Fever with Rash

Marimel G. Reyes-Pagcatipunan,MD, FPPS,FPIDSP

Pediatric Infectious Disease Specialist
Associate Professor, University of the Philippines,Manila
College of Medicine
Attending Pediatrician-UP-PGH

Cutaneous Manifestations of Systemic

Infections (Rashes)
Many different types of viruses, bacteria, fungi,
protozoan and metazoan agents cause illnesses
associated with rashes
When an exanthem occurs, it often offers important
clues to the etiology of a patients illness

By skin examination alone, it is difficult to differentiate a

rash from a systemic infection vs primary cutaneous
(local) diseases
Consider exposure, season, incubation period, age, location, associated ssxs

Erythematous Maculopapular Exanthems

Infectious Agent
Parvovirus
Adenoviruses 1, 2, 3, 4, 7, 7a
Human herpesvirus 6
Epstein Barr virus
Coxsackieviruses A2, A4, A5, A7, A9, A10, A16, B1-B5
Echoviruses 1-7, 9, 11, 13, 14, 16-19, 22, 25, 30, 33
Enterovirus 71
Dengue virus
Rubella virus
Mumps virus
Measles virus
Hepatitis B virus
Mycoplasma pneumoniae
Staphylococcus aureus
Streptococcus pyogenes
Neisseria meningitidis
Bartonella henselae
Treponema pallidum
Leptospira species

Illness
Erythema infectiosum
Roseola infantum
Infectious mononucleosis

Dengue Fever
German Measles
Mumps
Measles
Hepatitis
Staphylococcal Scarlet Fever
Scarlet Fever
Meningococcemia
Cat-scratch fever
Secondary syphilis
Leptospirosis

Vesicular Exanthems
Infectious Agent
Herpes simplex virus type 1 and 2
Varicella-zoster virus
Variola virus
Orf virus
Coxsackieviruses A4, A5, A8, A10, A16
Coxsackieviruses B1-3
Echoviruses 6, 9, 11, 17
Enterovirus 71
Mumps virus
Measles virus
Streptococcus pyogenes
Bacillus anthracis
Mycobacterium tuberculosis
Candida albicans
Necator americanus

Illness
Cold sores, genital herpes, or neonatal herpes
Chickenpox or herpes zoster
Smallpox
Ecthyma contagiosum

Mumps
Atypical measles
Impetigo
Anthrax
Papulonecrotic tuberculids
Congenital cutaneous candidiasis
Hookworm disease

Petechial and Purpuric Exanthems

Infectious Agent
Human Parvovirus B19
Varicella-zoster virus
Cytomegalovirus
Coxsackieviruses A4, A9, B2-B4
Echoviruses 4, 7, 9
Rubella virus
Measles virus
Streptococcus pyogenes
Streptococcus pneumoniae
Neisseria gonorrheae
Neisseria meningitidis
Haemophilus influenzae
Pseudomonas aeruginosa
Bartonella henselae
Treponema pallidum
Toxoplasma gondii

Illness
Glove and socks syndrome
Hemorrhagic chickenpox
Congenital cytomegalovirus infection

Rubella or congenital rubella

Hemorrhagic or atypical measles
Scarlet fever or septicemia
Pneumococcal septicemia
Gonococcemia
Meningococcemia
H. Influenzae septicemia
Ecthyma gangrenosa
Cat-scratch fever
Congenital syphilis
Congenital toxoplasmosis

Kinds of Rashes
Localized, non-palpable flat lesion of any color measuring <1cm
in diameter

Macule

Palpable, elevated, solid lesion of any color measuring <1cm in

diameter

Papule
Image courtesy of the Atlas of Philippine Dermatology 1st ed. Maano C. Et al. Editors Section of Dermatology, UP Manila

Kinds of Rashes

Plaque

Nodule
Image courtesy of the Atlas of Philippine Dermatology 1st ed. Maano C. Et al. Editors Section of Dermatology, UP Manila

Kinds
of Rashes
Kinds
of Rashes

Vesicle

Bulla
Image courtesy of the Atlas of Philippine Dermatology 1st ed. Maano C. Et al. Editors Section of Dermatology, UP Manila

Kinds
of Rashes
Kinds
of Rashes

Collection of pus in the skin, having the size of a vesicle (e.g.

