http://www.sginf.ch/ssi-home/education/doc-slides/rath-barbara.

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DIFFERENTIAL DIAGNOSIS OF FEVER

Differential

Diagnosis of Fever
Barbara Rath, M.D.
University Childrens Hospital Basel
(UKBB)

Where and how should we measure body

temperature?

What constitutes normal temperature?

What constitutes fever?

What causes fever?

What is Fever of Unknown Origin (FUO)?

Barbara Rath 2007

Barbara Rath 2007

WHERE AND HOW

SHOULD WE MEASURE
BODY TEMPERATURE?

ath 2007
Barbara R

Thermometer (Santorio Sanctorius, 1592)

Thermoscope (Galileo Galilei, 1592):

First instrument to measure temperature
Barbara Rath 2007

Barbara Rath 2007

Barbara Rath 2007

Curved thermometers for sublingual insertion (BMJ 1912;1:1137)

Benjamin Rush (1745-1B8a1rb3a)ra: A
ra
RatM
h 2o
00
7 l Thermometer (1812)

Barbara Rath 2007

VARIATIONS IN SUBLINGUAL
TEMPERATURE BY LOCATION

THE INFRARED AURAL THERMOMETER

D

TM thermometersalthough convenienttend to give highly variable

readings that correlate poorly with simultaneously obtained oral or rectal
readings. Mackowiak P A in: Mandel
G L, Bennett J E, Dolin R (Eds) Principles and
th

Once outstanding issues are addressed, the tympanic site is likely to

become the gold standard for measuring temperature in children. El-Radhi

infrared ear thermometry would fail to diagnose fever in three or four

out of every ten febrile children (with fever38C or above). Dodd S R, et al:

ITT measurements more accurately reflect core temperatures than any

other measurement site during febrile and nonfebrile periods in children.

Our findings suggests that infrared ear thermometry does not show
sufficient agreement with an established method of temperature
measurement to be used in situations where body temperature needs to
be measured with precision. Craig J V, et al: Lancet 2002; 360: 603-609.

Practice of Infectious Diseases, 6 Ed, 2005, pg 704

A S, Barry W: Arch Dis Child 2006; 91: 351-356.

Clin Epidemiol 2006; 59: 354-57

Nimah M M, et al: Pediatr Crit Care Med 2006; 7: 48-55.

Difference max vs min = 0.9C or 1.8F

Barbara Rath 2007

DIFFERENTIAL DIAGNOSIS OF FEVER

Where and how should we measure body

temperature?

What constitutes normal temperature?

What constitutes fever?

What causes fever?

What is Fever of Unknown Origin (FUO)?

Barbara Rath 2007

Barbara Rath 2007

WHAT IS NORMAL BODY TEMPERATURE?

D

35.7C (96.2F)

36.0C (96.8F)

36.5C (97.7F)

37.0C (98.6F)

37.5C (99.5F)

37.7C (99.9F)

Barbara Rath 2007

NORMAL CORE TEMPERATURE

NORMAL BODY TEMPERATURE?

Best site(s) to determine true normal core temperature is:

Carl Rheinhold August Wunderlich: Das Verhalten der Eigenwrme in
Krankenheiten (Leipzig,1868)

Hypothalamic artery

Pulmonary artery

Rectum (5 cm)

Sublingual artery (oral)

Tympanic membrane

D Analyzed ~million observations on ~25,000 adults

D 22 cm long, mercury-in-glass thermometer
D Used axillary site, twice daily, x15-20 minutes
D Temperature oscillates even in health persons according to time

of day by 0.5C = 0.9F

D Women have slightly higher normal temperatures than men and

D Temporal artery
D

Axillary artery

Skin (umbilicus)

often show greater and more sudden changes of temperature

Barbara Rath 2007

Barbara Rath 2007

NORMAL BODY TEMPERATURE?

NORMAL ADULT ORAL TEMPERATURES

37.0C
98.6F

When the organism (man) is in a normal condition,

the general temperature of the body maintains itself
at the physiologic point: 37C = 98.6F

PROBLEM:
D

Tests with one of Wunderlichs thermometers

suggest that his instruments may have been
calibrated higher than todays instruments by as
much as 1.4 to 2.2C.

* Mackowiak P A, Worden G: Clin Inf Dis 1994; 18: 458-67.

