Objective: To explore the etiologies and clinical characteristics of fever of unknown origin (FUO) and to provide clues for early diagnosis of FUO. Methods: The data about etiology, age, sex, clinical course, length of hospital stays and the expression levels of inflammatory factors in fever phase of 357 pediatric inpatients who were diagnosed with FUO in Children's Hospital of Fudan University from 1 January 2016 to 31 December 2020 were collected and retrospectively analyzed. Participants were grouped into infectious disease, inflammatory disease, malignancy and others and according to the classification of diseases and also grouped into those aged<1 year, 1-<3 years,3-<6 years, 6-<12 years and 12-<18 years. Comparisons between groups were performed using the Mann-Whitney U test, Kruskal-Wallis H test and χ² test. Results: Among the 357 patients (217 males and 140 females). The age of onset was 3.9 (1.3, 9.2) years and visiting age was 5.1 (2.0, 9.3) years. The time-consuming of diagnosis was 94 (66, 213) days. The hospital stay was 8 (6, 14) days. The most frequently identified cause of FUO was infectious diseases (163 cases, 45.7%), followed by non-infectious inflammatory diseases (133 cases, 37.2%), malignancy (21 cases, 5.9%) and others (40 cases, 11.2%). The patients at younger age were more likely to be attacked by malignancy, oncologic diagnoses, and others, nevertheless patients at older age were more likely to be attacked by non-infectious inflammatory diseases oppositely (9.8 (3.6, 11.5) vs. 3.0 (1.2, 7.0), 2.3 (1.0, 5.2), 0.9 (0.5, 1.8) years, U=41.30, 15.94, 37.08, all P<0.01);106 (65%) patients were male, and 57 (35%) patients were female. This result indicated that boys were more susceptible to infectious diseases (χ²=14.73, P<0.01). Analysis of inflammatory factors in serum among 103 patients, interleukin (IL)-6 level in 40 infectious diseases patients (9 (2, 38) ng/L) was significantly lower than those of 6 tumor patients (89 (64, 599) ng/L) and 57 non-infectious inflammatory diseases patients (25 (8, 78) ng/L, U=51.05, 15.70, both P<0.05), no significant difference was observed in IL-2, IL-4, IL-10, tumor necrosis factor α and interferon among the groups (all P>0.05). The patients grouped into those aged 1-<3 years and 3-<6 years were more likely to be attacked by infectious diseases (51.3% (59/115) and 57.1% (40/70)), while patients grouped into those aged 6-<12 years and 12-<18 years were more likely to be attacked by non-infectious inflammatory diseases (55.6% (65/117) and 72.4% (21/29)). Conclusions: Infectious disease is still the main cause of FUO in children and the boys are more susceptible to infectious diseases. However, the morbidity of non-infectious inflammatory diseases increases to number 1 in FUO of children over 6 years of age.
Aged ; Child ; Communicable Diseases/complications* ; Female ; Fever of Unknown Origin/etiology* ; Humans ; Length of Stay ; Male ; Neoplasms/complications* ; Retrospective Studies

OBJECTIVE: To investigate the clinical significance of bone marrow unclassifiable cells in diagnosis of fever of unknown origin(FUO). METHODS: The clinical data of 60 patients with FUO admitted in the first affiliated hospital of Xi'an Jiaotong university from June 2014 to May 2016 were collected, and 60 patients with FUO were divided into 2 group: group A(30 cases) in which the unclassifiable cells in bone marrow were observed by bone marrow examination, and group B(30 cases) in which the unclassifiable cells in bone marrow not were found by bone marrow examination. The clinical characteristics, bone marrow features, immunophenotypes of bone marrow cells and prognosis of patients in 2 groups were analyzed retrospectively. RESULTS: Out of 30 patients in group A, 18 were diagnosed as malignant tumors including 12 cases of lymphoma, while out of 30 patients in group B, 5 cases were diagnosed as malignant tumor, including 3 cases of lymphoma. For the patients with non-tumor diseases, the bone marrow unclassifiable cells disappeared after the patients condition was improved. CONCLUSION The bone marrow examination including the smear and biopsy shonld be performed routinely for the patients with FUO. If the unclassifiable cells are observed morphologically in bone marrow of patients with FUO, the disease of patients should be considered as malignant tumor, especially, lymphoma.
Bone Marrow ; Bone Marrow Cells ; Bone Marrow Examination ; Fever of Unknown Origin ; Humans ; Retrospective Studies

