Inflammatory Laboratory Workup
A comprehensive inflammatory workup should include a complete blood count with differential, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and a complete metabolic panel as the foundational tier 1 screening tests. 1
Tier 1: Initial Screening Panel
The first-line inflammatory workup consists of readily available tests that can be obtained at most clinical facilities:
- Complete Blood Count (CBC) with manual differential to assess for lymphopenia, neutrophilia, thrombocytopenia, leukocytosis, or anemia 1
- Erythrocyte Sedimentation Rate (ESR) - values >20 mm/h in men and >30 mm/h in women are considered elevated, with moderate elevation (50-100 mm/h) indicating significant underlying disease 2
- C-reactive protein (CRP) - the preferred acute-phase reactant due to superior standardization, acceptable precision down to 0.3 mg/L, and better correlation with acute disease activity than ESR 1, 3
- Complete Metabolic Panel including sodium, potassium, glucose, creatinine, liver enzymes (AST, ALT), and albumin to identify hyponatremia, hypoalbuminemia, azotemia, and hepatic involvement 1, 2
CRP is superior to ESR for evaluating acute inflammatory conditions because it rises and falls more rapidly with changes in inflammation, has better standardization through proficiency testing programs, and demonstrates acceptable coefficients of variation at clinically relevant levels. 1, 3
Tier 2: Extended Inflammatory Assessment
When tier 1 screening reveals elevated inflammatory markers (ESR and/or CRP) plus at least one additional abnormality, proceed to more comprehensive testing:
- Ferritin - typically ranges from 500-2,000 ng/dL in inflammatory conditions, though levels <30 μg/L indicate iron deficiency without inflammation 1, 3
- D-dimer - frequently elevated in systemic inflammatory states 1
- Lactate dehydrogenase (LDH) - marker of tissue damage and inflammation 1
- Procalcitonin - can be profoundly elevated in inflammatory conditions even without bacterial infection 1
- Troponin T and BNP/NT-proBNP - essential when cardiac involvement is suspected, though BNP is an acute-phase reactant and may be elevated in inflammatory conditions without cardiac disease 1
Specialized Inflammatory Markers
Additional testing should be guided by clinical context:
- Fibrinogen - acute-phase reactant with acceptable precision and standardization, though less favored than CRP for routine use 1
- Serum albumin and pre-albumin - assess nutritional status and degree of inflammation, particularly in chronic inflammatory conditions 3
- Cytokine panels (IL-6, TNF, IL-10) - when available, can assist in diagnostic evaluation but should not dictate treatment choices and are not required for treatment planning 1
Critical Interpretation Caveats
Several factors can artificially alter inflammatory marker results:
- ESR is affected by anemia, azotemia, elevated immunoglobulins, rheumatoid factor, female sex, and advancing age - all can increase ESR independent of inflammatory activity 2
- CRP has superior specificity but normal levels do not exclude active inflammation, particularly in ulcerative colitis where some patients have active disease without CRP elevation 3
- Ferritin interpretation requires context - in the presence of active inflammation, levels up to 100 μg/L may still represent iron deficiency rather than adequate iron stores 3
Condition-Specific Considerations
The inflammatory workup should be tailored based on clinical presentation:
- For suspected infection: Add blood cultures, stool cultures, and Clostridium difficile toxin testing; consider fecal calprotectin for intestinal inflammation 1, 3
- For cardiac symptoms: Include troponin, BNP, EKG, and echocardiogram to evaluate for myocarditis, pericarditis, or coronary involvement 1
- For rheumatologic concerns: Add rheumatoid factor, anti-CCP antibodies if joint symptoms present; consider ANA and ANCA only if clinical signs suggest specific autoimmune conditions 1, 2
- For pediatric fever with SARS-CoV-2 exposure: Include SARS-CoV-2 PCR and serology testing as part of MIS-C evaluation 1
Monitoring Strategy
For persistent or unexplained elevation, repeat ESR and CRP in 2-4 weeks to determine if elevation is persistent or transitory. 2 During active inflammatory disease, monitor ESR every 1-3 months until remission is achieved, then every 3-6 months once low disease activity is maintained. 2