Clinical case A 54-year-old woman with a medical history of rheumatoid arthritis presents to the emergency department (ED) with generalized fatigue. She has had several days of intermittent fevers and chills, body aches, and pain in most joints, particularly her left elbow. In the ED, her vital signs are T 37.5°C, HR 79 BPM, BP 142/76 mm Hg, RR 15 per minute, and 99% saturation on room air. Physical examination reveals a patient with widespread pain, stiffness, swelling in most joints, and a swollen and tender left elbow. The differential diagnosis includes flares of rheumatoid arthritis versus septic arthritis. Would inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) change the clinical course or management in the emergency department? |
What are ESR and CRP?
ESR and CRP are acute phase reactants with concentrations that change in response to inflammation, both acutely and chronically. ESR and CRP are widely used to monitor and detect multiple inflammatory conditions.
Erythrocyte sedimentation rate (ESR) measures the rate at which red blood cells settle in a test tube, a factor in the concentration of fibrinogen in the blood, which increases during inflammation. ESR is an indirect and imperfect measure of the inflammatory response and can be affected by multiple processes in addition to an acute phase response, including hematologic conditions, obesity, renal failure, heart failure, aging, female sex, pregnancy, and medications.
C-reactive protein ( CRP) is produced by the liver in response to infection or acute inflammation and plays a role in cell death and apoptosis. Therefore, CRP is a more direct measure of the inflammatory response, but it can also be affected by many other processes, including age, sex, race, and body mass index.
Although ESR and CRP are biomarkers of inflammation , the interpretation of their increase in acute inflammation is different, since the response patterns are different for each test.
CRP begins to rise within hours of the onset of an infection or inflammatory condition, has a constant half-life of approximately 18 hours, and will return to normal levels within 3 to 7 days of resolution of the underlying process.
In contrast, ESR levels increase more slowly in response to inflammation and infection and will remain elevated longer as long as excess fibrinogen remains in the serum.
As a result, CRP is a more sensitive marker of the acute inflammatory response, especially during the first days of a process.
Clinical utility
Elevations in ESR and CRP indicate that inflammation is present , but the tests and levels do not specify where. Furthermore, elevations in levels, especially a rapid increase in CRP, occur in a wide spectrum of disorders and diseases including infections, trauma, tissue necrosis, malignancies, and autoimmune disorders.
ESR and CRP are neither sensitive nor specific for any condition and should only be used in conjunction with a good history and physical examination. Even so, these laboratory parameters continue to serve as an important complement in the diagnosis, monitoring, and clinical management of acute and chronic inflammatory conditions.
Best practices advise against routinely ordering an ESR to evaluate inflammation in an undifferentiated patient and instead ordering a CRP when evaluating acute inflammation . This is because CRP will be elevated in the early days of an acute inflammatory response, making it more sensitive and specific during this phase compared to ESR, which may be normal at this time. After resolution of a known inflammatory source, ESR may remain elevated and it may be useful to maintain the trend for days, while CRP will return to normal more quickly.
These temporal trends in CRP and ESR concentrations may help elucidate the timing and nature of an inflammatory process. For example, a patient with elevated CRP and normal ESR probably has an acute infectious, ischemic, or thromboembolic process present . On the other hand, a patient with normal CRP and elevated ESR would probably have a more subacute or chronic autoimmune, systemic inflammatory or malignant process . This is why, in general, ESR is more useful in monitoring chronic inflammatory diseases, while CRP is more useful in monitoring and diagnosing acute inflammatory diseases.
In particular, in practice, the combination of ESR and CRP interpretation results in greater accuracy and diagnostic utility. This is why both tests are usually ordered simultaneously, although their peaks theoretically appear at different times during the acute phase response and some arguments can be made for their individual use.
Normal values
Although acute phase reagents, such as ESR and CRP, are not disease specific nor can they consistently distinguish an acute from a chronic inflammatory process, they have utility in certain emergency settings. Normal ESR and CRP values are listed below, and it is important to note that minimal increases in ESR and CRP are less useful than larger increases.
Normal ESR values include:
Normal values for the standard PCR test include:
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Of note, there are two PCR tests available: the standard PCR test and the high-sensitivity PCR (hs-CRP) test. Both tests perform the same thing and do not change the interpretation of CRP values, but the hs-CRP test can detect and report lower levels of elevation compared to the standard test.
