What is C-reactive protein (CRP) used for?

What is C-Reactive Protein (CRP) Used For?

CRP is primarily used as a non-invasive biomarker to detect and monitor inflammation, particularly in inflammatory bowel disease (IBD), cardiovascular risk stratification, and acute infections, though its clinical utility varies significantly by context and it should never be used alone to rule out serious disease.

Primary Clinical Applications

Inflammatory Bowel Disease Assessment

CRP serves as a readily available biomarker for assessing disease activity in IBD, though with important limitations:

• In Crohn's Disease: CRP <5 mg/L can help rule out endoscopic inflammation in patients with symptomatic remission and known endoscopic remission, though the evidence is low certainty due to false-negative rates exceeding 5% 1.

• In Ulcerative Colitis: CRP performs poorly with only 63% sensitivity for detecting moderate to severe endoscopic inflammation 1, 2. Approximately 18.5% of patients with mild symptoms and normal CRP may still have moderate to severe endoscopic activity 1.

• Treatment Monitoring: In symptomatically active Crohn's disease, biomarker-based assessment (including CRP) combined with symptoms is superior to symptoms alone for treatment adjustments 1.

• Initial Workup: All patients aged 16-40 with new lower GI symptoms suspected of IBD should have CRP measured alongside full blood count, urea & electrolytes, coeliac screen, and stool culture in primary care 1.

Cardiovascular Risk Stratification

• CRP values <1.0 mg/L indicate low cardiovascular risk, 1.0-3.0 mg/L average risk, and >3.0 mg/L high cardiovascular risk 3.

• In patients with intermediate cardiovascular risk (10-20% 10-year CHD risk), elevated CRP may reclassify them to high risk, potentially indicating need for statin therapy 3.

Acute Infection and Inflammation Detection

• CRP increases 4-6 hours after inflammatory trigger and peaks at 36-50 hours, making it useful for monitoring acute inflammatory states 4, 5.

• CRP can rise above 500 mg/L during acute illness, with median values varying by condition: acute bacterial infections ~120 mg/L, non-bacterial infections ~32 mg/L, inflammatory diseases ~65 mg/L 3.

• In neonatal sepsis, two CRP measurements 24 hours apart that are <10 mg/L are useful in excluding sepsis 4.

Critical Limitations and Pitfalls

When CRP Fails to Detect Inflammation

Never rely on a single normal CRP to exclude inflammation in high-risk scenarios 2:

• In ulcerative colitis, 18.5-37% of patients may have normal CRP despite active disease 2.

• Approximately 5.5% of asymptomatic Crohn's patients with normal CRP may have moderate to severe endoscopic activity 2.

• Neutropenia, immunodeficiency states, and immunosuppressive therapy can blunt CRP response despite active inflammation 2.

• NSAID use within the past 6 weeks may affect CRP concentrations and mask inflammatory responses 1, 2.

Fecal Calprotectin is Superior for IBD

• Fecal calprotectin demonstrates greater sensitivity than CRP for detecting intestinal inflammation 1.

• For ruling out IBD in primary care: calprotectin <100 μg/g suggests IBS is likely, 100-250 μg/g warrants repeat testing or routine gastroenterology referral, and >250 μg/g requires urgent gastroenterology referral 1.

• Fecal calprotectin is a validated biomarker for endoscopic and histological disease activity and can inform treatment escalation or de-escalation decisions 1.

Practical Management Algorithm

For Elevated CRP (≥10 mg/L)

1. Repeat testing and examine for sources of infection or inflammation 3.

2. Screen for infection/injury symptoms and measure body temperature 3.

3. Consider magnitude of elevation to guide differential diagnosis (bacterial infection vs. inflammatory disease vs. malignancy) 3.

4. Identify and treat the specific underlying condition 3.

5. Repeat CRP after clinical recovery to confirm normalization 3.

For IBD Monitoring

1. Initial assessment: Measure CRP alongside fecal calprotectin in all suspected IBD cases 1.

2. Active disease: Perform interval biomarker assessment every 2-4 months in patients being treated for active symptoms 1.

3. After symptom resolution: Obtain endoscopic evaluation 6-12 months after treatment initiation to confirm mucosal healing, as normal CRP does not reliably exclude endoscopic activity 1.

4. If CRP normal but suspicion high: Use fecal calprotectin or fecal lactoferrin as alternative markers 2.

Key Clinical Caveats

• CRP normalizes more quickly than ESR during resolution of inflammation 3.

• A normal CRP level should never delay antibiotic coverage in suspected serious bacterial infections 6.

• CRP results should not be used to monitor cardiovascular treatment due to significant variation independent of treatment modality 3.

• Persistently unexplained marked elevation of CRP (>10 mg/L) after repeated testing should prompt evaluation for non-cardiovascular causes 3.