Causes Of Fever Of Unknown Origin Research Articles

Fever of Unknown Origin with Cardiac Mass: Challenging and Interesting Case

: Investigating the source of fever of unknown origin (FUO) is usually one of the diagnostic challenges for clinicians. Furthermore, it is one of the most important causes that should always be considered is cardiac causes. In this case, we evaluated a patient with a cardiogenic cause of FUO; despite all the studies, no definite cause was found, but it responded to empiric treatment.

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

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

Update on Fever of Unknown Origin in Children: Focus on Etiologies and Clinical Approach.

Fever of unknown origin (FUO) can be caused by four etiological categories of diseases. The most common cause of FUO in children is represented by infections, followed by inflammatory conditions and neoplastic causes; a decreasing quote remains still without diagnosis. Despite the fact that several diagnostic and therapeutic approaches have been proposed since the first definition of FUO, none of them has been fully validated in pediatric populations. A focused review of the patient's history and a thorough physical examination may offer helpful hints in suggesting a likely diagnosis. The diagnostic algorithm should proceed sequentially, and invasive testing should be performed only in select cases, possibly targeted by a diagnostic suspect. Pioneering serum biomarkers have been developed and validated; however, they are still far from becoming part of routine clinical practice. Novel noninvasive imaging techniques have shown promising diagnostic accuracy; however, their positioning in the diagnostic algorithm of pediatric FUO is still not clear. This narrative review aims to provide a synopsis of the existent literature on FUO in children, with its major causes and possible diagnostic workup, to help the clinician tackle the complex spectrum of pediatric FUO in everyday clinical practice.

Fever of Unknown Origin in Children: The Challenge of History Taking

A fever of unknown origin (FUO) in children is usually described as a fever of at least 8 days duration with no apparent diagnosis after initial investigations, including taking medical history and preliminary laboratory assessment. Infectious diseases are the most common cause of FUO, followed by rheumatologic and neoplastic conditions. In this report, we present a case of a 15-year-old Caucasian boy with a silent past medical history, who presented at our Pediatric ER department with a three-day history of fever, fatigue, and abdominal pain with diarrhoea. Initial laboratory testing and microbiological work-up were non-significant. At hospital admission, a broad infectious diagnostic work-up was pursued, including serologies and polymerase-chain-reaction (PCR) for CMV, EBV, HAV, Parvovirus, Toxoplasma gondii and Adenovirus, all negative. Given mild splenomegaly and linfadenopathy, systemic Juvenile Idiopathic Arthritis (s-JIA) was suspected, as well as Multi-inflammatory Syndrome in Children (MIS-C), but the patient did not meet their main diagnostic criteria. Malignancy was ruled out by a negative bone marrow fine-needle aspiration cytology and whole-body PET-CT scan. On hospital day 8, Brucella was identified on a new set of blood cultures and a combined antibiotic therapy was started with IV Gentamicin plus per os Doxycycline. The patient’s general conditions rapidly improved, and both fever and diarrhoea resolved. A reassessment of the patient’s medical history before discharge revealed exposure to unpasteurized soft cheese in the weeks prior to the onset of symptoms. This case underlines the importance of taking a complete medical history, as well as a full diagnostic work-up to unveil unusual infectious etiologies behind FUO. After the preliminary negative microbiological tests, a connective tissue disease was ruled out (i.e. lack of cutaneous or articular involvement), as well as malignancy, which led to a closer evaluation for infection and the diagnosis of Brucellosis.

