[Fever of unknown origin. Fever caused by bacteria].
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Bacterial Infections↗
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[Fever of unknown origin. Fever in hematologic system diseases and malignant tumors].
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Adolescent↗
18F-FDG PET and PET/CT in fever of unknown origin.
Fever of unknown origin (FUO) was originally defined as recurrent fever of 38.3 degrees C or higher, lasting 2-3 wk or longer, and undiagnosed after 1 wk of hospital evaluation. The last criterion has undergone modification and is now generally interpreted as no diagnosis after appropriate inpatient or outpatient evaluation. The 3 major categories that account for most FUOs are infections, malignancies, and noninfectious inflammatory diseases. The diagnostic approach in FUO includes repeated physical investigations and thorough history-taking combined with standardized laboratory tests and simple imaging procedures. Nevertheless, there is a need for more complex or invasive techniques if this strategy fails. This review describes the impact of (18)F-FDG PET in the diagnostic work-up of FUO. (18)F-FDG accumulates in malignant tissues but also at the sites of infection and inflammation and in autoimmune and granulomatous diseases by the overexpression of distinct facultative glucose transporter (GLUT) isotypes (mainly GLUT-1 and GLUT-3) and by an overproduction of glycolytic enzymes in cancer cells and inflammatory cells. The limited data of prospective studies indicate that (18)F-FDG PET has the potential to play a central role as a second-line procedure in the management of patients with FUO. In these studies, the PET scan contributed to the final diagnosis in 25%-69% of the patients. In the category of infectious diseases, a diagnosis of focal abdominal, thoracic, or soft-tissue infection, as well as chronic osteomyelitis, can be made with a high degree of certainty. Negative findings on (18)F-FDG PET essentially rule out orthopedic prosthetic infections. In patients with noninfectious inflammatory diseases, (18)F-FDG PET is of importance in the diagnosis of large-vessel vasculitis and seems to be useful in the visualization of other diseases, such as inflammatory bowel disease, sarcoidosis, and painless subacute thyroiditis. In patients with tumor fever, diseases commonly detected by (18)F-FDG PET include Hodgkin's disease and aggressive non-Hodgkin's lymphoma but also colorectal cancer and sarcoma. (18)F-FDG PET has the potential to replace other imaging techniques in the evaluation of patients with FUO. Compared with labeled white blood cells, (18)F-FDG PET allows diagnosis of a wider spectrum of diseases. Compared with (67)Ga-citrate scanning, (18)F-FDG PET seems to be more sensitive. It is expected that PET/CT technology will further improve the diagnostic impact of (18)F-FDG PET in the context of FUO, as already shown in the oncologic context, mainly by improving the specificity of the method.
Aged↗
Immunoscintigraphy (BW 250/183) in neonates and infants with fever of unknown origin.
Fever of unknown origin is defined as a temperature above 39.0 degrees C together with a white blood cell count > or = 15,000 mm-3, the duration of fever exceeding 2 weeks and a correct diagnosis not being obtained in the first week of hospitalization. In neonates and infants with fever of unknown origin, the localization of the infectious focus is often difficult and unsatisfactory. In this retrospective study, the clinical value of 99Tcm-labelled antigranulocyte antibodies for this group of patients was investigated. Thirty-two immunoscintigrams were performed using 185-259 MBq 99Tcm-labelled antigranulocyte antibodies (BW 250/183) in 30 neonates and infants (21 boys, 9 girls, mean age 29.4 +/- 2 months), who had fever of unknown origin. Immunoscintigraphy was carried out as whole-body images (n = 7) or single planar images (n = 25) 4 h and 24 h post-injection. In children with known cardiac failure, single photon emission tomography of the thorax was performed to diagnose endocarditis (n = 2). For verification, the results of the immunoscintigrams were compared with radiology (conventional radiography = 14, MRI = 5, CT = 3), biopsy (n = 2), blood culture (n = 10) and clinical follow-up after specific therapy. In 11 of 30 children (36%), the diagnosis of an infective focus was possible with immunoscintigraphy. The sensitivity and specificity of diagnosing infective foci was 72% and 95% respectively (n = 11; colitis = 2, infection of the central permanent catheter tip = 2, middle ear infection = 1, spondylitis/discitis = 3, osteomyelitis = 2, umbilical infection = 1). In vertebral body infections, all lesions were photopenic. In 18 children (60%), no infective focus was found on immunoscintigraphy. In this group of children, the main reason (n = 5) for fever of unknown origin was chronic juvenile rheumatoid arthritis. No uptake was seen in two infants with cardiac failure and suspected endocarditis on SPET. In 3 of the 18 patients (17%), localization of an infective focus was not possible with immunoscintigraphy or on other examinations. In these patients, the fever disappeared spontaneously after a few days of antibiotic therapy. In conclusion, we have shown that 99Tcm-anti-NCA-95 scanning is a safe method with a high sensitivity and specificity for detecting infectious foci in neonates and infants with fever of unknown origin. Furthermore, this method is easy to perform, since no withdrawal of blood is necessary.
