The video version of this podcast can be found here:

·      https://youtu.be/kk5ADBP1J9M

My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode I go through guidance on inflammatory markers, ESR and CRP. For this I have reviewed a number of guidelines and publications, particularly South Tees Hospitals NHS Trust, York and Scarborough Hospitals NHS Trust and Bristol, North Somerset and South Gloucestershire ICB. A full list of the sources consulted can be found below.

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

 

Disclaimer:

The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions.

In addition, transmission of this Content is not intended to create, and receipt by you does not constitute, a physician-patient relationship with Dr Fernando Florido, his employees, agents, independent contractors, or anyone acting on behalf of Dr Fernando Florido.

 

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release] 

 

There is a podcast version of this and other videos that you can access here:

 

Primary Care guidelines podcast:

 

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148


There is a YouTube version of this and other videos that you can access here: 

  • The Practical GP YouTube Channel: 

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk


The sources consulted can be found here:

·      BJGP article: https://bjgp.org/content/69/684/e462

·      BNSSG guideline: https://remedy.bnssg.icb.nhs.uk/adults/investigations/inflammatory-marker-testing/?utm

·      Clinical audit: https://gps.northcentrallondon.icb.nhs.uk/cdn/serve/service-downloads/1551452026-75436315473b66e9567181d4bb9736a3.pdf?dl=1&utm

·      South Tees Hospitals: https://www.southtees.nhs.uk/services/pathology/tests/c-reactive-protein-crp/?utm and https://www.southtees.nhs.uk/services/pathology/tests/esr/

·      York and Scarborough Hospitals: https://www.yorkhospitals.nhs.uk/seecmsfile/?id=4123

·      Medcentral: https://www.medcentral.com/pain/chronic/erythrocyte-sedimentation-rate-c-reactive-protein-old-useful-biomarkers-pain-treatment?utm

 

Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I am Fernando, a GP in the UK. Today, we are looking at the guidance on inflammatory markers, ESR and CRP, focusing on what is relevant in Primary Care only.

For this I have reviewed a number of NHS guidelines and medical publications. A full list of the sources consulted can be found in the episode description.

Right, without further ado, let’s jump into it.

The most commonly used inflammatory markers are Erythrocyte Sedimentation Rate (or ESR) and C-Reactive Protein (or CRP).

ESR and CRP are not only frequently ordered in Primary Care but the rate of testing also appears to be increasing. It is estimated that for every 1000 inflammatory marker tests done there are 236 false positives, which leads to 710 GP appointments, 229 blood test appointments and 24 referrals in the following six months. Furthermore, there are concerns about excessive testing because clinicians often check multiple inflammatory markers simultaneously.

So, this is the reason why it is generally advised to avoid using these tests for screening or as a rule-out for patients with non-specific symptoms.

But let's start with the basics.

Inflammation is a fundamental response to injury, infection, or disease. It involves a complex cascade of immune mediators, which leads to the production of acute-phase reactants, that is, proteins that increase in response to inflammation. This is where ESR and CRP come into play.

Let’s have a look at them individually and in a little bit more detail.

And let’s start with CRP.

What makes CRP clinically useful?

  • firstly, CRP is used to assess the progression of inflammation and infection.
  • Unlike ESR, CRP test measures the level of just one specific protein.

·      CRP is primarily produced in response to inflammation and can be elevated due to for example, infection, tissue damage, autoimmune diseases, postoperative situations and cancer.

  • CRP is produced in the liver by hepatocytes and is triggered by Interleukin-6. However, CRP can also be generated by adipocytes and obesity can sometimes cause low-level elevations in CRP (generally <20 mg/L)in obese people.
  • In liver failure, CRP levels may be unexpectedly low.
  • CRP rises rapidly following an insult (like infection or inflammation) within 6 hours, peaks at around 48 hours and responds rapidly to treatment, because it has a short half-life of about 18 hours, meaning it falls quickly once inflammation resolves, making CRP a useful marker for both diagnosis and monitoring.

·      Increases in CRP values are non-specific for many disease processes and should not be interpreted without a complete clinical evaluation.

  • We should interpret CRP with caution and, for example, it is possible that CRP may be normal in myeloma and in patients with some connective tissue diseases.
  • However, because it is a direct marker of inflammation, CRP is generally more sensitive than ESR, particularly in the early stages of the acute phase response.

The fact that CRP rises and falls quickly in response to changes in inflammation makes CRP particularly useful in monitoring acute conditions, such as:

·      Bacterial infections – especially sepsis and pneumonia

·      Postoperative inflammation – distinguishing infection from normal healing and

·      Chronic inflammatory diseases – such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) for example.