Pyrexia of unknown origin (PUO) and the cost of care in a tertiary care institute in Sri Lanka

BackgroundDespite advancements in diagnostic technology, pyrexia of unknown origin (PUO) remains a clinical concern. Insufficient information is available regarding the cost of care for the management of PUO in the South Asian Region.MethodsWe retrospectively analyzed data of patients with PUO from a tertiary care hospital in Sri Lanka to determine the clinical course of PUO and the burden of the cost incurred in the treatment of PUO patients. Non-parametric tests were used for statistical calculations.ResultsA total of 100 patients with PUO were selected for the present study. The majority were males (n = 55; 55.0%). The mean ages of male and female patients were 49.65 (SD: 15.55) and 46.87 (SD: 16.19) years, respectively. In the majority, a final diagnosis had been made (n = 65; 65%). The mean number of days of hospital stay was 15.16 (SD; 7.81). The mean of the total number of fever days among PUO patients was 44.47 (SD: 37.66). Out of 65 patients whose aetiology was determined, the majority were diagnosed with an infection (n = 47; 72.31%) followed by non-infectious inflammatory disease (n = 13; 20.0%) and malignancies (n = 5; 7.7%). Extrapulmonary tuberculosis was the most common infection detected (n = 15; 31.9%). Antibiotics had been prescribed for the majority of the PUO patients (n = 90; 90%). The mean direct cost of care per PUO patient was USD 467.79 (SD: 202.81). The mean costs of medications & equipment and, investigations per PUO patient were USD 45.33 (SD: 40.13) and USD 230.26 (SD: 114.68) respectively. The cost of investigations made up 49.31% of the direct cost of care per patient.ConclusionInfections, mainly extrapulmonary tuberculosis was the most common cause of PUO while a third of patients remained undiagnosed despite a lengthy hospital stay. PUO leads to high antibiotic usage, indicating the need for proper guidelines for the management of PUO patients in Sri Lanka. The mean direct cost of care per PUO patient was USD 467.79. The cost of investigations contributed mostly to the direct cost of care for the management of PUO patients.

Localized retroperitoneal Rosai-Dorfman-Destombes disease as a cause of fever of unknown origin in adults. Case report and review of the literature.

Rosai-Dorfman-Destombes disease (RDD) is a rare “R” group histiocytic disease with a prevalence of 1:200,000. Herein, we present an extr4mely rare case with localized retroperitoneal RDD manifested as a fever of unknown origin (FUO). This case was managed in an academic setting and illustrates the challenging diagnostics of RDD and FUO. A 53-years-old female was admitted with complaints of night sweats, fever to 39.5 °C, 10 kg weight loss, fatigue, weakness, abdominal discomfort, and headache. On physical examination, there was no peripheral lymphadenomegaly or liver or spleen enlargement. Blood analysis revealed a hemoglobin 10.8 g/dL, elevated C-reactive protein level of 100.6 mg/L, and fibrinogen 6.57 g/L. Blood, throat, and urine cultures and serology tests were negative. Abdominal ultrasonography, transthoracic echocardiography, radiography, and computed tomography of the abdomen were normal. The PET scan showed a retroperitoneal conglomerate on the left side of the aorta. Subtotal resection of the conglomerate was performed. Microscopic examination revealed dilated sinusoids containing a large number of S100+ and CD68+ histiocytes, with marked emperipolesis. The patient recovered uneventfully. Eight months later, she was afebrile and free of complaints, with a 5 kg weight gain and negative PET/CT findings. Localized abdominal RDD can cause FUO and should be considered in the differential diagnosis of localized retroperitoneal masses. PET/CT is useful for diagnosis, staging, and follow-up. Surgery is indicated for biopsy in cases of diagnostic uncertainty or decompression in symptomatic extranodal forms, but can be a definitive treatment for localized RDD. • The localized abdominal RDD could be a possible cause of FUO. • RDD should be considered in the differential diagnosis of localized retroperitoneal mass and FUO. • FDG-PET/CT is a useful diagnostic tool for initial diagnosis, staging, and follow-up. • In localized RDD, the surgery can be a definitive treatment.

Fever of unknown origin (FUO) in children: a single-centre experience from Beijing, China

ObjectiveTo date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the...

