Tag Archives: C-reactive protein

Do You Really Need Both a CRP and ESR?

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An erythrocyte sedimentation rate (ESR) and a C-reactive protein (CRP) are often ordered together, but many times provide similar information.  An ESR is a measure of acute phase proteins in the plasma.  A CRP is a proinflammatory acute phase reactant “which responds to infection and trauma by activating the complement/phagocytosis components of the immune system.”

Inevitably with the two tests, there is a higher sensitivity; for example, with osteomyelitis, one study found the paired testing had a 98% sensitivity compared with a 95% sensitivity for CRP alone (not statistically significant).  However, the authors note that “concordant or discordant results also have been found to lack clinical utility.”  As a consequence, the authors decided to investigate the costs of pairing these tests.  At their 739 tertiary care hospital, the additional cost resulted in charges between $250,000-400,000 more than ordering a single test.  They extrapolate the cost to $300 million nationally.

Take-home message: If you were spending your own money &/or trying to be a good steward of someone else’s, could you justify the expense of routinely obtaining both an ESR and a CRP?

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What physicians can learn from fast-food restaurants and …

Hepcidin for sepsis recognition

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While this blog has discussed hepcidin’s essential role in iron homeostasis (see below), it performs well as a marker of sepsis as it is also an acute phase reactant (J Pediatr 2012; 162: 67-71).

Hepcidin is known to contribute to host defense by depriving microbes of access to iron and through direct antimicrobial properties.  In this study, the authors compared the performance of hepcidin to C-reactive protein (CRP) from the serum of 44 infants with late-onset sepsis.  Specimens were obtained in the acute and convalescent periods.

Results:

  • Hepcidin levels were increased 4-fold in infants with sepsis compared without infants who were not septic (P<.0001).  Levels returned to normal following therapy.
  • Hepcidin levels >92.2 ng/mL correctly identified 91% of all infants (PPV 100%, NPV 87%, specificity 100%, sensitivity 76%)
  • Models combining hepcidin with CRP did not perform better than hepcidin alone.
  • Hepcidin values were comparable to CRP, and possibly more useful.  The authors stated that a CRP value of >7.95 mg/dL had a PPV of 89%, NPV 74%, specificity of 96%, and sensitivity of 47%.
  • Hepcidin has been reported to peak at 6 hours after interleukin-6 injection in humans whereas CRP peaks 24-48 hours after an inflammatory stimulus.

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Biomarkers identify patients who benefit and how

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Fecal calprotectin and serum CRP levels are helping to identify which patients benefit most from biologic therapies, how frequently to dose individuals and how well inflammation correlates with changes in CDAI.  Several abstracts from ACG highlight these issues:

Abstract #1175: Fecal calprotectin concentration and clinical remission in patients with active Crohn’s disease treated with certolizumab pegol: results from PRECiSE 1 (Sandborn W et al).

Abstract #1164: Baseline C-reactive protein is associated with disease progression in  patients with Crohn’s disease (Colmbel J-F et al).

Abstract #1165: Association of baseline C-reactive protein with maintenance of remission in patients with moderate to severe Crohn’s disease treated with adalimumab (Sandborn W et al)

Abstract 1175 uses a post hoc analysis of patients with active Crohn’s disease (CD) who were treated with certolizumab or placebo for 26 weeks.  Baseline calprotectin concentrations were higher in patients who achieved remission.  Another interesting finding of this study was that placebo patients did not have improvement in calprotectin levels.  So, even though some patients  had improvement in CDAI scores, indicating subjective improvement, inflammatory activity did not decline.  This is another indicator of how flawed a CDAI is for indicating the effectiveness of an IBD therapy.

Abstract 1164 looked at 238 patients with moderate to severe CD who were randomized to placebo arm in the CHARM study.  These patients were given open-label adalimumab for induction (80 mg week 0, 40 mg week 2) followed by blinded weekly placebo treatment from weeks 4-56 with a switch to open-label adalimumab after week 12 for a disease flare.  Higher baseline CRP levels in patients with moderate or severe CD were associated with higher disease scores after four weeks and after one year.  This suggests that a patient with higher CRP is more likely to have disease progression without adequate treatment.

Abstract 1165 examined the relationship between CRP and remission in CHARM patients. In the high baseline CRP group, 39 patients received adalimumab every other week, 28 weekly, and 34 received placebo.  In the low baseline CRP group, there were 42 every other week patients, 33 weekly, and 39 placebo patients.  In the high baseline CRP group, remission rates were 50% higher in the weekly treatment group compared to the every other week group.  Patients with low baseline CRP had similar results when treated weekly versus every other week.  Thus, patients with high baseline CRP are more likely to benefit from dose escalation and low CRP patients are more likely to have coexistent issues contributing to their symptoms (eg. IBS).

One other caveat: CRP production is geneticallly-determined and some patients do not make CRP in spite of active inflammation.

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Additional calprotectin references:

  • -IBD 2010; 16: 482. Calprotectin correlated with inflammation of ileum after pouch creation in children.
  • -IBD 2009; 12: 1851. Calprotectin was the only marker to correlate with endoscopic activity; n=134.
  • -JPGN 2009; 48: 48. Good sensitivity/specificity of calprotectin & lactoferrin. Up to 96% sensitivity & specificity.
  • -Clin Gastro & Hep 2008; 6: 1218. Lack of correlation between clinical symptoms and fecal biomarkers. However, biomarkers do correlate with mucosal/endoscopic disease. n=164.
  • -IBD 2008; 14: 1392. Monitoring IBD activity level c calprotectin & lactoferrin; n=15.
  • -IBD 2008; 14: 1229. Clinical utility in assessing histological relapse in kids. n=73 over 8yrs…may allow avoidance of invasive tests; cut off of 275mcg/gm had 97% sensitivity/neg pred value 85% pos pred value/specificity at predicting relapse.
  • -IBD 2008; 14: 669. Fecal calprotectin good at predicting relapse in pediatric IBD w cutoff of 400.

C-reactive protein references:

  • -J Pediatr 2011; 159: 340. CRP helps identify IBD.
  • -Clin Gastro & Hepatology 2011; 9: 421. CRP predicts response to IFX. n=718. those with high CRP had 91% response vs 83% in pts with NL CRP.
  • -Gastro 2004; 126: 1574-81. Crohn’s review. High CRP suggests likely response to anti-TNFα treatment.
  • -JPGN 2004; 38: 509-12. CRP more reliable than ESR for IBD.
  • -NEJM 1999; 340: 448. Review on acute phase reactants. CRP better than ESR as ESR is an indirect measure (resistance of plasma, due to fibrinogen, to the falling of RBCs) & broader range for CRP.