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TUBERCULOSIS PLEURAL EFFUSION
MD Examination Answer — 15 Marks
1. INTRODUCTION & EPIDEMIOLOGY (1 mark)
Tuberculous pleural effusion is the most common cause of an exudative pleural effusion in many parts of the world. In Africa, pleural TB represents >30% of all TB cases (partly due to HIV co-infection). It is relatively uncommon in the US (~3.6% of TB cases). It may represent primary TB (3–6 months after initial infection) or reactivation TB.
2. PATHOGENESIS (2 marks)
Caused by rupture of a subpleural caseous focus into the pleural space, introducing mycobacterial antigens. Two overlapping mechanisms:
A. Delayed Hypersensitivity (Classical)
- Sensitised T-lymphocytes react to mycobacterial proteins → cytokine-driven vascular permeability → exudate
- Explains historically negative culture results (~80%)
B. Paucibacillary Direct Infection (Modern)
- Improved liquid culture + biopsy identifies bacilli in >60% of cases
- Initial neutrophilic acute inflammation → evolves to lymphocyte-driven chronic reaction + granuloma formation
- Lymphocyte activity inversely correlates with culture positivity
- Sufficient lymphocytic activity can sterilise the pleural space → explains spontaneous resolution
TB Pleuritis vs. TB Empyema — a spectrum, not two distinct diseases:
| Feature | TB Pleuritis | TB Empyema |
|---|
| Mechanism | Paucibacillary + immune reaction | High mycobacterial load |
| Fluid | Serous, lymphocytic exudate | Purulent |
| Culture | Usually negative | Positive |
| Spontaneous resolution | Possible | Unlikely |
In HIV co-infection: more systemic features, culture-positive effusions more common, more prevalent when CD4 >200 cells/μL.
3. CLINICAL FEATURES (2 marks)
Acute presentation (~2/3 cases): cough, pleuritic chest pain (~75%), fever, dyspnea — mimics bacterial pneumonia
Chronic presentation (~1/3 cases): low-grade fever, weakness, weight loss, night sweats
Effusion characteristics:
- Almost always unilateral
- Usually small to moderate in size (occasionally massive)
- Up to 86% have coexisting parenchymal disease — effusion always on the same side
- Even without radiographic parenchymal involvement, induced sputum is positive in ~55%
Rare complications: TB empyema (with pneumothorax + bronchopleural fistula), empyema necessitans, fibrothorax
4. RADIOLOGY (1 mark)
(A) PA CXR: left apical consolidation + left basal effusion. (B) CT: encapsulated posterior effusion + tree-in-bud anteriorly. (C) Mediastinal window: "split-pleura" sign (arrows). — Murray & Nadel's
- CXR: unilateral homogeneous opacity; obliterated costophrenic angle; associated apical/upper lobe consolidation
- CT chest: encapsulated/loculated collections; smooth pleural enhancement ("split-pleura" sign); mediastinal lymphadenopathy; tree-in-bud nodules
- Ultrasound: free vs. loculated; guides thoracentesis
5. PLEURAL FLUID ANALYSIS (3 marks)
All TB effusions are exudates by Light's criteria:
- PF protein / serum protein > 0.5
- PF LDH / serum LDH > 0.6
- PF LDH > 2/3 upper limit of normal serum LDH
Biochemistry:
| Parameter | Finding |
|---|
| Protein | >3 g/dL; often >5 g/dL (characteristic of TB) |
| LDH | Elevated |
| Glucose | Normal or mildly reduced |
| pH | Normal (reduced in empyema) |
Cytology:
- Lymphocyte-predominant (hallmark) — small mature lymphocytes
- PMN predominance in ~11% (early disease)
- Mesothelial cells: characteristically absent or very sparse
Diagnostic Markers:
| Marker | Cut-off | Notes |
|---|
| ADA (Adenosine Deaminase) | >40 IU/L | Most clinically useful; released by T-lymphocytes; sensitivity ~90%, specificity ~90% |
| IFN-γ | >140 pg/mL | High accuracy; requires direct ELISA — NOT IGRA (insufficiently sensitive on PF) |
| PCR (mycobacterial DNA) | Positive | Variable sensitivity; high specificity |
| AFB culture (PF) | Positive | Low sensitivity (~30–40%); liquid media improves yield; gold standard if positive |
| AFB smear (PF) | Positive | Very low sensitivity (<20%) |
Key point: ADA + differential cell count + clinical context used in combination substantially improves diagnostic accuracy. ADA >50 IU/L in a lymphocytic exudate (Cecil's cut-off) is strongly suggestive.
