Causes Of Fever Of Unknown Origin Research Articles

Clinical Etiologies of Fever of Unknown Origin in 500 Cases.

To investigate the distribution and change of the causes of fever of unknown origin(FUO). The clinical data of 500 inpatients with FUO in our center between December 2003 and June 2014 were retrospectively analyzed. The diagnostic methods,etiologies,and their possible relationship with age,sex,fever duration,and period. Of these 500 FUO patients,452(90.4%)were confirmed to be with fever caused by conditions including infectious diseases [(n=231,46.2%;e.g.tuberculosis(32.9%,76/231)],connective tissue diseases(CTD)(n=99,19.8%),neoplasms(n=58,11.6%),miscellaneous causes(n=64,12.8%). The causes were not identified in 48 cases(9.6%).The proportion of CTD in female patients was significantly higher than that in male patients(26.3% vs. 14.5%,P=0.025),whereas the proportion of neoplasms in male patients was significantly higher than that in female patients(14.5% vs. 8.0%,P=0.001). Infectious diseases was the most common cause in all age groups,CTD ranked the second in the 21-39-year group and 40-59-year group,and neoplasm was the second most coomon cause in the over 60 year group. Thus,the distribution of FUO etiologies significantly differed in different age groups(χ(2)=43.10,P=0.000). The duration of fever in patients with neoplasms [60(28,90)d] was longer than that in patients with infectious diseases [28(21,42)d,Z=-4.168,P=0.000] or CTD [30(21,60)d,Z=-2.406,P=0.016)]. Compared with the level in 2003-2008,the proportion of CTD significantly increased in 2009-2014(13.7% vs. 23.8%,χ(2)=8.598,P=0.003),along with the dicrease of the proportions of infectious diseases,neoplasms and miscellaneous diseases were decreased(all P>0.05). Infectious diseases(in particular,tuberculosis)remains the major cause of FUO. CTD and neoplasms also play important roles in the development of FUO. The distributions of the FUO etiologies have certain differences in terms of age,sex,duration of fever,and period.

Fever of unknown origin

More than 50years after the first definition of fever of unknown origin (FUO), it still remains a diagnostic challenge. Evaluation starts with the identification of potential diagnostic clues (PDCs), which should guide further investigations. In the absence of PDCs a standardised diagnostic protocol should be followed with PET-CT as the imaging technique of first choice. Even with a standardised protocol, in a large proportion of patients from western countries the cause for FUO cannot be identified. The treatment of FUO is guided by the final diagnosis, but when no cause is found, antipyretic drugs can be prescribed. Corticosteroids should be avoided in the absence of a diagnosis, especially at an early stage. The prognosis of FUO is determined by the underlying cause. The majority of patients with unexplained FUO will eventually show spontaneous remission of fever. We describe the definition, diagnostic workup, causes and treatment of FUO.

Fever in Children and Fever of Unknown Origin.

Fever is the most common symptom in children and can be classified as fever with or without focus. Fever without focus can be less than 7 d and is subclassified as fever without localizing signs and fever of unknown origin (FUO). FUO is defined as a temperature greater than 38.3 °C, for more than 3 wk or failure to reach a diagnosis after 1 wk of inpatient investigations. The most common causes of FUO in children are infections, connective tissue disorders and neoplasms. Infectious diseases most commonly implicated in children with FUO are salmonellosis, tuberculosis, malaria and rickettsial diseases. Juvenile rheumatic arthritis is the connective tissue disease frequently associated with FUO. Malignancy is the third largest group responsible for FUO in children. Diagnostic approach of FUO includes detailed history and examination supported with investigations. Age, history of contact, exposure to wild animals and medications should be noted. Examination should include, apart from general appearance, presence of sweating, rashes, tonsillitis, sinusitis and lymph node enlargement. Other signs such as abdominal tenderness and hepatosplenomegly should be looked for. The muscles and bones should be carefully examined for connective tissue disorders. Complete blood count, blood smear examination and level of acute phase reactants should be part of initial investigations. Radiological imaging is useful aid in diagnosing FUO. Trials of antimicrobial agents should not be given as they can obscure the diagnosis of the disease in FUO.

