Monoarthropathies are common and carry a broad differential including infection, trauma, lupus, rheumatoid arthritis, or crystal arthropathies.1–3 Of these, the can’t miss diagnosis is septic arthritis, as delayed treatment can cause irreversible joint destruction with a fatality rate up to 11% if not treated.4 Yikes.
The Patient
You are working in minor treatment and a 70-year-old gentleman presents with pain in his left knee that has been worsening over the past week. It is painful to ambulate, and the knee has been quite swollen and red the last couple of days. There is no history of trauma. What do you do?
Septic Arthritis
Septic arthritis arises due to either direct inoculation of a joint, or secondarily via hematogenous spread.5 The people more likely to be afflicted include those with rheumatoid arthritis or another inflammatory disorder. Other risk factors include a prosthetic joint, low socioeconomic status, intravenous drug use, alcohol abuse, diabetes, previous intra-articular joint injection, or some other cutaneous ulcer/skin infection.6 Larger joints are more often involved, with the knee being affected in approximately 50% of cases.5 Staphylococci and Streptococci are the major causes and MRSA is more common recently, particularly in IV drug users.7,8
The Work-Up
After a thorough history and physical, the gold standard test involves analysis of the synovial fluid.6 However, an arthrocentesis is not without its risks. The risk of iatrogenic infection from the procedure is estimated to be between 0.01-0.037% in the general population, and 0.05% in the immunocompromised.9,10 There is a theoretical risk of bleeding with the procedure, but the risk of clinically significant hemorrhage in patients on warfarin who are in a therapeutic range is <10%.11 While this procedure is clearly necessary in the right clinical setting, wouldn’t it be nice if there were serum markers to guide our decision whether an arthrocentesis is necessary?
Inflammatory Serum Markers
Essentially both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are markers of inflammation. Infection causes inflammation, and thereby increases the levels of acute phase reactants such as ESR and CRP. The question however, is whether these tests add anything useful to the picture. Do patients with septic arthritis actually exhibit higher levels of these serum markers? Do they aid us in differentiating between other conditions with a similar presentation? And are they sensitive enough for us to confidently rule-out septic arthritis and forgo further invasive testing such as arthrocentesis when they come back negative?
The Research
An excellent systematic review from 2011 by Carpenter et al. examined the validity of classic history & physical exam findings and common serological markers used in evaluating septic arthritis.12 After screening titles/abstracts to identify appropriate literature, they were left with 32 primary studies from which they found the following:
| Table 1. Average sensitivities and specificities of various cut offs for ESR and CRP in Septic Arthritis. Adapted from Carpenter et al.12 | ||||
| Serum Marker | Avg. Sensitivity (%) | Avg. Specificity (%) | Avg. (+)LR | Avg. (-)LR |
| ESR | ||||
| >15mm/hr | 66 | 48 | 1.3 | 0.71 |
| >20mm/hr | 75 | 11 | 0.84 | 2.4 |
| >30mm/hr | 89 | 29 | 1.3 | 0.17 |
| >50mm/hr | 72 | 42 | 1.4 | 0.4 |
| >100mm/hr | 41 | 94 | 7.0 | 0.6 |
| CRP | ||||
| >10mg/L | 89 | 27 | 1.3 | 0.5 |
| >100mg/L | 83 | 49 | 2.0 | 0.5 |
| >150mg/L | 73 | 83 | 4.5 | 0.3 |
| >200mg/L | 44 | 85 | 2.9 | 0.7 |
Carpenter et al. found a large spread in the data including estimated sensitivities of an ESR>50mm/hr ranging from 42-92%.12 Similarly the sensitivity, specificity and likelihood ratios for CRP varied significantly from study to study and they concluded that the overall quality of evidence was very poor. They stated that “No cutoff for ESR or CRP significantly increases or decreases the post-test probability of septic arthritis.”
Since the 2011 review there have been several other studies examining this issue. Their findings are summarized in Table 2:
| Table 2. Average sensitivities and specificities for various cut offs of ESR and CRP (Summary of the evidence since Carpenter et al.13,14) | ||||
| Serum Marker | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) |
| ESR | ||||
| >15-25 mm/hr | 97 | 60 | 40 | 100 |
| >50mm/hr | 72 | 60 | n/a | n/a |
| >100mm/hr | 34 | 84 | n/a | n/a |
| CRP | ||||
| >15-18mg/L | 92 | 24 | 76 | 79 |
| >100mg/L | 58 | 66 | n/a | n/a |
More recently in 2016, Borzio et al. examined patient factors and laboratory parameters that may be associated with septic arthritis. They looked at the results of 458 patients who had received knee aspirates, 22 of which were confirmed to have septic arthritis via positive synovial fluid culture. They only examined ESR, and reported no significant difference between the septic arthritis and non-septic arthritis groups.15
These subsequent studies are in line with those examined by Carpenter et al., and do not appreciably change our overall assessment of the evidence.
Conclusion
As shown in the aforementioned studies, ESR and CRP fail to significantly impact our post-test probability of septic arthritis.12 In a practical sense, this means that ESR and/or CRP results do not (or shouldn’t) change our management decisions.
Bottom Line
While ESR and CRP may be higher in patients with septic arthritis, the tests are not reliable enough to change our management and synovial fluid analysis is essential for the diagnosis of septic arthritis.
This post was uploaded by Sean Nugent (@sfnugent).
[bg_faq_start]References
Reviewing with the Staff
A patient with an acute monoarthritis presents an extremely difficult diagnostic dilemma. There is no cutoff value of WBC, ESR, or CRP at which the posttest probability of septic arthritis is significantly increased, nor any value below which septic arthritis can safely be ruled out. An arthrocentesis must be performed if there is an acute, unexplained and atraumatic painful joint effusion. Septic arthritis must be considered regardless of a patient history of gout or rheumatoid arthritis, and even if crystals are seen on aspiration as both diseases can occur concurrently. Consider the use of ultrasound guided arthrocentesis as it increases the success of the procedure, decreases pain and total time of the procedure. Use caution in strict white blood cell (WBC) cutoffs as patients may have a septic joint even with a WBC <40,000, in fact MRSA-associated septic arthritis has been shown to have lower synovial WBC counts. If a dry tap is encountered, attempt the aspiration with a larger gauge needle with a smaller syringe and compress the contralateral joint gutter to allow fluid to shift towards the needle. Gentle rotation of the bevel in the joint can also sometimes increase the success rate.
In summary, no serum lab will change your management, however you may be asked to order these tests for your consulting orthopedics or rheumatology services. If the history and/or physical exam demonstrate a monoarthropathy, septic arthritis must be considered and is the diagnosis to rule out.
Aaron Sobkowicz