CRP
Background
- C-reactive protein (CRP) is an acute-phase reactant produced by the liver in response to IL-6 stimulation during inflammation, infection, or tissue injury.
- It is one of the most commonly ordered inflammatory markers in the ED but is nonspecific — it rises in virtually any inflammatory state.[1]
- CRP rises within 6–8 hours of an inflammatory stimulus, peaks at ~48 hours, and has a plasma half-life of ~19 hours[1]
- Levels fall rapidly with resolution of the stimulus, making CRP useful for trending disease activity
- CRP is produced exclusively by hepatocytes; severe liver failure may blunt the CRP response[1]
- Two assays exist:
- Standard CRP: Measures levels typically >10 mg/L; used for detecting infection and inflammation
- High-sensitivity CRP (hs-CRP): Measures levels <10 mg/L; used for cardiovascular risk stratification (not typically useful in acute ED settings)
Normal Values
- Normal: <10 mg/L (some labs use <5 mg/L or <3 mg/L as cutoff)
- Mild elevation: 10–50 mg/L — viral infections, mild inflammation, most autoimmune flares
- Moderate elevation: 50–100 mg/L — significant bacterial infection or active inflammatory disease
- Marked elevation: >100 mg/L — strongly suggests serious bacterial infection, sepsis, major trauma, or severe pancreatitis[2]
- Extreme elevation: >200 mg/L — often seen in sepsis, necrotizing soft tissue infection, or extensive burns
ED Applications
Where CRP adds value
- Trending: Serial CRP measurements are more useful than a single value — a rising CRP suggests clinical deterioration; a falling CRP supports treatment response
- Pediatric fever without source: CRP >80 mg/L increases the likelihood of serious bacterial infection in febrile children[3]
- Appendicitis: A normal CRP (especially combined with normal WBC and no left shift) has a high negative predictive value for appendicitis, particularly if symptoms >24 hours[4]
- Septic arthritis vs. transient synovitis: CRP >20 mg/L is one of the Kocher criteria for distinguishing septic arthritis in the pediatric hip[5]
- Undifferentiated infections: A CRP <20–40 mg/L makes serious bacterial infection less likely in low-risk patients, though it does not rule it out
- Osteomyelitis: CRP elevated in >95% of cases; useful for monitoring treatment response
- Neonatal sepsis: Serial CRP (at presentation and 24–48 hours later) used alongside blood cultures to guide antibiotic duration in neonatal sepsis evaluations
Where CRP does NOT help
- CRP cannot distinguish between bacterial and viral infection at moderate elevations (10–80 mg/L) — significant overlap exists
- CRP does not localize infection (will be elevated in pneumonia, UTI, cellulitis, abscess equally)
- A single normal CRP early in illness (<12 hours from symptom onset) does not exclude serious infection — CRP may not have risen yet
- Extremely elevated CRP (>200 mg/L) is not specific to infection — also seen in rheumatologic flares (gout, rheumatoid arthritis, crystal arthropathies), malignancy, and major surgery/trauma
Causes of Elevated CRP
- Bacterial infection (including sepsis, pneumonia, meningitis, intra-abdominal infections)
- Viral infections (usually milder elevation)
- Autoimmune/rheumatologic disease (Rheumatoid arthritis, lupus, vasculitis, IBD, gout)
- Tissue injury (surgery, trauma, burns, MI)
- Malignancy (especially lymphoma, renal cell carcinoma)
- Pancreatitis
- Deep venous thrombosis / pulmonary embolism
Causes of Low/Normal CRP Despite Active Disease
- Very early infection (<6–8 hours from onset)
- Severe hepatic failure (impaired CRP synthesis)
- Immunosuppressive therapy (some biologics, e.g., tocilizumab/IL-6 inhibitors, directly suppress CRP production regardless of active infection — this is a critical pitfall)[1]
- SLE flares (CRP often modestly elevated or normal in lupus flares, unlike most other autoimmune conditions — a markedly elevated CRP in a lupus patient suggests superimposed infection rather than flare)
CRP vs. Other Inflammatory Markers
- CRP vs. ESR: CRP rises and falls faster than ESR; CRP is preferred for acute ED decision-making. ESR is affected by anemia, polycythemia, and paraproteinemias
- CRP vs. procalcitonin: Procalcitonin is more specific for bacterial infection and is preferred for guiding antibiotic decisions in pneumonia and sepsis. CRP is more sensitive but less specific
See Also
References
- ↑ 1.0 1.1 1.2 1.3 Pepys MB, Hirschfield GM.
- C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-1812.
- ↑ Clyne B, Olshaker JS. The C-reactive protein. J Emerg Med. 1999;17(6):1019-1025.
- ↑ Sanders S, et al. Systematic review of the diagnostic accuracy of C-reactive protein to detect bacterial infection in nonhospitalized infants and children with fever. J Pediatr. 2008;153(4):570-574.
- ↑ Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg. 2004;91(1):28-37.
- ↑ Kocher MS, et al. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. J Bone Joint Surg Am. 1999;81(12):1662-1670.