Diagnosis of Brachiocephalic Thrombophlebitis as the Cause of Fever of Unknown Origin by 18F-FDG-PET/CT.

Fever of unknown origin (FUO) represents a challenge in diagnosis and treatment. The role of 18Ffluorodeoxyglucose positron emission tomography (FDG-PET) / computed tomography (CT) in the differential diagnosis of this entity is presently well established. We report the case of a patient with infectious/inflammatory symptoms but no evident localization and subsequent relapse, in which PET/CT showed its ability to not only determine the exact localization of a thrombophlebitic focus as cause of FUO, but also to monitor and determine the success of treatment. After performing a FDG-PET/CT and detecting a thrombophlebitis in the brachiocephalic vein, low molecular heparins were introduced in the course of therapy. Soon (about 24 hours) thereafter, clinical symptoms significantly decreased and could no longer be observed. After continuing the antibiotic and anticoagulant therapy for 4 weeks, a follow-up PET/CT scan was performed. That scan no longer showed abnormal uptake in the previous intravascular localization. Consequently, we suggest that PET/CT is a diagnostic modality feasible to identify and monitor therapy response of intravascular thrombophlebitic foci.

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.

Predictive Significance of Peripheral Blood Smears in Patients with Fever of Unknown Origin: A Retrospective Study of 2871 Cases.

Fever of unknown origin (FUO) is a common manifestation and diagnostic problem especially in primary care. Pointing out a diagnosis of FUO often requires numerous noninvasive and invasive procedures. Peripheral blood (PB) smear examination frequently provides many timely and valuable diagnostic clues in various disorders. Few assessments of PB smear morphologic examinations used in the diagnostic evaluation of FUO have been reported. To determine whether PB smears have important roles in exploring the causes of FUO, we collected PB smears of 2871 FUO patients from Beijing Chao-yang Hospital affiliated to Capital Medical University from September 2012 to August 2014. Combined with relevant clinical data, we analyzed the PB morphologic features in all the FUO patients. We found the presence of atypical lymphocytes (64.33%), nuclear left shift (46.33%), toxic granulation, vacuolization, and 4 cases of malaria in FUO patients, markedly more than the health control group (p < 0.05), and morphologically consistent with the diagnosis of infectious diseases. Notably, the presence of blasts or immature cells in 26 cases (9%o) and the abnormal changes of leukocytes, erythrocytes or platelets in 4 cases provided predictive information for exploring the causes of FUO, followed by bone marrow smears and other procedures to further confirm the diagnosis as hematological diseases, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), Evans syndrome, agranulocytosis, immune thrombocytopenic purpura (ITP). Our findings demonstrate that a timely and careful observing of PB smears is helpful for clarifying the diagnosis and contributes to appropriate treatment in patients with FUO.

Prevalence of malignancy in patients with fever of unknown origin (FUO) demonstrated in 18F-FDG PET-CT – prospective multi-centre study

Purpose 18F-FDG PET-CT plays an important role in the management of fever of unknown origin. FUO is defined as “body core temperature <38.3°C on several occasions lasting for <3 weeks but no cause found despite routine clinical investigations for <1 week in hospital”. Malignancy is an important cause of FUO, and the aim of this study is to demonstrate prevalence of malignancy as a cause of FUO demonstrated in PET-CT.

