1. Among 100 children presenting to one children’s hospital for prolonged febrile illnesses, the majority of cases were of an infectious etiology (52 cases).
2. Significantly more febrile illnesses in younger children were due to infectious causes, while those due to inflammatory conditions were significantly more likely to occur in older children.
Original Date of Publication: April 1975
Study Rundown: The issue of prolonged febrile illness in children presents a diagnostic challenge to pediatric practitioners. At the time of this study’s publication, there were no guidelines for diagnosis and management of children with fevers of unknown origin (FUO), a term still without a clear definition even today. It is often defined as temperature > 38.3˚C for at least 8 days without any obvious cause following initial outpatient or hospital evaluation. This study investigated prolonged fever in 100 children in order to better define guidelines for the care of those with FUO, defined in this study as a temperature > 38.5˚C, > 5 times during a two-week period. Of the 100 records included, the most common fever etiology was infection (52 cases). Findings indicated that significantly more young children had fevers of infectious etiologies, while significantly more older children had collagen-inflammatory fever etiologies. Based on the findings that 62% of children had stories and presentations consistent with etiology, researchers recognized the importance of a thorough history and physical in diagnosis. With 80% of children receiving antibiotics prior to official diagnosis and no resolution in their symptoms, the use of antibiotic therapy prior to hospitalization was discouraged and use of diagnostic cultures encouraged. In addition, erythrocyte sedimentation rate (ESR) testing and protein analysis were deemed more useful than complete blood count (CBC) and urinalysis (UA). Other procedures and imaging techniques were helpful when indicated by the history and physical.
This study was limited by its small sample size, lack of patient racial/ethnic diversity, and use of only one institution as a source of patient reports. Decades and multiple studies and reports on FUO later, many of the conclusions drawn from this landmark study still stand. Infection remains the most common cause of prolonged febrile illness. The importance of history and physical in diagnosing children with FUO continues to be emphasized; however specific recommendations for initial testing include CBC, ESR, C-reactive protein, blood cultures, UA and culture, chest radiograph, tuberculosis testing, electrolytes, and blood urea nitrogen, creatinine, liver panel, and HIV serology. Further workup including radiography is recommended based off of history and physical.
In-Depth [retrospective cohort study]: A total of 100 patient (65% male, 91 white) records of children seen at a tertiary children’s hospital for prolonged fever during 1966 to 1973 were included in analysis. Prolonged fever defined as a temperature of > 38.5˚C on > 5 times during a two-week period without final diagnosis from a referring physician. Temperatures were taken either rectally or using some other equivalent. Results were analyzed using X2 testing with final diagnoses as determined by laboratory testing when appropriate and then categorized as “infectious-presumed viral,” “infectious-nonviral,” “collagen-inflammatory,” “malignancy,” “miscellaneous,” or “undiagnosed.” In addition, fever patterns, use of antipyretics, symptoms, physical findings, laboratory results, and radiologic findings were recorded.
Of 100 patients, most were diagnosed with infectious causes of their fevers (52 cases), with 17 secondary to presumed viral illness, 20 due to collagen-inflammatory disorders, 6 secondary to malignancy, and 10 from miscellaneous causes. When cases were divided by age into either younger than 6 years of age (52 cases) or older than 6 years of age (48 cases), it was found that significantly more younger patients were diagnosed with infection than older patients (34 v. 18, p < 0.05), while significantly more of those diagnosed with collagen-inflammatory diseases were older than 6 years of age compared to younger individuals (16 v. 4, p < 0.05). The most common presenting symptoms of febrile patients were head, ear, eye, nose, and throat symptoms (72 cases). Only 27 patients had physical signs directly related to their final diagnoses. White blood cell count and low hematocrit from CBC did not significantly relate to fever etiology. ESR was significantly related to nonserious fever etiology in the 20 children with ESR < 10 mm/hr. Thirty-four of 74 children tested had reversed albumin-globulin ratios. Of these, significantly more patients with collagen-inflammatory disease had reversal compared to those with viral diagnoses (75% v. 20%, p < 0.05). In addition, electrophoresis patterns differed significantly among patients with viral disorders showing a uniform decrease in albumin and increase in globulin.
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