Which pleural fluid tests should be performed to confirm tuberculous pleural effusion in an adolescent patient?

Diagnostic Testing for Tuberculous Pleural Effusion in Adolescents

Send pleural fluid for differential cell count, acid-fast bacilli staining and mycobacterial culture, and adenosine deaminase (ADA) measurement, with pleural biopsy for histology and culture if diagnosis remains uncertain. 1, 2

Essential Pleural Fluid Tests

Cytology (Differential Cell Count)

• Aspirated pleural fluid must be sent for differential cell count in all cases. 1
• Tuberculous effusions typically show lymphocyte predominance, though 10% may be predominantly neutrophilic. 1
• A lymphocyte-predominant exudate raises the possibility of tuberculosis or malignancy and mandates further investigation. 1

Microbiological Analysis

• Pleural fluid must be sent for acid-fast bacilli staining, mycobacterial culture, and M. tuberculosis PCR. 1
• Acid-fast bacilli stains are positive in only 10-20% of tuberculous pleural effusions, making culture essential despite low sensitivity. 2, 3
• PCR has low sensitivity but provides more rapid results than standard culture. 1
• Send pleural fluid in anaerobic blood culture bottles to improve yield. 1

Adenosine Deaminase (ADA)

• Request ADA measurement in all lymphocytic exudative pleural effusions. 2
• ADA levels >40-47 U/L are highly suggestive of tuberculosis in lymphocytic effusions. 2, 3, 4
• In high TB prevalence areas with compatible clinical context, ADA >40 U/L justifies empirical antitubercular treatment. 2, 4
• In low TB prevalence areas, use ADA primarily as an exclusion test (cutoff 41.5 U/L provides 97.1% sensitivity). 2

Interferon-Gamma (IFN-γ)

• IFN-γ offers even higher diagnostic accuracy than ADA when available, though cost may limit routine use. 2, 5
• Pleural fluid IFN-γ is the most sensitive and specific biological marker for tuberculous pleurisy. 5

Tissue Diagnosis When Needed

Pleural Biopsy Indications

• Perform pleural biopsy for histological examination and culture in doubtful cases or low prevalence areas. 2, 6
• Tissue sampling for culture and sensitivity remains the preferred diagnostic approach regardless of ADA results. 2
• Pleural biopsy sent for both histology and culture improves diagnostic rate to approximately 90%. 2
• Look for caseating granulomas with acid-fast bacilli on histology. 4

Complementary Investigations

Additional Testing

• Perform Mantoux testing when lymphocytes predominate, particularly with suggestive history. 1
• Ultrasound may demonstrate pleural thickening and diffuse small nodules on the pleural surface suggestive of tuberculosis. 1
• Consider induced sputum collection, which can be diagnostic in approximately 50% of cases. 4

Critical Pitfalls to Avoid

• Do not rely on biochemical analysis (pH, glucose, LDH) alone—these are unnecessary for tuberculosis diagnosis in children. 1
• Do not assume all lymphocytic effusions are tuberculous; malignancy must be systematically excluded, especially if blood-stained or with atypical features. 1, 7
• Be aware that high ADA levels can occur in empyemas, rheumatoid pleuritis, and some neoplasias, reducing specificity in low prevalence settings. 2
• Avoid large volume aspiration and general anesthesia if mediastinal mass or lymphadenopathy is present, as this poses significant mortality risk. 1, 7
• Remember that 10% of tuberculous effusions are neutrophil-predominant, so do not exclude tuberculosis based on cell count alone. 1