NORMAL RECTAL TEMPERATURE

HEALTHY INFANTS & CHILDREN
AGE

* Mean, Median: 98.2F

Mackowiak P A et al: JAMA 1992;

Barbara Rath 2007

268: 1578-80
Barbara Rath 2007

Normal body temperature is a range of

values, affected by:

TEMPERATURE F & C (SD)

Age: Infant > child > adolescent, adult

< 3 MOS

99.5 (0.8)

37.5 (0.4)

Sex: females > males (mean: 0.2C, 0.3F)

3 MOS

99.4 (0.8)

37.4 (0.4)

Race: Black > Caucasian (mean: 0.1C, 0.1F)

6 MOS

99.5 (0.6)

37.5 (0.3)

Time of day: afternoon > early morning

1 YEAR

99.7 (0.5)

37.6 (0.2)

Level of Activity: post-exercise > resting

3 YEARS

99.0 (0.5)

37.2 (0.2)

Meals: hot > cold; chewing, smoking

5 YEARS

98.6 (0.5)

37.0 (0.2)

Ambient temperature

7 YEARS

98.3 (0.5)

36.8 (0.2)

Placement within site of measurement

9 YEARS

98.1 (0.5)

36.7 (0.2)

Duration of measurement (Hg thermometers)

11 YEARS

98.0 (0.5)

36.7 (0.2)

Nature & calibration of device used

13 YEARS

97.8 (0.5)

36.5 (0.2)

Watson E H: Growth and Development of Children (1978); Herzog L W, Coyne L J: Clin Pediatr 1993; 32:
Barbara Rath 2007

Barbara Rath 2007

SITE

MEAN

RANGE

C
F
C
NORMAL TEMPERATURES
vs SITE

AXILLARY

36.4 97.5

34.7 37.3

SUBLINQUAL

36.6 97.9

35.5 37.5

RECTAL

37.0 98.6

36.6 37.9

TYPICAL DAILY TEMPERATURE FLUCTUATION (PO, ADOLESCENT)

El-Radhi A S, Barry W: Arch Dis Child 2006; 91: 351-356
Richardson G S, et al: Sleep 1982; 5 (SBuaprbpa2
ra):R
Sa8th2 2007

Barbara Rath 2007

DIFFERENTIAL DIAGNOSIS OF FEVER

Where and how should we measure body temperature?

What constitutes normal temperature?

What constitutes fever?

What causes fever?

What is Fever of Unknown Origin (FUO)?

Sund-Levander M, Forsberg C, Wahren LK. Normal oral, rectal, tympanic and

axillary body temperature in adult men and women:
a systematic literature review. Scand J Caring Sci 2002;16(2):122-8.
Barbara Rath 2007

HISTORY OF FEVER
Sumerian (2500 BC): inflammation
or hot thing meaning fever

Barbara Rath 2007

HISTORY OF FEVER
Sumerian (2500 BC): inflammation
or hot thing meaning fever

Egyptian (1700 BC): fever

Egyptian (1700 BC): fever

Chinese (2nd Century): hot disease

Chinese (2nd Century): hot disease

Barbara Rath 2007

Barbara Rath 2007

WHAT IS FEVER?
PHYSIOLOGIC DEFINITION

A state of elevated core temperature which is often,

but not necessarily, part of the defensive responses of
multicellular organisms (host) to the invasion of live
(microorganisms) or inanimate matter recognized as
pathogenic or alien

WHAT IS FEVER?
CLINICAL DEFINITION

A pyrogen-mediated rise in body temperature above the

normal range

- IUPS Commission for Thermal Physiology (2001)

Barbara Rath 2007

Barbara Rath 2007

WHAT IS NOT FEVER?

HYPERTHERMIA

WHAT TEMPERATURE = FEVER?

A failure of thermoregulatory homeostasis due to

uncontrolled heat production1, inadequate heat
dissipation2, or defective thermoregulation3 leading to
an unregulated rise in body temperature in which
pyrogenic cytokines are not directly involved and
against which standard antipyretics are generally
ineffective.

37C (98.6F)

37.7C (100F)

38C (100.4F)

38.3C (101F)

39.1C (102.4F)

1. Malignant hyperthermia, exercise, endocrine, drug (e.g. thyroxine)

2. Neonates, bundling, heat stroke, drug (e.g. atropine)
3. Neonates, CNS damage
Barbara Rath 2007

Barbara Rath 2007

WHAT TEMPERATURE = FEVER?

