1276
CMDT 2013
30
Common Problems in Infectious Diseases & Antimicrobial Therapy Peter V. Chin-Hong, MD B. Joseph Guglielmo, PharmD
cc
Common Problems in Infectious Diseases FEVER OF UNKNOWN ORIGIN (FUO)
``
E s s e n t i a l s o f di a g n o s i s
Illness of at least 3 weeks duration. `` Fever over 38.3°C on several occasions. `` Diagnosis has not been made after three outpatient visits or 3 days of hospitalization. ``
with at least 2 days for cultures to incubate (see Chapter 31). Although not usually considered separately, FUO in solid organ transplant recipients is a common scenario with a unique differential diagnosis and is discussed below. For a general discussion of fever, see the section on fever and hyperthermia in Chapter 2.
A. Common Causes Most cases represent unusual manifestations of common diseases and not rare or exotic diseases—eg, tuberculosis, endocarditis, gallbladder disease, and HIV (primary infection or opportunistic infection) are more common causes of FUO than Whipple disease or familial Mediterranean fever.
B. Age of Patient
``General Considerations The intervals specified in the criteria for the diagnosis of FUO are arbitrary ones intended to exclude patients with protracted but self-limited viral illnesses and to allow time for the usual radiographic, serologic, and cultural studies to be performed. Because of costs of hospitalization and the availability of most screening tests on an outpatient basis, the original criterion requiring 1 week of hospitalization has been modified to accept patients in whom a diagnosis has not been made after three outpatient visits or 3 days of hospitalization. Several additional categories of FUO have been added: (1) Hospital-associated FUO refers to the hospitalized patient with fever of 38.3°C or higher on several occasions, due to a process not present or incubating at the time of admission, in whom initial cultures are negative and the diagnosis remains unknown after 3 days of investigation (see Health care-associated Infections below). (2) Neutropenic FUO includes patients with fever of 38.3°C or higher on several occasions with < 500 neutrophils per microliter in whom initial cultures are negative and the diagnosis remains uncertain after 3 days (see Chapter 2 and Infections in the Immunocompromised Patient, below). (3) HIVassociated FUO pertains to HIV-positive patients with fever of 38.3°C or higher who have been febrile for 4 weeks or more as an outpatient or 3 days as an inpatient, in whom the diagnosis remains uncertain after 3 days of investigation
In adults, infections (25–40% of cases) and cancer (25–40% of cases) account for the majority of FUOs. In children, infections are the most common cause of FUO (30–50% of cases) and cancer a rare cause (5–10% of cases). Autoimmune disorders occur with equal frequency in adults and children (10–20% of cases), but the diseases differ. Juvenile rheumatoid arthritis is particularly common in children, whereas systemic lupus erythematosus, granulomatosis with polyangiitis (formerly Wegener granulomatosis), and polyarteritis nodosa are more common in adults. Still disease, giant cell arteritis, and polymyalgia rheumatica occur exclusively in adults. In the elderly (over 65 years of age), multisystem immune-mediated diseases such as temporal arteritis, polymyalgia rheumatica, sarcoidosis, rheumatoid arthritis, and granulomatosis with polyangiitis (formerly Wegener granulomatosis) account for 25–30% of all FUOs.
C. Duration of Fever The cause of FUO changes dramatically in patients who have been febrile for 6 months or longer. Infection, cancer, and autoimmune disorders combined account for only 20% of FUOs in these patients. Instead, other entities such as granulomatous diseases (granulomatous hepatitis, Crohn disease, ulcerative colitis) and factitious fever become important causes. One-fourth of patients who say they have been febrile for 6 months or longer actually have