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Despite advancements in medical technology, the challenges of diagnosing fever of unknown origin (FUO) and inflammation of unknown origin (IUO) persist. Positron emission tomography/computed tomography (PET/CT) has been used to assess these conditions; however, it is unclear which patients most benefit from this approach. This study aimed to assess the clinical value and optimal use of fluorine-18-labelled-fluorodeoxyglucose (18F-FDG)-PET/CT in patients with FUO/IUO. We reviewed FDG-PET/CT scans conducted at our department between January 2014 and December 2020 to further assess FUO/IUO. FUO was defined as a fever lasting over three weeks without a diagnosis based on conventional assessment. IUO was defined as prolonged inflammation with a body temperature below 38.3 ℃ and without a diagnosis after conventional diagnostic procedures. The efficacy of FDG-PET/CT was determined based on the diagnostic outcomes achieved by integrating imaging findings with histopathological or microbiological evidence, clinical criteria, or follow-up assessments. We conducted crude and age-sex adjusted logistic regression for potential risk factors to determine the degree of burden on demographic and clinical characteristics. Forty-five patients with FUO/IUO underwent FDG-PET/CT, and final diagnoses were made in 32 patients (71.1%). The percentages of diagnostic categories were 53.3%, 8.9%, and 6.7% for non-infectious inflammatory diseases, malignancy, and infection, respectively. In multivariable logistic regression analysis, IUO was the only independent predictor of the efficacy of FDG-PET/CT in the final diagnosis (odds ratio, 67.02; 95% confidence interval, 4.02–1119). Our results indicate that IUO was associated with a higher diagnostic yield compared to those with FUO. [ABSTRACT FROM AUTHOR]

Background: A considerable portion of patients with fever of unknown origin (FUO) present concomitant lymphadenopathy. Diseases within the spectrum of FUO accompanied by lymphadenopathy include lymphoma, infections, and rheumatic diseases. Particularly, lymphoma has emerged as the most prevalent etiology of FUO with associated lymphadenopathy. Distinguishing between benign and malignant lymph node lesions is a major challenge for physicians and an urgent clinical concern for patients. However, conventional imaging techniques, including PET/CT, often have difficulty accurately distinguishing between malignant and benign lymph node lesions. This study utilizes PET/CT radiomics to differentiate between lymphoma and benign lymph node lesions in patients with FUO, aiming to improve diagnostic accuracy. Results: Data were collected from 204 patients who underwent 18F-FDG PET/CT examinations for FUO, including 114 lymphoma patients and 90 patients with benign lymph node lesions. Patients were randomly divided into training and testing groups at a ratio of 7:3. A total of 15 effective features were obtained by the least absolute shrinkage and selection operator (LASSO) algorithm. Machine learning models were constructed using logistic regression (LR), support vector machine (SVM), random forest (RF), and k-nearest neighbors (KNN) algorithms. In the training group, the area under the curve (AUC) values for predicting lymphoma and benign cases by LR, SVM, RF, and KNN models were 0.936, 0.930, 0.998, and 0.938, respectively. There were statistically significant differences in AUC between the RF and other models (all P < 0.001). In the testing group, the AUC values for the four models were 0.860, 0.866, 0.915, and 0.891, respectively, with no statistically significant differences observed among them (all P > 0.05). The decision curve analysis (DCA) curves of the RF model outperformed those of the other three models in both the training and testing groups. Conclusions: PET/CT radiomics demonstrated promising performance in discriminating lymphoma from benign lymph node lesions in patients with FUO, with the RF model showing the best performance. [ABSTRACT FROM AUTHOR]

Introduction: Adult-onset Still's disease is a rare systemic autoinflammatory disease. We present a case of a young man with a constellation of symptoms and myopericarditis as a complication of this disease. Case: A 36-year-old Hispanic man with no significant past medical history developed a quotidian fever pattern following an upper respiratory tract infection. He initially presented with chest pain concerning for myocardial infarction and underwent cardiac catheterization, which revealed non-obstructive coronary artery disease. He was found to have myopericarditis, significant neutrophilic leukocytosis, and hyperferritinemia. He improved on high-dose corticosteroids but developed steroid-induced psychosis, and 4 months from symptom onset, he finally received tocilizumab, which eventually induced remission without adverse reactions. Discussion: Adult-onset Still's disease should be considered in a patient with fevers of undetermined origin. Due to its multisystemic involvement, adult-onset Still's disease is often a diagnosis arrived at after an extensive cardiac, hematologic, malignant, and infectious workup. Imaging, laboratory testing, and bone marrow biopsy were necessary to rule out alternative etiologies of this patient's presentation. Steroids are the mainstay of treatment because they are easily affordable, although the high risk of adverse effects makes them less desirable. Interleukin-1 inhibitors (anakinra or canakinumab) and interleukin-6 inhibitor tocilizumab are the steroid-sparing biologic agents of choice but are cost-prohibitive. Conclusion: Adult-onset Still's disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays. [ABSTRACT FROM AUTHOR]

