Clinical Features of Spontaneous Remission in the Classic Fever of Unknown Origin:A Retrospective Study

Objective To summarize the clinical features of spontaneous remission in classic fever of unknown origin(FUO).Methods Medical records of 121 patients diagnosed with FUO at admission in Peking Union Medical College Hospital between January 2018 and June 2018 were reviewed retrospectively.Patients who were discharged without etiological diagnoses were followed for 2 years.The clinical features and outcomes of these patients were summarized.Multivariate logistic regression was used to analyze related factors of spontaneous remission of FUO.Results After excluding 2 patients who lost to follow-up,the etiology of 119 FUO patients were as follows:infectious diseases in 30(25.2%)cases,connective tissue diseases in 28(23.5%)cases,tumor diseases in 8(6.7%)cases,other diseases in 6(5.0%)cases,and unknown diagnoses in 47(39.5%)cases.Totally,41 patients experienced spontaneous remission of fever(the median time from onset to remission was 9 weeks,ranging from 4 to 39 weeks).In patients with spontaneous remission in FUO,lymphadenopathy was less common clinical manifestation,the levels of inflammatory markers including leukocyte count,neutrophil count,neutrophil ratio,C-reactive protein,and ferritin were lower,and the proportion of CD8 positive T lymphocytes expressing CD38 was lower.Multivariate logistic regression analysis of factors with a P-value<0.05 in univariate analysis shown that white blood cell count(OR:0.S45,95%CI:0.306-0.971,P=0.039),neutrophil count(OR:2.074,95%CI:1.004-4.284,P=0.049),and proportion of neutrophils(OR:0.928,95%Cl:0.871-0.990,P=0.022)were independent significant factors associated with spontaneous remission in FUO.Conclusions This study suggested that most patients discharged with undiagnosed classic FUO would remit spontaneously.Thus,for patients with stable clinical conditions,follow-up and observation could be the best choice.Patients with lower level of some inflammatory factors may have a high likelihood of spontaneous remission in classic FUO.

Infectious causes of fever of unknown origin in developing countries: An international ID-IRI study

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

Major causes of fever of unknown origin at Peking Union Medical College Hospital in the past 26 years

Background Despite the recent advances in medicine, fever of unknown origin （FUO） remains a diagnostic and therapeutic challenge even to expert physicians. To increase the knowledge of FUO, we conducted a retrospective study to investigate the causes of FUO and the change of major causes of FUO during the past 26 years. Methods The clinical data were retrospectively analyzed from 997 patients with FUO hospitalized at the Peking Union Medical College Hospital （PUMCH） between January 2004 and October 2010. Furthermore, the results were compared to that reported in previous studies of FUO in PUMCH since 1985. Results Of the 997 FUO cases, definite diagnosis was eventually achieved in 797 （79.9%） patients. The most common cause of FUO was infectious diseases （479 cases, 48.0%）, with tuberculosis accounting for 45.3% （217/479） of the cases of infections. One hundred and sixty-eight （16.9%） patients were diagnosed with connective tissue diseases, with Still＇s disease and vasculitis accounted for 31.5% （53/168） and 24.4% （41/168） of this category, respectively. Neoplasms and miscellaneous causes were found in 7.9% （79/997） and 7.1% （71/997）, respectively. However, no definite diagnosis had been made in the remaining 200 （20.1%） cases until they were discharged from the hospital. Conclusions During different periods, infectious diseases, especially tuberculosis, were the leading etiology of FUO and the proportion of tuberculosis had no significant difference. While the frequency of neoplasms was descending, the proportion of lymphoma in neoplasm was ascending; the frequency of undiagnosed＇cases was increasing, but in most FUO cases the causes can be diagnosed eventually after careful analysis of clinical data.

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℃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.

Applied Value of Monitoring Serum Hepcidin in Differential Diagnosis of Infection versus Tumor Fevers

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored.A total of 432 fever patients were selected according to the domestic fever of unknown origin（FUO） diagnostic criteria from our hospital between June 2010 and November 2013.Venous blood samples were taken on the day 1,5,10 after admission.The infection group（98 cases） and the tumor group（50 cases） were set up based on the clinical and laboratory findings.ELISA was used to determine the serum hepcidin and IL-6 levels.SPSS 13.0 was used for statistical analysis.Hepcidin showed obvious descending trend on the 10 th day in both the bacterial infection group（66 cases） and the virus infection group（32 cases）,and the descending trend was similar to that of inflammatory indexes such as procalcitonin（PCT）,hypersensitive C-reactive protein（h-CRP）,erythrocyte sedimentation rate（ESR）,white blood cell（WBC）,and ferritin.Serum hepcidin showed no obvious differences in the tumor group on the day 1,5,10 after admission.In the infection groups,serum hepcidin was positively correlated with IL-6（r=0.687,P=0.000） and CRP（r=0.487,P=0.026）,but had a poor correlation with blood sedimentation,ferritin,PCT and WBC（P〉0.05）.Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.

