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Key Clinical Message: A thirty‐eight year‐old male presented with a seven‐week history of persistent fever accompanied by recurrent night sweats, chills, arthralgias, headache, and chest tightness.Initial laboratory testing showed non‐specific elevation of inflammatory markers, but was otherwise unremarkable.A palmar rash developed one week later, prompting testing for syphilis. Fluorescent treponemal antibody absorption (FTA‐ABS) and rapid plasma reagin (RPR) tests were both positive.Penicillin G was administered and the patient recovered uneventfully.Our case emphasizes the need for increased syphilis screening to ensure proper diagnosis and prompt treatment. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Adult‐onset Still's disease is a rare inflammatory condition with diverse clinical features. Yamaguchi criteria aid diagnosis, and pleural effusion and elevated ferritin levels are important markers. Steroids are the first‐line treatment. Adult‐onset Still's disease (AOSD) is a rare systemic inflammatory condition with an unknown etiology. It is characterized by, spiking fever, arthritis, evanescent rash, sore throat, serositis, hepatomegaly, splenomegaly, and lymphadenopathy. It is a diagnosis of exclusion and has infections, systemic autoimmune and inflammatory rheumatic diseases, malignancy, and adverse drug reactions as its differential diagnosis. Because of these characteristics, diagnosis is frequently delayed, posing a significant challenge for physicians. While several classification criteria can be used to diagnose Still's disease, they have limitations in terms of sensitivity and specificity. The Yamaguchi criteria are considered the most sensitive and commonly used, requiring the presence of at least five characteristics, with at least two being major diagnostic criteria. Steroid therapy is the first‐line treatment for AOSD patients. In this case report, we present a 56‐year‐old female patient who developed pleurisy a few months after a car accident, subsequently diagnosed with adult‐onset Still's disease. [ABSTRACT FROM AUTHOR]

Pediatric neoplastic diseases account for about 10% of cases of fever of unknown origin (FUO), and most neoplastic disease cases are leukemia, lymphoma, and neuroblastoma. Brain tumors are rarely reported as the cause of FUO, although craniopharyngioma, metastatic brain tumor, and Castleman's disease have been reported. We report a case of intracranial mesenchymal tumor (IMT) with a FET:CREB fusion gene, which had inflammatory phenotype without neurological signs. A 10‐year‐old girl was admitted with a 2‐month history of intermittent fever and headache, whereas her past history as well as her family history lacked special events. Sepsis work‐up showed no pathological organism, and empirical antibiotic therapy was not effective. Bone marrow examination showed a negative result. Cerebrospinal fluid examination showed elevated protein as well as cell counts, and head magnaetic resonance imaging showed a hypervascular mass lesion with contrast enhancement in the left cerebellar hemisphere. The patient underwent tumor excision, which made the intermittent fever disappear. Pathological examinations resembled those of classic angiomatoid fibrous histiocytoma (AFH), but the morphological features were distinct from the AFH myxoid variant; then we performed break‐apart fluorescence in situ hybridization and confirmed the tumor harbored the rare EWSR1::CREM fusion gene (Ewing sarcoma breakpoint region 1 gene (EWSR1) and cAMP response element binding (CREB) family gene). Consequently, we diagnosed the condition as IMT with EWSR1::CREM fusion. Elevated serum concentration of interleukin 6 (IL‐6) was normalized after tumor resection, which suggested the fever could be caused by tumor‐derived IL‐6. This is the first case of IMT with EWSR1::CREM fusion that showed paraneoplastic symptoms associated with the IL‐6/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Although brain tumors are rarely diagnosed as a responsible disease for FUO, they should be considered as a cause of unknown fever even in the absence of abnormal neurological findings. [ABSTRACT FROM AUTHOR]

Microscopic polyangiits (MPA) is an autoimmune vasculitis that is challenging to diagnose because it can present with myriad of manifestations. We present a case of a woman who presented with prolonged fever. Her diagnosis of MPA was realized after fluorine‐18 fluorodeoxyglucose positron emission tomography/computed tomography (F‐18 FDG‐PET/CT) showed abnormal diffuse renal uptake in the cortex, leading to a kidney biopsy. Our report supported the value of FDG‐PET/CT as a diagnostic tool in a patient with febrile illness without localizing symptoms or signs. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of excessive immune system activation. We report a case of HLH in a 20‐year‐old primigravid woman who presented with postpartum fevers. She was successfully treated with dexamethasone and anakinra, a deviation from the HLH‐94 protocol, to preserve her ability to breastfeed. [ABSTRACT FROM AUTHOR]

