FUO

The classic definition of FUO from the early 1960s was: fever greater than 38 degrees Celsius on several occasions over a 3 week period of time with week worth of hospital investigations. With changes in our healthcare system, it is now generally accepted that the definition applies if only 2-3 weeks have past and there have been initial investigations performed (the list of which tests varies)

When thinking about FUO remember the 4 major categories
Inflammatory, Infectious, Malignancy and up to 50% do not end up with a diagnosis (and generally have a good prognosis)

A prospective study from the Netherlands illustrates this

A proposed algorithm based on existing evidence was created by a Toronto internist and published in Archives of Internal Medicine. Dont forget that investigations should be tailored/expanded based on a comprehensive history and physical.

Fever

Today we discussed fever and some of its nuances. Some points:

The definition of a fever depends where you look; Sapira's textbook uses oral temperature of 37.9 as a cutoff; definitions of febrile neutropenia use multiple readings of 38.0 or single reading of 38.3. Fever of unknown origin definitions typically use 38.3

Some classic fever patterns (use with caution; most patients do not obey these "rules"!)

Relapsing (hours or days of fever, then days without): Hodgkin's, TB, malaria, familial mediterranian fever

Pel-Ebstein: seen in 16% of Hodgkin's- hours to days with then days to weeks without

Tertian- recurs q48h (3rd day)- P. vivax, P. ovale

Quartian- q72h (4th day)- P. malariae

Some diagnostic possibilities with a very high fever (over ~40)

1) Drug reactions (including neuroleptic malignant syndrome and hypersensitivity reactions)
2) Causes of "normal" fever with superimposed autonomic dysfunction as in diabetic autonomic neuropathy
3) "Heat stroke" (overwhelming activity with impaired cooling mechanisms)
4) Infections (classically CNS infections, malaria, and deep-seated abscesses- esp. empyema, hepatic, etc)
5) Intoxications (amphetamines, ecstasy overdoses causing serotonin syndrome)

Fever of unknown origin

Usually defined as fever (as defined above) for 3 weeks or more with uncertain etiology after investigations (used to specify 1 week hospitalization, but this definition is now challenged since more tests can be done as outpatient)

Major categories for FUO:

1) infection (massive list...)
2) inflammatory (temporal arteritis, adult Still's, RA, SLE, IBD, sarcoid, FMF...)
3) malignancy (lymphoma, leukemia, RCC, HCC, pheo)
4) drugs (NMS, serotonin syndrome, EtOH withdrawal, etc)
5) necrosis (PE, MI, massive stroke)
6) hyperthyroidism
7) hepatic (any process including viral hepatitis, infiltration, etc)
8) hemolysis

Based on this study from local investigators, there is evidence for
-applying Duke's criteria for endocarditis
-CT abdomen
-liver diopsy
-nuclear medicine scan to detect inflammation or malignancy
-temporal artery biopsy in elderly patients

Click here for a study from the Netherlands proposing a graded diagnostic algorithm for evaluating FUO