1

(An Approach to Prolonged Fever of Unknown

Origin)
. .

.




[Prolonged fever and Perplexing
fever; Fever of unknown origin (FUO); Pyrexia of unknown
origin]


..1961 Petersdorf Beeson
(Classic FUO)

(1)

1. 3
2. 38.3 101

Last update: February 9, 2004

3.

1
Petersdorf Beeson
3

(Self-limited
diseases) 3

..1991 Durack Street

(2)

Petersdorf Beeson 3
1 3
3

Last update: February 9, 2004

Durack Street

(2)

4
1
Classic
FUO

(3,4)

1 (FUO)
( Durack DT, Street AC. Fever of unknown
origin - reexamined and redefined. Curr Clin Top Infect Dis 1991; 11: 3551.)

(2)

Classic FUO

Nosocomial

Neutropenic

HIV-related

FUO

FUO

FUO

neutrophil

/.

1-2

.
*

Last update: February 9, 2004

.
*

500

4
.
3

4
*

infection, M.

diseases

M. avium-

embolism

spp.

Inflammatory

C. difficile
pulmonary

perianus

Aspergillus
Candida spp.

Primary HIV

tuberculosis,
intracellulare,

Cytomegaloviru

septic

thrombophlebiti
s
#

>38.3 C 101 F

classic FUO 39-88

3
(autoimmune diseases)
(miscellaneous disorders) granulomatous hepatitis,
pulmonary embolism, pancreatitis, factitious fever, erythema
maltiforme, inflammatory bowel disease, thyroiditis, aortic
dissection, Kikuchi-Fujimoto disease

6-53 ( 2)
3
classic FUO 1950 1970

Last update: February 9, 2004

connective tissue diseases
1980 1990
connective tissue diseases

classic FUO

classic FUO

Last update: February 9, 2004

6
2 classic FUO
:

()

Petersdorf&Beeson:

100

36

19

17

19

105

30.5

31.4

12.4

9.6

16.2

133

31

19.5

15

12.5

22

50

42

30

16

Likuni et al.: 1982-

167

28.8

14.4

30.7

14.4

11.8

Tabak et al.: 1984-

117

34

19

23

10

14

De Kleijn et al.:

167

25.8

12.6

22.7

7.8

31.1

185

10.8

9.7

18.4

8.1

53

100

53

17

11

14

1952-1957(
)

Larson et al.: 19701980 ()

5

Barbado et al.:

1968-1981 ()
1981-1986 ()
1992 ()
2001 ()

1992-1994

()

10

Vanderschueren et
al.: 1990-1999
()

11

Kejariwal et al.:

1998-2001 ()
12

Last update: February 9, 2004

classic FUO
Chantada

(13)

113

81
36
connective tissue diseases

connective
tissue diseases juvenile rheumatoid arthritis

classic FUO

classic FUO
classic
FUO 87-95

(14)

25-35
connective tissue diseases 2531 temporal arteritis, rheumatoid arthritis
polymyalgia rheumatica
Stills disease, systemic lupus erythematosus variants

Last update: February 9, 2004

rheumatoid arthritis
12-23

Classic FUO
classic FUO

National
Institutes of Health
347 35
(factitious fever)
classic FUO

Last update: February 9, 2004

doxycycline chloramphenicol
rickettsiosis





3

classic FUO
(systematic review)

1.
2.

Last update: February 9, 2004

10

1. sinus tenderness

2. temporal artery nodule

pulsation temporal arteritis
3.
periapical abscess oral ulceration
disseminated histoplasmosis penicilliosis
connective tissue disease systemic
lupus erythematosus, Behcets disease
4. petechiae
Roths spot
cytoid body
systemic lupus erythematosus
5.
thyroiditis
6. murmur

7.

