Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study.
OBJECTIVE
Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers.


METHODS
A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted.


METHODS
This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011.


RESULTS
The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease.


CONCLUSIONS
The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.
Department of General Medicine, Juntendo University School of Medicine, Japan.
Toshio
T
Naito
Keito
K
Torikai
Masafumi
M
Mizooka
Fujiko
F
Mitsumoto
Kenji
K
Kanazawa
Shiro
S
Ohno
Hiroyuki
H
Morita
Akira
A
Ukimura
Nobuhiko
N
Mishima
Fumio
F
Otsuka
Yoshio
Y
Ohyama
Noriko
N
Nara
Kazunari
K
Murakami
Kouichi
K
Mashiba
Kenichiro
K
Akazawa
Koji
K
Yamamoto
Mika
M
Tanei
Masashi
M
Yamanouchi
Shoichi
S
Senda
Susumu
S
Tazuma
Jun
J
Hayashi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001799:Blood Sedimentation; D001831:Body Temperature; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D003937:Diagnosis, Differential; D005260:Female; D005335:Fever of Unknown Origin / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007239:Infections / Q000150:complications / Q000175:diagnosis*; D007249:Inflammation / Q000150:complications / Q000175:diagnosis*; D007564:Japan; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood; D012189:Retrospective Studies
D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide