From the Guidelines
An erythrocyte sedimentation rate (ESR) greater than 100 mm/hr necessitates an immediate and comprehensive diagnostic workup due to its strong association with significant inflammation and potential life-threatening conditions. This is supported by a systematic review and meta-analysis published in JAMA Internal Medicine in 2020 1, which highlights the importance of ESR in diagnosing conditions such as giant cell arteritis.
Initial Evaluation
The workup should begin with a thorough history and physical examination, focusing on symptoms of infection, autoimmune disease, and malignancy. Key areas to investigate include:
- Symptoms of infection such as fever, chills, or localized signs of infection
- Symptoms suggestive of autoimmune diseases like rheumatoid arthritis, lupus, or giant cell arteritis
- Symptoms that could indicate malignancy, such as unexplained weight loss, night sweats, or lymphadenopathy
Laboratory Tests
Initial laboratory tests should include:
- Complete blood count (CBC) to evaluate for anemia, leukocytosis, or leukopenia
- Comprehensive metabolic panel (CMP) to assess liver and kidney function
- Urinalysis to check for signs of infection or malignancy
- C-reactive protein (CRP) to complement the ESR finding and assess the level of inflammation
- Blood cultures if there is suspicion of bacteremia or endocarditis
- Chest X-ray to evaluate for pulmonary infections or malignancies
Specialized Tests
Based on the clinical presentation, consider the following specialized tests:
- Rheumatoid factor, anti-nuclear antibody (ANA), and serum protein electrophoresis (SPEP)/urine protein electrophoresis (UPEP) for autoimmune conditions and multiple myeloma
- CT scans for suspected occult malignancy
- Temporal artery biopsy for patients over 50 with headache or visual changes suggesting giant cell arteritis, as supported by the diagnostic accuracy of ESR >100 mm/h in this context 1
- Infectious disease workup may include HIV testing, tuberculosis screening, and endocarditis evaluation
Urgency and Prognosis
The urgency of this workup cannot be overstated, as an ESR >100 mm/hr is rarely benign and often indicates serious underlying pathology such as infection, vasculitis, malignancy, or advanced autoimmune disease. Prompt diagnosis and treatment are crucial to improve morbidity, mortality, and quality of life outcomes. The ESR reflects the rate at which red blood cells settle in a tube of unclotted blood over one hour, with elevated levels resulting from increased fibrinogen and other acute phase reactants that cause red cells to stack together (rouleaux formation) and settle more rapidly, as indicated by the study 1.
From the Research
Workup for Elevated Erythrocyte Sedimentation Rate (ESR)
The workup for an elevated ESR greater than 100 involves several steps and considerations:
- Initial Evaluation: An elevated ESR is a non-specific indicator of inflammation and can be seen in various conditions, including infections, autoimmune disorders, and malignancies 2.
- Rheumatologic Tests: Serum rheumatologic tests, such as rheumatoid factor, antinuclear antibody, and anti-double-stranded DNA antibodies, can help confirm a clinically suspected diagnosis of rheumatoid arthritis, systemic lupus erythematosus, or other autoimmune disorders 2.
- Complete Blood Count (CBC): A CBC can provide valuable information on disease activity and prognosis in rheumatic disorders, including systemic lupus erythematosus and rheumatoid arthritis 3.
- Inflammatory Biomarkers: CBC-derived inflammatory biomarkers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), and platelet to lymphocyte ratio (PLR), can assess disease activity and response to treatment in rheumatoid arthritis and determine the prognosis of renal involvement in systemic lupus erythematosus 3.
- Autoantibody Testing: Testing for anti-human leukocyte antigen (anti-HLA) antibodies can help identify patients with systemic lupus erythematosus and scleroderma, and associated clinical factors 4.
- Disease-Specific Testing: Depending on the suspected underlying condition, additional testing may be necessary, such as anti-dsDNA antibodies for systemic lupus erythematosus or anti-citrullinated protein antibody for rheumatoid arthritis 5.
- Correlation with Clinical Measures: ESR and C-reactive protein (CRP) levels are poorly correlated with clinical measures of disease activity in rheumatoid arthritis, systemic lupus erythematosus, and osteoarthritis patients, highlighting the need for a comprehensive evaluation 6.
Key Considerations
- An elevated ESR greater than 100 requires a thorough workup to determine the underlying cause.
- A combination of rheumatologic tests, CBC, and inflammatory biomarkers can help assess disease activity and prognosis.
- Autoantibody testing and disease-specific testing can aid in diagnosing underlying conditions.
- Correlation with clinical measures is essential to ensure accurate diagnosis and treatment.