Seroprevalence, clinical profile and knowledge, attitudes, and practices (KAPs) of brucellosis in North India in patients with pyrexia of unknown origin and chronic joint pain

Introduction: Brucellosis is a significant but lesser-known cause of pyrexia of unknown origin (PUO) in India. Studies documenting the prevalence of Brucellosis in different parts of India are sparse and few. Clinicians thus usually don’t consider it in their differential diagnosis. This study assesses its prevalence in two groups: febrile patients with unknown etiology and individuals presenting with arthritis and/or joint pains. Knowledge, Attitude, and Practices (KAP) among clinicians about the disease was evaluated.Materials and Methods: This is a prospective study conducted at a tertiary care center of North India catering to urban, semi-urban, and rural populace. Ninety-two patients with fever of unknown origin, arthralgia, or similar constitutional symptoms were recruited in this study. Detailed clinical history was elicited from all patients as per predesigned proforma and a rigorous physical examination was conducted. Following primary screening to rule out malaria, enteric fever, and leptospirosis, secondary screening for Brucellosis was done by Rapid Screen Test (PUO screen) and IgM and IgG ELISA. A predesigned survey was used for assessing KAP among clinicians about Brucellosis.Results: Brucella infection was diagnosed in 27 (29.3%) cases. The most common symptoms among the patients apart from fever were arthralgia (77.8%), fatigue (70.8%), pallor (66.1%), headache (59.2%), backache (53.8%) and cough (33.3%). PUO screen is a specific test for brucellosis but lacks sensitivity. It detects acute cases but misses chronic cases. IgM ELISA being more sensitive should be used for confirmation. Low ODs point to chronic brucellosis which was confirmed by IgG ELISA. Normal CRP levels in patients with PUO and chronic joint pains should point to brucellosis. KAP revealed that 25% to 50% of doctors considered Brucella in their differential diagnosis of acute and chronic fever respectively while 10% Orthopedics considered it in cases of arthralgia.Conclusion: Our results highlight the significance of Brucella as a cause of PUO and arthralgia. Brucellosis is an underrecognized but important cause of pyrexia of unknown origin and chronic joint pain. It should be actively suspected, diagnosed, and treated.International Journal of Human and Health Sciences Vol. 06 No. 01 January’22 Page: 80-88

Etiology and clinical characteristics of fever of unknown origin in 357 pediatric patients

Objective: To explore the etiologies and clinical characteristics of fever of unknown origin (FUO) and to provide clues for early diagnosis of FUO. Methods: The data about etiology, age, sex, clinical course, length of hospital stays and the expression levels of inflammatory factors in fever phase of 357 pediatric inpatients who were diagnosed with FUO in Children's Hospital of Fudan University from 1 January 2016 to 31 December 2020 were collected and retrospectively analyzed. Participants were grouped into infectious disease, inflammatory disease, malignancy and others and according to the classification of diseases and also grouped into those aged<1 year, 1-<3 years,3-<6 years, 6-<12 years and 12-<18 years. Comparisons between groups were performed using the Mann-Whitney U test, Kruskal-Wallis H test and χ² test. Results: Among the 357 patients (217 males and 140 females). The age of onset was 3.9 (1.3, 9.2) years and visiting age was 5.1 (2.0, 9.3) years. The time-consuming of diagnosis was 94 (66, 213) days. The hospital stay was 8 (6, 14) days. The most frequently identified cause of FUO was infectious diseases (163 cases, 45.7%), followed by non-infectious inflammatory diseases (133 cases, 37.2%), malignancy (21 cases, 5.9%) and others (40 cases, 11.2%). The patients at younger age were more likely to be attacked by malignancy, oncologic diagnoses, and others, nevertheless patients at older age were more likely to be attacked by non-infectious inflammatory diseases oppositely (9.8 (3.6, 11.5) vs. 3.0 (1.2, 7.0), 2.3 (1.0, 5.2), 0.9 (0.5, 1.8) years, U=41.30, 15.94, 37.08, all P<0.01);106 (65%) patients were male, and 57 (35%) patients were female. This result indicated that boys were more susceptible to infectious diseases (χ²=14.73, P<0.01). Analysis of inflammatory factors in serum among 103 patients, interleukin (IL)-6 level in 40 infectious diseases patients (9 (2, 38) ng/L) was significantly lower than those of 6 tumor patients (89 (64, 599) ng/L) and 57 non-infectious inflammatory diseases patients (25 (8, 78) ng/L, U=51.05, 15.70, both P<0.05), no significant difference was observed in IL-2, IL-4, IL-10, tumor necrosis factor α and interferon among the groups (all P>0.05). The patients grouped into those aged 1-<3 years and 3-<6 years were more likely to be attacked by infectious diseases (51.3% (59/115) and 57.1% (40/70)), while patients grouped into those aged 6-<12 years and 12-<18 years were more likely to be attacked by non-infectious inflammatory diseases (55.6% (65/117) and 72.4% (21/29)). Conclusions: Infectious disease is still the main cause of FUO in children and the boys are more susceptible to infectious diseases. However, the morbidity of non-infectious inflammatory diseases increases to number 1 in FUO of children over 6 years of age.