Folliculitis, pustular acne)

Pustule

Loss of skin or mucous membrane deeper than an erosion (e.g.

Decubitus ulcer)

Ulceration
Image courtesy of the Atlas of Philippine Dermatology 1st ed. Maano C. Et al. Editors Section of Dermatology, UP Manila

Kinds of Rashes:
Variants
Maculopapular Confluent,
erythematous rash made up of both
macular and papular lesions.
Purpura Papular or macular
nonblanching lesions that are due
to extravasation of red blood cells.
Glossary. In: Dermatologic Manifestations of Infectious Diseases, Peterson PK, Dahl MV (eds), The Upjohn Company,
Kalamazoo, Michigan 1982, p.4.

Differential Diagnosis of Fever and Rash

Based on Appearance of Rash

Macules, Papules, Nodules, or Plaques

Bacterial

Viral

Fungal

Protozoal/
Parasitic

Bartonella
henselae

Coxsackie
viruses A and B

Blastomyces
dermatitidis

Leishmania tropica Erythema

miltiforme

Candida spp

Necator americanus SLE

Leptospira sp

Non-infectious

Dengue virus
M. tuberculosis

Measles

Coccidiodes
immitis

Onchocerca
volvulus

Dermatomyositis

M. pneumoniae

Human
herpesvirus 6

Cryptococcus
neoformans

Schistosoma

Drug
hypersensitivity

N. gonorrheae

Kawasaki (?)

Stongyloides
stercoralis

Gianotti-Crosti
syndrome

N. meningitidis

Rubella

Toxoplasma gondii

Inflammatory
bowel disease

S. Typhi

Echoviruses

Other
disseminated
deep fungal
infections in
immunocompro
mised patients

Trichinella spiralis

Pityriasis rosea

Common Causes of Fever and Rash in

Infants and Toddlers

Rubella

From Latin meaning "little red"

Discovered in 18th century - thought to

be variant of measles

First described as distinct clinical entity

in German literature

Congenital rubella syndrome (CRS)

described by Gregg in 1941

German Measles
(Rubella)

2yr old w/ mild, slight fever, Forscheimer

spots, maculopapular rash, generalized
lymphadenopathy

Courtesy : AAP,CDC images; http://www.webmd.com/skin-problems-and-treatments/picture-of-rubella

Rubella Virus

Togavirus

RNA virus

One antigenic type

Rapidly inactivated by chemical

agents, ultraviolet light, low pH, and
heat

Rubella Pathogenesis

Respiratory transmission of virus

Replication in nasopharynx and
regional lymph nodes
Viremia 5-7 days after exposure with
spread to tissues
Placenta and fetus infected during
viremia

Rubella Clinical Features

Incubation period 14 days
(range 12-23 days)
Prodrome of low-grade fever
Maculopapular rash 14-17 days after
exposure
Lymphadenopathy in second week

Rubella rash

Rubella Complications
Arthralgia or arthritis
adult female
children

up to 70%
rare

Thrombocytopenic
purpura
Encephalitis
Neuritis
Orchitis

1/3,000 cases
1/6,000 cases
rare
rare

Rubella Laboratory Diagnosis

Isolation of rubella virus from clinical

specimen (e.g., nasopharynx, urine)
Positive serologic test for rubella IgM
antibody
Significant rise in rubella IgG by any
standard serologic assay (e.g.,
enzyme immunoassay)

Rubella Epidemiology
Reservoir

Human

Transmission

Respiratory
Subclinical cases may
transmit

Temporal

pattern

Communicability

Peak in late winter and spring

7 days before to 5-7 days
after rash onset
Infants with CRS may shed
virus for a year or more

Rubella Case Definition

Acute onset of generalized maculopapular

rash, and
Temperature of >99F (37.2 C), if
measured, and
Arthralgia or arthritis, lymphadenopathy, or
conjunctivitis

Measles (Rubeola)

Summer, 1 yr old with fever, cough,

coryza, conjunctivitis,
maculopapular rash, Koplik spots

Measles

Highly contagious viral illness

First described in 7th century
Near universal infection of childhood
in prevaccination era
Common and often fatal in
developing areas

Measles Virus

Paramyxovirus (RNA)
Hemagglutinin important surface
antigen
One antigenic type
Rapidly inactivated by heat and light