Last update: February 9, 2004

11

8. testicular nodule
disseminated granulomatosis histoplasmosis
genital ulceration Behcets disease
9. splinter hemorrhage, Oslers
node, Janeway spots, palpable purpura digital
ulceration
vasculitis

Pizzo

(15)

Lohr

(16)

60

Last update: February 9, 2004

12

classic FUO

(potentially diagnostic clues)

Mourad

(17)

(Systematic review)

(Evidence-based recommendations)

non-invasive tests

1.
2. (complete blood count)

3. Routine blood chemistry lactic dehydrogenase, bilirubin
liver enzymes
4.
5.
6.
7. (serology)

Antinuclear antibodies, rheumatoid factor

Anti-HIV

Cytomegalovirus IgM antibodies heterophil antibody

test ( mononuclearlike syndrome)

Last update: February 9, 2004

13

Q-fever serology ()

Hepatitis serology ( liver

enzyme)

1. Abdominal CT scan

lymphoproliferative disorders
19

(18)

2. (Nuclear imaging)

(18-19)

Technetium

111

Gallium,

67

99m

Indium

111

Indium-labeled white blood cell scan

antigranulocyte antibodies

99m

Tc-labeled

antigranulocyte antibodies BW 250/183-based scan

IgG antibodies

111

Indium-labeled IgG

antigranulocyte antibodies

IgG antibodies


(biodistribution)

Last update: February 9, 2004

14

99m

Tc-labeled

antigranulocyte antibodies (BW 250/183)-based scan

93-94
( 40-75)

111

Indium-labeled IgG

111

Indium-

labeled white blood cell scans 45-82

69-86

Gallium nuclear scan

67

67 78

111

Indium-labeled white blood cell scans

F fluorodeoxyglucose (FDP) positron emission

18

tomography (PET) scan

FDP-PET
white blood cell scans

111

Indium-labeled

Gallium nuclear scan

67

111

Indium-labeled white blood cell scans FDP-PET

FDP-PET

Gallium nuclear

67

(19-20)

3. Duke criteria
82
99
4. (Liver biopsy)
14-17
liver function test
Last update: February 9, 2004

15

(21)

ultrasonography CT scan

(blinded method)
5. temporal artery biopsy
ESR
50 ./. temporal arteritis
color duplex ultrasonography
temporal artery
93
6. leg doppler imaging deep venous
thrombosis
2-6

classic FUO
0-2

(22)

surgical abdominal exploration

CT scan
CT scan
exploratory
laparotomy laparoscopic biopsy

Last update: February 9, 2004

16

ultrasound needle biopsy

68

de Kleijn

(24)

(23)

classic FUO

167 .. 1992-1994

(screening tests)

immunology,
microbiologic serology, endocrine, echocardiogram, imaging



79

ultrasound

Last update: February 9, 2004

17

empirical therapeutic trial

aspirin
naproxen

rifampicin

(25)

empirical therapeutic trial

empirical therapy

Last update: February 9, 2004

18

empirical treatment

(11, 17, 26-27)

4-5

polymyalgia rheumatica,
vasculitis autoimmune diseases

Last update: February 9, 2004

19

5 3.2

Last update: February 9, 2004

20

1. Petersdorf RG, Beeson PB. Fever of unexplained origin:

Report on 100 cases. Medicine 1961; 40: 1-30.
2. Durack DT, Street AC. Fever of unknown origin - reexamined
and redefined. Curr Clin Top Infect Dis 1991; 11: 35-51.
3. Mackowiak PA, Durack DT. Fever of unknown origin. In:
Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and
Bennetts principles and practice of infectious diseases. 5

th

ed.

Philadelphia: Churchill Livingstone 2000; 623-33.

4. Mourad O, Palda V, Detsky AS. A comprehensive evidencebased approach to fever of unknown origin. Arch Intern Med
2003; 163: 545-51.
5. Larson EB, Featherstone HJ, Petersdorf RG. Fever of
undetermined origin: diagnosis and follow-up of 105 cases,
1970-1980. Medicine (Baltimore). 1982; 61: 269-92.
6. Barbado FJ, Vazquez JJ, Pena JM, et al. Fever of unknown
origin: a survey on 133 patients. J Med 1984; 15: 185-92.
7. . Fever of unknown origin.
3. 1995: 954-63.
8. Likuni Y, Okada J, Kondo H, Kashiwazaki S. Current fever of
unknown origin 1982-1992. Intern Med 1994; 33: 67-73.
9. Tabak F, Mert A, Celik AD, et al. Fever of unknown origin in
Turkey. Infection 2003; 31: 417-20.
10.

