Diagnostic Challenges and Risk Stratification of Periprosthetic Joint Infection in Patients with Inflammatory...

Background/Objectives: Accurate detection of periprosthetic joint infection (PJI) in patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), remains challenging due to overlapping inflammatory parameters and the influence of immunosuppressive regimens. Methods: A narrative review was conducted using PubMed/MEDLINE (2010-2025). Search terms included "periprosthetic joint infection", "inflammatory arthritis", "rheumatoid arthritis", "diagnosis", "biomarkers", "synovial fluid", and "immunosuppression". Eventually, 50 studies were included. Results: IA patients diagnosed with PJI are more frequently younger, female, and present with a higher burden of comorbidities and an increased rate of false-positive histological findings and culture-negative infections. Standard biomarkers, such as serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), as well as synovial fluid white blood cell count and polymorphonuclear leukocyte percentage, have a low to moderate value for diagnosing PJI in patients with IA. Optimal thresholds for these tests differ from those recommended by the Musculoskeletal Infection Society (MSIS). Alpha-defensin has demonstrated superior diagnostic performance among synovial fluid biomarkers included in MSIS criteria. Novel markers, such as serum bactericidal permeability-increasing protein (BPI) and neutrophil elastase-2 (ELA-2), as well as synovial C-reactive protein and calprotectin, along with molecular techniques like polymerase chain reaction (PCR), are showing increasing potential. Conclusions: Disease and treatment-related confounders hinder PJI diagnosis in IA. Adjusted thresholds and IA-specific approaches are needed. Further research should validate emerging biomarkers, among which BPI, ELA-2, and synovial CRP show the greatest diagnostic potential and guide perioperative immunosuppressive strategies.