This document discusses fever of unknown origin (FUO) in children. It defines FUO as a fever over 38°C that cannot be explained after 3 weeks of outpatient evaluation or 1 week of inpatient evaluation. Potential causes are divided into infectious and non-infectious categories. A thorough history, physical exam, and targeted investigations are important to identify the cause. Based on patient location and immune status, FUO can be further classified as classic, healthcare-associated, immune deficient, or HIV-related FUO. The most common causes vary according to these classifications.

1. FEVER OF
UNKNOWN ORIGIN
- Dr.Apoorva.E
PG,DCMS

2. NORMAL BODY TEMPERATURE
• The hypothalamus is the heat-regulating center of
the body
• The normal body temperature ranges from 37.0
degree C and 37.5 degree C
• Evening temperatures being 0.5 degree C higher
than in the morning.
• Rectal temperature>oral temperature (0.4 degree C)
>axillary temperature (1 degree C)

3. • A rectal temperature with a glass- mercury or
digital-electronic thermometer is considered the
gold standard for taking temperatures
• Liebermeisters rule -The pulse rate rises about 15
beats/min for each degree centigrade rise of fever

4. FEVER
• Fever is a controlled increase in body
temperature above the normal hypothalamic
set point
• A rectal temperature of 38 degree C or more
(100.4 degree F)
• A temperature of 40 degree C or more is
termed as hyperpyrexia

5. PATHOGENESIS OF FEVER

8. PATTERNS OF FEVER
Intermittent fever - Fever that touches the
baseline for a few hours during the day.
• Seen in malaria, acute pyelonephritis, local
boils,furuncles,kala azar,sepsis

9. • Types of intermittent fever :
- Quotidian fever, with a periodicity of 24 hours,
typical of Plasmodium falciparum
- Tertian fever,with a 48 hour periodicity,typical
of Plasmodium vivax or Plasmodium ovale
-Quartan fever,with a 72 hour periodicity,typical
of Plasmodium malariae

11. Remittent fever - Fever that fluctuates by more
than 1.5 degree F but never touches the baseline
in 24 hours
• Seen in infective endocarditis

12. Continuous fever - Fever that never touches the
baseline in 24 hours and fluctuates by less than
1.5 degree F in a day.
• Seen in enteric fever,lobar
pneumonia,brucellosis,typhus.

14. Pel-ebstein fever - Fever lasting for 3-10 days
followed by an afebrile period of 3-10 days
• Seen in hodgkins lymphoma

15. CLASSIFICATION OF FEVER
Fever with focus Fever without focus
Fever
without
localizing
signs
Fever of
unknown
origin
( refers to a rectal
temperature of 38 degree
C or higher as the sole
presenting feature)

16. FEVER OF UNKNOWN ORIGIN
• Children with fever,documented by a health care
provider,for which cause could not be identified
even after 3 weeks of evaluation as an outpatient
or after 1 week of evaluation in the hospital

17. CLASSIFICATION
• 4 categories :
1. Classic FUO
2. Health care associated FUO
3. Immune deficient FUO
4. HIV – related FUO

18. CLASSIC FUO
• Definition: fever of > 38 degree C ,lasted for > 3
wks, >2 visits or 1 wk in hospital
• Patient location : community , clinic or hospital
• Leading causes : cancer , infections , inflammatory
conditions, undiagnosed , habitual hyperthermia
• History emphasis : H/O travel , contacts , animal &
insect exposure , medications , immunization ,
family history , cardiac valve disorder

19. • Examination emphasis : oropharynx , temporal
artery , abdomen , lymph nodes , spleen , joints ,
skin , nails , genitalia , lower limb deep veins .
• Investigation emphasis : Imaging , biopsies ,
erythrocyte sedimentation rate , skin test
• Management : Observation , outpatient
temperature chart , investigations , avoidance of
empirical drug treatment
• Time course of disease : For months

20. HEALTH CARE ASSOCIATED FUO
• Definition : Fever of > 38 degree C ,lasted for > 1
week , not present or incubating on admission
• Patient location : Acute care hospital
• Leading causes : Hospital acquired infections ,
post- operative complications , drug fever
• History emphasis : Operation & procedures ,
devices used , anatomic considerations , drug
treatment

21. • Examination emphasis : Wounds , drains , devices
, sinuses , urine
• Investigation emphasis : Imaging , bacterial
cultures & other microbiological investigations
• Management : Depends upon situation
• Time course of disease : Lasts for weeks .

