FEVER OF UNKNOWN ORIGIN

Historical: 1907- Richard Cabot (MGH) described series of pts w/ long fevers, found 3 leading causes: 1) typhoid, 2) TB, 3) sepsis/endocarditis. 1961- Beeson, Petersdorf published prospective series, defined FUO: 1) illness > 3 wks, 2) fever > 101 on several occ, 3) no dx after 1 wk in hospital.

Definition: Modified 2ndary to decreased hospitalization in modern era: 1) illness > 3 wks, 2) fever > 101 (38.3), 3) no dx after 1 wk intensive evaluation.

Etiologies: The “Top Seven”(account for 50%)- TB, endocarditis, lymphoma, solid tumor, Still’s, vasculitis, common rheumatologic disorder.

1. Infection (30-40%)

Localized

a. endocarditis

b. intrabdominal infection- hepatic, diverticular, splenic, subphrenic, pancreatic, biliary, psoas, pelvic

c. UTI- pyelo, perinephric, prostatic

d. osteomyelitis

e. URI- dental abcess, sinusitis

f. infected peripheral vessels

Generalized- bacterial, MTB, fungus, viral (CMV!), parasitic

1. Neoplasia (20-30%)

a. lymphoproliferative- lymphoma most common (Pel-Ebstein fever)

b. leukemia- AML

c. MDS

d. solid tumors- RCCa most common, atrial myxoma

1. Rheumatologic (10-20%)

a. adult Still’s disease

b. giant-cell arteritis, PMR- exclusively > 50y

c. other vasculitis- Wegner’s, Takayasu’s, PAN, cryoglobulinemia

d. other rheum- SLE, RA, Sjogren’s

1. Miscellaneous (15-20%)

a. granulomatous- Crohn’s, sarcoid

b. EtOH hepatitis- AST:ALT > 2:1, <600

c. vascular- PE, hematoma

d. drug- almost always remits w/in 72h of stopping

e. hereditary- FMF(recurrent fever, peritonitis, leukocytosis)

f. endocrine- hyperthyroid, subacute thyroiditis, adrenal insufficiency

g. factitious

1. No dx (5-15%): prognosis GOOD

Diagnostic workup:

1. History

a. focus on: prior medical problems, surgeries, travel, exposure to animals and TB, PPD

b. pattern and height of fever, chills, sweats, bradycardia NOT generally helpful

1. Physical exam

a. eyes- sclera, conjunctivae, dilated fundus exam

b. nodes

c. skin and mucous membranes- rash, petechiae, Osler/Janeway, ulcers

1. Labs/imaging

a. initial- CBC, UA/Cx, SMA7, LFTs, BCx(3 in 24hrs), CXR

b. further studies (individually tailored)- AbdCT, BM Bx, Liver Bx, TA Bx, ChestCT, ESR, ANA, RF, ACE, CMV, PPD, HIV

General prinicples:

1. Horses and zebras

2. Sutton’s Law

3. Back to the drawing board

Hirschman. Clin Inf Dis. 1997; 24: 291-302