Fever Of Unknown Origin Group Research Articles

Development and validation of the AF score for diagnosis of adult-onset Still's disease in fever of unknown origin

ObjectiveTo develop and validate a diagnostic score to identify adult-onset Still's disease (AOSD) in fever of unknown origin (FUO). MethodsA single center, retrospective case-control study of inpatients with FUO from January 2018 to December 2021. Using clinical and laboratory data from 178 cases with AOSD and 486 cases with FUO, we developed an AOSD/FUO (AF) score with a Bayesian Model Averaging approach. AF score and Yamaguchi's criteria were evaluated by sensitivity, specificity, accuracy, and positive/negative predictive value for diagnosis of AOSD in developmental and validation samples. ResultsPersistent pruritic eruptions (PPEs) in patients with rashes was higher in AOSD group than FUO group (52.3% vs 7.4%; P < 0.01). PPEs yielded a specificity of 97.5% and a sensitivity of 44.9%. AF score = PPEs × 3.795+Evanescent rash × 2.774+Serum ferritin × 1.678+Myalgia × 0.958+Neutrophil count × 0.185+Platelet count × 0.004. A cut-off value ≥ 5.245 revealed the maximizing sensitivity of 88.7% and specificity of 95.8% in discriminating AOSD from FUO in the validation group. And AF score improved the accuracy from 82.6% to 93.3% compared with Yamaguchi's criteria. ConclusionsWe developed and validated a new score which can identify AOSD in FUO with higher classification accuracy than Yamaguchi's criteria. Future multi-centric prospective studies need to be designed to confirm the diagnosis value of AF score.

Human brucellosis and fever of unknown origin

BackgroundHuman brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted.MethodsWe retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records.ResultsThe percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05).ConclusionBrucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

Fever of unknown origin: evaluation of 110 classical and HIV-associated cases in the last decade

ABSTRACT Background Fever is one of the critical symptoms of collagen vascular diseases, malignancies, and infectious diseases. Patients with a fever of unknown origin (FUO) were evaluated to determine the etiology. Methods In this study, 110 cases with FUO who were admitted to two hospitals with a total of 800 beds, in which 5000 daily outpatient patients were admitted between 2006 and 2016 have been evaluated retrospectively. Anamnesis and the findings were obtained from hospital records. Patients with a temperature higher than 38.3°C and lasting three weeks or longer without diagnosis despite one week of investigation in the hospital were included as FUO cases in this study. Nosocomial and neutropenic cases were excluded from the present study. Results Fifty-seven patients were male (52%), and the mean age was 40.2 ± 17.2. The distribution of the classic and HIV-associated cases was 85 (77.3%) and 18 (16.4%). Tuberculosis (TB) was the most frequent disease in both groups. The etiology was infectious in 68.2%, autoimmune in 14.5%, and neoplastic in 5.4%. There was no case of collagen vascular disease in the HIV-associated FUO group. Conclusion As a result of our study, infectious diseases and TB were still the leading factors that caused FUO. TB has been notably found higher in the HIV-associated group than the classic group. FUO is usually either a rare cause or an unusual clinical presentation of a well-known infectious disease in Turkey. Therefore, it should be noted that various manifestations of extra-pulmonary tuberculosis may be considered a FUO case.

The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study

BackgroundFever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET).MethodsProspective study to...

Diagnostic accuracy of procalcitonin, interleukin-6 and interleukin-8 for predicting Gram-negative bacteremia in febrile neutropenia patients with acute lymphoblastic leukemia

Background. Currently available biomarkers are not specific and sensitive enough for early detection of bacterial infection in patients with cancer who have febrile neutropenia. The objective of this study was to assess diagnostic accuracy of interleukin-6 (IL-6), interleukin-8 (IL-8) and procalcitonin (PCT) in the identification of Gram-negative bacteremia at the beginning of a febrile episode in pediatric oncology patients with acute lymphoblastic leukemia (ALL). Methods. A total of 40 episodes of febrile neutropenia in 27 childhood cancer patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to the recommendations of manufacturers. Patients were classified into Gram-negative bacteremia (GNB) and fever of unknown origin (FUO) groups. Results. The median concentration of IL-6, IL-8 and PCT were higher in the GNB group compared to the FUO group (65.4 vs. 409.0 pg/ml, P = 0.0025; 166.0 vs. 883.0 pg/ml, P = 0.0002; 0.27 vs. 0.44 ng/ml, P = 0.0169, respectively). The areas under the curves (AUCs) for both IL-6 and IL-8 were 0.94 and 0.93, respectively, indicating that these cytokines discriminated patients with Gram-negative bacteremia with excellent accuracy, whereas PCT had lower diagnostic accuracy (AUC = 0.76). Conclusions. IL-6 and IL-8 evaluation might be used as an additional diagnostic tool for the prediction of Gram-negative bacteremia in pediatric patients with ALL during febrile neutropenia episodes.

