Pyrexia of unknown origin (PUO) and the cost of care in a tertiary care institute in Sri Lanka.

BACKGROUND: Despite advancements in diagnostic technology, pyrexia of unknown origin (PUO) remains a clinical concern. Insufficient information is available regarding the cost of care for the management of PUO in the South Asian Region. METHODS: We retrospectively analyzed data of patients with PUO from a tertiary care hospital in Sri Lanka to determine the clinical course of PUO and the burden of the cost incurred in the treatment of PUO patients. Non-parametric tests were used for statistical calculations. RESULTS: A total of 100 patients with PUO were selected for the present study. The majority were males (n = 55; 55.0%). The mean ages of male and female patients were 49.65 (SD: 15.55) and 46.87 (SD: 16.19) years, respectively. In the majority, a final diagnosis had been made (n = 65; 65%). The mean number of days of hospital stay was 15.16 (SD; 7.81). The mean of the total number of fever days among PUO patients was 44.47 (SD: 37.66). Out of 65 patients whose aetiology was determined, the majority were diagnosed with an infection (n = 47; 72.31%) followed by non-infectious inflammatory disease (n = 13; 20.0%) and malignancies (n = 5; 7.7%). Extrapulmonary tuberculosis was the most common infection detected (n = 15; 31.9%). Antibiotics had been prescribed for the majority of the PUO patients (n = 90; 90%). The mean direct cost of care per PUO patient was USD 467.79 (SD: 202.81). The mean costs of medications & equipment and, investigations per PUO patient were USD 45.33 (SD: 40.13) and USD 230.26 (SD: 114.68) respectively. The cost of investigations made up 49.31% of the direct cost of care per patient. CONCLUSION: Infections, mainly extrapulmonary tuberculosis was the most common cause of PUO while a third of patients remained undiagnosed despite a lengthy hospital stay. PUO leads to high antibiotic usage, indicating the need for proper guidelines for the management of PUO patients in Sri Lanka. The mean direct cost of care per PUO patient was USD 467.79. The cost of investigations contributed mostly to the direct cost of care for the management of PUO patients.

Fever of Unknown Origin in Adults.

Fever of unknown origin is defined as a clinically documented temperature of 101°F or higher on several occasions, coupled with an unrevealing diagnostic workup. The differential diagnosis is broad but is typically categorized as infection, malignancy, noninfectious inflammatory disease, or miscellaneous. Most cases in adults occur because of uncommon presentations of common diseases, and up to 75% of cases will resolve spontaneously without reaching a definitive diagnosis. In the absence of localizing signs and symptoms, the workup should begin with a comprehensive history and physical examination to help narrow potential etiologies. Initial testing should include an evaluation for infectious etiologies, malignancies, inflammatory diseases, and miscellaneous causes such as venous thromboembolism and thyroiditis. If erythrocyte sedimentation rate or C-reactive protein levels are elevated and a diagnosis has not been made after initial evaluation, 18F fluorodeoxyglucose positron emission tomography scan, with computed tomography, may be useful in reaching a diagnosis. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. Depending on clinical indications, this may include liver, lymph node, temporal artery, skin, skin-muscle, or bone marrow biopsy. Empiric antimicrobial therapy has not been shown to be effective in the treatment of fever of unknown origin and therefore should be avoided except in patients who are neutropenic, immunocompromised, or critically ill.

Fever of unknown origin: a retrospective review of pediatric patients from an urban, tertiary care center in Washington, DC.

