CRP vs.

ESR
Assessing and Measuring
the
Inflammatory Response
 ESR:CRP
ESR and CRP are some of the most
commonly requested tests by New
Zealand general practitioners. ESR is
being performed about twice as often as
CRP, but it is now recognised that in most
situations CRP provides more valuable
information to the clinician.
 What do we recommend?

Choose CRP first on most occasions

Seldom request ESR and CRP

simultaneously
 Why do we make these
recommendations?
1. CRP shows a rapid response to infection and
inflammation: increasing within hours of stimulus,
and returning rapidly to normal following resolution.

2. There are distinct ranges of normal and abnormal in

CRP reference ranges, without variations for age or
gender.

3. CRP is not affected by conditions such as pregnancy,

intercurrent drug use, anaemia and plasma protein
variations.
4. There is seldom any value in requesting ESR and CRP
simultaneously.
 What is the best test to use in
different situations?
There are few studies that compare the use
of ESR and CRP.

The best approach is to consider the various

clinical questions that may be posed
during the course of the consultation.
Table 1: Choosing CRP or ESR
Question CRP ESR Comments

Screening asymptomatic patients? Unlikely to be useful

I know this patient is ill but I don’t Actual level of CRP


know why helpful
Could this patient have a significant CRP good, ESR slow

bacterial infection response
Could the patient have post-op CRP good, ESR slow

infection? response
Has the infection responded to this CRP good, ESR slow

antibiotic response

Is this RTI more serious than it seems?  Level of CRP useful

Is this patient responding to a trial of

CRP good, ESR slow
steroid therapy? 
response

Does this patient have PMR? PMR with a normal ESR

 
occasionally occurs
Table 1 continued….
Question CRP ESR Comments
CRP more sensitive indicator
Monitoring PMR   
of activity
Does this patient have temporal GCA with a normal ESR
  
arteritis/GCA? occasionally occurs
CRP more sensitive indicator
Monitoring temporal arteritis/GCA? 
of activity
What is the cause of this/these Little CRP more sensitive indicator
use ? 
inflamed joints? of activity
CRP better measure of the
Monitoring rheumatoid arthritis   
disease activity
CRP normal during flare, but
Monitoring SLE?   
elevated during infection
Many different causes which
Why is the platelet count elevated?   
may include inflammation
Prediction of cardiovascular
? Role not yet established
disease
Screening Asymptomatic patients
• CRP and ESR are not suitable as a screen in asymptomatic patients.
• They should only be requested on patients in whom the clinical evaluation
has given some indication of a disease process.

Polymyalgia rheumatica
• There is little evidence to suggest CRP is a suitable diagnostic test for the
diagnosis of PMR.
• It is reccommended both ESR and CRP are requested when considering PMR
as a diagnosis, CRP is recommended for the monitoring of PMR.

Temporal (giant cell) arteritis

• It is recommended that CRP and ESR should be tested simultaneously,
which will result in a higher sensitivity for diagnosis.

CRP as a cardiovascular disease risk factor

• At this stage, High Sensitivity-CRP (Hs-CRP) does not have a definitive role
as a cardiovascular disease risk factor.
Infection
• CRP is useful when considering an atypical infection, as it can be helpful in
differentiating between bacterial and viral infections.
• AS the CRP increases above 100mg/L, the likelihood of a bacterialinfection
becomes greater than viral infection

Rheumatoid Arthritis
• Neither CRP or ESR are of use when diagnosing rheumatoid arthritis, as there are
other defined diagnostic criteria.
• CRP is considered a better measure of the disease activity and it is known that
sustained high levels of CRP are associated with worse outcomes.

Malignancy
• Given the non-specif nature of the acute phase response, a definite role of CRP
measurements in the management of cancer patients, other than in cases of
intercurrent infection has not yet been established.
CRP as an indication of severity
• When a patient is ill but the diagnosis is not known, the
level of CRP may provide additional information to assist
in reaching a diagnosis.
• As the CRP levels rises significantly higher, more urgent
review of the patient becomes necessary.

Table 2: CRP as an indication of severity

CRP (mg/L)
10 – 40 Mild Inflammation, viral or bacterial infection
40 – 100 Moderate Inflammation, viral or bacterial
infection
100 – 200 Marked inflammation, bacterial infection
> 200 Severe bacterial infection or extensive trauma
 Result interpretation
Table 3: CRP and ESR Reference ranges

CRP (mg/L) <5

ESR (mm/hour) Female Male

Child 1 -10 1 – 10 1 - 10
Adult < 50 years 1 – 20 1 – 15
Adult > 50 years 1 - 30 1- 10
 How do ESR and CRP differ
• Measuring CRP in the laboratory is a more direct
measure of the inflammatory process.
• By contrast ESR is a more indirect measure