The Use of Chitotriosidase as a Marker of Active Sarcoidosis and in the Diagnosis of Fever of Unknown Origin (FUO).

Sarcoidosis is a multi-organ inflammatory granulomatosis with a lung-predominant involvement. The aim of this study was to investigate the use of serum chitotriosidase (CHIT1) in patients with fever of unknown origin (FUO); the patients with confirmed diagnosis of active sarcoidosis were compared with ones affected by inactive or treated sarcoidosis. CHIT1 activity was evaluated in 110 patients initially admitted at the hospital as FUOs. The overall performance of CHIT1 for active sarcoidosis diagnosis was assessed by performing an area under the receiver operating characteristic curve analysis (AUROC). The sarcoidosis patients were significantly older than the FUO patients not affected by sarcoidosis (p < 0.01). CHIT1 showed a good accuracy as a biomarker for active sarcoidosis in patients explored for FUO (AUROC 0.955; CI 95% 0.895–0.986; p < 0.001). A CHIT1 value >90.86 showed 96.8% sensitivity (84.2–99.9) and 85.5% specificity (75–92.8) in discriminating active sarcoidosis from other causes of FUO. CHIT1 significantly discriminated active versus inactive/under treatment sarcoidosis patients (with lower enzyme activity) (ROC analysis, sensitivity: 96.9%, specificity: 94.7%, value >83.01 nmol/mL/h, AUROC: 0.958, 0.862–0.994, p < 0.001) compared to ACE (ROC analysis, sensitivity: 25.8%, specificity: 93.7%, value >65 UI/L). In conclusion, CHIT1 is a reliable/sensitive biomarker of active sarcoidosis, with values significantly decreasing in remitted/treated patients. It significantly discriminates active sarcoidosis from FUO patients, providing a useful tool in the diagnosis-assessing process.