Fever of unknown origin (FUO) can be caused by many factors and usually presents as a high fever without a clear diagnosis. Although some treatments may relieve symptoms, they do not stabilise the condition and relapses are commonly reported. In this case, a 20-year-old male complained of recurring high fever (around 39-40 degrees Celsius) without reason for over two years. He had been hospitalised many times without a clear diagnosis. Applying fang zheng 方证 differentiation, the patient was prescribed Chai Ling Tang (Bupleurum and Poria Decoction) combined with Wai Tai Fu Ling Yin (Poria Decoction) as well as Ban Xia Hou Po Tang (Pinellia and Magnolia Bark Decoction). After three months of medication, the patient’s temperature stabilised, his body weight slowly increased and his other symptoms also improved. [ABSTRACT FROM AUTHOR]

Background: Fever of unknown origin (FUO) is a common condition worldwide in children that remains a diagnostic challenge. The causes of FUO vary depending on the patient's age, residency, and the time of study. Therefore, this study aimed to identify the common aetiologies of FUO at Alexandria University Children's Hospital under the current diagnostic abilities and newly emerging diseases. Methods: The current prospective observational study included all children fulfilling the definition of FUO admitted at Alexandria University Children's Hospital from January 2020 to December 2021 using a steps approach for investigations. Results: A total of 110 children with fever of unknown origin (FUO) were included in this study; the average duration of fever was 36.76 ± 31.73 days. In most of the enrolled cases 105/110 (95.4%) the definite etiology of FUO was identified. The common causes were collagen vascular diseases (30.9%), infectious diseases (28.2%), miscellaneous conditions (19.1%), and malignancy (17.3%). Among collagen vascular diseases, systemic lupus erythematosus (SLE) (47.1%) and systemic onset juvenile idiopathic arthritis (sJIA) (38.2%) were the most common. In the infectious category, Katayama fever (16.1%), brucellosis (12.9%), and urinary tract infection (UTI) (12.9%) were the most frequently observed. Post-Covid MIS-C (52.4%) was the most common in the miscellaneous category. Children in the infectious category had significantly higher neutrophil [5.76 (2.28–7.92) × 10^3/µl] and lymphocytic counts [ 4.2 (2.04–5.91) × 10^3/µl]; (P < 0.001 and < 0.010 respectively). Moreover, in the collagen category the median lymphocytic count was lower [1.95 (1.47–2.73) × 10^3/µl] with a significantly (P < 0.010) higher neutrophil/ lymphocyte ratio [2.30 (1.53–3.91)]. Conclusion: Collagen vascular diseases, infectious diseases, miscellaneous, and malignancy were the most common causes of FUO. Katayama fever, urinary tract infections (UTI), and brucellosis were the most common causes in the infectious category. Post-Covid MIS-C and hemophagocytic lymphohistiocytosis were the most common diagnoses in the miscellaneous category. [ABSTRACT FROM AUTHOR]

Abstract Despite advancements in medical technology, the challenges of diagnosing fever of unknown origin (FUO) and inflammation of unknown origin (IUO) persist. Positron emission tomography/computed tomography (PET/CT) has been used to assess these conditions; however, it is unclear which patients most benefit from this approach. This study aimed to assess the clinical value and optimal use of fluorine-18-labelled-fluorodeoxyglucose (18F-FDG)-PET/CT in patients with FUO/IUO. We reviewed FDG-PET/CT scans conducted at our department between January 2014 and December 2020 to further assess FUO/IUO. FUO was defined as a fever lasting over three weeks without a diagnosis based on conventional assessment. IUO was defined as prolonged inflammation with a body temperature below 38.3 ℃ and without a diagnosis after conventional diagnostic procedures. The efficacy of FDG-PET/CT was determined based on the diagnostic outcomes achieved by integrating imaging findings with histopathological or microbiological evidence, clinical criteria, or follow-up assessments. We conducted crude and age-sex adjusted logistic regression for potential risk factors to determine the degree of burden on demographic and clinical characteristics. Forty-five patients with FUO/IUO underwent FDG-PET/CT, and final diagnoses were made in 32 patients (71.1%). The percentages of diagnostic categories were 53.3%, 8.9%, and 6.7% for non-infectious inflammatory diseases, malignancy, and infection, respectively. In multivariable logistic regression analysis, IUO was the only independent predictor of the efficacy of FDG-PET/CT in the final diagnosis (odds ratio, 67.02; 95% confidence interval, 4.02–1119). Our results indicate that IUO was associated with a higher diagnostic yield compared to those with FUO.

