Transcript VIRAL DISEASES part II - A.T. Still University

VIRAL DISEASES
Part II
Adam Wray, D.O.
April 11, 2006
Molluscum contagiosum
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Poxvirus
MCV-1 to -4 and
variants
MCV-2 in HIV
Worldwide
Children, sexually
active adults and
immunosuppressed
Direct contact
Molluscum contagiosum
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Lesions are smooth surfaced,
firm and dome shaped pearly
papules
Central umbilication
Clinical pattern depends on the
group affected
When restricted to only the
genital area in a child the
possibility of sexual abuse
must be considered
Secondary infections may
occur
Molluscum histopath
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Acanthosis and cup shaped
Eosinophilic and later basophilic inclusion bodies
in the prickle cell layer (Henderson-Patterson
bodies)
Molluscum contagiosum
Treatment
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Topical tretinoin or imiquimod
Extraction
Light cryotherapy
Cantharadin
Surgical tape
Curettage
Podophyllotoxin
Subcutaneous IFN-alpha
5-FU
HAART for AIDS patients
Human monkeypox
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Rare, sporadic zoonosis caused by
orthopoxvirus
More than 90% of cases occur in children
under 15
Fatality rate of 11%
Disease is clinically similar to smallpox
Fever followed by vesiculopustular eruption
Develop following contact with wildlife
sources
Human to human transmission may occur
Picornavirus group
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Single stranded RNA
Only coxsackieviruses, the echoviruses,
and enterovirus type 71 are significant
causes of skin disease
Herpangina
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Disease of children worldwide
Coxsackievirus, echovirus and
enterovirus 71
Acute onset of fever, ha, sore
throat, dysphagia, anorexia,
and sometimes a stiff neck
Yellowish white, vesicles in the
throat, surrounded by an
intense areola
Most frequently on the anterior
faucial pillars, tonsils, uvula, or
soft palate
Herpangina
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Lesions coalesce and
ulcerate leaving a
shallow crater
Lesions disappear in
5-10 days
Treatment is
supportive
Topical anesthetics or
allopurinol
mouthwash
Hand-Foot-and-Mouth Disease
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Infection begins with a
fever and sore mouth
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90% have oral involvement
Lesions are small rapidly
ulcerating vesicles
surrounded by a red areola
Lesions on hands and
feet run parallel to skin
lines
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Red papules that quickly
turn to gray vesicles
surrounded by a red halo
Hand-Foot-and-Mouth Disease
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Typically lasts less than a week
Treatment is again supportive
Topical anesthetics
Coxsackievirus A-16
Distribution and presence of skin lesions
differentiates this from herpangina
CNS disease in 80% of enterovirus 71 HFMD in
Taiwanese outbreak; no CNS disease with
Coxsackie A-16
Eruptive pseudoangiomatosis
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Young children during or immediately
following a viral illness develop blanchable
red papules that resemble angiomas
Face trunk and extremities
Resolve spontaneously within 10 days
Echoviruses 25 and 32 have been
implicated; and more recently EBV
PARAMYXOVIRUS GROUP
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RNA viruses
Measles
Rubella
Measles
(rubeola, morbilli)
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Worldwide disease
Commonly affects children under
age of 15 months
Respiratory spread with an
incubation of 9-12 days
Immunizations are highly
effective
Prodrome- fever, malaise,
conjunctivitis and prominent
upper respiratory symptoms
Measles
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A macular or maculopapular eruption appears
after 1-7 days
Anterior scalp line and behind the ears
Quickly spreads over the face and involves the
entire body by day 3
Purpura may be present
Koplik’s spots are pathognomonic, appear during
the prodrome
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Appear first on the buccal mucosa nearest to the
lower molars as 1mm white papules on an
erythematous base.