Since 2020, the coronavirus disease 2019 pandemic has led to the widespread practice of hand hygiene and wearing face masks, not only among medical personnel, but also among the general population. Thus, the impact of the coronavirus disease 2019 pandemic on the incidence of febrile neutropenia should be verified. This study aimed to examine the incidence of febrile neutropenia in hospitalized patients receiving chemotherapy at Kanazawa University Hospital. Among inpatients at the Department of Urology receiving chemotherapy, we compared the incidence of febrile neutropenia between 317 cases in 2018–2019 and 276 cases in 2020. We retrospectively analyzed the factors of febrile neutropenia via binomial logistic regression analysis based on patient characteristics and the characteristics of primary diseases, with statistical significance set at p < 0.05. Febrile neutropenia occurred in 20/317 cases in 2018–2019 and 1/276 cases in 2020, with a significant decrease in the latter (p = 0.005). In a multivariate analysis, we identified the following independent risk factors for febrile neutropenia: non‐coronavirus disease 2019 era (p = 0.005), first course of therapy (p = 0.005), malnutrition (p = 0.032), and past history of febrile neutropenia (p = 0.018). Due to the coronavirus disease 2019 pandemic, hygiene policies for medical personnel and quarantine measures for patients were thoroughly implemented. Therefore, the incidence of febrile neutropenia in 2020 decreased to 1/15 of the previous incidence. Thus, the hygiene for medical personnel and patients during the expected period of chemotherapy‐induced neutropenia is important for febrile neutropenia prevention. [ABSTRACT FROM AUTHOR]

Background: Inflammation of unknown origin (IUO) is a challenging situation in internal medicine. Objectives: To describe the final diagnoses in IUO and assess the helpfulness of 18F‐fluorodesoxyglucose positron emission tomography with computerized tomography (18F‐FDG‐PET/CT) in the diagnosis strategy. Results: A total of 317 IUO patients with 18F‐FDG‐PET/CT were enrolled. A diagnosis was reached in 228 patients: noninfectious inflammatory diseases (NIID) (37.5%), infectious diseases (18.6%), malignancies (7.9%), and non‐systemic‐inflammatory miscellaneous diseases (7.9%). The two leading causes of NIID were polymyalgia rheumatica and giant cell arteritis. 18F‐FDG‐PET/CT results were classified as true positive in 49.8% of patients and contributory in 75.1% of overall IUO patients (after the complete investigation set and a prolonged follow‐up). In multivariate analysis, only C‐reactive protein minimum level (≥50 mg/L) was associated with the contributory status of 18F‐FDG‐PET/CT. Conclusion: Within the wide spectrum of IUO underlying diseases, 18F‐FDG‐PET/CT is helpful to make a diagnosis and to eliminate inflammatory diseases. Obese patients constitute a specific group needing further studies. [ABSTRACT FROM AUTHOR]

This article discusses a case of giant-cell arteritis (GCA) in a 78-year-old woman who presented with a low-grade fever of unknown origin. The patient initially visited a dental clinic for toothache and jaw claudication, but no dental issues were found. The patient was then referred to a clinic where a slightly enlarged left temporal artery without pulsation and tenderness was observed. Ultrasonography revealed thickened walls in the temporal artery frontal branches, confirming the diagnosis of GCA. Prompt diagnosis and treatment with prednisolone led to the resolution of symptoms. The article emphasizes the importance of considering GCA in elderly Asian patients with fever and temple pain and highlights the usefulness of ultrasonography for diagnosis. [Extracted from the article]

The article presents a case study of eight pediatric cases initially diagnosed with Kawasaki disease (KD) but later confirmed to have underlying autoinflammatory diseases (AIDs). It is reported that the patients exhibited recurrent febrile episodes, posing a diagnostic challenge. It further underscores the importance of considering AIDs in fevers of unknown origin.

Aims: 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.Methods: A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Transient fever is not uncommon postcardiac surgery, usually related to underlying clinical process such as inflammation related to the physiological insult or infection. Here, we present a case series of two patients who underwent repair for type A aortic dissection with Gelweave graft prosthesis who had persistent fevers, leukocytosis, and raised inflammatory markers persisting months after surgery. Both patients were found to have sterile perigraft fluid collections. Comprehensive investigations excluded common causes of postoperative inflammation, as well as rarer causes of fever of unknown origin. The presence of this idiopathic inflammatory state lead to extended hospitalization and resource utilization, prompting need for further characterization of its mechanism and proper management. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis poses a diagnostic dilemma due to the absence of specific clinical and laboratory findings, especially in adults. Despite greater recognition of the disease, secondary idiopathic forms are still reported. [ABSTRACT FROM AUTHOR]

Aim: To characterise Bartonella infections in a paediatric population requiring hospital admission and review its treatment. Methods: Longitudinal observational retrospective data analysis of children and adolescents admitted with Bartonella infection at a paediatric tertiary hospital from 2010 to 2019. Results: We identified 16 cases of bartonellosis, with a mean age of 8.0 ± 4.5 years old, no sex predominance and 14 had contact with cats. Most of the cases occurred in fall and winter. Clinical presentations included osteomyelitis/arthritis (n = 9), hepatosplenic disease (n = 2), lymphadenitis (n = 2), neuroretinitis (n = 2) and encephalitis (n = 1). Clinical diagnosis was confirmed by serology (n = 16) and Bartonella DNA detection in patient's lymph nodes/hepatic lesion (n = 3). Therapeutic approach varied according to the clinical presentation: azithromycin in lymphadenitis, rifampicin plus ciprofloxacin in hepatosplenic disease, rifampicin and doxycycline in neuroretinitis, ceftriaxone in encephalitis and azithromycin, cotrimoxazole or rifampicin plus azithromycin, cefuroxime, ciprofloxacin or doxycycline in osteomyelitis/arthritis. Immunodeficiency was excluded in seven patients. Seven patients' cats were screened by veterinarians and treated when infected (n = 5). Conclusions: In these clinical presentations, where other infections may be involved, a high index of suspicion is necessary, with emphasis on the epidemiological context. The association of systemic forms with immunodeficiency did not occur in our study. The lack of recommendations for treatment of atypical infection makes the approach of these cases a challenge. Randomised control studies are essential to define the best approach in each case. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life‐threatening clinical syndrome, which may present with FUO. The possible diagnosis of HLH must be considered in the differential diagnosis when a patient presents with FUO. [ABSTRACT FROM AUTHOR]

