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Aims:Fever of unknown origin (FUO) remains a diagnostic challenge for clinicians. The current diagnostic approach includes a detailed medical history, physical examination, laboratorytestsand imaging techniques(chest X-ray, ultrasound, CT, MRI). 18F-FDG PET/CT (18fluoro-deoxyglucose PET/CT) is a non-invasive diagnostic imaging technique, which is widelyused in oncology. The purpose of our narrative review was to summarize the knowledge for the diagnostic role of 18F-FDG PET/CT in the diagnostic approach of patients with FUO, as reported in the literature. Methodology:We undertook a search of literature published in PubMed until February 2019.Results:Various studies showed that 18F-FDG PET/CT could play an important role as a second-line explorative technique in the diagnosis of patients with FUO. 18F-FDG PET/CT presents high diagnostic accuracy in large vessel vasculitis, in orthopedic prosthetic infections, in chronic osteomyelitisand in prosthetic valve endocarditis. However, 18 -FDG/PET has some limitations such as the assessment of urine tract due to the excretion into the urine but also become of the high glucose metabolism in some organs such as the brain.Conclusions: Overall, PET/CT gains increasing interest in the diagnosis of FUO and should be considered by the clinicians in the exploration of those patients
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Objective@#The clinical presentation, outcome, and risk factors for mortality in children with Fever of Unknown Origin (FUO) were determined. @*Methods@#Medical records of pediatric patients admitted for FUO from January 2009 to December 2013 were reviewed. Clinical manifestations, physical exam findings, diagnostic work-ups and final diagnosis were determined, as well as the relationship between final diagnosis and risk for mortality. @*Results@#Fifty-seven patients with FUO were included. Weight loss, cough, colds, and rashes were common symptoms while pallor, lymphadenopathies, and hepatomegaly were common physical exam findings. All patients underwent Phase I evaluation for FUO, while 73.7% underwent further diagnostic tests. A specific etiology was established in 96.5% of cases: infectious, 43.9%, connective tissue disease, 38.6%, and hematologic/oncologic, 14%. Two cases remained to have no specific diagnosis. Majority of patients had a benign course and were discharged improved (84.2%). The mortality rate is 15.8% and was not associated with any disease category (p-value 0.204). @*Conclusion@#FUO in children occurs across all age groups. Its clinical presentations are varied and non-specific and common signs and symptoms are pallor, lymphadenopathies, weight loss, cough, colds. and joints pains. Infection is the most common cause of FUO in children, followed by connective tissue diseases and hematologic and oncologic diseases. The mortality rate from FUO is 15.8%.
Subject(s)
Fever of Unknown OriginABSTRACT
Aim: To assess whether a significant correlation exists with serum Interleukin-6 cytokine levels in patients with Classic Fever of Unknown Origin (FUO) compared with healthy controls. The levels of IL-6 cytokine were tested as a proinflammatory cytokine which may belong to microorganisms that cause disease. Study Design: This is a case control, single center study. Place and Duration of Study: The study was conducted in the University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria in patients with classic FUO who were treated between 2009 and 2012 were included in this study. Methodology: A total of 75 patients with classic FUO within the age range of 15 – 65 years were tested for IL-6 cytokine in comparison with 75 healthy controls. The sample size was calculated using Fisher’s formula. Results: In patients with FUO, 39% of patients demonstrated elevated levels of IL-6 while 20% of healthy controls demonstrated elevated levels (>200 pg/ml) of serum IL-6, while 12% and 15% respectively were in standard range of 0 - 6.4 pg/ml which is considered low. Gender differences were noted and mean values of IL-6 were higher in males (FUO mean±SD 136.7±161.8; Healthy controls mean±SD 132.3±183.5) than in females (FUO mean±141.6±133.9; Healthy controls mean±SD 97.8±134.2). Healthy male control had a value of 520.5 pg/ml with little difference to the male patients with FUO (575 pg/ml), p=0.91) while IL-6 concentrations in the female group who had FUO (407.5 pg/ml vs 367.5 pg/ml, p=0.16) showed greater difference in value in comparison to the healthy which trended towards statistical significance. We found that most patients (39%) with FUO have higher values of ≥ 200 pg/ml than the healthy controls. Conclusions: Serum IL-6 cytokine level is generally higher in males than in females and most patients (39%) with FUO have a higher value of ≥ 200 pg/ml than the healthy controls. IL-6 levels trended towards statistical significance and may help to discriminate females with FUO as compared their healthy controls.
