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Objective: Bone marrow examination is valuable for identifying the cause of fever of unknown origin (FUO) in HIV-infected patients. Based on the outcomes of bone marrow examination of patients with FUO, we aimed to develop a predictive model for identifying the factors that can increase the diagnostic yield of bone marrow examination., Design: For this retrospective cohort study, we enrolled HIV-infected patients, aged more than 15 years and diagnosed with FUO, at Songklanakarind Hospital in Southern Thailand, between January 2009 and December 2019., Methods: Evaluations were based on bone marrow aspiration, biopsy, and culture; any missing data were imputed with regression imputation., Results: Among the final 108 included patients, 44 (40.74%) showed positive bone marrow results. The diagnoses mainly comprised histoplasmosis, penicilliosis, and tuberculosis. Bone marrow examination led to treatment modifications in approximately 33% patients. Platelet count less than 150 000 cells/μl, alkaline phosphatase (ALP) level at least 200 U/l, and no previous antibiotic treatment were significantly associated with higher diagnostic yields. The HIV bone marrow (HIVBM) model, comprising of spleen size, hematocrit (Hct), platelet count before bone marrow examination, ALP level at admission, and previous antibiotic treatment, was generated as a nomogram to predict the diagnostic yield of bone marrow examination in HIV-infected patients with FUO., Conclusion: The results of this study indicate that the HIVBM model can be used to predict the diagnostic yield of bone marrow examination, and therefore assist in clinical decision-making regarding bone marrow procedures, to be performed for identifying the origin of fever in HIV-infected patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Fever of unknown origin in adolescents is a challenging disease state for which potential underlying etiology can include infectious, non-infectious inflammatory, and malignancy processes. Careful and thorough history (including exposure history), serial examination, and targeted laboratory and imaging testing is critical for these patients. In adolescents in which an etiology is discovered, infectious etiology remains the most prevalent, followed by non-infectious inflammatory diseases. In patients with non-diagnostic overall reassuring work up, the prognosis is typically self-limiting and favorable., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prolonged fever of 38.3°C or higher for at least 3 weeks' duration has been termed fever of unknown origin if unexplained after preliminary investigations. Initially codified in 1961, classification with subgroups was revised in 1991. Additional changes to the definition were proposed in 1997, recommending a set of standardized initial investigations. Advances in diagnosis and management and diagnostic testing over the last 3 decades have prompted a needed update to the definition and approaches. While a 3-week fever duration remains part of the criteria, a lower temperature threshold of 38°C and revised minimum testing criteria will assist clinicians and their patients, setting a solid foundation for future research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to the absent or deficient activity of lysosomal hydrolase a-galactosidase A (α-Gal A), which leads to the accumulation of its substrates in various organs and tissues. Classic clinical manifestations include angiokeratomas, proteinuria, renal failure, neuropathic pain, and left ventricular hypertrophy. Fever is one of the rare symptoms that may occur during FD., Methods: Three Chinese Han patients with FD referred to Peking Union Medical College Hospital were reported. The complete medical records were established, and detailed data were collected. Whole-exome sequencing by next-generation sequencing and α-Gal A enzyme activity assay were performed to confirm the diagnosis., Results: These three patients all presented with recurrent fever of unknown origin initially, accompanied with arthralgia/arthritis and other symptoms. We identified two known variants in the GLA gene, c.1176_1179delGAAG and c.782G>A (p.G261D), and a novel variant c.440G>A (p.G147E) which is likely pathogenic in our patient., Conclusions: FD should be considered as a rare cause of recurrent fever of unknown origin. The coexistence of gene variants related to systemic autoinflammatory diseases may make the clinical phenotypes of FD more complex and prone to recurrent fever., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The diagnosis and treatment of fever of unknown origin (FUO) are huge challenges to clinicians. Separating the etiologies of FUO into infectious and non-infectious disease is conducive to clinical physicians not only on making decisions rapidly concerning the prescription of suitable antibiotics but also on further analysis of the final diagnosis. In order to develop and validate a diagnostic tool to efficiently distinguish the etiologies of adult FUO patients as infectious or non-infectious disease, FUO patients from the departments of infectious disease and internal medicine in three Chinese tertiary hospitals were enrolled retrospectively and prospectively. By using polynomial logistic regression analysis, the diagnostic formula and the associated scoring system were developed. The variables included in this diagnostic formula were from clinical evaluations and common laboratory examinations. The proposed tool could discriminate infectious and non-infectious causes of FUO with an area under receiver operating characteristic curve (AUC) of 0.83, sensitivity of 0.80 and specificity of 0.75. This diagnosis tool could predict the infectious and non-infectious causes of FUO in the validation cohort with an AUC of 0.79, sensitivity of 0.79 and specificity of 0.70. The results suggested that this diagnostic tool could be a reliable tool to discriminate between infectious and non-infectious causes of FUO.

Background: Bone marrow biopsy (BMB) is an accepted investigation in fever of unknown origin (FUO) to uncover haematological malignancies, such as lymphoma, and sometimes infections. With the advance in imaging modalities, such as 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to identify the focus of lymphoma, BMB may not contribute to the diagnosis when there are no other clinical features to suggest an underlying haematological disease., Aim: To investigate the utility of BMB in determining the cause of FUO, when there are no other indications for BMB., Methods: Medical records of adult patients who had BMB performed for FUO or febrile illness from 1 January 2005 to 31 December 2014 in four metropolitan tertiary hospitals in Melbourne, Australia were reviewed. Patients with other concurrent indications for BMB, known human immunodeficiency virus infection and previously diagnosed connective tissue diseases were excluded., Results: Seventy-three patients were included in the study. Fifty-one patients had a final diagnosis for fever (systemic inflammatory diseases, infective, malignancy or other) while 22 patients had no diagnoses. In only 10 patients (13.7%) did BMB contribute to the diagnosis, finding either malignancy or granulomata. However, all these diagnoses could have been made without BMB. Two patients with diffuse large B-cell lymphoma had normal BMB. FDG-PET was helpful in making a diagnosis in eight (25%) out of 32 patients., Conclusion: Performing BMB in patients with FUO and no other haematological abnormalities is of very limited value, and other investigations, such as FDG-PET, may be more likely to help establish a definitive diagnosis., (© 2019 Royal Australasian College of Physicians.)