Fever of Unknown Origin - Different Centuries, Different Patterns

Background: Imaging techniques used in the last decades, and reported changes in various disease prevalence, may have dramatically influenced causes of Fever of Unknown Origin (FUO) Objectives: Our study’s objectives were to identify changes in prevalence and etiologies of FUO, since our previous study two decades ago, to clarify the most beneficial diagnostic strategies, and to investigate the long-term outcomes of undiagnosed and diagnosed patients Methods: Medical files with “fever” as a cause for admission and at least one-week hospitalization were evaluated. Patients were screened based on Petersdorf’s classic criteria. An interview was performed three months to twelve years after hospitalization Results: 3691 patients fit our primary selection criteria in 2004-2016; 141 patients fit Petersdorf’s criteria for FUO. The most common cause of FUO was infectious disease (39%), mainly bacterial (29%), though decreased from our previous study (39% vs 55%). There were dramatic increases in the incidence of malignancy (19% vs 7.9%) and inflammatory (20% vs 2%) etiologies and less undiagnosed cases (22% vs 32.7%). Weakness and weight loss were the most common co-complaints (80% all coexisted). Elevated ESR (97%), elevated CRP (95%) and anemia (80%), were the most common pathologic laboratory examinations found. Abdominal CT, blood cultures and serology proved to be the most valuable diagnostic tests. Long-term follow up interviews revealed that a final diagnosis was often reached during the patients’ next admission (20% out of 70%). 2% of patients died during the feverish episode and 34% died three months to twelve years after the episode Conclusions: Infections (mainly bacterial) remain the most common cause for FUO in southern Israel in the 21th century; although there is a remarkable increase in the rate of vasculitis and malignancy. When PET is not available, a thorough clinical examination including appropriate laboratory and imagine examination, as well as precise history taking are essential. Blood cultures and abdominal CT are the most useful diagnostic tests. Most undiagnosed cases resolved within days of discharge or are diagnosed in a following admission

Sub-Acute Thyroiditis Presenting as Pyrexia of Uknown Origin

Introduction: Pyrexia of unknown origin (PUO) is often a diagnostic challenge. Common causes currently reported include non-infectious inflammatory disorders (NIID) (30.6%), infections (23.1%), malignancy (10.7%) and miscellaneous (12.4%). However, 23.1% remain undiagnosed despite extensive investigations. Fever is a component of subacute thyroiditis (SAT) in 28-83% of subjects reported in the literature. But its presentation as a PUO is reported only in a handful of subjects. Case Presentation: A 71-year-old Asian male presented with evening fevers of 2-3 weeks duration. He had no accompanying sweats, cough, breathlessness, or weight loss. He had a past history of TB, polio, hydatid cyst and hypertension for which he was on treatment. He was a teetotaler. Several family members living in his native land had active TB and he visited them often. Clinical examination at initial presentation was unremarkable. He interrupted investigations to go back to Asia, and became unwell for over 6 weeks with evening fevers and sweating, a weight loss of over 7 kg, and a poor appetite. At this point he had no neck pain, palpitations or bowel abnormalities. Clinical examination continued to be normal upon his return to the UK and in the Endocrine Clinic. Investigations: Investigations were done to exclude (a) infections - There was no growth of pathogenic organisms in repeated blood, urine and sputum cultures. Screening tests for TB, hepatitis, and glandular fever were negative. Blood screens for malarial parasites, amoebic and Brucella serology, and stools examination and culture were also negative. Echocardiography was normal. (b) Malignancy - Urine Bence Jones proteins and serum protein electrophoresis were normal. Bone marrow examination was suggestive of Leishmaniasis but a PCR test excluded this diagnosis. Humoral markers of malignancy were negative. CT scans of the thorax, abdomen and pelvis were normal and did not show any evidence of visceral abnormalities (c) NIID - CRP 120, ESR 130, with blood tests consistent with iron deficiency. Autoimmune screening for dsDNA, ANA, ANCA were negative. Upon return to the UK a PET/CT scan showed the diffuse tracer uptake in both thyroid lobes and changes consistent with a large left lobe. Free thryroxine was 28pmol/l (reference range 9-19.1), and TSH was undetectable (<0.004 mU/l). Thyrotrophin receptor antibodies were negative. Management and conclusion He was given carbimazole initially but this was stopped as he became severely hypothyroid. This hypothyroidism persisted for several months even after stopping carbimazole but reversed spontaneously. He therefore had a biphasic pattern of thyroiditis typical of SAT. There are only 9 previous cases reported of SAT presenting as PUO. Although SAT is a rare cause of PUO, early thyroid testing and if necessary, functional thyroid imaging should be considered in subjects with PUO to confirm it.

Etiology of fever of unknown origin in children.

