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8/11/2019 Fever in Children and FUO
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Lecture Lecture FKUI 2012
Fever in Children
Sri Rezeki S Hadinegoro
Dept of Child Health
Faculty of Medicine, University of Indonesia
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Fever Normal body temperature
Definition of fever
Pathogenesis & pathophysiology of fever
Pattern of fever
Fever in the clinical setting
Treatment
Fever of unknown sources/ fever ofunknown origin (FUO)
Topics
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Normal body temperature reached highest levelin early evening (5-7 p.m)
Young children: relatively high rectal temperature
predominate Diurnal temperature
children have more fluctuated than adult
Gradually decreased towards adult levels beginning
at 2 years of age, trend stabilizes soon after puberty
Normal Body Temperature
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Diurnal pattern of body temperature
Diurnal temperature in children more fluctuated
than in adults
N
ormalbodytemperature
36.2-37.5
oC
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Location ThermometerNormal
temperatureRange, mean (oC)
Fever (oC)
Axilla Mercury, electronic 34.7 37.3; 36.4 37.4
Sublingual Mercury, electronic 35.5
37.5; 36.6 37,6Rectal Mercury, electronic 36.6 37.9; 37.0 38.0
Ear Infra red emission 35.7 37.5; 36.6 37.6
Measurement of body temperature
Recommendation site of measurementAge < 4 weeks: electronic thermometer axilla
Age >4 weeks to 5 years: electronic thermometer axilla,
mercury thermometer axilla, infrared tympanic thermometer
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Fever is increased body temperature of 10Cor greater above mean temperature
Clinical setting
Rectal temperature > 38.00C
Oral temperature > 37.60
C Axillary temperature > 37.40C
Tympanic membrane > 37.60C
Definition
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En
dogenpyrog
en,cytokine
Febrile response ismediated byendogenouspyrogens (EP,
cytokines) inresponse toinvadingexogenouspyrogens,
primarilymicroorganisms ortheir product(toxins)
Hypothal
amuscentre
Endogenouspyrogen acts onthermosensitiveneurons in
hypothalamus,which upgradethe set point viaprostaglandins
Setpoint,prostaglandin
Body reacts byincreasing theheat productionand decreasing
the heat loss untilthe bodytemperaturereaches thiselevated set point
Pathogenesis of Fever
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Most common cause of fever in children
Fever
Hypersensitivity
reaction
Auto
immune
diseases
Malignancy
Infection
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Mechanisms of Fever Production
Cytokine
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Cytokines play a pivotal role in theimmune response by activation of the B
cells and T cell lymphocytes
Production of fever is strongly evidence asa defence body mechanism
Fever become harmfull or fatal byoverproduction of cytokines or imbalance
between cytokine & their inhibitors(severe infection and septic shock)
Pathogenesis of Fever
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Fever is an interleukin-1 (IL-1) mediatedelevation of the thermoregulatory set
point of the hypothalamic centre
In response to an upward displacementof the set points, an active process
occurs in order to reach the new setpoint
Minimizing heat loss withvasoconstriction and shivering
Pathophysiology of Fever
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The regulation of body temperature
in the hypothalamic center
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Behavioral means of raising body temperature
a warmer environment,
adding more clothing,
curling up in bed,
drinking warm liquids.
