Abstract
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.
Highlights
Fever of unknown origin (FUO) is defined as a condition of body temperature higher than 38.3 ◦C on at least two occasions; duration of illness lasting more than 3 weeks or multiple febrile episodes in more than 3 weeks; not immunocompromised; and diagnosis uncertain
Eight patients from the outpatients sarcoidosis follow-up were added to the third group of inactive sarcoidosis patients
When a patient is considered to have a fever of unknown origin (FUO), this represents a real challenge in the internal medicine setting, requiring experience and diagnostic tools to achieve a final diagnosis, which is essential to the specific treatment and, hopefully, improvement for the patient
Summary
Fever of unknown origin (FUO) is defined as a condition of body temperature higher than 38.3 ◦C on at least two occasions; duration of illness lasting more than 3 weeks or multiple febrile episodes in more than 3 weeks; not immunocompromised; and diagnosis uncertain. Sarcoidosis is sometimes found among patients with fever of unknown origin (FUO) [3], which is usually a clinical and diagnostic challenge in internal medicine; it is a multi-systemic inflammatory disease showing granuloma formation in virtually any organ, with a prevalence in the lungs. In FUO patients showing compatible clinical symptoms and non-necrotizing granulomas, the diagnosis of sarcoidosis is established by exclusion of other diseases with similar histological or clinical picture. Chest radiography and CT images are usually indicative of pulmonary disease; the diagnosis cannot be exclusively based on imaging and requires a complete clinical and pathological correlation and laboratory tests
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