Objectives: To determine the etiology of Fever of Unknown Origin (FUO) in children. Study Design: Prospective Observational study. Setting: Department of Pediatric Medicine, The Children's Hospital, Lahore. Period: August 2019 to January 2020. Material &amp; Methods: A total of 45 children aged between 01 to 180 months (15 years), having FUO were included. FUO was defined as a temperature of greater than 100.4ºF documented by a health care provider, persisting over a period of three weeks and for which no cause could be identified after at least 8 days of evaluation. All the study information was analyzed by using standard software SPSS 20. The quantitative variables like age and duration of fever before hospital admission were presented as mean and standard deviation. Qualitative variables like sex, antibiotic therapy use before definitive diagnosis and various diagnoses made were presented as frequencies and percentages. Results: The patient’s age range was from 01 to 180 months with mean of 80±45.12 months and male to female ratio was 2.2:1. Definitive diagnosis was made in 37(82.2%) patients. Infections were the predominant cause of FUO (44.4%) followed by malignancy (24.4%). Tuberculosis was the most common infection while Acute Lymphoblastic leukemia dominated the malignancy. Systemic lupus erythematosus was the most commonly diagnosed connective tissue disorder. There was a significant association between duration of fever and the ultimate diagnosis (p=0.01). Conclusion: Infectious diseases were the most common cause of FUO followed by malignancy, connective tissue disorders and miscellaneous causes.

Fever of unknown origin (FUO) on a land on cross-roads between Asia and Europa; a multicentre study from Turkey.

The differential diagnosis of Fever of Unknown Origin (FUO) is still a major clinical challenge despite the advances in diagnostic procedures. In this multicentre study, we aimed to reveal FUO aetiology and factors influencing the final diagnosis of FUO in Turkey. A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated. The etiologic distribution of FUO was infections (44.9%), malignancies (15.42%), autoimmune/inflammatory (11.68%) diseases, miscellaneous diseases (8.41%) and undiagnosed cases (19.62%). Brucellosis (10.25%), extrapulmonary tuberculosis (6.54%) and infective endocarditis (6.54%) were the most frequent three infective causes. Solid malignancies (7.1%) and lymphoma (5.6%), adult-onset still's disease (6.07%) and thyroiditis (5.14%) were other frequent diseases. The aetiological spectrum did not differ in elderly people (P<.05). Infections were less frequent in Western (34.62%) compared with Eastern regions of Turkey (60.71%) (P<.001, OR: 0.31, 95% Cl: 0.19 to 0.60). The ratio of undiagnosed aetiology was significantly higher in elderly people (p: 0.046, OR: 2.34, 95% Cl: 1.00 to 5.48) and significantly lower in Western Turkey (P: .004, OR: 3.07, 95% Cl: 1.39 to 6.71). Brucellosis, extrapulmonary tuberculosis and infective endocarditis remain to be the most frequent infective causes of FUO in Turkey. Solid tumours and lymphomas, AOSD and thyroiditis are the other common diseases. The aetiological spectrum did not differ in elderly people, on the other hand, infections were more common in Eastern Turkey. A considerable amount of aetiology remained undiagnosed despite the state-of-the-art technology in healthcare services.

Utility of a Simple Scoring System in Differentiating Bacterial Infections in Cases of Fever of Unknown Origin.

Infectious disease is the leading cause of fever of unknown origin (FUO). Serum inflammatory markers historically used to diagnose bacterial infection have sufficient diagnostic sensitivity but low specificity. This study aimed to develop a simple scoring system for differentiating bacterial infections from other causes of early-stage FUO. This study included a retrospective cohort of patients presenting with FUO at the Huashan Hospital (January 2014 to June 2017). The diagnostic utility of serum inflammatory markers for bacterial infection was evaluated using the receiver operating characteristic (ROC) curve analysis. Relevant markers were subsequently measured prospectively in a separate cohort of FUO patients (December 2017 to May 2019). A scoring system was based on inflammatory markers and other test results. Bacterial infection was identified in 34% of patients in the retrospective cohort. The area under the ROC curve (AUC) was 0.644 (95% confidence interval [CI], .595-.693) for C-reactive protein, 0.624 (95% CI, .573-.675) for procalcitonin, and 0.646 (95% CI, .595-.697) for serum ferritin (SF) in diagnosing bacterial infection. Bacterial infection was found in 29% of cases in the prospective cohort. A model based on serum amyloid A (SAA) and SF levels and neutrophil percentage yielded an AUC of 0.775 (95% CI, .695-.854). Validation analysis indicated lower probability (<15%) of bacterial infection for patients with a score <16.5 points. A scoring system based on SAA and SF levels and neutrophil percentage can help distinguish bacterial infection from other causes of FUO, potentially reducing antibiotic use.

