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January 23, 2013

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Fever of unknown origin

Fever of unknown origin in children: a systematic review

Amy Chow, Joan L Robinson

Edmonton, Alberta, Canada

Background: There are no previous systematic reviews Key words: collagen vascular disease;

of published pediatric case series describing the etiology of fever of unknown origin;

fever of unknown origin (FUO). The purpose of collecting infection;

these data is to determine the etiologies for children with malignancy

FUO in both developing and developed countries.

Methods: The database Ovid Medline R (1950 to

Systematic review

Introduction

F

August 2009 week 4) and Ovid Embase (1980 to 2010 week

2) were used to conduct the search. Studies in any language ever of unknown origin (FUO) was firstly

were included if they provided the diagnosis in a series of 10 described in 1961 and defined as well-documented

or more children with FUO. The diagnosis of each child at fever of at least 3 weeks duration with no apparent

the time of publication of the study was recorded. source after 1 week of investigations. [1] I t is now

generally accepted that unexplained fever that persists

Results: There were 18 studies that met the inclusion

criteria, describing 1638 children. The diagnosis at the longer than 1 week in a child warrants preliminary

time of publication was malignancy for 93 children (6%), investigations as fever from viral infections generally

collagen vascular disease for 150 (9%), miscellaneous resolves within that time frame. Therefore, most recent

non-infectious conditions for 179 (11%), infection for 832 case series of pediatric FUO require persistence of

(51%), and no diagnosis for 384 (23%). There were 491 fever for only 1 or 2 weeks with negative preliminary

bacterial infections (59% of all infections) with common

investigations, and the investigations required varied by

diagnoses being brucellosis, tuberculosis, and typhoid

study.

fever in developing countries, osteomyelitis, tuberculosis,

This study summarized the literatures on pediatric

and Bartonellosis in developed countries, and urinary

FUO to determine the relative incidence of different

tract infections in both. For children with no diagnosis

etiologies, expecting that etiology will vary by

after investigations, most had fever that ultimately

geographical location related to the economy of the

resolved with no sequelae.

region, the presence of vectors of infection, and the

Conclusions: About half of FUOs in published case

availability of diagnostic tests.

series are ultimately shown to be due to infections with

collagen vascular disease and malignancy also being

common diagnoses. However, there is such a wide variety

Methods

of possibilities that investigations should primarily be

driven by the clinical story. Search methods for identification of studies

The database Ovid Medline R (1950 to August 2009

World J Pediatr 2011;7(1):5-10

week 4) and Ovid Embase (1980 to 2010 week 2) were

used to conduct the search. Key words and phrases used

to refine the search included "fever of unknown origin"

and "pyrexia of unknown origin", limited to children

0 to 18 years. The search was then further limited to

include clinical trials, meta-analysis, epidemiologic

studies, evaluation studies, validation studies, review

Author Affiliations: Department of Pediatrics and Stollery Children's

articles, retrospective and prospective studies. All

Hospital, University of Alberta, Edmonton, Alberta, Canada (Chow A,

Robinson JL)

abstracts were then reviewed.

Corresponding Author: Joan L Robinson, MD, FRCPC Room 8213,

Aberhart Centre One, 11402 University Avenue, Edmonton, AB Canada

Study characteristics

T6G 2J3 (Tel: 780-***-****; Fax: 780-***-****; Email: abqezq@r.postjobfree.com)

Studies were included if they provided the diagnosis

doi:10.1007/s12519-011-0240-5

in a series of 10 or more inpatients or outpatients of

Children's Hospital, Zhejiang University School of Medicine, China and

less than 18 years of age evaluated for FUO persisting

Springer-Verlag Berlin Heidelberg 2011. All rights reserved.

World J Pediatr, Vol 7 No 1 . February 15, 2011 . www.wjpch.com 5

World Journal of Pediatrics

for a minimum of one week duration. Because one had recurrent intussusception that may be due to the

initial fever.[6]

of the goals of the study was to look at the incidence

in different geographic areas, no language restriction The 18 included studies published from 1968 to

was applied. Studies were excluded if they included 2008 consisted of 8 studies (all more than a decade

only acute FUO (fever for less than one week) or old) from only 3 developed countries (Germany, USA

focused only on long-term follow-up of children with and Spain) and 10 studies from developing countries

(Table 1). [8-25] T he number of children in each case

unexplained FUO.

series varied from 10 to 221 (median 89.5) for a total of

1638 children (770 males; 628 females; 240 unknown).