Possibility of scrub typhus in fever of unknown origin (FUO) cases: An experience from Rajasthan

Fever of unknown origin (FUO) has multiple causes. Scrub typhus is less known cause of FUO in India. The present study reports a recent epidemic of scrub typhus amongst cases of FUO from different areas of Rajasthan, India. There was high mortality in undiagnosed cases of FUO which lead to the diagnosis of scrub typhus. To study the possibility of scrub typhus as a causative factor in FUO cases by qualitative detection of IgM antibodies with ELISA. From September 2012 to December 2012, 271 serum samples of FUO cases were analysed for IgM antibodies to Orientia tsutsugamushi along with dengue, malaria, typhoid, tuberculosis and brucellosis. Scrub typhus IgM antibodies by ELISA were detected in 133 (49.1%) patients. Scrub typhus positivity was significantly higher among female in comparison to males (P<0.05). Maximum positivity of scrub typhus was found in females of 46-60 years age group. The laboratory parameters were abnormal in most of the patients as evident by thrombocytopenia (63%), deranged liver functions (56%) and renal functions (25%). The present study emphasises the importance of scrub typhus among cases of FUO especially after rainy season and during early cooler months. The study also highlights the significance of ELISA method for rapid and early reporting and ruling out scrub typhus in FUO cases.

PROLONGED PYREXIA WITH ACUTE RENAL INSULT - UNRAVELING THE PUZZLE AND SOLVING THE ENIGMA

Abstract:A middle aged man with prolonged pyrexia was referred to us with a diagnosis of FUO (Fever of unknown origin). He was evaluated by various investigations and a diagnosis of Tuberculosis was established. On anti tubercular treatment (ATT) he developed complication of acute renal injury –non oliguric renal failure, from which he recovered fully after the puzzle was successfully solved &amp; managed accordingly. Even though he was proved to have rifampicin induced acute intersticial nephritis(AIN) by biopsy , he had varied &amp; unconventional presentation like without oliguria, without peripheral blood eosinophilia, and more so particularly on the maiden administration of rifampicin. Thus our case highlights the importance of quickly establishing the cause for FUO, and also need for greater vigilance on part of physicians to solve unconventional presentations of complications arising out of treatment.

Fever of Unknown Origin as an Onset for Late-Onset Systemic Lupus Erythematous

Introduction: Systemic lupus erythematous (SLE) is among rheumatic diseases of unknown etiology. Fever of unknown origin (FUO) has been rarely reported to be the presenting sign of SLE. Presence of four or more SLE criteria is diagnostic for the disease. However, presentations may occur serially which make it much more difficult to diagnose an already questioned FUO. Case Presentation: Our case of SLE, presenting with a long history of unidentified FUO, was a 73-year-old man treated due to various diagnoses in different medical services before referring to the department of infectious diseases at Imam Khomeini Hospital. None of the previous treatments were effective to resolve his fever. In infectious ward, we performed multiple diagnostic tests to approach the FUO, and the patient serially presented some criteria of SLE. Therefore, we referred the patient to the rheumatology ward with late-onset systemic lupus erythematous (LO-SLE) for more work ups and management. Discussion: FUO in elderly has a wide range of differential diagnoses and Infection with tuberculosis, immunologic and pulmonary diseases, other multisystem diseases, tumors, and medications are presented on the top. SLE has rarely been mentioned after the age of 50 as a cause of FUO; but due to more severe damages to the body organs, its potential should be considered. Although our case presented only three criteria of SLE, this diagnosis was confirmed and treated by the rheumatologist; thus the symptoms and signs gradually improved.

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.

Analysis of 256 cases of classic fever of unknown origin.

The causes of fever of unknown origin (FUO) vary depending on the region and time period. We herein present a study of patients with classic FUO where we investigated differences based on patient background factors, such as age and causative diseases, and changes that have occurred over time. We extracted and analyzed data from the medical records of 256 patients ≥18 years old who met the criteria for classic FUO and were hospitalized between August, 1994 and December, 2012. The median age of the patients was 55 years (range: 18-94 years). The cause of FUO was infection in 27.7% of the patients (n=71), non-infectious inflammatory disease (NIID) in 18.4% (47), malignancy in 10.2% (26), other in 14.8% (38), and unknown in 28.9% (74). The most common single cause was human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (n=17). NIID and malignancy were more common in patients ≥65 years old than in patients <65 years old. During 2004-2012, compared to 1994-2003, infections and "other" causes were decreased, whereas NIID, malignancy, and unknown causes were increased. FUO associated with HIV/AIDS is increasing in Japan. In addition, as in previous studies in Japan and overseas, our study showed that the number of patients in whom the cause of FUO remains unknown is increasing and exceeds 20% of all cases. The present study identified diseases that should be considered in the differential diagnosis of FUO, providing useful information for the future diagnosis and treatment of FUO.