22. IMMUNE DEFICIENT FUO
• Definition : Fever of > 38 degree C , lasted for
> 1 wk & negative culture after 48 hrs
• Patient location : Hospital or clinic
• Leading causes : Majority are due to
infections but cause has been documented in
only 40-60%
• History emphasis : Stage of chemotherapy ,
drugs administered , underlying
immunosuppressive disorders

23. • Examination emphasis : Skin folds , IV sites ,
lungs, perianal area
• Investigation emphasis : Chest radiograph ,
bacterial cultures
• Management : Antimicrobial treatment
• Time course of disease : Lasts for days .

24. HIV – RELATED FUO
• Definition : Fever of >38 degree C , >3 wks for
outpatients , >1 wk for inpatients & HIV infection
confirmed
• Patient location : Community , clinic or hospital
• Leading causes : HIV (primary infection) , typical
& atypical mycobacteria , CMV , toxoplasmosis ,
cryptococcosis , lymphomas , immune
reconstitution inflammatory syndrome (IRIS)
• History emphasis : drugs,exposures,risk
factors,travel,contacts,stage of hiv infection

25. • Examination emphasis : Mouth , sinuses , skin ,
lymph nodes , eyes , lungs,perianal area.
• Investigation emphasis : Blood & lymphocyte
count , serologic tests , chest X-ray , stool
examination, biopsies of lung , bone marrow &
liver for cultures and cytologic tests , brain
imaging
• Management : Antiviral & antimicrobial
protocols , vaccines , revision of treatment
regimen , good nutrition
• Time course of disease : Lasts for weeks to
months

26. CAUSES OF PUO
•Infectious causes • Non infectious causes
Infectious causes
-> Bacterial –
salmonella,brucellosis,meningococcal,mycoplasma
pneumonia,TB,actinomycosis
-> Sphirochaetal -B burgdorferi ,leptospirosis ,relapsing
fever,syphillis
-> Parasitic-
amoebiasis,giardiasis,toxoplasmosis,babesiosis,malaria
-> Fungal-blastomycosis,histoplasmosis,coccidiodomycosis

27. -> Chlamydial -lym venereum,psittacosis
-> Rickettsial -Q fever,tick borne typhus,rocky
mountain spotted fever
-> Viruses –CMV,HIV,hepatitis
-> Local septic infection -dental abscess,subphrenic
abscess,sinusitis,tonsillitis,hepatic
abscess,bronchiectasis,mastoiditis
-> Local infection without pus formation -
UTI,ulcerative colitis ,diverticulitis,phlebitis,regional
enteritis

28. Non infectious causes
-> Collagen vascular disorders -JRA ,SLE ,behcets
disease,juvenile dermatomyosis
-> Neoplastic -leukaemia ,lymphoma,neuroblastoma,wilms
tumour
-> Metabolic - gout,porphyria
-> Endocrine - thyrotoxicosis ,addisons disease
-> HS reactions - serum sickness
-> Misc - liver cirrhosis ,familial mediterannean fever
,poisoning ,sarcoidosis ,whipples disease ,factitious fever

29. HISTORY
History should be taken from the child or reliable
informant
• AGE
-> 1-5 yrs - common causes are RTI,UTI,diarrhoea and
osteomyelitis
->5-10 yrs-measles,mumps,chicken pox,typhoid
->10yrs- TB, typhoid ,rheumatic fever
• GENDER -> Females-urinary tract infections,pelvic
infections
-> Males-allergic fever(hay fever), typhoid ,
tuberculosis,malaria

30. • ADDRESS -> endemic regions for malaria and
japanese encephalitis,epidemics,out breaks in
that area
• CHIEF COMPLAINTS -> History of fever and
other symptoms should be taken in
chronological order,give clue towards system
involved
eg:-
fever,dysuria ,loin pain –UTI
fever ,drowsiness ,convulsions - meningitis,
encephalitis