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An 85-year-old male patient with a history of asthma and hypertension was admitted to our hospital because of a fever of unknown origin. He complained of fever, fatigue, and weakness of lower extremities, which was considered due to infection, and he was administered antibiotics. Although his fever improved, there was little improvement in his condition or laboratory data. Enhanced-contrast computed tomography showed irregular hypertrophy of the aorta with contrast effect in the outer aortic wall and pulmonary embolism. He was diagnosed with Takayasu arteritis and pulmonary embolism. His clinical condition and aortic wall enhancement improved following steroid and anticoagulant drug therapy.
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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. 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/mm3 (5 to 1144 cells /mm3) and 23% patients had CD4 counts <50 cells/mm3. 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.
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Takayasu arteritis is a chronic vasculitis involving the large vessels. At diagnosis, ischemic symptom are usually present in the affected vessels. However, fever of unknown origin (FUO) is rare as an initial presentation and renders the condition difficult to diagnose. In this case report, we describe a patient who presented with a fever of unknown origin. A 68-year-old female was diagnosed with Takayasu arteritis after fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) was performed at the prepulseless stage. FDG PET-CT can assist in the early diagnosis of Takayasu arteritis patients with FUO and can improve the prognosis of such patients.
Subject(s)
Aged , Female , Humans , Diagnosis , Early Diagnosis , Fever of Unknown Origin , Fever , Prognosis , Takayasu Arteritis , VasculitisABSTRACT
The patient was a 14 year-old female. She had been hospitalized repeatedly since infancy for suspected tonsillitis. During this time, she experienced high fever for about a week once a month. In her school years, she often had a recurrent fever with cervical adenitis, with only a mild inflammatory reaction. We diagnosed her symptom as one of a periodic fever syndrome, triggered by the frequent administered antipyretic drugs for fevers of unknown origin (FUO). We also suspected that there was liver tension, based on her abdominal and back examination, and we prescribed yokukansan. After a 3-month course of yokukansan, she no longer experienced these fevers. Most case reports of FUO describe the use of bupleurum root drugs and tonic formulas as treatment. Although yokukansan has traditionally been used for FUO in older texts, to our knowledge, there are no reports on such use clinically. In the present patient's case, the yokukansan may have reduced or eliminated some type of trigger for the fevers, or it may have affected the regulation of cytokines.
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<b><i>Abstract</i></b><br><b>Objective</b> : To investigate the causes of fever of inpatients hospitalized in the Department of General Practice at Jichi Medical University Hospital.<br><b>Methods</b> : We reviewed all medical records of the patients hospitalized in the Department of General Practice at this hospital between April 2003 and March 2004. Patients were selected as the “febrile group” by following criteria, 1) body temperature exceeded 37.5°C on admission, 2) fever and fever of unknown origin (FUO) were included in the clinical problems, and the causes of fever were described.<br><b>Results</b> : A total of 464 patients were hospitalized and 221 patients (47.6%) were categorized as the “febrile group”. The most common cause of fever was infection (67.4%), followed by malignant disease (4.1%), collagen disease (3.2%), miscellaneous diseases (10.4%). 26 patients were classified as fever of unknown origin (FUO). Among FUO patients, collagen disease was the most common cause (34.6%), and undiagnosed cases was 26.9% that was similar to past reports. Although the rates of malignant disease and collagen disease were about sixteen percent in each generation from thirties to fifties as the cause of fever, only one patient met the criteria of classical FUO.<br><b>Conclusions</b> : The most common cause of fever was infection. Systematic survey including hospitalization is needed early in case an outpatient doesn't cure fever unexpectedly. Noninfectious inflammatory diseases emerge as an important category of the causative disease of FUO.
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Hepatic involvement is common in miliary and extra-pulmonary tuberculosis but is usually clinically silent. Therefore, it is rarely diagnosed. We report the case of a patient that presented with prolonged fever and hepatomegaly. Liver biopsy revealed non-necrotizing granulomas that led in turn to the diagnosis of generalized tuberculosis and HIV infection. The patient reported an old untreated tuberculosis and depression of the immune system provoked the reactivation of this old tuberculosis focus. We describe the clinical course of the disease and the challenges associated with the complexity of the treatment. Diagnosis of hepatic tuberculosis requires a high degree of suspicion especially in AIDS patients who show atypical presentations. However, it is a potential curable disease and good results have been obtained with the four drug regimen.