Antibodies, Monoclonal↗
Carcinoma of colon presenting as fever of unknown origin.
Fever of unknown origin (FUO) is defined as fever of more than 38.3 degrees C, the cause of which remains elusive after 1 week of intensive investigation. Most cases of FUO are restricted to infections, malignancies, and inflammatory diseases. FUO was previously reported as the presenting symptom of a few solid tumors such as lymphoma, renal cell carcinoma, and hepatocellular carcinoma. Colon carcinoma manifesting as FUO has been rarely reported. We describe three female patients who presented with classical FUO and microcytic anemia. As a control, we retrospectively evaluated 28 matched patients with carcinoma of colon and no fever. The evaluation included review of patient files, clinical and laboratory data, and pathologic specimens. In the three patients (mean age, 58 years) who presented with FUO and had left-sided colon carcinoma and microcytic anemia, pathologic evaluation of the tumor tissues demonstrated a severe organized inflammatory process forming abscesses in the pericolic fat. The 28 control matched patients showed no such histopathologic changes. In patients presenting with FUO, especially those who present with microcytic anemia, even with no bowel disturbances or elevated carcinoembryonic antigen levels, diagnostic workup should include a search for occult colorectal carcinoma. In our three cases, it appears that microabscesses in the pericolic fat are the cause of fever.
Abdominal Abscess↗
Value of FDG PET in patients with fever of unknown origin.
Fever of unknown origin (FUO) is a diagnostic challenge, because the cause of such fever may be manifold. Studies on the use of positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG), for the diagnosis of inflammation in patients with osteomyelitis or HIV have been promising and suggest its use in patients with FUO. In this study, we used FDG PET in 16 patients with FUO in whom conventional diagnostics had not been conclusive. In 12 patients, (75%) non-physiological accumulations of FDG were found which led to the final diagnosis in 11 patients (69%). FDG PET was negative in four patients (25%). Two of these patients had rheumatic fever, while in the other two patients the origin of fever could not be detected within 3 months after PET by any other laboratory or imaging means. These findings point to the high sensitivity of FDG whole-body PET for the detection of morphologically assessable foci as an origin of FUO. Moreover, they suggest a high negative predictive value of FDG PET in the setting of FUO, since in no patient with a negative FDG PET could a morphological origin of the fever be determined. In conclusion, FDG whole-body PET appears to be a promising diagnostic tool in patients with FUO, in whom conventional diagnostics had been unsuccessful.
Adult↗
[Esophageal carcinoma presenting as fever of unknown origin].
Fever of unknown origin presents both a clinical and diagnostic challenge and is usually caused by inflammatory and neoplastic diseases. We present a unique case of a previously healthy 77-year-old woman whose sole complaint was fever. Complete hospital investigation failed to reveal the underlying process. 4 months after the onset of fever, dysphagia appeared and she was then diagnosed as suffering from squamous cell carcinoma of the esophagus. The question of early barium swallow X-ray in such cases is raised.
Aged↗
Fluordeoxyglucose positron emission tomography contributes to management of pediatric liver transplantation candidates with fever of unknown origin.
