How to use: C-reactive protein

S McWilliam, A Riordan Arch Dis Child Educ Pract Ed 2010;95:55-58

Compiled by Dr. Abu Iqbal

Paediatrics & Neonatology

CRP
CRP is a protein synthesised and secreted by the liver in response to inflammatory cytokines, particularly IL-6. It plays this role by mediating
Phagocytosis activating the complement cascade and by producing further inflammatory cytokines. CRP forms complexes by binding to polysaccharides and peptopolysaccharides present on bacteria CRP also binds to components of damaged host cells
Ballou SP, Kushner I. Adv Intern Med 1992

Du Clos TW. Ann Med 2000

Normal CRP
In normal individuals serum CRP is <10 mg/l. CRP is highly elevated by serious bacterial infections (SBIs) up to 150350 mg/l, but less highly elevated by acute viral infection, to 2040 mg/l. However, some viral infections can cause elevations >100 mg/l eg,
adenovirus, mumps and measles
Jaye DL, Waites KB. Pediatr Infect Dis J 1997

Synthesis
CRP synthesis increases within 46 h of an inflammatory trigger and doubles every 8h It peaks at 3650 h levels decrease rapidly with the resolution of inflammation due to a short half-life of 47 h
Young B, Gleeson M, Cripps AW. Pathology 1991 Pepys MB, Baltz ML. Adv Immunol 1983

Sensitivity & Specifity

Sensitivity of CRP for identifying SBI from 63% to 95%, and
specificity from 40% to 91%

London: RCOG Press, 2007. www.rcog.org.uk, http://www.nice.org.uk

How should CRP be used in neonates with suspected sepsis?

The upper limit of normal has been established as 10 mg/l there can be a poor CRP response on the first day of postnatal life in full-term infants, and for longer in preterm infants

Hengst JM.Adv Neonatal Care 2003 Jaye DL, Waites KB. Pediatr Infect Dis J 1997

Ruling in sepsis
The sensitivity of a raised CRP for neonatal sepsis 35% to 94% and specificity from 60% to 96% May be raised for other reasons
prolonged rupture of membranes, maternal fever during labour fetal distress, perinatal asphyxia or shock periventricular and intraventricular haemorrhages pneumothoraces, and meconium aspiration pneumonitis
Hengst JM.Adv Neonatal Care 2003

Ruling out sepsis

Serial CRP values 2448 h after the onset of symptoms have an improved sensitivity and specificity when compared with single CRP values at presentation. 78.9% to 98% and specificity from 84% to 97%. Two consecutive CRP levels <10 mg/l 24 h apart, 848 h after presentation, have a negative predictive value for sepsis of 99% Thus, two serial CRP levels <10 mg/l, at least 24 h apart, can accurately identify infants who are unlikely to be infected or have a resolved infection
Benitz WE, Han MY, Madan A, et al. Pediatrics 1998

Serial CRP levels that fail to decrease, or that continue to rise after 48 h of antibiotic therapy, suggest
treatment failure (such as fungal infection) and indicate the need for further clinical review and microbiological investigation

Jaye DL, Waites KB. Pediatr Infect Dis J 1997 Kksal N, Harmanci R,Cetinkaya M, et al. Turk J Pediatr 2007

Clinical bottom line

CRP levels begin to increase 46 h after an inflammatory trigger and peak at 3650 h CRP levels that fail to decrease, or continue to rise, after 48 h of antibiotic therapy suggest treatment failure In children presenting with fever without focus, a single CRP level is not sensitive or specific enough to identify all children with SBI In children with pneumonia, a single CRP value >4060 mg/l is weakly predictive of bacterial pneumonia. A CRP value below this cutoff should not in itself be a reason to withhold antibiotics In a child with a limp, a CRP level of >20 mg/l suggests septic arthritis of the hip rather than transient synovitis In infants with suspected neonatal sepsis, a single CRP level at presentation is not useful alone in either diagnosing (if raised) or excluding sepsis (if normal) In infants being treated for suspected neonatal sepsis, serial CRP levels are useful in excluding that diagnosis if two CRP measurements 24 h apart are <10 mg/l. Serial CRP levels that fail to decrease or that increase after 48 h suggest treatment failure.