The preliminary investigations of prolonged fever of unknown origin (FUO) in primary health care are
Full blood count, CRPand ESR
urinalysis and bacterial culture
imaging studies as considered necessary (chest x-ray, maxillary sinus imaging).
If the blood picture is normal, CRP and ESR within normal limits and the fever is fluctuating and of low grade, a specific underlying cause is only rarely found. In these cases, fever gradually resolves in over 80% of children.
If the blood picture has abnormal features, the inflammatory markers are elevated and no obvious cause for the fever is found or empiric antimicrobials are considered, investigations are continued in specialist health care.
Fever in infants under the age of 3 months requires investigations as an emergency case Acutely Ill Infant. This article addresses prolonged fever in children. See also the article Fever in a child Fever in a Child.
Terminology
Fever
As a general rule the upper limit of normal body temperature in a child is 38°C when measured from the rectum and 37.5°C when measured from the axilla.
Occasionally the body temperature of a totally healthy child may increase to 38°C after a bout of high activity or in the evenings.
FUO and FWS (fever without a source)
Prolonged FUO denotes fever of at least 8 days duration where no apparent diagnosis has been established despite hospital investigations.
The definition FWS may also be used of fever of less than 7 days duration where no apparent cause has been identified.
These terms also define the urgency of evaluation: FWS often requires urgent evaluation whereas the evaluation of FUO does not require the same degree of urgency.
Aetiology
Even though the aetiology of fever shows geographical variation, the most common cause is an infection. The aetiology can be roughly divided into the below groups.
Infections (20-77%)
Prolonged viral infection (mononucleosis Mononucleosis most common)
The evaluation of the aetiology of fever should be started by defining the nature of the fever; this will be beneficial in the planning of further investigations. Does the patient have
prolonged fever after an obvious infection
periodic fever recurring at certain intervals or
prolonged fever without an apparent reason (FUO)?
It is most important to obtain a comprehensive history. The following questions regarding the nature of the fever are also useful for the evaluation of its aetiology.
Duration of fever, how high is the fever, is there any variation for example as regards the time of the day?
Why has the temperature been taken? Does the child look unwell?
Who has taken the child's temperature?
What type of thermometer has been used and which anatomical site has been used for the measurements?
Are antipyretic medications of benefit?
Are there particular symptoms that occur before or during fever? Weight loss? Fatigue?
Ethnic background (e.g. hereditary fevers, infections in immigrant children)
Development of height and weight
Travel history, contact with animals and infectious sources?
Physical examination
An accurate history is obviously the cornerstone of the examination. The child should also be examined when febrile as in some cases that is the only time when, for instance, skin or joint symptoms develop.
Preliminary investigations often provide enough information to guide the initial evaluation.
Full blood count
CRP, ESR
Urinalysis and bacterial culture
EBV and CMV serology
(Blood cultures × 3)
Bacterial stool examinations
In suspected cases of inflammatory bowel disease faecal calprotectin testing is recommended. The possibility of tuberculosis (interferon-gamma release assay, IGRA), HIV infection and, especially after foreign travel Fever in a Returning Traveller, tropical diseases, particularly malaria, should be borne in mind.
Malaria should be excluded on emergency basis in all febrile patients who have a history of travelling in areas affected by malaria even if appropriate prophylactic medication was used.An infectious disease specialist should be consulted in the case of a febrile patient returning from the tropics.
Imaging studies
Chest x-ray should always be taken.
Paranasal sinus imaging (ultsasonography, x-rays) in children over 6 years.
Abdominal ultrasonography is a routine investigation.
Other imaging studies, such as a skeletal x-ray examination, MRI, PET-CT or scintigraphy, are sometimes necessary (e.g. if osteomyelitis is suspected).
Treatment
Empiric antimicrobials may sometimes be useful in the diagnostic workup but should only be prescribed after comprehensive evaluation. The decision to prescribe antimicrobials is made in specialist health care.
References
Antoon JW, Peritz DC, Parsons MR, et al. Etiology and Resource Use of Fever of Unknown Origin in Hospitalized Children. Hosp Pediatr 2018;8(3):135-140. [PubMed]
Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol 2017;31(4):596-609. [PubMed]