The document summarizes guidelines on the diagnosis and treatment of pleural tuberculosis. It discusses that pleural TB usually presents as a pleural effusion caused by the immune response to mycobacterial antigens in the pleural space. A diagnosis is made through diagnostic thoracentesis and examination of pleural fluid for characteristics of an exudative effusion as well as testing for adenosine deaminase levels and acid-fast bacilli. Treatment involves a standard 6-month course of anti-tubercular therapy. Complications can include fibrothorax, empyema, and bronchopleural fistula.

1. Dr Suresh Kumar Yogi
MBBS & MD
(RESPIRATORY MEDICINE)
INDEX-TB GUIDELINES - Guidelines on
extra-pulmonary tuberculosis for India

2. INTRODUCTION
 Pleural TB is the second most common form of EPTB.
 Pleural TB is a common cause of pleural effusion in India.
 Pleural TB usually presents with pleural effusion caused by the
immune system’s response to the presence of mycobacterial
antigens in the pleural space, generating inflammation and
causing fluid to accumulate.
 The effusion will usually resolve spontaneously even without
ATT, but patients who are not treated are at risk of recurrent
active TB infection.

3. PATHOGENESIS AND IMMUNOLOGY
 TB may affect the pleura at different stages of pulmonary
or systemic disease and by the number of different
mechanisms.
 Pleural effusion is a manifestation of either primary
infection or reactivation of latent tuberculosis
 Pleural effusion is believed to occurs secondary to rupture
of a subpleural caseous focus in the lung into the pleural
space.
 Rupture of such a focus allows the TB protein to enter the
pleural space and generate hypersensitivity responsible for
most clinical meifestations.
Text book of tuberculosis - 3rd edition S K Sharma

4.  Pleural effusions may also be seen with direct contiguous
spread of the disease to the pleura or by haematogenous spread.
 The intense inflammatory reaction obstructs the lymphatic
pores in the parietal pleura, causing proteins to accumulate in
pleural space with subsequent retention of fluid.
 Delayed hypersensitivity reaction plays an important role in the
development of TB pleural effusion.
 Mycobacterial antigens enter the pleural space and interact
with T-lymphocytes previously sensitized to mycobacteria,
resulting in delayed hypersensitivity reaction and accumulation
of fluid.
Text book of tuberculosis-3rd edition S K SHARMA

5.  Nearly eight-fold increase in mycobactrial antigen sensitized T-
lymphocytes in pleural fluid than that found in the peripheral
blood
 The ratio of CD4+ [helper-inducer] to CD8+
[suppressor/cytotoxic] lymphocytes is also much higher in TB
pleural fluid as compared to peripheral blood [3:4 vs 1:7] .
 Significantly higher interferon-γ [IFN-γ] levels, suggestive of
predominantly T-helper cell type 1 [Th1] type immunity in the
pleural space.
Text book of tuberculosis-3rd edition S K SHARMA

6. Immunological processes
NETROPHILS
GRANULOMA
FORMATION
MACROPHAGES
LYMPHOCYTES
IL-2
IFN-γ
TNF-α
IFN-γ
IL-1
IFN-γ
first 24 hours
second to fifth day
CD4+/CD8+ratio4.3,
Helps
After 3 to 4 days,
IL-12
TGF-β
IL-10
Th1-
cells
regulator of T-cell
proliferation
Created by dr. s k yogi

7.  After phagocytosing mycobacteria, macrophages act as
antigen presenting cells and present TB antigen to T-
lymphocytes.
 This results in activation of T-lymphocytes and subsequent
promotion of macrophage differentiation and granuloma
formation.
 Some components of the mycobacterial cell wall, such as
protein/proteoglycan complex and lipoarabinomannan, can
stimulate macrophages to produce TNF-α, which regulates
granuloma formation
Text book of tuberculosis-3rd edition S K SHARMA

8. CLINICAL MANIFESTATIONS
 Tuberculosis pleural effusion is typically a disease Of young
men
 < 1 month of duration
 Non-productive cough [70%] and chest pain [75%] are the two
most common symptoms at presentation.
 Fever, night sweats, weakness, weight loss, anorexia and
fatigue.
On physical examination
 Non-specific signs of pleural effusion,
 Dullness to percussion and the occasionally pleural rub at
auscultation
Text book of tuberculosis-3rd edition S K SHARMA

9. Patients who should be investigated for
Pleural TB
Presumptive pleural TB
 A patient with cough, chest pain or shortness of breath,
with or without fever and weight loss.
 With evidence of a pleural effusion on examination or
chest X-Ray.