Adenovirus infection is commonly associated with self‐limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life‐threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death. Although hepatic abscesses mediated by adenovirus have been described in other immunosuppressed patient populations, it has very rarely been described in liver transplant recipients. Here, we report two adult cases of hepatic abscesses following liver transplantation secondary to adenovirus infection and describe the successful treatment of these patients. Adenovirus should be considered as an uncommon etiology of hepatic abscess and unexplained fevers in adults following liver transplantation. [ABSTRACT FROM AUTHOR]

Adult‐onset Still's disease may cause intestinal pseudo‐obstruction via a cytokine storm. Early diagnosis and treatment are the key for patient survival before the development of serious complications such as macrophage activation syndrome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Orthohantaviruses are geographically widely distributed and present various clinical manifestations from mild symptoms to the severe form of haemorrhagic fever with renal syndrome (HFRS) in Eurasia. Official registration of HFRS in Kazakhstan started in the year 2000. However, the true prevalence of human infections by orthohantaviruses within Kazakhstan is unknown. The aim of this study was to investigate of the seroprevalence of orthohantavirus infections in patients with fever of unknown origin (FUO) in two regions, Almaty and Kyzylorda region. Methods: Paired serum samples from 802 patients with FUO were screened for the presence of orthohantavirus IgG and IgM antibodies by ELISA. Positive samples were further tested by immunoblotting and indirect immunofluorescence tests (IIFT) to determine the respective orthohantavirus serotypes. Suspected acute serum samples were additionally checked by a RT‐PCR to identify viral RNA. Results: In total 178/802 (22.2%) serum samples reacted with orthohantavirus IgG antibodies and 4/802 (0.5%) with IgM antibodies. All positive samples were tested by immunoblotting which resulted in 2.9% positive samples with IgG antibodies against Puumala (PUUV), Hantaan (HTNV) and Dobrava (DOBV) virus serotypes in Almaty region and 5.4% to PUUV and DOBV serotypes in Kyzylorda region, respectively. In the IFFT, 1.9% positive samples from Almaty and 3.1% from Kyzylorda were confirmed for PUUV and DOBV serotypes. Out of four IgM ELISA positive samples only three were positive against PUUV in the immunoblot and showed weak positive reactivity for the Saaremaa (SAAV), PUUV and HTNV serotypes in the IFFT. Conclusions: This study demonstrates the presence of orthohantavirus infections among patients with FUO in Kazakh regions that were so far considered as non‐endemic. The healthcare system needs to be prepared accordingly in order to be capable of detecting cases and providing adequate management of patients. [ABSTRACT FROM AUTHOR]

Introduction: Fever of unknown origin (FUO) with pulmonary lesions is a common syndrome in respiratory diseases, which can be caused by infection, cancer, connective tissue disease and other rare diseases of South China. In patients with FUO associated with pulmonary lesions, pathogeny should be identified and followed by an appropriate treatment strategy. Objective: This study aimed to investigate the etiological distribution and clinical features of FUO with pulmonary lesions and to analyze the efficiency of different diagnostic methods for certain disease categories. Methods: Patients hospitalized at the Guangzhou Institute of Respiratory Health from July 2012 to December 2016 who had fever ≥38.3°C that lasted ≥21 days, in whom the chest X‐ray or computed tomography (CT) revealed definite pulmonary infiltration, and for whom, despite being examined for a week, no definitive diagnosis could be made, were considered for this study. Results: A total of 104 patients were identified as having FUO with lung lesions, and 89.4% (93/104) patients were definitively diagnosed. Infectious disease was the most common cause (46.2%, 48/104). Histopathology was instrumental in the diagnosis of the causes of FUO with pulmonary manifestations, 47.3% (44/93) patients were diagnosed through histopathology, 35.4% (17/48) with infectious disease and 55.2% (16/29) with connective tissue diseases as the etiology were definitely diagnosed using histopathology. Conclusion: Most FUO with pulmonary lesions are identified during infections and autoimmune diseases. The most important diagnostic measure for FUO with pulmonary lesions is histopathology. Additionally, lung biopsy must be encouraged in multi‐level hospitals in the future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A 77‐year‐old woman underwent F‐18 FDG PET/CT for evaluation of fever focus. Diffuse and intense hepatosplenic uptake was noted and lymphoma or tuberculosis was proposed. Liver biopsy revealed chronic granulomatous inflammation with Langerhans‐type giant cells and necrosis. A follow‐up PET/CT after anti‐tuberculosis treatment revealed that the hepatosplenic uptake had resolved. [ABSTRACT FROM AUTHOR]

