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Clinical Opal - To CRP or not to CRP? That is the question

01 September 2022 - Dr Simon Morgan

She has no significant past medical history and is not taking any regular medications. She does not smoke and drinks about 20g alcohol/week. She is married with two children. She tells you that life is “very busy”, but she denies feeling depressed. 

There are no other symptoms, nor red flag features, on further history. Her examination is unremarkable. 

Based on Sally’s presentation, what is the role of investigations of her fatigue at this stage? And in particular, would you order inflammatory markers?


Sally is presenting with the most common undifferentiated symptom in general practice, fatigue. And while there are multiple possible (and potentially serious) causes of tiredness, a 2016 systematic review found that serious somatic disease e.g. anaemia, malignancy, is only very rarely found in fatigued primary care patients.1

Australian guidelines recommend postponement of ordering investigations, especially when psychosocial factors are prominent and/or when the pre-test probability of disease is low. They advocate a watchful-waiting approach in the absence of red flags, highlighting the risks of false positive results and a cascade of additional harmful investigations. In patients with unexplained or persisting fatigue, the guidelines recommend the judicious use of tests, including urine dipstick, FBC, ferritin, BSL, TSH, EUC, LFT, and ESR or C-reactive protein (CRP). 

However, a cohort study looking at the value and consequences of inflammatory marker testing in primary care published in the BJGP in 2019 found that they have very poor sensitivity (<50%) for identifying serious disease. They identified an 85% false positive rate for the primary outcomes of cancer, infection, and autoimmune condition, leading to high rates of unnecessary follow up GP appointments, repeat blood tests, and specialist referrals. The authors concluded that inflammatory markers ‘should not be used as a rule-out test’.2


1. Stadje et al,. The differential diagnosis of tiredness: a systematic review. 2016 Oct 20;17(1):147. doi: 10.1186/s12875-016-0545-5. 

2.Watson J et al,. Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the Clinical Practice Research Datalink. Br J Gen Pract. (2019) Jul;69(684):e470-e478. doi: 10.3399/bjgp19X704321. Epub 2019 Jun 17. P


Dr Simon Morgan
Dr Simon Morgan

Simon is a GP based in Newcastle, NSW, and a senior medical educator with Medcast.  He also has medical education roles with the RACGP and GPSA.

Over the past three decades, Simon has worked in clinical and educational roles in NSW and the NT, as well as in the Republic of Ireland. He has published over 75 peer reviewed journal articles, and in 2018 received the RACGP Corliss award for his contribution to medical education.

Simon is passionate about high quality education and training. He has particular interests in GP supervisor professional development and the rational use of tests and medicines. He is a proud member of Doctors for the Environment. He spends his spare time drinking craft beer and pretending that he is a musician in the Euthymics, an all-GP band.

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