6. DIAGNOSIS (2 marks)
Gold standard: Pleural biopsy showing caseating granulomas or positive AFB culture of biopsy tissue.
Stepwise Approach:
Step 1 — Thoracentesis
Send for: biochemistry, cytology + differential, AFB smear & culture, ADA, IFN-γ, PCR
Step 2 — Sputum
Induced sputum AFB smear + culture → positive in ~50% even without radiographic parenchymal involvement
MODS assay: liquid culture with drug susceptibility; faster, cheaper; WHO-approved for resource-limited settings
Step 3 — Pleural Biopsy (if above inconclusive)
- Thoracoscopy (medical / VATS): ideal — highest yield; direct visualization + directed biopsy
- Image-guided percutaneous needle biopsy: replaced closed biopsy in high-income settings
- Blind needle biopsy (Abrams needle): important in high-TB-prevalence/resource-limited settings; combine with ADA + differential; ultrasound guidance improves yield
- Biopsy culture yield > pleural fluid culture yield
Diagnostic criteria (any one):
- Caseating granuloma on pleural biopsy
- Positive AFB culture (fluid / biopsy / sputum)
- ADA >40 IU/L + lymphocytic exudate + compatible clinical picture + exclusion of alternative diagnoses
7. TREATMENT (2 marks)
Antituberculous Therapy (ATT)
Same regimen as pulmonary TB:
| Phase | Duration | Drugs |
|---|
| Intensive phase | 2 months | HRZE — 2HRZE |
| Continuation phase | 4 months | HR — 4HR |
| Total | 6 months | |
(H = Isoniazid, R = Rifampicin, Z = Pyrazinamide, E = Ethambutol)
Response:
- Fever resolves: ~2 weeks
- Effusion resolves: ~6 weeks
- Residual pleural fibrosis: ~50% at 1 year (usually no functional impairment)
Corticosteroids
- May reduce time to resolution and residual fibrosis
- Evidence is low quality; more adverse events
- Always start ATT first, then add steroids if indicated
- Caution in HIV patients (possible Kaposi sarcoma risk)
Therapeutic Thoracentesis
- For large effusions causing significant dyspnea
- Not routinely required for small-moderate effusions on ATT
Intrapleural Fibrinolytics
- May improve drainage and reduce residual thickening
- Clinical benefit uncertain; not routine practice
Paradoxical Worsening
- Effusion worsens after starting ATT or new effusion develops during treatment for pulmonary TB
- First exclude wrong diagnosis; if TB confirmed → continue ATT (immune reconstitution reaction)
8. DIFFERENTIAL DIAGNOSIS OF LYMPHOCYTIC EXUDATE (1 mark)
| Condition | Key Distinguishing Feature |
|---|
| Malignant effusion | Positive cytology; low ADA; imaging mass |
| Lymphoma | Very high LDH; CT mediastinal mass |
| Rheumatoid pleurisy | Glucose <30 mg/dL; RF positive; low complement |
| Chylothorax | Triglycerides >110 mg/dL; milky fluid |
| Fungal (Cryptococcus) | Immunocompromised; antigen titre positive |
| Sarcoidosis | Bilateral; hilar lymphadenopathy; ACE elevated |
9. COMPLICATIONS (1 mark)
| Complication | Notes |
|---|
| Fibrothorax / Trapped lung | ~50% at 1 year; rarely requires decortication |
| TB Empyema | Purulent, culture positive; requires drainage ± surgery |
| Empyema necessitans | Rare; spontaneous percutaneous decompression |
| Bronchopleural fistula | Complicates TB empyema after lung rupture |
| Paradoxical worsening | During ATT; immune reconstitution |
| MDR-TB | Culture + drug susceptibility testing essential |
RAPID REVISION TABLE
| Feature | TB Pleural Effusion |
|---|
| Type | Exudate (Light's criteria) |
| Side | Unilateral (almost always) |
| Cells | Lymphocyte-predominant |
| ADA | >40 IU/L |
| IFN-γ | >140 pg/mL |
| Protein | Often >5 g/dL |
| Gold standard | Pleural biopsy (granuloma/AFB) |
| Treatment | 2HRZE + 4HR |
| Fever resolution | ~2 weeks |
| Effusion resolution | ~6 weeks |
| Residual fibrosis | ~50% at 1 year |
Sources: Murray & Nadel's Respiratory Medicine; Harrison's 22E; Goldman-Cecil Medicine; Sharma SK — Textbook of Tuberculosis & NTM Diseases, 3rd Ed; Light RW — Pleural Diseases