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Acute schistosomiasis is a systemic hypersensitivity reaction against the migrating schistosomula and eggs. A variety of clinical manifestations appear during the migration of schistosomes in humans: cercarial dermatitis, fever, pneumonia, diarrhoea, hepatomegaly, splenomegaly, skin lesions, liver abscesses, brain tumours and myeloradiculopathy. Hypereosinophilia is common and aids diagnosis. The disease has been overlooked, misdiagnosed, underestimated and underreported in endemic areas, but risk groups are well known, including military recruits, some religious congregations, rural tourists and people practicing recreational water sports. Serology may help in diagnosis, but the finding of necrotic-exudative granulomata in a liver biopsy specimen is pathognomonic. Differentials include malaria, tuberculosis, typhoid fever, kala-azar, prolonged Salmonella bacteraemia, lymphoma, toxocariasis, liver abscesses and fever of undetermined origin. For symptomatic hospitalised patients, treatment with steroids and schistosomicides is recommended. Treatment is curative in those timely diagnosed.
Subject(s)
Animals , Female , Humans , Male , Schistosomiasis mansoni , Acute Disease , Schistosomiasis mansoni , Schistosomiasis mansoni , Schistosomiasis mansoni , Schistosomiasis mansoni/transmission , SchistosomicidesABSTRACT
Evaluation of a fever of unknown origin (FUO) is complex. Recently, PET scanning has been approved for screening in FUO evaluation. We treated three cases of FUO associated with increased FDG uptake in the bone marrow of the femur and tibia on the fusion PET/CT; all three had the same pattern of uptake. Bone marrow biopsies revealed mature lymphocyte and histiocyte infiltration and myxoid changes in one case, and cortical bone involvement in another case. The cases were all young females who had fever with neutropenia and relative lymphocytosis that lasted for several weeks and then remitted spontaneously. Even though the results of the studies were not diagnostic, the unique uptake pattern on PET/CT and the histology might be related to the cause of the illness and should be studied further to assess the association with classic FUO.
Subject(s)
Female , Humans , Biopsy , Bone Marrow , Femur , Fever , Fever of Unknown Origin , Histiocytes , Lymphocytes , Lymphocytosis , Mass Screening , Neutropenia , Positron-Emission Tomography , TibiaABSTRACT
Including malignancy, various disease can show abnormal uptake in bone marrow.1,2) We report a case of non-specific inflammatory FDG uptake in bone marrow mimicking malignancy. A 35-year old woman with fever of unknown origin (FUO) underwent 18F-FDG PET/CT to find out fever focus and unknown malignancy. 18F-FDG was injected and imaged 1hr after injection with Discovery ST (GE, USA). 18F-FDG PET/CT whole body image showed abnormal uptake in lower extremities (Fig. 1). MRI and biopsy was also done in the sites of abnormal uptake. PET and MRI suspect malignancy (Fig. 2, 3), but biopsy result was non-specific inflammatory process (Fig. 4). The patient was improved her clinical condition after antibiotics therapy.
Subject(s)
Female , Humans , Anti-Bacterial Agents , Biopsy , Body Image , Bone Marrow , Fever , Fever of Unknown Origin , Fluorodeoxyglucose F18 , Lower ExtremityABSTRACT
We report the case of a 59-year-old man who presented with classical-type fever of unknown origin (FUO) during observation of hypertension and polycystic kidney. The presence of malignancy was suspected based on elevation of tumor marker levels. We examined the patient carefully and attempted diagnostic imaging, but definitive diagnosis was difficult due to the presence of multiple hepatic cysts. Hepatic biopsy detected adenocarcinoma, but identifying whether lesions were primary cholangiocellular carcinoma or metastases was difficult, and we were ultimately unable to diagnose the tumors as cholangiocellular carcinoma until autopsy. Polycystic kidney with hepatic cysts and complicated by cholangiocellular carcinoma is rare, but should be considered among the differential diagnosis for FUO, which itself is frequently encountered.
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Anti-glomerular basement membrane disease is an autoimmune disorder characterized progressive renal failure and/or lung hemorrhage. Most of patients present with acute renal failure or acute nephritic feature such as hematuria, proteinuria, and leukocyturia in urinalysis. A part of patients present with pulmonary hemorrhage, anemia, tachypnea, and cyanosis. It is accompanied with transient fever and myalgia but fever of unknown origin (FUO) is very rare condition. We report the atypical case of anti-glomerular basement membrane mediated rapidly progressive glomerulonephritis which presented with FUO and shock after methylprednisolone pulse therapy.
