What is the diagnostic approach for tuberculous (TB) pericarditis?

How to Diagnose Tuberculous Pericarditis

Diagnostic pericardiocentesis should be considered in all patients with suspected tuberculous pericarditis, with pericardial fluid analyzed for M. tuberculosis culture, PCR (Xpert MTB/RIF), adenosine deaminase (ADA), and lymphocytic cell count. 1

Stage 1: Initial Non-Invasive Evaluation

Clinical Assessment and Risk Stratification

• Look for constitutional symptoms: fever, night sweats, and weight loss are key features 1
• Calculate the pericardial score in endemic areas: fever (1 point), night sweats (1 point), weight loss (2 points), globulin >40 g/L (3 points), and peripheral WBC count <10×10⁹/L (3 points)—a score ≥6 is highly suggestive of TB pericarditis 1, 2
• Assess for high-risk features: fever >38°C, subacute course (symptoms over days/weeks), large pericardial effusion (>20 mm diastolic echo-free space), cardiac tamponade, or failure to respond to NSAIDs 1

First-Line Investigations (All Patients)

• ECG: may show low voltage QRS complexes with electrical alternans in tamponade 3
• Transthoracic echocardiography: assess for pericardial effusion and thickening, evaluate for tamponade physiology 1, 2
• Chest X-ray: reveals pulmonary TB in 30% of cases and may show cardiomegaly 1, 2, 4
• Blood tests: CRP, ESR, complete blood count with differential, cardiac biomarkers (troponins, CK), renal and liver function 1, 5
• IGRA testing (QuantiFERON-TB Gold or ELISpot): more useful than tuberculin skin testing, which is negative in 30% due to anergy 1, 5, 4

Second-Line Imaging (High-Risk Patients)

• CT or MRI of chest: look for pericardial thickening >3 mm, mediastinal and tracheobronchial lymphadenopathy (>10 mm with hypodense centers and matting), sparing hilar nodes 1, 2
• Culture sputum, gastric aspirate, and urine for M. tuberculosis in all patients 1, 2

Stage 2: Pericardiocentesis (Diagnostic Gold Standard)

Indications

• Therapeutic pericardiocentesis is absolutely indicated for cardiac tamponade 1
• Diagnostic pericardiocentesis should be considered in all patients with suspected TB pericarditis 1

Essential Pericardial Fluid Tests

1. Direct culture for M. tuberculosis: definitive but slow (takes weeks) 1
2. PCR testing (Xpert MTB/RIF): more specific (100%) but less sensitive (75%) than ADA 1, 2
3. Adenosine deaminase (ADA): sensitivity 93%, specificity 97% when ≥40 IU/L; very high levels predict progression to constriction 2
4. White cell count and cytology: lymphocytic exudate favors TB pericarditis 1
5. Interferon-gamma (IFN-γ): offers superior accuracy compared to ADA for microbiologically confirmed TB pericarditis 2
6. Biochemical tests: protein and LDH to distinguish exudate from transudate 1

A "probable" diagnosis can be made with proof of TB elsewhere plus unexplained pericarditis with lymphocytic exudate and elevated ADA levels. 2

Stage 3: Pericardial Biopsy

Indications for Biopsy

• Therapeutic biopsy: as part of surgical drainage for tamponade relapsing after pericardiocentesis or requiring open drainage 1
• Diagnostic biopsy in non-endemic areas: recommended for patients with >3 weeks of illness without etiologic diagnosis from other tests 1
• Diagnostic biopsy in endemic areas: not required before starting empiric anti-TB treatment 1

Pericardial biopsy showing inflammatory granulomas and acid-fast bacilli provides definitive diagnosis. 4, 6

Stage 4: Empiric Antituberculosis Therapy

Endemic Areas

• Empiric anti-TB chemotherapy is recommended for exudative pericardial effusion after excluding malignancy, uremia, trauma, purulent pericarditis, and autoimmune diseases 1

Non-Endemic Areas

• Empiric anti-TB treatment is NOT recommended when systematic investigation fails to yield a diagnosis 1
• Diagnostic biopsy is preferred before initiating treatment in these settings 1

Common Pitfalls and Caveats

• Tuberculin skin testing is not helpful in adults regardless of TB prevalence due to high rates of anergy 1, 4
• Pericardial fluid cultures may be negative despite true TB pericarditis; rely on combined clinical, imaging, and biochemical findings 3, 6
• Normal inflammatory markers do not exclude TB pericarditis, especially if already on anti-inflammatory treatment 7
• Cardiac biomarker elevation may indicate concomitant myocarditis rather than isolated pericardial disease 7, 5
• Even with appropriate treatment, constrictive pericarditis develops in 17-40% of cases, emphasizing the importance of early diagnosis 2, 8