Fever of Unknown Origin: A Retrospective Study of 95 Children in an Iranian Referral Hospital

Fever of unknown origin (FUO) is a common manifestation in paediatrics and is a diagnostic problem especially in primary care. The present study aims to revue the causes of FUO in an Iranian referral tertiary care hospital. Information on 95 patients referred to the Children’s Medical Center Hospital, Tehran, between 2004 and 2006 with a primary diagnosis of FUO was evaluated retrospectively. Infectious diseases were diagnosed in 26.3% (n=25) of the cases, while malignant and non-infectious inflammatory diseases constituted 7.4% (n=7) and 14.7% (n = 14), respectively. Urinary tract infections, acute lymphoid leukaemia and Kawasaki disease were the most commonly diagnosed conditions. Urinary tract infection accounted for approximately half of the infectious cases (n=14). Conclusive diagnostic factors included history and examination in 21 cases, analysis of different specimens (i.e., urine analysis, urine culture, serology, peripheral blood and cerebrospinal fluid [CSF] examination) in 12 cases, culture in nine cases and serological tests in four cases. Infection and malignancy in patients aged under three years, and inflammatory diseases in patients aged over three years were more common. In patients aged under three years urine culture, bone marrow aspiration and peripheral blood smear proved more helpful in arriving at a final diagnosis of FUO, while in patients aged over three years, history and physical examination also contributed to the final diagnosis.

Diagnostic contribution of 18F-FDG-PET/CT in fever of unknown origin

Fever of unknown origin (FUO) remains one of the most compelling diagnostic issues in medicine. We aimed to evaluate the potential clinical contribution of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in the identification of the underlying cause of FUO. Fifty consecutive patients (27 men and 23 women; age range 16-88 years) with FUO based on the revised definition criteria were included in the study. A diagnostic protocol including biochemistry, histopathology, and microbiological tests was performed and the patients were followed up. FDG-PET was performed in 25 of the 50 patients (12 males and 13 females; age range 16-88 years) in order to determine the etiology of the patient's fever. PET-CT images were obtained with the Gemini Philips TF (18)F-FDG-PET/CT camera after a 60-min 'standard uptake' period following an injection of a mean 330 MBq (range 290-370 MBq) intravenous (18)F-FDG. A total of 21 patients were available for analysis of the diagnostic contribution of PET/CT (two patients were undiagnosed and two had non-contributory PET/CT findings). (18)F-FDG-PET/CT was able to precisely detect the cause of fever in 60% of the cases (n=15). The accuracy, sensitivity, and specificity of this imaging modality were 90.5%, 93.8%, and 80%, respectively. Among the cases with a true-positive (18)F-FDG-PET/CT finding (i.e., 15 cases), the identified underlying causes of FUO included localized infection (n=7), non-infective inflammatory process (n=5), and malignancy (n=3). Further studies to confirm the high diagnostic yield of (18)F-FDG-PET/CT observed in the present study would lend support to the inclusion of this imaging modality in the initial diagnostic work-up of patients with suspected FUO.

Diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin

The aim of this study was to systematically review and perform a meta-analysis of published data on the diagnostic value of F-fluorodeoxyglucose (F-FDG) PET/CT in the diagnosis of patients with fever of unknown origin (FUO). A comprehensive computer literature search of studies published through 31 March 2012 on the use of F-FDG PET/CT in patients with FUO was performed in PubMed/MEDLINE, Embase, and Scopus databases. The pooled sensitivity of F-FDG PET/CT in patients with FUO on a per-patient-based analysis was calculated. The area under the receiver-operating characteristic curve was calculated to measure the accuracy of F-FDG PET/CT in the diagnosis of patients with FUO. Fifteen studies comprising 595 patients with FUO were included in this meta-analysis. The pooled sensitivity of F-FDG PET/CT in detecting the cause of FUO was 85% (95% confidence interval 81-88%) on a per-patient-based analysis. The area under the receiver-operating characteristic curve was 0.88. F-FDG PET/CT demonstrated high sensitivity for the diagnosis of patients with FUO. F-FDG PET/CT is an accurate technique in this setting, but the possibility of false-positive results should be kept in mind. This meta-analysis demonstrated the value of F-FDG PET/CT in the diagnosis of patients with FUO.

