Transcript Viral Exanthems

“Your living is determined not so much by what life brings to you as
by the attitude you bring to life; not so much by what happens to
you as by the way your mind looks at what happens.”
Kahlil Gibran
Dr. Nehal Draz
VIRAL EXANTHEMS
Definition
 Exanthem is the medical name given to a
widespread rash that is usually
accompanied by systemic symptoms such
as fever, malaise and headache.
It is usually caused by an infectious
condition such as a virus, and represents
either a reaction to a toxin produced by
the organism, damage to the skin by the
organism, or an immune response.
 Exanthems may also be due to a drug
(especially antibiotics).
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 exanthems during childhood are very
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common and are usually associated with
the following viral skin infections:
Common winter and summer viruses
including respiratory and enteroviruses
respectively
Chickenpox (varicella)
Measles (morbilli)
German measles (rubella)
Roseola
Fifth disease (erythema infectiosum)
Laterothoracic exanthem
signs and symptoms of
exanthems
Most non-specific rashes appear as spots or
blotches and may or may not be itchy.
The rash is usually widespread and may be
more extensive on the trunk and
extremities.
In most cases, prior to the rash appearing,
patients may have symptoms of general
unwellness (prodroma) that include:
 Fever
 Malaise
 Headache
 Loss of appetite
 Abdominal pain
 Irritability
 Muscular aches and pains
These signs and symptoms may vary
depending on the cause of the
exanthem..
Viral exanthems often occur in small
epidemics so there may be other
children effected at the same time.
Varicella (Chicken Pox)
 Mild, highly contagious
disease chiefly
affecting children
 Mode of transmission:
- airborne droplets and
direct contact from
varicella patients
- Vesicular fluid of
Zoster patients can be
the source of Varicella
in susceptible children
Pathogenesis:
 VZV infects the mucosa of the upper
respiratory tract
 Multiplies in the regional LNs
 Primary viremia and spread to liver and
spleen
 Secondary viremia follows with viral spread
to the skin
 Typical rash occurs
 VZV remains latent in the dorsal root
ganglia for life
Clinical Picture:
 Incubation period: 10-21 days
 Symptoms: mild fever & rash
 Rash: first appears on the trunk, then face
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and limbs
Flat macules become papules then vesicles
Followed by crust formation
The crust is often shed off and heals without
scarring
Cropping is a characteristic feature of
varicella rash: fresh vesicles appear in crops,
so that all stages of macules, papules, vesicles
& crusts are seen at the same time
More severe in adults
Complications
 1- pneumonia especially in adults, may
be fatal
 2- rarely: fulminant encephalitis,
which may be a manifestation of
Reye’s syndrome that occurs as a
consequence of salicylates intake
during infection
Congenital Varicella Syndrome & Neonatal
Varicella
 Primary maternal infection during the 1st
trimester may lead to congenital
varicella syndrome ( serious & fatal):
skin lesions, hypoplasia of limbs,
chorioretinitis & CNS defects
 Primary maternal infection near the time
of birth can lead to widely disseminated
infection in the new born with mortality
rate of 35%
 If rash began a week or more before delivery,
maternal Abs transferred via placenta – baby
gets the infection but escapes clinical disease
Treatment
Acyclovir
 Inhibits viral DNA polymerase enzyme
 Used in immunocompromised patients
with chicken pox, zoster, or varicella
complicated with pneumonia, keratitis,
& neonatal Varicella
Doesn’t affect latency
Zoster (shingles)
 Sporadic disease in
adults or
immunocompromised
patients
 Results from
reactivation of latent
VZV
 Rash similar to
varicella but limited to
a nerve distribution to
the skin innervated by
a dorsal root ganglion
(dermatom)
Complications:
 If affecting the eye via trigeminal
nerve: keratitis, conjunctivitis & iritis
 It can affect the brain via the
cranial nerve leading to Bell’s palsy
 Post Herpetic neuralgia: Very painful,
Likely due to nerve damage from
zoster outbreak, Lasts for months
after zoster resolves & Does not
respond to antiviral treatment
Diagnosis
 Depends mainly on clinical picture
&
serology:
Specific VZV Abs using CFT, Nt,
or ELISA
Prevention
1- Active
immunization
2- Passive
immunization
 Live attenuated
 Varicella zoster
varicella vaccine
Single dose, age: 1-12
yrs
immunoglobulins (VZIG)
Given to:
- Immunocompromised
children exposed to
infection
- Mothers infected near
term(before delivery)
and their infants (
immediately after
delivery)
Measles (robeola)
 One of the most contagious respiratory infections
 It can nearly affect every person (in a given
population) by adolescence, in the absence of
immunization programs
Mode of transmission:
