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Psittacosis is a rare zoonotic disease caused by a gram-negative obligate intracellular bacterium Chlamydia psittaci , which is transmitted through contact with infected birds. It comprises approximately 1% of all community-acquired pneumonia cases. However, this can be just the tip of the iceberg pertaining to the lack of routine testing and awareness of this disease entity, thereby requiring a high index of suspicion for its diagnosis. We report a case of a 37-year-old male presenting with high-grade fever with chills, acute onset of dyspnea, dry cough, arthralgia, and myalgia which was not responding to broad-spectrum empirical antibiotics and supportive care. We started evaluating the patient as a case of pyrexia of unknown origin (PUO), but the fever workup turned out to be inconclusive. This prompted us to revisit the history. It was found that the patient owned a parrot that was sick for the last 15 days. The temporal correlation of the illness with a history of exposure made us suspect psittacosis, which was confirmed by treatment with doxycycline resulting in a drastic improvement in the patient's condition. By this, we want to highlight that history remains the time-tested guide for diagnosing and treating PUO., (© Journal of the Association of Physicians of India 2024.)

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., (© 2024. The Author(s).)

Despite advancements in diagnostic modalities, delineating the etiology of fever of unknown origin (FUO) remains a significant challenge for clinicians. Notably, cases with hematological malignancies often have a poor prognosis due to delayed diagnosis. This study investigated the potential of readily obtainable laboratory markers to differentiate hematological causes from other etiologies during the early stages of FUO. A retrospective analysis was conducted on the medical records of 100 patients who fulfilled the modified FUO criteria between January 2010 and April 2023. Hematological etiologies were identified in 26 of the 100 patients. Peripheral blood neutrophil, lymphocyte, platelet counts, and the systemic immune inflammation (SII) index, were significantly lower in the hematological group compared to the non-hematological group. Conversely, serum ferritin levels were demonstrably higher in the hematological group. ROC analysis identified a neutrophil-to-ferritin ratio (NFR) cutoff value of < 8.53 as optimal for predicting hematological etiology. Subsequent multivariate analysis demonstrated that the NFR was the sole independent predictor of hematological etiology (p = 0.013).This study proposes a novel approach for early diagnosis of a potentially life-threatening subset of FUO patients. The NFR presents as an inexpensive and readily available marker for predicting hematological etiology in FUO cases., (© 2024. The Author(s).)

We present a case of a girl in her early childhood with a background of chromosomal deletion 10q21.2, hypothyroidism, second-degree atrioventricular block, developmental delay, gastroesophageal reflux disease, constipation and recurrent fevers. She had subcutaneous nodules, which represented panniculitis. Diagnosis of fever of unknown origin (FUO) associated with panniculitis was very challenging despite the involvement of geneticist, dermatologist, rheumatologist and paediatrician. To detect possible malignant cases and start treatment plans promptly, the case emphasises the need for a comprehensive diagnostic examination, which includes an early biopsy of nodular lesions. To maximise patient outcomes in complicated paediatric presentations, it emphasises the need for continual multidisciplinary teamwork and close monitoring. This case adds to the body of knowledge on the treatment of panniculitis and FUO in paediatric patients, highlighting the need of a comprehensive approach to treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To analyse the performance of the urine Gram stain for predicting a positive urine culture (UC) in young infants with fever without source (FWS) and pyuria., Design: Observational study; secondary analysis of a prospective registry-based cohort study., Setting: Paediatric emergency department; tertiary teaching hospital., Patients: Infants ≤90 days old with FWS, pyuria and urine Gram stain requested seen between 2010 and 2022., Main Outcome Measure: Performance of the Gram stain, defined as positive if any bacteria were seen, for predicting urinary tract infection (UTI: UC by urethral catheterisation growing >10 000 CFU/mL of a single bacterial pathogen)., Results: Among 367 febrile infants with pyuria, 281 (76.6%) had a positive Gram stain and 306 (83.3%) had a positive UC (277; 90.5% Escherichia coli ).Rates of positive UC in patients with positive and negative Gram stains were 97.2% and 38.4%, respectively (p<0.01), showing a sensitivity of 89.2% (95% CI: 85.2% to 92.2%) and a specificity of 86.9% (95% CI: 76.2% to 93.2%). Sensitivity was lower for diagnosing UTIs caused by bacteria other than E. coli (69.0% vs 91.3% for UTIs caused by E. coli ; p<0.01).Two (2.1%) of the 86 infants with negative Gram stains were diagnosed with bacteraemia unrelated to a UTI ( Streptococcus pneumoniae and Staphylococcus aureus )., Conclusions: Around a third of infants with pyuria and a negative Gram stain will eventually be diagnosed with a UTI. These patients have a higher rate of UTIs caused by bacteria other than E. coli . Bacterial infections other than UTIs should also be considered in such cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The diagnosis and management of fever of unknown origin pose significant challenges in the field of infectious diseases, as it is influenced by various factors. Infectious diseases have long been recognized as the primary etiology of fever of unknown origin. However, not all infectious diseases can definitively identify the causative pathogen and infection sites., Case Presentation: we present a case report of an individual with fever, nausea, and anorexia but did not report any abdominal pain. Physical examination revealed no signs of abdominal tenderness. Repeated imaging studies including enhanced CT and color US of the appendix, only one color US suggested the possibility of appendicitis. Despite effective anti-infective treatment, the patient continued to experience low-grade fever, leading to the decision for laparoscopic exploration and subsequent appendectomy. Pathological findings confirmed the presence of appendicitis. After the surgical procedure, the patient's temperature and infectious markers returned to within normal range, ultimately leading to a diagnosis of appendicitis., Conclusions: The atypical symptoms and signs, along with the negative imaging results, contribute to the under diagnosis of appendicitis and the progression of fever of unknown origin, thereby exacerbating the physical, mental, and economic burden on patients. Consequently, there are valuable insights to be gained regarding the management of both appendicitis and fever of unknown origin., (© 2024. The Author(s).)