Five-year clinico-laboratory data from 99 (one HIV seropositive) adults (mean age = 41.3 ± 20.4 years) who underwent bone marrow examination for fever persisting for ≥ 1 week were analysed and correlated with microbiological characteristics. Infections, reactive marrow changes and haematolymphoid malignancies were most commonly associated with fever. A high concordance rate of 71% was noted between aspiration and trephine biopsies. Bone marrow granulomas (BMG) were seen exclusively on sections and were most commonly of tubercular and typhoidal in origin (two Salmonella Typhi, one Salmonella Paratyphi A). The common aetiologies associated with fever and cytopenia(s) were BMG, acute leukaemia and haemophagocytic lymphohistiocytosis (HLH; n = 3). The yield from bone marrow culture was inferior compared to other body fluids. In conclusion, bone marrow histology is superior to smears in the evaluation of prolonged fever. Marrow culture may not be useful in immunocompetent individuals other than if Salmonellosis is suspected.

Competing Interests: None

"Cepacia syndrome", caused by Burkholderia cepacia complex and often associated with cystic fibrosis, carries a high mortality rate. It is rare for Burkholderia multivorans, a species within the B. cepacia complex, to cause cepacia syndrome even among patients with cystic fibrosis. This is the first reported fatal case of cepacia syndrome caused by B. multivorans occurring in a pediatric liver transplant recipient who does not have cystic fibrosis. We describe the unique characteristics of this pathogen among the non-cystic fibrosis population and the importance of early recognition and treatment., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Focal myositis is an uncommon inflammatory pseudotumor of the skeletal muscle that may mimic neoplastic and inflammatory diseases. We present one case of focal myositis involving the left proximal vastus lateralis and vastus intermedius, and left soleus showing intense FDG uptake on FDG PET/CT. This case indicates that focal myositis should be considered as a differential diagnosis in patients with focal hypermetabolic muscular lesions, including benign and malignant tumors, necrotizing autoimmune myopathy, nodular fasciitis, myositis ossificans, and muscular sarcoidosis.

Background: Fever of unknown origin is often a diagnostic dilemma for clinicians due to its extremely broad differential. One of the rarer categories of disease causing fever of unknown origin is malignancies; of these, soft tissue sarcoma is one of the least common. Soft tissue sarcomas make up < 1% of all adult malignancies and often do not present with any systemic manifestations or neoplastic fevers., Case Presentation: A 73-year-old Caucasian woman presented with a 2-week history of fever and profound fatigue. The only other symptom she endorsed was a transient history of left knee pain, initially thought to be unrelated. There was no clear cause on initial examination and routine investigations, but her C-reactive protein was significantly elevated at 207 mg/L. Blood cultures and a urine culture were drawn. She was admitted to hospital for further investigation and placed on empiric antibiotics. Her blood cultures were negative, but she had one further fever in hospital. Computed tomography scans did not yield a cause of her fever. No vegetations were seen on echocardiography. Antibiotics were stopped as she did not seem to have an acute infectious cause of her fever. No new symptoms developed. She felt well enough to proceed with out-patient follow up and was discharged after 8 days in hospital. At 1-month post-discharge: no resolution of symptoms, but she endorsed a recurrence of her left knee pain. Ultrasound and magnetic resonance imaging revealed a 4.5 × 6.8 × 11.6 cm soft tissue mass, identified as a sarcoma on biopsy. She subsequently underwent a distal femur resection. Final staging was pT2bN0M0. She underwent adjuvant radiation therapy, but was found to have developed metastatic disease., Conclusion: This case revealed an atypical presentation of a rare soft tissue sarcoma as the cause of the illness. The etiology behind a fever of unknown origin can be difficult to elucidate, making the approach to investigation particularly important. Repeated history-taking and serial physical examinations can be crucial in guiding investigations and ultimately arriving at a diagnosis. In addition, we believe this case highlights the adage that no seemingly innocuous symptom should be left out when working up a condition with such an extensive and complex differential.

This case describes a patient being considered for combined liver-kidney transplantation for Caroli's disease with a failed renal transplant. A chronic septic focus could not be located with standard imaging techniques, such as ultrasonography and computed tomography. This case report highlights the observation that a retained non-functioning transplant can be the cause of fever of unknown origin and PET-CT can be useful in diagnosing these challenging cases., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The management of children with fever without apparent sources (FWAS) is difficult. This study aimed to evaluate the diagnostic accuracy of procalcitonin (PCT) in detecting serious or invasive bacterial infection (SBI or IBI) in children with FWAS. Areas covered: A systematic review of literature from 2007 to 2017 was performed on Medline. Twelve studies were included, involving 7,260 children with FWAS and analyzing the diagnostic performance of PCT. Four meta-analyses were performed to calculate pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve for PCT in detecting SBI and IBI, at two different thresholds. Considering IBI, PCT sensitivity and specificity at a threshold of 0.5 ng/mL were 0.82 and 0.86, respectively; at a threshold of 2 ng/mL sensitivity and specificity were 0.61 and 0.94, respectively. In detecting SBI, PCT performance was lower, with 55% sensitivity and 85% specificity at a threshold of 0.5 ng/mL, and 30% sensitivity and 95% specificity at a threshold of 2 ng/mL. Expert commentary: Considering IBI, results showed high diagnostic accuracy for PCT. Conversely, PCT performance in diagnosis of SBI was poor. These findings suggest that PCT level determination could be helpful in detecting meningitis, bacteremia and sepsis in children with FWAS.