Emergency Department
As in the hospital setting, ESR and CRP should only be used as a complement to clinical evaluation. They are often more valuable in long-term clinical management than in the acute ED setting, and are unlikely to alter the direct care provided in the ED. Although normal ranges exist, cut-off values also vary depending on the diagnosis.
There are three main cases in which ESR and CRP can be of value to the emergency department physician:
A. Back pain : In the emergency department, some crucial diagnoses related to back pain include vertebral osteomyelitis, spinal epidural abscess, and malignancy . When ESR or CRP is elevated in the setting of back pain, sensitivity can range from 94% to 100%, and there are often significant elevations in ESR and CRP, even in the absence of leukocytosis.
Spinal epidural abscess:
– ESR is more sensitive, but CRP is also usually elevated according to the available literature.
– Consider this diagnosis and the need for further MRI imaging if ESR > 20 mm/h and CRP > 1 mg/dL.
– The ESR can be > 100 mm/h, and there is a worse prognosis if the CRP > 11.5 mg/dL.
Vertebral osteomyelitis
– 90% of patients with ESR levels >30 mm/h and CRP >10 mg/L.
Malignant neoplasms/spinal tumors
– Elevations of ESR and CRP are generally observed, particularly if the disease is systemic.
Conclusion:
ESR and CRP elevations can help discern the likelihood of an infectious process that would warrant an MRI , but normal values should not be used to rule out serious diagnoses such as spinal epidural abscess or osteomyelitis in high-risk patients (those with neurological deficits). . If used as part of a diagnostic pathway for spinal epidural abscess in a patient with intermediate or low pretest probability, a subthreshold ESR can be used to exclude it.
B. Skin and soft tissue infections : In the ED, it is important to determine which patients warrant hospital admission and when to consider necrotizing soft tissue infections (NTSIs) as a potential diagnosis.
Cellulitis:
– The average ESR and CRP levels for more severe disease presentation requiring longer hospitalization are 70 mm/h and 10 mg/dL, respectively.
– The average ESR and CRP levels for less severe disease presentation requiring shorter hospitalization are 50 mm/h and 4 mg/dL, respectively.
– There is often a tendency to monitor the response to therapy.
Necrotizing soft tissue infections (NTIs):
– Clinical scoring tools, such as the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, incorporate CRP, but it remains a clinical diagnosis.
Conclusion: Across the spectrum of skin and soft tissue infections, ESR and CRP may be useful in detecting disease severity and monitoring treatment and may possibly help determine final disposition, but should not change management. of the emergency department nor the need for a surgical consultation in people with N necrotizing soft tissue infections.
C. Bone and joint pain : In the emergency department, the primary diagnostic goal when evaluating patients with bone and joint pain often includes evaluation for septic arthritis and osteomyelitis.
Septic arthritis:
An ESR > 15 mm/h and a CRP > 2 mg/dL have a sensitivity > 90% for the diagnosis of septic arthritis . However, these elevations are not specific and lower cutoff values have much lower sensitivity (19). The definitive diagnosis is made based on the analysis of the synovial fluid (20).
Osteomyelitis:
In non-diabetic patients , the combination of an ESR >45.5 mm/h and a CRP >3.45 mg/dL has a sensitivity of 33% and a specificity of 84% for the diagnosis of osteomyeltis. In diabetic patients , the combination of an ESR > 60 mm/h and a CRP > 7.9 mg/dL increases the probability of osteomyelitis as a diagnosis.
Conclusion: If you are concerned about a septic joint, ESR and CRP levels should not change the need for arthrocentesis. ESR and CRP levels cannot rule out osteomyelitis; however, higher elevations should increase clinical concern.
Of note, many pediatric and neonatal clinical guidelines incorporate ESR, CRP, and other acute phase reagents into their algorithms, which are not discussed here.
Pearls and traps -ESR and CRP are neither sensitive nor specific for infection, and cut-off values for significant elevations are based on the pathological process in question. Inflammatory markers may be falsely elevated or decreased depending on concomitant conditions. – Do not routinely order ESR and PCR, as elevations are common across a spectrum of diseases and false positives can be distracting. The results of these tests should not replace clinical judgment. -It may be useful to order ESR and CRP for back pain in the emergency department, but normal values should not dissuade the doctor from ordering an MRI if the suspicion of an infectious process is high. -There is some utility in ordering ESR and CRP for skin/soft tissue/bone and joint conditions, although the levels may be more useful for long-term treatment than for clinical decision making in the ED. |