Whipple disease (WD) is a rare chronic multisystem infectious disorder caused by the bacterium Tropheryma whipplei (T. whipplei) and is more prevalent than previously thought. Its diagnosis is often delayed by months to years owing to its rarity, non-specific manifestations and insidious course. WD classically presents with polyarthropathy followed months to years later by the development of gastrointestinal symptoms, which often lead to the diagnosis. Pyrexia of unknown origin (PUO) without gastrointestinal involvement is an extremely rare presentation. We describe a case of WD presenting as genuine PUO following immunosuppression with the tumour necrosis factor-alpha monoclonal antibody adalimumab for seronegative polyarthropathy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In addition to tumor imaging, advanced high-tech PET/CT imaging is increasingly used to elucidate the underlying causes of fever of unknown origin caused by various inflammatory processes, including pyelonephritis. Two clinical cases of whole-body PET/CT with 18F-FDG glucose, which allowed to visualize the molecular and cellular features of acute pyelonephritis as the cause of fever of unknown origin, are presented in the article. The scientifically based mechanisms of this process and the reliability of the results are discussed.

Background: Diagnosis of fever of unknown origin remains challenge for pediatricians. Lymphadenopathy is a separate entity that mainly originates from infection or malignancy., Methods: 168 patients with FUO accompanied by lymphadenectasis were reviewed. 33 lymph node tissue samples were examined by mNGS. Differences in clinical characteristics were compared among different disease groups. The value of mNGS in diagnosing and improving the clinical situation was assessed., Results: Multivariate analysis revealed that hepatosplenomegaly and LDH levels were associated with infectious diseases. Arthralgia was correlated with non-infectious inflammatory diseases. Weight loss and a node located in supraclavicular region may indicate neoplastic diseases. mNGS-positive rate was 60.60%, higher than that obtained with traditional methods. Treatment for 3/4 patients was adjusted according to the pathogen detected by mNGS, and antibiotics uses was discontinued or degraded in over 1/2 of the patients according to mNGS results., Conclusions: Clinical characteristics of children with lymphadenopathy related to FUO have limited diagnostic value for distinguishing different kinds of diseases, while mNGS of lymph node tissue serves as a useful tool for identifying infectious diseases, especially those caused by rare pathogens. mNGS results can lead to not only adjustments in targeted treatment but also further confirmation of underlying diseases., Impact Statement: 1. The clinical features of children with FUO and lymphadenopathy differ according to disease group,although multivariate analysis indicated little diagnostic value for these features. 2. mNGS on lymph node tissue from children with FUO may serve as a efficient tool for distinguishing infectious diseases from other diseases. This is especially useful when a diagnosis cannot be determined with traditional methods. 3. mNGS targeted treatment can be administered in a timely manner and some underlying diseases can be indicated., (© 2024. The Author(s).)

Leprosy is a chronic infectious disease that mainly affects the skin and peripheral nerves, it can also invade deeper tissues and organs, including mucous membranes, lymph nodes, testes, eyes, and internal organs. Severe cases can result in deformities and disabilities. We encountered the case of a 39-year-old male with unexplained fever, headache and rash. The patient's lesions were taken for histopathological examination and slit skin smear analysis. Further, the patient was detected of Mycobacterium leprae (M.leprae) nucleic acid sequences in the cerebrospinal fluid (CSF) and plasma, and M.leprae gene targets in the skin lesion tissue and blood. The patient was eventually diagnosed with multibacillary leprosy and type II leprosy reaction. These results suggest the possibility of bacteremia in patients with leprosy to some extent, and observation implies the potential invasion of CSF by M.leprae or its genetic material., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Jiang, Shi, Zhang, Jiang, Wang, Zeng and Wang.)

We present a case of a 56-year-old female with rheumatoid arthritis (RA) who has been on methotrexate for 9 years and has been complaining of high-grade fever for the past 1 month with no localizing signs and symptoms. She was thoroughly evaluated before being labeled as pyrexia of unknown origin. Histoplasmosis was suspected after bone marrow aspiration smear examination. The presence of histoplasma antigen in the urine confirmed our diagnosis. Fever responded after 2 weeks of liposomal amphotericin B and patient discharged in stable condition on tablet itraconazole., (© Journal of the Association of Physicians of India 2024.)

