Is adenosine testing used in the diagnosis or management of tuberculosis (TB)?

Adenosine Deaminase Testing in Tuberculosis Diagnosis

Adenosine deaminase (ADA) testing is recommended for the diagnosis of extrapulmonary tuberculosis, particularly in pleural, peritoneal, pericardial, and meningeal TB, but is not used for routine pulmonary TB diagnosis where nucleic acid amplification tests are preferred. 1

Role of ADA Testing in TB Diagnosis

Extrapulmonary TB Diagnosis

ADA testing has established utility in several forms of extrapulmonary TB:

• Pleural TB: ADA levels in pleural fluid show high sensitivity and specificity for TB diagnosis 1
• TB Meningitis: ADA testing in cerebrospinal fluid can aid diagnosis with sensitivity around 79% and specificity of 91% 1
• Peritoneal TB: ADA testing in ascitic fluid demonstrates excellent diagnostic performance with sensitivity of 91.7-100% and specificity of 92-100% 2, 3
• Pericardial TB: ADA is recommended as an indirect test for tuberculous infection in pericardial fluid 1

Diagnostic Algorithm for Extrapulmonary TB

When extrapulmonary TB is suspected, the following approach is recommended:

1. Collect appropriate fluid specimens (pleural, cerebrospinal, ascitic, or pericardial)
2. Perform cell counts and chemistries on fluid specimens 1
3. Measure ADA levels in the fluid 1
4. Interpret results in context of clinical presentation and other laboratory findings

Interpretation of ADA Results

• Pleural fluid: Elevated ADA supports TB diagnosis
• CSF: Threshold values significantly affect performance - 4 U/L provides >93% sensitivity but <80% specificity, while 8 U/L threshold gives <59% sensitivity but >96% specificity 1
• Ascitic fluid: ADA has high diagnostic accuracy with sensitivity of 93% and specificity of 94% 3

Limitations and Caveats

1. Not for pulmonary TB diagnosis: For pulmonary TB, nucleic acid amplification tests (NAATs) are the recommended rapid diagnostic method rather than ADA 1

2. Confirmatory testing needed: ADA provides supportive evidence but is not definitive for TB diagnosis; it must be interpreted within the clinical context 1

3. Variable performance: ADA performance varies by:

   • Sample type (better in some fluids than others)
   • Threshold values used for interpretation
   • Endemic vs. non-endemic settings

4. False positives: ADA can be elevated in other conditions, limiting specificity in some settings 4, 5

5. Not for treatment monitoring: While serum ADA levels may decrease with treatment 6, guidelines do not recommend routine use of ADA for monitoring treatment response

Current Guideline Recommendations

The American Thoracic Society/Infectious Diseases Society of America/CDC guidelines specifically recommend:

• "We suggest that adenosine deaminase levels be measured, rather than not measured, on fluid collected from patients with suspected pleural TB, TB meningitis, peritoneal TB, or pericardial TB" (conditional recommendation, low-quality evidence) 1

The European Society of Cardiology guidelines for pericardial diseases recommend:

• "Diagnostic pericardiocentesis should be considered in all patients with suspected tuberculous pericarditis" with ADA testing as one of the recommended indirect tests for tuberculous infection 1

In conclusion, while ADA testing is not used for routine pulmonary TB diagnosis, it plays an important role in the diagnostic workup of extrapulmonary TB, particularly when fluid samples can be obtained from affected sites. It should be used as part of a comprehensive diagnostic approach that includes clinical assessment, microbiological testing, and molecular methods when available.