Fever of Undetermined Origin in Elderly Patients : Causes and Clinical Characteristics

Background and study aim: Fever of Undetermined Origin (FUO) continues to be a diagnostic challenge particularly in elderly patients. Reporting local experience is important in guiding clinicians about the epidemiologic pattern in different region. This study aimed to determine causes, clinical presentations and the laboratory findings of FUO among elderly persons ≥ 65 years in comparison with younger patients. Patients and Methods: This study was conducted on 54 patients during one year duration from the period between January 2015 and January 2016. Patients were divided into two equal groups of 27 patients who were suffering from FUO. The first one (G1) consisted of elderly patients ≥ 65 years and the second group (G2) consisted of patients younger than the age of 65. All patients in this study were subjected to complete history taking adequate physical examinations in addition to routine laboratory investigations and specific investigations (according to case). Conclusion: Urinary tract infection, chronic calcular cholecystitis and malignancy are important causes for FUO in elderly patients followed by miscellaneous causes as post chemotherapy and drug fever. Non-elderly group showed statistical significant increase in typhoid fever, HIV infection, infective endocarditis, intra-abdominal abscess and auto immune disorders when compared to elderly group.


INTRODUCTION
In 1961, Petersdorf and Beeson introduced the definition of fever of undetermined origin (FUO) that subsequently became standard-namely, fever of more than 3-weeks duration, fever higher than 38.3 o C on several occasions, and diagnosis uncertain after 1 week of study in hospital [1].
Because hospital admission is so expensive and thorough diagnostic testing now can be performed in outpatient settings, the definition of classic FUO was modified to remove the requirement that a hospital be the setting for 1 week of evaluation.The revised criteria require an evaluation of at least 3 days in the hospital, three outpatient visits, or 1 week of logical and intensive outpatient testing without determining the fever's cause [2].
Febricity in the elderly can be defined as temperature exceeding 37.2°c taken orally or of ear drum, or higher than 37.5°c taken rectally [4].
The diagnostics of FUO in the elderly often differs from the young patients; the manifestation of a disease is often nonspecific in older patients.The physiologic reserves are diminished in the elderly as well as their immunity.In the elderly many other accompanying diseases may affect the diagnosis, treatment, and the outcome of the illness.The symptoms and signs of many illnesses are atypical or less prominent in older patients, which obviously complicate diagnosis.Thus for instance, cognitive function disorders can be the only sign of infection in the elderly [5].
This study aimed to determine causes, clinical presentations and the laboratory findings of FUO among elderly persons ≥65 years in comparison with younger patients.

PATIENTS AND METHODS
This cohort study was conducted on 54 patients admitted to El-Mehalla Fever Hospital, Tanta Fever Hospital and Zagazig University Hospitals during one year duration from the period between January 2015 and January 2016.Patients with FUO of any type with consideration of temperature <37.2°C orally or <37.5°C per rectum for elderly patients ≥ 65 years and <38.3°C orally for younger patients were included.
Patients were divided into two equal groups of 27 patients who were suffering from FUO.The first one (G1) consisted of elderly patients ≥ 65 years and the second group (G2) consisted of patients younger than the age of 65.
After ethical approval of the study, an informed consent was taken from all patients.All cases were followed up in hospital setting.
All patients were subjected to : Full history taking: Including: age, sex, residence, occupation, travelling abroad, exposure to animals or vectors, drug history, family history, sexual history, history of special habits, the magnitude of the temperature readings and the patterns of fever.Elderly group showed statistical significant increase in urinary tract infection (UTI) and chronic calcular cholecystitis, while non-elderly group showed statistical significant increase in typhoid fever, HIV infection, infective endocarditis and intra-abdominal abscess when compared to elderly group.In this study serum creatinine showed statistically significant increase in elderly group, although it was still in the normal range.It may remain within the reference range despite marked renal impairment in patients with low muscle mass, so the sensitivity of serum creatinine for the early detection of kidney disease is poor [20].

An
In the present study, there was no statistical significant difference in FUO categories (classic,

Statistical analysis : Data
* Highly significant.Fever in elderly group showed statistically significant increased percentage of the continuous pattern, on the other hand sweating was significantly prominent in non-elderly group.
collected throughout history, basic clinical examination, laboratory investigations and outcome measures coded, entered and analyzed using Microsoft Excel software.Data were then imported into Statistical Package for the Social Sciences (SPSS version 20.0) (Statistical Package for the Social Sciences) software for analysis.According to the type of data qualitative represent as number and percentage, quantitative continues group represent by mean ± SD.The following tests were used to test differences for significance;.RESULTSTable (1): Fever Pattern of elderly group versus non elderly groupNB: * Significant.*

Table ( 2
) : Laboratory investigation of elderly group versus non elderly group

Table ( 3
) : FUO categories of elderly group versus non elderly group NB: * Significant.** Highly significant.There was no statistical significant difference in FUO categories between both groups.

Table ( 4
): Causes of FUO in both groups * Highly significant.There was no statistical significant difference in causes of FUO between both groups.

Table ( 6
): Non infectious causes of FUO in both groups NB: * Significant.** Highly significant.Elderly group showed statistical significant increase in hepatocellular carcinoma, post chemotherapy, drug fever and septicemia while non-elderly group showed statistical significant increase in auto immune disorder when compared to elderly group.
who reported miscellaneous causes to be responsible for 4.3%, 5% and 23% of cases of FUO.This discrepancy may be due to different study population.In our study, undiagnosed causes were 22.2% in elderly group ≥65 versus 14.8% in group <65.This agreed with Ali-Eldin et al. [30], Hu et al. [28] Kejariwal et al. [31] who reported undiagnosed causes to be responsible for 12.9%, 14.1% and 14% of cases of FUO in group <65.Also agreed with Naito et al. [26] MIR et al. [24] and Stamatis et al. [27] who reported undiagnosed causes to be responsible for 23.1%, 23% and 20.5% of cases of FUO in elderly group ≥ 65.CONCLUSIONWe concluded that, Urinary tract infection, chronic calcular cholecystitis, malignant causes (including hepatocellular carcinoma) and miscellaneous causes (as post chemotherapy, drug fever and septicemia) are important causes for FUO in elderly patients.Non-elderly group showed statistical significant increase in auto immune disorders when compared to elderly group.Also we found that categories of FUO (classic, nosocomial, Immune deficient, and FUO associated with HIV infection) in elderly patients did not differ from non-elderly patients.