31. HOPI
• ONSET

32. • GRADE

33. • DURATION
fever

34. • PROGRESSION -> Viral fever peaks in 2 days and declines
-> Bacterial fever worsens day by day without treatment
-> Parasite fever like malaria shows cyclical cold,hot and
sweating stages.
• TYPE -> Continuous-Pneumonia ,uti
-> Remittent-Viral, collagen vascular diseases
-> Intermittent - Malaria , Brucellosis
-> Step ladder fever-Typhoid.
• Associated with ->
Chills and rigors- Malaria,brucellosis ,otitis media
Myalgia- brucellosis,dengue,bartonellosis
Sweating-Meningitis , TB ,Bacteraemia ,Malaria

35. • History of travel to endemic areas,how long,any
precautions.
• Epidemics in resident area
• Pets - toxoplasmosis,visceral larva migrans
• Contact with animals – leptospirosis,brucellosis
• Tick bites-relapsing fever, Q fever
• Blood transfusion - malaria,hepatitis-B
• Migrating joint pains - Rheumatic fever
• Loss of weight-malignancies
• History of recurrent fever,oral thrush -
immunocompromised
• Joint pains,rash,photosensitivity - autoimmune

36. • Past history - of surgeries(occult infection)
• Family history - similar complaints suggest
infectious disease,genetic background-familial
dysautonomia(recurrent hyperpyrexia)
• Personal history - diet -> unpasteurized
milk(brucellosis,TB),raw egg (salmonella)
• Loss of appetite - malignancies ,TB
• Immunization history - vaccination induced
fever. e.g,DPT,measles
• Treatment history - drug induced fever

37. PHYSICAL EXAMINATION
• Careful and complete examination
• Repetitive examination to pick up subtle or new
signs
• Look for the child’s general appearance, built and
nourishment,
for temperature pattern ,
pulse rate –relative bradycardia in typhoid, meningitis
dengue,
Skin – look for rashes , petechiae, splinter
hemorrhages, subctaneous nodules

38. Eye
-> Anemia- malaria, kala azar ,ALL , SABE
-> Icterus – infectious hepatitis, malaria, weil’s
disease,liver abscess
-> Proptosis – orbital tumor , thyrotoxicosis, orbital
infection , wegener granulomatosis ,
metastases(neuroblastoma)
-> Roth’s spots – infective endocarditis
-> Uveitis – sarcoidosis, SLE, kawasaki
disease,vasculitis
-> Chorioretinitis – CMV, toxoplasmosis , syphilis

39. Tenderness to tapping over sinus – sinusitis
Oral cavity - Hyperemia of pharynx
Tender tooth –> periapical abscess
Recurrent oral candidiasis –> disorder of immune system
Neck - Enlargment or tenderness of thyroid gland –> thyroiditis
Heart- Murmur –> infective endocarditis
Abdomen –
Splenomegaly –> malaria, kala azar , CML
Abdominal tenderness -> pelvic abccess
Loin tenderness -> pyelonephritis
Hepatomegaly- > liver abscess , primary or metastatic malignancy

40. Muscle and bone –
Point tenderness- occult osteomyelitis or bone
marrow invasion from neoplasms
Painful and swollen joints – arthritis –> rheumatic
fever
Rectal examination – pelvic abscess,adenitis

41. INVESTIGATIONS
• On IP or OP basis,
determined on a case by case basis,
OP if chronic
• CBC,DC
• Urine analysis
• Blood smear
• ESR
• Serologic tests
• Tuberculin test
• Blood and urine culture
• Bone marrow examination( aspiration and biopsy)
• Xray ,2D ECHO,USG,CT , MRI , Radionuclide scans