Now, let's talk about Erythrocyte Sedimentation Rate (or ESR).

Unlike CRP, ESR does not measure a specific protein. Instead, ESR reflects the rate at which red blood cells settle in plasma over one hour and it is measured in millimetres per hour (mm/hr), determined by the amount of clear liquid at the top of the test tube after one hour. During inflammatory states, fibrinogen and other plasma proteins increase which cause red cells to stick together, making them fall more quickly.

So, what are the key characteristics of ESR?

  • It is an indirect measure of inflammation.
  • ESR rises more slowly than CRP and can take up to 7 days to peak, making it less useful for acute diagnosis and treatment monitoring. Importantly, ESR may be normal, especially in the early stages, in conditions like cancer, connective tissue disease, and infection, so a normal ESR cannot exclude these diagnoses.
  • ESR is best for measuring immunoglobulin load which is useful in connective tissue diseases, myeloma, and some haematological malignancies.
  • ESR is influenced by multiple factors, including age, sex, anaemia, and hyperlipidaemia, meaning that ESR levels are higher in females and with increasing age.

·      And finally, samples taken during difficult venepuncture may give erroneous results which may not be accurate on short, clotted or haemolysed samples.

So, if ESR is less specific than CRP, why should we ever want to use ESR instead of CRP?

Well, ESR is best used in chronic inflammatory conditions. Examples are:

·      Polymyalgia Rheumatica (or PMR)

·      Temporal Arteritis (or Giant Cell Arteritis, GCA) and

·      Multiple Myeloma and other haematological malignancies

So, let’s recap because this is the interesting part. We know that both ESR and CRP indicate inflammation, but when should we use one over the other?

Well, from a general point of view CRP should be the first line test in most cases. On this basis, we should use CRP when:

  • we need rapid information on acute infections or inflammatory conditions.
  • We want a result with distinct normal and abnormal reference ranges, without variations for age or gender
  • we want to monitor treatment response, since CRP normalises quickly or
  • we suspect acute problems like bacterial infections, post-operative infections, or autoimmune flare-ups.

However, we should use ESR when:

  • we are dealing with chronic inflammatory conditions, such as PMR or GCA.
  • we need a marker of long-term inflammatory burden. Or when
  • we are investigating haematological malignancies like myeloma.

Next, let's discuss some common pitfalls and limitations of these tests.

Firstly, in respect of requesting ESR & CRP Together we should point out that

  • In most cases, requesting both ESR and CRP together is unnecessary.
  • CRP should be the first choice for most inflammatory conditions so this means that CRP alone is enough in the majority of cases.
  • However, exceptions could be PMR, GCA, and haematological malignancies, where having both tests may be useful.

Secondly, we should avoid Over-reliance on Inflammatory Markers result. This is because:

  • A raised ESR or CRP does not automatically mean infection or autoimmune disease.
  • Because many non-pathological factors can increase ESR, including pregnancy, ageing, and obesity. And because
  • We should always correlate results with the patient’s history and clinical signs.

And thirdly, we have the pitfall of False Positives & Incidental Findings

  • And let’s remember that for every 1,000 inflammatory marker tests done, 236 are estimated to be false positives and that
  • This can lead to unnecessary GP consultations, additional tests, and patient anxiety.

Before we conclude, let’s look at the interpretation of results.

So, how should we Interpret ESR and CRP?

Well, when we receive an inflammatory marker result, we should always ask ourselves:

·      Is the elevation significant?

·      Does it correlate with the patient’s symptoms? And

·      Does it change the management plan?

Whilst you could think that this is obviously the trickiest part, in fact, interpretation should be relatively straightforward as long as there is a clear indication against which the test result can be evaluated.

The difficulty lies in the interpretation of an ‘incidental’ abnormality, when no specific disease is suspected. In these cases, we should carry out a systems review, focusing on infection, autoimmune conditions, and malignancy, plus examination of the patient. If a cause is suspected, then we should carry out further specific investigations.

However, if no obvious source can be found the test should be repeated. How soon this should happen will depend on our clinical judgement. Whilst some NHS guidelines indicate that some patients over the age of 50 or 60 with persistently raised inflammatory markers have an increased cancer risk, the presence of a raised inflammatory marker alone is not enough to warrant a cancer pathway referral. This is because ESR and CRP have a low sensitivity rate which is less than 50%.

And that is it, a review of inflammatory markers in Primary Care.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.

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