- Large repiratory droplet
-airborne
Most infectious in the early stage
Before the rash appears
Pathogenesis & clinical picture
 Replication initially in the upper &
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lower respiratory tract
Followed by LNs replication
Viremia & growth in a variety of
epithelial tissue
Incubation period: 1-2 wks
In 2-3 days, no rash but fever,
running nose, cough & conjunctivitis
 Koplick spots: slightly raised white dots,
2-3 mm in diameter are seen on the inside
of the cheek shortly before rash onset
persist for 1-3 days
 A characteristic maculopapular rash
extending from face to extremities
involving palms & soles : this seems to be
associated with T-cells attacking virally
infected endothelial cells in small blood
vessels
 The rash lasts from 3-7 d & may be
followed by skin exfoliation
1-Respiratory
symptoms
2-Koplick
spots
Persist 1-3 days
Disappear after the rash onset
2-3 days
3-Maculopapular
rash
Lasts for 3-7 days
4-Skin
exfoliation
Long life immunity due to IgG neutralizing Abs
Diagnosis
 Depends mainly on clinical picture
& serology:
 ELISA is used for detection of IgM or
IgG
 For IgM single serum specimen 1-2 wks
after the rash onset
 For IgG, paired acute & convalescent
sera are necessary
 Four fold or more rise in IgG titer
indicates infection
complications
I- Respiratory
 Otitis media & bacterial pneumonia:
common
 Giant cell pneumonia in patients with
impaired CMI ( rare but fatal)
II- Neurological
 Postinfectious encephalitis. Few days
after the rash (1:1000)
 Subacute sclerosing panencephalitis
(SSPE) (1:100.000)
Prevention
Passive
immunization
Measles IGs
- For
immunocompromised patients
-Intramuscular within 6 days of exposure
-Prevent measles symptoms in 80% of cases
Active immunization
Measles vaccine
-Live attenuated
-Given by subcutaneous injection
-Long term immunity
-Monovalent form or MMR vaccine
Rubella
 1- German measles: acute febrile
illness with rash & lymphadenopathy
affecting children & young adults
 2- Congenital Rubella Syndrome:
Serious abnormalities of the fetus as
a consequence of maternal infection
during early pregnancy
Postnatal rubella (German measles)
Pathogenesis & clinical picture
 Mode of transmission: droplet
 Initial viral replication occurs in the
respiratory mucosa followed by
multiplication in the cervical lymph nodes
 Viremia develops with spread to other
tissues. As a result the disease
symptoms develop in 50% of cases after
an incubation period of 12-23 days
 Possibly 50% of infections are
apparently subclinical
 Fever & malaise (prodromal symptoms) for
1-2 days
 Maculopapular rash appears on the
face,then the trunk, then the extremities
and disappears within 3 days
 Suboccipital and postauricular
lymphadenopathy
 Extremely rare complications, self limiting
encephalopathy
complications
 Extremely rare (1/6000)
 Rubella encephalopathy
 6 days after the rash appears
 Complete recovery with no sequalae
Diagnosis
 Depends mainly on clinical picture
& serology:
 ELISA is used for detection of IgM or
IgG
 For IgM single serum specimen 1-2 wks
after the rash onset
 For IgG, paired acute & convalescent
sera are necessary
 Four fold or more rise in IgG titer
indicates infection
Congenital rubella
 Congenital rubella is a group of
physical problems that occur in an
infant when the mother is infected
with the virus that causes German
measles.
 Congenital rubella is caused by the
destructive action of the rubella virus on
the fetus at a critical time in
development.
 The most critical time is the first
trimester (the first 3 months of a
pregnancy). After the fourth month, the
mother's rubella infection is less likely
to harm the developing fetus.
 The rate of congenital rubella has
decreased dramatically since the
introduction of the rubella vaccine.
 Risk factors for congenital rubella
include:
 Not getting the recommended rubella
immunization
 Contact with a person who has rubella
(also called the 3-day measles or
German measles)
 Pregnant women who are not vaccinated
and who have not had rubella risk
infection to themselves and damage to
their unborn baby.
Clinical picture
 Transient symptoms:
 growth retardation, anemia &
thrombocytopenia
 Permanent defects: congenital heart
diseases, total or partial blindness,
deafness & mental retardation
 Progressive rubella panencephalitis:
Extremely rare slow virus disease,
develops in teens with death within 8
yrs
Laboratory Diagnosis
During Pregnancy
 Detection of maternal
IgM or rising IgG in
serum
 Then, detection of
rubella Ag in the
amniotic fluid by DIF
After Birth
 Live newborn:
detection of IgM
antirubella Abs in the
serum of the baby by
ELISA
 Stillbirth: virus isolation
on MKTC
Prevention of congenital rubella
vaccinate
-Women in the childbearing age
-School age children
Pregnancy should be avoided 3 months after vaccination
Maternal rubella infection confirmed during the first trimester????
