Brucella Prostatitis: A Rare Manifestation of Fever of Unknown Origin, Detected by FDG PET/CT.

ABSTRACT: FDG PET/CT is a well-documented imaging investigation to evaluate fever of unknown origin (FUO). Brucellosis is one of the causes of FUO, which can be missed as it requires a longer incubation period for growth on culture media. Rarely, it can involve the prostate. Here, we present a case of FUO with initial negative blood and urine cultures and no localizing signs or symptoms. 18F-FDG PET/CT revealed hypermetabolism in the prostate and seminal vesicles. A repeat blood and urine culture showed the growth of Brucella species after 5 days of incubation, and the patient responded to Brucella-directed antibiotic therapy.

Role of 18 F-FDG PET/CT for providing a targeted approach for etiology of PUO.

AIM: This study aimed to evaluate the potential role of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in providing a targeted approach for diagnosing the etiology of Pyrexia of Unknown Origin (PUO). METHODS: A total of 573 PUO patients were included in this ambispective study, with a mean age of 39.40 ±â€…4.6 years. Patients underwent FDG PET/CT scans using dedicated hybrid scanners. PET/CT data were interpreted by experienced nuclear medicine physicians. The study analyzed the guidance provided by FDG PET/CT for appropriate biopsy sites and assessed concordance between PET/CT findings and histopathological examination. RESULTS: Out of the 573 patients, a final diagnosis was reached for 219 patients, including malignancy, infectious causes, noninfectious inflammatory causes (NIID), and precancerous conditions. FDG PET/CT played a crucial role in guiding clinicians to appropriate biopsy sites, contributing to a higher diagnostic yield. Concordance between PET/CT findings and histopathological examination emphasized the noninvasive diagnostic potential of PET/CT in identifying underlying causes of PUO. Overall, FDG PET/CT contributed to guiding the appropriate site of biopsy or concordance of the first differential diagnosis with the final diagnosis in 50.05% of cases. CONCLUSION: This study highlights the valuable role of FDG PET/CT in providing a targeted approach for diagnosing PUO, showcasing its potential in guiding clinicians towards appropriate biopsy sites and improving the diagnostic yield. The findings underscore the importance of integrating FDG PET/CT into the diagnostic pathway for PUO, ultimately enhancing patient management and outcomes. Further prospective studies are necessary to validate these results and refine the integration of FDG PET/CT in the diagnosis of PUO.

Assessing the clinical utility of abdominal computed tomography in sepsis patients with unknown origin: A retrospective cohort study.

Early identification of the sources of infection in emergency department (ED) patients of sepsis remains challenging. Computed tomography (CT) has the potential to identify sources of infection. This retrospective study aimed to investigate the role of CT in identifying sources of infection in patients with sepsis without obvious infection foci in the ED. A retrospective chart review was conducted on patients with fever and sepsis visiting the ED of Linkou Chang Gung Memorial Hospital between July 1, 2020 and June 30, 2021. Data on patient demographics, vital signs, clinical symptoms, underlying medical conditions, laboratory results, administered interventions, length of hospital stay, and mortality outcomes were collected and analyzed. Of 218 patients included in the study, 139 (63.8%) had positive CT findings. The most common sources of infection detected by CT included liver abscesses, acute pyelonephritis, and cholangitis. Laboratory results showed that patients with positive CT findings had higher white blood cell and absolute neutrophil counts and lower hemoglobin levels. Positive blood culture results were more common in patients with positive CT findings. Additionally, the length of hospital stay was longer in the group with positive CT findings. Multivariate logistic regression analysis revealed that hemoglobin levels and positive blood culture results independently predicted positive CT findings in patients with fever or sepsis without an obvious source of infection. In patients with sepsis with an undetermined infection focus, those presenting with leukocytosis, anemia, and elevated absolute neutrophil counts tended to have positive findings on abdominal CT scans. These patients had high rates of bacteremia and longer lengths of stay. Abdominal CT remains a valuable diagnostic tool for identifying infection sources in carefully selected patients with sepsis of undetermined infection origins.