10. DIAGNOSIS
X-ray of chest
 All
 To confirm presence of a pleural effusion and look for underlying
pulmonary disease
 Progress may be monitored using CXR.
 unilateral in >90 %, small to moderate in size
HIV test
 All
 EPTB is associated with HIV infection.
 All patients should be offered integrated counseling and testing.

11. Pleural aspiration/thoracocentesis
 All
 Most patients do not require complete therapeutic drainage of their
pleural effusion, unless it is causing respiratory compromise; in which
case, specialist monitoring is required during and following drainage.
 All patients should have a diagnostic sample of pleural fluid taken.
Send specimen for:
a) Glucose, protein, ADA and lactate dehydrogenase (LDH) levels
( Send concurrent blood sample for serum protein and LDH);
b) Differential cell count;
c) Microscopy and culture for Mtb; and
d) Cytology

12. Pleural TB usually causes an exudative effusion, defined on
the basis of Light’s criteria-
 Pleural fluid/ serum protein >0.5;
 Pleural fluid/serum LDH >0.6;
 Pleural fluid LDH > two-thirds the upper limit of serum
LDH) (Light R.W., 1972)

13. Adenosine deaminase activity (ADA) level has supportive role in
diagnosis of pleural TB (Greco, 2003) (Liang, 2008).
 High ADA level can be found in other causes of pleural effusion
such as empyema, rheumatoid serositis and lymphoma
(Porcel,2010).
 > 70 U/L – highly likely to be pleural TB
 40–70 U/L – indeterminate level, other risk factors need to be
considered
 <40 U/L – low likelihood of pleural TB, investigate for other
causes

14. Sputum samples for microscopy
 In selected patients whenever concurrent pulmonary and pleural TB
is suspected.
Tuberculin Skin Test
 In a patient with exudative pleural effusion , positive tuberculin skin
test [TST] strongly suggests the diagnosis of TB, in populations with
a low prevalence of TB infection,
 Whereas the diagnostic value is lower in countries with a high
prevalence of TB.
 NO Recommendation by INDEX –TB GUIDLINES

15. Pleural biopsy(closed or thorascopic)
 In selected patients, where diagnosis is uncertain despite other
tests, or where pleural malignancy is significant differential
diagnosis.
 High yield than pleural fluid
 Thoracoscopically-obtained specimens have a higher
diagnostic yield than closed pleural biopsy.
 The endoscopic appearance of pleural TB is well described. It
is characterized by greyish-white granulomata covering the
entire parietal and diaphragmatic pleura, and in particular, the
costovertebral gutter.

16. Endoscopic appearance of pleural TB

17. Send biopsy specimen for:
1.In normal saline
 Xpert MTB/RIF test;
 Microscopy and culture for Mtb with drug susceptibility
testing;
2. In formalin
 Histopathology

18. CT scans of chest and abdomen
In selected patients
 Uncertain diagnosis
 Suspected malignancy
 In HIV-positive patients who are at higher risk of
disseminated TB
Ultrasound of chest
 In selected patients
 More sensitive in picking up pleural effusion than CXR

19. Recommendation:
 Xpert MTB/RIF should not be used to diagnose pleural
TB .
(strong recommendation, high quality evidence for
specificity, low quality evidence for sensitivity).