Fever is not dangerous
Fever is a body defence mechanism
Morbidity & mortality due to underlying disease
Fever does not damage the central nervous system
Fever controlled by a hypothalamic centre
Pathophysiology of Fever
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Characterized bydiscomfort
Result ofdecreased heat loss
throughvasoconstriction &
increased heatproduction through
shivering
Child feels cool,skin feels cold to
the touch
New level ofthermoregulatoy set
point
Balance heatproduction & heat loss,
at a higherhypothalamic set point
Flushed or pink faceappearance signifies
that fever has peaked
Child feels comfortwithout shivering
Occur either bylysis (falling
gradulally within 2-3 days to a normal
level) or crisis(falling within a
few hours tonormal level)
Phase of temperature
raise
Phase of temperature
stabilization (fastigium)
Phase of falling
temperature or
defervescence
Phase of Fever
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Pattern Diseases
Continuous Typhoid fever, malignant malaria falciparum
Remittent Most viral or bacterial diseases
Intermittent Malaria, lymphoma, endocarditis
Septic or hectic Kawasaki disease, pyogenic infection
Quotidian Malaria (P.vivax)
Double quotidian Juvenile rheumatoid arthritis, some drug fever
(carbamazepine), Kalaazar, gonococcalarthritis
Relapsing/periodic Quartana & tertiana malaria, brucellosis
Recurrent fever Familial Mediterranean fever
Pattern of Fever
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Continuous Fever (sustained fever)Typhoid fever, malignant malaria falciparum
Sustained increased body temperature with maximal
fluctuation 0,40C for 24 hours periode
Diurnal body temperature does not significance appear
Normallevel
37.5
0C
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Remittent FeverMost viral or bacterial diseases
Temperature decreased every day but never reach normal level withfluctuation more than 0.50C per 24 hours
The most frequent fever pattern in pediatric practice, no spesific forcertain diseases
Diurnal variation showed particularly if fever due to infection process
Normallevel
37.5
0C
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Intermitent FeverMalaria, lymphoma, endocarditis
Every day body temperature reached normal level at themorning and highest level at noon
This pattern is the second most frequent found in pediatricpractices
at noon
morning
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Quotidian FeverMalaria (P.vivax)
Body temperature
increased gradually within every four days
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Periodic FeverPattern of Fever in Malaria
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Recurrent fever
Borrelia (louse borne), ticks borne disease
Normal level of body temperature
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Fever with rash (Acute Exanthema)
Measles, Rubeola
Skin rash (maculopapular rash) appeared when body
temperature reached the highest level
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Biphasic FeverDengue fever, poliomyelitis, leptospirosis, yellow fever, Colorado tick fever,
spirillary rat-bite fever, African hemorrhagic fever (Marburg, Ebola, Lassa)
Camelback fever pattern or saddleback feverShowed two fever episodes in one disease
Temperature
0C
Time of fever defervescence
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9/2/2014
Fever with rash (Acute Exanthema)
Natural history of diseases
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9/2/2014
Fever with rash (Acute Exanthema)
Rash distribution
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Exanthemas
9/2/2014
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9/2/2014
Varicella Zoster Infection
Presence of all stages of lesions in one area
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Differential diagnosis Acute Exanthema
Maculopapular eruptions Measles
Rubella
Scarlet fever
Meningococcemia
Toxoplasmosis
Cytomegalovirus infecton
Roseola infantum
Enteroviral infection
Drug eruptions
Miliaria Kawasaki disease
others
9/2/2014
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Differential diagnosis of Acute Exanthema
Papulovesicular eruptions
Varicella-zoster infection
Smallpox
Excema herpeticum
Coxsackie virus infection
Rickettsial pox
Impetigo
Insect bites
Drug eruptions
Molluscum contagiosum
Papular urticaria
others
9/2/2014
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370
C
400C
Complications
Day -15 Day 0 Day 7 Day 21
Incubation
periodAsymtomatic
Invasive phaseIntermitent fever
Headache
Fatique
Abdominal discomfortConstipation
Diarrhoea
Toxic phaseContinuous fever
Bradycardia
Hepatomegaly
SplenomegalyConstipation
Diarrhoea
Rose spot
Convalescence
period
Typhoid Fever, Typhus AbdominalisHistory of illness
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SymptomsChills (rigor), myalgia, headaches, anorexia, excessivesleep, fatigue, thirst, delirium, scanty urine (oliguria)
Signs
Drowsiness, irritability, tachycardia, tachypnoea,increased BP, flushed face, grunting, decrease in GFR1.5 time the basalmetabolic rate (1 degree C = 10% increase of insensible water loss)
Prevent & treated by providing extra fluid to the
Febrile convulsion Mostly has a familial history of febrile convulsion
Genetically hypothalamic center susceptible to high bodytemperature (imbalance of thermoregulator)
Incidence in 6 months to 4 years of ages
Prevent & treated by antipyretic & anticonvulsion drug
Potential Complication (1)
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Hyperpyrexia(by Dubois)
Imbalance between heat production and loss, not controlled centrally
Rectal temp 41.10
C or higher or axillary/tympanic temp >400C
Young infants with hyperpirexia suggested tohave severe infection (serious bacterial