Aim: This study aimed to evaluate the potential role of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in providing a targeted approach for diagnosing the etiology of Pyrexia of Unknown Origin (PUO)., Methods: A total of 573 PUO patients were included in this ambispective study, with a mean age of 39.40 ± 4.6 years. Patients underwent FDG PET/CT scans using dedicated hybrid scanners. PET/CT data were interpreted by experienced nuclear medicine physicians. The study analyzed the guidance provided by FDG PET/CT for appropriate biopsy sites and assessed concordance between PET/CT findings and histopathological examination., Results: Out of the 573 patients, a final diagnosis was reached for 219 patients, including malignancy, infectious causes, noninfectious inflammatory causes (NIID), and precancerous conditions. FDG PET/CT played a crucial role in guiding clinicians to appropriate biopsy sites, contributing to a higher diagnostic yield. Concordance between PET/CT findings and histopathological examination emphasized the noninvasive diagnostic potential of PET/CT in identifying underlying causes of PUO. Overall, FDG PET/CT contributed to guiding the appropriate site of biopsy or concordance of the first differential diagnosis with the final diagnosis in 50.05% of cases., Conclusion: This study highlights the valuable role of FDG PET/CT in providing a targeted approach for diagnosing PUO, showcasing its potential in guiding clinicians towards appropriate biopsy sites and improving the diagnostic yield. The findings underscore the importance of integrating FDG PET/CT into the diagnostic pathway for PUO, ultimately enhancing patient management and outcomes. Further prospective studies are necessary to validate these results and refine the integration of FDG PET/CT in the diagnosis of PUO., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We present a rare pediatric case of cardiac inflammatory pseudotumor (IPT) with a unique presentation of fever of unknown origin with markedly elevated inflammatory markers. A right atrial mass was discovered incidentally by echocardiography. The cardiac magnetic resonance (CMR) signal characteristics and mass location were not consistent with any of the common benign cardiac tumors of childhood. The presence of high signal intensity on T2 imaging and late gadolinium enhancement, in conjunction with intense metabolic activity at the mass site on positron emission tomography (PET), raised the possibility of an inflammatory or malignant mass. The diagnosis of IPT was confirmed by biopsy. Our case highlights the utility of PET imaging to confirm the inflammatory nature and extent of an IPT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Fever of unknown origin and inflammation of unknown origin are highly challenging diagnostic conditions. The current practice for evaluating patients is to conduct a positron emission tomography-computed tomography (PET-CT) scan as either a first- or a second-line modality. We aimed to assess the contributory effect of PET-CT to the diagnosis and compare it with the contributory effect of CT alone., Methods: We performed a systematic review and meta-analysis. We included all cohorts that examined the contribution of PET-CT to the investigation of classical fever of unknown origin and inflammation of unknown origin. The primary outcome was the contribution of PET-CT to the final diagnosis. Secondary outcomes were sensitivity and specificity of PET-CT and CT scans, and contribution of a CT scan. We pooled the results of all studies and calculated the pooled contributory effect of PET-CT., Result: Thirty-six studies (3516 patients) were included in the systematic review. The pooled contribution of PET-CT was 75.4%. The compiled sensitivity and specificity values for all studies were 85.9% and 59.5%, respectively. Five studies (405 patients) compared between the PET-CT component and the total body CT component. The pooled contribution of a CT scan was 68%. The summed sensitivity and specificity values of a CT scan for all studies were 63.1% and 84.4%, respectively., Conclusions: PET-CT has a contributory effect of 75% for the diagnosis of fever of unknown origin and inflammation of unknown origin. PET-CT had superior sensitivity and inferior specificity vs the CT scan., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Fever in children is one of the most common reasons for outpatient visits as well as in-patient evaluation, often causing anxiety among parents and caregivers. Fever can be a standalone feature or be associated with other localising symptoms and signs like rash, lymphadenopathy, or any other organ system involvement with or without a focus of infection. The etiologies of fever vary depending on the clinical setting and epidemiology. India being a tropical country, sees a distinct spectrum of tropical infections. Physicians need to stay updated on the prevalent diseases in their region and the unique factors that may influence the clinical presentations and course of fever in the cohort of children they manage. The challenge lies in balancing the benefit of early treatment for severe diseases versus the harms of unnecessary investigations and treatment for self-resolving illnesses., Objectives: This review aims to provide a comprehensive overview of fever in children, covering its etiology, clinical features, and management strategies. This review offers an algorithmic approach to fever tailored to the Indian setting to guide physicians in identifying the disease based on clinical symptoms and signs, ordering essential laboratory investigations, and initiating appropriate management promptly., Content: The review categorises fever into various segments like fever with localising signs like rash, lymphadenopathy, fever due to infection localised to a particular organ system, and fever without a focus including fever of unknown origin. It delves into the diverse etiological factors contributing to fever in each of these categories, encompassing infectious and non-infectious origins. It gives pointers to identify the etiology from history, examination, and confirm them with judicious use of diagnostic investigations with emphasis on identifying the red flag signs that require immediate attention, especially in vulnerable groups like neonates and young infants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Evaluation of guidelines in actual practice is a crucial step in guideline improvement. A retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Prospective observational multicenter cross-sectional study, including children 3 days to 16 years old presented for FWS at one of seven emergency departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated, and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low-risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, fewer bacterial cultures (blood, urine, and cerebral spinal fluid), and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections., Conclusions: We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing, and antibiotic treatment., What Is Known: • Despite the development of national guidelines, variation in practice is still substantial in the assessment of febrile children to distinguish severe infection from mild self-limiting disease. • Previous retrospective research suggests low adherence to national guidelines for febrile children in practice., What Is New: • In case of non-adherence to the Dutch national guideline, similar to the National Institute for Health and Care Excellence (NICE) guideline from the United Kingdom, physicians have used fewer resources than the guideline recommended without increasing missed severe infections., (© 2024. The Author(s).)

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., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Juan Manuel Vásquez-Jiménez, Sebastián Mackenzie, Jorge Pulido-Arenas, Santiago Bernal-Macías, Javier Ricardo Garzon, Ivonne Tatiana Ordóñez, Néstor Fabián Correa, Oscar Muñoz.)

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., (© 2024. The Author(s).)

Autoinflammatory diseases are characterized by inflammatory manifestations in various organ systems, whereby recurrent febrile episodes, musculoskeletal complaints, gastrointestinal and cutaneous symptoms frequently occur accompanied by serological signs of inflammation. Autoinflammatory diseases include rare monogenic entities and multifactorial or polygenic diseases, which can manifest as a variety of symptoms in the course of time. Examples of monogenic autoinflammatory diseases are familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and the recently described VEXAS (vacuoles, E1 enzyme, X‑linked, autoinflammatory and somatic) syndrome. For non-monogenically determined autoinflammatory diseases, the most important representatives in adulthood are adult-onset Still's disease (AOSD) and the Schnitzler syndrome, in which a polygenic susceptibility and epigenetic factors are more likely to play a role., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Fever is a frequent and important symptom in patients with rheumatological diseases and can be an expression of activity of the underlying rheumatological disease. There is great variability in the incidence of fever as a symptom of the disease between individual diseases. The growing understanding of the molecular signatures of the diseases can help to explain these discrepancies: A genetic overactivation of potently pyrogenic cytokines is the reason why fever is nearly always present in autoinflammatory syndromes. In contrast, fever is less common in polyarthritis and myositis and mostly limited to severe courses of disease. In the diagnostic work-up of fever, frequent differential diagnoses, such as infections, malignancies, side effects of drugs and hypersensitivity reactions should be considered. This article provides an overview of the physiology of the development of fever, describes the relevance of fever in individual rheumatological diseases and proposes a workflow for the clinical clarification of rheumatological patients who present with fever., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Fever can be due to infectious or noninfectious causes and results from the body's natural response to exogenous or endogenous pyrogens. Laboratory tests including complete blood count, differential blood count, C‑reactive protein, erythrocyte sedimentation rate and procalcitonin do not have sufficient sensitivity and specificity to definitively detect or rule out an infectious (bacterial, viral, parasitic) cause of fever. Blood cultures should be carried out when bacteremic or septic illnesses are suspected. Fever is not always present in infections and can be absent, especially in older and immunocompromised patients. If fever is suspected, core temperatures should be taken, e.g., rectally, orally or invasively. Depending on the clinical situation, infectious causes must be excluded as the most likely cause of an acutely occurring fever. The investigation of long-standing fever (fever of unknown origin, FUO) can be complex and some infectious diseases should first be ruled out, whereby a syndromic classification often helps to clarify the cause of the fever., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up., Methods: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models., Results: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I 2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I 2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I 2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I 2 0 %)., Conclusion: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Total body computerized tomography (TBCT) is frequently used as a diagnostic tool for fever of unknown origin (FUO) workup instead of a recommended fluorodeoxyglucose positron emission tomography FDG-PET/CT. We have assessed the TBCT diagnostic yield on a large, unselected cohort of patients with FUO., Methods: We performed a single-center retrospective cohort study, examining all patients hospitalized in internal medicine between 2012 and 2019 with a documented fever and three negative blood cultures who subsequently had a total-body CT performed. After manually reviewing, we included 408 who met the criteria of FUO. We defined a positive study as a scan that led to the documented final diagnosis., Results: A total of 164 patients (40.2 %) had a positive TBCT result. The majority of positive CT findings were of infectious etiologies (58.5 %), followed by neoplasms (22.8 %) and inflammatory disorders (14.0 %), with the chest (43.9 %) and abdomen (29.8 %) most affected. Using a logistic regression model, a positive scan results were associated with an elevated CRP (p<0.001). Decision tree analysis showed that 55 % of scans of patients with an elevated CRP (>6 mg/dL), low hemoglobin and high leucocyte count (>18000/ml) were positive. Patients without an elevated CRP had a positive scan in only 26 % of tests, and those with also an elevated albumin (>4 gr/dL) and low CRP had positive scan in only 11 % of cases., Conclusions: TBCT has a clinically significant yield under specific clinical scenarios in medical patients with FUO- reaching 55 % in patients with an elevated CRP and leukocyte count and low hemoglobin. It is reasonable to proceed to TTBCT when FDG-PET/CT is unavailable and in well-defined clinical situations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: ECIL-2021 recommends discontinuing empirical antibiotic therapy (EAT) in febrile-neutropenic children after 72 h of treatment and at least 24-48 h of apyrexia in the case of fever of unknown origin (FUO). These guidelines are rarely applied to high-risk children's neutropenia., Material and Methods: We retrospectively included all consecutive FUO episodes occurring during profound neutropenia ≥ 10 days in children in our institution. We evaluated the safety of EAT discontinuation in patients for whom the ECIL guidelines were followed compared to those for whom they didn't. We used a combined criterion of mortality and intensive care unit admission at 30 days. We identified risk factors for recurrent fever after EAT discontinuation., Results: Fifty-one FUO episodes occurred in 37 patients. EAT discontinuation followed ECIL guidelines in 19 (37 %) episodes. No deaths and-or transfers in ICU occurred in the ECIL group. The duration of EAT was shorter by nine days in the group following ECIL guidelines (p < 0.001). We observed 14 (27 %) episodes of recurrent fever. Mucositis was significantly associated with recurrent fever (p < 0.01)., Conclusion: EAT discontinuation seems feasible and safe in FUO during prolonged febrile neutropenia in children. However, mucosal lesions should prompt thorough surveillance due to the risk of recurrent fever., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Abstract: A case of a 61-year male presented with chief complaints of fever for three months. Diagnosis of hemophagocytic lymphohistiocytosis was made after liver biopsy when Positron-Emission Tomography revealed multiple fluoro deoxy glucose avid lesions in the liver. The patient of this disease typically presents with fever, splenomegaly, hyperferritinemia, hypertriglyceridemia, raised liver enzymes, and marrow features suggestive of hemophagocytosis. The treatment is usually systemic corticosteroids, chemotherapy with etoposide, cyclosporine, or hematopoietic stem cell transplantation, depending on the cause. A diagnosis like hemophagocytic lymphohistiocytosis can easily be missed in developing countries with low resources like Nepal. Hence, this disease should be suspected in patients presenting with pyrexia of unknown origin by treating physicians.

