Criteria for classical FUO:

(*REF: Arch IM 10-9-95;155:1989 De Kleijn E.M. - Netherlands)

Indium 111-labled polyclonal human IgG scintigraphy has the overall sensitivith of 81% & specificity of 69%. The positive predictive value was 69% & negative predictive value was 82%. It is helpful.

Nosocomial FUO:
Fever of >101 F (38.3 C) occurs on several occasions in a hospitalized pt, in whom infection was not present or incubating on admission. 3 days of investigation, including at least 2 days' incubation of cultures is the minimum duration for this dx.

Occult nosocomial infections (infected sinusitis in intubated pts, prosthetic devices infection, acalculous cholecystitis, Clostridium difficile toxin in the stool), infected IV lines, recurrent pulm. embolism, transfusion-related viral infection, & drug fever are possible diagnoses .

Neutropenic FUO:
Fever of >101 F (38.3 C) on several occasionis in a pt with <500 neutrophil/cc, with no diagnosis after 3 days of investigation, including at least 2 days' incubation of cultures.

These pts are susceptible to bacterial & fungal bacteremic infections & to infections involving catheters, including septic thrombophlebitis, as well as to perianal infections. Candida & Aspergillus infections are common. Viral infections due to herpes simplex or CMV are sometimes causes of FUO in this group.

HIV-associated FUO:
Fever of >101 F on several occasions over a period of >4 weeks for outpts or >3 days' duration in the hospital pt with HIV infection, with no diagnosis after 3 days of investigation, including at least 2 days' incubation of cultures. Hiv infection alone may be a cause. Mycobacterium avium intracellulare (MAI), toxoplasmosis, CMV, TB, Pneumocystis carinii, salmonellosis, cryptococcosis, histoplasmosis, non-Hodgking's lymphoma, and importantly, drug fever are all possible causes.


Differential Diagnosis of Diseases causing FUO in adults in the U.S.

A. Infections (36% in 1952-57, 23% in 1980-89)
1. Systemic infections

2. Localized infections & abscesses

B. Neoplasms (19% in 1952-57, 31% in 1970-80, 7% in 1980-89)
1. Hematologic: Lymphoma, Hodgkin's disease, acute leukemia, multiple myeloma, myelodysplastic syndromes
2. Non hematologic: hepatoma, hypernephroma, atrial myxoma, colorectal carcinoma, widespread metastatic cancer, etc.

C. Collagen vascular disease (13% in 1952-57, 16% in 1970-80, 22% in 1980-89)
1. Lupus (SLE), Rheumatoid arthritis, Polymyalgia rheumatica +/ temporal/giant cell arteritis Adult Still's disease, Sarcoidosis, Inflammatory Bowel Disease, Temporal Arteritis, & other vasculitis.

2. Behcet's disease, Erythema multiforme, erythema nodosum, polyarteritis nodosa, relapsing   polychondritis, Rheumatic fever, Takayasu's aortitis, Weber-Christian disease, Wegener's granulomatosis.

D. Other specific causes (25% in 1952-57, 10% in 1970-80, 27% in 1980-89)
1. Granulomatous diseases: sarcoidosis, idiopathic granulomatous hepatitis, starch peritonitis, & infectious granulomatous diseases as TB, brucellosis, histoplasmosis, Etc.

2. Inflammatory bowel disease

3. Drug fever

4. Factitioius fever

5. Misc: Familial Mediterranean fever, Whipple's disease, thyrotoxicosis, Neuroleptic Malignant Syndrome (NMS), post-seizure fever.  

6. Recurrent pulm. embolism, post-MI syndrome, subacute thyroiditis, tissue infarction/necrosis.

7. Thermorefulatory disorders: Central: brain tumor, CVA, encephalitis, hypothalamic dysfunction. Peripheral: hyperthroidism, pheochromocytoma.

E. Undiagnosed (7% in 1952-57, 12% in 1970-80, 23% in 1980-89)


History and Physical

Standard Fever Evaluation

Extended Fever Evaluation

  1. History and Physical: Assess possible focus (pain, heat, redness)
  2. Standard Evaluation
  3. Intravenous (IV) catheter assessment (Culture)
  4. If all Negative then consider Nuclear Medicine Scans
  5. Abdominal (with Pelvic) CT Scan
  6. Echocardiogram
  7. Bone Marrow - biopsy with cultures rule out infiltrating disease (malignancy, infection)
  8. Vascular biopsy - to evaluate for arteritis
  9. HIV Test - additional causes of FUO should be considered in HIV+ persons (see below)


HIV Positive Patients with FUO

1.Infectious and non-infectious causes of FUO in HIV+ generally correlate with CD4 count

2.Physical Exam should focus on the following:

3.CD4+ Counts <200/µL

4. If all tests are negative, proceed to further evaluations as outlined in Extended Evaluation for FUO above

OutlineMed Inc. Copyright 1996-1998


1997 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever  
Clinical Infectious Diseases 1997;25:551-73 (348 kb PDF)