ESR & CRP: Lab Test Pearls for Nurse Practitioners
If you haven’t done so already, read my blog post on understanding lab reference ranges to provide context for variation of lab reference ranges we see in practice.
Questions to always ask yourself when ordering a lab test:
Will this change my management? (i.e. have I already reached the treatment threshold? Will this test change my plan?)
Will this lab test help me rule in, or rule out, a specific diagnosis?
Refresh yourself on pre-test probability, sensitivity and specificity, and negative and positive predictive values if you haven’t in a while. These are important diagnostic test principles that help inform diagnostic testing in practice. Now - let’s get into ESR & CRP labs in primary care.
I realized I had fallen into the habit of routinely ordering both ESR and CRP inflammatory markers without taking a moment to consider whether it was necessary. Now, I ask myself: when is it appropriate to order both? When should we choose ESR over CRP, and vice versa, in primary care? Let’s explore these questions through a few case examples.
ESR
Case #1: you’re seeing a 55-year-old female with a 6 week history of intermittent headaches. While going through your list of red flags for a headache presentation, she reports intermittent jaw pain. She denies any scalp tenderness or vision changes. Your primary concern is ruling out giant cell arteritis.
What is ESR? It stands for erythrocyte sedimentation rate. It measures the rate at which red blood cells fall to the bottom (i.e. sedimentation) (1). The RBCs typically fall at a faster rate (i.e. high ESR) in people with inflammatory conditions (1). It is an indirect measure of inflammation.
Clinical Relevance: It is representative of chronic disease processes including infections, cancer, or autoimmune disorders (1). It is overly sensitive and non-specific and can be elevated in healthy asymptomatic people. ESR has higher false positive and false negative rates compared with CRP (2). Importantly, it is not specific for any single disease but is used in combination with other tests to determine the presence of increased inflammatory activity (1). Some patients with serious infection, cancer, or inflammatory disorders may have a normal ESR (1). Compared with CRP, ESR is superior at detecting low-grade bone and joint infections and monitoring disease activity in systemic lupus erythematosus (2). It is useless as a stand-alone test and must be used in combination with clinical suspicion and other tests to determine the underlying illness. It should not be ordered in healthy asymptomatic people.
ESR Reference Ranges
Females typically have higher ESR levels than males, and levels increase naturally as people age. The normal reference range varies depending on the lab reporting the values, but generally are as follows (1):
Male <50 years old: ≤15 mm/hr
Female <50 years old: ≤ 20 mm/hr
Male >50 years old: ≤20 mm/hr
Female >50 years old: ≤30 mm/hr
Children: ≤10 mm/hr
What causes Abnormal ESR Levels?
*this is not an exhaustive list
Back to the case: your pre-test probability for giant cell arteritis (GCA) is moderate to high, therefore ordering an ESR will be helpful as an initial test. You also realize regardless of the results (normal or elevated), the gold standard test for GCA is a temporal artery biopsy. If your pre-test probability is high, your patient will need this test regardless of the result. ESR is a useful test for helping diagnose GCA and polymyalgia rheumatica, however lower ESR levels do not rule out the diagnosis (1).
Note: if your pre-test probability for GCA is high, either refer to the emergency department or treat while awaiting the results of tests or referrals.
Ordering a CRP in this case is also very reasonable because ESR has a high rate of false negatives - that being said ordering ESR as a stand-alone test initially wouldn’t be wrong either. Let’s dive into CRP!
PEARL # 1: ESR is an indirect marker of inflammation, represents chronic disease processes, and has a high rate of false negative and false positive results (compared with CRP). It is not used as a stand-alone test to make a diagnosis.
CRP
Case # 2: A 30-year-old male presents with a 4-week history of diarrhea, intermittent bloody stools, fecal urgency and general malaise. Your differential diagnosis includes inflammatory bowel disease.
What is CRP? It stands for C-reactive protein. CRP is a protein synthesized by the liver. Levels rise in response to inflammation (3).