The diagnostic value of 18F-FDG PET/CT in identifying the causes of fever of unknown origin

This study investigated the clinical significance of 18F-fluorodeoxyglucose positron emission tomography / computed tomography (18F-FDG PET/CT) in identifying the causes of fever of unknown origin (FUO). Patients with a fever who received an 18F-FDG PET/CT examination were retrospectively selected. The means of the two groups were compared using an independent-samples t-test. Among the 89 included patients, 66 were diagnosed using 18F-FDG PET/CT. The sensitivity, specificity and diagnostic accuracy of 18F-FDG PET/CT for the diagnosis of patients with FUO were 84.5%, 25.8%, and 64.0%, respectively. The detection rates of 18F-FDG PET/CT for neoplastic diseases, infectious diseases and non-infectious inflammatory diseases were 100%, 61.3%, and 75%, respectively. The difference in C-reactive protein (CRP) levels between the two groups was statistically significant. 18F-FDG PET/CT has great clinical importance in diagnosing and identifying causes of FUO and improves the accuracy of FUO diagnosis when combined with serum CRP levels.

Highlighting the Role of Infections in the Etiology of Fever of Unknown Origin Pointing out Toxoplasmosis; in Port Said Governorate

Background and study aim: Fever of unknown origin (FUO) is a state of febrile illness for more than three weeks, with a body temperature greater than 38.3 °C on several occasions and uncertain diagnosis. Conditions blamed for FUO were categorized as infectious diseases, non-infectious inflammatory diseases, neoplasms along with miscellaneous causes. This study aims to identify the infectious causes of FUO counting the parasitic causes in Port-Said Fever Hospital/ Egypt. Patients and Methods: 341 patients admitted to Port-Said Fever Hospital/ Egypt during the period from November 2017 till May 2018 complaining of prolonged fever ≥ 3 weeks, without a definite diagnosis, were included in this study. Complete history taking and clinical data including pattern, duration and degree of temperature, in addition to other co-morbidities, radiological examination, laboratory investigations, and clinical evaluation were reported for each patient. Results: The majority of affected cases were adult males, lived in urban areas, and were in contact with animals. Luncheon and beef were the commonest types of consumed food among the studied population. The uppermost detected infection was tuberculosis (17%) followed by typhoid and Brucella infection (11.7% for each), toxoplasmosis and hepatitis were detected in 2.9% and 1.8% respectively. After investigations, 5.9% of the studied group had hepato-splenomegaly and 77.4% of them presented with lymphocytosis. Clinically, 78.9% of patients had lymphadenopathy and 1.8% had jaundice. Additionally, 75.4% of cases presented with an intermittent fever while 24.6% with continuous fever. Approximately 57.2% of them had fever for three weeks and the majority of patients had fever ≥ 39°c. Conclusion: Tuberculosis, typhoid fever, and brucellosis signified the major identified infectious causes for FUO in Port Said governorate/Egypt. Toxoplasmosis can be represented as one of FUO infectious causes. Patients with toxoplasmosis either presented with lymphadenopathy or not, all of them had hepatosplenomegaly, high CRP, leucocytosis, and eosinophilia.

Diagnostic Value of 18F-FDG-PET/CT in Patients with FUO.