Les examens biologiques au cours des fièvres prolongées et récurrentes

Summary Fever of unknown origin (FUO) are defined by a fever greater than 38.3 °C evolving during at least 3 weeks and without diagnosis despite appropriate explorations. This clinical entity is not so uncommon. More than 200 causes of FUO have been reported. Despite medical advances, they remain unexplained in 10 to 30% of cases after exhaustive work-up. So FUO is a challenging medical problem. Clinical evaluation remains the basis of the initial evaluation of the patient with FUO. Newer diagnostic modalities, including blood chemistry, immunological tests and molecular methods have important role in the assessment of these patients. We will discuss in this review terminology, common causes of FUO and technical innovation.

Fieber ungeklärter Ursache

Fever of unknown origin (FUO) is defined as sustained unexplained fever despite intensive diagnostic evaluation and represents a particular diagnostic challenge. It can be classified into different categories, e.g. classical, nosocomial, neutropenic and HIV-associated FUO, which is based on the patient-specific clinical and immunological situation. Infections, malignant diseases and non-infectious inflammatory diseases have to be considered as the most important causes of FUO; however, no definitive diagnosis can be established in a substantial number of FUO patients despite an extensive diagnostic work-up. The present review focuses on the important diagnostic aspects as well as therapeutic options in FUO patients.

Fever of unknown origin as the first manifestation of colonic pathology

Fever of unknown origin (FUO) is an entity caused by more than 200 diseases. Haematologic neoplasms are the most common malignant cause of FUO. Fever as a first symptom of colonic tumour pathology, both benign and malignant, is a rare form of presentation. Our work is a descriptive study of a series of 23 patients with colonic tumoral pathology who presented with fever of unknown origin. The mean age was 67.6 years; 56.5% of patients were men and 43.5% were women. Primary malignant neoplasia was the most common diagnosis. Blood cultures were positive in 45% of the samples. Coagulase-negative staphylococci were the most common cause of bacteraemia. Nine of 10 faecal occult blood tests performed were positive. Fever secondary to colon neoplasms, both benign and malignant, usually presents with a bacteraemic pattern, with positive results for blood-culture tests in a high percentage of cases.

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.

F-18 FDG-PET/CT in evaluation of patients with fever of unknown origin

This study was carried out to evaluate the diagnostic utility of FDG-PET/CT in patients with fever of unknown origin (FUO). Medical records of 103 patients who underwent FDG-PET/CT and anatomic imaging as a part of FUO workup were analyzed. Final diagnosis of the cause of FUO was reached based on serologic assays, cultures, biopsy, surgery or 6 months of clinical follow-up. The definite cause of fever was established in 69/103 patients. Abnormal FDG uptake was found in 63/103 patients and contributed to the final diagnosis (TP) in 62 patients (98.48 %). Of the remaining 40 patients with negative PET/CT, the final definite cause of fever (FN) could be determined only in seven patients (17.5 %). PET/CT had a sensitivity, specificity, positive predictive value and negative predictive value of 90, 97, 98.4 and 82.5 % compared to 43.5, 67.6, 73.2 and 37.1 %, respectively, for anatomic imaging. FDG-PET/CT had a higher accuracy (92.2 vs. 51.5 %; p = 0.003) compared to anatomic imaging for suggesting a cause of FUO. PET/CT showed high sensitivity and specificity in suggesting a definite diagnosis in the evaluation of FUO.