Fever of unknown origin (FUO) frequently complicates the management of pediatric patients with terminal chronic liver failure during the pretransplantation period and may lead to increased morbidity and mortality. Nonhepatic origins of systemic infections may render the patient unsuitable for transplantation whereas infections within the liver may require organ resection for a cure. Therefore, accurate localization of the infection focus is critical for optimal management of children on the waiting list for liver transplantation. Here we report our experience using [18 F]fluordeoxyglucose (FDG)-positron emission tomography (PET) to detect the origin of infection in 11 children with biliary cirrhosis presenting with FUO during the waiting period for liver transplantation. In 5 children, positive intrahepatic FDG-PET signals correlated with bacterial cultures of the excised liver and/or anatomic or histologic signs of infection. Based on the FDG-PET findings, these patients underwent transplantation after continuous antibiotic treatment with ongoing, recurrent episodes of fever. In 6 children, no abnormal hepatic FDG-PET signals were found and no infections could be detected in the liver. Transplantation in these patients was performed only after becoming afebrile. Standard imaging techniques did not reveal abnormalities compatible with infection in any of the children. In conclusion, in children with biliary cirrhosis and FUO on the waiting list for liver transplantation, information obtained by FDG-PET imaging may be useful for decisions on therapy and suitability for liver transplantation.
Anti-Bacterial Agents↗
Fever of unknown origin.
Fever of unknown origin (FUO) is defined as a temperature elevation of 101 degrees F (38.3 degrees C) or higher for 3 weeks or longer, the cause of which is not diagnosed after 1 week of intensive in-hospital investigation. This article discusses the causes, diagnosis, and treatment of FUOs.
Fever of Unknown Origin↗
Use of immunoscintigraphy in the diagnosis of fever of unknown origin.
Fever of unknown origin (FUO) has been defined as an elevation in temperature (38 degrees C) for at least 2-3 weeks despite intensive investigation. The value of immunoscintigraphy with the technetium-99m-labelled anti-granulocyte antibody anti-NCA-95 (BW 250/183, IgG1) was studied retrospectively in 34 consecutive patients with FUO. Every effort was made to confirm a diagnosis, including methods such as ultrasonography, computed tomography, magnetic resonance imaging, bacteriological tests, surgical intervention and clinical follow-up. In 58.8% of the patients, an infectious cause for the fever was found, in 30.2% of the patients, a benign or malignant haematological disease, pancreatitis or thyrotoxicosis was found. No cause for fever could be found in 11%. The overall diagnostic sensitivity and specificity of immunoscintigraphy for infection were 40% and 92% respectively. The positive predictive value was calculated to be 88% and the negative predictive value was calculated to be 52%. False-negative scans were especially noted in patients with endocarditis, pneumonia and small brain abscesses, where the lesions did not exceed a diameter of 0.5 cm. If patients with endocarditis were excluded, the imaging sensitivity and specificity were increased to 57% and 95%. This study demonstrates that 99mTc-anti-NCA-95 scanning is able to localize infectious causes of FUO, other than endocarditis.
Adult↗
Approach to the adult patient with fever of unknown origin.
Fever of unknown origin (FUO) in adults is defined as a temperature higher than 38.3 degrees C (100.9 degrees F) that lasts for more than three weeks with no obvious source despite appropriate investigation. The four categories of potential etiology of FUO are classic, nosocomial, immune deficient, and human immunodeficiency virus-related. The four subgroups of the differential diagnosis of FUO are infections, malignancies, autoimmune conditions, and miscellaneous. A thorough history, physical examination, and standard laboratory testing remain the basis of the initial evaluation of the patient with FUO. Newer diagnostic modalities, including updated serology, viral cultures, computed tomography, and magnetic resonance imaging, have important roles in the assessment of these patients.
Algorithms↗
Mycobacteriosis in patients with fever of unknown origin.
Fever of unknown origin (FUO) is a common syndrome. A total of 94 patients (57 men and 37 women; mean age, 56.3 +/- 19 years, range, 18-86 years) who met the criteria of FUO were included in this study. Mycobacteriosis was diagnosed in 22 (23%) of these patients (13 men and 9 women), including 9 with disseminated disease and 13 with pulmonary disease. There was no significant statistical difference in age, sex, short-term survival status (3 months), and other clinical parameters between patients with and without mycobacteriosis. Clinical manifestations may be specific or nonspecific. The most common initial presentations in patients with mycobacteriosis were respiratory tract symptoms, mainly of cough and dyspnea, observed in 11 (50%) patients, and disturbance of consciousness in 6 (27%). The associated conditions included malnutrition (4 patients, 18%), diabetes mellitus (3, 14%), and renal failure (3, 14%). Four (18%) patients had a history of pulmonary tuberculosis or tuberculous spondylitis in their early adulthood. The 2 most common findings on chest radiograph were interstitial (41%) and nonspecific infiltrative (32%) patterns. In conclusion, mycobacteriosis remains the leading cause of FUO in southern Taiwan and it is important to screen for this treatable disease in all cases of FUO.
