What additional labs should be ordered for a patient with elevated C-Reactive Protein (CRP)?

Additional Laboratory Tests for Elevated CRP

For patients with elevated C-Reactive Protein (CRP), additional laboratory testing should include a complete blood count with differential, erythrocyte sedimentation rate (ESR), and targeted tests based on clinical presentation to identify the underlying cause of inflammation. 1

Initial Evaluation of Elevated CRP

• A complete blood count with differential should be ordered to assess for leukocytosis, neutrophilia, and other cellular abnormalities that may indicate infection or inflammation 2
• ESR should be performed alongside CRP as these markers provide complementary information about the inflammatory process 1, 3
• Blood cultures should be obtained if fever is present, symptoms are of acute onset, or if there is suspicion of bloodstream infection 1
• Chest X-ray should be considered, particularly if respiratory symptoms are present or pneumonia is suspected 1

Additional Testing Based on Clinical Presentation

For Suspected Respiratory Infection:

• If pneumonia is suspected based on symptoms (new focal chest signs, dyspnea, tachypnea, pulse rate >100, fever >4 days), a chest X-ray should be performed to confirm the diagnosis 1
• Note that CRP levels <20 mg/L with symptoms for >24 hours make pneumonia highly unlikely, while levels >100 mg/L make pneumonia likely 1

For Suspected Joint/Bone Infection:

• If prosthetic joint infection is suspected, synovial fluid analysis should include total cell count, differential leukocyte count, and culture for aerobic and anaerobic organisms 1
• Consider withholding antimicrobial therapy for at least 2 weeks prior to synovial fluid collection to increase the likelihood of recovering an organism 1

For Suspected Cardiovascular Disease:

• Lipid profile should be ordered as CRP provides complementary risk information to traditional cardiovascular risk factors 1
• CRP levels should be categorized as: low risk (<1.0 mg/L), average risk (1.0-3.0 mg/L), and high risk (>3.0 mg/L) for cardiovascular disease 1

Monitoring Inflammatory Response

• For patients already on antibiotics, follow-up CRP should be checked after approximately 4 weeks of therapy 4
• A decrease of at least 25-33% in inflammatory markers after 4 weeks suggests reduced risk of treatment failure 4
• If CRP remains elevated or increases despite treatment, consider additional diagnostic testing to identify potential treatment failure or alternative diagnoses 4

Interpretation of CRP and ESR Discordance

• When CRP and ESR results are discordant (differing by 2 or more quartiles), which occurs in approximately 12% of patients, consider the following patterns 3:
  • High CRP/low ESR: More common in infections (particularly urinary, gastrointestinal, pulmonary, and bloodstream infections) and myocardial infarction 3
  • High ESR/low CRP: More common in connective tissue diseases (like SLE), bone/joint infections, and cerebrovascular events 3

Important Considerations

• If CRP is ≥10 mg/L, search for obvious sources of infection or inflammation, as this level may obscure prediction of coronary risk 1
• CRP lacks specificity for infection type (bacterial vs. viral) and should always be interpreted alongside clinical findings 4, 5
• CRP responds more rapidly than ESR to both onset and resolution of inflammation, making it particularly useful for monitoring acute infections 6
• Microbiological tests such as cultures and Gram stains are not routinely recommended in primary care for LRTI 1

Remember that elevated CRP is a nonspecific marker of inflammation that requires clinical correlation and targeted testing to determine the underlying cause 7, 5.