42. NO INDOLENT
BACTERIAL
INFECTION
SEVERE
BACTERIAL
INFECTION

43. BLOOD SMEAR -> WITH GIEMSA
OR WRIGHT STAIN
MALARIA
TRYPANOSOMIASIS
RELAPSING FEVER
BABESIOSIS

44. ESR >30 mm ->
inflammation -> further
evaluation
ESR >100 mm ->
TB/malignancy/autoimmune/
kawasaki disease

45. • BLOOD CULTURES –
- Normally aerobic culture is done as anaerobic
culture gives low yield
- Repeated culture done in case of infective
endocarditis and osteomyelitis
- Poly microbial infection suggests GI infection.
• RADIOLOGICAL EXAMINATION –
of sinuses,mastoid,GIT,chest
• SEROLOGIC TESTS – widal test,ANA,RF,
for inf mononucleosis,cmv,brucellosis,toxoplasmosis

46. • RADIONUCLEIDE SCANS - These are mainly
helpful in detecting abdominal abscess &
osteomyelitis and in multifocal disease.
• ECHOCARDIOGRAPHY - detects vegetations on
valve leaflets in infective endocarditis
• ULTRASONOGRAPHY detects intra- abdominal
abscesses of liver and spleen
• CT SCAN AND MRI - detection of neoplasms,CT
scan guided aspiration and biopsy,MRI for
detecting osteomyelitis

48. FEVER WITHOUT LOCALIZING SIGNS
• Fever of acute onset,with duration of <1 wk and
without localizing signs is a common diagnostic
dilemma in children < 36 months of age .
• Etiology and evaluation of this type depends
upon age of the child
• 3 age groups are considered :
I. Neonates
II. Infants > 1 month to 3 months of age .
III. Children > 3 months to 3 yrs of age .

51. NEONATES
• Neonates having fever without focus show limited
signs of infection -> difficult to clinically distinguish
between a serious bacterial infection & self limited
viral illness
• Every febrile neonate has to be hospitalized
• 7% risk of having serious bacterial infection
(sepsis,meningitis,UTI,enteritis,osteomyelitis,
pneumonia,septic arthritis)
• Organisms responsible - Group B streptococcus &
Listeria(Late onset sepsis & meningitis) ,
Ecoli,HSV,Enterovirus

52. • Blood ,urine ,CSF should be cultured
• CSF study should include cell counts, glucose,
protein levels,gram stain & culture
• HSV & Enterovirus polymerase chain reaction
• Stool culture,chest radiograph
• Combination antibiotics- ampicillin and
cefotaxime is recommended,
acyclovir if HSV is suspected.

53. 1 MONTH TO 3 MONTHS
• Majority of the cases are of viral origin
• Respiratory syncytial virus and influenza A in
winter season
• Entero virus in summer

54. • Also suspect serious bacterial infections
• Common bacteria : Group B
streptococci,listeria,salmonella
enteritis,ecoli,pneumococus,meningococcus,
hiB,staph aureus
• Common conditions : Pyelonephritis > Otitis media
> Pneumonia > Skin and soft tissue infections
• Based on blood ,urine ,CSF cultures,these infants
are classified in to low and high risk groups

57. •With out
antibiotics
under close
observation
• Empirical
antibiotic
therapy
• Ampicillin plus
either ceftriaxone/
cefotaxime
• If CSF shows
abnormal findings,
vancomycin
included against
penicillin resistant
S.Pneumoniae
LOW RISK HIGH RISK

58. 3 MONTHS TO 36 MONTHS
• 30% of these infants with fever have no
localizing signs of infection
• Majority are viral but serious bacterial
infection do occur
• Pathogens are same as in 1 to 3 months of age
• S.pneumoniae,meningococcus,salmonella,hiB
account for most of occult bacteremia

59. • Risk factors indicating occult bacteremia
1.temperature >39° c
2.WBC count >15000/micro litre
3.elevated ANC,band count
4.elevated CRP
5.elevated ESR
• It may resolve spontaneously without sequelae
or can lead to localized infections like meningitis,
pneumonia etc

60. • Management :
Child 3-36 mo and temperature
38-39 ° C
Reassurance that diagnosis is
likely self-limiting viral
infection, but advise return if
fever persists,temperatures >
39 ° C and
new signs / symptoms
Child 3-36 mo and temperature
> 39 ° C
-Hospitalization and prompt
antimicrobial therapy based on
the blood, urine ,CSF cultures
• Immunize against Hib and S.pneumoniae with
conjugate vaccine

61. THANK YOU