PEDIATRIC LITERATURE

What do
Pediatric and
ER Residents
Think ?

Rudolphs Pediatrics
D

Textbook of Pediatric Emergency Medicine

D

Survey: 132 Pediatric Programs, 38 Emergency Medicine Programs

Baraff L J: Management of the febrile child: A survey of pediatric and
emergency medicine residency directors. Pediatr Inf Dis J 1991; 10: 795
Barbara Rath 2007

The temperature most commonly used to define

fever threshold in children is 38C (100.4F),
rectal, although lower oral temperatures in
adolescents and adults (37.2 - 37.8C) may
indicate a febrile response.

For the appropriately dressed child who has

been at rest 30 minutes, rectal temperature of
38C (100.4F) is fever
Barbara Rath 2007

WHAT TEMPERATURE = FEVER?

THE PEDIATRIC ID LITERATURE

WHAT TEMPERATURE = FEVER?

& MORE PEDIATRIC LITERATURE.

The most commonly accepted minimum

temperature defining fever is 38C
(100.4F).

Generally, the accepted range of rectal temperature

is 36.1C to 37.8C (97F to 100F)..Clearly, a
body temperature slightly above an arbitrary upper
limit of 37.8C (100F) does not always imply a
pathologic process.

Pediatric Infectious Diseases. Principles and Practice

fever is defined as rectal temperature

above 38C (100.4F).

Nelsons Pediatrics
D No definition given

Principles and Practice of Pediatric Infectious Diseases

In general, values higher than 37.8C (100F) are
considered to be fever

Textbook of Pediatric Infectious Disease

Current Pediatric Therapy

D

Pediatrics (Osborn, DeWitt, First)

D No definition given
Barbara Rath 2007

WHAT TEMPERATURE = FEVER?

THE JOURNALS.

Barbara Rath 2007

Fever as an Adverse Event

Following Immunization (AEFI)

Contemporary Pediatrics (1997)

D

Rectal temperature >38 C (100.4 F)

Tympanic temperature >38 C (100.4 F)

Oral temperature >37.8 C (100 F)

Axillary temperature >37.2 C (99 F)

Berlin C W Jr: Fever in children. A practical approach to management

Barbara Rath 2007

Fever as an AEFI The Brighton

Collaboration Case Definition

Barbara Rath 2007

FEVER vs NORMAL ADULT ORAL TEMPS

37.0C
98.6F

Fever is defined as the endogenous elevation of

at least one measured body temperature
of >= 38 C.

The value of >38C is accepted as reflecting an abnormal elevation of temperature,

irrespective of device, anatomic site, age, or environmental conditions.

While it is recognized that this value is to some extent arbitrary, it is based upon a
conservative interpretation of definitions proposed and used by clinicians,
investigators, and the public at large.

S. Michael Marcy et al., Vaccine 2004; 22: 551-556

Barbara Rath 2007

38 C
100.4 F

* Mean, Median: 98.2F

Mackowiak P A et al: JAMA 1992;

268: 1578-80
Barbara Rath 2007

INDIVIDUAL VARIATIONS AND THE

DEFINITION OF FEVER

Statement:
D

DIFFERENTIAL DIAGNOSIS OF FEVER

Where and how should we measure body

temperature?

What constitutes normal temperature?

What constitutes fever?

What causes fever?

What is Fever of Unknown Origin (FUO)?

She always runs a low temperature and

37.5 is a fever for her

Response:
D You will never convince the caregiver to
the contrary, so work with it: There are no
data to confirm or refute this observation.

Barbara Rath 2007

Barbara Rath 2007

WHAT CAUSES FEVER?

Sumerian (3000 BC)

Egyptian (1700 BC)

Chinese (1000 BC)

Demonic possession
Imbalance of good and evil

Indian (800 BC 1000 AD)

D
D

Evil spirits (Nergal & Ashakka)

Fire demons Takman & Yakshma

Disturbances of the humours: bile, air, phlegm

Greek and Roman (400 BC 200 AD)

D

Excess of phlegm vs blood, yellow bile, black bile

Excess of yellow bile vs phlegm, blood, black bile

Medieval (500 1350 AD)

Renaissance (1300 1600 AD)

18th Century
D Friction from blood rushing through the vessels; inflammation..