Measles Epidemiology

Reservoir

Human

Transmission

Temporal pattern

Peak in late winterspring

Communicability

4 days before to 4 days after

rash onset

Respiratory
Airborne

Measles Clinical Case Definition

Generalized rash lasting >3 days, and

Temperature 101F (>38.3C), and
Cough or coryza or conjunctivitis

Measles Pathogenesis

Respiratory transmission of virus

Replication in nasopharynx and
regional lymph nodes
Primary viremia 2-3 days after
exposure
Secondary viremia 5-7 days after
exposure with spread to tissues

Measles Clinical Features

Incubation period 10-12 days

Prodrome
Stepwise increase in fever to

103F or higher
Cough, coryza, conjunctivitis
Koplik spots

Kopliks spots

Measles Clinical Features

Rash

2-4 days after prodrome, 14 days after

exposure
Maculopapular, becomes confluent
Begins on face and head
Persists 5-6 days
Fades in order of appearance

Measles Rash

Measles Complications
Condition
Diarrhea
Otitis media
Pneumonia
Encephalitis
Hospitalization
Death

Percent reported
8
7
6
0.1
18
0.2

Based on 1985-1992 surveillance data

Measles Complications by Age Group

Measles Laboratory Diagnosis

Isolation of measles virus from a

clinical specimen (e.g., nasopharynx,
urine)
Significant rise in measles IgG by
any standard serologic assay (e.g.,
EIA, HA)
Positive serologic test for measles
IgM antibody

Chickenpox
(Varicella zoster)

3 yr old w/ generalized,
pruritic vesicular rash (in
crops), mild fever

Varicella Zoster Virus

Herpesvirus (DNA)
Primary infection results in varicella
(chickenpox)
Recurrent infection results in
herpes zoster (shingles)
Short survival in environment

Varicella Epidemiology

Reservoir

Human

Transmission

Airborne droplet
Direct contact with lesions

Temporal pattern

Peak in winter and early

spring (U.S.)

Communicability

1-2 days before to 4-5

days after onset of rash
May be longer in
immunocompromised

Varicella Pathogenesis

Respiratory transmission of virus

Replication in nasopharynx and regional
lymph nodes
Repeated episodes of viremia
Multiple tissues, including sensory
ganglia, infected during viremia

Varicella Clinical Features

Incubation period 14-16 days (range

10-21 days)
Mild prodrome for 1-2 days
Rash generally appears first on
head; most concentrated on trunk
Successive crops over several days
with lesions present in several
stages of development

Rashes of Varicella Infection

Extensive varicella infection

Herpes Zoster (Shingles)

Reactivation of varicella zoster virus

Can occur years or even decades after
illness with chickenpox
Generally associated with normal aging and
with anything that causes reduced
immunocompetence
Lifetime risk of 20 percent in the United
States
Estimated 500,000- 1 million cases of zoster
diagnosed annually in the U.S

Varicella Complications

Bacterial infection of skin lesions

Pneumonia (viral or bacterial)
Central nervous system manifestations
Reye syndrome
Hospitalization: 2-3 per 1,000 cases
Death: 1 per 60,000 cases
Postherpetic neuraligia (complication of
zoster)

Groups at Increased Risk of

Complications of Varicella

Persons older than 15 years

Infants younger than 1 year
Immunocompromised persons
Newborns of women with rash onset
within 5 days before to 48 hours after
delivery

Congenital Varicella Syndrome

Results from maternal infection

during pregnancy
Period of risk may extend through
first 20 weeks of pregnancy
Low birth weight, atrophy of
extremity with skin scarring, eye
and neurologic abnormalities
Risk appears to be small (less than
2%)

Varicella Laboratory Diagnosis

Isolation of varicella virus from clinical

specimen
Rapid varicella virus identification using
PCR (preferred, if available) or DFA
Significant rise in varicella IgG by any
standard serologic assay (e.g., enzyme
immunoassay)

Herpes simplex
1 and 2
1 yr old w/ fever, irritability, tender
submandibular adenopathy, ulcerative
enanthem on gingiva and mucous
membranes of mouth, and perioral vesicular
lesions
Most common clinical manifestation in
children = gingivostomatitis

Herpes Simplex

HSV viruses are enveloped, doublestranded, DNA viruses

Usually involve the face and skin
above the waist
HSV-2 usually involve the genitalia
and skin below the waist in sexually
active adolescents and adults
HSV-2 is the most common in
neonates

