What is the significance of an isolated elevated Erythrocyte Sedimentation Rate (ESR)?

From the Guidelines

An isolated elevated Erythrocyte Sedimentation Rate (ESR) is not a definitive indicator of disease activity and does not warrant escalation of immunosuppressive therapy in the absence of other signs of disease activity. This is based on the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and takayasu arteritis, which conditionally recommends clinical observation and monitoring without escalation of immunosuppressive therapy for patients with increased levels of inflammation markers alone 1.

Key Points to Consider

• Increases in ESR can be non-specific and may not necessarily indicate active disease 1
• Elevated ESR may warrant more frequent clinical and/or radiographic assessments for active disease, but should not be used as the sole basis for treatment decisions
• A complete medical history, physical examination, and possibly additional tests like CRP, complete blood count, or specific tests based on symptoms are necessary to determine the cause of an elevated ESR
• Non-disease factors such as pregnancy, older age, female gender, anemia, obesity, or certain medications can also elevate ESR
• The ESR value itself and how it changes over time can provide important diagnostic clues, but should never be interpreted alone without clinical context

Clinical Implications

• Healthcare providers should exercise caution when interpreting isolated elevated ESR results and consider the clinical context and other diagnostic findings before making treatment decisions
• Patients with elevated ESR should be closely monitored for signs of disease activity and undergo further testing as needed to determine the underlying cause of the elevated ESR 1

From the Research

Significance of Isolated Elevated Erythrocyte Sedimentation Rate (ESR)

• An isolated elevated ESR can be significant in various clinical contexts, as it may indicate underlying inflammation, infection, or malignancy 2, 3.
• Studies have shown that ESR can be elevated in patients with rheumatic diseases, such as polymyalgia rheumatica and seronegative rheumatoid arthritis 2.
• In patients with previous rheumatic disease, an elevated ESR may indicate a flare of the underlying disease 2.
• However, an extraordinarily high ESR level should raise suspicion for non-rheumatic diagnoses, such as infection and malignancy, even in the presence of a previously diagnosed rheumatic disease 2.
• The mechanism underlying ESR is complex and involves the interaction of various laboratory test parameters, including serum protein electrophoresis, immunoglobulin levels, and complement C3 levels 3.
• ESR has been shown to have a positive correlation with C-reactive protein (CRP) levels, but the two markers have different roles and should be used in a context-dependent manner 3.
• In patients with systemic lupus erythematosus, ESR has been shown to have limited utility in detecting infections, with poor sensitivities and specificities observed 4.
• However, combined use of ESR and CRP may yield higher diagnostic accuracy in assessing inflammation, especially in orthopedic conditions 5.

Clinical Implications

• An isolated elevated ESR should be interpreted in the context of the patient's clinical presentation and medical history 2, 3.
• Further investigation, including advanced radiological studies, may be justified in patients with an extraordinarily high ESR level to rule out malignancy 2.
• The use of ESR and CRP as markers of inflammation should be tailored to the specific clinical context, taking into account the limitations and potential biases of each marker 3, 4, 5.