Demonic possession
Fermentation and putrefaction in the blood and gut

Barbara Rath 2007

Barbara Rath 2007

Non-Infectious Causes
Hyperthyroidism

Cerebral Hemorrhage

Hodgkin Disease

Drug Fever

Pulmonary Infarction

Dermatomyositis

Hypernephroma

Bronchogenic CA

Reginoal Ileitis

Myocardial Infarction

Aplastic Anemia

Pheochromocytoma

Leukemia

Periatrieritis Nodosa

Fracture

Thrombophlebitis

Rheumatic Fever
Rheumatic Arthritis

Barbara Rath 2007

Barbara Rath 2007

Infectious causes
Cerebral Abscess
Meningitis
Infectious Mononucleosis
Tracheobronchitis Pneumonia
Subphrenic Abscess Infectious
Exanthema Appendicitis Osteomyelitis
Septic Arthritis

Sinusitis
Dental Abscess Tuberculosis
Subacute Bacterial Endocarditis
Empyema Pyelonephritis
Diverticulitis Prostatic Abscess
Cellulitis

ANATOMY OF THERMOREGULATION

PATHOGENESIS OF FEVER

Mackowiak P A: Arch Int Med 199B8a;rb1ar5a 8R:a1th8270007-1881

Mackowiak P A:BA
arrbcahraIn
RtatM
he
2d
001
7998; 158:1870-1881

TRUE NORMAL CORE TEMPERATURE

PATHOGENESIS OF FEVER

Best site(s) to determine true normal core temperature is:

D

Hypothalamic artery

Pulmonary artery

Rectum (5 cm)

Sublingual artery (oral)

Tympanic membrane

D Temporal artery
Acetaminophen,
Ibuprofen

Axillary artery

Skin (umbilicus)

Mackowiak P A:BA
arrbcahraIn
RtatM
he
2d
001
7998; 158:1870-1881

Barbara Rath 2007

FUO IN CHILDREN

DIFFERENTIAL DIAGNOSIS OF FEVER

Fever of unknown origin

is characterized by daily fever persisting for more than 3 weeks.

Where and how should we measure body temperature?

What constitutes normal temperature?

What constitutes fever?

What causes fever?

Chronic episodic fever of unknown origin

is characterized by fever lasting for a few days to a few weeks,
followed by a fever-free interval and a sense of well-being.

What is Fever of Unknown Origin (FUO)?

Barbara Rath 2007

infectious,
rheumatologic disorders, and
malignancy.

Mediterranean fever,
the hyper-immunoglobulin D syndrome,
familial Hibernian fever,
Behcet disease,
the syndrome of periodic fever,
aphthous stomatitis, pharyngitis and adenitis, and
cyclic neutropenia.
Barbara Rath 2007

FUO IN CHILDREN

FUO IN CHILDREN

Majeed HA. Curr Opin Rheumatol. 2000 Sep;12(5):439-44.

Barbara Rath 2007

Barbara Rath 2007

Barbara Rath 2007

Barbara Rath 2007

ALSO RULE OUT:

Hay Fever
Cabin Fever
Island Fever
World Cup Fever
Saturday Night Fever

Know where to
look!!!

Barbara Rath 2007

Barbara Rath 2007

1
0

Clinical
Vignettes..

Barbara Rath 2007

CASE #1: NEONATE WITH FEVER

A 3 week old boy comes to your office because he slept

through his noon feeding time, seems sleepier than
usual to the parents, and had a rectal temperature of
38.1C (100.6F). Examination is entirely normal,
including vital signs and temperature. He has a brisk,
strong cry and good muscle tonus, but the cry is not
sustained and he sucks only briefly on his bottle and
then becomes quiet.

Barbara Rath 2007

YOUR NEXT STEP IS.?

D

Admit, start antimicrobial Rx (cefotaxime + ampicillin

or ceftriaxone + ampicillin or gentamicin + ampicillin)

Admit, get lab studies, and start antimicrobial Rx

Admit, observe without lab studies or antimicrobials

Get lab studies and await results to decide if pt needs

admission or can be followed from home

What else would you like to know or do?