BACKGROUND: Fever of unknown origin (FUO) continues to challenge clinicians to determine an etiology and the need for treatment. This study explored the most common etiologies, characteristics, and average cost of hospitalization for FUO in a pediatric population at an urban, tertiary care hospital in Washington, DC. METHODS: Records from patients admitted to Children's National Health System between September 2008 and April 2014 with an admission ICD-9 code for fever (780.6) were reviewed. The charts of patients 2-18 years of age with no underlying diagnosis and a temperature greater than 38.3 ºC for 7 days or more at time of hospitalization were included. Final diagnoses, features of admission, and total hospital charges were abstracted. RESULTS: 110 patients qualified for this study. The majority of patients (n = 42, 38.2%) were discharged without a diagnosis. This was followed closely by infection, accounting for 37.2% (n = 41) of patients. Rheumatologic disease was next (n = 16, 14.5%), followed by miscellaneous (n = 6, 5.4%) and oncologic diagnoses (n = 5, 4.5%). The average cost of hospitalization was 40,295 US dollars. CONCLUSIONS: This study aligns with some of the most recent publications which report undiagnosed cases as the most common outcome in patients hospitalized with FUO. Understanding that, often no diagnosis is found may reassure patients, families, and clinicians. The cost associated with hospitalization for FUO may cause clinicians to reconsider inpatient admission for diagnostic work-up of fever, particularly given the evidence demonstrating that many patients are discharged without a diagnosis.

Outcomes of a clinical pathway for primary outpatient management of pediatric patients with low-risk febrile neutropenia.

BACKGROUND: Fever and neutropenia is a common reason for nonelective hospitalization of pediatric oncology patients. Herein we report nearly five years of experience with a clinical pathway designed to guide outpatient management for patients who had low-risk features. PROCEDURES: Through a multidisciplinary collaboration, we implemented a clinical pathway at our institution using established low-risk criteria to guide outpatient management of pediatric oncology patients. Comprehensive chart review of all febrile neutropenia episodes was conducted to characterize outcomes of patients with low-risk febrile neutropenia following clinical pathway implementation. RESULTS: Between April 1, 2013, and October 1, 2017, there were 169 cases of febrile neutropenia managed in our Pediatric Oncology Unit. Sixty-seven (40%) of these episodes were defined as low risk and managed either entirely in the outpatient setting (41 episodes, 24%) or with a step-down strategy involving a very brief inpatient stay (26 episodes, 15%). There were no intensive care unit admissions or deaths among the low-risk patients. Of those identified as low risk, seven patients (10%) required subsequent hospitalization during the follow-up period, two for inadequate oral intake, two for persistent fevers, one for cellulitis, one for seizure unrelated to the febrile episode, and one for a positive blood culture. CONCLUSIONS: Following implementation of a clinical pathway, the majority of patients designated as low risk were managed primarily in the outpatient setting without major morbidity or mortality, suggesting that carefully selected low-risk patients can be successfully treated with outpatient management and subsequent admission if warranted.

Cardiac and vascular causes of persistent fever: A systematic review.

Fever of unknown origin refers to a prolonged fever with an unknown cause despite adequate medical evaluations. This condition often leads to unnecessary extensive laboratory work-ups and antimicrobial therapies. The atypical presentations often cause a delayed diagnosis and an improper treatment with an increased morbidity rate. In cardiac surgical patients, fever of unknown origin remains an intriguing problem during the diagnostic process of cardiac surgical diseases. Cardiac myxoma or aortic dissection are often misdiagnosed when patients present with fever of unknown origin as an onset symptom. Under such circumstances, medical examinations by echocardiography and chest computed tomography, particularly fluorodeoxyglucose-positron emission tomography/computed tomography, have been proved crucial for early diagnosis. A better understanding of the clinical features of cardiac surgical disorders presenting with fever of unknown origin would facilitate early diagnosis of fever of unknown origin. A further decision-making of prompt treatment of choices of a cardiac operation is important for improving patients' outcomes.

Pyrexia of unknown origin.

The syndrome of pyrexia of unknown origin (PUO) was first defined in 1961 but remains a clinical challenge for many physicians. Different subgroups with PUO have been suggested, each requiring different investigative strategies: classical, nosocomial, neutropenic and HIV-related. This could be expanded to include the elderly as a fifth group. The causes are broadly divided into four groups: infective, inflammatory, neoplastic and miscellaneous. Increasing early use of positron emission tomography-computed tomography (PET-CT) and the development of new molecular and serological tests for infection have improved diagnostic capability, but up to 50% of patients still have no cause found despite adequate investigations. Reassuringly, the cohort of undiagnosed patients has a good prognosis. In this article we review the possible aetiologies of PUO and present a systematic clinical approach to investigation and management of patients, recommending potential second-line investigations when the aetiology is unclear.