Herpes simplex

HSV-1 direct contact with infected

oral secretions or lesions
HSV-2 direct contact with infected
genital secretions or lesions through
sexual activity
Incubation period: 2 days to 2 weeks
(beyond neonatal period)

Herpes simplex

Neonatal: 1. disseminated disease involving

multiple organs , liver and lungs 2. localized CNS

disease 3. disease of the skin,eyes, and mouth
HSV should be considered in neonates with fever,
irritability, and abnormal CSF findings, esp in the
presence of seizures
Neonatal herpetic infections often are severe, high
mortality and morbidity even with antiviral therapy
Recurrent skin lesions are common and may be
with CNS sequelae if skin lesions occur frequently
during the 1st 6 months of life.

Herpes simplex

Children and adolescents:

most are

asymptomatic
Gingivostomatitis-usually by HSV-1: fever,
irritability, tender submandibular adenopathy and
an ulcerative enanthem in gingiva and mucous
membranes of mouth, often with perioral vesicular
lesions
Genital herpes- usually by HSV-2: most common in
adols and adults, vesicular or ulcerative lesions of
the genital organs, perineum or both
Eczema herpeticum- vesicular lesions
concentrated in the areas of eczematous
involvement

Herpes simplex

After primary infection- HSV persists

for life in a latent form
For herpes labialis- trigeminal
ganglion
For genital herpes- sacral ganglia
Reactivation of latent occurs with no
symptoms
When symptomatic- single or grouped vesicles in
the perioral region ( cold sores); or penis,
scrotum,vulva,cervix,perianal area, thighs or back

Herpes virus

Herpes virus

Neonatal herpes infection

Neonatal genital herpes

Herpes simplex

Diagnosis: HSV virus grows readily

in cell culture; confirmationfluorescent antibody staining and
enzyme immunoassays
HSV DNA in CSF- PCR, cultures are
usually negative
Treatment: acyclovir, valacyclovir
hydrochloride, famciclovir and
penciclovir

Roseola infantum
(Exanthem subitum, Human herpesvirus 6)
1 yr old w/ high fever (3-7 days), followed by maculopapular rash (neck -> trunk ->
extremities) lasting for hours to days, (10-15% with seizures)

Courtesy of AAP, Uptodate.com, Michael Brady, MD.

Human Herpesvirus 6 Roseola

Herpesviridae family- strains of HHV6 belong to 1 or 2 major groups,

variants A and B ( primary infections
in children)
Humans are the only host
Transmission: close contact,
secretions
Incubation period: 9-10 days

Roseola

Diagnostic test: virus isolation from

peripheral blood specimen as well as
seroconversion
PCR- does not differentiate between
primary and reactivation or viral
persistence

Roseola

Clinical manifestation: fever ( high

grade) persists for 3-7 days
followed by an erythematous
maculopapular rash lasting for hours
to days
Virus persists and may reactivate
Treatment: Supportive

Roseola rash

Fifth Disease, Erythema Infectiosum

Parvovirus B19 nonenveloped,

single-stranded DNA virus that
replicates only in human erythrocytes
precursors
Incubation period: 4-14 days but can
be as long as 21 days
Rash and joint symptoms occur 2-3
weeks after infection
Diagnostics: Immunocompetent host;
detection of serum parvovirus B-19
IgM

Fifth Disease

Recognized as erythema infectiosum

mild systemic symptoms, fever and a
distinctive rash
Facial rash- intensely red with slapped
cheek appearance with circumoral
pallor
Symmetric, maculopapular, lace-like
and often pruritic rash may also occur
in the trunk, moving peripherally to
involve the buttocks, arms and thigh.

Fifth Disease
Treatment: Only supportive care
CONTROL MEASURES:
Children with EI may attend child care or
school, because they no longer are contagious
once the rash appears.
Hand hygiene and proper disposal of used
tissues.