De Kleijn EM, Vandenbroucke JP, van der Meer JW. Fever

of unknown origin (FUO). I A. prospective multicenter study of

Last update: February 9, 2004

21

167 patients with FUO, using fixed epidemiologic entry

criteria. The Netherlands FUO Study Group. Medicine
(Baltimore) 1997; 76: 392-400.
11.

Vanderschueren S, Knockaert D, Adriaenssens T, et al.

From prolonged febrile illness to fever of unknown origin

The challenge continues. Arch Intern Med 2003; 163: 103341.
12.

Kejariwal D, Sarkar N, Chakraborti SK, Agarwal V, Roy S.

Pyrexia of unknown origin: a prospective study of 100 cases.

J Postgrad Med 2001; 47: 104-7.
13.

Chantada G, Casak S, Plata JD, Pociecha J, Bologna R.

Children with fever of unknown origin in Argentina: an

analysis of 113 cases. Pediatr Infect Dis J 1994; 13: 260-3.
14.

Norman DC. Fever in the elderly. Clin Infect Dis 2000; 31:

148-51.
15.

Pizzo PA, Lovejoy FH Jr, Smith DH. Prolonged fever in

children: review of 100 cases. Pediatrics 1975; 55: 468-73.

16.

Lohr JA, Hendley JO. Prolonged fever of unknown origin: a

record of experiences with 54 childhood patients. Clin Pediatr

1977; 16: 768-73.
17.

Mourad O, Palda V, Detsky AS. A comprehensive

evidence-based approach to fever of unknown origin. Arch

Intern Med 2003; 163:545551.
18.

Quinn MJ, Sheedy PF, Stephens DH, Hattery RR.

Computed tomography of the abdomen in evaluation of

Last update: February 9, 2004

22

patients with fever of unknown origin. Radiology 1980; 136:

407-11.
19.

Becker W, Meller J. The role of nuclear medicine in

infection and inflammation. Lancet Infect Dis 2001; 1: 32633.

20.

Kjaer A, Lebech AM, Eigtved A, Hojgaard L. Fever of

unknown origin: prospective comparison of diagnostic value of

(18) F-FDG PET and (111) In-granulocyte scintigraphy. Eur J
Nucl Med Mol Imaging. Published online: 17 January 2004.
DOI: 10.1007/s00259-003-1425-5.
21.

Holtz T, Moseley RH, Scheiman JM. Liver biopsy in fever

of unknown origin. A reappraisal. J Clin Gastroenterol 1993;

17: 29-32.
22.

Volk EE, Miller ML, Kirkley BA, Washington JA. The

diagnostic usefulness of bone marrow cultures in patients with

fever of unknown origin. Am J Clin Pathol 1998; 110: 150-3.
23.

Rajwanshi A, Gupta D, Kapoor S, et al. Fine needle

aspiration biopsy of the spleen in pyrexia of unknown origin.

Cytopathology 1999; 10: 195-200.
24.

de Kleijn EM, van Lier HJ, van der Meer JW. Fever of

unknown origin (FUO). II. Diagnostic procedures in a

prospective multicenter study of 167 patients. The Netherlands
FUO Study Group. Medicine (Baltimore) 1997; 76: 401-14.
25.

Vanderschueren S, Knockaert DC, Peetermans WE,

Bobbaers HJ. Lack of value of the naproxen test in the

differential diagnosis of prolonged febrile illnesses. Am J Med
2003; 115: 572-5.
Last update: February 9, 2004

23

26.

Knockaert DC, Dujardin KS, Bobbaers HJ. Long-term

follow-up of patients with undiagnosed fever of unknown

origin. Arch Intern Med 1996; 156: 618-20.
27.

Arnow PM, Flaherty JP. Fever of unknown origin. Lancet

1997; 350: 575-80.

Last update: February 9, 2004