Etiology Of Fever Of Unknown Origin Research Articles

Fever of unknown origin in pediatrics: causes and clinical characteristics in a single centre experience

BackgroundFever of unknown origin (FUO) is a common condition worldwide in children that remains a diagnostic challenge. The causes of FUO vary depending on the patient's age, residency, and the time of study. Therefore, this study aimed to identify the common aetiologies of FUO at Alexandria University Children’s Hospital under the current diagnostic abilities and newly emerging diseases.MethodsThe current prospective observational study included all children fulfilling the definition of FUO admitted at Alexandria University Children's Hospital from January 2020 to December 2021 using a steps approach for investigations.ResultsA total of 110 children with fever of unknown origin (FUO) were included in this study; the average duration of fever was 36.76 ± 31.73 days. In most of the enrolled cases 105/110 (95.4%) the definite etiology of FUO was identified. The common causes were collagen vascular diseases (30.9%), infectious diseases (28.2%), miscellaneous conditions (19.1%), and malignancy (17.3%). Among collagen vascular diseases, systemic lupus erythematosus (SLE) (47.1%) and systemic onset juvenile idiopathic arthritis (sJIA) (38.2%) were the most common. In the infectious category, Katayama fever (16.1%), brucellosis (12.9%), and urinary tract infection (UTI) (12.9%) were the most frequently observed. Post-Covid MIS-C (52.4%) was the most common in the miscellaneous category. Children in the infectious category had significantly higher neutrophil [5.76 (2.28–7.92) × 10^3/µl] and lymphocytic counts [ 4.2 (2.04–5.91) × 10^3/µl]; (P < 0.001 and < 0.010 respectively). Moreover, in the collagen category the median lymphocytic count was lower [1.95 (1.47–2.73) × 10^3/µl] with a significantly (P < 0.010) higher neutrophil/ lymphocyte ratio [2.30 (1.53–3.91)].ConclusionCollagen vascular diseases, infectious diseases, miscellaneous, and malignancy were the most common causes of FUO. Katayama fever, urinary tract infections (UTI), and brucellosis were the most common causes in the infectious category. Post-Covid MIS-C and hemophagocytic lymphohistiocytosis were the most common diagnoses in the miscellaneous category.

Distribution of the causes of fever of unknown origin in China, 2013-2022.

Fever of unknown origin (FUO) has long been a cause for concern among clinicians, and its spectrum has evolved with progress in medicine. This study aimed to investigate the distribution of causes of FUO in China between 2013 and 2022 to facilitate the clinical understanding of the etiology of FUO. Case series of FUO in China published between 2013 and 2022 were retrieved from PubMed, Wanfang Data, and CNKI databases and retrospectively analyzed. The rates of different causes of FUO were calculated, and these data were compared with previously published distributions of causes of FUO in China. The causes of FUO with the highest rates from the 51 identified case series (n = 19,874) were infectious, autoimmune, and neoplastic diseases (59.6%, 14.3%, and 7.9%, respectively). A comparison of a subset (43 case series subdivided by disease category, n = 16,278) with previously reported data revealed an increased rate of FUO attributed to infectious diseases in the past decade, with a significantly higher rate attributed to bloodstream infections (10.0% vs. 4.8%) and a significantly lower rate attributed to tuberculosis (9.3% vs. 28.4%), compared with the rates from the previous period. In contrast, the rates of FUO attributed to both autoimmune and neoplastic diseases decreased, with significantly decreased rates attributed to adult-onset Still's disease among autoimmune diseases (4.6% vs. 8.5%) and lung cancer among neoplastic diseases (0.6% vs. 1.6%). Despite an overall increase in the rate attributed to infectious diseases, that attributed to tuberculosis has decreased. The rates attributed to both autoimmune and neoplastic diseases have also decreased.