A 59-year-old woman suffered from fever and upper abdominal pain. The computed tomography (CT) scan revealed a liver lesion. Conventional imaging techniques (CT, magnetic resonance imaging, contrast-enhanced ultrasonography) did not allow for a consistent diagnosis. Fine needle biopsy of the liver lesion was performed. Histologically, fibrotic inflammation was found and an inflammatory pseudotumor (IPT) diagnosed. Despite treatment with steroids and antibiotics, the size of the IPT increased; thus, surgical resection was necessary. In case of fever of unknown origin, IPT should be considered as a potential diagnosis.

Background: Fever of unknown origin (FUO) was first described in 1961 as fever >38.3°C for at least 3 weeks with no apparent source after 1 week of investigations in the hospital. Infectious disease comprises the majority of cases (40-60%). There is no related research on FUO in children in Taiwan. The aim of this study is to determine the etiologies of FUO in children in Taiwan and to evaluate the relationship between the diagnosis and patient's demography and laboratory data., Methods: Children under 18 years old with fever >38.3°C for >2 weeks without apparent source after preliminary investigations at Taipei Veterans General Hospital during 2002-2012 were included. Fever duration, symptoms and signs, laboratory examinations, and final diagnosis were recorded. The distribution of etiologies and age, fever duration, laboratory examinations, and associated symptoms and signs were analyzed., Results: A total of 126 children were enrolled; 60 were girls and 66 were boys. The mean age was 6.7 years old. Infection accounted for 27.0% of cases, followed by undiagnosed cases (23.8%), miscellaneous etiologies (19.8%), malignancies (16.6%), and autoimmune disorders (12.7%). Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were the most commonly found pathogens for infectious disease, and Kawasaki disease (KD) was the top cause of miscellaneous diagnosis., Conclusions: Infectious disease remains the most common etiology. Careful history taking and physical examination are most crucial for making the diagnosis. Conservative treatment may be enough for most children with FUO, except for those suffering from malignancies., (Copyright © 2015. Published by Elsevier B.V.)

This study was designed to evaluate the diagnostic value of common inflammatory markers with regard to fever of unknown origin (FUO). We investigated 383 patients who were hospitalized with FUO at the Henan Province People's hospital between January 2009 and June 2015. Of all the cases, infectious diseases accounted for 33.9%, neoplasms for 21.1%, collagen vascular diseases for 25.1%, miscellaneous diseases for 4.7%, and no diagnosis for 15.1%. Patients in the neoplasm group were older than those in the infectious disease, collagen vascular disease, and miscellaneous disease groups (p = 0.006, p < 0.0001, and p = 0.001, respectively). The duration of fever before admission of patients in the neoplasm and collagen vascular disease group was longer than that of patients in the infectious disease group (p = 0.002 and p = 0.007, respectively). The diagnostic time after admission of patients from the neoplasm and collagen vascular disease groups was longer than that for patients from the infectious disease group (both p < 0.0001). Serum ferritin levels of patients in the infectious disease group were lower than those of patients in the neoplasm and collagen vascular disease groups (p = 0.029 and p = 0.032, respectively), while serum procalcitonin (PCT) levels in the infectious disease group was higher than that in the neoplasm and collagen vascular disease groups (p = 0.016 and p = 0.007, respectively). Therefore, FUO remains a clinical problem in China and serum ferritin and PCT may be useful in discriminating infectious from non-infectious causes (neoplasms and collagen vascular diseases) in patients with FUO.

Introduction: Fever of unknown origin (FUO) is one of the most challenging diagnostic dilemmas in the field of infectious diseases and tropical medicine. Clinicians should use the frequency distribution of disorders causing FUO to guide their diagnostic approach in patients with prolonged, unexplained fevers meeting the definition of FUO., Methodology: The present study was undertaken to examine the etiologies, clinico-epidemiologic profile, and prognosis of classical FUO in patients reporting to the Alexandria Fever Hospital in Egypt. Records of 979 patients admitted to the fever hospital (from January 2009 to January 2010) and diagnosed as having FUO were examined carefully. FUO was defined as three outpatient visits or three days in the hospital without elucidation of cause of fever., Results: A total of 979 cases (57.0% males and 43.0% females), with ages ranging from 0.2 to 90 years, were investigated. The mean duration of fever before hospitalization was 31 ± 10 days. The etiology of FUO was delineated in 97% of cases, and only 3% remained undiagnosed. Diagnoses were grouped into five major categories. Infectious causes of FUO were strongly associated with better outcome (73.7% improved). Smoking, contact with animals or birds, drug addiction, and HIV seropositivity were important risk factors associated with infections., Conclusions: Infections are the most common cause of FUO, followed by collagen vascular diseases, in our region. A three-step diagnostic work-up approach is recommended to be applied in Egypt in order to improve the quality of medical service provided to FUO patients.

Aim: Tuberculosis is a common disease in India with significant morbidity and mortality. Limited data is available on the description of tubercular lymphadenopathy on endoscopic ultrasound., Methods: Retrospective data of 116 lymph nodes in 113 patients was evaluated at a tertiary care center. Lymphadenopathy in the mediastinum and abdomen were included. The study was aimed at identifying the endoscopic ultrasound (EUS) features of tubercular lymphadenopathy and comparing them with reactive lymphadenopathy in patients with pyrexia of unknown origin., Results: The following features were suggestive of tubercular lymphadenopathy (n = 55) as compared to reactive lymphadenopathy (n = 61): hypoechoic echotexture (94.5% vs. 75.4%, p 0.004), patchy anechoic/hypoechoic areas (30.2% vs. 0%, p = 0.000), calcification (24.5% vs. 0%, p = 0.000), sharply demarcated borders (34.5% vs. 9.8%, p = 0.001), pus like material on aspirate (18.2% vs. 0%, p 0.000), and conglomeration of lymph nodes (10.9% vs. 0%, p = 0.009). The tubercular lymph nodes were significantly larger than reactive nodes at long axis and short axis diameter (2.4 ± 1.1 vs. 1.6 ± 0.6 cm, p < 0.001 and 1.5 ± 0.7 vs. 0.9 ± 0.3 cm, p = 0.001 respectively). On cytopathological examination, presence of necrosis (92.7% vs. 0%, p = 0.000) and granulomas (78.1% vs. 0%, p = 0.000) favored tubercular as compared to reactive lymphadenopathy., Conclusion: EUS features like hypoechoic echotexture, patchy anechoic/hypoechoic areas, calcification, sharply demarcated borders, conglomeration, purulent aspirate, larger size, and cytopathological presence of necrosis/granulomas are suggestive of tubercular as compared to reactive lymphadenopathy.

Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson's χ2 and student's t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson's χ2 and Fisher's exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28-16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever--aOR: 0.56 [0.40-0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71-0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which can be used to triage patients for appropriate care in the clinical setting.

Objectives: Renal transplant may be complicated by cytopenia, fever of unknown etiology, or hematolymphoid malignancies. Bone marrow biopsy may be indicated to evaluate these complications. However, to the best of our knowledge, no previous study has systematically documented the characteristics of bone marrow biopsy in these patients. The present study reports the range of bone marrow findings in renal transplant recipients., Materials and Methods: We selected 85 patients who underwent bone marrow biopsy among 1745 renal transplant recipients who had transplant at Ba şkent University from January 1990 to December 2013. The files of these patients were reviewed for age, sex, age at renal transplant, underlying renal disease, donor type, immunosuppressive therapy, presence or absence of acute humoral or cellular rejection, duration between transplant and bone marrow biopsy, indication for bone marrow biopsy, and histopathologic diagnoses of bone marrow biopsies., Results: The most common cause of renal insufficiency leading to transplant in this patient group was unknown etiology, observed in 24 patients (28.2%). The most common indication for bone marrow biopsy was blood cytopenia, detected in 56 patients (65.9%). Neoplastic involvement of the bone marrow was detected in 6 patients (7.1%), all of which were hematolymphoid malignancies. Corticosteroids were the most commonly used immunosuppressive agents, administered to all patients., Conclusions: Bone marrow biopsy provides important information in renal transplant recipients, especially in cases of neoplastic bone marrow involvement, specific inflammation, and amyloidosis, which are uncommon in this patient group. The overall diagnostic use is related to the individual situation of each patient.

Aims: The utility of bone marrow aspiration and biopsy (BMAB) as a diagnostic tool in patients with HIV/AIDS and fever of unknown origin (FUO) is a subject of debate. Because highly active antiretroviral therapy has reduced incidence of opportunistic infections, it is important to reassess the efficacy of BMAB for this diagnostic purpose. To our knowledge, no such studies have been performed in Harris County which has the highest incidence of HIV in the state of Texas., Methods: We reviewed all BMABs from patients with HIV/AIDS and FUO or persistent cytopenia(s) from 2007 to 2011., Results: Of 57 evaluable patients, BMAB was positive in 24 samples by acid fast bacilli (AFB) or Gomori methenamine silver (GMS) stains (17.5%), presence of granuloma and/or lymphohistiocytic aggregates (31.6%), culture (21.0%) or a combination. Cultures demonstrated Mycobacterium avium/intracellulare (4), M tuberculosis (2), M gordonae (1), Histoplasma capsulatum (3) and Cryptococcus neoformans (2). There were three cases in which a pathogen was grown in culture but that had a negative of 'direct examination' on tissue sections (negative AFB and GMS special stains, no morphological evidence of granuloma/lymphohistiocytic infiltrates)., Conclusions: This study supports the use of diagnostic BMAB as a rapid decision-making tool in patients with HIV and FUO in the proper clinical setting. BMAB demonstrated infection-related evidence prior to positive bone marrow culture in 75% of cases. Special stains and blood cultures had similar diagnostic yield, but BMAB offers faster results. Thus, this procedure assists in clinical decision making and the refinement of treatment in a more timely manner., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We present a case of heterogeneous and strongly increased myocardial and valvular 18F-FDG uptake on 18F-FDG PET/CT in an HIV-positive patient with productive cough, fever, weight loss, and progressive dyspnea for 6 months. Contrast-enhanced CT did not reveal the cause of fever, but hyperechogenic valvular lesions on echocardiography in combination with PET/CT findings are suggestive of endocarditis/myocarditis. Postmortem histology 3 weeks after PET/CT showed Aschoff bodies with Anitschkow cells, pathognomonic for rheumatic carditis. This case illustrates that rheumatic heart disease can be detected on 18F-FDG PET/CT and demonstrates the value of 18F-FDG PET/CT in patients with fever of unknown origin.

Bone marrow (BM) examination is included in the diagnostic algorithm of fever of unknown origin (FUO), although its role is not clearly determined. The purpose of this study was to assess the role of BM studies in patients with FUO. We retrospectively reviewed 45 consecutive patients (25% human immunodeficiency virus-positive) with FUO who underwent a BM study in the University Hospital of Salamanca from 2000 to 2010. We analysed the diagnostic role of BM smears, multiparameter flow cytometry analysis, histology and microbiological cultures. Five patients (11%) were finally diagnosed by BM study (three had an infectious disease and two were found to have haematological malignancies), all of whom were immunocompetent patients. Histology was the most useful study (diagnosis was obtained in 4/5 patients), while BM cultures did not establish the final diagnosis in any patient. Flow cytometry established the diagnosis in one patient, although this patient was also diagnosed by histology. In conclusion, BM study is useful for establishing the aetiology of FUO. BM biopsy for histological examination should be always mandatory if a BM examination is performed., (© 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

Relapsing polychondritis (RP) is a rare autoimmune disease that affects cartilage and multiple organ system. We describe a case of RP presenting with fever, conjunctivitis and inflammatory signs of the right knee. Infectious and neoplastic diseases were excluded by imaging and laboratory examinations. After 17 days of admission the patient reported coughing and odynophagia, and, a physical examination showed red ears. Otorhinolaryngological examination demonstrated arytenoid chondritis. RP was diagnosed based on four McAdam's criteria. The patient was medicated with oral prednisone, and a positive clinical response was noted. Severe disease may require high doses of corticosteroids or immunosuppressive agents and the biological treatment may be beneficial. Beginning manifestations, such as fever, are often unspecific, leading to RP misdiagnosis. In this case, close attention to the patient's clinical history and a detailed physical examination were fundamental in concluding the correct diagnosis, and consequently beginning the appropriate medication.

