Which laboratory tests are used to measure inflammatory markers?

Laboratory Tests to Measure Inflammatory Markers

High-sensitivity C-reactive protein (hs-CRP) is the single best laboratory test for measuring inflammation in clinical practice, based on superior analyte stability, assay precision, commercial availability, and standardization capabilities. 1, 2

Primary Inflammatory Marker: hs-CRP

Order hs-CRP as your first-line inflammatory marker for any patient requiring inflammation assessment. 2 The American Heart Association and CDC specifically recommend hs-CRP over all other inflammatory markers due to its optimal laboratory characteristics. 1

Measurement Protocol

• Obtain two hs-CRP measurements, optimally 2 weeks apart, and average the results to reduce within-individual variability. 2
• Perform testing only when the patient is metabolically stable without obvious acute infection or inflammatory conditions. 2
• Report results in mg/L to 1 decimal point only. 2
• Testing can be done fasting or nonfasting—it makes no difference. 2

Interpretation of hs-CRP Results

• Low risk: <1.0 mg/L 2
• Average risk: 1.0-3.0 mg/L 2
• High risk: >3.0 mg/L 2
• If hs-CRP ≥10 mg/L: Search for obvious infection or inflammation, discard that result, and repeat testing in 2 weeks. 2

The high-risk tertile (>3.0 mg/L) demonstrates a 2-fold increase in relative risk for inflammatory complications based on data from 15 populations involving 40,000 persons. 2

Secondary Inflammatory Markers (When hs-CRP is Insufficient)

Erythrocyte Sedimentation Rate (ESR)

Use ESR primarily for monitoring chronic inflammatory conditions, not for acute diagnosis. 3, 4 ESR has a much longer half-life than CRP, making it less useful for acute presentations but valuable for tracking diseases like giant cell arteritis, polymyalgia rheumatica, and rheumatoid arthritis over time. 5, 3

Normal values:

• Men: ≤20 mm/h 5
• Women: ≤30 mm/h 5
• Moderate elevation: 50-100 mm/h suggests significant underlying disease 5
• Highly elevated: ≥100 mm/h is an independent prognostic factor for mortality 5

Clinical applications where ESR is specifically useful:

• Giant cell arteritis: ESR >40 mm/h has 93.2% sensitivity 5
• Polymyalgia rheumatica: Monitor every 1-3 months during active disease 5
• Osteomyelitis in diabetic foot infections: ESR ≥70 mm/h has 81% sensitivity and 80% specificity 5

Complete Blood Count (CBC) with Differential

Order CBC with differential to assess white blood cell count as a general indicator of cellular inflammatory response, though it lacks specificity for distinguishing bacterial versus viral infections. 2, 6 The differential count remains clinically useful when high-grade bacteremia is suspected, despite being examiner-dependent. 6

Fibrinogen

Fibrinogen is clinically available but problematic for routine use due to lack of standardization between functional and immunoassay methods. 1 Only consider fibrinogen when combined with ESR and CRP for diagnosing prosthetic joint infections, where ≥2 of 3 abnormal tests (ESR >27 mm/h, CRP >0.93 mg/L, fibrinogen >432 mg/dL) achieve 93% sensitivity and 100% specificity. 5

Context-Specific Inflammatory Markers

For Intestinal Inflammation (Crohn's Disease, Ulcerative Colitis)

• Fecal calprotectin (preferred) or lactoferrin have higher sensitivity and specificity than serum markers for detecting intestinal inflammation and differentiating from irritable bowel syndrome. 2
• CRP should be assessed, though patients may have normal CRP despite active disease. 2
• Albumin to evaluate nutritional status and disease severity. 2
• CBC to assess for anemia from chronic blood loss. 2

For Prosthetic Joint Infections

Order the triad of ESR, CRP, and serum interleukin-6 as strongly recommended by the American Academy of Orthopaedic Surgeons. 5 When at least 2 of 3 tests are abnormal, sensitivity reaches 93% and specificity 100%. 5

Markers NOT Recommended for Routine Clinical Use

Do not order the following inflammatory markers in routine clinical practice: 1, 2

• Cytokines (IL-6, TNF-α, IL-1): Require frozen samples at -70°C, lack standardization, and have short half-lives limiting clinical utility. 1
• Serum amyloid A (SAA): Only one commercial assay available for research use only, with problematic standardization due to multiple phenotypes. 1
• Soluble adhesion molecules (sICAM-1, sVCAM-1, E-selectin, P-selectin): Precluded for routine use due to stability issues and lack of standardization. 1

These markers are confined to research settings and should not be ordered in clinical practice. 1

Critical Pitfalls to Avoid

• Never rely on a single hs-CRP measurement—within-individual variability requires averaging two measurements. 2
• Do not use hs-CRP for monitoring therapy response—the role of inflammatory markers in treatment monitoring has not been established. 2
• Do not interpret elevated inflammatory markers in isolation—other conditions (inflammatory bowel disease, rheumatoid arthritis, chronic alcoholism) can cause mildly to moderately increased levels. 2
• Avoid ESR testing on blood samples from patients positive for hepatitis virus or HIV due to biohazard concerns. 6
• Do not order ESR for acute infections—CRP rises within 12-24 hours and peaks at 48 hours, making it superior for acute presentations. 5

When CRP and ESR Are Discordant

ESR remains elevated longer than CRP after inflammation resolves, which commonly creates discordance. 5, 4 This is particularly prevalent in chronic inflammatory diseases. 4

Factors causing falsely elevated ESR with normal CRP:

• Anemia 5
• Azotemia 5
• Female gender (women have higher baseline ESR) 5
• Advanced age 5

Factors causing elevated CRP with normal ESR:

• Acute infection (CRP rises faster) 3
• Early inflammation (before ESR elevation) 3
• Obesity (can elevate CRP independently) 5