I Have a Child With a Prolonged Fever

What is considered a prolonged fever?
Prolonged fever, or Fever of Unknown Origin (FUO), is generally defined as a fever that persists beyond 14 days, which distinguishes it from common, self-resolving (often viral) illnesses which may include fever that lasts a week or longer, but generally not as long as two weeks.

What are common causes of an FUO?
Many different diseases may present as an FUO, including:

• Infections - urinary tract, upper respiratory tract, bone and joint, central nervous system, endocarditis
• Autoimmune diseases - juvenile rheumatoid arthritis, systemic lupus erythematosis, polyarteritis nodosum, inflammatory bowel disease
• Malignancies -leukemia, lymphoma, neuroblastoma
• Miscellaneous - factitious fever, drug fever, etc.

A significant percentage of cases self-resolve over a period of weeks to months without ever coming to a specific diagnosis. When approaching a child with prolonged fever, it is helpful to remember that the child more often has an occult presentation of a common disease than a truly rare disease.

What are the key parts of the evaluation of an FUO?
The most important information is generally revealed by the history and physical examination. Significant clues may be identified only after serial histories and exams. Important elements of the history and examination include:

• Fever pattern, weight loss, and other constitutional symptoms, such as anorexia and night sweats (not discriminatory among diagnoses, but an indicator of disease severity)
• Exposures: ill contacts, residence and travel, animals, insects, unpasteurized dairy products, wild game, medications, tuberculosis contacts, HIV risk factors
• Symptoms/signs that may help discriminate among possible diagnoses, e.g., rash, joint findings, cardiac/respiratory or genitourinary symptoms/signs, or other localizing abnormalities. A normal examination suggests a favorable prognosis.

What laboratory tests should be done for a child with an FUO?
Screening laboratory evaluations can be extremely helpful in identifying clues and assessing the “degree of worry” one should have. These can be obtained over the course of several evaluations or they can be “front-loaded”, with more tests done at the first evaluation if the child is clinically concerning. Repeating basic hematology and chemistry tests and cultures over time may be revealing. A recommended screening approach includes the following:

First Level Screening Laboratory Evaluation

• Complete blood count
• Erythrocyte sedimentation rate
• C-Reactive protein
• Urinalysis
• Blood culture – shouldn’t be forgotten!
• Urine culture – even in the absence of suggestive symptoms!
• Chest radiograph – relatively high yield even without respiratory symptoms!

Second Level Screening Laboratory Evaluation

• Repeat complete blood count, erythrocyte sedimentation rate, C-reactive protein, urinalysis
• Repeat blood culture, urine culture
• Liver function tests, lactate dehydrogenase (LDH), uric acid, blood urea nitrogen, creatinine
• Stool heme test
• Antinuclear antibody, rheumatoid factor
• Mantoux skin test (PPD)
• Save serum for additional testing as needed

What evaluations should be done if screening testing doesn’t provide the answer?
Extensive “shotgun” laboratory evaluations are generally not very helpful in discerning the cause of an FUO. The yield is greater if additional work-up is individualized according to the clues from the history, physical exam, and screening laboratory studies. Tests that may be useful in pursuing clues include:

• Stool cultures (gastroenteritis symptoms; possible enteric fever)
• Serologies (cat scratch disease – cat/dog exposure; Epstein-Barr virus)
• Imaging targeted to organ-specific symptoms/signs (sinus CT scan; cranial CT or MRI; skeletal imaging; gastrointestinal imaging; etc.
• Tissue biopsy of an involved organ
• Abdominal imaging (ultrasound or CT scan) may also be warranted and has a relatively high yield

During this phase of the evaluation, consultation with appropriate subspecialists (Infectious Diseases, Rheumatology, and/or Oncology) may be helpful to further organize the diagnostic evaluation.

Because the prognosis for children with prolonged fever is generally favorable (moreso than in adults), one can generally be patient in the evaluation of a child with FUO. The tempo of the workup should be tailored to the degree of illness and the level of worry suggested by screening laboratory results.

Should the child with prolonged fever be hospitalized?
Hospitalization can be considered if the clinical and laboratory picture is worrisome, if the fever history is unreliable, or if it would assist in coordination of consultations and diagnostic tests.

Should empiric therapy (e.g, antibiotics or corticosteroids) be tried?
Empiric therapy such as antibiotics or corticosteroids should generally not be administered unless a specific diagnosis warranting their use is uncovered. In the absence of a diagnosis, such empiric treatment often provides transient responses (at best) and frequently masks the diagnosis, resulting in a more prolonged course.