Abstract Background A considerable portion of patients with fever of unknown origin (FUO) present concomitant lymphadenopathy. Diseases within the spectrum of FUO accompanied by lymphadenopathy include lymphoma, infections, and rheumatic diseases. Particularly, lymphoma has emerged as the most prevalent etiology of FUO with associated lymphadenopathy. Distinguishing between benign and malignant lymph node lesions is a major challenge for physicians and an urgent clinical concern for patients. However, conventional imaging techniques, including PET/CT, often have difficulty accurately distinguishing between malignant and benign lymph node lesions. This study utilizes PET/CT radiomics to differentiate between lymphoma and benign lymph node lesions in patients with FUO, aiming to improve diagnostic accuracy. Results Data were collected from 204 patients who underwent 18F-FDG PET/CT examinations for FUO, including 114 lymphoma patients and 90 patients with benign lymph node lesions. Patients were randomly divided into training and testing groups at a ratio of 7:3. A total of 15 effective features were obtained by the least absolute shrinkage and selection operator (LASSO) algorithm. Machine learning models were constructed using logistic regression (LR), support vector machine (SVM), random forest (RF), and k-nearest neighbors (KNN) algorithms. In the training group, the area under the curve (AUC) values for predicting lymphoma and benign cases by LR, SVM, RF, and KNN models were 0.936, 0.930, 0.998, and 0.938, respectively. There were statistically significant differences in AUC between the RF and other models (all P 0.05). The decision curve analysis (DCA) curves of the RF model outperformed those of the other three models in both the training and testing groups. Conclusions PET/CT radiomics demonstrated promising performance in discriminating lymphoma from benign lymph node lesions in patients with FUO, with the RF model showing the best performance.

Fever of unknown origin is a difficult syndrome for differential diagnosis. Absence of a key feature, variety of causes and the lack of single examination algorithm makes difficult further diagnosis. The presented clinical case describes a 53-year-old patient with a prolonged fever of more than 1.5 months, pain syndrome in the facial area. During outpatient monitoring, the cause was not clarified. At the inpatient stage, a comprehensive examination was conducted for all classes of causes. The revealed changes in the thyroid gland and thyrotoxicosis made it possible to diagnose subacute thyroiditis. According to the literature, subacute thyroiditis is one of the rare causes of fever of unknown origin. Prescription of glucocorticosteroid made it possible to achieve complete regression of clinical symptoms in 4 days. After 5 months, subclinical hypothyroidism was achieved. The nosological approach and multidisciplinary interaction contributed to the correct tactics and a favorable outcome of the disease.

Abstract Introduction Adult-onset Still’s disease is a rare systemic autoinflammatory disease. We present a case of a young man with a constellation of symptoms and myopericarditis as a complication of this disease. Case A 36-year-old Hispanic man with no significant past medical history developed a quotidian fever pattern following an upper respiratory tract infection. He initially presented with chest pain concerning for myocardial infarction and underwent cardiac catheterization, which revealed non-obstructive coronary artery disease. He was found to have myopericarditis, significant neutrophilic leukocytosis, and hyperferritinemia. He improved on high-dose corticosteroids but developed steroid-induced psychosis, and 4 months from symptom onset, he finally received tocilizumab, which eventually induced remission without adverse reactions. Discussion Adult-onset Still’s disease should be considered in a patient with fevers of undetermined origin. Due to its multisystemic involvement, adult-onset Still’s disease is often a diagnosis arrived at after an extensive cardiac, hematologic, malignant, and infectious workup. Imaging, laboratory testing, and bone marrow biopsy were necessary to rule out alternative etiologies of this patient’s presentation. Steroids are the mainstay of treatment because they are easily affordable, although the high risk of adverse effects makes them less desirable. Interleukin-1 inhibitors (anakinra or canakinumab) and interleukin-6 inhibitor tocilizumab are the steroid-sparing biologic agents of choice but are cost-prohibitive. Conclusion Adult-onset Still’s disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays.

