What labs should be drawn to evaluate a patient's inflammatory status and autoimmune activity?

Laboratory Evaluation for Inflammatory Status and Autoimmune Activity

For evaluating inflammatory status and autoimmune activity, obtain ESR, CRP, complete blood count with differential, rheumatoid factor (RF), anti-CCP antibodies, and ANA at baseline, with additional autoantibody testing guided by clinical suspicion of specific connective tissue diseases.

Core Inflammatory Markers

ESR and CRP should be performed at baseline in all patients being evaluated for inflammatory and autoimmune conditions 1. These markers provide complementary information:

• CRP is superior for acute inflammatory assessment due to its shorter half-life, stability in serum without special processing, and superior standardization across laboratories 2, 3
• ESR is more useful for monitoring chronic inflammatory conditions like polymyalgia rheumatica and temporal arteritis due to fibrinogen's longer half-life 3, 4
• Both markers together provide optimal assessment, as CRP correlates more closely with clinical parameters while ESR has established utility in chronic disease monitoring 1, 3

Important Caveats for Inflammatory Markers

• More than 40% of patients with rheumatoid arthritis have normal ESR or CRP at presentation, so normal values do not exclude inflammatory disease 5, 6
• CRP may remain normal in systemic lupus erythematosus despite active disease, making it less reliable in this specific condition 7
• If CRP exceeds 10 mg/L, repeat testing is needed to evaluate for acute infection or inflammation 2

Complete Blood Count with Differential

A full blood count with differential should be obtained at baseline 1. This provides multiple inflammatory indicators:

• Neutrophilia (granulocytosis) indicates active systemic inflammation and should be monitored at each visit in autoinflammatory diseases 1
• Neutrophil-to-lymphocyte ratio (NLR) can assess disease activity in rheumatoid arthritis and predict renal involvement in SLE 8
• Mean platelet volume (MPV) and platelet-to-lymphocyte ratio (PLR) serve as prognostic inflammatory biomarkers in rheumatic disorders 8

Autoantibody Testing Strategy

First-Tier Autoantibodies

RF and/or anti-CCP antibodies should be performed when evaluating for rheumatoid arthritis, as these predict RA diagnosis, persistent synovitis, and worse radiographic outcomes 1. However, negative tests do not exclude RA progression, as more than 30% of RA patients are seronegative 1, 5.

ANA testing should be performed when connective tissue disease is suspected 1. If ANA is positive, proceed with:

• Anti-dsDNA antibodies for SLE diagnosis and monitoring 1, 7
• Antibodies to extractable nuclear antigens (anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-RNP) to identify specific connective tissue disease subtypes 1, 7, 9
• Anti-centromere antibody for CREST syndrome 4
• Anti-histone antibody for drug-induced lupus 4

Additional Specialized Testing

If connective tissue disease/systemic inflammatory disorder is suspected, additional autoantibody tests should be considered 1:

• Immunoglobulins should be measured at baseline 1
• Anti-phospholipid antibodies when evaluating for antiphospholipid syndrome 7, 4
• Complement levels (C3, C4) are essential for SLE evaluation and monitoring, particularly for lupus nephritis 7

Advanced Inflammatory Markers (When Available)

Serum amyloid A (SAA) and S100 proteins may be used as inflammatory markers where available 1. These are particularly useful in:

• Monitoring systemic inflammation in autoinflammatory diseases at each visit 1
• SAA has limited clinical validation and does not outperform CRP in predictive ability 2

Biochemistry Panel

Comprehensive biochemistry testing should include 1:

• Liver function tests to assess hepatic involvement and monitor medication toxicity 1
• Renal function (creatinine, BUN) to detect kidney involvement 1
• Glucose and urate as part of baseline metabolic assessment 1

Monitoring for Complications

Urinalysis should be performed every 6-12 months to monitor for proteinuria, which may indicate AA amyloidosis in chronic inflammatory conditions 1. For SLE specifically, urine protein-to-creatinine ratio and microscopic urinalysis for cellular casts should be assessed to screen for lupus nephritis 7.

HLA Typing (Selected Cases)

HLA typing (HLA-B27 and HLA-DR) should be considered when spondyloarthropathy or specific autoimmune conditions are suspected based on clinical features 1.

Practical Testing Algorithm

1. Initial evaluation: ESR, CRP, CBC with differential, RF, anti-CCP, ANA 1, 2
2. If ANA positive: Complete SLE panel (anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-RNP, C3, C4) 1, 7
3. If inflammatory arthritis: Add imaging (hands/feet X-rays) to laboratory assessment 1
4. Ongoing monitoring: Repeat ESR/CRP when clinically relevant; CBC and urinalysis every 6-12 months 1