Barbara Rath 2007

Barbara Rath 2007

LAB STUDIES YOU COULD ORDER ARE?

D

CASE #1: NEONATE WITH FEVER

(CONTD)

CBC and differential

UA/UC

Blood culture

D CBC: 7,600 WBC with 44N, 47L, 7M, 2E; Hgb 11/33

CSF analysis and culture

D Cath UA: yellow, cloudy. Sp gr 1.010, pH 7.0. Sugar,

Chest P-A & lateral radiograph

Sedimentation rate (ESR)

C-reactive protein (CRP)

Procalcitonin

IL-6 or IL-8

Lab results:

protein, ketones, bili all neg. Hgb 1+, LE 1+, nitrite

neg. Micro: WBC 10-25/HPF, bacteria few.
D CSF: clear, 1 RBC, 4 WBC (2 PMNs), sugar 52, protein 69,

Gram stain neg.

D Chest film: normal
D Two days later lab reports >100,000 E coli in the urine

D CD11b, CD64
D

Granulocyte colony stimulating factor

Barbara Rath 2007

Mishra U K, et al: Arch Dis Child Fetal Neonatal Ed 2006; 91: F208-F212

Barbara Rath 2007

10

THE VALUE OF THE LABORATORY IN

EVALUATION OF NEONATAL INFECTION

THE VALUE OF THE LABORATORY IN

EVALUATION OF NEONATAL INFECTION

the usefulness of a test will depend above

all, on the clinical condition of the baby. If the
baby is really very sick, the test will not give
very much additional informationif the baby is
evidently wella positive test result (will) not
dramatically increase the probability that the
baby is infected

BUT, what about the baby that isnt really very

sick and isnt evidently well..?

Tests and Panels for Early Onset Neonatal Sepsis

D PPV: 5% - 69% (Mean: 36%)

D NPV: 93% - 100% (Mean: 97.5%)

Tests and Panels for Late Onset Neonatal Sepsis

D PPV: 71% - 93% (Mean 79%)

D NPV: 75% - 97% (Mean 86%)

Weinberg G A, DAngio C T in Remington J S, Klein J O: Infectious Diseases of

the Fetus and Newborn Infant, 6th Ed, 2006, Pg 1216.

Chiemsa C, et al: : Clin Chem 2004; 50: 279-187

Barbara Rath 2007

ROCHESTER LOW-RISK CRITERIA FOR

SERIOUS BACTERIAL ILLNESS (0-3 MO)
Hx: Term (>37 Weeks)

Barbara Rath 2007

TAIWAN LOW-RISK CRITERIA FOR

SERIOUS BACTERIAL ILLNESS (0-28 DAYS)

No antimicrobials

PE:

Never hospitalized

D Appears well

No unexplained hyperbilirubinemia

D No evidence ear, eye, soft tissue infection

No chronic or underlying illness

Not hospitalized longer than mother

LAB:
D WBC 5,000 15,000
D Absolute band <1500

PE: Appears generally well

D Spun urine <10 WBC/HPF

No evidence skin, bone, soft tissue, joint,

or ear infection

D CRP <20 mg/L

D [ESR <30 mm/hr]

Lab: WBC 5000-15,000

Absolute band <1500
Spun urine <10 WBC/HPF
Stool <5 WBC/HPF (if diarrhea)

Chiu C-H et al: Pediatr InBfearcbtarD

saJth 129
a iR
00974;13:946-949 & 1997;16: 59-63

Barbara Rath 2007

YOUNG INFANT OBSERVATION SCALE (0-2 MO)

MANAGEMENT OF THE FEBRILE INFANT

AFFECT
D Smiles or not irritable (1)*
D Irritable, consolable (3)
D Irritable, not consolable (5)

Decisions on management of febrile (or afebrile)

infants should be based mostly on an overall clinical
impression, not a single clinical measurement such
as temperature nor a single lab value such as the
WBC count

RESPIRATORY STATUS & EFFORT

D No impairment, vigorous (1)

D Mild-moderate compromise (tachypnea, retractions,

grunting) (3)
D Respiratory distress or inadequate effort (apnea,

respiratory failure (5)

Clinical observation has been objectified to some

extent in the Young Infant Observation Scale and the
Yale Observation Scale
Barbara Rath 2007