Background: Recurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking., Methods: We performed a retrospective multicentre study of patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality., Results: Of 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death., Conclusion: This study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 48-year-old male was admitted to Peking Union Medical College Hospital presented with intermittent fever for two years. The maximum body temperature was 39 ℃, and could spontaneously relieve. The efficacy of antibacterial treatment was poor. He had no other symptoms and positive signs. He had a significant weight loss, and the serum lactate dehydrogenase increased significantly. It was highly alert to be lymphoma, but bone marrow smear and pathology, and PET-CT had not shown obvious abnormalities. Considering high inflammatory indicators, increased ferritin and large spleen, the patient had high inflammatory status, and was treated with methylprednisolone. Then the patient's body temperature was normal, but the platelet decreased to 33×10 9 /L. During hospitalization, he had suddenly hemoperitoneum and hemorrhagic shock. He was found spontaneous spleen rupture without obvious triggers, and underwent emergency splenectomy. The pathological diagnosis of spleen was diffuse large B-cell lymphoma.

Objectives: To analyze the performance of commonly used blood tests in febrile infants ≤90 days of age to identify patients at low risk for invasive bacterial infection (bacterial pathogen in blood or cerebrospinal fluid) by duration of fever., Methods: We conducted a secondary analysis of a prospective single-center registry that includes all consecutive infants ≤90 days of age with fever without a source evaluated at 1 pediatric emergency department between 2008 and 2021. We defined 3 groups based on caregiver-reported hours of fever (<2, 2-12, and ≥12) and analyzed the performance of the biomarkers and Pediatric Emergency Care Applied Research Network, American Academy of Pediatrics, and Step-by-Step clinical decision rules., Results: We included 2411 infants; 76 (3.0%) were diagnosed with an invasive bacterial infection. The median duration of fever was 4 (interquartile range, 2-12) hours, with 633 (26.3%) patients with fever of <2 hours. The area under the curve was significantly lower in patients with <2 hours for absolute neutrophil count (0.562 vs 0.609 and 0.728) and C-reactive protein (0.568 vs 0.760 and 0.812), but not for procalcitonin (0.749 vs 0.780 and 0.773). Among well-appearing infants older than 21 days and negative urine dipstick with <2 hours of fever, procalcitonin ≥0.14 ng/mL showed a better sensitivity (100% with specificity 53.8%) than that of the combination of biomarkers of Step-by-Step (50.0% and 82.2%), and of the American Academy of Pediatrics and Pediatric Emergency Care Applied Research Network rules (83.3% and 58.3%), respectively., Conclusions: The performance of blood biomarkers, except for procalcitonin, in febrile young infants is lower in fever of very short duration, decreasing the accuracy of the clinical decision rules., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Acute undifferentiated fever (AUF) is defined as any febrile illness with a duration of ≤14 days without evidence of localized infection. Most outpatient services and a significant inpatient load in India are contributed by AUF. COVID-19 has recently added to the existing list of common etiologies of AUF. While the rapid diagnostic test (RDT) kits, which are widely used for the detection of common etiologies of AUF, are unreliable, the rise of various inflammatory markers may help identify the probable etiology. This not only results in better diagnosis but also prepares the physician for close monitoring and pooling of resources., Aim: To identify the probable etiology of AUF through inflammatory markers., Objective: To understand the clinical and biochemical parameters as possible predictors of adverse outcomes in AUF., Materials and Methods: This was a prospective observational study carried out in the Department of Medicine in a tertiary care hospital. The total duration of the study was 1 year. A total of 400 AUF patients [both outpatient department (OPD) and inpatient department (IPD)] fulfilling the eligibility criteria were taken up for the study after consent. Various inflammatory markers, namely erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin levels along with basic blood and biochemical tests were measured in all qualifying patients at their first visit. The level of rise of all the measured inflammatory markers was analyzed for clues toward identifying the etiology. Also, the possible predictors of adverse outcomes, as defined in the study, were analyzed. Outcome variables are described as mean ± standard deviation. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, New York, United States of America) and SPSS (Statistical Product and Service Solutions; SPSS Inc., United States of America) version 21., Results: The common etiologies in our study contributing to AUF were dengue (31.5%), COVID-19 (18.5%), enteric fever (12.7%), scrub typhus (9.0%), and malaria (6.0%). In 76 cases (19%), the fever was undiagnosed. Enteric fever had highly elevated CRP (>30 mg/L) and moderately elevated D-dimer, ferritin, and procalcitonin. Both nonsevere dengue and COVID-19 had highly elevated D-dimer (>750 ng/mL), but in nonsevere dengue, CRP, ferritin, and procalcitonin were only mildly elevated, whereas in COVID-19, CRP and ferritin were moderately elevated with mildly elevated procalcitonin. Scrub typhus had highly elevated CRP and ferritin [more than four times the upper limit of normal (ULN)], but D-dimer and procalcitonin were only mildly elevated. The mean serum procalcitonin level in enteric fever is significantly higher than the other etiologies of AUF. Our study was correctly able to identify 90.8% of nonsevere dengue, 87.8% of typhoid, 83.6% of COVID-19, and 91.4% of scrub typhus patients based on the inflammatory markers level. Obesity, diabetes (both types 1 and 2), hypertension, coronary artery disease (CAD), malignancy, chronic kidney disease (CKD), and chronic lung disease were significantly associated with adverse outcomes. A significant delay in visiting the hospital after the onset of fever was found in all etiologies of AUF, which had adverse outcomes., Conclusion: Our study is one of the few studies comparing the rise in the level of various inflammatory markers among the common etiologies of AUF. The novelty of the study is that it aids in identifying the probable etiology of AUF with good confidence through the levels of inflammatory markers. Also, our study highlights the high-risk factors associated with adverse outcomes in AUF., (© Journal of the Association of Physicians of India 2024.)

Abstract: Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of investigations for the confirmation of diagnosis. Thymomas are rare mediastinal tumors that present as anterior mediastinal mass; however, thymomas presenting as pyrexia of unknown origin has rarely been reported in the literature. We report an interesting case of a middle-aged male who presented as pyrexia of unknown origin due to thymoma., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Purpose: Prophylactic anti-infective strategies are used in patients with cancer to decrease the risk for infection. Dietary restrictions do not allow raw vegetables and fresh fruits to limit the introduction of potentially harmful pathogens in the gastrointestinal tract, but the efficacy is unclear., Patients and Methods: In this study analyzing the impact of the dietary restrictions on infectious complications, all children treated between April 2014 and March 2018 for ALL and AML or non-Hodgkin lymphoma (NHL) were included. Dietary restrictions were standard until March 2016, but were stopped in April 2016. Patients with dietary restrictions (treated April 2014-March 2016) and patients not advised for dietary restrictions (treated April 2016-March 2018) were compared regarding infectious complications, including bloodstream infection, pneumonia, diarrhea, and fever of unknown origin (FUO)., Results: Eighty-six patients (25 female; 62 ALL; nine AML, 15 NHL) experienced 223 infections. The 46 patients with dietary restrictions and the 40 patients without food restrictions did not significantly differ regarding the number of infections per patient, bloodstream infections, pneumonia, diarrhea, FUO, admission to intensive care, and death., Conclusion: Our data suggest that dietary restrictions do not affect the risk for infectious complications. Therefore, the indication of dietary restrictions should be reconsidered in pediatric patients with cancer.