We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.

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

Purpose: Intensification of antileukemic treatment and progress in supportive management have improved the survival rates of children with acute myeloid leukemia (AML). However, morbidity and early mortality in these patients are still very high, especially in children with acute monoblastic leukemia (AML FAB M5). Inflammatory syndromes complicating the management of these children after application of cytosine arabinoside and due to hyperleukocytosis at initial presentation have been reported. Hemophagocytic lymphohistiocytosis (HLH) has been described as a serious and life-threatening acute complication during treatment of different oncologic entities; however, data on HLH in children with AML FAB M5 are extremely rare., Methods: A retrospective study of all children with AML FAB M5 treated at our institution between 1993 and 2013 was performed to describe the clinical characteristics of patients who developed an inflammatory syndrome with HLH during oncologic treatment., Results: Three of 10 children developed an inflammatory syndrome with fever, elevation of C-reactive protein, hyperferritinemia, elevation of soluble interleukin-2, and hemophagocytosis during prolonged aplasia following the first cycle of chemotherapy not responding to broad-spectrum antibiotics. No infectious agents could be identified; the initial symptoms occurred 17, 18, and 28 days after diagnosis of AML, respectively. The children immediately responded to dexamethasone; however, the same syndrome was observed again after the second cycle of chemotherapy and, in one patient, also after the third cycle., Conclusions: Treating physicians should be aware of an inflammatory syndrome resembling HLH in children with monoblastic leukemia since this problem might extremely complicate management and supportive care of these children. The co-incidence of monoblastic leukemia with HLH might be explained by cytokines released from the monoblastic leukemic cells themselves.

The subset of patients who have both fever of unknown origin (FUO) and a nondiagnostic pleural effusion on presentation has not been previously investigated. A retrospective search of all patients classified as 'classic' FUO one week after admission to a department of general internal medicine identified 71 patients over 15 years. Seven were found to have associated pleural effusion(s) on admission (9.8%). In three patients thoracic large vessel pathology was diagnosed (chronic aortic dissection, giant cell arteritis and Takayasu arteritis). In these patients, the pleural effusion was predominantly left-sided, small to moderate in amount and nondiagnostic on thoracentesis. The effusions resolved spontaneously or with appropriate treatment. Thus, in patients with prolonged fever and systemic symptoms, a 'bland' left-sided pleural effusion may be a diagnostic clue to underlying inflammation of large thoracic arteries. Pleural irritation due to its anatomical proximity to the large arteries on the left side of the thorax may underlie the pathogenesis. Recognition of this sign may lead to a more timely diagnosis of occult thoracic large vessel pathology.

Objectives: Fever suggests the presence of microbial infection in critically ill patients. The aim was to compare the role of old and new biomarkers in predicting absence or presence of microbial infection, its invasiveness and severity in critically ill patients with new onset fever., Methods: We prospectively studied 101 patients in the intensive care unit with new onset fever (>38.3 °C). Routine infection parameters, lactate, procalcitonin (PCT), midregional pro-adrenomedullin (MR proADM), midregional pro-atrial natriuretic peptide (MR proANP) and copeptin (COP) were measured daily for three days after inclusion. Likelihood, invasiveness (by bloodstream infection, BSI) and severity of microbial infection were assessed by cultures, imaging techniques and clinical courses., Results: All patients had systemic inflammatory response syndrome; 45% had a probable or proven local infection and 12% a BSI, with 20 and 33% mortality in the ICU, respectively. Only peak PCT (cutoff 0.65 ng/mL at minimum) was of predictive value for all endpoints studied, i.e. BSI, septic shock and mortality (high risk infection) and infection without BSI, shock and mortality (low risk infection), at areas under the receiver operating characteristic curves varying between 0.67 (P = 0.003) and 0.72 (P < 0.001). In multivariable analysis, the combination of C-reactive protein and lactate best predicted high risk infection, followed by PCT. For low risk infection, PCT was the single best predictor., Conclusions: In critically ill patients with new onset fever, plasma PCT as a single variable, among old and new biomarkers, best helps, to some extent, to predict ICU-acquired, high risk microbial infection when peaking above 0.65 ng/mL and low risk infection when peaking below 0.65 ng/mL., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Strongyloides is endemic in parts of the United States. Most often it is asymptomatic but it has a wide range of clinical presentations. Because of the unusual capacity of strongyloides for autoinfection, it can cause hyperinfection, when it effects the pulmonary and gastrointestinal systems, or disseminated infection, when other organs are involved. Both hyperinfection and disseminated strongyloides usually occur in immunosuppressed patients. We report a case of hyperinfection with strongyloides in a man presenting with fever of unknown origin who was not immunosuppressed.

Four children were diagnosed with chronic disseminated candidiasis (CDC) during treatment for hematological malignancies. All presented with persistent fever, not responsive to broad-spectrum antibiotics, abdominal distension and hepatosplenomegaly. Two children needed artificial ventilation because of respiratory insufficiency. The time between onset of neutropenic fever and diagnosis of CDC ranged from 20-49 days. Ultrasound and computed tomography failed to demonstrate CDC during the neutropenic phase. All children needed a liver or spleen biopsy to establish the diagnosis of CDC. Three of four patients continued chemotherapy during treatment for the fungal infection. All patients had a favorable outcome, both in terms of the invasive Candida infections, as well as their underlying malignancies.