Subject(s)
Humans , Acute Kidney Injury , Anemia , Anti-Glomerular Basement Membrane Disease , Basement Membrane , Cyanosis , Fever of Unknown Origin , Fever , Glomerulonephritis , Hematuria , Hemorrhage , Lung , Methylprednisolone , Myalgia , Proteinuria , Renal Insufficiency , Shock , Tachypnea , UrinalysisABSTRACT
Fever of unknown origin (FUO) means fever that does not resolve spontaneously in the period expected for self-limited infection and whose cause cannot be ascertained despite considerable diagnostic efforts. We experienced a case of FUO associated with systemic vasculitis, which was diagnosed with clinical manifestation, radiographic findings, the presence of anti-neutrophil cytoplasmic antibody (ANCA), and renal biopsy. A 54-year-old female was admitted to our hospital with remittent fever of 3 months. A paranasal sinus (PNS) view revealed maxillary and ethmoidal sinusitis, and urine analysis showed microscopic hematuria. We performed a renal biopsy on the basis of positive ANCA and microscopic hematuria. The renal biopsy showed pauci-immune crescentic glomerulonephritis without granuloma, interstitial inflammation, and small vessel vasculitis. Under the diagnosis of ANCA-associated systemic vasculitis, she was treated with steroid and cyclophosphamide. She showed marked clinical improvement.
Subject(s)
Female , Humans , Middle Aged , Antibodies, Antineutrophil Cytoplasmic , Biopsy , Cyclophosphamide , Diagnosis , Ethmoid Sinusitis , Fever of Unknown Origin , Fever , Glomerulonephritis , Granuloma , Hematuria , Inflammation , Malaria , Systemic Vasculitis , VasculitisABSTRACT
Fever of unknown origin (FUO) means fever that does not resolve spontaneously in the period expected for self-limited infection and whose cause cannot be ascertained despite considerable diagnostic efforts. We experienced a case of FUO associated with systemic vasculitis, which was diagnosed with clinical manifestation, radiographic findings, the presence of anti-neutrophil cytoplasmic antibody (ANCA), and renal biopsy. A 54-year-old female was admitted to our hospital with remittent fever of 3 months. A paranasal sinus (PNS) view revealed maxillary and ethmoidal sinusitis, and urine analysis showed microscopic hematuria. We performed a renal biopsy on the basis of positive ANCA and microscopic hematuria. The renal biopsy showed pauci-immune crescentic glomerulonephritis without granuloma, interstitial inflammation, and small vessel vasculitis. Under the diagnosis of ANCA-associated systemic vasculitis, she was treated with steroid and cyclophosphamide. She showed marked clinical improvement.
Subject(s)
Female , Humans , Middle Aged , Antibodies, Antineutrophil Cytoplasmic , Biopsy , Cyclophosphamide , Diagnosis , Ethmoid Sinusitis , Fever of Unknown Origin , Fever , Glomerulonephritis , Granuloma , Hematuria , Inflammation , Malaria , Systemic Vasculitis , VasculitisABSTRACT
This is a case report of miliary tuberculosis in adult with normal simple chest X-ray finding in early state of FUO. Miliary tuberculosis is fatal, which have nonspecific presenting symptoms. Then, a high index of suspicion and diagnostic persistence, are required for early treatment and cure.
Subject(s)
Adult , Humans , Thorax , Tomography, X-Ray Computed , Tuberculosis, MiliaryABSTRACT
Fever of unknown origin (FUO) is caused by infections (30-40%), neoplasms (20-30%), collagen vascular diseases (10-20%), and numerous miscellaneous diseases (15-20%). The literatures also reveal that 5-15% of FUO cases defy diagnosis, despite extensive studies. Diagnostic advances continuously modify the spectrum of FUO-causing diseases. Modern imaging techniques (e.g., ultrasound, CT scan, MRI) enable early detection of abscesses and solid tumors that used to be difficult to diagnose. But the correct diagnosis can be delayed because the tumor, such as rare hematologic malignancy, is difficult to be detected by various imaging studies. Intravascular lymphomatosis (IVL) is a rare form of non-Hodgkin's lymphoma and generally fatal disease characterized by extensive proliferation of neoplastic mononuclear cells within the lumina of blood vessels. The prognosis is usually extremely poor, with rapid death despite chemotherapy. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. Most patients with IVL present with FUO and nonspecific cutaneous and neurologic manifestations. Peripheral nerve system or pulmonary involvements are not common as initial menifestations. We report a case of intravascular lymphomatosis, presenting as FUO with peripheral polyneuropathy. We made early diagnosis of IVL by video-assisted thoracoscopic lung biopsy. She is improving with good performance after the 4th cycle of chemotherapy till now.