Adolescent↗
Is laparotomy necessary in the diagnosis of fever of unknown origin?
Fever of unknown origin (FUO) is a diagnostic challenge for the practising physician. Detailed medical history, physical examination, non-invasive laboratory tests, and radiologic examinations compose the first level in the diagnostic approach to the FUO. When a diagnosis cannot be established with these procedures, some invasive diagnostic techniques and finally exploratory laparotomy are performed. Although advanced diagnostic measures and imaging-guided less invasive procedures have decreased the need, laparotomy remains as a final diagnostic method for FUO cases. In this study we evaluate the role and importance of laparotomy in the diagnosis of our FUO cases. In 17 out of 126 patients (8 male, 9 female, the median age 35.8 years) hospitalized in our clinic between 1982 and 2002 with the diagnosis of FUO, the diagnosis was established by laparotomy. The diagnosis was made directly in 13 patients, and indirectly (by excluding other diseases) in 2 patients. In several FUO series, the contribution of laparotomy to the diagnosis of FUO was reported as 27-100%. This rate was found to be 88% in the present study. During laparotomy on 17 cases, tissue samples were taken from spleen, liver, intra-abdominal and mesenteric lymph nodes. Pathologic examination of these tissue samples revealed miliary tuberculosis in 4; non-Hodgkin's lymphoma in 3; Hodgkin's lymphoma in 3; liver tumour in 1; hairy cell leukemia in 1; peritonitis carcinomatosis in 1. In the patients with miliary tuberculosis, the liver (3) and/or spleen (2), and/or lymph node (3) revealed caseating granulomas. Laparotomy diagnosed 3 of 5 cases whose abdominal ultrasonography and computerized tomography were normal. In conclusion, although advanced diagnostic methods decreased the need for laparotomy in FUO, if non-invasive and invasive diagnostic measures fail, laparotomy may contribute to the diagnosis. The selection of the patient and the timing are important for laparotomy.
Adolescent↗
Circulating and ex vivo production of pyrogenic cytokines and interleukin-1 receptor antagonist in 123 patients with fever of unknown origin. The Netherlands Fever of Unknown Origin Study Group.
Circulating and ex vivo production of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, and IL-1 receptor antagonist (ra) and the diagnostic utility of these cytokines were studied in 123 patients with fever of unknown origin (FUO). Diagnoses were infections, 28; neoplasms, 14; noninfectious inflammatory diseases (NIID), 32; miscellaneous diseases, 10; and none made, 39. IL-1beta, IL-6, and IL-1ra concentrations were higher in patients with infections, neoplasms, and NIID than in healthy controls. Patients with infections had higher concentrations of TNF-alpha than controls. The ex vivo production of IL-1beta and IL-1ra in all patients with FUO did not differ from that in controls; however, production of TNF-alpha was lower in patients with neoplasms and NIID, and IL-6 production was lower in patients with neoplasms. Thirty-five patients with fever did not have elevated cytokines. Although some significant differences were found among the diagnostic subgroups, there was wide variation. Thus, measurement of these cytokines does not aid in the diagnosis of FUO.
Adolescent↗
[Differential diagnosis in fever of unknown origin].
Fever is one of the most frequent and important symptoms in pediatrics. Most cases are caused by self-limiting viral or easily treatable bacterial infections. If after 5-7 days no cause of the ongoing fever has been found, the condition is termed fever of unknown origin, a working diagnosis which often poses a diagnostic challenge. The ultimate cause may be an infectious disease, a chronic inflammatory disorder, a malignancy, or another rare disease. The cause may also remain obscure or the fever can finally disappear. Here we elaborate the diagnostic work-up and symptomatic treatment.
Adolescent↗
[A clinical analysis of 40 patients with the unknown origin fever].
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Adolescent↗
[A case of fever of unknown origin].
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Fever of Unknown Origin↗