Data extraction

Definitions of FUO varied widely. The values for the

Data were recorded on the demographics and diagnosis

definition of fever varied from minimum 37.5 degrees

at the time of publication for enrolled children. The data

Celsius to minimum 38.9 degrees Celsius. The duration

were separated for studies from advanced economies

of fever ranged from 1 week to 3 weeks with the

(developed countries) versus emerging or developing

Systematic review

majority of the papers requiring a minimum of 2 to 3

economies (developing countries) using International

weeks duration. In terms of the site of investigation,

Monetary Fund classification from 2008 (Imf-

1316 children were inpatients during at least part of

advanced-un-least-developed-2008.svg).

their investigation, 209 were outpatients and for 113 it

was not specified.

Data analysis

The total number of patients with a diagnosis of

This was purely a descriptive study so it was not possible

malignancy was 93 (6%), of which 41 had leukemia,

to report study quality or risk of bias. The etiologies

16 had lymphoma, 23 had other types of malignancy

of fever were classified into the following groups: a)

i n c l u d i n g n e u r o b l a s t o m a, Wi l m s t u m o u r, a n d

infectious diseases, b) malignancy, c) collagen vascular

myeolodysplastic syndrome, and 13 had an unspecified

disease (CVD), d) miscellaneous diseases including

malignancy. The number of patients with a diagnosis of

hemophagocytic lymphohistiocytosis, inflammatory

collagen vascular disease was 150 (9%), of which 90

bowel disease, and any other conditions with a proven

had juvenile idiopathic arthritis, 22 had systemic lupus

etiology, and e) no etiology established at the time of

erythematosis, 27 had some other forms of CVD and 11

publication. Infectious diseases where classified as

patients had an unspecified type of CVD. One hundred

bacterial, fungal, parasitic, or as infectious syndromes

and seventy-nine patients had a miscellaneous non-

with no specified pathogen.

infectious etiology for their fever (11%) (Table 2) with

nonspecified autoimmune disease and inflammatory

bowel disease predominating in developing countries and

Results Kawasaki disease in developed countries.

The search revealed 643 abstracts of which 18 studies Infection was by far the most commonly identified

met the inclusion criteria (13 in English, 2 in French, etiology of FUO in all studies. In total, 832 patients

2 in Spanish and 1 in Polish). Six other studies were (51%) had a final diagnosis of infection with bacterial

excluded as they included children up to 21 years of i nfections followed by infectious syndromes being

age, [1] the duration of fever was less than 1 week in the most common etiologies. There were 491

some children,[2,3] there were less than 10 patients in bacterial infections (59% of all infections) with

the study,[4] or the study was limited to children with common diagnoses of brucellosis, tuberculosis, and

unexplained FUO following a full evaluation. [5,6] typhoid fever in developing countries, osteomyelitis,

Only the latter two studies provided data on a long- tuberculosis, and Bartonellosis in developed countries,

term follow-up of children with FUO. One study and urinary tract infections in both (Table 3). There

looked at children referred to a rheumatology clinic were 58 patients with viral infections (7% of all

with a mean follow-up of 5 years: 32 of 37 children infections) with Epstein-Barr virus (EBV) accounting

had resolution of their fever with no diagnosis, 3 for over half of cases. Another 193 patients (23%

had persistent periodic fever, and 2 had a diagnosis of those with infections) had infectious syndromes

of Crohn's disease. [7] A nother study from Chicago associated with pneumonia accounting for fully one-

reported follow-up of 19 children for a mean of 3.5 quarter of these in developing countries. Fungal

years after assessment: 16 had resolution of their infection was diagnosed in only 3 of the 832 patients,

fever with no established etiology, 2 were eventually but 86 had parasitic infections (10%), predominantly

diagnosed with juvenile idiopathic arthritis, and 1 leishmaniasis in developing countries.

