What lab tests are used to diagnose and monitor inflammation?

Laboratory Tests for Inflammation

The most clinically useful and widely available laboratory tests for assessing inflammation are high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC), and fibrinogen, with hs-CRP being the preferred single marker due to its superior standardization, precision, and predictive ability. 1

Primary Inflammatory Markers for Clinical Use

High-Sensitivity C-Reactive Protein (hs-CRP)

• hs-CRP represents the best candidate inflammatory marker currently available based on clinical chemistry characteristics, with acceptable precision down to or below 0.3 mg/L 1
• The assay has standardized proficiency testing through the College of American Pathologists and ongoing standardization programs at the Centers for Disease Control and Prevention 1
• hs-CRP demonstrates predictive abilities for cardiovascular events within the lower, previously "normal" ranges, making it superior to traditional CRP testing 1
• Approximately 20% of patients with active inflammatory disease (such as Crohn's disease) may have normal CRP levels, which is an important limitation to recognize 2
• Biologic agents targeting specific inflammatory cytokines may disproportionately affect CRP levels, requiring careful interpretation in patients on these medications 3

White Blood Cell Count (WBC)

• WBC count is widely available and has documented association with inflammatory conditions across multiple prospective studies 1
• Elevation of WBC is a cardinal sign of inflammation from trauma, ischemia, infection, and other pathologic conditions 4
• The neutrophil-to-lymphocyte ratio (NLR) derived from the complete blood count can assess disease activity and treatment response in rheumatoid arthritis and predict COVID-19 severity 5, 6
• WBC dynamics show exponential decay during inflammatory recovery, providing a universal recovery trajectory marker 4

Fibrinogen

• Fibrinogen is an acute-phase reactant with widely available assays and acceptable coefficients of variation 1
• Multiple prospective epidemiological studies have documented associations between fibrinogen levels and cardiovascular disease, with gradation of risk across measured ranges 1
• The assay has international standardization through the 2nd International Standard for Fibrinogen, Plasma 1

Erythrocyte Sedimentation Rate (ESR)

• ESR should be monitored at each clinical visit for patients with autoimmune and autoinflammatory diseases, providing complementary information to CRP 3
• ESR and CRP together offer more comprehensive assessment than either marker alone, as recommended by EULAR/ACR guidelines 3
• Traditional ESR testing lacks sufficient specificity to appraise disease activity when used in isolation 5

Additional Inflammatory Markers with Clinical Utility

Complete Blood Count-Derived Parameters

• Mean platelet volume (MPV) can determine prognosis of renal involvement in systemic lupus erythematosus 5
• Platelet count shows delayed linear growth during inflammatory recovery and co-regulates with WBC dynamics 4
• Red cell distribution width (RDW) serves as an inflammatory biomarker with prognostic value in rheumatic disorders 5
• Platelet-to-lymphocyte ratio (PLR) has prognostic utility in assessing disease activity 5, 6
• Hemoglobin levels are negatively associated with development of inflammatory complications and can indicate chronic inflammation 6

Specialized Inflammatory Markers

• Serum amyloid A (SAA) has international standardization but limited clinical availability compared to CRP 1
• Fecal calprotectin (not a blood test) has 93% sensitivity and 96% specificity for diagnosing inflammatory bowel disease, with thresholds of 100-250 μg/g stool warranting further investigation 2

Markers Limited to Research Settings

Several inflammatory markers are only stable when frozen, limiting their clinical utility 1:

• Adhesion molecules (intercellular adhesion molecule-1, selectins)
• Cytokines (interleukin-1, interleukin-6, tumor necrosis factor-α)
• These markers lack widely available commercial assays and standardization programs 1

Clinical Application Algorithm

For general inflammation assessment:

1. Order hs-CRP as the primary marker due to superior standardization and precision 1
2. Include complete blood count with differential to assess WBC, calculate NLR, and evaluate platelet dynamics 5, 4
3. Add fibrinogen when cardiovascular risk stratification is needed 1

For autoimmune disease monitoring:

1. Check both ESR and CRP at each clinical visit as they provide complementary information 3
2. Monitor complete blood count parameters including MPV, NLR, PLR, and RDW for disease activity and prognosis 5
3. Account for medication effects, particularly biologics, which may disproportionately suppress CRP 3

Important Caveats

• Inflammatory markers can be elevated from sources other than the primary disease process, including atherosclerosis in other arteries, systemic inflammation from connective tissue diseases, and local infections such as gingivitis, prostatitis, bronchitis, or urinary tract infections 1
• The profile of inflammatory markers depends on severity, chronicity, and mechanisms of the inflammatory process, as well as individual immune system capacity 7
• While sensitive indicators of inflammation, these markers generally lack specificity to identify the offending cause, requiring clinical correlation 7
• Individual biomarkers have not been strongly associated with specific pathologic events, making pattern recognition and serial monitoring more valuable than single measurements 7