Abstract: Background: Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. Methods: We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas‐kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. Results: Twenty‐three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post‐transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy‐proven rejection, graft loss, death, or documented infections compared to UF‐free patients during the first‐year post‐transplant. Conclusion: UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first‐year post‐transplant. [ABSTRACT FROM AUTHOR]

Abstract: Primary bone marrow lymphoma (PBML) represents non‐Hodgkin lymphoma (NHL) that primarily arises in the bone marrow (BM) without lymphadenopathy. This condition has various definitions and can be masked by prolonged fever, leading to delayed diagnosis. We aimed to identify clinical features and risk indicators of PBML. We enrolled 269 adults with fever of unknown origin (FUO) who underwent a BM study for potential PBML. Thirty patients were diagnosed with PBML (26 and 4 patients in the training and validation cohort, respectively), and 20 patients (67%) showed initial manifestation of hemophagocytic lymphohistiocytosis (HLH). Among PBML patients in the training cohort, their median overall survival is short (8 days), with pneumonia being the most common direct cause of early mortality, followed by life‐threatening HLH. Despite extremely poor prognoses, some B‐cell PBML patients who survived 30 days after BM studies achieved long‐term survival with rituximab‐based treatment. To assist general practitioners in early PBML diagnosis when approaching adults with naïve FUO, we identified several risk indicators, including elevated serum alkaline‐phosphate levels, lowered serum immunoglobulin‐G levels, cytopenia in ≥2 lineages, and peripheral blood leukoerythroblastosis. Our recently published scoring system, which can predict hematological BM disease in FUO adults, showed excellent ability in recognizing PBML early, with high sensitivity and specificity. We conclude that PBML is a specific “clinical” phenotype of NHL; moreover, we have identified diagnostic clues for early identification of FUO adults with underlying PBML, which should be considered a hematological emergency once suspected in any adult with FUO. [ABSTRACT FROM AUTHOR]

Objective: To present a case of Adult-onset Still's disease (AOSD) initially suspected to be odontogenic inflammation.Background: Adult-onset Still's disease is a rare, complex autoinflammatory disease and a known cause of fever of unknown origin.Materials and Methods: The patient had both a fever and dental pain. Following meticulous examination, the patient was diagnosed with AOSD.Conclusion: Clinicians should keep in mind that a patient such as AOSD may visit their clinics. [ABSTRACT FROM AUTHOR]

Key Clinical Message Adult-onset Still's disease (AOSD) due to visceral leishmaniasis (VL) has not been previously reported. This case report analyzes a single episode of AOSD probably due to a visceral leishmaniasis successfully treated with pentamidine isethionate and prednisone. [ABSTRACT FROM AUTHOR]

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) is delayed by most physicians. This study aimed to identify early parameters and suitable scoring systems for the risk of HLH. Clinical and laboratory data collected ≤3 days after admission were defined as early parameters and used to calculate the number of HLH-2004 criteria met and bone marrow (BM) score. Between January 2006 and February 2016, 233 immunocompetent adults with naïve fever of unknown origin who underwent a BM study were enrolled to mimic patients at risk of HLH and randomly assigned into the developmental or validation cohort. Hemophagocytic lymphohistiocytosis was finally diagnosed in 47 patients, with non-Hodgkin lymphoma as the major etiology (51.1%). Upon admission, four-fifths of patients who developed subsequent HLH fulfilled ≤3 of 8 HLH-2004 criteria, and 6 early parameters were independent predictors of HLH: anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelet count < 100 × 103 /μL), leukoerythroblastosis, hyperbilirubinemia (total bilirubin > 2 × upper normal limit), hyperferritinemia (ferritin > 1000 ng/mL), and splenomegaly. Compared with the HLH criteria met upon admission, the BM score was an independent predictor (odds ratio = 1.621; 95% confidence interval, 1.355-1.940) with excellent discrimination (area under the receiver operating characteristic curve = 0.920; 95% confidence interval, 0.883-0.958). The sensitivity and specificity for a BM score cutoff of 10 points were 95% and 75%, respectively. When approaching immunocompetent adults with a continuously high fever, the BM score at initial admission assists with early identification of patients at risk of HLH. [ABSTRACT FROM AUTHOR]

