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Adenosine Deaminase (ADA -Synovial Fluid)

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ADA activity measured in joint fluid.

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Adenosine Deaminase (ADA) - Synovial Fluid

  • Why is it done?
    • The test measures adenosine deaminase enzyme levels in synovial fluid (joint fluid) to aid in the diagnosis of tuberculous arthritis (TB arthritis) and other inflammatory joint conditions
    • Primary indications include: suspected tuberculosis of the joint, evaluation of chronic monoarthritis, differentiation of TB arthritis from other causes of joint inflammation, and assessment of synovial fluid in patients with unexplained joint effusions
    • The test is typically performed during arthrocentesis (joint fluid aspiration) when TB arthritis is clinically suspected or when other diagnostic methods have been inconclusive
    • Particularly useful in endemic regions with high tuberculosis prevalence and when clinical presentation suggests tuberculous etiology
  • Normal Range
    • Normal/Negative Result: ADA levels less than 10 U/L (units per liter), typically reported as negative or normal
    • Borderline/Intermediate Result: ADA levels between 10-15 U/L, requiring clinical correlation and repeat testing or additional diagnostic confirmation
    • Positive/Elevated Result: ADA levels greater than 10 U/L (many laboratories use 10 U/L as cutoff, some use 15 U/L), strongly suggestive of tuberculous arthritis with sensitivity 50-100% and specificity 78-100% depending on cutoff values and laboratory methods
    • Unit of Measurement: U/L (units per liter) or IU/L (international units per liter)
    • Interpretation Summary: Normal results make TB arthritis less likely; elevated results support TB diagnosis but require confirmation with culture, PCR, or clinical findings
  • Interpretation
    • Elevated ADA (>10 U/L): Indicates T-lymphocyte activation and supports diagnosis of tuberculous arthritis; the enzyme is released from activated T cells responding to mycobacterial antigens
    • Markedly Elevated ADA (>20 U/L): Strong evidence for tuberculous arthritis with high specificity; may also be elevated in fungal infections and other granulomatous joint diseases
    • Normal ADA (<10 U/L): Makes TB arthritis unlikely but does not completely exclude it; other causes of monoarthritis should be investigated (rheumatoid arthritis, osteoarthritis, crystal-induced arthritis, other infections)
    • Factors Affecting Results: ADA isoenzyme distribution (ADA-1 is elevated in TB), disease duration, mycobacterial load, host immune status, concurrent immunosuppression, and presence of coinfections (HIV, fungal)
    • Clinical Significance: ADA testing has high negative predictive value; when combined with clinical presentation, synovial fluid characteristics (elevated lymphocytes, high protein, low glucose), and other diagnostic methods (culture, PCR, imaging), it substantially aids in TB diagnosis and helps prevent diagnostic delays in resource-limited settings
    • Result Patterns: High ADA with lymphocytic predominance, elevated protein, and low glucose strongly suggests TB; normal ADA with other inflammatory findings suggests non-TB etiology
  • Associated Organs
    • Primary Organ Systems: Musculoskeletal system (joints), immune system (T lymphocytes), and indirectly the respiratory system (site of primary TB infection)
    • Medical Conditions Associated with Abnormal Results: Tuberculous arthritis (TB of the spine/Pott's disease, TB of large joints like knee and hip), tuberculous tenosynovitis, fungal arthritis (histoplasmosis, cryptococcosis, coccidioidomycosis), atypical mycobacterial infections (MAC), sarcoidosis, and occasionally severe viral arthritis
    • Diseases This Test Helps Diagnose: Tuberculous arthritis (most important), and assists in differential diagnosis of chronic monoarthritis by excluding TB when ADA is normal
    • Potential Complications with Abnormal Results: If TB arthritis is present and untreated: progressive joint destruction, severe cartilage and bone damage, permanent disability, joint ankylosis, disseminated tuberculosis to other organs including lungs and CNS, pathological fractures, and spinal cord compression if vertebral involvement occurs
    • Risk Factors for TB Arthritis: HIV/AIDS, immunosuppressive therapy, malnutrition, diabetes mellitus, renal disease, malignancy, endemic TB exposure, and prior TB infection
  • Follow-up Tests
    • If ADA is Elevated (Elevated): Mycobacterium tuberculosis culture and sensitivity, PCR or GeneXpert MTB/RIF for TB detection, Ziehl-Neelsen stain for acid-fast bacilli, chest X-ray to detect pulmonary TB, CT/MRI of affected joint, synovial biopsy for histopathology and culture, TB skin test (TST) or interferon-gamma release assay (IGRA), and HIV testing
    • If ADA is Normal (Negative): Synovial fluid cell count and differential, gram stain and bacterial culture, crystal analysis (polarizing microscopy), synovial protein and glucose levels, imaging studies (ultrasound, X-ray, MRI), rheumatologic workup (RF, anti-CCP, ANA), and consideration of fungal or viral testing if clinically indicated
    • Complementary/Related Tests: Synovial fluid total and differential cell count, synovial glucose and protein, lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ADA isoenzymes (ADA-1 and ADA-2)
    • Monitoring Frequency: If TB arthritis diagnosed: clinical evaluation every 2-4 weeks initially, imaging at baseline and 3-6 months, and follow-up cultures to confirm treatment response; ADA typically not repeated as it measures acute inflammation
    • Further Investigations: Repeat arthrocentesis may be needed if diagnosis remains uncertain, whole blood interferon-gamma release assay to assess TB infection status, and evaluation for disseminated TB if joint involvement confirmed
  • Fasting Required?
    • Fasting Required: No. Fasting is not required as this test involves synovial fluid analysis obtained via arthrocentesis, not blood draw
    • Patient Preparation Requirements: Inform physician of active infections or bleeding disorders; routine medications may be continued; adequate informed consent should be obtained prior to arthrocentesis
    • Procedure Preparation: Patient may need to change into hospital gown; local anesthesia or sedation may be used; joint should be exposed and skin cleaned with antiseptic solution prior to needle insertion
    • Medications to Avoid: Anticoagulants (warfarin, dabigatran, rivaroxaban) should be discussed with physician; aspirin and NSAIDs ideally discontinued 3-5 days prior if possible; no specific restrictions for other medications unless they predispose to bleeding
    • Special Instructions: Rest the affected joint for 24 hours following arthrocentesis; apply ice for pain relief; take oral analgesics if needed; report signs of infection (fever, increased joint swelling, warmth, redness) immediately; fluid collection must be performed using sterile technique and specimens should be transported promptly to laboratory to maintain cell viability

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