The definition of fever of unknown origin (FUO) in an immunologically normal host requires an oral or rectal temperature ≥ 38.0°C (100.4°F) at least twice a week for more than 3 weeks and a noncontributory history and physical examination. FUO should not be confused with fevers of shorter duration variously termed “fever without localizing signs” (< 7 days) and “fever without source” (FWS) (7–14 days). Management of patients with comorbidity factors such as acquired or congenital immunodeficiency, neutropenia, and occurrence of fever during prolonged hospital stays is not considered in the following discussion since the differential diagnosis and evaluation of these patients vary considerably.
Because of the ready availability of more sensitive polymerase chain reaction (PCR) and serologic antibody assays and more precise radiographic scanning procedures, the assigned etiologies of FUO in children, as well as in adults, have changed over the past 3 decades, and more causes of fever are diagnosed earlier in the course of illness by primary care physicians.
Three pathogens now account for most identified infectious disease causes of FUO: Epstein-Barr virus, Bartonella henselae (cat scratch disease), and Escherichia coli urinary tract infections (Table 223-1). All can be confirmed with serologic assays or cultures for the respective pathogens. Cat scratch disease can also be confirmed with compatible liver lesions documented by abdominal sonogram or computed tomography (CT) scan.
TABLE 223-1Etiology of Fever of Unknown Origin in Children |Favorite Table|Download (.pdf) TABLE 223-1 Etiology of Fever of Unknown Origin in Children
|Disease Category ||1970–1980 ||1980–1990 ||1990–1996 ||1991–2015 |
|Infectious ||38% ||22% ||44% ||21% |
| Epstein-Barr virus ||2% ||8% ||15% ||4% |
| Cat-scratch disease ||0% ||2% ||5% ||2% |
| Urinary tract infection ||5% ||4% ||4% ||2% |
| Osteomyelitis ||1% ||1% ||10% ||1% |
| Tuberculosis ||2% ||0% ||0% ||1% |
| Others ||28% ||7% ||10% ||11% |
|Autoimmune ||17% ||6% ||8% ||6% |
| Juvenile idiopathic arthritis || ||3% ||3% ||4% |
| Systemic lupus erythematosus || ||1% ||2% ||1% |
| Others || ||2% ||2% ||1% |
|Malignancy ||9% ||2% ||3% ||4% |
| Leukemia || ||1% ||1% ||1% |
| Lymphoma || ||1% ||1% ||1% |
| Others || ||0% ||1% ||2% |
|Others ||18% ||3% ||2% ||8% |
|No diagnosis ||18% ||67% ||43% ||61% |
Over 60% of children who now present with FUO resolve their fever without determination of a cause, in contrast to only 10% to 20% in series published 20 to 30 years ago. In addition, a higher percentage of children with malignancies are now definitively diagnosed earlier in the course of illness, and such cases lead to an overall reduction in total cases of FUO. A greater percentage of the remainder likely have viral illnesses that are more difficult to diagnose but more likely to resolve without intervention.
An oral or rectal temperature ≥ 38°C (100.4°F) is 2 standard deviations above the average for normal children and most appropriately defines fever. Rectal recordings are preferred for younger children. Tympanic and temporal artery temperatures are so unreliable that they cannot be used to monitor febrile patients. Many parents believe that any temperature above the average—that is, ≥ 37°C (98.6°F)—is abnormal and seek consultation for these observations. Unless there are other clinical findings, either historically or during physical ...