Subject(s)
Humans , Abscess , Biopsy , Blood Vessels , Brain , Collagen , Diagnosis , Drug Therapy , Early Diagnosis , Fever of Unknown Origin , Fever , Hematologic Neoplasms , Lung , Lymphoma , Lymphoma, Non-Hodgkin , Neurologic Manifestations , Peripheral Nerves , Polyneuropathies , Prognosis , Skin , Tomography, X-Ray Computed , Ultrasonography , Vascular DiseasesABSTRACT
Fever of unknown origin (FUO) is caused by infections (30-40%), neoplasms (20-30%), collagen vascular diseases (10-20%), and numerous miscellaneous diseases (15-20%). The literatures also reveal that 5-15% of FUO cases defy diagnosis, despite extensive studies. Diagnostic advances continuously modify the spectrum of FUO-causing diseases. Modern imaging techniques (e.g., ultrasound, CT scan, MRI) enable early detection of abscesses and solid tumors that used to be difficult to diagnose. But the correct diagnosis can be delayed because the tumor, such as rare hematologic malignancy, is difficult to be detected by various imaging studies. Intravascular lymphomatosis (IVL) is a rare form of non-Hodgkin's lymphoma and generally fatal disease characterized by extensive proliferation of neoplastic mononuclear cells within the lumina of blood vessels. The prognosis is usually extremely poor, with rapid death despite chemotherapy. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. Most patients with IVL present with FUO and nonspecific cutaneous and neurologic manifestations. Peripheral nerve system or pulmonary involvements are not common as initial menifestations. We report a case of intravascular lymphomatosis, presenting as FUO with peripheral polyneuropathy. We made early diagnosis of IVL by video-assisted thoracoscopic lung biopsy. She is improving with good performance after the 4th cycle of chemotherapy till now.
Subject(s)
Humans , Abscess , Biopsy , Blood Vessels , Brain , Collagen , Diagnosis , Drug Therapy , Early Diagnosis , Fever of Unknown Origin , Fever , Hematologic Neoplasms , Lung , Lymphoma , Lymphoma, Non-Hodgkin , Neurologic Manifestations , Peripheral Nerves , Polyneuropathies , Prognosis , Skin , Tomography, X-Ray Computed , Ultrasonography , Vascular DiseasesABSTRACT
BACKGROUND: Physicians find fever of unknown origin (FUO) a difficult problem to solve. Analysis of the causes of FUO may be useful in the diagnosis of FUO. We investigated the causes of FUO in the last two decades from 1980 to 1999 and compared the two decades to seek for a trend of changes of the causes of FUO. METHODS: Among 854 patients diagnosed as FUO on discharge, we retrospectively reviewed 278 patients compatible with the Petersdorf's criteria through inpatient and outpatient medical records. RESULTS: There were 144 (51.5%) men and 134 (48.2%) women. Among the 98 patients in the 1980s, infectious disease was the cause in 37 (37.8%) patients, collagen vascular disease in 17 (17.3%), malignancy in 8 (8.2%), miscellaneous in 11 (11.2%), and unidentifiable cause in 25 (25.5%) patients. Among the 180 patients in the 1990s, infectious disease was the cause in 45 (25.0%) patients, collagen vascular disease in 37 (20.5%), malignancy in 34 (18.9%), miscellaneous in 45 (25.0%), and unidentifiable cause in 19 (10.6%) patients. According to the order of frequency, the causes of infectious disease were pulmonary tuberculosis (19.4%), extrapulmonary tuberculosis (8.2%), liver abscess (4.1%) in the 1980s and extrapulmonary tuberculosis (17.2%), pulmonary tuberculosis (4.4%), liver abscess (1.1%) in the 1990s. The diagnostic methods for evaluation of FUO were culture (45.6%), radiology (17.6%), serology (16.2%), and biopsy (10.3%) in the 1980s and radiology (31.5%), biopsy (26.9%), culture (21.5%) and serology (20.0%) in the 1990s. CONCLUSION: Among the causes of FUO, infectious disease decreased and collagen disease and malignancy increased with time. The most common cause of infectious disease was pulmonary tuberculosis in the 1980s but extrapulmonary tuberculosis in the 1990s. Use of radiology and biopsy as diagnostic methods for FUO increased.