Episode #6 – The Fever & The Worm

Defining fever of unknown origin (FUO)

• The classic definition of FUO comes from the 1961 study by Petersdorf and Beeson, which included adults with:
  • • Fever >=38.3C on several occasion
    • Duration of fever at least 3 weeks
    • Uncertain diagnosis after 1 week in hospital
• This has been refined over time, particularly eliminating the in-hospital evaluation as much of the FUO evaluation can often be done largely in the outpatient setting.  The definition has also been adjusted with suggestions to classify based on nosocomial, neutropenic, or HIV and immunocompromised host-associated categories
• In pediatrics, studies of FUO have used various definitions as well. In general though, FUO in children should be considered after minimum of 14 days of daily documented temperatures >38.3C without apparent cause (after repeated physical exams and screening labs)

What information do we need to begin the FUO evaluation?  A comprehensive history and physical exam is the first and most crucial step!!  Here are some key topics and questions to ask:

• How is the temperature assessed?  
  • • By touch? Thermometer? If thermometer, which type and where?
    • Fever noted by both caregiver and others?
• Frequency and timing of fever
  • • How long, how high, when in the day?  Fever diaries are a useful tool to have patients or patient families complete.  These should include: date and time of fever, height/duration of fever, method of assessing fever, associated symptoms, response to antipyretics
    • When the child is febrile, do they appear ill or have symptoms?
    • Does the fever respond to ibuprofen or acetaminophen?
    • Do their symptoms persist despite fever resolution?
    • Do they sweat with fever?
• Symptoms?  
  • • Red eyes?
    • Pharyngitis/sore throat?  Mouth ulcers?
    • Gastrointestinal complaints?
    • Limb or bone pain?
• Medication list!  Everything including over the counter supplements
• Sick contacts
• Travel history (back to birth)
• Tick/insect exposures
• Animal contacts
• Diet: any raw meat or seafood? Pica?

Here is a summary of the general initial steps in FUO evaluation.

• Stop all nonessential medications
• CBC, differential, smear
• ESR and CRP
• Aerobic and anaerobic blood cultures
• UA and urine culture
• Chest X-ray
• Serum electrolytes, BUN/Cr
• LFTs
• TB screening
• HIV testing
• After this, can use targeted evaluation based on history, physical exam, results of basic screening tests
  • • Examples to investigate from ID perspective might include: Brucella, Bartonella, Leptospirosis, Malaria, TB, Salmonella, Toxoplasma, Tularemia, Typhoid fever
    • If no cause is identified, you would likely need to consider imaging as well.  We won’t dive too far into this here

So what do children with FUO end up being diagnosed with?

FUO is usually caused by common disorders, often with an unusual presentation, and infections have been the most commonly identified causes of FUO in children.  This systematic review from 2011 looked at 18 pediatric studies (1638 children) and found an infectious cause for FUO in 51% of children.  The infectious causes are outlined in Table 3 of the paper below.  Younger children (under 6 yo) were also more likely to have infectious cause of FUO compared to older children.

Chow A, Robinson JL. Fever of unknown origin in children: a systematic review. World J Pediatr. 2011;7(1):5-10. doi:10.1007/s12519-011-0240-5