EANM consensus document on the use of [18F]FDG PET/CT in fever and inflammation of unknown origin.

PURPOSE: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [18F]FDG-PET/CT in FUO and IUO based on current evidence. METHODS: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with "patients with FUO/IUO" as population, "[18F]FDG-PET/CT" as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness. RESULTS: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations. CONCLUSION: FUO and IUO remains a clinical challenge and [18F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50-60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients.

Rare cardiac inflammatory pseudotumor in a toddler: Complementary roles of cardiac magnetic resonance and positron emission tomography.

We present a rare pediatric case of cardiac inflammatory pseudotumor (IPT) with a unique presentation of fever of unknown origin with markedly elevated inflammatory markers. A right atrial mass was discovered incidentally by echocardiography. The cardiac magnetic resonance (CMR) signal characteristics and mass location were not consistent with any of the common benign cardiac tumors of childhood. The presence of high signal intensity on T2 imaging and late gadolinium enhancement, in conjunction with intense metabolic activity at the mass site on positron emission tomography (PET), raised the possibility of an inflammatory or malignant mass. The diagnosis of IPT was confirmed by biopsy. Our case highlights the utility of PET imaging to confirm the inflammatory nature and extent of an IPT.

The Contribution of 18F FDG PET-CT for the Investigation of Fever of Unknown Origin and Inflammation of Unknown Origin.

BACKGROUND: Fever of unknown origin and inflammation of unknown origin are highly challenging diagnostic conditions. The current practice for evaluating patients is to conduct a positron emission tomography-computed tomography (PET-CT) scan as either a first- or a second-line modality. We aimed to assess the contributory effect of PET-CT to the diagnosis and compare it with the contributory effect of CT alone. METHODS: We performed a systematic review and meta-analysis. We included all cohorts that examined the contribution of PET-CT to the investigation of classical fever of unknown origin and inflammation of unknown origin. The primary outcome was the contribution of PET-CT to the final diagnosis. Secondary outcomes were sensitivity and specificity of PET-CT and CT scans, and contribution of a CT scan. We pooled the results of all studies and calculated the pooled contributory effect of PET-CT. RESULT: Thirty-six studies (3516 patients) were included in the systematic review. The pooled contribution of PET-CT was 75.4%. The compiled sensitivity and specificity values for all studies were 85.9% and 59.5%, respectively. Five studies (405 patients) compared between the PET-CT component and the total body CT component. The pooled contribution of a CT scan was 68%. The summed sensitivity and specificity values of a CT scan for all studies were 63.1% and 84.4%, respectively. CONCLUSIONS: PET-CT has a contributory effect of 75% for the diagnosis of fever of unknown origin and inflammation of unknown origin. PET-CT had superior sensitivity and inferior specificity vs the CT scan.

Nuclear Medicine Imaging Tools in Fever of Unknown Origin: Time for a Revisit and Appropriate Use Criteria.

Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing.

Fever of unknown origin in pediatrics: role of nuclear medicine.

Fever of unknown origin (FUO) is a debated issue in numerous scientific studies in adult patients with a not jet-defined workflow in a clinical and diagnostic setting. Few works are published about pediatric patients even if FUO represents a challenging, not infrequent scenario in hospital and outpatient recovery. The fever might be the onset symptom of a transient mild infection or the beginning of a more difficult-to-diagnose and serious pathological condition. In the adult workflow 18FDG PET-CT is nowadays playing a relevant role, considering the limited spread of conventional 99mTc-HMPAO-White Blood Cells scintigraphy. It represents a robust tool for diagnosing the eventual site of infection, but it is limited by procedural complexity and long duration, up to 24 hours. The WBC-scintigraphy is also not suitable for children, only for young adults or adolescents, considering the relevant blood sample entity and the procedural risk for sensitive subjects. The most assessed clinical and diagnostic know-how on Pediatric FUO are summarized and a synthetic flow-chard is presented to support the clinical management and to choose the best diagnostic pathway.

The yield of total body CT in the workup of fever of unknown origin in hospitalized medical patients.