Conventional diagnostic imaging is often ineffective in revealing the underlying cause in a considerable proportion of patients with fever of unknown origin (FUO). The aim of this study was to assess the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with FUO. We retrospectively reviewed 18F-FDG-PET/CT scans performed on 50 consecutive adult patients referred to our department for further investigation of classic FUO. Final diagnosis was based on histopathological and microbiological findings, clinical criteria, or clinical follow-up. Final diagnosis was established in 39/50 (78%) of the patients. The cause of FUO was infection in 20/50 (40%), noninfectious inflammatory diseases in 11/50 (22%), and malignancy in 8/50 (16%) patients. Fever remained unexplained in 11/50 (22%) patients. 18F-FDG-PET/CT scan substantially contributed to the diagnosis in 70% of the patients, either by identifying the underlying cause of FUO or by directing to the most appropriate site for biopsy. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG-PET/CT for active disease detection in patients with FUO were 94.7%, 50.0%, 84.0%, 85.7%, and 75.0%, respectively. In conclusion, whole-body 18F-FDG-PET/CT is a highly sensitive method for detection of the underlining cause of FUO or for correctly targeting suspicious lesions for further evaluation.

Role of FDG-PET/CT in children with fever of unknown origin

PurposeTo determine the role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) in children with fever of unknown origin (FUO).MethodsThis retrospective single-center study included 110 children (0–18 years) with FUO who underwent FDG-PET/CT between 2010 and 2019. The diagnostic value of FDG-PET/CT for identifying cause of fever was calculated, treatment modifications after FDG-PET/CT were assessed, and logistic regression analyses were performed to identify clinical and biochemical factors associated with FDG-PET/CT outcome.ResultsIn 53 out of 110 patients (48%), FDG-PET/CT identified a (true positive) cause of fever. Endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) were the most common causes of FUO. In 42 patients (38%), no cause of fever was found on FDG-PET/CT. In 58 out of 110 patients (53%), treatment modifications were made after FDG-PET/CT. FDG-PET/CT achieved a sensitivity of 85.5%, specificity of 79.2%, positive predictive value of 84.1%, and negative predictive value of 80.9%. On multivariate logistic regression, C-reactive protein was positively associated with finding a true positive focus of fever on FDG-PET/CT (OR = 1.01 (95% CI 1.00–1.02) per mg/L increase in CRP), while leukocyte count was negatively associated with finding a true positive focus of fever (OR = 0.91 (95% CI 0.85–0.97) per 109 leukocytes/L increase).ConclusionFDG-PET/CT is a valuable diagnostic tool in the evaluation of children with FUO, since it may detect a true underlying cause in almost half (48%) of all cases where none was found otherwise. It allows full-body evaluation in patients without disease-specific symptoms on one examination. CRP and leukocyte count were significantly associated with FDG-PET/CT results, which may contribute to a priori assessment on the outcome of FDG-PET/CT. Future research could be aimed at evaluating more patient-specific factors to prospectively estimate the added value of FDG-PET/CT in children with FUO.

Pericardial sarcoidosis presenting as PUO diagnosed on FDG PET CT scan.

Pyrexia of unknown origin (PUO) is a common problem in day-to-day practice. FDG PET CT is an established investigation that aids in identifying the cause of PUO. Due to its high sensitivity PET detects an occult hypermetabolic focus in the body where CT helps in anatomical localization, vascularity, enhancement characteristics of the lesion detected on PET. It helps to differentiate benign versus malignant cause and target biopsy. Tuberculosis, lymphoma, pyelonephritis, thyroiditis appear hypermetabolic on FDG PET CT. Pericardial sarcoidosis is rare and not reported in literature as a cause of PUO. Presented here is a case of PUO secondary to pericardial granulomatosis diagnosed on PET CT. Cardiac MRI also helps in better tissue characterization and associated myocardial involvement of sarcoidosis. Histology confirmed the diagnosis of pericardial sarcoidosis in this case.