69

Slapped Cheek

Epstein-Barr Virus

Etiologic agent of classic infectious

mononucleosis- B-lymphotopic
herpesvirus
Humans are the only source of EBV
Transmission:Close contacts, viable
in saliva for several hours outside
the body; occl by blood transfusion
Incubation period: estimated 30-50
days

EBV

Clinical manifectation: fever,

exudative pharyngitis,
lymphadenopathy,
hepatosplenomegaly and atypical
lymphocytosis
Usually unrecognized in infants and
young children
Rash can occur in patients treated
with Ampicillin or other Penicillins

EBV

Exanthems- ampicillin rash

treated frequently with antibiotics for
suspected strep pharyngitis or
bacterial lymphadenitis
Develops 5-10 days after treatment
then resolves within a few days of
discontinuation.
Maculopapular and pruritic on trunk,
face and extremities

EBV

Infection : replication of the EBV in B

lymphocytes and the resulting
lymphoproliferation usually is
inhibited by natural killer cells
Diagnosis: viral isolation does not
indicate acute infection
Serologic testing: IgM appears in the
1st 2 weeks and gradually disappear
in 6 months

EBV rash

EBV

Hand, Foot, and Mouth Syndrome

3 yr old pre-schooler w/ fever, papulovesicular lesions in the anterior of the
mouth and on the hands and feet
Enteroviruses, HSV, but most commonly Coxsackievirus A16

Hand, Foot, and Mouth Syndrome

Fever, papulovesicular lesions in the anterior of the mouth,

on the hands, feet, and buttocks
Enteroviruses, HSV, but most commonly Coxsackievirus A16

Hand, Foot, and Mouth Syndrome

Contact Precautions

Low-grade fever with an average

temperature of 38.3C and duration of 23 days , Anorexia, Malaise , Abdominal
pain , Sore mouth, Cough

Hand, Foot, and Mouth Syndrome

incubation period: 3-6 days

Coxsackievirus infection is highly contagious.
During epidemics: horizontal transmission from child to child and
from mother to fetus.
Transmission: direct contact with nasal and/or oral secretions, fecal
material, or aerosolized droplets in a fecal-oral or oral-oral route.

Hand, Foot, and Mouth Syndrome

A typical cutaneous
lesion has an
elliptical vesicle
surrounded by an
erythematous halo.
The long axis of the
lesion is oriented
along the skin lines.

The lesions on the hands and feet are present for 5-10 days.
The mucosal and cutaneous lesions heal spontaneously in 57 days.

Fever and Rash Emergencies

Meningococcemia
Necrotizing Fasciitis
Staphylococcal Scalded Skin Syndrome

Staphylococcal Scalded Skin Syndrome

2 yr old boy with sudden onset of painful

erythematous rash (more prominent around
the neck, axillae and periorificial areas)
+Nikolski's sign, mild fever

mage courtesy of the Atlas of Philippine Dermatology 1st ed. Maano C. Et al. Eds Section of Dermatology, UP Manil. Up-to-date.c
Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.

Meningococcemia

Abrupt: fever, chills, malaise, rash (macular petechial)

Indistinguishable from rash of other viral infections
Purpuric rash occurs in severe sepsis
May be caused by other bacterial pathogens e.g. S pneumoniae
Rapid disease progression
Fulminant: purpura, limb ischemia, coagulopathy, pulmonary edema,
shock, coma, death within hours
Associated w/ Death: young age, absence of meningitis, coma,
hypotension, leukopenia, thrombocytopenia
http://www.meningococcal.org/the_rash.html www.vaccineinformation.org/photos/meniaap003.jpg Copyright American Academy of Pediatrics
http://www.vaccineinformation.org/photos/menicdc004.jpg Courtesy Centers for Disease Control and Prevention. AAP Redbook 28th ed.

Meningococcemia
Flu-like illness followed within 48 hrs by a
rash in 70-90% of patients
> petechial/purpuric in 60-70%
> maculopapular in 10-15%
> purpura fulminans in 5-10%
Peak age: <1 yr old (3 to 5 months)

striking involvement of the

extremities with relative sparing of the skin on body

Characteristic angular, necrotic lesions in infant

with meningococcemia

Courtesy of Charles V Sanders. (The Skin and Infection: A Color Atlas and Text, Sanders, CV, Nesbitt, LT Jr (Eds), Williams & Wilkins, Baltimore, 1995).;
www.vaccineinformation.org/photos/meniaap001.jpg Copyright American Academy of Pediatrics

Children + fever + skin lesions

Infection may not only be skin deep.

Many different types of viruses, bacteria, fungi,

protozoan and metazoan agents cause cutaneous
manifestations.
Recognition is key to making a good diagnosis and
instituting early and appropriate infection control and
treatment management.

Babies are Happy when they are Healthy !!