PERIPHERAL PERFUSION
D Pink, warm extremities (1)
D Mottled, cool extremities (3)
D Pale, shock (5)
* No infant who smiled had an SBI
Bonadio W A, et al: PediaBtarrbIanrfa D
Rais
thJ20109
7 93; 12: 111-114

11

EFFICACY OF LOW-RISK CRITERIA FOR EXCLUDING

SERIOUS NEONATAL BACTERIAL INFECTIONS

Taiwan Criteria

Ooooooops

11-month old male infant with 12 hr Hx low grade

fever, irritability, intermittent crying. PE: alert,
playful, smiling. Red pharynx, left TM red and
bulging, flat fontanelle.

5 hrs later: T 39.9C, increasingly lethargic, bulging

fontanelle.

CSF cloudy, 8,200 WBC, sugar 45 mg%, protein

160 mg%, Gram-positive diplococci seen. Culture

D PPV: 33.6%
D NPV: 99.2% (bacteremia/meningitis: 100%)

Afula Criteria
D PPV: 32%
D NPV: 99.4%

Rochester Criteria
D PPV: 27%*, 35%, 12%
D NPV: 94%*, 97%, 99%

Young Infant Observation Scale (7)

D PPV: 37%
D NPV: 96%
* Ferrera P C, et al: Am J Emerg Med 1997; 15: 299-302
Gara G, et al: Acad Emerg Med 2005; 12: 921-925.
Jaskiewicz J A, et al: PediBaatrribcasra1R9a9t4h;29040:7390-396

grew S pneumoniae penicillin-R

Baptist E C: Meningitis in the child with a smile. Arch Pediatr
Ba9
rb:a1
ra1R
t h 2007
Adolesc Med
1995; 14
7a9

CASE #2: FEVER IN 18-MONTH OLD

(CONTD)

CASE #2: FEVER IN AN 18-MONTH OLD

An 18-month old girl is brought to your office on a Thursday

morning with a fever for 4 days up to 103.8F by TM
thermometer. Her parents tell you she first felt warm when
being put to bed on Monday and since then has been more
whiny, tires somewhat more easily than usual, appetite is off a
bit, but she is otherwise active, alert, and generally unfazed.

ROS: Otherwise normal

PMH: Non-contributory. Immunizations up to date.

Family Hx: All well

Social Hx: No travel, friends are well.

Barbara Rath 2007

The enhanced urinalysis (hemocytometer count of

unspun urine + Gram stain) was normal (no
organisms and <10 cells/mm3). WBC: 6,400 with
74%L, 21%P, 5%M, 0E. Chest film was normal.

The next day she still has a fever, but that afternoon
the mother calls back concerned because a rash
broke out. You tell her to bring the child in to see you.

On PE you note a faint pink macular rash most

prominent on the neck and trunk, slight on the face
and extremities. The child is now afebrile. The
mother has OCD and kept a q 4 hr record of her
daughters temperatures
Barbara Rath 2007

Barbara Rath 2007

Barbara Rath 2007

12

CASE #2: FEVER IN 3-36 MONTH OLD

(CONTD)

The most likely diagnosis is infection due to:

D HHV 6
D HHV 7
D

Echovirus 16(Boston exanthem), 9, 11, 25, 27, 30

Coxsackievirus A6, A9, B1, B2, B4, B5

D Adenovirus 1, 2, 3, 14
D Parainfluenza 1
D Rotavirus
D Parvovirus B19
Cherry J D in Feigin, Cherry, Demmler, Kaplan Eds):
th
Textbook of Pediatric Infectious Dise
s,ra5 Ra
Etdhit2io0n0,7Pg 772.
Baasre
ba

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Barbara Rath 2007

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Barbara Rath 2007

13

DOES TEMPERATURE MATTER?

SIGNIFICANCE OF FEVER 41.1C

Of no predictive value

Clinical assessment reliably identified those children with hyperpyrexia

and serious complicationsand should be used to guide management
decisions
Bonadio W A, et al: Pediatr Inf Dis J 1989; 8: 120-122

Highly febrile young children need to be evaluated as thoroughly and

carefully as any other febrile child but do not merit special
consideration.
Alpert G, et al: Pediatr Inf Dis J 1990; 9: 1611-63

We advise treatment with antibiotics for all children with hyperpyrexia who
do not have a confirmed viral illness and for all children with
hyperpyrexia and a confirmed viral illness who are ill enough to require
hospitalization
Krugman S, Katz SL, Gershon AA, Wilfert CM. Infectious diseases of
children. 9th ed. St. Louis, Missouri: Mosby Year Book Inc. 1992.

