Ep 5 – Tips and hacks on the use of ESR & CRP in primary care

[MUSIC PLAYING] Hello, I'm Kevin Fernando, a GP partner at North Barric Health Centre near Edinburgh, an education director of GP notebook education. Welcome to our new GP notebook podcast, a bite size regular chat for all of us working in primary care. Podcasts will cover clinical tips and hacks, as well as hot topics to help make our lives a wee bit easier. But ultimately, to help improve the lives of our patients in primary care. Today, we will be covering some tips and hacks on the optimal use of CRP and ESR in primary care, to reduce unnecessary testing, referrals, and hopefully ultimately to help reduce our workload in primary care. So we saw a 70-year-old lady in clinic recently who presented with non-specific malaise over the preceding four weeks with mild headache and pain in her left knee. Pass medical history consists of some generalized osteoarthritis affecting her back and both of her knees. There was nil of note yielded on systemic inquiry. Examination was unremarkable. So we ran the gauntlet and we checked some blots. FPC, LFT, UNE were all normal. ESR though was 33, and CRP was two. So what do we do next? Well, we seem to have some discordant results here. Don't we? ESR appears to be elevated, whereas CRP is within the normal range. I was always taught at medical school that CRP stood for clinician reassurance protein. But this hasn't really given us any reassurance here. In fact, it's introduced someone's certainty, and that's the last thing we need in primary care, isn't it, more uncertainty? So should I have checked both inflammatory markers? Or was it a pointless thing to do, like putting indicator lights on range rovers? Or should I not even have checked the inflammatory markers in the first place? So here we're going to talk about the use of CRP and ESR in primary care. Well, we had a really useful, large observational study published in the BJGB during July 2019, and also a very helpful BMJ rational testing paper published way back in 2012. But still some very relevant messages to us all working in primary care about the use of CRP and ESR. Now both of these tests, as we know, are commonly requested in primary care for the diagnosis and monitoring of inflammatory conditions, infections, autoimmune conditions, as well as malignancies. And we've seen a significant increase in test requests over the last 15 years, especially for CRP. Often we also check both ESR and CRP, which does make a rod for own backs, doesn't it? Because often we do see discodent results and ESR within the normal range, but perhaps the CRP out with the normal range. How do we make sense of this in primary care? As a whole with inflammatory markers, false positive test results are also more common, leading to increased appointments, tests, and also possibly referrals. So which is better ESR or CRP? Well actually, we have little evidence comparing both of these tests. We have no evidence-based guidelines. But that recent observational study I mentioned to you does provide some useful information on the diagnostic accuracies of ESR and CRP, and whether we should check both together or not. But as always, the guiding principle is to treat the patient sat in front of us and not the numbers. So a little bit of background next on ESR and CRP. So a useful rule of thumb by no means evidence-based is for looking at the upper limit of normal of ESR. For a woman, it's half her age. So your 60-year-old lady is allowed, if you like, in ESR up to 30. Whereas for a man, it's generally half the age minus 10. So for your 60-year-old man, an ESR of up to 20. So a useful rule of thumb there. Be aware that there are a number of factors that affect ESR. We've already mentioned gender and age, but also factors such as pregnancy, temperature, drugs, including the anti-platelet, such as aspirin, smoking, plasma protein concentrations, and red blood cell factors such as hematocrit. ESR rises over 24 to 48 hours, but decreases very slowly, taking weeks off into normalize. Now we do need to be aware, if we ever see an ESR of over 100 millimeters power, this is a suspicious for significant underlying illness. In fact, an ESR over 100 has a 97% positive predictive value for serious underlying illness, particularly we need to rule out malignancy such as myeloma and renal cancer, but also giant cell arteritis too. Previous evidence has suggested that ESR is best for suspected myeloma, but actually, if we have a strong clinical suspicion of myeloma, the better tests are protein electrophoresis and/or unary benched-john proteins. Similarly, in the context of rheumatoid arthritis, if we have strong suspicion of rheumatoid arthritis, even with normal inflammatory markers, we should be referring to our rheumatology colleagues. This is a clear message from the updated nice NG100 rheumatoid arthritis guideline published in 2018. And this recommendation was made, of course, so we can consider early demod therapy for those with rheumatoid arthritis to hopefully prevent long-term joint destruction and disability. What about CRP then? Well, it rises more rapidly in response to infection. Usually within 12 hours, the half-life of CRP is actually 12 to 24 hours, so we would expect it approximately half every