We report the first case demonstrating an association between Kawasaki disease (KD) and erythema nodosum (EN). A 3-year-old girl presented with EN as an initial manifestation of KD. At the initial visit, she showed high fever of 40℃, injection of the oropharynx, cervical lymphadenopathy, and red-purple cutaneous nodules, particularly on the lower limbs. She complained of severe pain in the neck and cutaneous lesions. Initially, the development of EN was attributed to Salmonella spp infection, which was detected in stool culture. However, the patient did not respond to high-dose ampicillin/sulbactam to which the Salmonella spp is sensitive. Echocardiography performed as screening for fever of unknown origin revealed medium-sized aneurysms of the left anterior descending artery. EN masked the diagnosis of KD, and the patient developed a coronary artery lesion. KD should be considered in the differential diagnosis of refractory EN in pediatric patients.
Aneurysm ; Arteries ; Bacterial Infections ; Child, Preschool ; Coronary Vessels ; Diagnosis ; Diagnosis, Differential ; Echocardiography ; Erythema Nodosum ; Erythema ; Exanthema ; Female ; Fever ; Fever of Unknown Origin ; Humans ; Lower Extremity ; Lymphatic Diseases ; Masks ; Mass Screening ; Mucocutaneous Lymph Node Syndrome ; Neck ; Oropharynx ; Salmonella ; Skin ; Subcutaneous Tissue

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.
Diagnosis ; Electrons* ; Fever of Unknown Origin* ; Fever* ; Histiocytic Necrotizing Lymphadenitis ; Humans ; Korea ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Retrospective Studies ; Tertiary Care Centers

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.
Diagnosis ; Electrons* ; Fever of Unknown Origin* ; Fever* ; Histiocytic Necrotizing Lymphadenitis ; Humans ; Korea ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Retrospective Studies ; Tertiary Care Centers

Adult-onset Still's disease (AOSD) is a rare systemic febrile disorder of unknown etiology. AOSD is characterized by spiking fever, arthralgia, sore throat, skin rash, and multi-organ involvement but is difficult to diagnose due to the lack of specific clinical features. AOSD is most frequently observed among young adults. We describe the case of an 18-year-old male patient with multiple cerebral infarction who was diagnosed with AOSD based on the clinical features observed during rehabilitation treatment after the diagnosis of ischemic stroke. Clinical symptoms of the patient was controlled with steroid therapy. If cerebral infarction is accompanied by unusual clinical features as non-infectious fever, rash, and arthralgia, AOSD should be considered in young stroke patient.
Adolescent ; Arthralgia ; Cerebral Infarction* ; Diagnosis ; Exanthema ; Fever ; Fever of Unknown Origin ; Humans ; Male ; Pharyngitis ; Rehabilitation ; Still's Disease, Adult-Onset* ; Stroke ; Young Adult

Respiratory-gated ¹⁸F-fluorodeoxygluocse (¹⁸F-FDG) PET/CT has been successfully used to better localize malignancies in the lung or upper abdominal organs. However, clinical usefulness of respiratory-gated ¹⁸F-FDG PET/CT in detection of fever focus has not been reported yet. A 68-year-old male patient with a history of living donor liver transplantation and biliary stenting was referred for ¹⁸F-FDG PET/CT due to fever of unknown origin (FUO). To find the accurate fever focus, respiratory-gated and non-gated ¹⁸F-FDG PET/CT was performed. Respiratory-gated PET/CT readily revealed prominent hypermetabolic lesion in the distal common bile duct (CBD) area where previous surgical graft was in situ. Maximum standardized uptake value (SUVmax) and SUVratio (SUR) were greater in the gated PET/CT (SUVmax 5.4 and SUR 3.5) than in the non-gated PET/CT (SUVmax 4.6 and SUR 3.0). Fever dramatically subsided after removal of the graft in the CBD. This case report implies that respiratory-gated ¹⁸F-FDG PET/CT can visualize upper abdominal fever focus with better contrast than the conventional non-gated method.
Aged ; Common Bile Duct ; Fever of Unknown Origin ; Fever ; Humans ; Liver Transplantation ; Living Donors ; Lung ; Male ; Methods ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Respiratory-Gated Imaging Techniques ; Stents ; Transplants