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Erythematous lesions
of the measles
exanthem
Pink macules with minimally elevated
papules with confluence
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Koplik’s Spots
cluster of tiny bluish white papules with
an erythematous areola on buccal
mucosa opposite premolar teeth
Measles
Complications
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OM
Pneumonia
Encephalitis
Thrombocytopenic purpura
Infection in pregnant patients is
associated with fetal death
RUBEOLA
management
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Acute
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Vitamin A
decreases morbidity and mortality
given to severe measles even if no nutritional deficit
is suspected
<1yr old exposed to measles tx with immune serum
globulin
vaccine
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MMR given at 12-15 months, and 4-6 years
Rubella
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German measles, 3-day measles
benign contagious viral disease
etiology
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transmission
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Togavirus
inhalation of aerosolized respiratory
droplets
incubation
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12-23 days
Vaccination gives lifelong immunity
RUBELLA
clinical manifestations
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Prodrome- 1-5 days
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mild symptoms of malaise, headache, sore
throat, eye pain, and moderate temperature
elevation
Pain on lateral and upward eye movement is
characteristic
precedes eruption by a few hours to a day
children are usually asymptomatic
RUBELLA
clinical manifestations
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Eruptive phase
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begins on neck or face
spreads to trunk and extremities in hours
lesions are pinpoint to 1 cm, round or oval,
pinkish or rosy red, macules or
maculopapules (purplish lesions of measles
and fine punctate yellow-red lesions of
scarlet fever)
discrete, grouped or coalesced
arthritis of phalangeal joints may be seen
in women
RUBELLA
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Diagnosis
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course and prognosis
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Clinical, posterior cervical, suboccipital, and
postauricular lymphadenitis occurs in more than
half
can be confirmed with serology
typically mild, requiring only symptomatic
treatment
lesions last 24 -48 hours, followed by
desquamation
prevention
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MMR given at 12-15 months, and 4-6 years
Rubella
RUBELLA
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Forchheimer Spots
Pin-head sized red
macules or petechiae
on the soft palate and
uvula start with onset
of rash
Congenital Rubella Syndrome
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Infants born to mothers who have had rubella
during the first trimester of pregnancy
transplacental transmission as high as 80% in
the first trimester
Typical anomalies include IUGR, deafness,
mental retardation, cataracts, retinopathy,
cardiac defects, and “blueberry muffin” rash.
Prior to pregnancy antibody titer should be
verified. Immunization is contraindicated
in pregnancy.
Congenital Rubella
Asymmetric Periflexural
Exanthem of Childhood (APEC)
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AKA unilateral laterothoracic exanthem
Children 8 mo to 10 yrs
Cause is unknown
Viral origin has been proposed
Symptoms of mild upper respiratory or
gastrointestinal infection usually precede
the eruption
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Erythematous
macules and
papules involving
the axilla, lateral
trunk and flank.
In this patient the
exanthem
progressed to
bilateral distribution
but maintained leftsided predominance
Asymmetric Periflexural Exanthem
of Childhood (APEC)
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Erythematous papules coalesce to form
poorly marginated morbilliform plaques
Mild pruritis
Lesions begin unilaterally, close to a
flexural area, usually the axilla
Centrifugal spread to adjacent trunk
and extremity
The contralateral side is involved in
70% of cases, asymmetrical nature is
maintained
Asymmetric Periflexural Exanthem
of Childhood (APEC)
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Lymphadenopathy is
seen in 70%
Last 2-6 weeks on
average
Resolves
spontaneously
Topical steroids or
oral antibiotic are of
no benefit
Oral antihistamines
PARVOVIRUS GROUP
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Parvovirus B19 is the most common agent in this
group to cause human disease.
More common in the spring in temperate climates
Erythema infectiosum papular purpuric gloves and
socks syndrome, arthropathy, aplastic crisis in
hereditary spherocytosis and sickle cell disease, and
chronic anemia in immunosuppressed patients are
clearly related to parvovirus B19.
Children with aplastic crisis due to parvovirus B19
usually do not have a rash.
Erythema Infectiosum
(Fifth Disease)
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Worldwide benign infectious exanthem occurs
in late winter, early spring.
Parvovirus B19
Spread by respiratory droplets
Viral shedding has stopped by the time the
exanthem has appeared
Incubation 4-14 days
prodrome
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pruritus, low-grade fever, sore throat, malaise
seen in 10% of cases
Erythema Infectiosum
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Three distinct overlapping stages
facial erythema. Red papules on the
cheeks that rapidly coalesce.