Introduction: Studies on fever of unknown origin (FUO) in patients of chronic kidney disease and end stage renal disease patients on dialysis were not many. In this study, we used 18 F-FDG PET/CT scan whole body survey for detection of hidden infection, in patients on dialysis, labelled as FUO. Methods: In this retrospective study, 20 patients of end stage renal disease on dialysis were investigated for the cause of FUO using 18F-FDG PET/CT scan. All these patients satisfied the definition of FUO as defined by Petersdorf and Beeson. Any focal abnormal site of increased FDG concentration detected by PET/CT, either a solitary or multiple lesions was documented and at least one of the detected abnormal sites of radio tracer concentration was further examined for histopathology. Findings: All patients were on renal replacement therapy. Of these, 18 were on hemodialysis and two were on peritoneal dialysis. 18F-FDG PET/CT scan showed metabolically active lesions in 15 patients and metabolically quiescent in five patients. After 18F-FDG PET/CT scan all, but one patient had a change in treatment for fever. Anti-tuberculous treatment was given in 15 patients, antibiotics in four patients and anti-malaria treatment in one patient. Discussion: The present study is first study of 18F-FDG PET/CT scan in patients of end stage renal disease on dialysis with FUO. The study showed that the 18 F FDG PET/CT scan may present an opportunity to attain the diagnosis in end stage renal disease patients on dialysis with FUO. [ABSTRACT FROM AUTHOR]

Malignant lymphoma was suspected based on his clinical presentation and laboratory results; however, contrast-enhanced computed tomography (CT) revealed no enlarged lymph nodes, and random skin biopsy showed no evidence of malignancy to suggest intravascular lymphoma. Computed tomography, hospital general medicine, fever of unknown origin, lymphoma, positron emission tomography Keywords: computed tomography; fever of unknown origin; hospital general medicine; lymphoma; positron emission tomography EN computed tomography fever of unknown origin hospital general medicine lymphoma positron emission tomography 280 281 2 07/05/22 20220701 NES 220701 We presented a case of primary bone lymphoma (PBL) which demonstrated fever of unknown origin. [Extracted from the article]

Background Identification of aetiology for fever of unknown origin ( FUO) is challenging, due to the high rates of undiagnosed cases. The current diagnostic approach includes initially first-line procedures such as general examination and various laboratory tests and basic imaging techniques followed by second-line tests such as more advanced imaging techniques including 18F fluorodeoxyglucose positron emission tomography ( FDG PET) and tissue biopsies. If no diagnosis is obtained, more invasive measures may be in order such as liver biopsy and exploratory laparotomy. Materials and methods This review article is based on the relative published material found on MEDLINE and Pub Med up to August 2014. We looked for the terms 'fever of unknown origin, FDG PET' in combination with 'cancer, infection and autoimmune disease'. Results Several clinical studies have investigated the utility of the FDG PET during the diagnostic approach of FUO. Recent evidence suggests that FDG PET has the advantage of total body imaging and may depict all common causes of FUO such as infections, noninfectious inflammatory causes and tumours because they all exhibit glucose hypermetabolism. Depiction of an abnormal lesion on FDG PET could guide clinicians to the next diagnostic procedure (another imaging method, culture, biopsy or surgery) to establish the diagnosis. Conclusions Emerging evidence suggests that FDG PET, when available, may provide critical diagnostic information early during evaluation of FUO. [ABSTRACT FROM AUTHOR]

Background Outpatient quick diagnosis units ( QDUs) have become an increasingly recognized alternative to hospitalization for the diagnosis of a number of potentially serious diseases. No study has prospectively evaluated the usefulness of QDU for the diagnosis of unexplained fever. Materials and methods We prospectively assessed patients referred to QDU due to fever of uncertain nature ( FUN), defined as a temperature > 38 °C during at least 1 week and no diagnosis after a previous evaluation. We also evaluated consecutive patients with FUN who were hospitalized during the same period. QDU and hospital costs were analysed by micro-costing techniques. Results We evaluated 176 QDU patients and 168 controls. QDU patients were younger and required fewer investigations than controls. QDU patients had higher prevalence of viral infections (36% vs. 8%, P < 0·001) and lower prevalence of bacterial infections (6% vs. 46%, P < 0·001) and malignancies (2% vs. 14%, P < 0·001). While time-to-diagnosis of QDU patients was longer than length-of-stay of controls (25·82 vs.12·89 days, P < 0·001), 56% of QDU patients only required up to two visits. Cost per QDU patient was €644·59, while it was €4404·64 per hospitalized patient. Conclusions QDU patients with FUN were younger and had less serious diseases than controls including more viral and less bacterial infections and fewer malignancies. Mainly owing to untimely diagnostic reports, time-to-diagnosis was longer in QDU patients. Cost-savings in QDU were substantial. Using objective tools to evaluate the condition severity and general health status of FUN patients could help decide the most appropriate setting for their diagnostic study. [ABSTRACT FROM AUTHOR]

