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C reactive protein (CRP)


  • CRP was 1st described in 1930 by Tillet and Francis.
  • C-reactive protein plays a key role in the host's defence against infection by activating the complement system and acts as an opsonin for bacterial sequences and nuclear material which has been expressed from a cell during apoptosis, and thus enhances phagocytosis thereby helping to fight infections as well as protect against auto-immune disease.
  • It was so named because it reacts with the C-polysaccharide of Streptococcus pneumoniae.
  • C-reactive protein elevation is part of the acute-phase response to acute and chronic inflammation.
  • It out-performs erythrocyte sedimentation rate (ESR) in terms of responsiveness (and thus sensitivity) and specificity for inflammation.
    • the ESR reflects concentrations of fibrinogen and alpha-globulins. It is influenced by immunoglobulins that are not acute-phase proteins. These proteins all have half-lives of days to weeks, and there is a significant lag time between changes at the clinical level and variations in the ESR. This, plus the influence of various other factors on the ESR such as diurnal variation, anaemia, food intake and red cell morphology, makes it an imprecise guide to disease activity in most cases.
    • however, ESR remains helpful in certain clinical situations such as the detection of paraproteinaemias, which often do not elicit an acute phase response.
  • raised CRP is 90% sensitive for presence of significant inflammation (but does take some 12 hours to go up)
  • a raised CRP has sensitivity of around 75% and specificity of around 67% for sepsis but this depends on the cutoff used and the clinical setting
    • viral infections generally cause a mild or no rise in CRP, but some viruses will cause a high CRP such as the hepatitis viruses
    • burn injury causes a high CRP
    • various non-infective inflammatory conditions cause a high CRP such as Crohn's disease
    • activation of sympathetic nervous system may cause a raised CRP such as major trauma, severe haemorrhage, and this response appears to be able to be blocked by beta adrenergic blockers
    • procalcitonin generally has a higher sensitivity and specificity for sepsis (and in paediatrics as well as with Covid-19 better differentiates viral vs bacterial infection), rising earlier than CRP and levels correlate with degree of severity and respond to treatment success (and a fall of 25% over 5 day period is a predictive survival indicator for septic shock patients), and is more predictive of late mortality from sepsis 1)
  • is predominantly made in the liver and is secreted in increased amounts within six hours of an acute inflammatory stimulus - primarily stimulated by IL-6, but response is enhanced by IL1-B and TNF-a.
  • The plasma concentration can double at least every eight hours, reaching a peak after about 50 hours. After effective treatment or removal of the inflammatory stimulus, concentrations can fall almost as rapidly as the 5-7 hour plasma half-life of labelled exogenous C-reactive protein.
  • C-reactive protein responses may be reduced by severe hepatocellular impairment, but renal dysfunction can elevate concentrations of C-reactive protein.
  • baseline concentrations for a normal individual is in part genetically determined.

Causes of major elevations of CRP > 60

  • bacterial infections
  • gastroenteritis
  • hypersensitivity complications of infections such as erythema nodosum & rheumatic fever
    • CRP is a good marker of disease activity in Crohns (but not for UC) and can be predictive of the need for colectomy.
    • CRP is a good marker of psoriasis severity in the case of untreated psoriatic patients who do not have disease related arthritis 3)
    • CRP is usually > 100 in subacute thyroiditis
  • renal transplantation
  • cancers such as lymphoma & sarcoma (usually no higher than 130 and there is a signficant correlation with B symptoms)
    • CRP can be a useful prognostic marker for non-Hodgkin lymphoma 4)
    • a falling CRP can be a marker of response to chemotherapy for some cancers
  • necrosis such as AMI, tumour embolisation & acute pancreatitis
  • trauma such as burns, major haemorrhage, or fractures
    • in patients with Mycoplasma pneumoniae infection, mean CRP without hepatitis is around 70, mean CRP with hepatitis is around 140 5)
  • some viral infections may cause a high CRP such as:
    • adenovirus
    • influenza, although usually a high CRP > 70 in a patient with influenza suggests a bacterial infection or severe pneumonitis
    • coronavirus pneumonitis including COVID-19 coronavirus (2019-nCoV / SARS-CoV-2)
      • CRP > 50 appears to correlate with likelihood of hypoxaemia 6) and CRP > 100 with mortality risk 7)
    • acute viral hepatitis
      • almost all have CRP > 32, and most have CRP > 100 8)9)
  • severe acute gout or pseudogout
  • systemic lupus erythematosus (SLE) with active serositis (median CRP levels of 76mg/L)

Causes of mild-moderate elevations of CRP 15-60mg/L

  • early CRP rise in infections or resolving infections (or other causes of major elevations)
  • inflammatory disease such as:
    • rheumatoid arthritis - median levels in active disease are 20–40 mg/liter 10)
      • whilst ESR levels tend to correlate with disease activity in SLE, CRP levels can be quite low in the absence of serositis
      • median levels in active disease are around 15mg/liter 11)
      • a very high proportion of uninfected lupus patients were found to have clinically significant CRP elevations, which did not, however, correlate with disease activity
      • a minority with active lupus have levels > 60mg/L for example:
        • median CRP level was 76 mg/L in patients with serositis without infection
        • in the absence of serositis, chronic synovitis, or Jaccoud's arthropathy, lupus patients with CRP > 60mg/L suggests bacterial infection or other cause
      • ∼10% of patients with inactive lupus and without infection were found to have CRP levels >10 mg/liter
  • graft vs host disease
  • cancer such as leukaemia
    • pre-treatment CRP > 15 is a marker for poorer outcomes in those with DLBCL non-Hodgkin lymphoma 12)
  • alcoholic hepatitis
  • viral infections such as influenza
  • mild-mod gout
  • other inflammatory processes such as abdominal aortic aneurysm (AAA) 13)

Causes of minimal elevations of CRP

  • obesity
  • renal impairment
  • “low grade inflammation states” such as:
  • “metabolic syndrome” - the constellation of risk factors for cardiovascular disease and type 2 diabetes, which are generally associated with obesity and insulin resistance.
  • 7% of “normal” young adults have a CRP > 10mg/L (higher rates for women, blacks, and those aged over 70yrs)
    • approximate upper limit of the reference range (mg/L) for CRP adjusted for age:
      • for men: (age in years)/5
      • for women: (age in years/5) + 6

Other references

crp.txt · Last modified: 2023/01/14 22:58 by wh

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