Trautner B W, et al: Pediatrics 2006; 118: 34-40

Barbara Rath 2007

Barbara Rath 2007

DOES AGE MATTER?

INCIDENCE OF SEVERE SEPSIS BY AGE

Angus DC, Linde-Zwirble WT, Lidicker J, Clermonte G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States:
analysis of incidence, outcome, and associated costs oBfacrabraer.aCR
ria
t tC
ha2re
0 0M
7ed 2001; 29:1303 10.

Otitis Media

41%

DOES AGE MATTER?

MORTALITY DUE TO SEPSIS BY AGE

Girard TD, Opal SM, Ely EW. Insights into severe sepsis in older patients: from epidemiology to evidence-based management.
Clin Infect Dis 2005;40(5):719-27.

Barbara Rath 2007

37%

ViralA
Syndrome
9% MATTER?
DOES
HIGH WBC18%
COUNT

Pneumonia
15%
Children 2-24 mo old (mean:13%
10 mo), 1992-1994,
T38.5C
UTI
12%
13%
D Leukocytosis
(LK): 15,000
24,999
(n = 94)

Gastroenteritis
7%
5%
D Extreme
leukocytosis (EL):
25,000
(n = 69)
Aseptic meningitis
2%
6%
Diagnoses
Diagnosis
LK
EL
Adenitis
2%
6%
Proven SBI LK vs EL:
17% vs 25%
Bacteremia
1%
2%
Other*

4.6%

7%

CASE #3: 16 YEAR OLD BOY WITH FEVER

A 16-year old boy comes to your office with his father who is
concerned because the boy had a fever for several days, but today
woke up with a fever to 40C, flushed face, chills, vomited once,
and even seemed a bit delirious about an hour before. He has
been quite well otherwise except for an aching knee since he
tripped and fell about a week ago.

31% vs 49%

ROS: Otherwise non-contributory

25,000-29,999:

PMH: Non-contributory

Family Hx: All well, non-contributory

Social Hx: no travel, non-contributory. Friends are well

Proven + Probable
SBI: 35% vs 52%
Hospitalized:

RR SBI: 1.36
30,000:
RR SBI: 1.73

D All immunizations, including meningococcal vaccine.

rba
07
*Periorbital cellulitis (3), meningitis, cellulitisB,am
arsatoRiadtihtis2,0o
steo, septic arthritis (1 each)
Barbara Rath 2007

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CASE #3: 16 YEAR OLD BOY WITH FEVER

(CONTD)

PE: On examination you confirm the high fever, pulse

of 132; BP 97/65; sick-looking young man. Sa02: 89%.
Right knee is mildly swollen and faintly pink. Otherwise,
PE normal without any rash, petechiae, or mucous
membrane involvement.

Barbara Rath 2007

Barbara Rath 2007

CASE #3: 16 YEAR OLD BOY WITH FEVER

(CONTD)

Labs & X-ray

D WBC: 9700, 43% N, 28% B, 20% L, 9% M, toxic

granulations noted; Hgb 15.3, Pl 120,000

D UA: 8-10 RBC / HPF
D ESR: 85 mm/hr, CRP: 47
D D dimers (+), fibrin split products (+)
D ALT: 52, AST: 38
D Serum albumin: 2.43 g/dL
D Na: 125
D Creatinine 2.0; BUN 20
D Chest radiograph: bilateral nodular densities

Barbara Rath 2007

Barbara Rath 2007

SOME POSSIBLE ETIOLOGIES

D

NEISSERIA MENINGITIDIS

GROUP A STREPTOCOCCUS

STAPHYLOCOCCUS AUREUS

SALMONELLA TYPHOSA

RICKETTSIA RICKETTSII

ERHLICHIA CHAFEENSIS

LEPTOSPIRA SPP

Barbara Rath 2007

Barbara Rath 2007

15

SCENARIO #4: Hes had a fever, but hes

been teething...

