Everything you need to know about C-reactive protein (CRP) – the most important inflammatory marker out there

What is CRP?

The CRP marker is a protein called C-reactive protein, or in short CRP.
This protein, which is formed in our liver, was discovered in 1930. It was labelled with the letter “C” because the discovery of the protein was associated with the “C” antigen that is found on the capsule surrounding the evil pneumococcus bacteria.
I’ll be coming back to this pneumococcus bacteria later. I have an important point I’d like to cover that is related to it.

A marker of infection or inflammation? And what’s the difference between the two?

The terms infection and inflammation are slightly different, and I think it’s worthwhile to take a minute to explain this difference.
Inflammation – in an inflammation, pathogens (viruses or bacteria), are not necessarily involved.
Infection – this is an infectious process that usually involves viruses or bacteria. Indeed, all infections carry inflammation too within them and so sometimes a urinary tract infection will be referred to as an inflammation in the urinary tract.
This protein, CRP, rises as a response to both inflammations and infections and consequently it can be elevated in both rheumatological diseases and bacterial infections.
Let me put the cart before the horse here and inform you that if your child has a fever for 3 days, we will usually not suspect a rheumatological disease at this point but we do want to determine whether their fever is due to a bacterial infection. So, when the CRP level is elevated this will indicate a bacterial infection, and if it is low, this will usually indicate a viral infection.
This is a simplified way of looking at it. But I will elaborate below.

How long after the onset of an infection does the CRP level begin to increase?

The elevation occurs within hours, approximately 6-8 hours after the start of an infection.
This interval of time is both an advantage and a disadvantage, as some children will visit the Emergency Room and will have their blood drawn hours after the start of their fever, and then the CRP level will typically be quite low.
Take, for example, an infant under the age of 1 month, who visits the Emergency Room due to fever. We are all aware that a newborn with fever, must be examined in the Emergency Room (read more about this here). Often, the infant will arrive to the ER several hours after the onset of fever. The CRP level will not be very high right at this point, even if this child does have a bacterial infection going on.

What are the units used for this measurement?

This protein is tested using 2 different measurements, depending on the laboratory performing the test:
Milligram per deciliter (mg/dl), where the normal range is 0-0.5
Milligram per liter (mg/L), where the normal range if 0-5.
Do not confuse between the two units of measurements.

Should I be concerned if I see any number outside the normal CRP range?

Absolutely not. Healthy people can sometimes have slightly abnormal CRP results too and that is why physicians often overlook or ignore minor elevations.
Furthermore, if a child has been sick for a couple of days and their CRP level is elevated (for example 3mg/dl or 30mg/l which are both actually the same number), then this is considered normal, and there is no reason to be concerned.
A good pediatrician will know how to use this marker proper, will consider the timing of the test relative to the onset of illness and will know what to make of the results.
Obviously, seeing a child who has had fever for over 12 hours with low CRP levels is always the most straight forward scenario. Such parameters indicate a low possibility of an underlying severe bacterial infection. However, not every single result outside the normal range is considered pathological.

Where is it best to test for CRP?

Or in other words, where do they usually test for CRP?
This test is usually performed in emergency clinics or at the primary care physician’s office when a child presents with 2 or 3 days of fever. Parents often ask “why don’t we do a complete blood count (CBC)” because they have gotten used to the idea that a CBC will help differentiate between a viral or bacterial infection, but this isn’t very accurate. Performing a CBC in children with 2 days of fever, to help distinguish between a viral and bacterial infection, is pretty much like flipping a coin. It is not an accurate enough method.
If, in addition to the CBC (read more about CBCs here), we are able to test for CRP, then we’ve actually made progress.
When the CRP level is very high, we need to move forward in trying to figure out where the bacterial infection is hiding. For example, it could be a urinary tract infection, or a bacterial pneumonia (more about this here).
When the CRP level is low, it is a lot more indicative than a normal CBC. Low CRP levels usually indicate a viral infection.
But each case needs to be studied separately and all parameters are to be taken into consideration before determining the next step for the child.

What is CRP velocity?

You are now about to become CRP pros my friends!
CRP velocity is a term used to describe how fast a CRP measurement has risen in between two different blood tests drawn during the same illness. Keep in mind that the CRP could either increase, drop or could possibly stay the same level in between two tests.
When is this useful?
Sometimes, in children that are hospitalized or children with a prolonged illness we happen to draw blood twice for the same illness. The CRP velocity, whether it is has increased or decreased, provides us with a lot of information about an illness.

Some examples for use of CRP velocity

Bob has had fever for 2 days and his CRP level is 1mg/dl. At this point, I’m not concerned. Two days later he comes back to the office with worsening symptoms, so I test his blood for CRP levels again. The CRP level now measures 14mg/dl. I am now concerned and will need to search for the underlying bacterial infection. The fact that the CRP increased so quickly within 2 days indicates a bacterial infection.
Dave, on the other hand, has also had fever for 2 days. His first CRP level was 1mg/dl. This does not concern me so I send him home. When he comes back 2 days later because his fever hasn’t resolved, his CRP level measures 1.5mg/dl. There is still nothing to be concerned about.
Molly is hospitalized with severe pneumonia, usually caused by a bacteria called pneumococcus (remember the pneumococcus I mentioned when discussing the discovery of the CRP protein?). Upon admission her CRP level is 30mg/dl. A few days later, following the start of treatment, her CRP level drops to 15mg/dl. That’s great. She is responding to her treatment. At this point we continue treatment and continue monitoring.

What do we know about rheumatological diseases and CRP?

Since CRP rises because of inflammatory processes, and not only infections, lots of parents whose children have high CRP levels worry that their child might be developing an inflammatory disease.
We tend to use the CRP marker to differentiate between a viral and bacterial infection. It does not make sense to consider a rheumatological disease in a child who has had 2 days of fever, when such diseases are so much less common than simple bacterial infections.
But again, we must always study each patient’s case separately. The CRP level plays a major role in the diagnosis of the Kawasaki disease, for example, which we see in children who present with 5 days of fever together with the characteristic signs of the disease. You can read more about Kawasaki here.

In summary, CRP is one of the more important markers in pediatrics. I used to own a machine at my clinic that tested for CRP levels by analyzing one single drop of blood and provided a result within 30 seconds. I used to use it a couple times a week and it saved me from extensive workup, redundant investigations and even medical errors on several occasions.

This marker is both our present and future. We must always remember to use it wisely, though.