infection)
Potential Complication (2)
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Classification Definition Most frequentetiology
Duration offever
Fever with
localizing signs
Acute febrile illness with
focus infection which could
be diagnosed by anamnesis &
physical examination
Upper respiratory
tract infection
(URTI)
< 1 week
Fever without
localizing signs
Acute febrile illness without
focus infection diagnosed
after anamnesis & physical
examination
Viral infection,
urinary tract
infection (UTI)
< 1 week
Fever of
unknown
origin
Fever occured minimal 3
weeks, no established
diagnosis yet after 1 week
investigation at hospital
Infection, juvenile
idiopathic arthritis
> 1 week
Classification of Fever
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Organ system DiseasesUpper airway infections Viral URTI, otitis media,tonsillitis,
laryngitis, herpetic stomatitis
Pulmonary Bronkhiolitis, pneumonia
Gastrointestinal Gastroenteritis, hepatitis, appendicitis
CNS Meningitis, encephalitis
Exanthems Campak, chicken pox
Collagen Rheumathoid arthritis, Kawasaki disease
Neoplasma Leukemia, lymphoma
Tropics Kala azar, cickle cell anemia
Main causes of
fever due to disease of localized signs
Acute febrile illness with focus of infection, which can be diagnosedafter history & physical examination
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About 20% all febrile episodes demonstrate no localizing signs
Most common cause is a viral infection
Most occuring during the first few years of life
Fever without localizing signs
Serious infections occured in 1% cases:
serious bacteriemic infections (SBIs)Children 3-24 months have the highest incidence (3-4%),
aged 7-12 months demonstrating twice incidenceassociation with high fever >39.50C
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Etiology Causes Diagnostic tools
Infections Bacteremia/sepsis
Most virus (HH-6)
UTI
Malaria
Ill looking, high CRP, leukocytosis
Well appearing, nomal CRP, WBC
Urine dipsticks
In malarial area
FUO Juvenile idiopathicarthritis
Pre-articular, rash, splenomegaly, high
antinuclear factor, CRP
Post vaccination DTwP, measles Time of fever onset in relation to the time
of vaccination
Drug fever Most drug History of drug intake, diagnosis of
exclusion
Usual causes of fever without localized signs
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Fever of Unknown Origin = FUO
(Fever of Unknown Source)
FUO defined when fever without localizingsigns persists for one week during which
evaluation in hospital fails to detect the
cause
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Cause of FUO
Infection 60%-70% Localized infections
Systemic infections
Collagen diseases 20%
Neoplasma 2% Miscellenous 5%-10%
Lack of laboratory facilitiesNo experience to certain cases (rare case)
Not do the history on travel abroad, animal exposure,
prior use antibiotics
Repeated physical examinations are more helpful
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Causes Diseases Reasons of being a case of FUOInfection (60%-70%) Repeated history taking & repeated
physical examination
Localized Sinusitis
Endocarditis
Occult abscess
Sinus radiograph not performed or
negativePreviously unsuspected of having cardiac
defect
Absence of clinical signs
Systemic ViralTB
Kawasaki disease
Fever is the only sign of diseaseExtrapulmonary, tuberculin test negative
Incomplete presentation, diagnosis not
considered
Principles causes of FUO
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Causes Diseases Reasons of being a case of FUO
Collagen
(about 20%)
JIA
SLE
Prearthritis presentation
Atypical manifestation
Neoplasma
(
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Algorithmic approach to FUO
Step 1 Repeated anamnesis, physical examination &
laboratory examination
Evaluation: is there any specific signs & symptoms
Step 2
Option 1: found the specific signs & symptomexamination additional specific lab
Option 2: no any specific signs & symptom repeatedFBC
Evaluation option 1 & 2, go to step 3 Step 3
More comprehensive examination, consultation toother specialist, including invasive procedure
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Anamnesis
Age Age < 6 years: UTI, local infection (abcess, osteomyelitis), JRA
Children > 6 years: TB, collitis, autoimmune disease, neoplasma
Characteristic of fever When, duration, and type of fever Non-specific symptoms (fatique, headache, stomac-ache, chill)
Epidemiological data Animal exposure
Travel aboard
Genetic
Drugs used
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Physical examinations
Detail physical examinations are needed
Special attention to certain part
Heart sound (endocarditis)
Joint, lymph nodes, muscle (myalgia),
Pain of extrimities (SLE)
Icterus (hepatitis)
Skin rash (vascular-collagen disease, Kawasaki disease)
Peritonsillar abscess
Mass intra abdominal
Blood stool
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Greenlow risk Yellow-intermediate Redhigh risk
Colour Normal colour of skin, lips,
tounge
Pallor reported parents Pale, mottled, blue
Activity Respond normal to social
cues, smiles, stay awake or
awakens quiclky
Stronge normal crying
Not responding normal
social cues, wakes with
prolonged stimulation
Decreased activity, no smile
No respond to social cues
Appear ill to health care
professional
Does not wake
Weak, high-piched crying
Respiratory Normal respiratory rate Nasal flaring, tachypnoeaOxygen saturation
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The Yale Observation Scale (YOS)
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The Yale Observation Scale
National Collaborating Centre for Womens and ChildrensHealth: Skor YOS + anamnesis + pemeriksaan fisik: sensitifitas 89%-93%
dan NPV 96%-98%.