The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia

BackgroundPrediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients. MethodsA total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups. ResultsMedian of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently. ConclusionsPCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia.

Significance of Interleukin-6 (IL-6) and C-reactive Protein (CRP) in Children and Young Adults With Febrile Neutropenia During Chemotherapy for Cancer

We evaluated the usefulness of interleukin-6 (IL-6) and C-reactive protein (CRP) at the onset of febrile neutropenia and 72 hours later, in identifying risk groups and assessing response to antibiotic therapy. All episodes of febrile neutropenia were divided in 3 study groups-microbiologically documented infection (MDI), clinically documented infection (CDI), and fever of unknown origin (FUO). Three outcome groups were defined as those responding to first-line antibiotics (R1), those responding to second-line antibiotics (R2), and those requiring antifungal therapy (RAF). Median values of IL-6 and CRP were compared between the groups. There were 57 episodes of febrile neutropenia among 26 patients younger than 25 years during 1 year of study period. On day 1, median IL-6 level was significantly lower in FUO group compared with CDI+MDI groups combined (P < 0.001). Rise in CRP on day 3 was highly significant to differentiate MDI group from other 2 groups (P < 0.001). The CRP also increased significantly on day 3 in RAF (P < 0.001) and R2 (P = 0.002) groups than in R1 group. Low level of IL-6 may help differentiate patients with FUO from those with documented infections. A rising CRP is indicative of serious infection.

The Diagnostic Value of Interleukin-6 and Interleukin-8 for Early Prediction of Bacteremia and Sepsis in Children With Febrile Neutropenia and Cancer

Early diagnosis of sepsis in children with febrile neutropenia and cancer still remains a challenge for modern medicine because of lack of specific laboratory markers and clinical signs especially at the beginning of the infection. The objective of this study was to evaluate the ability of interleukin-6 and interleukin-8 to predict bacteremia and sepsis during the first 2 days in oncohematologic patients with febrile neutropenia. A total of 61 febrile neutropenic episodes in 37 children were studied. Serum samples were collected on day 1 and day 2 from the onset of fever and analyzed using an automated random access analyzer. Neutropenic children with febrile episodes were classified into the following 2 groups: (1) fever of unknown origin group--patients with a negative blood culture--and (2) bacteremia/sepsis group--patients with a positive blood culture or clinical sepsis. High negative predictive values were found on day 1 for interleukin-6 and interleukin-8 (89% and 82%, respectively) for exclusion of bacteremia/sepsis. These interleukins could be used as a screening tool for the rejection of sepsis or bacteremia on the first day of fever in neutropenic children with cancer.

Clinical Features of 66 Lymphoma Patients Presenting with a Fever of Unknown Origin

To investigate the clinical characteristics, diagnostic approaches, short-term efficacy of treatment and prognosis of lymphoma patients presenting with a fever of unknown origin (FUO). We reviewed the records of 132 patients finally diagnosed with lymphoma in Huashan Hospital, half of whom initially presented with a FUO. The other 66 lymphoma patients without a history of FUO were diagnosed within a month when several patients in the FUO group were also diagnosed. The patients presenting with a FUO were predominantly young men (71.21%, p=0.35) characterized by a temperature ≥ 39°C (55/66, 83.33%). Compared with the non-FUO group, patients in the FUO group more often had pancytopenia and hypohepatia, 61.54% with hypoalbuminemia (p<0.0001), 15.50% with significantly elevated lactate dehydrogenase (LDH) (p<0.0001), 92.45% with elevated serum β(2) microglobulin (p=0.017), 93.48% with elevated urine β(2) microglobulin (p=0.002) and 30.77% with elevated alkaline phosphatase (p=0.001). Ninety-four percent of the FUO patients had aggressive lymphomas (p=0.012), with a poor performance status (96.97%, p=0.003), stage III/IV disease (96.97%, p<0.0001), night sweats (21.21%, p=0.026), unexplained weight loss (46.97%, p=0.002) and more than one extranodal site involved (65.15%, p=0.002). The patients in the FUO group also showed poor prognoses, and most of them were in the high-intermediate or high risk classification of the disease (96.61%, p<0.0001), with a low complete remission (CR) rate (61.11% vs. 93.75%, p=0.043). Twenty-one (15.91%) of all the patients were diagnosed based on the finding of lesion sites by Positron Emission Tomography/Computed Tomography (PET/CT) scanning, which had not been detected by conventional scans. Lymphoma presenting as FUO has a rapid progression and poor prognosis, and is difficult to diagnose. PET/CT scans can provide complementary information for an etiological diagnosis of a FUO and biopsy examinations are significant to establish an early diagnosis for patients presenting with a FUO.

