Laboratory Testing for RA-Related Pleural Effusion
For suspected rheumatoid arthritis-related pleural effusion, you must measure pleural fluid pH, glucose, and complement levels. 1 RA is unlikely to be the cause if glucose is above 1.6 mmol/L (29 mg/dL). 1
Essential Pleural Fluid Tests
Core RA-Specific Tests
- Pleural fluid glucose: Critical diagnostic marker; levels ≤1.6 mmol/L (29 mg/dL) strongly suggest RA etiology 1
- Pleural fluid pH: Should be measured in all non-purulent effusions; typically low in RA effusions 1
- Pleural fluid complement: Helps differentiate RA from other autoimmune causes like SLE 1
Standard Pleural Fluid Analysis
- Protein and LDH: To confirm exudative nature (RA effusions are exudates) 2
- Rheumatoid factor (RF): High titers in pleural fluid support RA diagnosis 3, 4
- Immune complexes: Detected in all RA pleural fluids using monoclonal RF, C1q, and Raji cell assays; levels typically higher than paired serum samples 4
Mandatory Exclusion Tests
- Cytology: Send 25-50 mL to exclude malignancy (60% sensitivity for malignant effusions) 1, 2
- Microbiological studies: Send 5-10 mL in blood culture bottles PLUS sterile containers for Gram stain, AAFB stain, and TB culture to exclude superimposed infection 1, 2
- Adenosine deaminase (ADA): To exclude tuberculosis, though note that ADA can be elevated in RA pleurisy 1, 2
Clinical Context and Interpretation
Characteristic RA Pleural Fluid Profile
- Appearance: Can be serous, turbid, yellow-green, milky, or hemorrhagic 1
- Biochemistry: Very low glucose (<1.6 mmol/L), low pH, high LDH, high RF titer 1, 3
- Complement: Low levels help differentiate from SLE 4
Critical Pitfalls to Avoid
Superimposed infection is common in RA pleural effusions 3. Always send microbiological samples even when RA is suspected, as infected empyema frequently complicates RA effusions. 3
Do NOT measure pleural fluid ANA as it mirrors serum levels and provides no additional diagnostic value. 1
In patients without active arthritis, pleural biopsy is mandatory to exclude tuberculosis or malignancy, as the "rheumatoid" nature cannot be confirmed by fluid analysis alone. 3
Procedural Recommendations
- Volume: Aspirate at least 25-50 mL for comprehensive analysis 1, 2
- Containers: Use both sterile vials AND blood culture bottles 1, 2
- Image guidance: Always use ultrasound or CT guidance to reduce complications 1, 2
Serum Tests
While pleural fluid analysis is diagnostic, consider:
- Serum RF and anti-CCP antibodies: Most RA patients are positive, though 30-40% may be negative 5
- ESR and CRP: Elevated in most but normal in 40% of RA patients 5
Note that serum biomarkers should not be used to diagnose autoimmune pleuritis and cannot substitute for pleural fluid analysis. 1