World J Pediatr, Vol 7 No 1 . February 15, 2011 . www.wjpch.com

6

Fever of unknown origin

Table 1. Case series of fever of unknown etiology in children, divided into developed and developing countries and listed in order of the year of publication

n

Study (country, Definition of fever of unknown origin Malignancy Collagen Miscellaneous Infection No diagnosis

year of vascular non-infectious at time of

publication) diseases diagnosis publication

Developed countries

[8]

Fever >39 C, WBC 15 103/ L, duration of fever

Germany 1998 30 0 5 (17%) 5 (17%) 15 (50%) 5 (17%)

minimum 2 weeks and with minimum 1 week of

inpatient evaluation

[9]

USA 1998 Documented daily fever 38 C for at least 14 days 146 4 (3%) 0 16 (11%) 64 (44%) 62 (42%)

without diagnostic signs or symtoms

[10]

Spain 1994 Fever >1 week with rectal temperatures >38.5 C 32 1 (3%) 7 (22%) 0 23 (72%) 1 (3%)

[11]

USA 1991 Fever 38 C at least twice a week for 3 weeks with 109 2 (2%) 8 (7%) 4 (4%) 22 (20%) 73 (67%)

a normal urinalysis and chest X-ray

[12]

Spain 1978 Rectal temperature >38.9 C on multiple occasions for 79 10 (13%) 7 (9%) 3 (4%) 52 (66%) 7 (9%)

minimum 3 weeks outpatient evaluation or minimum

1 week of inpatient evaluation

[13]

USA 1977 Fever >38.3 C with unknown souce after 3 weeks evaluation 54 7 (13%) 8 (15%) 11 (20%) 18 (33%) 10 (19%)

Systematic review

as an oupatient or 1 week inpatient evaluation

[14]

USA 1975 Rectal temperature >38.5 C on >4 occasions for at 100 6 (6%) 16 (16%) 14 (14%) 52 (52%) 12 (12%)

least a 2 week period

[15]

USA 1972 Rectal temperature >38.9 C for a minimum of 3 99 8 (8%) 11 (11%) 19 (19%) 29 (29%) 32 (32%)

weeks outpatient evaluation or minimum 1 week of

inpatient evaluation

Total developed 649 38 (6%) 62 (10%) 72 (11%) 275 (42%) 202 (31%)

countries

Developing countries

[16]

India 2008 Fever >2 weeks with unknown source after history, 49 6 (12%) 1 (2%) 2 (4%) 34 (69%) 6 (12%)

physical exam, and screening lab tests

[17]

Poland 2007 Rectal temperature >38.3 C for duration of 3 weeks 10 0 0 5 (50%) 5 (10%) 0

with no source on initial investigation

[18]

Tunisia 2006 Fever >17 days for kids between 2 and 15 yrs 110 3 (3%) 8 (7%) 9 (8%) 64 (58%) 26 (24%)

[19]

Serbia 2006 Fever >3 weeks with temperature >38.3 C & no 185 12 (6%) 24 (12%) 25 (14%) 70 (38%) 54 (29%)

diagnostic signs or symptoms

[20]

Georgia 2006 Fever >38 C for at least 3 days per week, lasting 52 2 (4%) 2 (4%) 1 (2%) 40 (77%) 7 (13%)

for more than 3 weeks and failure to diagnoze using

complete blood count, urinalysis and chest X-ray

[21]

Tunisia 2004 Fever for 2 weeks with unknown source 67 2 (3%) 14 (21%) 0 38 (57%) 13 (19%)

[22]

Turkey 2003 Fever >37.5 C for greater than 2 weeks with an 80 2 (3%) 5 (6%) 16 (20%) 47 (59%) 10 (13%)

unknown source

[23]

Turkey 2003 Fever >38.3 C for minimum of 3 weeks after 1 week 102 12 (12%) 7 (7%) 26 (25%) 45 (44%) 12 (12%)

intensive investigation

[24]

Argentina 1994 Fever 38.3 C for at least 3 weeks including 1 week 113 11 (10%) 16 (14%) 23 (20%) 41 (36%) 22 (19%)

of intensive investigation

[25]

Kuwait 1990 Rectal temperature 38.3 for a minimum 2 weeks as 221 5 (2%) 11 (5%) 0 173 (78%) 32 (14%)

an outpatient or >1 week investigation as an inpatient

Total developing 989 55 (6%) 88 (9%) 107 (11%) 557 (56%) 182 (18%)

countries

Total all countries 1638 93 (6%) 150 (9%) 179 (11%) 832 (51%) 384 (23%)

In total, 384 patients had FUO with no diagnosis at

Table 2. Miscellaneous diagnoses in children with fever of unknown origin

the time of publication (23%). Resolution of fever by

Developed Developing

Miscellaneous diagnosis

the time of publication in the absence of a diagnosis was

countries* countries

reported in 190 of these 384 patients (49%). Another 25

Autoimmune, non-specified 11 0

Drug-induced 7 1

patients had persisting fever, while the outcome was not

Toxins 2 0

reported for the remaining 169 patients.