Abstract Background Fever of unknown origin (FUO) is a common condition worldwide in children that remains a diagnostic challenge. The causes of FUO vary depending on the patient's age, residency, and the time of study. Therefore, this study aimed to identify the common aetiologies of FUO at Alexandria University Children’s Hospital under the current diagnostic abilities and newly emerging diseases. Methods The current prospective observational study included all children fulfilling the definition of FUO admitted at Alexandria University Children's Hospital from January 2020 to December 2021 using a steps approach for investigations. Results A total of 110 children with fever of unknown origin (FUO) were included in this study; the average duration of fever was 36.76 ± 31.73 days. In most of the enrolled cases 105/110 (95.4%) the definite etiology of FUO was identified. The common causes were collagen vascular diseases (30.9%), infectious diseases (28.2%), miscellaneous conditions (19.1%), and malignancy (17.3%). Among collagen vascular diseases, systemic lupus erythematosus (SLE) (47.1%) and systemic onset juvenile idiopathic arthritis (sJIA) (38.2%) were the most common. In the infectious category, Katayama fever (16.1%), brucellosis (12.9%), and urinary tract infection (UTI) (12.9%) were the most frequently observed. Post-Covid MIS-C (52.4%) was the most common in the miscellaneous category. Children in the infectious category had significantly higher neutrophil [5.76 (2.28–7.92) × 10^3/µl] and lymphocytic counts [ 4.2 (2.04–5.91) × 10^3/µl]; (P

Criteria classifying fever of unknown origin (FUO) patients remains subject to discrepancies. A minimal standardized set of investigative tests serves as the foundation for the qualitative criteria, whereas quantitative incorporates the length of evaluation (7 or 3 days). A systematic review of studies would help physicians anticipate the frequency of illness types that could influence management. Prospective studies published in Medline (PubMed), Embase, Scopus, and Web of Science databases from January 1, 1997 to July 31, 2022, were included. A meta-analysis estimated associated pooled proportions between these criteria and diagnostic outcomes adjusted to the International Classification of Diseases, 10th edition (ICD-10) definitions. Five qualitative studies corresponded to an increase of 15.3% (95% CI: 2.3%-28.3%, P =.021) in undiagnosed FUO proportions compared to eleven quantitative studies. Quantitative studies had 19.7% (95% CI: 6.0%-33.4%, P =.005) more in adjusted infectious disease proportions than qualitative studies. No significant differences in proportions between FUO defining criteria were noted for adjusted noninfectious inflammatory disorders (P =.318), oncology (P =.901), non-inflammatory miscellaneous disorders (P =.321), diagnostic evaluation process, gross national income (GNI), or World Health Organization (WHO) geographic region. Use of either qualitative or quantitative FUO criteria was associated with a statistically significant risk of over- or under-estimating infectious diseases and undiagnosed illnesses when using an ICD-10 adjusted FUO five-category system. Clinicians should anticipate differences depending on which criteria are used. While further research is warranted, qualitative criteria provide the best framework for study comparisons. [ABSTRACT FROM AUTHOR]

Fever in older adults poses unique challenges due to atypical symptoms, weakened immune responses, and comorbidities. This chapter explores the diverse presentations of fever in the elderly, emphasizing the importance of vigilant monitoring and tailored interventions by healthcare providers and caregivers. Challenges in temperature measurement, communication barriers, and polypharmacy further complicate fever management. The chapter discusses the differences between fever presentations in young and older individuals and addresses the complexities of managing fever in long-term care facilities. In addition, it highlights fever of unknown origin in older persons, stressing the need for timely diagnosis and tailored investigations. Finally, preventive strategies, including vaccination campaigns and infection control measures, are proposed to mitigate fever occurrences in older adults.

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

Background Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients. Methods A modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies. Results Among 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO. Conclusions These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research. [ABSTRACT FROM AUTHOR]

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

Introduction: Suspected infection or inflammation of unknown origin in in-patients remains challenging. Literature on [18F]FDG-PET/CT is abundant in classic fever of unknown origin (FUO), but evidence is complex and may not always reflect clinical reality. This study explores the application of [18F]FDG-PET/CT in a diverse clinical population of in-patients with suspected infection not defined by stringent FUO-criteria. Methods: Retrospective chart review of consecutive in-patients who underwent [18F]FDG-PET/CT in the workup of suspected infection or inflammation from 1 July 2022 to 31 December 2022 was conducted. We evaluated indications, diagnostic yield, and clinical impact of [18F]FDG-PET/CT, and compared the findings of [18F]FDG-PET/CT and stand-alone CT. Univariate logistic regression assessed associations between [18F]FDG-PET/CT outcome and clinical parameters. Receiver operating characteristic curve (ROC) analysis evaluated diagnostic performance. Results: 77 patients met the inclusion criteria. [18F]FDG-PET/CT established a diagnosis in 35% of cases, ruled out focal infection in 26%, and thus was helpful in 61% of patients. It prompted 72 additional examinations resulting in seven incidental diagnoses, including two cancers. Antibiotic treatment was changed in 26% of cases. Regression analysis found white blood cell counts (WBC) associated with true positive outcomes. [18F]FDG-PET/CT was compared to stand-alone CT findings, and was concordant in 69% of cases. Conclusions: Results were comparable to findings in more classic FUO. [18F]FDG-PET/CT was clinically helpful in 61% of cases but also prompted many additional examinations with relatively few clinically important findings. WBC count was a predictor of true positive outcome. CT and [18F]FDG-PET/CT were discordant in 31%, of cases, especially in cases of endocarditis and spondylodiscitis. [ABSTRACT FROM AUTHOR]

Background: Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. Case presentation: We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. Conclusions: To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure. [ABSTRACT FROM AUTHOR]

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

Background: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. Methodology: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. Results: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. Conclusions: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO. [ABSTRACT FROM AUTHOR]

The spectrum of HHV-8-associated disorders includes Kaposi's sarcoma, primary effusion lymphoma, multicentric Castleman's disease, and the recently described KSHV inflammatory cytokine syndrome (KICS), a life-threatening disorder complicating HIV infection. There have been no reports in the literature concerning non-immunosuppressed individuals affected with KICS. We report here a KICS-like illness occurring in two elderly Greek men without HIV infection or other recognizable cause of immunosuppression. [ABSTRACT FROM AUTHOR]

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BackgroundFever is a common symptom in children, but despite existing guidelines, pediatricians may not fully apply recommendations. Fever of Unknown Origin (FUO) is generally referred to as an unexplained prolonged fever. However, a standardized FUO definition and management is missing.ObjectiveTo collect updated data on the approach to fever and FUO among Italian pediatricians.MethodsA cross-sectional anonymous survey was conducted among a large sample of primary care and hospital pediatricians. The panel group formulated and proposed a practical FUO definition, using a modified Delphi approach. A 75% consensus was required to reach an agreement.ResultsAmong 620 respondents, paracetamol was the first-choice antipyretic for 97.7% of participants, followed by ibuprofen; 38.4% prescribed antipyretics based on a specific body temperature rather than on child's discomfort, while physical methods were almost completely abandoned. Alternate treatment was recommended by 19.8% (123/620) of participants, 16.9% (105/620) would prescribe antipyretics to prevent adverse events following immunization. Regarding FUO diagnosis, 58.3% (362/620) considered as cut-off a body temperature above 38°C; the duration required was one week according to 36.45% (226/620) of participants, two weeks according to 35.32% (219/620). The FUO definition proposed by the expert panel reached 81% of consent. Large agreement was observed on first-level laboratory and instrumental investigations in the diagnostic evaluation of FUO, whereas more discrepancies arose on second and third-level investigations. Compared to what participants reported for the treatment of non-prolonged fever, a significant decrease in the prescription of paracetamol as first-choice drug in children with FUO was observed (80.5%; P

This paper presents the diagnostic and therapeutic challenges encountered in an older woman with advanced HIV infection. Upon admission, the patient exhibited severe symptoms of interstitial pneumonia and cachexia. During hospitalization, the patient was diagnosed with SARS-CoV-2 infection and a wide spectrum of opportunistic pulmonary infections, including Pneumocystis jiroveci, Candida krusei, and Staphylococcus haemolyticus. Another major diagnostic challenge posed the patient’s prolonged fever, which persisted despite comprehensive treatment. This report underscores the importance of considering new HIV infections in older patients presenting complex clinical pictures, its significant mortality risk in older individuals, and the need for timely initiation and adjustment of antiretroviral therapy.

Fever of unknown origin (FUO), despite the wide diagnostic potential of modern medicine, remains a difficult problem for clinicians. Often, making a correct diagnosis requires a comprehensive examination of the patient, as well as the joint work of doctors from different specialties.A 57-year-old male patient was hospitalized due to an episode of loss of consciousness, unmotivated weight loss and daily evening temperature rises to 38-39о C, accompanied by chills and increased sweating. Previously, he was examined by a general practitioner, a cardiologist, and repeatedly by a hematologist. There was no evidence of an infectious disease, arrhythmias, multiple myeloma, lymphoproliferative disorders. Monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Blood tests revealed neutrophilia (9800 cells/ μl) and moderate anemia. The patient was hospitalized to determine the FUO cause. Heart auscultation revealed a systolic murmur in the mitral valve, which was previously absent. Echocardiography revealed a mobile masses on the mitral valve, severe mitral regurgitation, and therefore infective endocarditis was diagnosed. Empirical antibiotic therapy with ceftriaxone and levofloxacin was administered. Further blood culture revealed growth of a HACEK representative Aggregatibacter actinomycetemcomitans, sensitive to both drugs. Examination established the odontogenic nature of endocarditis. During treatment, stable normothermia and significant blood count improvement were achieved. However, fluoroquinolone therapy led to tendinopathy. Due to persistent grade 3 mitral regurgitation, the patient underwent routine mitral valve replacement. Further follow-up revealed satisfactory condition of the patient.A feature of this case is the atypical course of infective endocarditis, occurring under a hematological mask, which made its diagnosis difficult. When examining a FUO patient, infective endocarditis should be included in the range of possible causes, taking into account not only the typical clinical picture, but also the numerous masks of this disease.