day. And it takes about three to seven days to completely normalize, so much, much quicker than ESR. And importantly, it's not affected by the same multitude of factors as ESR. Now, a useful tip here, if you see an elevated ferritin, is to check a CRP, because as we know, ferritin is an acute phase protein, so it rises in any sort of acute inflammation. So if you have an elevated ferritin, but normal CRP, this is most suspicious of true iron overload and further investigation by way of iron studies is required. And I've put together a GP notebook short cut on interpretation of iron studies in primary care, which you can have a look at in your own time, which gives you a little bit more information about this. So let's return then to that large observational study published in the BMG VJGP during July 2019. It looked at the use of multiple inflammatory marketers in primary care, using the clinical practice research data link. And it compared the diagnostic accuracies of CRP and ESR, and also whether checking both together improved accuracy. So very relevant questions to us all working in primary care. And the bottom line was they found little difference in the accuracy of CRP and ESR. CRP had slightly superior diagnostic accuracy for infections, but was equivalent to ESR for autoimmune conditions and malignancies. So the authors concluded that CRP should generally be our first line test. And in Edinburgh, it's now recommended that we use CRP for the diagnosis and management monitoring of polymigral georomatico. What about checking both together? Was that a useful exercise? Well, actually, clear message from the authors here, testing multiple inflammatory markers simultaneously did not increase our ability to rule out disease in primary care. It was unsurprisingly associated with more abnormal and discordant results and also increased costs. And interestingly, the negative predictive value of a single test, either ESR or CRP, was similar to that of multiple tests. So no real advantage to testing multiple inflammatory markers simultaneously. And authors also noted overall, inflammatory markers have a low accuracy from predicting disease outcomes with the notable exception of polymigral georomatico. And we should, as always, trust our clinical judgment. And then over to that BMJ, rational testing paper published during 2012, some really helpful key take-home messages from this paper too. So the authors tell us normal inflammatory markers are actually only useful in ruling out very few specific conditions. Polymigral georomatico, giant cell arteritis, multiple myeloma, and infection of hip revisions. Raised inflammatory markers are, of course, very common and do increase the probability of a significant underlying condition, but further evidence, clinical, or otherwise, is required. We mustn't just rely on those inflammatory markers to establish a diagnosis. And indeed in Farmatory Markers are two non-speccessive. to be a useful tool for diagnosis and diagnosing any series underlying disease. We must always use our clinical judgment, history taking and examination skills to try and establish an underlying diagnosis. If we do see inflammatory markers raised incidentally and there are no real clues from the history of examination, then authors tell us a weight and sea approach is quite appropriate here to see if symptoms do declare themselves that may point towards an underlying possible diagnosis. That said, and as already mentioned, if we do see markedly elevated inflammatory markers particularly that ESR over 100, the likelihood of disease is much higher and we do need to focus our history, examination and investigations to establish the underlying diagnosis. And before I end, a quick note on point of care CRP testing, which of course is quite a different entity to what we've been talking about so far. There actually isn't emerging evidence base for point of care CRP testing for the clinical management of acute cough in adults. It's an evolving evidence base and appears to be increasingly effective as an antimicrobial stewardship intervention. However, what we lack are clinical decision rules, validated clinical decision rules and they persist uncertainty regarding thresholds of CRP at which we should consider treatment. So watch this space, I'll suddenly do a podcast on this in the future as that evidence base involves. So returning to our 70 year old lady, she reattended surgery a few days later for reassessment. Her headache had settled, but she was still feeling non-specifically unwell. There was nothing new elicited on history or examination and in fact inflammatory markers were not repeated. She gradually improved over the subsequent two weeks without the need for any further treatment or investigation. So thank you all for listening, I hope you found this podcast helpful. Please make sure to subscribe to our podcast, which are available on all major platforms. Get in touch via social media if you have any questions, comments or ideas for future podcasts. You should also visit us at gpnotebookeducation.com to not chop some cpd points, register for our gpnotebook clinic events and download free resources and shortcuts to make our lives a wee bit easier. But ultimately to help improve the lives of our patients in primary care.