Nilai total skor 6 pada kelompok umur 3 bulan-3 tahun, dapat
mendeteksi occult bacteriemia dengan NPV 97,4%.
Pratiwi , Tumbelaka AR. dkk. dalam penelitiannya diDepartemen IKA FKUI/RSCM, RS Fatmawati, dan RSHarapan Kita di Jakarta, 2010 256 kasus demam dengan skor 8 : sensitivitas 69,35%,
spesifisitas 90,2%, PPV 69,35%, NPV 90,2%, rasio kemungkinanpositif 7,08, dan rasio kemungkinan negative 0,34.
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Laboratory examination
Laboratorium examination as a tools forlooking to the cause
An important part to established the
diagnosis Recommend done gradually, not at the
same time for many examinations
Depend on severity of the disease
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Step 1 FBC, blood smear, blood cell morphology
Chest x-ray
Tick blood smear
BSR, CRP
Urine analysis
LCS, other body fluid depend on indication
Blood, urine, stool, nasopharyngeal swab cultureTuberculin test
Liver function test
Laboratory examination
* Note: in serious case, lab procedure should be performed more rapidly
b i i
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Step 2Serological test: Salmonella, toxoplasma, leptospira,
mononucleosis, CMV, histoplasma
Ultrasonography: abdominal, skull
Step 3 Bone marrow puncture
Intravenous pyelography
Paranasal sinus photography
Antinuclear antibody (ANA)
Barium enema examination
Scanning examination
Liver biopsy
Laparatomy diagnostic
Laboratory examination
M f hild d
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Ill-looking or
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Management of child aged 3-36 months
without a focus of infection
Ill-lookingchild
Hospitalizationadministerantibiotic
Not ill-lookingbody temperature
390C
Evaluate for SBIs
Option 1Urine dipstick, CBC, bloodculture, CXR, consider
antibiotic
Option 2Urine, no blood test,
evaluation if the conditionworsen
Option 3CBC, if WBC > 15.000/mm3,
blood culture, considerantibiotic
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ICU
FUO case clinical
setting
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Antipyretic act centrally by lowering thethermoregulatory set point of the hypothatalamic
center
Inhibition of cyclooxygenase, the enzyme responsible
for the conversion of arachidonic acid to prostaglandin
Antipyretic
The main indication for prescribing an antipyretic is notto reduce body temperature but to relieve the childs
discomfort & reduced parents anxiety
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Give rapid result and be effective in reducing fever by
at least 10C
Be available in liquid and suppository form
Have low rate of side effect in theurapeutic doses
Have low incidence of interaction with other
medications and rarely contraindication in pediatric
doses
Be safe
Be cost effective
Characteristic of an ideal antipyretic
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Para-aminophenolsParacetamol
Propionic acid derivates
Ibuprofen
Naproxen
Salicylates
Aspirin
Other NSAIDs
Diclofenac
Endogenous antipyretic
Arganine vasopressin
Physical measures
Bed rest
Tepid sponging
Medications & Physical Measures
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Antipyretic Oral Rectal Intravenous
Paracetamol Tablet500 mg
Liquid120mg/5ml or
250mg/5ml
Suppository60, 125, 500mg
Infusion 10mg
Children10-15 mg/kg at 4-6 hrs or60-75mg/kg per day
Same as oral 15mg/kg
Ibuprofen Tablet500 mg
Liquid
120mg/5ml or250mg/5ml
Suppository60, 125, 500mg
Children5mg/kg at 3-4 hrs, dose 10mg/kb more
potent & has longer lasting fever
suppression than PCT
Same as oral
Doses of antipyretics
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58
Broad or
narrow
spectrum
Bactericidal
or
bacteriostatic
Mono or
combined
Intravenous
or oral
Empiric or
definitive
Choose an
antibiotic
Antibiotic
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Antibiotic
prescription in
bacterial infection
59
Bacterialinfection
Culture(Gram stain)
Pathogen
identificationDefinitive
therapy
Narrowspectrum of
antibiotic
Cured
Empirical therapy
Guess
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Conclusions
FUO defined when fever without localizing signs persistsfor one week during which evaluation in hospital fails todetect the cause
60%-70% cause of FUO is infection
Reasons of being a case of FUOLack of laboratory facilities
No experience to certain cases (rare case)Not do the history on travel abroad, animal exposure,
prior use antibiotics
Repeated physical examinations are more helpful
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Conclusions
Antibiotic only used for bacterial infections
Culture should be done to confirmed the
etiology of infectious disease
Susceptibility test done together with
bacterial culture
Empirical antibiotic therapy should be
confirmed by definitive therapy