Haematology/oncology children are usually at risk for various infections after intensive chemotherapy. We evaluated the quantification of Th1/Th2 cytokines with a flow cytometric bead array (CBA) in 795 hospitalized haematology/oncology children (309 febrile and 486 afebrile patients) to seek for a diagnostic method for determination of the type and the severity of infection. Three hundred and nine febrile patients developed a total of 505 febrile episodes. Microbiological examination demonstrated a positive blood culture (microbiologically documented infection (MDI)) in 145/505 febrile episodes. The controls included 550 healthy children, 43 haemophagocytic lymphohistiocytosis (HLH) patients, 35 cytomegalovirus infection patients and 19 Epstein-Barr virus infection patients. Interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in febrile episodes were significantly higher than those in healthy children, and the cytokine profile was different from that of the HLH controls or the viral infection controls. IL-6 levels were much higher in MDI patients (usually >1000.0 pg/mL, 60/145) than in HLH patients (2/43); however, IFN-γ levels were only slightly increased in MDI patients, rarely being more than 100.0 pg/mL (8/145 vs. 39/43 in HLH patients). The median levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in febrile patients before antibiotic therapy were 3.9, 660.1, 122.7, 6.9 and 11.4 pg/mL, respectively, and returned to 3.3, 22.8, 9.6, 4.1 and 6.4 pg/mL, respectively, after infection was controlled. IL-6 and IL-10 levels were positively associated with septic shock and mortality rates. In conclusion, our results have demonstrated the usefulness of IL-6/IL-10/TNF-α/IFN-γ determination with CBA technology for the early rapid diagnosis, severity evaluation and assessment of therapy effect in febrile haematology/oncology children., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

Study Design: Retrospective study., Objectives: The purpose of the present study was to elucidate the clinical features of cervical pyogenic spondylitis and intraspinal abscess and to use this knowledge for early diagnosis and treatment., Summary of Background Data: Cervical pyogenic spondylitis and intraspinal abscess are relatively rare diseases in which accurate diagnosis is difficult at early stage. However, because both diseases can cause severe paralysis and vital crisis at advanced stages, early diagnosis and treatment are very important., Methods: Fourteen patients (men: 9, women: 5; average age at treatment: 65.4 y; age range: 49-89 y) with cervical pyogenic spondylitis and/or intraspinal abscess were treated in our hospital. We analyzed their initial symptoms, initial diagnosis, duration between the appearance of initial symptoms and final diagnosis, symptoms at final diagnosis, level of the affected cervical spine, predisposing factors, organisms, and treatments., Results: Initial symptoms included neck pain with fever (n=7), neck pain without fever (n=3), pharyngeal pain with fever (n=1), muscle weakness in both the upper and lower extremities (n=1), gait disturbance (n=1), and numbness of the lower extremities (n=1). Patients were initially diagnosed with meningitis (n=4), fever of unknown origin (n=2), cervical spondylosis (n=2), polymyalgia rheumatica (n=1), upper respiratory tract inflammation (n=1), metastatic spinal tumor (n=1), cervical spondylotic myelopathy (n=1), and cervical disc herniation (n=1). Of the 14 patients, 1 was correctly diagnosed with cervical pyogenic spondylitis., Conclusions: The initial symptoms of cervical pyogenic spondylitis and intraspinal abscess varied and neck pain with fever was not essential. Therefore, doctors should consider the possibility of cervical pyogenic spondylitis and repeat the assessments of the clinical examination for early diagnosis of this disease.

History and Clinical Findings: Five years ago a 52-year-old patient presented with arthritis of the small and large joints. Further symptoms were relapsing fever, unspecific gastrointestinal complaints with meteorism but no diarrhea, fatigue and impaired concentration. Subsequently increasing lower back pain developed. A lumbar-disc lesion was already known., Investigations: Inflammatory markers were elevated including leucocytosis. Gastroscopy with intestinal biopsies and colonoscopy remained without pathologic findings. Whipple's disease was excluded, but unspecific lymphozyte infiltration of the duodenal mucosa was described. Magnetic resconance imaging of the lumbar spine showed spondylodiscitis in L3/4 which was punctured, and polymerase chain reaction revealed Tropheryma whipplei DNA. Retrospectively, this was also found in the intestinal biopsies of three years ago., Diagnosis, Treatment and Course: After initial exclusion of Whipple's disease an unspecific systemic inflammatory disease had been presumed, and the patient had been treated with immunomodulatory therapies in alternating combinations. Steroids improved the symptoms but an increasing dosage of steroids was required. After the detection of Tropheryma whipplei and diagnosis of Whipple's disease the patient received ceftriaxon for a period of two weeks, subsequently cotrimoxazol for one year. Inflammatory activity decreased but unspecific symptoms remained almost unaffected., Conclusion: The differential diagnosis in patients with fever, elevated inflammatory markers and gastrointestinal symptoms must include Whipple's disease. A Tropheryma whipplei PCR from duodenal biopsies should be performed because of its higher sensitivity compared to histology alone., (© Georg Thieme Verlag KG Stuttgart · New York.)

This prospective study was designed to analyze the clinical spectrum of fever of unknown origin (FUO) among adult Egyptian patients admitted to Ain Shams University Hospitals during the period from May 2009 till the end of December 2010. All Egyptian patients fulfilling the criteria of FUO admitted during this period were followed up till reaching the diagnosis. 93 patients were included in the study. They were 48 (51.6%) females and 45 (48.4%) males, their ages ranged from 15 to 65 years (34.39 +/- 13.6). Infections were the commonest cause of FUO (41.94%) followed by malignancies (30.11%). While autoimmune diseases represented 15.05% and in 12.9% of patients the diagnosis was not established. Brucellosis and infective endocarditis were the commonest infections, while hematological malignancies were the commonest oncological diseases. Systemic lupus erythematosus (SLE) was the commonest auto-immune disease. Brucellosis, infective endocarditis, hematological malignancies and SLE must be considered in the differential diagnosis of adult FUO in Egypt.