Significance of F-18 FDG PET/MRI in the search for the etiology of inflammation of unclear origin and fever of unknown origin

PurposeTo evaluate the contribution of F-18 FDG-PET/MRI in the search for the etiology of the inflammation of unknown origin (IUO) and fever of unknown origin (FUO). Material and methodsThe study included 104 patients who underwent F-18 FDG-PET/MRI for IUO or FUO. The sensitivity, specificity, predictive values of the PET/MRI findings in relation to the final diagnosis of IUO/FUO were evaluated. A five-point Likert scale was used to semiquantitatively assess the probability of the cause of IUO/FUO based on PET/MRI finding. Furthermore, clinical (fever, arthralgia, weight loss, night sweats, age) and laboratory (C-reactive protein, leukocytes) parameters were monitored and compared with the true positivity rate of PET/MRI. ResultsIn patients with definitively identified etiology of FUO and IUO, FDG-PET/MRI achieved a sensitivity of 96 %, specificity of 82 %, and positive and negative predictive values of 92 and 90 %. The cause of the IUO was determined in 71 patients (68.3 %). In 33 (31.7 %) patients, the etiology of IUO/FUO remained unknown, while in 25 (75.8 %) of them the symptoms resolved spontaneously and in 8 (24.2 %) patients they persisted without explanation even after 12 months of the follow-up. The most significant parameter in relation to subsequent PET/MRI finding was increased level of CRP, which was present in 96 % of true positive PET/MRI and normal CRP level was present in 56 % of true negative PET/MRI. ConclusionBased on this study, FDG-PET/MRI is a suitable alternative for the investigation of IUO/FUO, this imaging technique has a very high sensitivity and negative predictive value.

18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO).

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

Unusual Case of Pseudomembranous Colitis Presenting as Fever of Unknown Origin Diagnosed by Tc-99m-HMPAO-labeled Leukocytes SPECT/CT.

The fever of unknown origin (FUO) represents a complex diagnostic challenge due to the wide range of etiologies that could cause it, including neoplastic, infectious, rheumatic/inflammatory, and miscellaneous disorders. Several nuclear medicine techniques have proven to be valuable tools for guiding etiologic diagnosis in the setting of FUO. One of these is technetium-99m (Tc-99m)-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte scintigraphy, which is a diagnosis method that allows in most cases the localization and evaluation of the extension of an occult infection. This paper presents an uncommon case of pseudomembranous colitis without diarrhea as etiology of FUO diagnosed by Tc-99m-HMPAO-labeled leukocytes.

Predictors for spontaneous resolution of classical FUO in patients undergoing PET-CT.

Spontaneous resolution is common in patients with classic fever of unknown origin (FUO). Identifying predictors of spontaneous resolution could reduce the usage of unnecessary, invasive tests or empirical therapy, and furthermore reduce patient anxiety. Identify predictors associated with spontaneous resolution of FUO. A single center, retrospective, cohort study. All hospitalized patients who underwent an [18F] FDG PET-CT scan for the investigation of classical FUO between 1/2012 and 1/2020 were included. We compared patients with spontaneous resolution of fever and clinical symptoms, to those who were diagnosed with a specific etiology of FUO (subdivided to infectious diseases, non-infectious inflammatory diseases (NIID), and malignancies). Epidemiologic characteristics as well as laboratory and PETCT study results were compared. Variables that were found to be associated with spontaneous resolution of FUO on univariate analysis (p < 0.1) were entered into a multivariable regression analysis. The results are reported as odds ratios (OR) and 95% confidence intervals (CI). A total of 303 patients were hospitalized for the investigation of classical FUO and underwent complete assessment. Fever resolved without a diagnosis in 84/303 patients (28%). Variables that were associated with spontaneous resolution of FUO on multivariable analysis included: no anemia, no hypoalbuminemia and no pathological FDG uptake on PET-CT. In 17.8% (15/84) of studies, PET-CT yielded false-positive results that led to additional unnecessary, invasive investigation. Patients without anemia or hypoalbuminemia, and those without uptake on PET-CT are more likely to have spontaneous resolution of classical FUO.

