What labs should be checked to assess inflammation in a patient presenting with symptoms of inflammation, considering their past medical history and potential chronic conditions such as rheumatoid arthritis (RA)?

Laboratory Testing for Inflammation Assessment

Order C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as your initial inflammatory markers, with CRP being the preferred test due to its superior reliability and lack of confounding by age, gender, or anemia. 1

Essential First-Line Inflammatory Panel

Core inflammatory markers:

• CRP is superior to ESR for monitoring inflammation because it provides a simple, validated, reproducible result that is not influenced by demographic factors 1
• ESR should still be measured at baseline for diagnostic and prognostic purposes, particularly in rheumatoid arthritis 2, 3
• Both markers together provide the most useful information in chronic inflammatory conditions 4

Complete initial workup includes:

• Full blood count with differential to assess for cytopenias and calculate inflammatory cell ratios 2, 3
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels 2, 3
• Alkaline phosphatase, calcium, 25-hydroxy-vitamin D, parathyroid hormone, and phosphate to exclude metabolic bone diseases 2

Conditional Autoimmune Testing Based on Clinical Context

For suspected rheumatoid arthritis or inflammatory polyarthritis:

• Anti-citrullinated protein antibodies (anti-CCP) with 90% specificity and 60% sensitivity—the most specific test for RA 1, 5
• Rheumatoid factor (RF) with 70% specificity but similar sensitivity to anti-CCP, providing complementary diagnostic information 1, 5
• Order both RF and anti-CCP simultaneously at initial presentation, as they are cornerstone tests for RA diagnosis and prognosis 3, 5

For uncertain diagnosis or suspected systemic disease:

• Antinuclear antibodies (ANA) if diagnosis remains uncertain after initial workup or symptoms suggest systemic lupus erythematosus or other connective tissue diseases 1, 3
• ANA serves as a screening test with 70-90% sensitivity and 90-95% specificity but should not delay rheumatology referral if clinical synovitis is present 1

For suspected spondyloarthropathy:

• HLA-B27 typing if symptoms suggest reactive arthritis, affect the spine, or involve axial/entheseal features 2, 1, 5
• Consider this particularly when inflammatory back pain is present with age of onset <45 years 3

Case-by-Case Considerations

Additional tests to consider based on specific clinical scenarios:

• Bone turnover markers (P1NP and CTx) in fasting blood samples to evaluate metabolic bone diseases 2
• Extractable nuclear antigens (anti-Ro, anti-La, anti-Sm, anti-RNP) if connective tissue disease features are present 3
• Urinalysis as part of standard initial workup for inflammatory arthritis 3

Monitoring After Treatment Initiation

Serial inflammatory marker assessment:

• Repeat CRP and ESR every 4-6 weeks after starting treatment to monitor disease activity and treatment response 1, 5
• Serial inflammatory markers guide treatment escalation but should not be the sole determinant of treatment decisions 1
• CRP is preferred for ongoing monitoring due to its rapid response to changes in disease activity 1

Critical Clinical Pearls and Pitfalls

Do not dismiss inflammatory disease based on normal acute phase reactants:

• Seronegative RA accounts for 20-30% of cases, so negative RF and anti-CCP do not exclude inflammatory arthritis 3, 5
• Acute phase reactants are poor predictors and can be normal even in active inflammatory arthritis 3, 5
• ESR has only 50% sensitivity and 80% specificity for inflammatory arthritis 3

Interpretation considerations:

• CRP >10 mg/L in acute coronary syndromes may have better predictive qualities, whereas >3 mg/L is more useful in stable disease 2
• Elevated CRP levels are influenced by multiple factors including elevated blood pressure, body mass index, cigarette smoking, metabolic syndrome, low HDL/high triglycerides, and chronic infections 2
• Persistently elevated CRP at diagnosis predicts severe disease with high risk of progressive joint erosions and functional deterioration 3

Timing and urgency:

• Refer to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected, regardless of autoantibody results 3, 5
• Do not delay treatment waiting for positive serology—early aggressive therapy prevents irreversible joint damage 3, 5