INTRODUCTION: Total body computerized tomography (TBCT) is frequently used as a diagnostic tool for fever of unknown origin (FUO) workup instead of a recommended fluorodeoxyglucose positron emission tomography FDG-PET/CT. We have assessed the TBCT diagnostic yield on a large, unselected cohort of patients with FUO. METHODS: We performed a single-center retrospective cohort study, examining all patients hospitalized in internal medicine between 2012 and 2019 with a documented fever and three negative blood cultures who subsequently had a total-body CT performed. After manually reviewing, we included 408 who met the criteria of FUO. We defined a positive study as a scan that led to the documented final diagnosis. RESULTS: A total of 164 patients (40.2 %) had a positive TBCT result. The majority of positive CT findings were of infectious etiologies (58.5 %), followed by neoplasms (22.8 %) and inflammatory disorders (14.0 %), with the chest (43.9 %) and abdomen (29.8 %) most affected. Using a logistic regression model, a positive scan results were associated with an elevated CRP (p<0.001). Decision tree analysis showed that 55 % of scans of patients with an elevated CRP (>6 mg/dL), low hemoglobin and high leucocyte count (>18000/ml) were positive. Patients without an elevated CRP had a positive scan in only 26 % of tests, and those with also an elevated albumin (>4 gr/dL) and low CRP had positive scan in only 11 % of cases. CONCLUSIONS: TBCT has a clinically significant yield under specific clinical scenarios in medical patients with FUO- reaching 55 % in patients with an elevated CRP and leukocyte count and low hemoglobin. It is reasonable to proceed to TTBCT when FDG-PET/CT is unavailable and in well-defined clinical situations.

Update on imaging in fever and inflammation of unknown origin: focus on infectious disorders.

BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostic challenges that often require an extensive work-up. When first-line tests do not provide any or only misleading clues, second-line investigations such as specialized imaging techniques are often warranted. OBJECTIVES: To provide an overview of the diagnostic value of imaging techniques that are commonly used in patients with FUO/IUO. SOURCES: MEDLINE database was searched to identify the most relevant studies, trials, reviews, or meta-analyses until 31 March 2023. CONTENT: The most important types of second-line imaging tests for FUO and IUO are outlined, including [67Ga]-citrate single-photon emission computed tomography/computed tomography (CT), labelled leukocyte imaging, [18F]-fluorodeoxyglucose positron emission tomography CT ([18F]-FDG-PET), and whole-body magnetic resonance imaging. This review summarizes the diagnostic yield, extends on potential future imaging techniques (pathogen-specific bacterial imaging and [18F]-FDG-PET/magnetic resonance imaging), discusses cost-effectiveness, highlights practical implications and pitfalls, and addresses future perspectives. Where applicable, we provide additional data specifically for the infection subgroup. IMPLICATIONS: Although many imaging examinations are proven to be useful in FUO and IUO, [18F]-FDG-PET/CT is the preferred second-line test when available as it provides a high diagnostic yield in a presumably cost-effective way.

FDG-PET/CT for investigation of pyrexia of unknown origin: a cost of illness analysis.

BACKGROUND: Our study aims to explore the current utilisation of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the diagnostic pathway of pyrexia of unknown origin (PUO) and associated cost of illness in a large tertiary teaching hospital in Australia. METHOD: 1257 febrile patients between June 2016 and September 2022 were retrospectively reviewed. There were 57 patients who met the inclusion criteria of "classical PUO", of which FDG-PET/CT was performed in 31 inpatients, 15 outpatients and 11 inpatients did not have an FDG-PET/CT scan. The patient demographics, clinical characteristics and inpatient cost were analysed, together with the diagnostic performance of FDG-PET/CT and impact on clinical management. RESULT: The mean age, length of stay and total cost of admission were higher for inpatients who received FDG-PET/CT versus those who did not. The median cost per patient-bed-day did not differ between the two groups. Inpatients who received earlier FDG-PET/CTs (≤ 7 days from admission) had shorter length of stays and lower total cost compared to those who received a later scan. A negative FDG-PET/CT scan, demonstrating no serious or life-threatening abnormalities resulted in subsequent discharge from hospital or outpatient clinic in 7/10 (70%) patients. There were 11/40 (28%) scans where ancillary abnormalities were identified, requiring further evaluation. CONCLUSION: FDG-PET/CT showed high diagnostic accuracy and significant impact on patient management in patients with PUO. FDG-PET/CT performed earlier in admission for PUO was associated with shorter length of stay and lower total cost.

