Tuberculous pleural effusion: diagnosis & management

ABSTRACT

Background: Tuberculosis (TB) is the world’s leading cause of death from infectious disease. The World Health Organization (WHO) recognized 6.3 million new TB cases in 2017, 16% corresponding to extrapulmonary forms; pleural tuberculosis (PT) is the most common extrapulmonary form in adults. PT diagnosis is often challenging because the scarcity of bacilli in pleural fluid (PF), sometimes requiring invasive procedures to obtain pleural tissue for histological, microbiological or molecular examination. In regions of medium and high disease prevalence, adenosine deaminase (ADA), interferon gamma (IFN-γ) and interleukin 27 (IL-27) dosages are useful to establish presumptive diagnosis in patients with compatible clinical/radiological picture who present with lymphocytic pleural effusion. PT treatment is similar to the pulmonary TB treatment regimen recommended by WHO.

Area covered: In this update, we present a PT review, including epidemiology, pathogenesis, clinical features, diagnosis, and therapy.

Expert opinion: There is no PF test alone accurate for PT diagnosis, despite the evolution in clinical laboratory. ADA, IFN-γ and IL-27 are valuable laboratory biomarkers; however, IFN-γ and IL-27 are quite expensive. Molecular tests present low sensitivity in PF, being useful for diagnostic confirmation. Multidrug therapy remains the PT treatment choice. Advancing research in immunotherapy may bring benefits to PT patients.

KEYWORDS:

• Biomarkers
• management
• mycobacterium tuberculosis
• pleural fluid
• pleural tuberculosis
• treatment

Article highlights

• PT is the most common EPTB form in adults; its occurrence varies according to prevalence settings, population age, and positive serology for HIV. PT may be a manifestation of primary infection with MTB or may be related to TB reactivation.

• PT can be acute or subacute; signs and symptoms include cough, chest pain, fever, anorexia, weight loss, night sweats, and varied intensity of dyspnea. Pleural effusion is usually unilateral; simultaneous involvement of the lungs can be seen on chest X-ray in up to 20% or chest CT (40-85%).

• For PT diagnosis, PF ADA, IFN-γ, and IL-27 have good sensitivity and specificity, although their usefulness depends on the prevalence setting. ADA has an excellent NPV, i.e., PF ADA values ≤ 40 U/L generally rule-out PT diagnosis in a median and high-risk region; for values greater than 70 U/L, PF ADA also presents a good PPV, including for HIV positive patients. IFN-γ and IL-27, although useful laboratory markers, present high cost, lack of a widely accepted cutoff and more sophisticated techniques for quantification, limiting their use in routine practice.

• The identification (microbiological or molecular) of MTB in PF or tissue samples remains the gold standard for diagnosis. Although PF bacilloscopy and culture usually have low yield, the use of automated liquid culture has increased PF culture positivity and has reduced time to results. Histological pleural tissue evaluation associated with tissue culture/molecular tests is also a good diagnostic approach at an acceptable cost. Image guided-pleural biopsy (transthoracic US and CT) can significantly increase the diagnostic yield.

• NAATs are used for rapid detection of MTB genome in specimens such as PF or pleural tissue. These assays have high specificity although with limited sensitivity, because they depend on the bacilli load present in the samples.

• For PT management, the therapeutic strategy is directly observed therapy (DOT) with the same regimen used for pulmonary TB (2HREZ/4HR). In case of resistance to any of the drugs or cases of MDR-TB, the treatment regimen should follow WHO and national treatment programs. The use of corticosteroids is controversial and should be carefully considered for selected patients with severe systemic symptoms. A discrete residual pleural thickening can be found in around 25% of PT patients, wich decreases over time, and usually, with no impact on pulmonary function. Tuberculous empyema is an uncommon chronic active infection on the pleural space, which often evolves with sequelae, such as fibrothorax. In these cases, it is recommended to clean out the pleural cavity in order to improve the response to specific therapy.

Acknowledgments

The authors thank BLF for the manuscript review.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

Laboratorio de Investigacao Medica (LIM 03), FAPESP, CNPq.