We report a case of isolated adrenocorticotropin deficiency caused by pembrolizumab. This condition can be fatal, but its rarity causes under-recognition. Oncologists should pay attention to adrenal insufficiency due to pembrolizumab. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to evaluate prospectively the usefulness of fluorodeoxyglucose-positron emission tomography/computed tomography ( FDG-PET/CT) in investigation of fever of unknown origin ( FUO) in HIV-positive patients and to determine whether HIV viraemia impacts on FDG-PET/ CT performance. Methods The FDG-PET/ CT results of 20 HIV-infected patients with FUO were analysed and compared with the FDG-PET/ CT results of 10 HIV-infected viraemic patients without FUO. The performance of FDG-PET/ CT for identifying the aetiology of FUO was assessed. Final diagnosis for FUO was based on histopathology, microbiological assays, or clinical and imaging follow-up. Results FDG-PET/ CT contributed to the diagnosis or exclusion of a focal aetiology of the febrile state in 80% of patients with FUO. The presence of increased FDG uptake in the central lymph node has 100% specificity for focal aetiology of fever, even in viraemic patients. The absence of hypermetabolic central lymph nodes in FUO patients has 100% negative predictive value for focal disease. Lymph node biopsy in central hypermetabolic areas allowed, in 100% of cases, identification of underlying disease in patients with FUO. Biopsy of peripheral lymph nodes should be performed in lymph nodes with maximum standardized uptake value (SUVmax) ≥ 6-8 (sensitivity 62.5%; specificity 75%) and avoided in lymph nodes with SUVmax = 0-4 (specificity 0%). High HIV viraemia does not prevent correct interpretation of FDG-PET/ CT. Conclusions As in HIV-negative patients, we confirm the usefulness of FDG-PET/ CT in investigation of FUO in HIV-positive patients even if they are viraemic. [ABSTRACT FROM AUTHOR]

Ovarian vein thrombosis usually occurs in pregnant patients, especially during the postpartum period. However, it is a rare complication following laparoscopic surgery in gynecology. The risk of a thromboembolic event is not well defined, and evidence-based guidelines regarding deep vein thrombosis prophylaxis in gynecological laparoscopic surgery are still lacking. Herein we report a rare case of ovarian vein thrombosis following total laparoscopic hysterectomy in a 35-year-old woman who developed a fever of unknown origin on postoperative day 3. A complete fever work-up was done. Her urine, vaginal stump and blood culture were all negative, and her white blood cell count was normal. CT revealed left ovarian vein thrombosis. The patient responded well to anticoagulation in conjunction with antibiotic therapy. [ABSTRACT FROM AUTHOR]

A 5-month old infant presented with a short history of fever of unknown origin. He initially appeared well although there was a resting tachycardia during periods of normal temperature, and pancytopenia. He remained febrile in spite of antibiotic therapy and by 48 h he had developed marked hepatosplenomegaly and coagulopathy. At 72 h a bone marrow aspirate and trephine biopsy showed haemophagocytosis. By this time the infant was encephalopathic and haemodynamically unstable with multi-organ dysfunction. Treatment with high-dose methylprednisolone and cyclosporin was commenced with an initial good response. Unfortunately the patient ultimately died of infective complications of treatment and reactivation of the underlying disease process. Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of the mononuclear phagocyte system characterised by proliferation of morphologically benign histiocytes resulting in hypercytokinaemia and uncontrolled activation of immune cells. The diagnosis of familial HLH should be considered in any infant with fever, splenomegaly and cytopenia of at least two cell lines. HLH may be cured by immunosuppressive therapy and eventual stem cell transplantation but rapid disease progression to multi-organ failure results in a high mortality. [ABSTRACT FROM AUTHOR]

Aim Adult-onset Still's disease ( AOSD) is a rare disease. Very few cases have been reported from the South- Asian region so the aim of this study is to assess the clinical and laboratory aspects of 15 patients with AOSD in a tertiary referral hospital in Karachi. Methods Retrospective data was collected from all patients diagnosed using Yamaguchi criteria for AOSD between January 2004 and December 2010 at Jinnah Medical College Hospital, Karachi. Results Data of 15 patients with AOSD were analyzed. Their ages ranged from 17 to 55 years, the male-to-female ratio being 6 : 1. The most common clinical features were fever and articular symptoms (100%), sore throat (60%), rash (53.3%), weight loss (93.3%), lymphadenopathy (40%) and elevated erythrocyte sedimentation rate (86.7%). All patients had leukocytosis with counts > 20 000/mm 3 were seen in 40%. Elevated liver enzymes were present in 80% of the case series and hyperferritinemia in 100% with a mean of 3962 ng/mL (range 555-13 865). Ambiguity in presentation and lack of serologic markers make diagnosis of AOSD difficult as 40% of patients were receiving empirical anti-tuberculous therapy prior to final diagnosis. Conclusion It is necessary for physicians to have a high index of suspicion for AOSD in patients with high-grade fever, arthralgia and leukocytosis. [ABSTRACT FROM AUTHOR]

This study investigates the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with 109 classical fever of unknown origin (FUO). Of the 48 18F-FDG PET/CT scans, 41 (85.4%) were interpreted as abnormal, and 25 (52.1% of all scans) were considered clinically helpful. The final cause of fever was determined in 41 patients (85.4%); infection (25%), malignancy (12.5%), non-infectious inflammatory disease (16.7%) and miscellaneous causes (31.3%). 18F-FDG PET/CT contributed to the final diagnosis of FUO in 65.8%. [ABSTRACT FROM AUTHOR]