Metagenomic next-generation sequencing for the diagnosis of fever of unknown origin in pediatric patients with hematological malignancy

Background and aimsThe aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in identifying microbiological etiologies in pediatric patients with hematological malignancies undergoing fever of unknown origin (FUO). MethodsA total of 147 children with hematological malignancy suffering febrile diseases without definite microbiological etiologies under conventional tests were enrolled. The clinical record, serum inflammatory biomarkers and mNGS results were analyzed. ResultsAt least one microorganism was identified by mNGS in 112 of 147 patients (76.2 %). Two or more types of organisms were detected simultaneously in 35.7 % (40/112) of samples. Of the 112 cases with positive mNGS results, the reported microorganisms were considered as etiologies of fever in 50 (44.6 %) cases. The initial antimicrobial regimens were adjusted according to the mNGS results in 48 cases, with 41 patients’ febrile diseases resolved. Totally, 27.9 % (41/147) of patients benefit from mNGS. High IL-6 (>390 pg/mL) level was associated with bacterial infection and could help to interpret the results of mNGS. ConclusionmNGS is a novel approach to determine the microbiological etiology of FUO in hematological malignancy patients, which benefits about a quarter of all patients tested. Integration of IL-6 can improve the diagnostic precision of bacterial infection.

CT-296 Isolated Bone Marrow Infiltration by Streptococcus Pneumoniae: An Unusual Etiology of Fever of Unknown Origin

Fever of unknown origin (FUO) in adults is defined as a temperature >38.3°C lasting for more than 3 weeks with no obvious source despite appropriate investigation. The differential diagnoses are infections, malignancies, autoimmune conditions, and miscellaneous. To our knowledge, isolated bone marrow infiltration by Streptococcus pneumoniae without bacteremia has not been reported yet in the literature. We report the case of a 48-year-old female patient, previously healthy, who presented for persistent fever of one-week duration. Initially, she complained of a 39°C fever without other associated symptoms except for daily night sweats. A complete infectious workup, including a full-body CT scan and screening for fungal or bacterial etiologies, was negative. Additionally, both transthoracic and transesophageal echocardiograms eliminated any signs of endocarditis. Subsequently, over the next two weeks, a complete autoimmune workup to test for a possible underlying rheumatologic disease was done but was all negative. To complete the endless FUO workup and in view of high suspicion of a malignancy, the patient performed an (FDG) PET CT scan along with a bone marrow biopsy that were both negative for any signs of malignancy, thus excluding any lymphoproliferative disease. One month after persistent fever, pan-cultures were serially repeated and remained negative. After developing a grade I thrombocytopenia, bone marrow aspirate with bone marrow culture were performed: no signs of malignancy or infiltration were found on the medullogram, but surprisingly, and after 48 hours of incubation, the bone marrow cultures turned positive for multi-sensitive Streptococcus pneumonia. We treated the patient with intramuscular ceftriaxone for an empirical period of 2 weeks. After only 3 doses of ceftriaxone, the fever subsided and the night sweats started to decrease gradually. After receiving a total of 14 days of antibiotics, we only monitored the patient clinically, without repeating the bone marrow cultures. Clinicians must be aware of this rare and unusual etiology of FUO. Bone marrow studies are routinely performed to exclude any lymphoproliferative disorder. In this perspective, we could draw a bone marrow culture while performing the regular aspiration studies to exclude possible isolated bone marrow infiltration by bacterial microorganisms.

Fever of unknown origin

Fever of unknown origin (FUO) is a diagnosis that describes a prolonged febrile illness without an established cause, despite investigations. From the first definition of the medical condition (given by Petersdorf and Beeson in 1961) the diagnostic criteria have changed over time, intending to improve the management and outcome of these patients. The main causes of FUO fall into 4 categories: infectious, non-infectious (inflammatory), neoplastic and diverse causes. The etiology of FUO has changed over time, due to ever-changing disease patterns and the development of diagnostic techniques. A significant percentage of patients with FUO remain without an etiologic diagnosis, despite advanced diagnostic tests. Gathering potentially diagnostic clues through history, physical examination and nonspecific key paraclinical abnormalities is the basis for the diagnosis of FUO.