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 Background Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. Case presentation H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient’s anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient’s body temperature gradually returned to the normal range and her mood improved significantly. Conclusion Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.

Background: While petechiae can be a sign of a serious underlying condition, the majority are benign. Frequently, an underlying cause is not identified despite extensive diagnostic testing. Petechiae may be caused by CMV infection which is rarely considered in the differential diagnostic process. Most immunocompetent adults with primary CMV infection are asymptomatic or develop a mononucleosis-like syndrome with fever and mild hepatitis. Case report: We report the case of a 30-year-old man who presented to an out-of-hours general physician consult with intermittent fever for three weeks. Examination showed petechiae on the upper extremities. Initial laboratory data revealed lymphocytosis and elevated liver enzyme tests. Further testing showed positive CMV throat swab and CMV/EBV immunoglobulin M and G. His symptoms resolved gradually without any treatment. Why should an emergency physician be aware of this?: This report shows that primary CMV infection can be a cause of petechiae. Emergency physicians should keep in mind that although uncommon, immunocompetent adults can experience acute symptomatic CMV infections characterized by an extended disease course and testing may avoid unnecessary and extensive diagnostic workup and repeated hospital contacts.

AbstractIntravascular large B-cell lymphoma (IVLBCL) is a rare subtype of malignant lymphoma (ML). Here, we present a case of IVLBCL initially suspected as invasive fungal rhinosinusitis (IFRS). A 64-year-old woman was referred to our hospital due to persistent fever, headache, and rhinorrhea. After admission, her overall condition rapidly deteriorated, leading to a diagnosis of septic shock. Blood examination revealed elevated serum lactate dehydrogenase and soluble interleukin 2 receptor levels suggestive of ML. Computed tomography revealed a high-density area with calcifications within the sinus cavity. Although IFRS was the primary suspicion, subsequent endoscopic sinus surgery disconfirmed this hypothesis based on histological findings. Unfortunately, the patient succumbed to multiple organ failure 12 days after admission, with an autopsy confirming IVLBCL. It is crucial to consider IVLBCL as a potential differential diagnosis in cases involving fever of unknown origin and progressive deterioration of the general condition.

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

Background: Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. Case presentation: H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient's anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient's body temperature gradually returned to the normal range and her mood improved significantly. Conclusion: Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range. [ABSTRACT FROM AUTHOR]

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

Fever in older adults poses unique challenges due to atypical symptoms, weakened immune responses, and comorbidities. This chapter explores the diverse presentations of fever in the elderly, emphasizing the importance of vigilant monitoring and tailored interventions by healthcare providers and caregivers. Challenges in temperature measurement, communication barriers, and polypharmacy further complicate fever management. The chapter discusses the differences between fever presentations in young and older individuals and addresses the complexities of managing fever in long-term care facilities. In addition, it highlights fever of unknown origin in older persons, stressing the need for timely diagnosis and tailored investigations. Finally, preventive strategies, including vaccination campaigns and infection control measures, are proposed to mitigate fever occurrences in older adults. [ABSTRACT FROM AUTHOR]