Table 4: Comparison of ESR and CRP

Results affected by: ESR CRP

Gender Yes No

Age Yes No

Pregnancy Yes No

Temperature Yes No

Drugs (eg. steroids, salicylates) Yes No

Smoking Yes No
 CRP and ESR patterns of response

Both CRP and ESR have characteristic

patterns of response (Figure 1). CRP
begins to rise within 4-6 hours of
stimulus, peaks within 36-50 hours, and
returns to normal 3-7 days following
resolution. ESR shows a much slower
response, taking up to a week to peak,
and up to several weeks to return to
normal.
Figure 1: CRP and ESR patterns of response
 Acute Phase Response
Following injury, trauma or infection of a tissue, a
complex series of reactions occur in an effort to prevent
ongoing tissue damage, and activate the repair
processes. This cumulative homeostatic process is
known as inflammation, and the early of reactions are
known as the acute phase response (APR).

The cells that most commonly initiate the APR are tissue
macrophages and blood monocytes. These cells release
cytokines such as IL-1 and TNF that control the migration
of leukocytes into tissue and orchestrate the inflammatory
response. Fever and leuckocytosis are among the most
obvious consequences. The biosynthetic activity of the
liver is profoundly affected.
 Acute Phase Response cont…
The pro-inflammatory cytokines IL-1 and TNF act
on hepatocytes to greatly increase production of
acute phase proteins such as CRP and serum
amyloid A protein (Figure 2). These proteins are
particularly useful for reflecting inflammation
because of the increase of up to 1000 fold from
resting levels. There are more moderate
increases in the level of other proteins such as
ferritin which may affect assessment of iron
status in the presence of inflammation. There is
a corresponding decrease in the synthesis of
some other proteins, most notably albumin
which may reach low levels in the presence of
sustained inflammation.
CRP is a better measure of acute
phase response
• CRP is more sensitive than ESR to subtle
changes in the acute phase response

• There are distinct ranges of normal and

abnormal in CRP reference ranges, without
variations for age and gender.

• CRP is not affected by conditions such as

pregnancy, intercurrent drug use, anaemia and
plasma protein variations.
Figure 2: The acute phase proteins
 ESR
The phenomenon now recognised as the
erythrocyte sedimentation rate was first
observed by ancient Greeks. They observed the
relationship between the sedimentation of red
blood cells and fibrinogen (or “phlegma”),and
used it as a means of detecting bad bodily
“humors”.16 The test used today was
introduced in 1918 by Robin Fahraeus, when he
recorded the erythrocytes of pregnant women
settled more quickly than the erythrocytes of
non pregnant women.
 ESR continued…
Normally, erythrocytes settle quite slowly, as the
gravitational force of the erythrocyte’s mass is
counteracted by the buoyant force of the erythrocyte’s
volume. In normal circumstances erythrocytes have a
net negative charge and therefore they repel each
other. Many plasma proteins are positively charged,
thereby reducing the repulsive forces and promoting
red cell aggregation, which in turn creates a higher
mass and therefore the cells settle much more quickly.
Fibrinogen and α- and β-globulins are major
contributors to the ESR17, and immunoglobulins to a
lesser extent. 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
 ESR continued….

If the haematocrit is reduced, as in anaemia for

example, the velocity of upward flowing plasma
is altered, resulting in the red cells aggregating
and therefore falling faster. As a result, in
conditions associated with moderate or severe
anaemia, the ESR is of limited use. In
conditions such as myeloma, the increase in the
level of immunoglobulins causes an increase in
red cell aggregability, resulting in an elevated
ESR.
 CRP
• C-reactive protein (CRP) belongs to the
pentraxin family of proteins, which has five
identical subunits. It was named because it
reacts with the somatic C polysaccharide of
Streptococcus pneumonae, and was first
discovered in 1930 by Tillet and Francis.
• Plasma levels begin increasing within 4-6 hours
following acute inflammatory stimulus and the
half-life of CRP is 5-7 hours, therefore the level
of CRP in the blood is regulated solely by its
own synthesis.
 CRP is reported to have several
main functions
• Anti-infective: CRP can opsonise particles for phagocytosis, and
activate complement via the classical pathway.
• Anti-inflammatory actions: CRP helps in preventing systemic
inflammation. CRP aids in the release of neutrophils from blood
vessels, while preventing white cell adhesion to vessels in non-
inflamed tissues. It is also able to stimulate the release of anti-
inflammatory molecules from monocytes.

• Scavenging actions: Although CRP does not bind to normal cell

membranes, it can bind avidly to cells that are undergoing
apoptosis or necrosis, possibly because it recognises particular
receptors that appear on the surface of dying cells. This in turn
binds and activates complement, initiating an inflammatory
reaction that attracts neutrophils and monocytes to the site.