Fever of Unknown Origin & Drug Fevers

Fever of Unknown Origin
Definition is variable, but basically requires 3 things:

1. Recurrent episodes of fever > 38.3
2. Lasting > 3 weeks
3. No clear source despite a reasonable hospital workup (> 1 week in the hospital)

DDx can be broken down into 3 main categories, plus miscellaneous:

1. Infectious - the most common etiologies are TB (often extrapulmonary) and occult abscesses (typically intraabdominal, but also dental abscesses).  Also, endocarditis, osteomyelitis, hepatitis, HIV, and rarer things like brucella, Q fever, bartonella.
2. Rheumatologic - including all sorts of vasculitis such as giant cell arteritis, Still's Disease, Lupus, others
3. Malignancy - any, but most commonly hematological (lymphoma, leukemia) and renal cell carcinoma, hepatocellular carcinoma
4. Miscellaneous - including Drug Fever (dx of exclusion - see below), Endocrine (Hyperthyroid, Pheo, Adrenal insufficiency), DVT/PE, Hematomas, Factitious, Familial Mediterranean Fever

Interestingly, diagnostic evaluation fails in 30-50% of patients, but these people still have a fairly good prognosis.

Overview of Drug Fevers

• Often start soon after initiation of drug, which is a clue, but unfortunately can occur weeks-months or even years after initiatiation.
• Often stop within 72 hours of stopping drug, which is helpful, but unfortunately can persist for weeks afterwards
• Most common classes of drugs are 1) Antibiotics - this often complicates the picture for obvious reasons.  Most commonly beta-lactams, sulfas, nitrofurantoin.                  2) Anticonvulsants, especially Phenytoin
• Sometimes occur with rash and eosinophilia, but these are unreliable findings.  Other (unreliable) clues can be liver/renal dysfunction and hematologic abnormalities. 

As you can see, drug fevers are difficult to diagnose, and should generally be a diagnosis of exclusion.

(Chanu Rhee MD, 10/8/10)