We present the case of a 73-year-old male with pyrexia of unknown origin (PUO). He was a returned traveller from Southern Africa and underwent extensive investigation to rule out an infective cause. This was mostly unrevealing but there was a notable transaminitis (ALT predominant) with normal bilirubin level. He showed no serological or clinical improvement despite antibiotic treatment. Subsequent CT-PET showed high mural uptake in the thoracic and abdominal aorta and its major branches, confirming the diagnosis of Large Vessel Vasculitis (LVV). This case highlights the importance of considering LVV in patients with PUO and with transaminitis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Amaç: Nedeni bilinmeyen ateş (NBA) etiyolojisi çoğu zaman klinisyenleri uğraştıran, tanı için invaziv işlemler gerektiren klinik bir tablodur. Kemik iliği kültürü ve biyopsisi ile lenf nodu biyopsisi bu amaçla tercih edilen invaziv girişimlerdir. Çalışmamızda NBA etiyolojisi araştırdığımız hastalarımıza ait bu incelemelerin tanıdaki rolü ve sonuçları tartışılmıştır.Materyal ve Metot: Ankara Atatürk Eğitim ve Araştırma Hastanesi Enfeksiyon Hastalıkları Kliniği’nde NBA etiyolojisine yönelik kemik iliği (Kİ) kültürü ve biyopsisi amacı ile Hematoloji ile konsülte edilen ve lenf nodu biyopsisi değerlendirilen hastalar incelenerek, tanıda bu invaziv girişimlerin rolü değerlendirilmiştir.Bulgular: Kemik iliği kültürü-biyopsisi yapılan 18 erkek, 14 kadın, toplam 32 hastadan alınan kemik iliği kültürlerinin altısında üreme saptandı. İki hastada eş zamanlı olarak hem kan, hem de kemik iliği kültüründe üreme vardı. İki hastanın sadece kemik iliği kültüründe Brucella spp. üredi.Kemik iliği biyopsilerinden 24’ü (%75,00) normoselüler, 6’sı (%19,00) hiperselüler, biri (%3,00) lenfoma tutulumu gösteren kemik iliği ve bir diğeri ise poliklonal plazma hücre artışı gösteren hiposelüler kemik iliği şeklinde raporlandı. Fizik muayenede lenfadenopatisi saptanan dokuz hastaya lenf nodu biyopsisi yapıldı. Lenf nodu biyopsileri ile bir hastada Leishmania spp., bir hastada EBV ve iki hastada diffüz büyük B hücreli non-Hodgkin lenfoma (NHL) saptandı. Sonuç: NBA etiyolojisinde kemik iliği biyopsisi ve kültürü ve lenf nodu biyopsisi invaziv tanısal girişimler olup, kemik iliği tutulumu ile seyreden brusella gibi zoonotik enfeksiyonlar başta olmak üzere lösemi, lenfoma, tüberküloz gibi durumları ortaya koymada altın standart testtir. NBA etyolojisi araştırılırken girişimsel hematolojik işlemlerin değeri göz ardı edilmemelidir. Birinci basamak hekimleri, bu işlemlerin gerekliliği ve zamanlaması konusunda bilgi sahibi olmalıdır.

Purpose: To evaluate the contribution of F-18 FDG-PET/MRI in the search for the etiology of the inflammation of unknown origin (IUO) and fever of unknown origin (FUO)., Material and Methods: The study included 104 patients who underwent F-18 FDG-PET/MRI for IUO or FUO. The sensitivity, specificity, predictive values of the PET/MRI findings in relation to the final diagnosis of IUO/FUO were evaluated. A five-point Likert scale was used to semiquantitatively assess the probability of the cause of IUO/FUO based on PET/MRI finding. Furthermore, clinical (fever, arthralgia, weight loss, night sweats, age) and laboratory (C-reactive protein, leukocytes) parameters were monitored and compared with the true positivity rate of PET/MRI., Results: In patients with definitively identified etiology of FUO and IUO, FDG-PET/MRI achieved a sensitivity of 96 %, specificity of 82 %, and positive and negative predictive values of 92 and 90 %. The cause of the IUO was determined in 71 patients (68.3 %). In 33 (31.7 %) patients, the etiology of IUO/FUO remained unknown, while in 25 (75.8 %) of them the symptoms resolved spontaneously and in 8 (24.2 %) patients they persisted without explanation even after 12 months of the follow-up. The most significant parameter in relation to subsequent PET/MRI finding was increased level of CRP, which was present in 96 % of true positive PET/MRI and normal CRP level was present in 56 % of true negative PET/MRI., Conclusion: Based on this study, FDG-PET/MRI is a suitable alternative for the investigation of IUO/FUO, this imaging technique has a very high sensitivity and negative predictive value., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Febrile conditions often have an infectious etiology. However, there are also fevers associated with occupational exposures. A detailed occupational history can hold the key to the diagnosis. In the case of exposure to organic dusts, the development of hypersensitivity pneumonitis (HP) is possible. Thus, HP should be considered in the presence of interstitial lung disease of unclear etiology. Failure to recognize this can have dramatic consequences and, in extreme cases, lead to lung transplantation. Differentially, organic dust toxic syndrome (ODTS) must be considered. The syndrome of metal fume fever provoked by inhalation of inorganic substances is usually benign and self-limiting. The disease manifests with fever, cough, and flu-like sensations., Competing Interests: Es bestehen keine Interessenskonflikte., (© 2024 Aerzteverlag medinfo AG.)