ETIOLOGY AND CLINICAL PROFILE OF FEVER OF UNKNOWN ORIGIN IN CHILDREN-A PROSPECTIVE OBSERVATIONAL STUDY IN PEDIATRICS DEPARTMENT OF DMCH, LAHERIASARAI, BIHAR

Background: Fever of unknown origin (FUO) is an important cause of morbidity and mortality in children, especially in tropical countries with varied aetiology and clinical presentation. Aim of this study is to determine the aetiology and outcome of FUO in Indian children. Study design is Prospective, observational study. Methods: We enrolled 75 children aged 1 to 12 years who were admitted with fever &gt;8 days to the pediatric department of DMCH, Laheriasarai, Bihar from November 2019 to June 2020. Initial evaluation included complete blood count, peripheral smear, urine analysis, chest radiography, blood culture and tuberculin test. Results: In 72 children (96%), a definitive diagnosis could be established, whereas 3 children (4%) remained undiagnosed. Most common aetiology of FUO was infectious disease (90.6%) followed by malignancy (4%) and collagen vascular disease (1.3%). Among the infections group, scrub typhus was found to be the commonest aetiology (52%). Conclusions: Infections were the most common etiological factor for FUO in children aged 1-12 years of our region.

Fever in the tropics: aetiology and clinical profile of fever of unknown origin in children-a prospective observational study in a tertiary care hospital in South India

Background: Fever of unknown origin (FUO) is an important cause of morbidity and mortality in children, especially in tropical countries with varied aetiology and clinical presentation. Aim of this study is to determine the aetiology and outcome of FUO in Indian children. Study design is Prospective, observational study. Methods: We enrolled 75 children aged 1 to 12 years who were admitted with fever &gt;8 days to the paediatric department from January 2015 to August 2016. Initial evaluation included complete blood count, peripheral smear, urine analysis, chest radiography, blood culture and tuberculin test. Results: In 72 children (96%), a definitive diagnosis could be established, whereas 3 children (4%) remained undiagnosed. Most common aetiology of FUO was infectious disease (90.6%) followed by malignancy (4%) and collagen vascular disease (1.3%). Among the infections group, scrub typhus was found to be the commonest aetiology (52%).Conclusions: Infections were the most common etiological factor for FUO in children aged 1-12 years of our region.

Aetiology of Fever of Unknown Origin: One-Year Experience in a Tertiary Care Hospital of Bangladesh

Background: Fever of unknown origin (FUO) is not an uncommon problem in general medical practice. Sometimes extensive investigations fail to reach an aetiological diagnosis; on the other hand, in few cases, fever resolves spontaneously. This study was aimed to evaluate the aetiology of FUO in a tertiary care setting.Methods: This cross-sectional study was done in the Department of Internal Medicine of BIRDEM General Hospital, Dhaka, Bangladesh from July 2012 to June 2013.Results: Among the 33 patients studied (1.23% of total admissions), 22 (66.7%) were male. Mean age of the study population was 40.2±7.9 years. Most patients (84.8%) were diabetic. Infection (20, 60.6%) was the commonest cause, followed by malignancy (9, 27.3%). Among the infective causes (20), extra-pulmonary tuberculosis (5, 25%) was the commonest, followed by liver abscess (4, 20%). Other less common causes were Kala-azar (1), malaria (2), histoplasmosis (2), melioidosis (1), cholecystitis (1), renal abscess (1), rickettsial fever (1), apical dental abscess (1) and infective endocarditis (1). Non-Hodgkin’s lymphoma (6), renal cell carcinoma (2) and hepatocellular carcinoma (1) constituted the malignant causes of FUO in this series. Systemic lupus erythematosus was the aetiology of FUO in 1 case. One case remained undiagnosed and 2 patients left hospital before a definite diagnosis could be made.Conclusion: Extra-pulmonary tuberculosis and non-Hodgkin’s lymphoma were the two most common causes of FUO in this study. Repeated history taking, clinical examinations and careful stepwise investigations can diagnose the aetiolgy in most cases of FUO.Birdem Med J 2016; 6(1): 7-11

Clinico-epidemiological profile of fever of unknown origin in an Egyptian setting: A hospital-based study (2009-2010).

