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Inflammatory Marker Testing

Checked: 23-02-2024 by Vicky Ryan Next Review: 23-02-2026

BNSSG Inflammatory Marker Testing Guideline

Inflammatory markers are not useful in primary care as ‘rule-out’ tests.(1)

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.(1)

What do we recommend?

Usually only one inflammatory marker test should be used.(2)
CRP should be the first line test in most circumstances (see table in document below).
Second line inflammatory markers differ across BNSSG; ESR is offered in Weston and UHBristol, plasma viscosity (PV) is offered by NBT. These should only be used for suspected temporal arteritis, as a second line test for polymyalgia rheumatica, for persistent bone pain in the over 60s or following secondary care request (see table in document below).
Avoid using inflammatory markers for screening or as a rule-out for patients with non-specific symptoms.

Which test should be used?

Clinical question	CRP	ESR*	PV*	Comments
Screening asymptomatic patients	No	No	No	Unlikely to be useful. False positives common and may generate increased workload.
To ‘rule-out’ significant underlying disease in patients with non-specific symptoms eg tiredness	No (1)	No	No	Inflammatory markers have low sensitivity and are therefore unsuitable as a rule-out test. False positives are common and may generate increased workload. (1) A small minority of patients with chronic fatigue will require referral to secondary care ME/CFS services if criteria are met, and CRP is recommended prior to referral in these patients.
Could this patient have a significant infection?	Yes	No	No	May be useful although not always necessary if symptoms and signs are clear cut. Point of care testing (if available) may reduce antibiotic prescribing in respiratory tract infections.(3)
Is this infection responding to antibiotic treatment?	Little use	No	No	For the vast majority of infections, repeat CRP testing is not indicated and assessment should be made on clinical grounds. Monitoring of CRP may be useful is some chronic infections (eg osteomyelitis (4))
Does this patient have polymyalgia?	Yes	Yes	Yes	Please refer to Polymyalgia Rheumatica (PMR) page. CRP and either ESR or PV* should be performed.
Does this patient have giant cell arteritis?	Yes	Yes	Yes	Please refer to Giant Cell Arteritis page. Both CRP and ESR or PV* are warranted – due to risks of serious complications if diagnosis is delayed.
Does this patient have inflammatory bowel disease?	Yes	No	No	Please refer to Inflammatory Bowel Disease (suspected) page. A normal inflammatory marker is not a rule-out test. Faecal calprotectin should be requested if inflammatory bowel disease is suspected.
What is the cause of this/these inflamed joints?	Yes	No	No	CRP is useful for secondary care triage of rheumatology referrals. However, normal inflammatory markers are not a rule-out; if clinical suspicion of inflammatory arthritis refer regardless of CRP results.
What is the cause of this patients raised platelets?	Yes	No	No	British Society for Haematology recommends peripheral blood smear, CRP and iron studies as first line tests to investigate thrombocytosis. Raised CRP suggests reactive thrombocytosis, due to underlying inflammatory or malignant cause.(5)
Could this patient aged >60 with persistent bone or back pain or unexplained fracture have underlying pathology?	No	Yes	Yes	NICE recommend FBC, calcium and PV or ESR, to screen for potential underlying pathology including myeloma.(6, 7) If a raised inflammatory marker is detected then request a myeloma screen (see below).
Does this patient have myeloma?	No	No	No	Please refer to Haematology - USC (2WW) page. If you suspect myeloma please order serum protein electrophoresis and urinary free light chains (Bence Jones protein) or serum free light chains, plus FBC, U+E, creatinine and calcium.
Monitoring of polymyalgia rheumatica	Yes	No	No	Inflammatory markers are useful when tapering steroids. CRP is generally more sensitive than ESR or PV. No need to routinely test both simultaneously.
Monitoring DMARDs	No	No	No	Inflammatory markers are not part of shared care protocols for DMARDs. Ask patients at each DMARD review if a) if they have a specialist out-patient appointment before the next routine blood test b) if their symptoms have flared such that they are needing to contact their GP or specialist team. Only do a CRP if the answer is yes to either one.
Blood tests prior to rheumatology secondary care review	Yes	No	No	CRPs are useful in monitoring disease activity, and are needed to allow the specialists to calculate the disease activity score. They are therefore needed before each specialist review, but are unnecessary to monitor safety of medication on routine reviews, whether or not the dose has recently been changed.
Is this *symptomatic* patient with inflammatory arthritis or inflammatory bowel disease experiencing a flare?	Yes	No	No	Raised inflammatory markers may be useful in confirming a disease flare and guiding appropriate management.

*Weston and UHBristol offer ESR as a second line test; NBT offers plasma viscosity (PV)

How do I interpret a raised inflammatory marker in primary care?

Interpretation should be relatively straightforward if there is a clear pretest hypothesis against which the test result can be evaluated. The difficulty lies in the interpretation of an ‘incidental’ abnormality, when no specific disease is suspected. A systems inquiry, focusing on infection, autoimmune conditions, and malignancy, plus examination of the patient should generally point towards specific investigations.(8) If no obvious source can be found the test should be repeated. Men over 50 and women over 60 with persistently raised inflammatory markers have a cancer risk which exceeds the 3% NICE threshold for urgent investigation.(9) However inflammatory markers have a low sensitivity at <50%, so they are not recommended as a test to rule in or out the possibility of cancer in those with non-specific symptoms.

References

Watson J SC, Whiting P, Banks J, Pyne Y, Hamilton W. Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the Clinical Practice Research Datalink. BJGP. 2019; 69 (684): e470-e478. DOI: 10.3399/bjgp19X704321
Watson J JH, Salisbury C, Whiting P, Banks J, Hamilton W. Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy. BJGP. 2019; 69 (684): e462-e469. DOI: https://doi.org/10.3399/bjgp19X704309
Eccles S, Pincus C, Higgins B, Woodhead M, Group GD. Diagnosis and management of community and hospital acquired pneumonia in adults: summary of NICE guidance. BMJ. 2014;349:g6722.
Van Asten SA, Nichols A, La Fontaine J, Bhavan K, Peters EJ, Lavery LA. The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis. Int Wound J. 2017 Feb;14(1):40–5.
Mathur Abhinav, Samaranayake Shehan, Storrar Neill PF, Vickers Mark A. Investigating thrombocytosis BMJ 2019; 366 :l4183
NICE Guideline. Suspected Cancer: recognition and referral [NG12]. 2015. Available at: https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-symptom-and-findings-of-primary-care-investigations#skeletal-symptoms
Koshiaris C, Van den Bruel A, Oke JL, Nicholson BD, Shephard E, Braddick M, Hamilton W. Early detection of multiple myeloma in primary care using blood tests: a case–control study in primary care. BJGP 2018; 68 (674): e586-e593. DOI: 10.3399/bjgp18X698357
Watson J, Round A, Hamilton W. Raised inflammatory markers BMJ 2012; 344 :e454
Watson J, Salisbury C, Banks J, Whiting P, Hamilton W. Predictive value of inflammatory markers for cancer diagnosis in primary care: a prospective cohort study using electronic health records. British journal of cancer. 2019;120(11):1045-51.

BNSSG Inflamatory Marker Testing - Background

Printable version of BNSSG Inflammatory Marker Testing Guidelines

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