Inflammation of unknown origin versus fever of unknown origin: Two of a kind

Objectives A vast literature exists on fever of unknown origin (FUO), characterized by prolonged and perplexing fevers > 38.3 °C. In contrast, no studies are available to guide the approach to inflammation of unknown origin (IUO), defined as prolonged and perplexing inflammation with temperatures < 38.3 °C. We aimed to determine the diagnostic yield, the case-mix, and the outcome of patients with IUO, relative to patients with FUO. Methods We matched 57 patients with IUO to 57 patients with FUO of the same gender (54% male) and a similar age (median: 67 years). Results A diagnosis was established in 35 patients with IUO (61%) and in 33 patients with FUO (58%) ( p = .70). The case-mix did not differ significantly ( p = .43). Non-infectious inflammatory disorders were the dominant diagnostic category in the IUO group (16 patients), while in the FUO group, similar numbers of malignancies [10], infections [9], and non-infectious inflammatory diseases [9] were diagnosed. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan contributed comparably to the diagnosis in both groups (in 18 of 50, 36%, patients with IUO and in 13 of 40, 33%, patients with FUO) ( p = .83). In both groups, 7 patients (12%) died during an average follow-up of 1 year. Conclusion Diagnostic yield, case-mix, contribution of FDG-PET scan and vital outcome were similar in patients with IUO and FUO. These data suggest that the 38.3 °C boundary may be arbitrary and that the diagnostic approaches used in FUO can be applied to IUO.

The predictive value of interleukin-8 (IL-8) in hospitalised patients with fever and chemotherapy-induced neutropenia

Aim To demonstrate whether serum Interleukin-8 (IL-8) is a relevant parameter to select hospitalised patients with chemotherapy-induced neutropenic fever with low or high probability of infection. Results 90 assessable febrile episodes in 73 patients were evaluated; 46% of the febrile episodes were microbiologically documented infection (MDI), 8% clinical documented infection (CDI), and 47% fever of unknown origin (FUO). Median IL-8 level was lower in the FUO group compared to CDI and MDI ( p < 0.0005). In 45 of 48 episodes (94%) with CDI/MDI, IL-8 level at the start was ⩾60 ng/l while in 18 of 21 episodes (86%) with IL-8 level <60 ng/l, no infectious cause was demonstrated. FUO and CDI/MDI patients with IL-8 ⩾60 ng/l and responsive on antibiotic treatment showed a decline of IL-8 levels within days in contrast to non-responding patients. Conclusions Serum IL-8 level can be a useful marker to identify hospitalised FUO patients with low probability of infection.

Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients?

Plasma concentrations of procalcitonin (PCT) have been shown to be elevated in bacterial and fungal infections. In contrast to C-reactive protein (CRP), PCT is not elevated in inflammations of noninfectious origin. Febrile inflammatory conditions are frequent in patients with hemato-oncological diseases. A reliable marker to discriminate infectious inflammations from drug-related and tumor-associated fever is still lacking. To evaluate the impact of PCT in this setting, PCT and CRP were prospectively measured in 95 febrile hemato-oncological patients. Infections could be identified in 40 of 95 patients: 38 of 95 had fever of unknown origin (FUO), 9 patients were suspected to suffer from drug-related fever, and 8 patients from tumor-associated fever. In the noninfection group (drug-related and tumor-associated fever), PCT levels were significantly lower than in patients with infections (P<0.001) or FUO (P<0.001). Differences were still highly significant comparing patients with suspected drug-related or tumor-associated fever alone with the infection or the FUO cohort. All eight patients with tumor-associated fever as well as eight of the nine patients with drug-related fever had PCT levels within the normal range (<0.5 micro g/l). CRP values only partially allowed discrimination between the various subgroups. Differences were significant between patients with drug-related fever and the infection (P=0.001) or FUO group (P=0.004). However, as CRP levels were far above the normal range also in the patients with drug-related fever, the significance of individual values was rather limited. In conclusion, PCT may provide useful additional information to assess the clinical significance of febrile conditions. PCT may facilitate the decision on when to initiate antimicrobial or cytotoxic therapy.

Fever and neutropenia: bacterial etiology revealed by serological methods

In a prospective study, 91 episodes of fever in neutropenic children with cancer were evaluated. Fifteen episodes were septicemias, verified by a positive blood culture, 62 were fevers of unknown origin, 6 were focal infections and 8 were of other etiologies (i.e. drug fevers and viral infections). Serum antibody responses to bacteria were measured in paired sera by an enzyme immunoassay method. Bacterial infection was demonstrated serologically in 20% of documented septicemias, in 35% of fevers of unknown origin and occasionally in the other groups. Tests were available and found positive in the fever of unknown origin group for Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and enterobacteria. Some had multiple etiology. In conclusion, bacterial serology is a promising method of identifying bacterial etiology in fever of otherwise unknown origin in neutropenic children with cancer.