Inflammatory bowel disease 12 6

Other than differences in the types of infections

Kawasaki disease 0 27

Factitious fever 2 9

as outlined above, the distribution of etiologies was

Hemophagocytic syndrome 0 10

similar in developed versus developing countries.

Immunodeficiency 1 9

Familial mediterranean fever 0 10

Others 37 35

Total 72 107

Discussion

*: USA, Germany, and Spain; : Tunisia, India, Turkey, Poland,

In the published case series, just over half of cases

Argentina, Serbia, Georgia, and Kuwait.

World J Pediatr, Vol 7 No 1 . February 15, 2011 . www.wjpch.com 7

World Journal of Pediatrics

of cases never have an established diagnosis, and it

Table 3. Infectious etiologies identified in children with fever of

unknown origin

appears the majority of these children eventually have

Developed* Developing resolution of the fever.

Infectious etiologies Total

countries

countries

When comparing data between developed and

Bacterial infections

developing nations, infection is consistently the most

Brucellosis 7 97 104

common cause of FUO but the types of infections

Urinary tract infection 21 40 61

Tuberculosis 22 39 61 vary. With regards to bacterial infections, Bartonella

Typhoid fever 7 47 54

infections were more commonly diagnosed in

Abscess 3 33 36

developed countries while brucellosis, typhoid fever,

Septicemia 9 23 32

tuberculosis, rickettsial infections, and abscesses

Osteomyelitis 25 4 29

Endocarditis 6 14 20 were more common in the developing nations. Viral

Pyelonephritis 11 8 19

etiologies for FUO were more commonly identified

Bartonellosis 10 5 15

in the developed countries, particularly EBV. When

Rickettsiae 0 12 12

looking at infectious syndromes, pneumonia was far

Systematic review

Mycoplasma 0 4 4

Lyme disease 2 0 2 more common in developing nations, presumably

Others 30 12 42

as diagnosis can be delayed because of poor access

Total bacterial 153 338 491

to oximetry or a chest radiography. Some of the

Viral Infections

differences are undoubtedly related to a higher

EBV 31 7 38

Enterovirus 4 0 4 incidence of infections such as tuberculosis or parasitic

CMV 4 3 7

disease in developing countries but other differences

HIV 1 2 3

may relate more to the availability of diagnostic tests.

HSV 1 2 3

The main limitation of the current study is that the

Hepatitis 1 2 3

published case series of FUO over the decades may not

Total viral 42 16 58

Infectious syndromes

be representative of FUO in general in 2010. There is no

Pneumonia 16 32 48

reliable way to judge the quality of the heterogeneous

Respiratory non-specified 6 32 38

descriptive studies included in this review. The data

Viral syndromes non-specified 17 12 29

are biased by inclusion of only limited geographic

Infectious mononucleosis 5 18 23

Meningitis 9 9 18 areas in the 18 studies with only one study from each

Sinusitis 7 3 10

of Asia, Africa, and South America. It is difficult to

Encephalitis 2 0 2

know if this is because clinicians from these continents

Others 9 16 25

did not submit manuscripts or because of publication

Total infectious syndromes 71 122 193

Fungal infections bias favoring studies from North America and Europe.

Blastomycosis 1 0 1

Some conditions such as Kawasaki disease were not yet

Histoplasmosis 1 0 1

recognized when the earliest studies were conducted

Fungal non-specified 0 1 1

while criteria for other diagnoses and the sensitivity

Total fungal 2 1 3

Parasitic infections of diagnostic tests changed over time. The incidence

Leishmaniasis 5 61 66

of vaccine-preventable diseases will have decreased

Malaria 1 10 11

in some countries. Many of the cases classified as

Infected hydatid cysts 1 6 7

" autoimmune" in older studies were likely CVDs.