Therapeutic
abortion
MMR
 Contains 3 live attenuated viruses:
mumps, measles and rubella
 Given in 2 doses
 The first dose: to children 12-15
months of age by subcutaneous
injection
Why not before that?
When is the second dose?
Contraindications?
Roseola
(Roseola infantum or exanthem subitum.)
 a disease caused by at least two viruses,
human herpes virus type 6 (HHV-6) and
possibly type 7 (HHV-7). These viruses are
in the same family as the cold sore virus
(causing herpes simplex and genital
herpes) and the varicella zoster virus
(causing chickenpox and shingles).
 These viruses have only been identified in
recent years and we are still learning
about the full range of diseases caused by
them.
Modes of transmission
 Roseola is spread from person to person
via respiratory fluids or saliva of
infected individuals.
 The incubation period for roseola is
approximately 9-10 days after
exposure.
 The exact period an infected person is
contagious for is unclear but it is most
likely spread during the febrile phase of
the illness when there are no outward
signs that the child is infected with the
virus.
Disease
 In many cases of roseola, the child
appears well with few or no signs or
symptoms. Typical cases are
characterised by the following:
 High fever (often up to 40 degC) for
3-5 days
 Upper respiratory symptoms such as
sore throat, cough, runny nose or
congestion
 Irritability and tiredness
 Rash appears around days 3 to 5 as
fever subsides
 Typically small pink or red raised spots (2-5
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mm in diameter) that blanch (turn white)
when touched
Some spots may be surrounded by a lighter
halo of pale skin
Starts on trunk and may spread to involve
the neck, face, arms and legs
Non-itchy, painless and does not blister
May fade within a few hours or persist for
as long as 2-3 days
 In some cases, a child may be
infected with the virus and never
develop the rash.
 Less commonly, the rash may appear
without a preceding fever.
 In most cases, particularly if fever
is low, the child is well.
 In about 5-15% of young children,
high fevers may trigger febrile
seizures.
 In some cases, a child may be
infected with the virus and never
develop the rash (subclinical).
 Less commonly, the rash may appear
without a preceding fever.
 In most cases, particularly if fever
is low, the child is well.
 In about 5-15% of young children,
high fevers may trigger febrile
seizures.
Complications
 Complications are rare with roseola in most children.
 The most common complication is febrile seizures/convulstions
that may occur in 5-15% of children. These are triggered by
the high fevers of roseola and may be alarming when seen for
the first time. Signs of a febrile seizure include:
 Loss of consciousness
 Jerking or twitching movements in the arms, legs or face for 2
to 3 minutes
 Wet or soiled pants in an unconscious, toilet-trained child
 Irritability
 These seizures are brief and not dangerous
Treatment
 There is no specific treatment for
roseola. The disease is usually mild and
self-limiting.
 Rest, maintaining fluid intake and
paracetamol for fever is all that is
usually required.
 warm baths or sponges can also be used
to help reduce fever.
 No treatment is necessary for the rash
as it does not itch or hurt and fades
spontaneously.
Erythema Infectiosum(5th
disease)
 It is caused by human B19 Parvovirus
 Affects mainly children, occasionally
adults
 Mode of transmission: respiratory
secretions, blood & vertical
 Fifth Disease is a
common childhood
exanthema,
characterized by
"slapped cheek"
facial erythema, as
well as a
maculopapular rash
over the trunk and
the extremities
 During the viremic
phase of the
infection, excess
antibodies lead to
the formation of
immune complexes,
which induce these
characteristic
childhood rashes.
 In adults, B19 infection leads to more
severe symptoms of polyarthropathy,
or inflammatory polyarthritis, rather
than a rash (as in children).
 These symptoms often resemble those
or rheumatoid arthritis in the
distribution of the joints affected
and the characteristics of the
inflammation
Laterothoracic exanthem
 also known as Asymmetric Periflexural
Exanthem of Childhood (APEC).
 An uncommon rash affecting young
children, which is suspected to be due
to a viral infection.
 occurs in winter and spring and
affects twice as many girls as boys.
 The average age is two, most cases
being between one and five years old.
 It usually starts in the
armpit or groin and
gradually extends
outwards, remaining
predominantly on one
side of the body.
 It may spread to the
face, genitalia, hands
or feet.
 The rash starts as tiny raised pink
spots, which may be surrounded by a
pale halo, then slowly becomes flat
and scaly. The middle of older
patches fades to a dusky grey.
 Occasionally the patches are net-like
or in rings. Little blisters or blood
spots may occur.
 The rash is usually quite itchy.
