C-Reactive Protein

Aka: C-Reactive Protein, C Reactive Protein, CRP, C-RP, High-Sensitivity CRP, hs-CRP

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II. Physiology

  1. Serum globulin synthesized in the liver
  2. Acute phase reactant increases with acute tissue injury or inflammation
  3. C-Reactive Protein binds Bacteria surface and facilitates Phagocytosis
  4. Rises more than 6 hours after triggering stimulus
  5. Peaks within 36-50 hours
  6. Short half life of 5-7 hours
    1. Rapidly declines after condition resolves

III. Indications

  1. Detection and monitoring of diseases below
    1. See efficacy below
    2. Does not significantly alter management in the emergency detection of serious Bacterial Infection
  2. Differentiating certain conditions
    1. Serious Bacterial Infection in children (Occult Bacteremia)
    2. Systemic Lupus Erythematosus
      1. CRP higher in Rheumatoid Arthritis
      2. CRP higher in other Arthritis
    3. Crohn's Disease
      1. CRP higher in Ulcerative Colitis
    4. Pyelonephritis
      1. CRP lower in cystitis
    5. Bacterial Infection
      1. CRP lower in Viral Infection
    6. Acute Bronchitis
      1. CRP lower in Asthma

IV. Causes: Increased

  1. General inflammatory conditions
    1. Inflammatory disease
    2. Infections
    3. Neoplastic disease
  2. Inflammatory disease
    1. Rheumatoid Arthritis
    2. Rheumatic Fever
    3. Inflammatory Bowel Disease
    4. Seronegative Arthritis (Reiter's Syndrome)
    5. Vasculitis (e.g. Hypersensitivity Vasculitis)
  3. Detection and monitoring of infection
    1. Bacterial Infection in Systemic Lupus Erythematosus
    2. Neonatal infection
    3. Postoperative Infection
    4. Intercurrent infection in Leukemia
    5. Pyelonephritis
  4. Detection of Tissue Injury
    1. Myocardial Infarction
    2. Transplant Rejection
    3. Neoplasia (e.g. Burkitt's Lymphoma)
  5. Cardiovascular disease risk
    1. See Cardiac Risk Factor
    2. See Cardiac Risk Management

V. Causes: Normal conditions with elevated CRP

  1. Medications (e.g. Oral Contraceptives)
  2. Third trimester of pregnancy
  3. NSAIDS may modify CRP (increased with Ibuprofen, decreased with Naproxen)

VI. Efficacy

  1. Serious Bacterial Infection in children
    1. CRP <10 mg/L has a Negative Predictive Value for Sepsis of 99%
    2. CRP >40 mg/L is more suggestive of serious Bacterial illness (but not sensitive or specific)
    3. Bilavsky (2009) Acta Paediatr 98(11): 1776-80 +PMID:19664100 [PubMed]
    4. McWilliam (2010) Arch Dis Child Educ Pract Ed 95(2): 55-8 +PMID:20351152 [PubMed]
    5. Yo (2012) Ann Emerg Med 60(5): 591-600 [PubMed]
  2. Serious Bacterial Infection in adults
    1. C-RP does not adequately distinguish serious Bacterial Infection in hospitalized adults
      1. Test Sensitivity for Bacterial Infection: 75%
      2. Test Specificity for Bacterial Infection: 67%
      3. Simon (2004) Clin Infect Dis 39(2): 206-17 +PMID:15307030 [PubMed]
  3. Septic Arthritis
    1. CRP is inadequate for ruling-in or ruling-out Septic Arthritis
      1. CRP >10 mg/ml still has a False Negative Rate of 13% for Septic Arthritis
      2. CRP >150 mg/ml still has a False Positive Rate of 17% for Septic Arthritis
      3. Carpenter (2011) Acad Emerg Med 18(8): 781-96 +PMID:21843213 [PubMed]
    2. CRP closely mirrors infectious process for monitoring
      1. Sensitivity: 95%
      2. Kallio (1997) Pediatr Infect Dis 16:411-2 [PubMed]
  4. Cardiovascular disease
    1. hs-CRP >3 mg/L predicts more ischemic episodes
      1. Rosenson (2003) Am J Cardiol 92:10i-18i [PubMed]
    2. Comparatively weak predictor of heart disease
      1. Odds Ratio C-RP: 1.45
      2. Odds Ratio Increased SBP: 1.50
      3. Odds ratio Tobacco Abuse: 1.87
      4. Odds Ratio Increased Total Cholesterol: 2.35
      5. Danesh (2004) N Engl J Med 350:1387-97 [PubMed]

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