Internal Medicine

0521779407-07 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:10

Fever of Unknown Origin 565

others can cause FUO such as brucellosis, Q fever, salmonella,

malaria, Whipple’s disease, cat-scratch disease and other Bar-

tonella infections, viral infections (especially cytomegalovirus,

Epstein-Barr), fungal infections such as coccidioidomycosis,

histoplasmosis (usually disseminated), toxoplasmosis; localized

infections: osteomyelitis, cholecystitis, occult abscess (hepatic,

subdiaphragmatic, intra-renal or perinephric, splenic, pelvic,

dental)

➣Neoplastic (20%–35%) – Hodgkin’s and non-Hodgkin’s lym-

phoma, acute leukemia, renal cell carcinoma, primary and

metastatic tumors of the liver, atrial myxoma; chronic lympho-

cytic leukemia and myeloma usually not associated with fever

unless there is concomitant infection

➣Autoimmune or Rheumatologic (10%–20%) – polyarteritis no-

dosa, polymyalgia rheumatica, systemic lupus, temporal arteri-

tis, cryoglobulinemia, Still’s disease, Wegener’s granulomatosis

➣Miscellaneous – granulomatous hepatitis, sarcoidosis, inflam-

matory bowel disease, familial Mediterranean fever, hyperthy-

roidism, recurrent pulmonary emboli, alcoholic hepatitis, drug

fever, factitious fever

➣Undiagnosed (10%–15%)

■Certain general principles helpful in determining etiology:

➣Most cases due to common diseases with unusual manifesta-

tions, not rare or exotic diseases (tuberculosis, endocarditis, and

cholecystitis more common causes than familial Mediterranean

fever or Whipple’s disease)

➣Duration of fever – infection, malignancy and autoimmune dis-

eases etiology of FUO in only 20% of patients with prolonged

fever (6 months or longer); granulomatous diseases (Crohn’s dis-

ease, sarcoidosis, granulomatous hepatitis) and factitious fever

more common etiologies; 25%-30% have no fever or underly-

ing disease at all – the normal circadian rhythm (temperature

1–2 degrees higher in afternoon than morning) interpreted as

abnormal

➣Episodic or recurrent fever (FUO with periods of 2 wks or longer

without fever) – similar in etiology to prolonged fever; familial

Mediterranean fever, recurrent embolic disease also considera-

tions

➣Immunologic status – neutropenic patients often have occult

bacterial or fungal infections; organ transplant recipients

on immunosuppressive medications prone to viral infections