Fever of unknown origin (FUO) is one of the most challenging diagnostic dilemmas in the field of infectious diseases and tropical medicine. Clinicians should use the frequency distribution of disorders causing FUO to guide their diagnostic approach in patients with prolonged, unexplained fevers meeting the definition of FUO. The present study was undertaken to examine the etiologies, clinico-epidemiologic profile, and prognosis of classical FUO in patients reporting to the Alexandria Fever Hospital in Egypt. Records of 979 patients admitted to the fever hospital (from January 2009 to January 2010) and diagnosed as having FUO were examined carefully. FUO was defined as three outpatient visits or three days in the hospital without elucidation of cause of fever. A total of 979 cases (57.0% males and 43.0% females), with ages ranging from 0.2 to 90 years, were investigated. The mean duration of fever before hospitalization was 31 ± 10 days. The etiology of FUO was delineated in 97% of cases, and only 3% remained undiagnosed. Diagnoses were grouped into five major categories. Infectious causes of FUO were strongly associated with better outcome (73.7% improved). Smoking, contact with animals or birds, drug addiction, and HIV seropositivity were important risk factors associated with infections. Infections are the most common cause of FUO, followed by collagen vascular diseases, in our region. A three-step diagnostic work-up approach is recommended to be applied in Egypt in order to improve the quality of medical service provided to FUO patients.

Clinical approach to fever of unknown origin in children.

Fever of unknown origin (FUO) can be caused by many clinical conditions and remains a diagnostic challenge in clinical practice. The etiology of FUO varies markedly among different age groups, geographic areas, and seasons. A four-stage investigative protocol for FUO is widely applied in clinical practice. The aim of this study was to evaluate the usefulness of this four-stage protocol for identifying the etiology of FUO in children. We enrolled children younger than 18 years of age who were admitted to the Taichung Veterans General Hospital during the period from January 2006 to December 2014 with FUO persisting for more than 3 weeks. The four-stage FUO investigative guideline was used to evaluate the etiology of fever in all patients enrolled in the study. The etiology of FUO was identified in 79 (84.9%) of the 93 patients enrolled in the study. The most common cause of FUO was infectious disease (37.6%), followed by malignancy (17.2%), miscellaneous disease (16.1%), and collagen vascular disease (14.0%). With respect to the four-stage survey of FUO, 36 of the 79 patients (45.6%) were identified in Stage 3, 28 patients (35.4%) in Stage 2, 13 patients (16.5%) in Stage 4, and only two patients (2.5%) in Stage 1. A well-designed systemic review of the epidemiological information, medical history, physical examination, laboratory analysis, and adequate invasive procedures provide adequate data to identify the most common causes of FUO in children.

PET Index of Bone Glucose Metabolism (PIBGM) Classification of PET/CT Data for Fever of Unknown Origin Diagnosis

ObjectivesFever of unknown origin (FUO) remains a challenge in clinical practice. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is helpful in diagnosing the etiology of FUO. This paper aims to develop a completely automatic classification method based on PET/CT data for the computer-assisted diagnosis of FUO.MethodsWe retrospectively analyzed the FDG PET/CT scan of 175 FUO patients, 79 males and 96 females. The final diagnosis of all FUO patients was achieved through pathology or clinical evaluation, including 108 normal patients and 67 FUO patients. CT anatomic information was used to acquire bone functional information from PET images. The skeletal system of FUO patients was classified by analyzing the standardized uptake value (SUV) and the PET index of bone glucose metabolism (PIBGM). The SUV distributions in the bone marrow and the bone cortex were also studied in detail.ResultsThe SUV and PIBGM of the bone marrow only slightly differed between the FUO patients and normal people, whereas the SUV of whole bone structures and the PIBGM of the bone cortex significantly differed between the normal people and FUO patients. The method detected 43 patients from 67 FUO patients, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 64.18%, 95%, 93.48%, 72.73%, and 83.33%, respectively.ConclusionThe experimental results demonstrate that the study can achieve automatic classification of FUO patients by the proposed novel biomarker of PIBGM, which has the potential to be utilized in clinical practice.