Toxoplasmosis 0 2 2

Total parasitic 7 79 86 Furthermore, the definition of FUO varied widely in

Unknown infections 0 1 1

the studies, and even were it uniform, the etiology of

Total infections 275 557 832

FUO for minimum one week likely differs from that of

*: USA, Germany, and Spain; : Tunisia, India, Turkey, Poland,

FUO for minimum three weeks. It is disappointing that

Argentina, Serbia, Georgia, and Kuwait. EBV: Epstein-Barr virus;

long-term outcome data are not available for the large

CMV: cytomegalovirus; HIV: human immunodeficiency virus; HSV:

herpes simplex virus.

number of children who had no diagnosis established

for their FUO. This review did not look specifically at

nonclassic FUO (nosocomial, human immunodeficiency

if FUO in children are eventually proven to be from v irus related, or FUO in the immunocompromised

infectious diseases. The majority of these infections are host).[26]

bacterial in origin. A wide variety of malignancies and A recent study from Greece demonstrated that

CVDs account for 6% and 9% of cases respectively, over 85% of adults with FUO had infection if they had

while a broad range of miscellaneous non-infectious two of the following: 1) serum ferritin

diagnoses comprise 11% of cases. About one-quarter eosinophils 60

World J Pediatr, Vol 7 No 1 . February 15, 2011 . www.wjpch.com

8

Fever of unknown origin

mg/L. [27] T here is a great need for large prospective Disclaimers: T his study was presented as a poster at the

Association of Medical Microbiology and Infectious Disease

pediatric studies in developed and developing countries,

Canada Annual Meeting in Edmonton, Alberta Canada May 6-8,

ideally validating this simple predictive scheme and

2010.

testing an algorithm for management.

Based on the current study, limited investigations

should be performed routinely in previously well

References

children with FUO since the differential diagnosis

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

is so extensive. Early diagnosis of malignancy can

on 100 cases. Medicine (Baltimore) 1961;40:1-30.

improve the prognosis so a complete blood count

2 Feigin RD, Shearer WT. Fever of unknown origin in children.

and differention would appear to be indicated. Blood Curr Probl Pediatr 1976;6:3-64.

cultures would be most useful in children with 3 Brewis EG. Undiagnosed fever. Br Med J 1965;9:107-110.

FUO in developing countries to rule out typhoid 4 Chien CH, Lee CY, Huang LM. Prolonged fever in children.

fever, brucellosis or "septicemia" but should also be Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1996;37:31-

performed in developed countries to rule out serious 38.

Systematic review

5 Dechovitz AB, Moffet HL. Classification of acute febrile

treatable infections such as infective endocarditis. If

illnesses in childhood. Clin Pediatr (Phila) 1968;7:649-653.

available, serology for EBV should also be considered

6 Talano JA, Katz BZ. Long-term follow-up of children with

with the initial work-up as EBV is the most common fever of unknown origin. Clin Pediatr (Phila) 2000;39:715-717.

viral etiology of FUO. Furthermore, most laboratories 7 Miller LC, Sisson BA, Tucker LB, Schaller JG. Prolonged

save serology samples for months, which may prove fevers of unknown origin in children: patterns of presentation

useful if acute and convalescent serologies are later and outcome. J Pediatr 1996;129:419-423.

8 Gratz S, Behr TM, Herrmann A, Meller J, Conrad M, Zappel

deemed to be useful for another infection. Based on

H, et al. Immunoscintigraphy (BW 250/183) in neonates and

the relatively high incidence of urinary tract infections

infants with fever of unknown origin. Nucl Med Commun

and pneumonia in all settings, all patients should have 1998;19:1037-1045.

a urine culture and a chest radiograph performed. A 9 Jacobs RF, Schutze GE. Bartonella henselae as a cause of

tuberculosis skin test should be ordered if the patient prolonged fever and fever of unknown origin in children. Clin

has any tuberculosis risk factors. Other investigations Infect Dis 1998;26:80-84.

for infections such as leishmaniasis should be 10 Rico Mari E, Andreu Alapont E, Guillamon T, Calvo Penades

I, Sanchez Lorente A. Fever of unknown origin in children:

considered in endemic regions. Other tests suggested

results of a diagnostic protocol. An Esp Pediatr 1994;41:155-

for the initial assessment in a 2001 review include

158.

serum protein electrophoresis, blood film examination, 11 Steele RW, Jones SM, Lowe BA, Glasier CM. Usefulness of

e rythrocyte sedimentation rate, rheumatoid factor, scanning procedures for diagnosis of fever of unknown origin

antinuclear antibodies, and antistreptolysin O in children. J Pediatr 1991;119:526-530.