20. Interferon-gamma
 Estimation of pleural fluid IFN-γ levels is reported to be useful
in differentiating TB from other pleural fluids.
 The IFN-γ can be estimated either by enzyme-linked
immunosorbent assay [ELISA] or radioimmunoassay [RIA].
 IFN-γ levels in patients with TB pleurisy are high, with
sensitivity and specificity ranging from 90 to 100 per cent.
 Expensive and still not widely available in india .
 NO Recommendation by INDEX –TB GUIDLINES
Text book of tuberculosis-3rd edition S K SHARMA

21. Lysozyme level
 lysozyme levels in TB pleural fluid have been reported to
be higher than in other exudative effusions.
 Pleural fluid to serum lysozyme ratio of more than 1 or
1.2 can differentiate better between TB and non-TB
pleural fluids.
 Not diagnostic.
 NO Recommendation by INDEX –TB GUIDLINES

22. Text book of tuberculosis-3rd edition S K SHARMA
Algorithm for diagnosis of tuberculosis
pleural effusion

23. NATURAL HISTORY
 In the short-term, TB pleural effusion seems to be a self
limited inflammatory process in most instances.
 The likelihood of subsequent development of pulmonary
TB is high.

24. Treatment
 2RHZE/4RHE, for total duration of 6 months.
 Recommendation:
Corticosteroids are not routinely recommended in pleural TB.
(conditional recommendation, low quality evidence).

25. Surgery
 No role in routine management
 Therapeutic thoracocentesis - only in cases of moderate-
severe effusion leading to significant breathlessness.
 Pleural thickening decreases with treatment, so
decortication should NOT be considered until patient has
undergone treatment for atleast 6 months.
Text book of tuberculosis-3rd edition S K SHARMA

26. Follow up
 Most patients who respond to treatment will have improvement
in their general condition by 2 weeks, and significant
improvement in pleural effusion by 6–8 weeks.
 A follow up CXR at 8 weeks after starting ATT is useful to
assess progress.
 Increasing size of effusion despite treatment may be due to
paradoxical reaction, or an alternative diagnosis requiring
further investigation.

27. COMPLICATIONS
 10 % cases have residual restrictive ventilatory defect after treatment
completion
 50% cases may have pleural fibrosis on chest X-Ray after 1 year of
treatment completion
Fibrothorax-
 Define as a pleural membrane of at least 5 mm thickness extending
across major portion of the hemithorax.
 Approximately 5% cases develop fibrothorax.
 A faster resolution of pleural effusion during the initial phase of
treatment may decrease the occurrence of significant pleural
thickening.

28. TB EMPYEMA-
 Characterized by chronic, active TB infection of pleural space.
 Usually represents the failure of primary TB effusion to resolve.
 Can also occur due to extension of infection from intrathoracic lymph
nodes or sub-diaphragmatic focus
 Develops in scar tissue resulting from pleurisy, artificial pneumothorax or
thorecoplasty.
 It is common to find AFB in smear examination or colture of pleural fluid.
 Treatment –
 Pleural space drainage
 Surgical – decortication, thoracoplasty, muscle flap,open drainage

29. Complicated
Empyema
Surgical management
Assess the condition of ipsilateral lung
Young and Healthy lung,
unfit for thoracotomy
Young and unhealthy lung
Old and unhealthy lung and
unfit for thoracotomy
Decortications Open drainage
Thoracoplasty
Open drainage
VATS - Unavailable,
unsuccessful or inappropriate
Closed drainage unsuccessful
unfitfit
Decortications Fenestration

30. Bronchopleural Fistula-
 Usually seen in patients with a previous healed TB, and especially in
patients with a previous therapeutic pneumothorax who were never treated
with chemotherapy.
 When such patients develop a bronchopleural fistula, their sputum
production usually increases in variable amount and some time
superinfaction .
 Air fluid level in pleural space
 Confirmed by – methylene blue or radiopaque dye
 Treatment –
 ATT
 Chest tube drainage- TB bronchopleural fistula does not heal
spontaneously
 Surgical management- decortications with or without thoracoplasty
6th edition of pleural diseases by W. Light

31. Thank you