Coexistence of FDG-Avid and FDG-Negative Aneurysms in a Patient With Fever of Unknown Origin.

ABSTRACT: A 68-year-old man with intermittent fever of unknown origin for 5 months underwent 18F-FDG PET/CT to detect causative lesion. An 18F-FDG-avid lesion was revealed in the left pelvic iliac vessel region and was highly suggestive of malignancy. One and a half months later, a giant left internal iliac artery aneurysm was identified by CT angiography, corresponding to the 18F-FDG-avid lesion. Combined with elevated inflammatory markers, he was finally diagnosed as having inflammatory internal iliac artery aneurysm. An abdominal aortic aneurysm with low 18F-FDG uptake was also identified.

Do statins decrease vascular inflammation in patients at risk for large-vessel vasculitis? A retrospective observational study with FDG-PET/CT in polymyalgia rheumatica, giant cell arteritis and fever of unknown origin.

OBJECTIVES: [18F] Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can detect the presence of large-vessel vasculitis (LVV) in patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and fever of unknown origin (FUO). The aim of this study was to evaluate whether statins could reduce FDG-PET/CT-assessed vascular inflammation in this group of patients. METHODS: Clinical, demographic, laboratory data, current pharmacological treatments, and cardiovascular risk factors of patients with PMR, GCA and FUO, who underwent FDG-PET/CT, were recorded. FDG uptake was measured at prespecified arterial sites with the mean standardised uptake value (SUV), and with a qualitative visual score, summed up to obtain a total vascular score (TVS). LVV was diagnosed if arterial FDG visual uptake was equal or higher of liver uptake. RESULTS: 129 patients were included (96 with PMR, 16 with GCA, 13 with both PMR and GCA, and 4 with FUO), of whom 75 (58.1%) showed LVV. Twenty out of 129 (15.5%) patients were taking statins. TVS was significantly lower in patients treated with statins (p=0.02), especially in the aorta (p=0.023) and femoral arteries (p=0.027). CONCLUSIONS: Our preliminary results suggest that statins may exert a potential protective role on vascular inflammation in patients with PMR and GCA. Statin use could spuriously decrease FDG uptake of the vessel walls.

Differential diagnosis of lymphoma with 18F-FDG PET/CT in patients with fever of unknown origin accompanied by lymphadenopathy.

PURPOSE: To investigate the value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the differential diagnosis of lymphoma in patients with fever of unknown origin (FUO) accompanied by lymphadenopathy and to develop a simple scoring system to distinguish lymphoma from other etiologies. METHODS: A prospective study was conducted on patients with classic FUO accompanied by lymphadenopathy. After standard diagnostic procedures, including PET/CT scan and lymph-node biopsy, 163 patients were enrolled and divided into lymphoma and benign groups according to the etiology. The diagnostic utility of PET/CT imaging was evaluated, and beneficial parameters that could improve diagnostic effectiveness were identified. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy were 81.0, 47.6, 59.3, and 72.7%, respectively. The lymphoma prediction model combining high SUVmax of the "hottest" lesion, high SUVmax of the retroperitoneal lymph nodes, old age, low platelet count, and low ESR had an area under the curve of 0.93 (0.89-0.97), a sensitivity of 84.8%, a specificity of 92.9%, a PPV of 91.8%, and an NPV of 86.7%. There was a lower probability of lymphoma for patients with a score < 4 points. CONCLUSIONS: PET/CT scans show moderate sensitivity and low specificity in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy. The scoring system based on PET/CT and clinical parameters performs well in differentiating lymphoma and benign causes and can be used as a reliable noninvasive tool. REGISTRATION NUMBER: This study on FUO was registered on http://www. CLINICALTRIALS: gov on January 14, 2014, with registration number NCT02035670.

