This study enrolled 882 KOA patients after those with known causes of increased CRP level and ESR were excluded; the enrolled patients were divided into four groups based on the preoperative CRP level and ESR. In total, 7 of the 247 patients with idiopathic CRP and/or ESR elevation had PJI within 90 days after primary TKA as a complication. Being a female and having elevated BMI and diabetes mellitus were all found to contribute to CRP and ESR elevation.
To date, there is no consensus or reliable clinical evidence on whether preoperative idiopathic CRP and ESR elevation is sufficient to affect the occurrence of PJI within 90 days after TKA. The results of this study suggest that preoperative idiopathic CRP and/or ESR elevation increase the risk of 90-day PJI after primary TKA. Xu C found that the rate of PJI was significantly higher in patients with both ESR and CRP elevation (12.5%, 4/32), which is similar to our results but with a higher infection rate. They found that patients with preoperative ESR and CRP elevation had a significantly greater risk of PJI than those with normal serum inflammatory marker levels (HR: 15.8, 95% CI: 2.57–96.7, P=0.003) after adjusting for confounding factors . We think that one of the reasons for this result is the long follow-up period in that study (mean follow-up after TKA, 43.7±11.7 months), which led to the influence of other factors, such as hematogenous infection, long-term smoking, or lack of control of chronic diseases in patients with poor basic health, which contributed to the onset of PJI. Another reason could be that in our study, the hyperplastic synovial membrane tissue was completely removed in all patients, and the duration of irrigation with 0.5% mucosal iodophor was prolonged in the CRP+ESR+ group in this study, which may have led to a much lower infection rate. However, Godoy G also found no statistically significant relationship between postoperative complications and the preoperative CRP level (P=0.5005) or ESR (P=0.1610) . In their study, 0 of 87 patients with preoperative CRP elevation developed infection, and only 3 of 151 patients with preoperative ESR elevation developed infection. However, in this study, CRP³8.3 mg/L and ESR³21 mm/h as elevated standards inevitably decrease the difference with the normal group. Another 2008 study by Pfitzner et al.  compared 25 patients with postoperative infections against a control group of 25 patients. The infected group had a higher average preoperative CRP (13-25 mg/L) than the control group (4-7mg/L), but this result was not statistically significant and not only KOA patients were included in those two studies. Meanwhile, based on the preoperative CRP and ESR level, CRP>10 mg / L and ESR> 30 mm/h were considered elevation in our study. However, elevation is determined by whether it exceeds the normal value twice in clinical practice. In this study, no patient developed PJI in the CRP++ESR++ (CRP³20, ESR³60) group and CRP+ESR++ (40³CRP³20, ESR³60) group, but 2 patients had infection in the CRP++ESR+ (CRP³20,60 ³ESR³30) group. Moreover, due to the limitation of the number of patients with idiopathic elevation in clinical practice, no further grouping and analysis of the difference in the infection rate among these groups were performed.
In this study, it was found that the CRP level and ESR in most patients with KOA were within the normal range. However, 28.00% (247/882) of patients had idiopathic CRP or ESR elevation; of these, patients with both CRP and ESR elevation accounted for 17.81%, and patients with either CRP or ESR elevation accounted for 10.93% and 71.26%, respectively. Per an abstract presented at the 2013 AAOS/AAHKS conference, 78 of 94 patients with KOA showed preoperative CRP and ESR elevation, with a rate of CRP and ESR elevation of 26.9% and 38.5%, respectively . Xu C found that patients with both CRP and ESR elevation and either CRP or ESR elevation accounted for 22.86% and 77.14%, respectively . CRP/ESR discordance occurred in 212 patients (12%), 105 of whom had high CRP/low ESR discordance (6%), and 107 of whom had high ESR/low CRP discordance (6%) among 1753 patients . Colombet I found a disagreement was observed in 33% (elevated ESR/normal CRP in 28%, normal ESR/elevated CRP in 5%) among 5777 patients . We believe that differences in the population and prevalence of multiple diseases in combination among regions may lead to differences in the distribution of the data.
In this study, diabetes mellitus (P = 0.0004) and an elevated BMI (P < 0.0001) were risk factors for an elevated CRP level. The female sex (P < 0.0001), BMI (P < 0.0001), and diabetes mellitus (P = 0.0036) were risk factors for an elevated ESR. Previous studies have shown that race, sex, BMI, comorbidities, a history of intraarticular injections, smoking, and even osteoarthritis severity and muscle strength changes [3-6] also affect the baseline CRP level and ESR, and female endocrine instability, atherosclerosis, plaque composition, obesity and chronic inflammation caused by local injection are more accepted reasons. In this study, since the patients in the CRP+ESR+ group underwent a synovial fluid test to exclude infection, this factor was not included as a variable.
The current criteria for CRP and ESR elevation do not take patient characteristics, which influence the baseline CRP level and ESR, into consideration. Meanwhile, the mean peak CRP level and ESR after surgery were similar among the groups of patients; however, in patients with preoperative CRP elevation, the CRP level and ESR may not normalize until 2 months after surgery , which is similar to our result; in our study, the mean CRP level and ESR in the CRP+ESR+ group persisted at an elevated level after the operation, and there was a significant difference in the CRP level and ESR among the four groups at 1 month (P <0.001) and 3 months (P <0.001) after the operation (Table 1); therefore, the baseline preoperative CRP level and ESR could affect the pattern of change in the CRP level and ESR over time after surgery. Thus, importantly, the CRP and ESR values or thresholds are dependent on the time period or the basic condition of the patient at the index arthroplasty . Therefore, whether we need to adjust or optimize the CRP and ESR thresholds in these patients to ensure the reliability of CRP and ESR in the preoperative evaluation and postoperative diagnosis of PJI requires further research.
There are several limitations to this study. First, the design was retrospective, and certain biases of retrospective studies cannot be avoided. Information such as smoking status, which can confound the results, may not have always been accurately documented. Second, changes in the ESR and CRP level should be dynamically detected before and after surgery, as the occurrence of PJI cannot be well predicted only by single preoperative ESR and CRP values. Third, the MSIS standard of PJI is not 100% and missed diagnosis may occur. Fourth, there were no cases of infection in the CRP+ESR- group, and we still need to increase the sample size to obtain more reliable results.