We report a case of apparent malaria infection presented with a syndrome of painless, generalized lymphadenopathy without granulomas shortly after exposure to fresh water in rural West Africa. Residual infection with Massilia timonae was diagnosed and successfully treated with co-trimoxazole.

Purpose: To assess the interobserver agreement on clinical history and physical examination when using a semi-structured questionnaire to evaluate patients with an acute febrile illness (AFI)., Methods: A cross-sectional study was conducted with outpatients aged 12 years and over, presenting with an AFI defined as fever up to 7 days and no evident focus of infection. Clinical data were collected independently by two physicians using a semi-structured questionnaire. Interobserver agreement was estimated using kappa coefficients with a 95% confidence interval (CI)., Results: A total of 140 patients (age range 13-73 years; 56.4% females) were enrolled. All symptoms showed weighted kappa values significantly greater than 0.6, indicating an at least substantial agreement. As most physical signs were infrequent and of mild intensity, they were recoded and analyzed as absent/present. Of the signs with prevalence ≥15%, exanthema, pallor, lymph node enlargement, and eye congestion showed agreements significantly greater than 0.6, while kappa confidence limits for pharyngeal erythema and dehydration included values classified as regular., Conclusions: High agreement was observed for most of the clinical data assessed, and symptom grading was feasible. Some physical findings were rare and their inclusion in a structured form may not be justified in this setting. The questionnaire application showed good reliability for the most frequent signs and symptoms and may prove to be useful at gathering data for surveillance and research at sentinel sites.

Objective: To determine the reliability of low-risk criteria to exclude serious bacterial infection (SBI) in febrile neonates aged ≤28 days., Methods: All febrile neonates who were hospitalized for fever evaluation were prospectively divided into 2 groups by risk status for SBI. The following criteria were used to define low risk: (1) unremarkable medical history; (2) well-appearing; (3) no focal signs of infection; (4) white blood cell count between 5000 and 15,000/mm(3); (5) normal urinalysis; (6) no mucoid or bloody diarrhoea., Results: Of the 465 enrolled neonates, 177 (38.1%) were considered high risk for SBI and 288 (61.9%) low risk. SBIs were found in 55 (31.1%) neonates in the high-risk group compared to 10 (3.5%) in the low-risk group (p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the criteria for all types of SBI were 84.6% (95% confidence interval (CI) 73.9-91.4%), 69.5% (95% CI 64.8-73.8%), 31% (95% CI 27.3-35.1%) and 96.5% (95% CI 94.3-98%), respectively., Conclusions: The defined criteria are not sufficiently reliable to exclude an SBI or an invasive SBI. We therefore suggest that all febrile neonates in this age group should be hospitalized for complete evaluation and consideration of empirical intravenous antibiotic treatment.

Background: Catheter-related infections (CRI) cause significant morbidity and mortality in cancer patients, particularly during episodes of chemotherapy-induced neutropenia. This study was performed to evaluate clinical features and outcomes of CRI in neutropenic cancer patients., Methods: We retrospectively analyzed clinical characteristics and outcome of febrile neutropenic cancer patients with CRI who visited the emergency department from January 1996 to June 2007., Results: A total of 51 neutropenic cancer patients with CRI were identified and 53 organisms were isolated from culture specimens. The mean ± standard deviation patient age was 50 ± 15 y and the most common underlying disease was lymphoma (n = 27, 53%). Gram-positive organisms accounted for 77% of all isolated pathogens (41/53). Initial catheter salvage was attempted in 38 episodes of CRI, of which 20 were successful. In the current study the overall success rate of catheter salvage attempts was 52.6%. The failure rate of catheter salvage was significantly higher in CRI caused by Gram-negative pathogens than by Gram-positive pathogens., Conclusion: Although catheter salvage should be cautiously attempted for cancer patients with CRI, it might not be a treatment option for neutropenic cancer patients with CRI caused by Gram-negative bacteria.

Nuclear medicine imaging procedures play an important role in the assessment of inflammatory diseases. With the advent of 3-dimensional anatomic imaging, there has been a tendency to replace traditional planar scintigraphy by CT or MRI. Furthermore, scintigraphic techniques may have to be combined with other imaging modalities to achieve high sensitivity and specificity, and some may require time-consuming labeling procedures. On the other hand, new developments such as combined SPECT/CT increase the diagnostic power of scintigraphy. Also, the advent of PET had a considerable impact on the use of nuclear medicine imaging techniques. In this review, we aim to provide nuclear medicine specialists and clinicians with the relevant information on rational and efficient use of nuclear medicine imaging techniques in the assessment of patients with osteomyelitis, infected vascular prostheses, metastatic infectious disease, rheumatoid arthritis, vasculitis, inflammatory bowel disease, sarcoidosis, and fever of unknown origin.

We report herein a case of microscopic polyangiitis (MPA), presenting onset with a spiking fever, liver/biliary dysfunction without jaundice and calf pain without elevation of serum creatine phosphokinase. During 1 month of careful examinations for initial diagnosis, the patient developed renal dysfunction and pulmonary hemorrhage. Based on the results of positive MPO-ANCA, renal and pulmonary involvements, the patient was diagnosed with MPA and treated with high-dose prednisolone and oral cyclophosphamide. Soon after initiation of the treatment, symptoms such as fever, calf pain, liver/biliary dysfunction and renal dysfunction disappeared with decrease of MPO-ANCA titer to the normal level.

