What is the management approach for patients with elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels?

From the Guidelines

Management of patients with elevated ESR and CRP requires a comprehensive approach that prioritizes identifying and treating the underlying cause, rather than solely focusing on the elevated markers themselves. The first step involves a thorough clinical evaluation, including a complete history, physical examination, and targeted laboratory testing based on presenting symptoms 1. Common causes of elevated ESR and CRP include infections, autoimmune disorders such as rheumatoid arthritis, malignancies, and inflammatory conditions.

Key considerations in the management of these patients include:

• Referral to a rheumatologist within 6 weeks of symptom onset for patients presenting with arthritis 1
• Use of clinical examination as the primary method for detecting arthritis, potentially supplemented by ultrasonography 1
• Assessment of risk factors for persistent and/or erosive disease, including the number of swollen joints, acute phase reactants (such as ESR and CRP), rheumatoid factor, and imaging findings 1
• Initiation of DMARDs (Disease-Modifying Antirheumatic Drugs) as early as possible, ideally within 3 months, for patients at risk of persistent arthritis, with methotrexate considered the anchor drug unless contraindicated 1

Treatment strategies should be guided by regular monitoring of disease activity, which includes tender and swollen joint counts, patient and physician global assessments, ESR, and CRP, typically assessed at 1- to 3-month intervals until the treatment target is reached 1. Non-pharmacological interventions, such as dynamic exercises and occupational therapy, can also be considered as adjuncts to drug treatment in patients with early arthritis 1.

It is crucial to remember that ESR and CRP are non-specific markers of inflammation and do not diagnose specific conditions; thus, treating elevated levels without identifying the underlying cause is inappropriate. In cases where no cause is found despite thorough investigation, a watchful waiting approach with periodic reassessment may be warranted. The management approach should always prioritize the patient's quality of life, morbidity, and mortality outcomes.

From the FDA Drug Label

After treatment with HUMIRA, a decrease in concentrations of acute phase reactants of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis A decrease in CRP concentrations was also observed in patients with Crohn’s disease, ulcerative colitis and hidradenitis suppurativa.

The management approach for patients with elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels may involve treatment with medications such as adalimumab (HUMIRA), which has been shown to decrease concentrations of these inflammatory markers in patients with certain conditions, including rheumatoid arthritis 2.

• Key points to consider:
  • Adalimumab binds to TNF-alpha and blocks its interaction with cell surface receptors, which can help reduce inflammation.
  • Treatment with adalimumab has been associated with decreases in CRP and ESR levels in patients with rheumatoid arthritis and other conditions.
  • Another medication, etanercept (Enbrel), has also been studied in the context of rheumatoid arthritis and has been shown to improve clinical responses, including reductions in inflammatory markers 3.

From the Research

Management Approach for Elevated ESR and CRP

The management approach for patients with elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels involves understanding the physiologic principles behind these tests and using them appropriately in clinical practice 4.

Key Considerations

• ESR and CRP are markers of inflammatory conditions and should be used in combination with clinical history and physical exam for diagnosis and monitoring of pathological conditions 5.
• Fibrinogen (for which ESR is an indirect measure) has a much longer half-life than CRP, making ESR helpful in monitoring chronic inflammatory conditions, whereas CRP is more useful in diagnosis as well as in monitoring responses to therapy in acute inflammatory conditions 4.
• Many factors can result in falsely high or low ESR and CRP levels, and it is essential to take note of these factors when interpreting test results 4, 5.

Clinical Application

• ESR and CRP lack sensitivity or specificity and should be used only in combination with clinical history and physical exam for diagnosis and monitoring of pathological conditions 5.
• The clinical application of these tests in diagnosis is best applied to conditions in which there is high or low clinical probability of disease 5.
• Discrepancies between ESR and CRP measurements are common, and numerous physiological factors, including noninfectious conditions and resolution of inflammation, can contribute to abnormally high ESR/low CRP readings or vice versa 5.

Reducing Unnecessary Testing

• Reducing unnecessary ESR orders and ESR/CRP co-ordering rates can be achieved through quality improvement projects, such as using a nonintrusive, normative nudge within the ESR order and a best practice advisory triggered when ESR and CRP are simultaneously ordered 6.
• This approach can lead to a significant decrease in ESR orders and ESR/CRP co-ordering rates, as seen in a study where inpatient ESR orders decreased by 53.3% and outpatient ESR orders decreased by 33.2% 6.

Associations with Diseases and Demographic Characteristics

• Extreme ESR elevations are associated with various diseases, including infection, autoimmune, malignancy, renal disease, and miscellaneous conditions 7.
• The leading diagnosis associated with extreme ESR elevations is infection, followed by autoimmune and malignancy 7.
• Statin or nonsteroidal anti-inflammatory drug use is associated with lower ESR in patients with giant cell arteritis, but not with lower CRP values 8.