Etiology and Resource Use of Fever of Unknown Origin in Hospitalized Children.

BACKGROUND: Fever of unknown origin (FUO) is a well-known pediatric presentation. The primary studies determining the causes of prolonged fever in children were performed 4 decades ago, before major advances in laboratory and diagnostic testing. Given that the distribution of diagnosed causes of adult FUO has changed in recent decades, we hypothesized that the etiology of FUO in children has concordantly changed and also may be impacted by a definition that includes a shorter required duration of fever. METHODS: A single-center, retrospective review of patients 6 months to 18 years of age admitted to the North Carolina Children's Hospital from January 1, 2002, to December 21, 2012, with an International Classification of Diseases, Ninth Revision diagnosis of fever, a documented fever duration >7 days before admission, and a previous physician evaluation of each patient's illness. RESULTS: A total of 1164 patients were identified, and of these, 102 met our inclusion criteria for FUO. Etiologic categories included "infectious" (42 out of 102 patients), "autoimmune" (28 out of 102 patients), "oncologic" (18 out of 102 patients), and "other" or "unknown" (14 out of 102 patients). Several clinical factors were statistically and significantly different between etiologic categories, including fever length, laboratory values, imaging performed, length of stay, and hospital costs. CONCLUSIONS: Unlike adult studies, the categorical distribution of diagnoses for pediatric FUO has marginally shifted compared to previously reported pediatric studies. Patients hospitalized with FUO undergo prolonged hospital stays and have high hospital costs. Additional study is needed to improve the recognition, treatment, and expense of diagnosis of prolonged fever in children.

Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.

[A 59-year-old woman with upper abdominal pain and fever]. / 59-jährige Patientin mit Oberbauchschmerzen und Fieber.

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

Fever of unknown origin, giant cell arteritis, and aortic dissection.

Giant cell arteritis is one of the most frequent causes of pyrexia of unknown origin after infectious or malignant causes have been ruled out. In this case report we describe a 66-year old female patient, who after five weeks of remitting fever developed a life-threatening, painless severe aortic dissection. The timely use of modern imaging technologies such as magnetic resonance angiography or positron emission computed tomography could in the future be of help to recognize aortic involvement early and to avoid this devastating complication in patients with fever of unknown origin.

Clinical approach to fever of unknown origin in children.

BACKGROUND/PURPOSE: Fever of unknown origin (FUO) can be caused by many clinical conditions and remains a diagnostic challenge in clinical practice. The etiology of FUO varies markedly among different age groups, geographic areas, and seasons. A four-stage investigative protocol for FUO is widely applied in clinical practice. The aim of this study was to evaluate the usefulness of this four-stage protocol for identifying the etiology of FUO in children. METHODS: We enrolled children younger than 18 years of age who were admitted to the Taichung Veterans General Hospital during the period from January 2006 to December 2014 with FUO persisting for more than 3 weeks. The four-stage FUO investigative guideline was used to evaluate the etiology of fever in all patients enrolled in the study. RESULTS: The etiology of FUO was identified in 79 (84.9%) of the 93 patients enrolled in the study. The most common cause of FUO was infectious disease (37.6%), followed by malignancy (17.2%), miscellaneous disease (16.1%), and collagen vascular disease (14.0%). With respect to the four-stage survey of FUO, 36 of the 79 patients (45.6%) were identified in Stage 3, 28 patients (35.4%) in Stage 2, 13 patients (16.5%) in Stage 4, and only two patients (2.5%) in Stage 1. CONCLUSION: A well-designed systemic review of the epidemiological information, medical history, physical examination, laboratory analysis, and adequate invasive procedures provide adequate data to identify the most common causes of FUO in children.

Management of Postembolization Syndrome Following Hepatic Transarterial Chemoembolization for Primary or Metastatic Liver Cancer.

