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Sarcoidosis is a multi-organ inflammatory granulomatosis with a lung-predominant involvement. The aim of this study was to investigate the use of serum chitotriosidase (CHIT1) in patients with fever of unknown origin (FUO); the patients with confirmed diagnosis of active sarcoidosis were compared with ones affected by inactive or treated sarcoidosis. CHIT1 activity was evaluated in 110 patients initially admitted at the hospital as FUOs. The overall performance of CHIT1 for active sarcoidosis diagnosis was assessed by performing an area under the receiver operating characteristic curve analysis (AUROC). The sarcoidosis patients were significantly older than the FUO patients not affected by sarcoidosis ( p  < 0.01). CHIT1 showed a good accuracy as a biomarker for active sarcoidosis in patients explored for FUO (AUROC 0.955; CI 95% 0.895–0.986;  p  < 0.001). A CHIT1 value >90.86 showed 96.8% sensitivity (84.2–99.9) and 85.5% specificity (75–92.8) in discriminating active sarcoidosis from other causes of FUO. CHIT1 significantly discriminated active versus inactive/under treatment sarcoidosis patients (with lower enzyme activity) (ROC analysis, sensitivity: 96.9%, specificity: 94.7%, value >83.01 nmol/mL/h, AUROC: 0.958, 0.862–0.994,  p  < 0.001) compared to ACE (ROC analysis, sensitivity: 25.8%, specificity: 93.7%, value >65 UI/L). In conclusion, CHIT1 is a reliable/sensitive biomarker of active sarcoidosis, with values significantly decreasing in remitted/treated patients. It significantly discriminates active sarcoidosis from FUO patients, providing a useful tool in the diagnosis-assessing process.

The Use of Chitotriosidase as a Marker of Active Sarcoidosis and in the Diagnosis of Fever of Unknown Origin (FUO)