Fever in Children and FUO

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


Natural history of diseases


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9/2/2014


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


* 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


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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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

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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

Documents

Fever in Children and FUO