BACKGROUND: Transarterial chemoembolization (TACE) is an established treatment in managing liver primary neoplasms or liver metastases. Postembolization syndrome (PES) is a common adverse event defined as fever without associated sepsis, pain in the right upper quadrant, and nausea and/or vomiting. OBJECTIVE: This integrative review aims to identify effective management strategies for PES or one of its characterizing symptoms (fever, pain, and nausea and/or vomiting). METHODS: Searches of electronic databases MEDLINE, EMBASE, and CINAHL were conducted. Fifteen articles were identified for inclusion. Seven addressed all symptoms of PES, and 8 studies focused on individual symptoms of PES. RESULTS: Interventions identified are intra-arterial lidocaine, oral and intravenous analgesics, steroids, wrist-ankle acupuncture, antibiotics, and 5-HT3 receptor antagonists. Findings are explicated according to individual symptoms of PES. Intra-arterial lidocaine, steroids, and a 5-HT3 receptor antagonist are found to offer potential benefit in the management of PES symptoms. CONCLUSION: A number of interventions have shown potential benefit in the management of PES. A systemic approach using combination therapy is necessary to effectively manage characterizing symptoms. Further research is needed to determine the impact of primary disease site, TACE technique, and chemotherapeutic agent on PES. IMPLICATIONS FOR PRACTICE: Oncology nurses are uniquely placed to undertake thorough patient assessment after TACE and implement early intervention to effectively manage PES.

[Neuroleptic malignant syndrome : Rare cause of fever of unknown origin]. / Malignes neuroleptisches Syndrom : Seltene Ursache für Fieber unklarer Genese.

Neuroleptic malignant syndrome (NMS) is a possible cause of fever of unknown origin (FUO) and is a potentially fatal adverse effect of various drugs, especially of neuroleptics. First generation antipsychotics, such as received by the patient described in this article, are more likely to cause NMS than second generation antipsychotics. The key symptoms are the development of severe muscle rigidity and elevated temperature associated with the use of neuroleptic medication. Malignant catatonia (MC) is an important differential diagnosis of NMS. While neuroleptics can trigger NMS and must be immediately discontinued if NMS occurs, neuroleptic therapy represents the first line treatment for MC. This article describes the case of a patient with schizoaffective disorder where initially the diagnosis of NMS was not clear. Eventually, fever and a markedly elevated serum creatine kinase (CK) led to the correct diagnosis and the appropriate therapy with dantrolene, bromocriptine and amantadine. Furthermore, a thorough review of the currently available literature on NMS is provided.

Cumplimiento y resultados de la aplicación del protocolo de abordaje de la fiebre sin foco en lactantes de 29 a 90 días en el Departamento de Emergencia Pediátrica del Centro Hospitalario Pereira Rossell / Compliance and results of applying a protocol for treatment of fever without a source in infants of 29-90 days of age at the Pediatrics Emergency Unit of the Pereira Rossell Hospital Center

Introducción: el abordaje diagnóstico y terapéutico de niños menores de 36 meses con fiebre sin foco (FSF) ha sido motivo de controversias, particularmente en el grupo 29 a 90 días de vida. Objetivos: evaluar el cumplimiento y describir los resultados del nuevo protocolo de abordaje diagnóstico y terapéutico en los niños de 29 a 90 días de vida que consultan con FSF en DEP-CHPR. Material y métodos: se realizó un estudio transversal, descriptivo retrospectivo, en el que se incluyeron los niños entre 29 y 90 días que consultan con FSF en el DEP-CHPR, entre el 1 de octubre de 2012 y el 30 de setiembre de 2013. Resultados: en el período analizado hubo 134 consultas de niños entre 29 a 90 días de vida por FSF. Cumplieron la pauta 99 (74%). Los diagnósticos al egreso fueron: fiebre sin foco evidente 82 (61%), infección respiratoria aguda viral 23 (17%), meningitis viral y/o encefalitis 11 (8%), infección urinaria 8 (6%), gastroenteritis 4 (3%), meningoencefalitis aséptica 2 (1,5%), otitis media 2 (1,5%), meningoencefalitis aguda supurada 1 (0,75%), exantema viral 1 (0,75%). En los pacientes que presentaron infecciones graves se cumplió la pauta en 20 de 22 pacientes (90%). La principal causa de no cumplimiento fue no realizar los estudios según pauta en 20 (57%). Conclusiones: se detectó un porcentaje aceptable de cumplimiento del nuevo protocolo, la no adherencia estuvo dada fundamentalmente en la no realización de los estudios pautados. El rendimiento en la detección de EBI, infecciones virales graves y bacteriemia fue bueno.