Fever of unknown origin (FUO) often is defined as a fever greater than 38.3 degrees C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory tests. In general, infection accounts for approximately one-fourth of cases of FUO, followed by neoplasm and noninfectious inflammatory diseases. No diagnosis is reached in up to 50% of cases. Scintigraphic methods, such as (67)Ga-citrate, labeled leukocytes, and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET), are often used in the diagnosis of FUO. In FUO, FDG-PET appears to be of great advantage because malignancy, inflammation, and infection can be detected. FDG-PET does not seem to contribute to a final diagnosis in patients with normal erythrocyte sedimentation rate and C-reactive protein. Image fusion combining PET and computed tomography facilitates anatomical localization of increased FDG uptake and better guiding for further diagnostic tests to achieve a final diagnosis. In conclusion, the body of evidence on the utility of FDG-PET in patients with FUO is growing and FDG-PET will probably become the preferred diagnostic procedure, especially when a definite diagnosis cannot easily be achieved. Because of favorable characteristics of FDG-PET, conventional scintigraphic techniques may be replaced by FDG-PET in institutions in which PET is available.

Aim: The aim of this study was to evaluate retrospectively the usefulness of [18F]fluorodeoxyglucose (FDG)-PET/ computed tomography (CT) in patients affected by human immunodeficiency virus and suffering from fever of unknown origin (HIV-associated FUO)., Material and Methods: Ten patients (six males, four females, age 24-48 years) suffering from HIV-associated FUO were studied by FDG-PET/CT. Final diagnosis was established either by microbiological or histopathological analysis or by a more than 6-month follow-up. FDG-PET/CT was regarded as 'helpful for diagnosis' when the abnormal uptake pointed to the organ or location where the cause of fever was thereafter identified., Results: Nine out of 10 FDG-PET/CT were abnormal and the cause of fever was further demonstrated by other diagnostic procedures. An infectious process (tuberculosis) was diagnosed in six patients and a neoplasm in three (two lymphomas, one Kaposi's sarcoma). FDG-PET/CT directly suggested sites for biopsy in six patients (tuberculous lymphadenitis and neoplasm). The only patient with normal FDG-PET/CT suffered from drug-induced fever., Conclusion: FDG-PET/CT is a valuable tool in patients with HIV-associated FUO. FDG-PET/CT was categorized as 'helpful for diagnosis' in nine out of the 10 patients we studied. Adding the CT anatomical landmarks to the PET findings allowed an accurate and easy localization of the sites to be punctured in the six patients in whom histopathological diagnosis was needed.

Aim: To describe a subset of cases with the unusual clinical and histomorphological presentation of anaplastic large cell lymphoma (ALCL) mimicking fever of unknown origin (FUO) and sepsis., Methods: A pathology database was searched using full term Systematized Nomenclature of Medicine codes for ALCL to identify 23ALCL cases from the period 1999-2006. Of those, five cases that did not have a correct premortem diagnosis were further analyzed to elucidate the reasons for delayed and incorrect pre-mortem diagnosis. The analyzed data included clinical presentation, duration of symptoms, duration of hospital stay, premortem presumed cause of death, white blood cell count, platelet count, anion gap and blood pH, liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase), lactate, coagulation tests (prothrombin time, partial thromboplastin time, fibrinogen, D-dimers), microbiology cultures, and radiology and surgical pathology reports. Autopsy reports were reviewed for description of major gross findings, initial clinical diagnosis, and cause of death., Results: Five fatal and pre-mortem unrecognized ALCL cases were characterized by rapid decline, with histologic findings showing predominantly extranodal involvement, intravascular lymphomatosis, and hemophagocytosis. The cases were also characterized by unusual clinical manifestations including a FUO, sepsis, and disseminated intravascular coagulation-like picture, lactic acidosis, hepatosplenomegaly, and absence of significant peripheral adenopathy., Conclusions: There is a distinct group of ALCLs with unique and specific clinical, gross autopsy, and histopathologic findings. Recognition of this clinical variant may facilitate early detection and potentially timely diagnosis and therapy.

The authors describe an atypical case of a patient having giant cell arteritis presenting only with fever, diagnosed by positron emission tomography and subsequently confirmed by temporal artery biopsy.

Background: (111)In-labelled leucocyte, imaging is often used to investigate patients with fever of unknown origin (FUO). Its diagnostic performance, however, has been variable and a broad range of sensitivities and specificities have been reported. The purpose of this investigation was to evaluate the usefulness of (111)In-labelled leucocytes scintigraphy in the detection of a cause of FUO in the light of a changing spectrum of diseases causing it and advances in investigational techniques., Materials and Methods: Sixty-one patients with a clinical diagnosis of FUO underwent whole-body (111)In-troponolate-labelled leucocyte scintigraphy in our department over a 2-year period between February 2004 and February 2006. Of these, 54 patients were retrospectively reviewed to identify a cause of FUO. Other parameters such as C-reactive protein (CRP), leucocyte count and radiological findings were also evaluated., Results: Leucocyte scintigraphy was found to be true positive in 12 patients, true negative in 24 patients, false positive in 10 patients and false negative in eight patients. The overall sensitivity of scintigraphy was 60%, specificity 71%, positive predictive value 55%, and negative predictive value 75%. There was no difference in the scintigraphic sensitivity between patients with spontaneous FUO and those with post-operative FUO although the latter showed a higher specificity and PPV. CRP and leucocyte count did not differ significantly between patients with true positive and true negative scintigrams. Overall, 83% of patients with abnormal radiological examinations had positive findings on scintigraphy and 87% of patients with negative findings on radiology had normal scintigraphy., Conclusion: Despite changes in disease spectrum and advances in investigational techniques, our results suggest that (111)In-leucocyte scintigraphy is still a useful technique in establishing the cause of FUO. A higher PPV of this test in post-operative situations makes it especially applicable in this category of patients. Equally, the higher NPV in patients with spontaneous FUO virtually excludes infection/inflammation. Finally, a higher pre-test probability based on the radiological tests seems to be important in the optimal use of leucocyte imaging.