Investigating synovial trace elements as diagnostic markers in acute septic arthritis: an exploratory study

OBJECTIVES: Acute arthritis requires a precise and rapid diagnosis, particularly to rule out an infectious cause, which constitutes a rheumatologic emergency. Cytological, bacteriological, and microcrystal analyses do not always clearly differentiate causes. We hypothesized that variation in metal concentrations in synovial fluid could provide additional clues for etiological orientation. Our objective was to evaluate their diagnostic value in acute arthritis. METHODS: We conducted a retrospective, single-center study (Rennes University Hospital) using synovial fluids from the SYNOLACTATE-PLUS cohort, involving patients with acute arthritis (< 30 days). Metal quantification was performed by ICP-MS on frozen, centrifuged synovial samples. Diagnostic performance was assessed using univariate logistic regression and area under the curve (AUC). RESULTS: Between 2019 and 2020, 105 patients (63.8% male; mean age 62.1 ± 17.1 years) were included. Monoarthritis predominated (66.7%), especially in the knee (78%). Two diagnostic groups were analyzed: septic (n = 8) and non-septic (n = 97). Iron and zinc levels were significantly higher in septic arthritis (iron: 84.2 µg/dl vs 44.0; zinc: 20.4 µmol/l vs 10.6; both p < 0.005). Copper and manganese were also elevated (p < 0.05), while strontium was decreased (29.4 vs 51.2 µg/l; p < 0.05). AUCs were 0.835 for iron, 0.825 for zinc, and 0.769 for manganese (p < 0.001). Sensitivity analysis showed high odds ratios: 27.0 for zinc/strontium ratio, 16.4 for zinc, and 13.0 for copper and manganese. CONCLUSION: Our results suggest that synovial metallomic profiling, especially iron, zinc, copper, manganese, and strontium, could improve etiological diagnosis of acute arthritis. Prospective validation is required. Key Points • Synovial fluid metal profile varies with the etiology of acute arthritis • Fe, Cu, Zn, Mn, Mg, Se, and Rb increase, while Sr decreases in septic arthritis • A prospective study is needed to confirm these preliminary findings.