BACKGROUND: 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.
METHODS: 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.
RESULTS: Five qualitative studies corresponded to an increase of 15.3% (95% CI: 2.3-28.3%, p=0.021) in undiagnosed FUO proportions compared to eleven quantitative studies. Quantitative studies had 19.7% (95% CI: 6.0-33.4%, p=0.005) 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=0.318), oncology (p=0.901), non-inflammatory miscellaneous disorders (p=0.321), diagnostic evaluation process, gross national income (GNI), or World Health Organization (WHO) geographic region.
CONCLUSIONS: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.

BACKGROUND: Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life.
OBJECTIVE: Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6-month prednisolone protocol and a 6-week protocol.
METHODS: Forty-four hospital cases from multiple referral centers in the United Kingdom (2015-2019). Twenty of 44 were treated with the 6-month protocol and 24/44 with the 6-week protocol.
METHODS: Prospective, randomized trial with 12-month follow-up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling.
RESULTS: All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6-month protocol and 9/24 (38%) of the 6-week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40-4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61-3.48; P = 0.40).
CONCLUSIONS: \"Short\" 6-week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone\'s adverse effects.

Non-Hodgkin\'s lymphomas (NHLs) are a group of lymphoproliferative diseases that originate from different cell types, namely B cells, T cells, or natural killer cells. Herein, we report the case of a 69-year-old male patient who presented with a gradual-onset, intermittent, low-grade fever for four months and a right-sided neck lump for two months. On examination, a right-sided enlarged lymph node sized 1 × 1 cm2 was noted, which was mobile, hard in consistency, and non-tender. No other lymphadenopathy was noted in other parts of the body. Imaging and biochemical studies done at the initial stages did not reveal features in favor of any lymphoproliferative disorders, and the two lymph node biopsies done two weeks apart were inconclusive as well. An extended panel of investigations was done in view of excluding other infective and inflammatory pathologies, which was negative, making the patient undiagnosed of any disease state despite being symptomatic for four months. Finally, the third lymph node biopsy tested positive, which paved the way for the diagnosis of NHL. This diagnosis underlines the importance of this case. Following the diagnosis, the patient was initiated on a few chemotherapeutic agents, after which a mild symptomatic improvement was achieved.

Pyrexia of unknown origin (PUO) is a prolonged fever lasting several weeks without an identifiable cause despite extensive medical evaluation. Many a time, its cause remains largely unknown even after collecting a detailed medical history, conducting comprehensive physical assessments, and performing various standard laboratory tests and imaging procedures. This case series presents two cases of pyrexia of unknown origin. The first case includes a unique and uncommon presentation of non-Hodgkin\'s lymphoma. In the second case, the patient\'s fever remained unexplained after various investigations and treatments. The two documented cases of PUO presented in this report aim to contribute to the understanding of its diverse etiology and diagnostic challenges. By highlighting unique presentations and diagnostic dilemmas, the cases aim to promote awareness and facilitate timely recognition and appropriate management of PUO.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease that is even rarer in the adult population. It requires a high degree of suspicion from the treating physician, and if diagnosed early, patients might have a survival benefit from this highly fatal condition. HLH is a disorder of immune regulation where the hyperactivity of cytokines attacks different cells, which leads to multiple organ dysfunctions. Varying presentations and similarities with other diseases make diagnosis difficult. Familial HLH is commonly seen in the pediatric population, while acquired or secondary HLH is seen in adults. Secondary HLH is commonly triggered by neoplasms, infections, rheumatological diseases, and other autoimmune diseases. Here is a case of HLH that presented as chronic undiagnosed fever. In this case report, we have discussed in detail this disease, its presentation, investigations, treatment, and other important information that will help practicing doctors better diagnose and treat HLH patients.

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.

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.

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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Hemophagocytic lymphohistiocytosis is usually considered a rapidly progressive fatal illness with poor outcomes. It is of two types: primary or familial and secondary. In patients with HIV, opportunistic infections are the secondary triggers of HLH. First line of management of infection associated HLH is treatment of the underlying infection. Here, we present a case of HLH in HIV infection due to disseminated histoplasmosis managed with liposomal amphotericin B, who required immunosuppressive therapy with intravenous immunoglobulin and dexamethasone due to nonresponse to primary therapy.