To Improve The Diagnostic Efficacy Of ¹⁸F-FDG PET/CT In Fever Of Unknown Origin

Objective:To analyze the etiology spectrum of fever of unknown origin（FUO）and compare the clinical characteristics of patients with different etiologies.To analyze the ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography(¹⁸F-FDG PET/CT)characteristics of different causes of FUO and the diagnostic efficacy for FUO,and to develop a diagnostic model based on clinical parameters and ¹⁸F-FDG PET/CT features for distinguishing between these causes.To investigate the value of ¹⁸F-FDG PET/CT in the differential diagnosis of lymphoma in patients with FUO accompanied by lymphadenopathy,and to develop a simple scoring system based on clinical parameters and features of ¹⁸F-FDG PET/CT to distinguish lymphoma from other etiologies.Methods:524 patients with classic FUO who were admitted to Wuhan Tongji Hospital from January 2016 to July 2021 were enrolled in this prospective study,and the standard diagnosis procedures were performed.All patients underwent ¹⁸F-FDG PET/CT scans in the absence of potential diagnostic clues.The etiological spectrum of FUO was analyzed and the clinical characteristics（including the general information,clinical symptoms and signs,laboratory examination）of patients with different etiologies were compared.The ¹⁸F-FDG PET/CT characteristics of patients with different causes and the diagnostic performance of ¹⁸F-FDG PET/CT were analyzed.Based on the data of 369 patients,the logistic regression analysis method was used to establish diagnostic prediction models to predict whether it is infectious disease,malignancy,or noninfectious inflammatory disease（NIID）.The other 155 patients comprised the validation cohort for verifying the diagnostic performance of the models.Another study recruited 163 patients with FUO accompanied by lymphadenopathy who underwent lymph node biopsy under the guidance of ¹⁸F-FDG PET/CT as the standard diagnostic procedure.They were divided into lymphoma（79 cases）and benign groups（84 cases）according to the etiology.The clinical characteristics and ¹⁸F-FDG PET/CT imaging characteristics of the two groups were compared and the diagnostic utility of ¹⁸F-FDG PET/CT imaging was evaluated.A lymphoma prediction model combining clinical parameters and ¹⁸F-FDG PET/CT results was established using logistic regression analysis.Results:Among 524 patients with FUO,infectious diseases accounted for 42.6%,malignancies 23.1%,NIIDs 20.8%,miscellaneous causes 4.2%,and unknown causes 9.3%.There were certain differences in general information,clinical symptoms and signs,and laboratory examination of patients with different etiologies.The levels of blood cell counts and inflammatory indicators among different etiologies were not only different at the time of admission,but also different from the limit value in the course of disease.The metabolic characteristics of the“hottest”lesion,the spleen,bone marrow,and lymph nodes varied for various causes.The accuracy of ¹⁸F-FDG PET/CT in the diagnosis of FUO was 49.8%.¹⁸F-FDG PET/CT features combined with clinical parameters achieved better discrimination in the differential diagnosis of FUO.The etiological diagnostic models included the following factors:multisite metabolic characteristics,blood cell counts,inflammatory indicators（erythrocyte sedimentation rate,C-reactive protein,serum ferritin,and lactate dehydrogenase）,immunological indicators（T-SPOT.TB,antinuclear antibody,and anti-neutrophil cytoplasm antibody）,specific symptoms and signs（weight loss,rash,and splenomegaly）,and age.In the testing cohort,the areas under the receiver operating characteristic curve（AUCs）of the infection prediction model,the malignancy diagnostic model,and the NIID prediction model were 0.89（95%CI 0.86–0.92）,0.94（95%CI 0.92–0.97）,and 0.95（95%CI 0.93–0.97）,respectively.The corresponding AUCs for the validation cohort were 0.88（95%CI 0.82–0.93）,0.93（95%CI 0.89–0.98）,and 0.95（95%CI0.92–0.99）,respectively.The sensitivity,specificity,positive predictive value（PPV）,and negative predictive value（NPV）of ¹⁸F-FDG PET/CT in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy were 81.0%,47.6%,59.3%,and 72.7%,respectively.The lymphoma prediction model combining parameters such as high ¹⁸F-FDG uptake of the“hottest”lesion,high ¹⁸F-FDG uptake of retroperitoneal lymph nodes,old age,low platelet count,and low ESR had an AUC of 0.93（95%CI 0.89–0.97）,a sensitivity of 84.8%,a specificity of 92.9%,a PPV of 91.8%,and an NPV of 86.7%.There was a lower probability of lymphoma for patients with a score<4 points.Conclusions:The most common causes of FUO are infectious diseases,malignancy,and NIID.There are some differences in the clinical features and ¹⁸F-FDG PET/CT features of various etiologies.¹⁸F-FDG PET/CT has a certain level of sensitivity and accuracy in diagnosing FUO,which can be further improved by combining it with clinical parameters.Diagnostic models based on ¹⁸F-FDG PET/CT show excellent performance in predicting infection,malignancy,and NIID,and can be used as reliable tools to discriminate the cause of FUO.¹⁸F-FDG PET/CT scans show moderate sensitivity and low specificity in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy.The scoring system based on ¹⁸F-FDG PET/CT and clinical parameters performs well in differentiating lymphoma and benign causes and can be used as a reliable noninvasive tool.