Clinical Relevance of CRP: It is a direct measure of inflammation and is representative of an acute disease process (3). It rises in 4-6 hours, peaks around 48 hours, and is more sensitive and specific for acute disease processes over chronic ones. Persistent elevations in CRP can be see in chronic inflammatory conditions like rheumatoid arthritis, or chronic infections (3). CRP is ordered in 3 circumstances:
To aid in the diagnosis of an inflammatory/autoimmune condition or infectious disease (4)
Monitoring of an inflammatory condition, or infectious disease not responding to treatment (e.g. monitoring antibiotic response to osteomyelitis) (4)
To review a therapeutic approach in primary prevention of cardiovascular disease in patients who are intermediate risk (4)
CRP Reference Ranges
< 0.3 mg/d (<3 mg/L)L: Normal (level seen in most healthy adults)
0.3 to 1.0 mg/dL (3-10 mg/L): Normal or minor elevation (can be seen in obesity, pregnancy, depression, diabetes, common cold, gingivitis, periodontitis, sedentary lifestyle, cigarette smoking, and genetic polymorphisms)
1.0 to 10.0 mg/dL (10-100 mg/L): Moderate elevation (Systemic inflammation such as RA, SLE, or other autoimmune diseases, malignancies, myocardial infarction, pancreatitis, bronchitis)
> 10.0 mg/dL (>100mg/L): Marked elevation (Acute bacterial infections, viral infections, systemic vasculitis, major trauma)
> 50.0 mg/dL (>500mg/L) : Severe elevation (Acute bacterial infections)
(4)
Back to the case: Ordering a CRP is reasonable in this case to assess for inflammatory bowel disease. The result is 15 mg/dL (150mg/L). This is not diagnostic of inflammatory bowel disease, but this has significantly increased your pre-test probability, therefore this patient requires further testing for diagnostic clarification (e.g. colonoscopy).
Note: ordering ESR wouldn’t be wrong if you suspect inflammatory bowel disease, but it’s recommended to order CRP as the preferred initial test (4).
Pearl # 2: CRP is a direct measure of inflammation and is more sensitive and specific for acute illness compared with ESR. It is the preferred first test to support a diagnosis of inflammatory/autoimmune or infectious conditions rather than ESR.
When do we order ESR and CRP at the same time?
There are few reasons to order both labs at the same time - unless you are following or diagnosing a rheumatologic disease. For example, if your index of suspicion is high for systemic lupus erythematosus, ordering a CRP and ESR is reasonable because some patients with this condition may have a normal CRP (2).
If a person has a rheumatologic disease (e.g. rheumatic arthritis), they are often monitored by a rheumatologist, and as a primary care provider, I like to leave it to the experts to monitor disease activity with inflammatory markers.
As you can see, there are a lot of nuances for ordering and interpreting these inflammatory markers, and they are not used as stand-alone tests to diagnose conditions. Nor should they be ordered in healthy asymptomatic persons (aside from potential cardiovascular disease risk stratification - not routinely ordered in primary care for this).
Key Take Home Points:
Try not to reflex order both CRP & ESR every time you suspect an inflammatory or infectious process.
CRP and ESR are not diagnostic tests – they are used in combination with the patients clinical presentation and other tests for diagnosis and prognostication.
CRP is more sensitive and specific for acute illness and is more responsive of changes in the patient’s condition.
ESR is superior at detecting low-grade bone and joint infections and monitoring disease activity in systemic lupus erythematosus (these patients may have normal CRP).
ReferencesStat pearls Tishkowski K, Gupta V. Erythrocyte Sedimentation Rate. [Updated 2023 Apr 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557485/Harrison M. Erythrocyte sedimentation rate and C-reactive protein. Aust Prescr. 2015 Jun;38(3):93-4. doi: 10.18773/austprescr.2015.034. Epub 2015 Jun 1. PMID: 26648629; PMCID: PMC4653962.Nehring SM, Goyal A, Patel BC. C Reactive Protein. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441843/Government of British Columbia (2023). C-Reactive protein and erythrocyte sedimentation rate testing. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/esr