 Sometimes other features of viral
infection occur at the onset of the
rash, such as a fever, sore throat,
cold, vomiting and/or diarrhoea.
 The lymph glands in the armpits and
groins may be enlarged.
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The rash lasts for several weeks, but
always resolves spontaneously within
three months.
VIRAL SKIN INFECTIONS
Herpes Simplex Viruses
Extremely wide spread in human population
Establish latency in nerve cells
Reactivation is common
There are two distinct types of HSVs: type
1 &type 2
 Structurally & morphologically
indistinguishable
 Exhibit sequence gene homology with
serological cross-reaction
 Can be distinguished by restriction enzyme
analysis of viral DNA and mode of
transmission
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Pathogenesis of HSV 1 &2
Sensory ganglia
replication
Initial
infection
site
Migration through
Neuron
Reactivation is through stress stimuli
such as UV light, fever,
hormonal changes,
surgical trauma to the neuron
Antibodies do not prevent reactivation
latency
HSV-1: trigeminal ganglia
HSV-2: sacral ganglia
Diseases caused by HSV-1
1- Oropharyngeal infections:
 Acute gingivostomatitis: occurs in early childhood
- Fever,
- painful vesicular lesions ; on gums, lips & oral
mucosa, these vesicles may rupture leaving a red
based ulcer which
- may be 2ry infected with candida albicans
forming white coat
 Herpes labialis (fever blisters or cold sores)
- Milder recurrent form
- Crops of vesicles at the mucocutaneous junction
of lips or nose
Herpes Labialis
Acute herpetic ginfivostomatitis
2- Herpetic Keratoconjunctivitis:
 Corneal ulcers and lesions of conjunctival
epithelium
 Recurrence takes the appearance of
dendritic ulcer or vesicles on the eye
lids
 Recurrent keratitis may lead to
permanent scarring ending with blindness
Keratitis
Vesicles around eye lid
3- Encephalitis
 Rare
 Involves temporal lobe with high mortality
4- Herpetic Whitlow:
 Fingers herpes infection
 In health care workers e.g. dentists & nurses
5- Eczema Herpeticum:
- Involves known eczematous areas with bacterial
superinfection
6- Disseminated infection:
Fatal esophagitis or pneumonia in immunocompromised
patients
Herpetic Withlow
Eczema Herpeticum
Diseases caused by HSV-2
1- Genital herpes:
 Sexually transmitted
 Vesiculoulcerative lesions of penis in males
and cervix, vulva, vagina, & perineum of
females
2- aseptic meningitis:
Self limited
3- Neonatal Herpes:
Aquired in utero,during, or after birth
Severe in the newborn so, pregnant females
with recurrent herpes should deliver by CS
Neonatal Herpes
Laboratory Diagnosis
 Specimen: Vesicular fluid- Corneal
scrapping
1- Direct Virus Demonstration:
a) L/M:
1. Tzanck smear – from the base of vesicles,
1% aq. soln. of toluidine blue ‘O’
shows multinucleated giant cells with
faceted nuclei & homogenously stained
‘ground glass’ chromatin (Tzanck cells)
2. Giemsa stained smear – intranuclear
Cowdry type A inclusion bodies
Tzanck smear
intranuclear Cowdry type A inclusion bodies
 B) Direct Immunofluorescence:
 Cell scrappings from lesions are stained
with monoclonal antibodies conjugated with
a fluorescence dye. Viral inclusion bodies
appear in UV microscope as a bright green
intranuclear particles
 C) PCR: for detection of viral DNA in CSF
 2- Viral Isolation: tissue culture: human
diploid fibroblasts, human amnion, human
embryonic kidney: CPC (syncytium
formation) seen in 24-48 hrs.
 3) Serology: useful in the diagnosis of
primary infection, Ab (IgM) detection by
ELISA, NT or CFT.
Treatment
Acyclovir
 Inhibits viral DNA polymerase enzyme
 topical, oral, or IV
Doesn’t affect latency
Human Papilloma Viruses (HPVs)
 More than 60 types based on DNA
homology
Cutaneous
warts
Genital
warts
Transmitted through
- Direct contact
- fomites
Sexual contact
Diseases
 A- Cutaneous: benign warts common in
hands and soles
 B- Mucosal:
- Genital warts
- Juvenile laryngeal papillomas
 C- Cervical carcinoma
Molluscum Contagiosum Virus
(MCV)
 It causes molluscum contagiosum
 A benign wart-like tumour
 Usually affects the face, arms or
genital organs
 May heal spontaneously within 2-6
weeks
contact
transmission
Direct & indirect including sexual
Laboratory diagnosis
 PCR for detection of viral DNA
 No serological tests……?
The virus is weakly immunogenic