Background. Hemophagocytic Lymphohistiocytosis (HLH), characterized by uncontrolled activation of immune cells leading to a hyperinflammatory state, is seldom considered in the initial differential diagnosis of FUO. The rarity of idiopathic HLH, especially in young individuals without an identifiable trigger, emerges as an uncommon and particularly challenging diagnosis. This case report presents a compelling narrative of a young female grappling with the complexities of FUO, ultimately revealing the rare and life-threatening entity of idiopathic HLH. Case report. A 25 year old female was referred to our hospital in view of persistent high grade fever since 3 months. Patient has no other complaints. Vitals stable. General and systemic examination normal. Lab investigations showed a total leukocyte count 18000 cell/μL, hemoglobin 9.2 g/dL, and platelets 68000 cells/μL. Other blood investigations showed erythrocyte sedimentation rate (ESR) 88 mm/h, C-reactive protein 21 mg/L, ferritin 670 ng/mL, triglyceride 281 mg/dL, and fibrinogen 1.2g/L. She also had transaminitis with AST 80, ALT 92 and ALP 1442. The entire infectious diseases panel was done which came negative for all, including viral serologies and hepatitis markers. Procalcotonin level was normal and no other relevant investigations came positive. Autoimmune panel analysis also came negative. Blood cultures came negative in two different samples. Also, there is no evidence of vegetation in echocardiography. Coming to the invasive investigations, bone marrow biopsy and aspiration were done to arrive at a diagnosis and it showed Hemophagocytosis. Endoscopy and colonoscopy were done, which came normal. CT thorax and abdomen also showed no significant abnormality, ruling out the probability of missing any gross malignancies. After all this extensive work up and according to Hscore, which is used to estimate an individual’s risk of having reactive hemophagocytic syndrome, this patient was diagnosed with HLH. According to the current HLH guidelines, initial treatment for the disease consists of etoposide, corticosteroids (dexamethasone), or cyclosporine is given for 8 weeks. The patient was started on the same above treatment regimen, but only with corticosteroids for a period of 8weeks, after consultation with Hematologist. No recurrence is seen in her 6-months of follow-up. The regimen was well tolerated by the patient. Studies also have shown that therapeutic plasma exchange also has a role in HLH treatment, which can be tried in familial and relapsing cases. Conclusion. In our case, this young female was diagnosed to have Idiopathic HLH, after ruling out all the familial and secondary causes of HLH including Infections, Malignancy and Autoimmune diseases. The patient was also started on treatment early after the bone marrow and other relevant investigations according to HScore suggested the diagnosis of HLH and the patient improved accordingly. Hence, apart from clearly knowing the etiology or clinical manifestations, HLH is associated with a high mortality rate if appropriate treatment not given. Generally, the underlying etiology determines the prognosis of the disease. But, it is not a good idea to delay the treatment in order to find the cause and type of HLH, because the exhaustive work up might lead to unacceptable delays in improvement and prognosis of the patient. The diagnostic work up and treatment should be done simultaneously in the patient, which has been done in our case and it lead to a good outcome. Though HLH is a fatal and dangerous disease and also highly challenging to make a diagnosis due its uncommon and largely variable clinical presentation, smart work up and early initiation of treatment will lead to better prognostic outcome. [ABSTRACT FROM AUTHOR]

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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]

ObjectiveTo report a survey on an outbreak of Pontiac fever associated with history of exposure to a bath center in Shanghai in 2020 for providing a reference to investigation of relevant epidemics. MethodsA questionnaire survey was conducted among 139 cases of fever of unknown origin (all with the history of exposure to a bath center) reported by fever clinics during 18 – 21 December, 2020 in Fengxian district of Shanghai. A subsequent case- control study was carried out among 74 cases with explicit information on activities in the bath center and 44 healthy controls ever exposed to the bath center during the same period. Deep throat sputum samples were collected from 15 cases for nucleic acid detections of multiple pathogens with reverse transcription-polymerase chain reaction (RT-PCR) and Legionella culture with buffered charcoal yeast-extract (BCYE) plate. Residual chlorine detector was used in field study to measure residual chlorine in water of various pools in the bath center. Logistic regression analysis was adopted to explore factors correlated with the incidence of the fever of unknown origin. ResultsThe most common observed symptoms among the 139 fever cases were weakness (proportion: 51.08%, case number: 71), headache (41.73%, 58), and myalgia (41.73%, 58). The median incubation period for the symptom incidence was 36 hours, with an range of 12 – 68 hours. In the case-control study, univariate analysis revealed that bathing in pools of the bath center was a risk factor for fever incidence (odds ratio [OR] = 9.036, 95% confidence interval [95%CI]: 3.521 – 23.189); multivariate logistic regression analysis also showed that the cases ever bathing in a special pool for body beatification was at a significantly increased risk of fever incidence (OR = 5.456, 95%CI: 3.521 – 23.189). Legionella nucleic acid was detected in 4 cases. Legionella strains were cultured in 4 environment swab samples collected in the bath center. The residual chlorine of water in two of bathing pools (0.2 mg/L and 0.09 mg/L) were lower than that of the national standard. ConclusionBased on epidemiologic evidence, clinical symptom of the cases, and laboratory test results, the outbreak of fever of unknown origin was a Pontiac fever caused by Legionella associated with the exposure to a bath center.