antibodies followed by bone marrow examination if 12 Cruz Guerrero G, Navarro Gonz lez J, Cintado Bueno C. Fever

no diagnosis had been made. [28] A 2 010 review also of unknown origin in children. An Esp Pediatr 1978;11:683-

692.

suggested a comprehensive metabolic profile including

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

uric acid and lactate dehydrogenase and quantitative

record of experiences with 54 childhood patients. Clin Pediatr

serum immunoglobulins. [26] I f initial investigations (Phila) 1977;16:768-773.

are not diagnostic but the patient seems relatively well 14 Pizzo PA, Lovejoy FH Jr, Smith DH. Prolonged fever in

when afebrile, it would be logical to follow the patient children: review of 100 cases. Pediatrics 1975;55:468-473.

closely and order further investigations as indicated 15 McClung HJ. Prolonged fever of unknown origin in children.

Am J Dis Child 1972;124:544-550.

by new signs or symptoms. Given the wide variety

16 Joshi N, Rajeshwari K, Dubey AP, Singh T, Kaur R. Clinical

of possible etiologies, empiric antibiotics should be

spectrum of fever of unknown origin among Indian children.

avoided unless there is a high index of suspicion for an Ann Trop Paediatr 2008;28:261-266.

untreated serious bacterial infection. 17 Iwanczak B, Pytrus T, Stawarski A, Mowszet K, Iwanczak F.

Management of fever without source in children. Przegl Lek

2007;64(Suppl 3):20-24.

18 Chemli J, Bouafsoun C, Boussetta S, Dalhoumi A, Harbi

Funding: No funding was received for this study.

A. Prolonged fever in children: about 110 cases. Journal de

Ethical approval: Not required.

Pediatrie et de Puericulture 2006;19:297-303.

Competing interest: T he authors have no conflict of interest

19 Pasic S, Minic A, Djuric P, Micic D, Kuzmanovic M,

related to publication of this study.

Contributors: Robinson J suggested doing the study. Both authors Sarjanovic L, et al. Fever of unknown origin in 185 paediatric

wrote the protocol. Chow A reviewed the literature. Both authors patients: a single-centre experience. Acta Paediatr 2006;95:463-

checked the data from each study and contributed to writing the 466.

manuscript. 20 Bakashvili LZ, Makhviladze MA, Pagava EK, Pagava

World J Pediatr, Vol 7 No 1 . February 15, 2011 . www.wjpch.com 9

World Journal of Pediatrics

KI. Fever of unknown origin in children and adolescents 25 Mouaket AE, el-Ghanim MM, Abd-el-Al YK, al-Quod N.

Prolonged unexplained pyrexia: a review of 221 paediatric

in Georgia: a review of 52 patients. Georgian Med News

cases from Kuwait. Infection 1990;18:226-229.

2006;(135):66-69.

26 Tolan RW Jr. Fever of unknown origin: a diagnostic approach

21 Chouchane S, Chouchane CH, Ben Meriem CH, Seket B,

to this vexing problem. Clin Pediatr (Phila) 2010;49:207-213.

Hammami S, Nouri S, et al. Prolonged fever in children.

27 Efstathiou SP, Pefanis AV, Tsiakou AG, Skeva II, Tsioulos DI,

Retrospective study of 67 cases. Arch Pediatr 2004;11:1319-

Achimastos AD, et al. Fever of unknown origin: discrimination

1325.

between infectious and non-infectious causes. Eur J Intern Med

22 Cogulu O, Koturoglu G, Kurugol Z, Ozkinay F, Vardar F,

2010;21:137-143.

Ozkinay C. Evaluation of 80 children with prolonged fever.

28 Akpede GO, Akenzua GI. Management of children with

Pediatr Int 2003;45:564-569.

prolonged fever of unknown origin and difficulties in the

23 Cift i E, Ince E, Do ru U. Pyrexia of unknown origin in

management of fever of unknown origin in children in

c hildren: a review of 102 patients from Turkey. Ann Trop

developing countries. Paediatr Drugs 2001;3:247-262.

Paediatr 2003;23:259-263.

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

Received May 1, 2010

Children with fever of unknown origin in Argentina: an

Accepted after revision July 23, 2010

analysis of 113 cases. Pediatr Infect Dis J 1994;13:260-263.

Systematic review

World J Pediatr, Vol 7 No 1 . February 15, 2011 . www.wjpch.com

10

for FUO persisting

Springer-Verlag Berlin Heidelberg 2011. All rights reserved.



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