Fever of Unknown Origin (FUO) in HIV Infection in the Era of Antiretroviral Treatment (ART) in India: Development of a Simple Diagnostic Algorithm

Objective: Fever of unknown origin (FUO) is a challenging problem among people living with HIV (PLHIV). With increasing access to Anti-retroviral treatment (ART), the spectrum of causes of FUO has evolved in the developed world. This study evaluated the etiology of FUO among PLHIV in the era of ART in India. Methodology: This prospective study was conducted at a tertiary-care institution in New Delhi, India. Sixty four PLHIV with a diagnosis of FUO were assessed by detailed clinical evaluation and immunological assessment. Specific investigations to identify the etiology of fever: microbiological and radiological investigations, bone marrow and histopathological examination of biopsies were performed. A simple diagnostic algorithm for FUO was developed based on the findings. Original Research Article Anuradha et al.; BJMMR, 7(10): 839-846, 2015; Article no.BJMMR.2015.396 840 Results: Sixty five episodes of FUO were studied. Seventy percent of subjects were men, 76% were <40 years of age, and 39% were receiving ART. The mean CD4 count was 156.57±178.43 cells/mm (5 to 1144 cells /mm) and 23% patients had CD4 counts <50 cells/mm. The mean duration of fever was 11.26±8.54 weeks. Infections were the most common cause for FUO, with Tuberculosis the most common (61.54%), particularly disseminated tuberculosis (41.54%). Cryptococcal meningitis (7.69%), bacterial pneumonia (4.62%), pyogenic abscesses (4.62%), Pneumocystis jirovecii pneumonia (PCP) (3.08%), visceral leishmaniasis (3.08%) were other infections observed. Non-infectious etiologies including lymphoma (4.62%) and progressive multifocal leucoencephalopathy (PMLE) (3.08%) were also seen. The etiology remained undiagnosed in 6.15% episodes. Importantly, two or more concurrent etiologies of fever were seen in 60% of patients. Conclusion: Infections especially Tuberculosis remain the most common cause of FUO in PLHIV even in the era of ART in developing countries like India. Multiple concurrent infections and a rising trend to non-infectious causes are being observed. A simple diagnostic algorithm will help diagnose majority of FUO even at the peripheral centers.

Fever of Unknown Origin in Children: A 6 year- Experience in a Tertiary Pediatric Egyptian Hospital.

Fever of unknown origin (FUO) is among the most conditions which poses challenge in diagnosis. The presence of information on regional patterns of FUO will shorten the time for diagnosis and reduces health services costs. There are almost no previous studies describing the etiology of FUO in children of Egypt or nearby countries. To determine different causes of FUO and the possible diagnostic procedures. Data of patients with FUO, presented to the Infectious Diseases Unit of Mansoura University Children Hospital, were retrospectively collected in a 6 year-period from May 2006 to May 2011. The study included children with a fever of 38.3° C or more documented by a health care provider and for which the cause could not be identified after 3 weeks of evaluation as an outpatient or after a week of evaluation in hospital. Patients were then categorized into 5 groups. 127 patients met the diagnostic criteria. Infectious diseases were the commonest causes of FUO in 46 cases (36.22%) followed by the miscellaneous causes in 38 cases (29.9%). Meanwhile, collagen vascular diseases and malignancy were diagnosed in 13 cases (10.2%) and 10 cases (7.87%) respectively. While, 20 cases (15.75%) remained undiagnosed. Infectious diseases are the commonest cause of FUO. The delay in diagnosis was due to atypical presentations or inappropriate use of antibiotic prior to the referral. Non infectious causes, malignancy and collagen or vascular disorders were diagnosed in rest of the patients. However, about 15% of our patients remained undiagnosed. The diagnosis was established by non-invasive means in more than two-third of the cases.