Background: Fever of unknown origin (FUO) in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of FUO. Methods: A multi-center study for infectious causes of FUO in lower middle-income countries (LMIC) and low-income countries (LIC) was conducted between January 1, 2018 and January 1, 2023. In total, 15 participating centers from seven different countries provided the data, which were collected through the Infectious Diseases-International Research Initiative platform. Only adult patients with confirmed infection as the cause of FUO were included in the study. The severity parameters were quick Sequential Organ Failure Assessment (qSOFA) ≥2, intensive care unit (ICU) admission, vasopressor use, and invasive mechanical ventilation (IMV). Results: A total of 160 patients with infectious FUO were included in the study. Overall, 148 (92.5%) patients had community-acquired infections and 12 (7.5%) had hospital-acquired infections. The most common infectious syndromes were tuberculosis (TB) (n=27, 16.9%), infective endocarditis (n=25, 15.6%), malaria (n=21, 13.1%), brucellosis (n=15, 9.4%), and typhoid fever (n=9, 5.6%). Plasmodium falciparum, Mycobacterium tuberculosis, Brucellae, Staphylococcus aureus, Salmonella typhi, and Rickettsiae were the leading infectious agents in this study. A total of 56 (35.0%) cases had invasive procedures for diagnosis. The mean qSOFA score was 0.76±0.94 {median (interquartile range [IQR]): 0 (0–1)}. ICU admission (n=26, 16.2%), vasopressor use (n=14, 8.8%), and IMV (n=10, 6.3%) were not rare. Overall, 38 (23.8%) patients had at least one of the severity parameters. The mortality rate was 15 (9.4%), and the mortality was attributable to the infection causing FUO in 12 (7.5%) patients. Conclusions: In LMIC and LIC, tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.

With a growing emphasis on value-based reimbursement, developing quality indicators for infectious diseases has gained attention. Quality indicators for fever of unknown origin and inflammation of unknown origin are lacking. An assembled group of international experts developed 12 quality measures for these conditions, which could be validated with additional study. [ABSTRACT FROM AUTHOR]

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, to some extent, a process of exclusion. AOSD has life-threating complications ranging from asymptomatic to severe, such as macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with cytokine storm production and monocyte/macrophage overactivation and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. For the treatment of MAS-HLH, the Histiocyte Society currently suggests high-dose corticosteroids, with the possible addition of cyclosporine A, anti-interleukin (IL)-1, or IL-6 biological drugs; the inclusion of etoposide is recommended for the most severe conditions. In all cases, a multidisciplinary collaboration involving the resources and expertise of several specialists (e.g., rheumatologist, infectiologist, critical care medicine specialist) is advised. Herein, we provide a detailed description of the clinical case of a previously healthy young woman in which MAS developed as a dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge; the condition was finally resolved by applying the HLH-94 protocol (i.e., etoposide in combination with dexamethasone). [ABSTRACT FROM AUTHOR]

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

Many clinical conditions can cause fever of unknown origin (FUO) in children, but the etiological diagnosis remains challenging despite the variety of inspection methods available at present. This study aims to investigate the effectiveness of droplet digital polymerase chain reaction (ddPCR) in identifying pathogens in children with FUO as a novel application. A 7-month-old boy failed to obtain etiology evidence for his disease through various tests. After collecting peripheral blood for ddPCR analysis, Staphylococcus aureus and Escherichia coli were detected, and Sanger sequencing confirmed the pathogens. During the disease, the child developed septic arthritis and osteomyelitis in the femur. Despite the patient's fever being removed, his limb activity improving, and inflammatory biomarkers decreasing, avascular necrosis of the femoral head remained after targeted antibiotic treatment and surgery. If the patient had undergone ddPCR analysis at an early stage, it may be possible to avoid sequelae. ddPCR helps identify pathogens in the diagnosis of children with FUO and could be a promising complementary tool.

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 The management of low-grade fever in adults has not been codified. This gap is related not only to the numerous possible aetiologies but also to the difficulty of escaping the monocausal model of diseases. This article explores the complex issue of positive signs in ‘psychogenic fever’ through Reimann’s 1930s series. The discussion emphasises Canguilhem’s positions regarding vital signs and proposes (1) a semantic clarification of ‘habitual hyperthermia’ and (2) an amendment of the Belgian diagnostic criteria based on the concept of functional disorder. This paper also suggests following Peirce’s pragmatism in the face of an uncommon clinical picture.

Abstract Background Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings. Methods To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA (n = 99), non-systemic JIA (n = 169), infections (n = 51), other inflammatory diseases (n = 126), and acute lymphoblastic leukemia (ALL, n = 147). In addition, samples from 23 healthy controls were included. Results The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies (r = 0.99, p

Iliopsoas abscess (IPA) rarely occurs in newborns and infants. Symptom triad, including fever, inguinal swelling or discoloration, and limited lower limb movement, is observed in most cases. Herein, we report a case of unusual IPA in an 82-day-old boy who presented with fever as the only symptom. To our best knowledge, there have been no reports of infant IPA presenting without localizing signs. This report highlights the importance of a high degree of suspicion for timely diagnosis of infant IPA when an infant presents only with fever.