Higher diagnostic yield of 18F-FDG PET in inflammation of unknown origin compared to fever of unknown origin.

OBJECTIVE: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is an important imaging technique in the workup of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Studies comparing the diagnostic yield of 18F-FDG PET between both entities are lacking. METHODS: Retrospective analysis of FUO/IUO patients who underwent 18F-FDG PET between 2000 and 2019 in the University Hospitals of Leuven (Belgium). 18F-FDG PET images were assessed for accuracy and contribution towards the final diagnosis. Logistic regression was performed to evaluate the association between meeting FUO or IUO criteria and diagnostic contribution of 18F-FDG PET with and without adjustment for confounders. RESULTS: Out of 604 patients, 439 (73%, mean age 56 years, 43% female) underwent 18F-FDG PET imaging, including 349 (79%) classified as FUO and 90 (21%) as IUO. Noninfectious inflammatory disorders were significantly more frequent in the IUO group (37% versus 25%; P = 0.03). 18F-FDG PET imaging had a sensitivity of 93% (89-96%), a specificity of 35% (29-42%), and made a positive contribution to the final diagnosis in 25% (21-29%) of cases. IUO was significantly associated with contributive 18F-FDG PET imaging compared to FUO (aOR 2.21 [95% CI 1.31-3.72]; P = 0.003). Among those with contributive 18F-FDG PET imaging, giant cell arteritis (IUO 25% versus FUO 12%) and polymyalgia rheumatica (IUO 17% versus FUO 1%) were numerically more frequent in the IUO group. CONCLUSION: The diagnostic contribution of 18F-FDG PET was higher among those with IUO, most likely due to differences in diagnostic spectrum.

FDG PET in Evaluation of Patients With Fever of Unknown Origin: AJR Expert Panel Narrative Review.

Fever of unknown origin (FUO) is a diagnostic challenge, with its cause remaining undiagnosed in approximately half of patients. Nuclear medicine tests typically are performed after a negative or inconclusive initial workup. Gallium-67 citrate and labeled leukocytes were previous mainstays of radionuclide imaging for FUO, although they had limited diagnostic performance. FDG PET/CT has subsequently emerged as the nuclear medicine imaging test of choice, supported by a growing volume of evidence. A positive FDG PET/CT result contributes useful information by identifying potential causes of fever, localizing sites for further evaluation, and guiding further management; a negative result contributes useful information by excluding focal disease as the cause of fever and predicts a favorable prognosis. In 2021, CMS rescinded a prior national noncoverage determination for FDG PET for infection and inflammation, leading to increasing national utilization of FDG PET/CT for FUO workup. This article reviews the current status of the role of FDG PET/CT in the evaluation of patients with FUO. The literature reporting the diagnostic performance and yield of FDG PET/CT in FUO workup is summarized, with comparison with historically used nuclear medicine tests included. Attention is also given to the test's clinical impact; protocol, cost, and radiation considerations; and application in children.

Emerging Trends in Radionuclide Imaging of Infection and Inflammation in Pediatrics: Focus on FDG PET/CT and Immune Reactivity.

The most common indication for 18F-FDG PET/CT is tumor imaging, which may be performed for initial diagnosis, staging, therapeutic response monitoring, surveillance, or suspected recurrence. In the routine practice of pediatric nuclear medicine, most infectious, inflammatory, and autoimmune processes that are detected on 18F-FDG PET/CT imaging - except for imaging in fever or inflammation of unknown origin - are coincidental and not the main indication for image acquisition. However, interpreting these "coincidental" findings is of utmost importance to avoid erroneously attributing these findings to a neoplastic process. We review the recent literature on fever of unknown origin as well as inflammation of unknown origin in pediatrics and then focus on the 18F FDG PET/CT imaging findings seen in two specific entities with increased immune reactivity: hemophagocytic lymphohistiocytosis syndrome and the immune-related adverse events associated with checkpoint inhibitors. We will subsequently close with two sections highlighting related topics and relevant references for further reading.