PURPOSE: Fever is one of the most common symptoms in children. In previous studies, infectious disease was the most common cause of pediatric fever of unknown origin (FUO). The aim of this study is to investigate the etiology, clinical characteristics and prognosis of pediatric FUO in 21 century with more diagnostics available and to analyze the factors for certain disease categories. METHODS: Among the children under 18 years old who were hospitalized at Samsung Medical Center from January 2000 to December 2014, the patients who met the criteria including fever of ≥38.0℃ for longer than ≥14 days and failure to reach a diagnosis after one week of investigations were included. RESULTS: Total 100 patients were identified. Confirmed diagnosis was achieved in 57 patients (57%). Among them, infectious diseases (n=19, 19%) were most common, followed by connective tissue diseases (n=15, 15%), necrotizing lymphadenitis (n=8, 8%), and malignancies (n=7, 7%). Children with fever duration over 28 days had a trend for higher frequency of connective tissue diseases (28.3%) except undiagnosed etiology. The symptoms such as arthritis, lymph node enlargement and only fever without other symptoms were significantly related with connective tissue diseases, necrotizing lymphadenitis and undiagnosed respectively (P<0.001). Ninety-two patients have become afebrile at discharge and 1 patient died (1%). CONCLUSION: Almost half of our patients were left without diagnosis. Although it has been known that infectious disease was most common cause of pediatric FUO in the past, undiagnosed portion of FUO have now increased due to development of diagnostic techniques for infectious diseases.
Arthritis ; Child* ; Communicable Diseases ; Connective Tissue Diseases ; Diagnosis ; Fever of Unknown Origin* ; Fever* ; Humans ; Lymph Nodes ; Lymphadenitis ; Prognosis

PURPOSE: Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of 18F-fluoro-2-deoxy-Dglucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting.METHODS: Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDGPET/CT to strengthen or confirma diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMVor EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study.RESULTS: Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT's sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n = 4), pulmonary fungal infection (n = 1), histoplasmosis (n = 1), cutaneous abscess (n = 1), inflammatory disorder (sacroiliitis) (n = 1), lymphoma (n = 3) and NSCLC (n = 3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases.CONCLUSIONS: FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.
Abscess ; Adenocarcinoma ; Diagnosis ; Electrons ; Endocarditis ; Fever of Unknown Origin ; Follow-Up Studies ; Graft vs Host Disease ; Hand ; Heart Transplantation ; Herpesvirus 4, Human ; Histoplasmosis ; Humans ; Kidney ; Lung ; Lung Diseases, Fungal ; Lymphoma ; Organ Transplantation ; Pneumonia, Bacterial ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies ; Sensitivity and Specificity ; Sepsis ; Seroconversion ; Transplants

Objective: The clinical presentation, outcome, and risk factors for mortality in children with Fever of Unknown Origin (FUO) were determined. Methods: Medical records of pediatric patients admitted for FUO from January 2009 to December 2013 were reviewed. Clinical manifestations, physical exam findings, diagnostic work-ups and final diagnosis were determined, as well as the relationship between final diagnosis and risk for mortality. Results: Fifty-seven patients with FUO were included. Weight loss, cough, colds, and rashes were common symptoms while pallor, lymphadenopathies, and hepatomegaly were common physical exam findings. All patients underwent Phase I evaluation for FUO, while 73.7% underwent further diagnostic tests. A specific etiology was established in 96.5% of cases: infectious, 43.9%, connective tissue disease, 38.6%, and hematologic/oncologic, 14%. Two cases remained to have no specific diagnosis. Majority of patients had a benign course and were discharged improved (84.2%). The mortality rate is 15.8% and was not associated with any disease category (p-value 0.204). Conclusion FUO in children occurs across all age groups. Its clinical presentations are varied and non-specific and common signs and symptoms are pallor, lymphadenopathies, weight loss, cough, colds. and joints pains. Infection is the most common cause of FUO in children, followed by connective tissue diseases and hematologic and oncologic diseases. The mortality rate from FUO is 15.8%.
Fever of Unknown Origin