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

Introduction: Fever of unknown origin (FUO) remains one of the most challenging clinical conditions. It demands an exhaustive diagnostic approach, considering its varied etiologies spanning infectious, autoimmune, inflammatory, and malignant causes., Patient Concerns: This report shows the journey of diagnosing a 28-year-old male who presented with persistent fever and lower-extremity weakness over 9 months. Despite seeking care at multiple hospitals, a definitive diagnosis remained elusive., Diagnosis: The patient underwent a series of evaluations in various specialties, including gastroenterology, infectious diseases, rheumatology, hematology, and cardiology. Multiple tests and treatments were administered, including antiviral therapy for hepatitis B and antibiotics for suspected infections., Interventions: After an initial misdiagnosis and unsuccessful treatments, a positron emission tomography-computed tomography scan and lymph node biopsy ultimately led to the diagnosis of peripheral T-cell lymphoma-T follicular helper type (PTCL-TFH) lymphoma. The patient was referred to the hematology clinic and initiated on CHOEP (cyclophosphamide, vincristine, etoposide, and prednisone) chemotherapy., Outcomes: The patient showed a positive response to CHOEP therapy, as indicated by a posttreatment positron emission tomography-computed tomography scan. He reported a significant improvement in his quality of life. Additional rounds of the same regimen were planned to further manage the lymphoma., Conclusion: This case emphasizes the importance of a comprehensive and persistent diagnostic approach in managing FUO. Initially, the focus on infectious causes led to extensive treatments, but the disease's progression and complications shifted attention to other specialties. The eventual diagnosis of PTCL-TFH lymphoma highlights the significance of advanced imaging techniques and multidisciplinary collaboration in uncovering elusive diagnoses. Thorough surveillance, timely reassessments, and repeated testing can uncover definitive changes critical for diagnosis. PTCL-TFH lymphoma, although rare, should be considered in the differential diagnosis of FUO, especially when initial evaluations are inconclusive., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: While presumably less common with modern molecular diagnostic and imaging techniques, fever of unknown origin (FUO) remains a challenge in kidney transplant recipients (KTRs). Additionally, the impact of FUO on patient and graft survival is poorly described., Methods: A cohort of adult KTRs between January 1, 1995 and December 31, 2018 was followed at the University of Wisconsin Hospital. Patients transplanted from January 1, 1995 to December 31, 2005 were included in the "early era"; patients transplanted from January 1, 2006 to December 31, 2018 were included in the "modern era". The primary objective was to describe the epidemiology and etiology of FUO diagnoses over time. Secondary outcomes included rejection, graft and patient survival., Results: There were 5590 kidney transplants at our center during the study window. FUO was identified in 323 patients with an overall incidence rate of .8/100 person-years. Considering only the first 3 years after transplant, the incidence of FUO was significantly lower in the modern era than in the early era, with an Incidence Rate Ratio (IRR) per 100 person-years of .48; 95% CI: .35-.63; p < .001. A total of 102 (31.9%) of 323 patients had an etiology determined within 90 days after FUO diagnosis: 100 were infectious, and two were malignancies. In the modern era, FUO remained significantly associated with rejection (HR = 44.1; 95% CI: 16.6-102; p < .001) but not graft failure (HR = 1.21; 95% CI: .68-2.18; p = .52) total graft loss (HR = 1.17; 95% CI: .85-1.62; p = .34), or death (HR = 1.17; 95% CI: .79-1.76; p = .43., Conclusions: FUO is less common in KTRs during the modern era. Our study suggests infection remains the most common etiology. FUO remains associated with significant increases in risk of rejection, warranting further inquiry into the management of immunosuppressive medications in SOT recipients in the setting of FUO., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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

A 74-year-old woman with a 34-year history of hemodialysis presented with an intermittent fever, which later coincided with recurrent bilateral shoulder and hip joint pain. Imaging studies suggested amyloid arthropathy, which was histologically confirmed by a synovial biopsy. Increasing β 2 -microglobulin clearance during dialysis alone attenuated the intermittent fever and joint pain, but the symptoms did not disappear until the administration of prednisolone 10 mg/day. Reported cases of dialysis-related amyloidosis with a fever imply that changing to blood purification methods with high β 2 -microglobulin clearance is crucial for controlling the condition long-term, whereas concurrent use of anti-inflammatory agents promptly alleviates the symptoms.

Introduction: Fever of unknown origin (FUO) poses a diagnostic challenge, often requiring a systematic evaluation to uncover its elusive cause. This case study delves into the presentation of a 42-year-old Chinese male with persistent fever, muscle pain, and a perplexing rash., Patient Concerns: The patient's symptoms included a prolonged fever, chills, muscle pain, and throat discomfort, with a history of pulmonary tuberculosis. Initial diagnoses of upper respiratory infection and unspecified infection were followed by antibiotic treatments, yet the fever persisted, accompanied by an exacerbating rash., Diagnosis: Extensive diagnostic investigations, including laboratory tests, imaging studies, and skin dermoscopy, provided valuable insights. The patient exhibited elevated inflammatory markers, hepatosplenomegaly, lymphadenopathy, and lung nodules. Differential diagnoses included adult-onset Still disease and drug-induced hypersensitivity syndrome., Interventions: The patient received a series of antibiotic treatments, which initially had limited success. Upon considering an autoimmune etiology, corticosteroids were introduced, followed by cyclosporine. The patient exhibited a positive response to this immunosuppressive therapy., Outcomes: Treatment adjustments were made, and the patient responded positively to a combination of corticosteroids and cyclosporine. His fever subsided, and laboratory markers normalized. One month after discharge, the patient showed continued improvement., Conclusion: FUO cases often demand a multidisciplinary approach, considering rare and uncommon diseases. This case underscores the importance of thorough evaluation, collaboration between specialties, and vigilant monitoring of treatment responses. The patient's unique presentation emphasizes the need to consider drug-induced reactions, even when symptoms deviate from typical disease patterns, highlighting the complexities in diagnosing and managing FUO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)