Role and interpretation of fluorodeoxyglucose‐positron emission tomography/computed tomography in HIV‐infected patients with fever of unknown origin: a prospective study

The aim of the study was to evaluate prospectively the usefulness of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in investigation of fever of unknown origin (FUO) in HIV-positive patients and to determine whether HIV viraemia impacts on FDG-PET/CT performance. The FDG-PET/CT results of 20 HIV-infected patients with FUO were analysed and compared with the FDG-PET/CT results of 10 HIV-infected viraemic patients without FUO. The performance of FDG-PET/CT for identifying the aetiology of FUO was assessed. Final diagnosis for FUO was based on histopathology, microbiological assays, or clinical and imaging follow-up. FDG-PET/CT contributed to the diagnosis or exclusion of a focal aetiology of the febrile state in 80% of patients with FUO. The presence of increased FDG uptake in the central lymph node has 100% specificity for focal aetiology of fever, even in viraemic patients. The absence of hypermetabolic central lymph nodes in FUO patients has 100% negative predictive value for focal disease. Lymph node biopsy in central hypermetabolic areas allowed, in 100% of cases, identification of underlying disease in patients with FUO. Biopsy of peripheral lymph nodes should be performed in lymph nodes with maximum standardized uptake value (SUVmax) ≥ 6-8 (sensitivity 62.5%; specificity 75%) and avoided in lymph nodes with SUVmax = 0-4 (specificity 0%). High HIV viraemia does not prevent correct interpretation of FDG-PET/CT. As in HIV-negative patients, we confirm the usefulness of FDG-PET/CT in investigation of FUO in HIV-positive patients even if they are viraemic.

Major causes of fever of unknown origin at Peking Union Medical College Hospital in the past 26 years

Background Despite the recent advances in medicine, fever of unknown origin (FUO) remains a diagnostic and therapeutic challenge even to expert physicians. To increase the knowledge of FUO, we conducted a retrospective study to investigate the causes of FUO and the change of major causes of FUO during the past 26 years. Methods The clinical data were retrospectively analyzed from 997 patients with FUO hospitalized at the Peking Union Medical College Hospital (PUMCH) between January 2004 and October 2010. Furthermore, the results were compared to that reported in previous studies of FUO in PUMCH since 1985. Results Of the 997 FUO cases, definite diagnosis was eventually achieved in 797 (79.9%) patients. The most common cause of FUO was infectious diseases (479 cases, 48.0%), with tuberculosis accounting for 45.3% (217/479) of the cases of infections. One hundred and sixty-eight (16.9%) patients were diagnosed with connective tissue diseases, with Still's disease and vasculitis accounted for 31.5% (53/168) and 24.4% (41/168) of this category, respectively. Neoplasms and miscellaneous causes were found in 7.9% (79/997) and 7.1% (71/997), respectively. However, no definite diagnosis had been made in the remaining 200 (20.1%) cases until they were discharged from the hospital. Conclusions During different periods, infectious diseases, especially tuberculosis, were the leading etiology of FUO and the proportion of tuberculosis had no significant difference. While the frequency of neoplasms was descending, the proportion of lymphoma in neoplasm was ascending; the frequency of undiagnosed cases was increasing, but in most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data.

Unexpected Significantly Reduced FDG Uptake in the Cerebrum Compared Against Normal Liver Uptake in a Dying Patient

F-18 FDG PET-CT scanning plays an important role in the management of fever of unknown origin (FUO). Some elderly patients with FUO can be in their terminal stage of life. An elderly woman was referred for a PET-CT scan to find the etiology of FUO. The scan was inconclusive but showed significantly reduced FDG uptake in the brain and heart, despite normal physiological uptake in the liver and bowel. The patient deceased within the hour post scan. Contrary to common belief, we have shown that cerebral glucose metabolism via cerebral perfusion may be compromised before hepatic and bowel perfusion in a dying patient. Conflict of interest:None declared.