Background: In Japan, an actual condition survey on childhood febrile diseases with fever of unknown origin has never been performed. We carried out a national survey on childhood febrile illnesses in order to collect useful information for the differential diagnosis. Methods: A nationwide survey using questionnaires was performed on febrile illness cases with fever of unknown origin (FUO) experienced by 2843 pediatrics institutions with sick beds during a 5-year period before 2007. FUO was defined as a febrile illness of at least 2 weeks' duration with a temperature ≥38°C, and failure to establish a diagnosis in spite of intensive evaluation during seven days' hospitalization. Results: Two hundred fifty-five of 2843 questionnaire-surveyed institutions had 960 FUO cases, of which 132 could not be diagnosed, and 828 could be diagnosed after detailed medical examinations. The diagnoses they clarified included infectious diseases in 190 cases (23%), rheumatic diseases in 448 cases (54%), neoplasms in 67 cases (8%), and others in 123 cases (15%). Conclusion: Clarification of illnesses that ought to be differentiated in the diagnostic approach to an FUO case is essential for arriving at its definitive diagnosis by exclusion. [ABSTRACT FROM AUTHOR]

Fever of unknown origin (FUO) in hemodialysis (HD) patients represents a diagnostic challenge because differential diagnosis includes diverse etiologies. Causes of FUO in the general population can be classified into 3 diagnostic categories: infections, tumors, and noninfectious inflammatory diseases. Also, chronic HD patients may have additional problems such as infections, the risk for which may be increased by the immunosuppression associated with uremia, vascular access-related infections, and nosocomial infections. Moreover, patients with chronically failed kidney transplants can have low-grade fever and abdominal pain, and if inflammation of the allograft is severe enough, it may result in a spontaneous rupture. Hence, it is important to rapidly recognize, diagnose, and manage these complications. In the present study, we report a case of FUO in an HD patient with a failed graft and discuss clinical approach and management of these patients. [ABSTRACT FROM AUTHOR]

Crowned dens syndrome (CDS) is rare, though likely underdiagnosed, typically presenting with fever, neck pain, and stiffness. Adequate clinical awareness may streamline diagnostics and therapeutics and avoid the need for invasive procedures. [ABSTRACT FROM AUTHOR]

Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein-Barr virus (EBV) serology, urine, stool or blood cultures, chest X-ray and tuberculin probe. Results: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self-limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus-associated haemophagocytic syndrome, one with VL and two unknown) died. Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO. [ABSTRACT FROM AUTHOR]

A revision of the criteria of fever of unknown origin (FUO), established in 1961, is desirable because of important evolutions in medical practice and the emergence of new patient populations. The development of rapid laboratory tests and powerful diagnostic tools, such as ultrasonography, computed tomography and magnetic resonance imaging often makes hospitalization unnecessary and new categories of patients such as those with HIV infection, neutropenia, immunosuppression and nosocomial illness require an approach different from classical FUO. The more then 200 reported causes of FUO can be classified into four diagnostic categories; infections, tumours, noninfectious inflammatory diseases (NIID) and miscellaneous. A uniform classification system is highly wanted to allow comparison between different series. The reports of the 1990s show slight changes in the distribution of causes, namely less infections, less tumours, more NIID and more undiagnosed cases. A uniform diagnostic strategy cannot be determined. The initial investigation should be directed by potentially diagnostic clues revealed by extensive history, meticulous physical examination and a standard set of laboratory tests. 18Fluoro-deoxy-glucose-positron-emitted-tomography is a new valuable total body scintigraphy in the search for the site of origin of the fever. In view of the rather good long-term prognosis, a wait-and-see strategy may be more appropriate than a systematic staged approach. Elderly patients and patients with episodic fever represent two specific groups of classical FUO that require a distinct approach. HIV-associated, nosocomial and neutropenic FUO should be considered as separate clinical entities. [ABSTRACT FROM AUTHOR]

Fever of unknown origin (FUO) means fever that does not resolve itself in the period expected for self-limited infection and whose cause cannot be ascertained despite considerable diagnostic efforts. The differential diagnosis is often different in older patients, and presentation of disease is frequently nonspecific and symptoms are difficult to interpret. Multisystem disease has emerged as the most frequent cause of FUO in the elderly, and temporal arteritis is the most frequent specific diagnosis. Infections, particular tuberculosis, remain an important group. FUO is often associated with treatable conditions in this age group. Early recognition and prompt initiation of appropriate empirical therapy are cornerstones of the strategy. [ABSTRACT FROM AUTHOR]

