuberculosis pleural effusion.
  • 17. PLEURAL FLUIDS STAINS AND CULTURE In immunocompetent patients AFB smear – rarely positive. In HIV patients AFB smear is positive – 20% Pleural fluid culture is positive ~ 40% Use of BACTEC system with bedside inoculation provides higher yield and faster results than do conventional methods.
  • 18. PLEURAL BIOPSY The demonstration of granuloma in the parietal pleura suggests TB Other common causes of granuloma fungal disease RA Sarcoidosis Acid fast stain is positive in 25%. Culture for AFB positive – 60% . Combination of three test. Positive in 91%.
  • 19. Standard recommendation for biopsy If ADA > 70 L:N > 0.75 – No biopsy If ADA – 40-70 : L:N > 0.75 Presumptive diagnosis of tuberculosis Biopsy if clinical picture is not supportive of tuberculosis ADA < 40- Clinical picture suggestive of tuberculosis – Pleural biopsy
  • 20. USG guided ( Tru cut ) biopsy of pleura Involvement of pleura is not uniform, so closed biopsy may miss actual site of lesions. Closed biopsy with cope or an abrams needle can obtain adequate specimen and achieve 57-80% diagnostic rate in tuberculosis pleuritis.
  • 21. DISADVANTAGES Air leakage Needle breakage May not be diagnostic Abrams needle wide bore, needs skin incision Nonspecific changes upto as high as 68% have been reported in the closed biopsy.
  • 22. USG GUIDED TRU CUT BIOPSY Advantages It can localize the minimal or loculated effusion it can demonstrate focal pleural thickening sensitivity for pleural tuberclosis – 86%
  • 23. TREATMENTS Goals To prevent the subsequent development of active tuberculsosis To relieve symptoms to prevent development of a fibrothorax
  • 24. ATT Average patient becomes afebrile without 2 week Complete resorption of fluid 6-12 weeks The incidence of pleural thickening at 6- 12 months -50%
  • 25. CORTICOSTEROIDS No role of systemic steroids If more than mildly symptomatic A therapeutic thoracentesis is recommended Severe symptoms & diagnosis has been established – Steroids
  • 26. Surgical procedure Large pleural effusion – thoracentesis, Decortication rarely necessary Tuberculosis Empyema ICTD + ATT
  • 27. HIV & TUBERCULOSIS PLEURAL EFFUSION Incidence – CD4 < 200- 0 ↓ CD> 200 - ↑ Overall incidence - ±↑↓ Duration of illness longer Chest pain less common
  • 28. Systemic manifestation – Fever, anemia, lymphadenopathy, organomegaly – common Mantoux test often negative (40%) AFB smear in pleural fluid -25% If CD4 count < 100. 50% positive fluid AFB smear positive Significant number of mesothelial cells in their pleural fluid Biopsy – Granuloma on pleural biopsy are less well formed In pleural fluid ,the level of albumin are relatively low The level of ADA in patients without AIDS are comparable.