Serum and Synovial Fluid Interleukin-6 for the Diagnosis of Periprosthetic Joint Infection

Abstract

Periprosthetic joint infection (PJI) is a severe complication of arthroplasty and causes unrelieved pain and joint dysfunction. Although standardised perioperative management has lowered the risk of hip and knee PJI to less than 2%, PJI is still a significant cause of revision surgery [1][2][3][4][5] . In contrast to aseptic loosening, PJI is often associated with a two-stage revision procedure and long-term antibiotic therapy. Given these adverse implications, an accurate diagnosis method for PJI is valuable in arthroplasty surgery. In the past decades, various diagnostic methods and guidelines have been established for diagnosing PJI. Unfortunately, in the absence of a gold standard test, it is still challenging to differentiate PJI from aseptic loosening 6 . A previous prospective cohort study reported that 25% of PJI patients were misdiagnosed with aseptic loosening in the first year after arthroplasty 7 . Periprosthetic tissue culture and histological examination are reliable diagnostic methods for PJI detection 8 ; however, neither method can guide the operative decision before revision surgery.Inflammatory biomarkers in the serum and synovial fluid can be evaluated before surgery 8 . Traditional biomarkers such as serum white cell count (WCC) and C-reactive protein (CRP) have limited diagnostic accuracy for PJI detection 9,10 . Previous meta-analysis indicated that the sensitivity of serum WCC for PJI detection is 0.45 9 . The pooled sensitivity and specificity of serum CRP are 0.82 and 0.77, respectively 10 . Recently, the diagnostic value of interleukin-6 (IL-6) for PJI detection was investigated. IL-6 is produced by lymphoid and non-lymphoid cells, and it participates in the inflammatory response 11 . Serum IL-6 levels increase with trauma, infection, and surgery [11][12][13] . In patients with aseptic prosthetic loosening, IL-6 levels decrease to the normal level within 48 h after arthroplasty 13 . However, following infection, IL-6 activates the release of CRP 14 . Therefore, the increase of IL-6 precedes that of CRP after infection; thus, IL-6 may be a more sensitive marker for PJI.The previous meta-analysis summarised the results of three studies and showed that high serum IL-6 level strongly indicates PJI 9 . Following this study, the diagnostic capacity of serum and synovial fluid IL-6 for PJI has been widely evaluated; however, there were some discrepancies in the results [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] . The objective of the present meta-analysis was to estimate the value of serum and synovial fluid IL-6 assessments for PJI diagnosis. ResultsSearch Results. A total 323 articles were identified following the database and bibliography search. After further screening, 257 articles were excluded, and 33 articles were excluded after full-text evaluation (Fig. 1).

Serum Globulin and Albumin to Globulin Ratio as Potential Diagnostic Biomarkers for Periprosthetic Joint Infection: A Retrospective Review

“…With regard to the newly emerged biomarkers for PJI, our biomarkers have better diagnostic performance than platelet [22], but its related parameter, platelet to mean platelet volume ratio, was shown to be effective when combined with ESR and CRP [9]. Additionally, the diagnostic performance of D-dimer and interleukin-6 in predicting PJI was inconsistent [5,[23][24][25][26][27]. For example, D-dimer was reported by Qin et al as a promising biomarker for diagnosing PJI [28] while Xu et al demonstrated that D-dimer had limited value [24].…”

New developments and future challenges in prevention, diagnosis, and treatment of prosthetic joint infection

“…Randau et al 89 observed that serum interleukin 6 (IL‐6) levels were significantly elevated in patients presented with PJI compared with healthy controls and those with aseptic loosening of the implants. A meta‐analysis, based on 17 studies involving greater than 700 patients, revealed that serum IL‐6 could achieve diagnostic accuracies of 83%, with 72% sensitivity and 89% specificity 90 . Intriguingly, combining serum IL‐6 with other serological tests such as CRP can markedly improve PJI diagnostic accuracy 61,62 .…”

Diagnostic Accuracy of D-Dimer in Periprosthetic Joint Infection: a diagnostic meta-analysis

“…According to previous studies, the incidence of PJI accounts for approximately 20% of revision arthroplasty. Hence, 0.2 pre-test probabilities was selected to calculate the post-test probability through the likelihood ratio and the pretest probability [28]. The post-test probability of PJI was 6%, indicating negative D-dimer results (Fig.7).…”