Introduction: diagnostic and therapeutic approach of children younger than 36 months with fever without a source has been controversial, particularly in those between 29 and 90 days of age who consult at the Pediatrics Emergency Unit Emergency Unit of the Pereira Rossell Hospital Center. Method: a transversal, descriptive, retrospective study was conducted, including children between 29 and 90 days who consulted for fever without a source at the Pediatrics Emergency Unit Emergency Unit of the Pereira Rossell Hospital Center between August 1, 2012 and September 30, 2013. Results: during the time of the study, there were 134 children between 29 and 90 days who consulted for fever without a source. Ninety nine of them (47%) meet the requirements. Diagnosis upon release were: fever without evidence of focus 82 (61%), acute viral respiratory infection 23 (17%), viral meningitis and/or encephalitis 11 (8%), urinary tract infection 8 (6%), gastroenteritis 4 (3%), aseptic meningoencephalitis 2 (1.5%), otitis media 2 (1.5%), acute suppurative meningoencephalitis 1 )0.75%), viral exanthema 1 (0.75). When patients presented severe infections the recommendations were followed in 20 out of 22 patients (90%). The main cause for non-fulfilment was failing to ask for exams according to recommendations in 20 (57%).

Prolonged febrile illness and fever of unknown origin in adults.

Fever of unknown origin has been described as a febrile illness (temperature of 101°F [38.3°C] or higher) for three weeks or longer without an etiology despite a one-week inpatient evaluation. A more recent qualitative definition requires only a reasonable diagnostic evaluation. Although there are more than 200 diseases in the differential diagnosis, most cases in adults are limited to several dozen possible causes. Fever of unknown origin is more often an atypical presentation of a common disease rather than an unusual disease. The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. Clinicians should perform a comprehensive history and examination to look for potentially diagnostic clues to guide the initial evaluation. If there are no potentially diagnostic clues, the patient should undergo a minimum diagnostic workup, including a complete blood count, chest radiography, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level testing. Further testing should include blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies. Human immunodeficiency virus and appropriate region-specific serologic testing (e.g., cytomegalovirus, Epstein-Barr virus, tuberculosis) and abdominal and pelvic ultrasonography or computed tomography are commonly performed. If the diagnosis remains elusive, 18F fluorodeoxyglucose positron emission tomography plus computed tomography may help guide the clinician toward tissue biopsy. Empiric antibiotics or steroids are generally discouraged in patients with fever of unknown origin.

Prolonged and recurrent fevers in children.

Some children referred for prolonged fever are actually not having elevated temperatures; the approach here requires dissection of the history and correction of health misperceptions. Others have well-documented fevers associated with clinical, laboratory, or epidemiologic findings that should point to a specific diagnosis. "Fever-of-Unknown-Origin" (FUO) is the clinical scenario of daily fever for ≥ 14 days that defies explanation after a careful history, physical examination, and basic laboratory tests. The diagnostic approach requires a meticulous fever diary, serial clinical and laboratory evaluations, vigilance for the appearance of new signs and symptoms, and targeted investigations; the pace of the work-up is determined by the severity of the illness. Approximately half of children with FUO will have a self-limited illness and will never have a specific diagnosis made; the other half will ultimately be found to have, in order, infectious, inflammatory, or neoplastic conditions. Irregular, intermittent, recurrent fevers in the well-appearing child are likely to be sequential viral illnesses. Monogenic autoinflammatory diseases should be considered in those who do not fit the picture of recurrent infections and who do not have hallmarks of immune deficiency. Stereotypical febrile illnesses that recur with clockwork periodicity should raise the possibilities of cyclic neutropenia, if the cycle is approximately 21 days, or periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, the most common periodic fever in childhood.