Fever of unknown origin (FUO) in children presents a diagnostic challenge. Differential diagnosis includes Systemic Onset Juvenile Idiopathic Arthritis (SJIA), an auto-inflammatory syndrome associated with activation of phagocytic cells which at presentation is difficult to differentiate from severe systemic infections. In this study, we investigated whether serum concentrations of the phagocytic pro-inflammatory protein S100A12 may help in the decision between antibiotic or immunosuppressive therapy in patients with FUO.
Serum samples were obtained from 45 healthy controls and 240 patients: 60 had SJIA, 17 Familial Mediterranean Fever (FMF), 18 Neonatal-Onset Multisystem Inflammatory Disease (NOMID), 17 Muckle Wells Syndrome (MWS), 40 Acute Lymphoblastic Leukemia (ALL), 5 Acute Myeloblastic Leukemia (AML), and 83 systemic infections. All samples were collected at presentation before initiation of anytreatment, and were analyzed for S100A12 by ELISA.
In SJIA patients the mean S100A12 serum level was 7,190 ng/ml (95% confidence interval ±2,690), in FMF 6,720 ng/ml (±4,960), in NOMID 720 ng/ml (±450), in MWS 150 ng/ml (±60), in infections 470 ng/ml (±160), in ALL 130 ng/ml (±80), and in AML 45 (±60) compared to 50 ng/ml (±10) in healthy controls. Sensitivity and specificity of S100A12 to distinguish SJIA from infections were 66% and 94% respectively.
S100A12, a marker of granulocyte activation, is highly overexpressed in SJIA and FMF, which may point to so far unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO.