# Diagnostic Challenge of Tuberculous Pleural Effusion: Elevated Adenosine Deaminase (ADA) as the Key Indicator in the Absence of Microbiological Confirmation

## TL;DR

A young man with suspected tuberculosis pleural effusion showed improvement with anti-tuberculosis treatment despite negative microbiology tests.

## Contribution

Highlights the clinical utility of elevated adenosine deaminase (ADA) in diagnosing tuberculous pleural effusion when microbiological confirmation is absent.

## Key findings

- Pleural fluid with lymphocytic exudate and elevated ADA levels can justify empirical anti-TB therapy in high probability cases.
- The patient improved significantly after starting anti-tuberculous therapy despite negative AFB smear, PCR, and cultures.
- Empirical treatment was effective when alternative diagnoses were excluded and the patient did not respond to antibiotics.

## Abstract

Tuberculous pleural effusion (TPE) is frequently paucibacillary. Consequently, acid-fast bacilli (AFB) smears, polymerase chain reaction (PCR), and mycobacterial cultures from pleural fluid are often negative. Pleural adenosine deaminase (ADA) is an important adjunct, but interpretation requires an appropriate clinical context. A previously healthy 20-year-old man presented with pleuritic chest pain, dyspnea, fever, and bilateral pleural effusions. Despite repeated negative microbiology for Mycobacterium tuberculosis (AFB smear, PCR, and cultures from sputum, bronchoalveolar lavage, pleural fluid, and pleural tissue) and a non-diagnostic pleural biopsy, pleural fluid was a lymphocyte-predominant exudate with markedly elevated ADA (126.5 and 100.0 U/L). The course was complicated by respiratory failure requiring intubation, surgical tracheostomy, video-assisted thoracoscopic surgery (VATS) decortication with talc pleurodesis, ventilator-associated pneumonia due to Pseudomonas aeruginosa, and only partial response to intrapleural alteplase for persistent loculations. Empirical first-line anti-tuberculous therapy (isoniazid, rifampin, pyrazinamide, ethambutol) was commenced on hospital day 66. Within 10 days, the patient showed improvement, pleural drainage ceased, oxygenation improved, and he was weaned from mechanical ventilation. He was discharged clinically stable after 117 days of hospitalization (on day 52 of anti-TB therapy). In high probability scenarios with lymphocytic exudate with high ADA and compatible clinical features, empirical anti-TB therapy can be justified despite repeatedly negative microbiology, particularly when alternative diagnoses are excluded and the patient fails to respond to appropriate antibiotics.