CASE #3: 16 YEAR OLD BOY WITH FEVER

Pt started on ceftriaxone, vancomycin, gentamicin

Blood culture grew out S aureus, methicillin-R

Severe staphylococcal sepsis in adolescents*

D 90% with bone and/or joint infection

Signs and symptoms significantly associated 4 days

before to 3 days after teething are:
Biting

Irritability

Drooling

Wakefulness

Rash on face

Appetite (solids)

Sucking

Ear-rubbing

Gum-rubbing

Temp Elevation*

D 90% with pulmonary septic emboli, pneumatocoeles, and/or

parapneumonic effusions
D 30% bacterial venous thrombophlebitis
D 50% Renal failure
D DIC
D Skin lesions: urticaria, e multiforme, papular-pustular

*Day of emergence vs before: 17% vs 12% >100F; 6% vs 3% >101F

* Gonzalez B E, et al: Pediatrics 2005; 115: 642-648

Macknin M L, et al: Pediatrics 2000; 105:747-752

Barbara Rath 2007

Teething and Fever (Contd)

Mean daily temp before 1st tooth eruption

Barbara Rath 2007

Scenario #5: His temperature was around

39
- Fever Detection by Palpation

~60% of parents use palpation as the usual method of fever

assessment

85% - 99% believe they can detect fever by palpation

Actual accuracy of parental palpation for fever:

D Sensitivity: 77%1, 84%2, 90%3 , 74%4
D Specificity: 82%, 76%, 78%, 86%
D Positive predictive value: 59%, 72%, 69%, 71%
D Negative predictive value: 85%, 91%, 91%, 94%

Temp >37.5C by day before tooth eruption,

46 infants, 15 with temp 38C
Jaber L, et al: Arch Dis Childh1992; 67:233

Barbara Rath 2007

Scenario #5: His temperature was around

39..*

If it is important to know the real temperature (and it may

not be) ask:
D Where
D What

did you take the temp?

kind of thermometer did you use?

How long did you leave it in place?

Around? Was it below 39 or above?

1. Katz-Sidlow R, et al: Ped Acad Soc Meeting; May 2, 2006; 2. Graneto J W, Soglin D F:
Ped Emerg Care 1996; 12: 183-184; 3. Ernst T N, Philp M: Amer J Dis Child 1985; 139:
546; 4.Banco L, Veltri D: Amer J Dis Child 1984; 138; 976-978.
Barbara Rath 2007

ANXIOUS PARENTS
170 parents of young febrile children who presented to a pediatric emergency
department (ED) with fever;
90- item questionnaire (State Trait Anxiety Inventory)
Parents were asked what they had previously thought about and how they felt
about the ED process.
Mean parental anxiety was 50.1 (95% CI 48.1, 52.2), significantly elevated from
adult standards (p < 0.0001).
A multivariate model comprising:
(1) feeling "not at all" well rested,
(2) having no other children,
(3) having thought about a blood test, and
(4) feeling worried about trusting the physician
was associated with elevated anxiety.
In conclusion, parents of febrile young children in the ED are very anxious.

* Translation: Im worried and I want you to worry too.

Barbara Rath 2007

Parkinson GW, Gordon KE, Camfield CS, Fitzpatrick EA. Anxiety in Parents of Young Febrile Children in a
Pediatric Emergency Department: Why is it El evated? Clinical Pediatrics 1999;38(4):219.
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16

SUMMARY

Normal body temperature varies widely

Fever can be arbitrarily defined as a temp of 38C (100.4F) at

any site using any approved instrument

Teething may be associated with minimal elevation in temperature

Palpation is not an accurate way to determine presence of fever,

but its not bad for its absence

Barbara Rath 2007

SUMMARY
Overall clinical impression, supported by
laboratory or imaging studies, rather than height
of temperature or abnormal lab values alone,
should be the major determinant for deciding
whether or not a child has a serious bacterial
illness.

Barbara Rath 2007

Acknowledgements
S MICHAEL MARCY, MD
CLINICAL PROFESSOR OF PEDIATRICS
UNIVERSITY OF CALIFORNIA LOS ANGELES
UNIVERSITY OF SOUTHERN CALIFORNIA
SCHOOLS OF MEDICINE
Team Lead, Brighton Collaboration Fever Working Group,
Member, Brighton Collaboration Steering Committee

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