A Clinical Analysis of 293 FUO Patients, A Diagnostic Model Discriminating infectious Diseases from Non-infectious Diseases

Objective A diagnostic model was established to discriminate infectious diseases from non-infectious diseases. Methods The clinical data of patients with fever of unknown origin(FUO) hospitalized in Xiangya Hospital Central South University, from January, 2006 to April, 2011 were retrospectively analyzed. Patients enrolled were divided into two groups. The first group was used to develop a diagnostic model: independent variables were recorded and considered in a logistic regression analysis to identify infectious and non-infectious diseases(αin = 0.05, αout = 0.10). The second group was used to evaluate the diagnostic model and make ROC analysis.Results The diagnostic rate of 143 patients in the first group was 87.4%, the diagnosis included infectious disease(52.4%), connective tissue diseases(16.8%), neoplastic disease(16.1%) and miscellaneous(2.1%). The diagnostic rate of 168 patients in the second group was 88.4%, and the diagnosis was similar to the first group. Logistic regression analysis showed that decreased white blood cell count(WBC < 4.0×109/L), higher lactate dehydrogenase level(LDH > 320 U/L) and lymphadenectasis were independent risk factors associated with non-infectious diseases. The odds ratios were 14.74, 5.84 and 5.11(P ≤ 0.01), respectively. In ROC analysis, the sensitivity and specificity of the positive predictive values was 62.1% and 89.1%, respectively, while that of negative predicting values were 75% and 81.7%, respectively(AUC = 0.76, P = 0.00).Conclusions The combination of WBC < 4.0×109/L, LDH > 320 U/L and lymphadenectasis may be useful in discriminating infectious diseases from non-infectious diseases in patients hospitalized as FUO.

Adult-onset Still's disease: A case report

Rationale: Fever of unknown origin (FUO) is a frequently observed phenomenon in clinical practice. Definite diagnosis of FUO is a great challenge in clinical practice since potential causes for FUO involve more than 200 diseases. Adult-onset Still's disease is a defined clinical entity and a known rare cause of FUO. Patient's concern: A 19-year girl was referred to the clinic with the concern of intermittent fevers and shivering for almost a year despite multiple investigations and consultations. She had undergone intensive serologic, radiologic, laboratory investigations to exclude infectious diseases, connective tissue diseases, and malignancy, and all the investigation showed no conclusive diagnosis. Diagnosis: Adult-onset Stills disease. Intervention: Steroids and supportive treatment. Outcomes:The symptoms were relieved within three days, and the patient became asymptomatic. Lessons: Physicians need to be familiar with the diagnostic criteria of adult-onset Still's disease, or it shall remain a diagnostic dilemma. Besides, all shivers are not infections.

Bartonellosis in transplant recipients:A retrospective single center experience

BACKGROUND Bartonellosis is a rare but challenging condition to diagnose with a spectrum of clinical presentations in the immunocompromised host.AIM To further characterize the presentation of Bartonella henselae(B.henselae)infections in solid organ and hematopoietic stem cell transplant recipients.METHODS We conducted a single-center retrospective study of all B.henselae testing for 5012 transplant recipients receiving care at a single institution between 2011 and 2018.RESULTS We identified 38 patients who underwent testing for B.henselae,and three of 38 were found to have bartonellosis.Two of the patients were renal transplant recipients who presented with visceral bartonellosis and symptoms concerning for post-transplant lymphoproliferative disorder.One autologous stem cell transplant recipient presented with cat scratch disease.We detail the clinical courses of these three cases and review the literature concerning the clinical presentations,differential diagnosis,and limitations of diagnostic tests for B.henselae infections in transplant recipients.CONCLUSION Although the incidence of B.henselae infection in transplant recipients is unknown,it merits inclusion in the differential diagnosis for fever of unknown origin in this population.

Adult-onset Still’s disease successfully treated with Chinese herbal medicine: A case report with 15-month follow-up

Adult-onset Still’s disease(AOSD) is a rare but clinically well-known, polygenic, and systemic autoinflammatory disease, which is characterized by spiking fever, evanescent skin rash, arthralgia, and sore throat.The application of non-steroidal anti-inflammatory drugs and glucocorticoids, which are first-line therapies of AOSD, is limited due to their side effects such as liver injury or disorder of blood glucose.Therefore, patients who suffer from systemic diseases in China prefer to seek help from Chinese herbal medicine(CHM), which is an important part of complementary and alternative medicine. In this case,we report a 28-year-old male badminton coach presenting with a 15-day history of fever and skin rash,accompanied by sore throat, fatigue, myalgia and chills. Additionally, hepatosplenomegaly, multiple lymphadenopathies, aminotransferase abnormality, and elevated inflammatory factor levels were observed during hospitalization. Infectious diseases, solid tumors, hematological diseases, and common autoimmune diseases were excluded. Not benefitting from antibiotic therapy, the patient was finally diagnosed with AOSD, after a careful examination, then showed rapid remission after a six-week treatment with CHM granules based on Xiaochaihu Decoction and Yinqiao Powder. After stopping the treatment, there was no relapse within a 15-month follow-up period. To the best of our knowledge, this is the first well-documented case of this successful treatment. The present case report suggests that CHM is a reliable choice for complementary and alternative therapy for AOSD, but confirming the utility of CHM for AOSD requires further support from prospective studies.