Abstract. Ritis K, Tzoanopoulos D, Speletas M, Papadopoulos E, Arvanitidis K, Kartali S, Sideras P (Democritus University of Thrace, Regional Hospital of Alexandroupolis, Alexandroupolis, Greece, and University of Umeå, Umeå, Sweden). Amplification of IS6110 sequence for detection of M. tuberculosis complex in HIV-negative patients with fever of unknown origin (FUO) and evidence of extrapulmonary disease. J Intern Med 2000; 248: 415–424. Objectives. Extrapulmonary tuberculosis (TB) constitutes the main cause of classic fever of unknown origin (FUO) in many populations. The aim of this study was to improve the diagnostic field of the disease using a nested polymerase chain reaction (PCR) assay, specific for the IS6110 insertion element of Mycobacterium tuberculosis complex, in order to achieve a more timely diagnosis and treatment. Setting. Twenty-four, HIV-negative classic FUO patients who were admitted to the Regional Hospital of Alexandroupolis between April 1997 and July 1999. Subjects and design. The above patients were considered as putative extrapulmonary TB after 3 weeks of in-patient investigation and underwent exhaustive examination for diagnosis of the disease. For this purpose, specimens were obtained from peripheral blood and bone marrow from these patients, as well as from damaged tissues, and analysed by both PCR and conventional methods. Anti-tuberculous treatment was initiated in 16 out of 24 patients and the response to this regimen was considered as the final criterion for diagnosis of tuberculosis. Results. Extrapulmonary TB was established in 11 patients. The PCR-based methodology, when applied to samples derived from bone marrow aspirations and suspected damaged tissues, was able to diagnose 10 of them, whereas the conventional methods were able to detect only two. Conclusions. Our results confirm the diagnostic value of molecular detection of M. tuberculosis in cases of FUO, thus supporting the application of PCR in tissue samples suspected of bacillus infection. Furthermore, our studies demonstrate that bone marrow aspiration specimens constitute an alternative, easy, safe and reliable source for such PCR analysis. [ABSTRACT FROM AUTHOR]

We present a case of fever of unknown origin and life-threatening stomatitis developed about 60 months after renal transplantation. He was 15 yr old at the transplantation. Bacterial, fungal, and viral infections were not evident. Fever and stomatitis were resistant to acyclovir and to any anti-bacterial or anti-fungal treatment. Graft biopsy revealed a small focus of acute vascular rejection, but the findings were not severe enough to be an etiology of the fever in this case. The administration of cyclosporine (CYA) was stopped 19 d before graftectomy, but the clinical picture was unchanged. Fever and stomatitis was resolved immediately after graftectomy and the discontinuation of immunosuppressants such as mizoribine (MZ) and prednisolone. Pathological changes of the graft included chronic transplant glomerulopathy, acute glomerulitis, and lymphocyte infiltration in peritubular capillaries. Thus we suppose that immunosuppressants were the cause of both fever and stomatitis in this case. We speculate that a fever in this case might be due to the immunosuppressant itself, i.e., CYA or MZ, or viral infection – probably herpes-simplex virus infection. It is probably the immunosuppressive state per se that may cause the resistance of his muco-cutaneous lesion to anti-viral agent. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fever of unknown origin (FUO) is defined as the body temperature higher than 38.3 °C on several occasions and lasting longer than 3 weeks, with the aetiology remaining uncertain after 1 week of investigation. In this study, we reviewed 57 patients with FUO hospitalised in our inpatient department between 1998 and 2003. The median age of the patients was 44 years (17–84), and 26 were males (46%), while 31 were females (54%). In 24 patients (42%), infectious diseases such as tuberculosis (12 patients) and brucellosis (5 patients) were found under the aetiology of FUO. Inflammatory rheumatic diseases were the second most common cause of FUO (17 patients, 30%), while malignancies were found in 10 patients (18%). In six patients (10%), aetiology could not be identified. In conclusion, infectious diseases especially tuberculosis and brucellosis are the leading causes of FUO in our country. [ABSTRACT FROM AUTHOR]

A woman presented with symptoms of salpingitis 7 months after delivery. Initially treated as pelvic inflammatory disease, the condition was revealed to be genital localization of miliary tuberculosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message Ingestion of foreign bodies is a common clinical problem, but intrahepatic migration is an exceptional occurrence. Clinical history is not helpful. Abdominal ultrasonography and CT are fundamental to exclude surgical causes of fever of unknown origin. Laparoscopic segmental liver resection is recommendable to avoid generalized peritonitis. [ABSTRACT FROM AUTHOR]

Background Random skin biopsy ( RSB) is a method for diagnosis of intravascular lymphoma ( IVL). However, the indications for RSB to diagnose IVL have not yet been established. The aim of this study was to determine the appropriate indications for RSB to diagnose IVL. Methods Thirty-two patients with fever of unknown origin ( FUO) and without skin lesion underwent RSB for diagnosis of IVL. Clinical data, including fever, neurological symptoms, hematologic disorders, organomegaly, bone marrow ( BM) study, hypoxemia and serum level of lactate dehydrogenase ( LDH), were evaluated. Results Seven of 32 patients were definitively diagnosed with IVL. In addition to FUO, 2 IVL patients also suffered from dyspnea and neurological disorders. Patients who had FUO with accompanying hematologic disorders, high LDH, negative BM study and no lymphadenopathy or hepatosplenomegaly had a significant tendency to have IVL by RSB ( P = .03). FUO with hypoxemia was also identified as a significant indication for RSB ( P = .02). Conclusions RSB is a reliable method for diagnosis of IVL, especially in patients with FUO and any 1 or more of the 4 following abnormalities: (1) hematologic abnormalities; (2) high serum LDH; (3) hypoxemia; and/or, (4) unusual neurological symptoms with co-existing hematologic abnormalities and without lymphadenopathy, hepatosplenomegaly or BM abnormality. [ABSTRACT FROM AUTHOR]