Resembles erysipelas. “slapped cheek.”
net pattern erythema. Fishnet like
pattern, begins on extremities then
extends to trunk
recurrent phase. Eruption may
reappear following emotional upset,
heat (esp bathing), exercise, or sunlight
exposure over next 2-3 weeks.
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Lacy, reticulated skin
eruption over the arm
during the second
stage of the
exanthem
Papular Purpuric Stocking and
Glove Syndrome
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Occurs in teenagers and young adults
Pruritus, edema, and erythema of the
hands and feet, and a fever is present
Lesions are sharply cut off at the wrists
and ankles
Mild erythema of the cheeks, elbows,
knees and groin
Syndrome resolves within 2 weeks
May be associated with HBV in adults.
Erythematous patches with petechiae
on the palms
ARBOVIRUS GROUP
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Comprise the numerous arthropod-borne
RNA viruses
West Nile Fever
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Flavavirus, endemic to E. Africa; first appeared
in eastern U.S. in ’99 and reached CA by 2004
A maculopapular eruption accompanied by
lymphadenopathy and fever characterize this
disease
The Culex mosquito is the vector
80% of those infected will be asymptomatic
Complications: seizures, flaccid paralysis, ataxia,
and ALOC. May have permanent neurologic
sequelae.
Sandfly Fever
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AKA phlebotomus fever and pappataci fever
Small pruritic papules appear after the bite
of a sandfly on face and neck; may appear
scarlatiniform.
Fever, ha, malaise, nausea, conjunctival
injection, stiff neck, and abdominal pains
suddenly develop
Recovery is slow, with recurring bouts of
fever
No specific treatment is available
Dengue
(break-bone fever)
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A common disease of tropical
regions throughout the world
Spread by Aedes aegypti
mosquito
Disease begins with a sudden
high fever, ha, back ache,
retroorbital pain, bone and
joint pain, weakness,
depression and malaise
A scarlatiniform or morbilliform
exanthem, especially on the
thorax and joint flexors may be
seen
Patient may recover fully at
this stage
Dengue
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In 1-7% of cases dengue
hemorrhagic fever
develops
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bleeding,
thrombocytopenia, and
hemoconcentration develop
30% with DHF will go on to
Dengue shock syndrome
Mortality 1-15%
Systemic steroids of no
benefit
Alphavirus
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Sindbis virus infection
Seen in Finland
Transmitted by the Culiseta mosquito
Multiple erythematous papules with a
surrounding halo associated with a fever
and prominent arthralgias
Symptoms resolve over a few weeks
PAPOVAVIRUS GROUP
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DS, DNA viruses
Slow growing
Replicate within the nucleus
Because they contain no envelope, they
are resistant to drying, freezing, and
solvents.
Verruca
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Human papillomaviruses include more than 100
types
Most types cause specific types of warts and
favor certain anatomic locations
Infections are described as clinical, subclinical
and latent
Peak age for cutaneous warts is teenage and
young adults
Caucasians have cutaneous warts twice as
frequently as other ethnicities.
Verruca vulgaris
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Commonly HPV 2
5% prevalence in children
Frequent emersion of hands in water is
a risk factor
Natural history is for spontaneous
resolution, half by 1 year and two thirds
by 2 years
Usually located on the hands
Present as elevated, rough, grayish
papules
Verruca vulgaris.
Note the characteristic
features of ‘church spire’ papillomatosis heaped with
ortho- and parakeratosis, acanthosis and koilocytosis.
Verruca vulgaris
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Diagnostic clue- warts do not have
dermatoglyphics
Occur anywhere on skin
Spread by autoinnoculation
Digitate or filiform warts on the face and
scalp
Verruca plana
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HPV 3, 10,28, and 41
Children and young adults
Flat-topped papules that are slightly
erythematous or brown
Generally multiple and grouped
Face, neck, dorsa of hands, wrists and knees
Men who shave and women who shave their
legs
Koebnerization
Highest rate of spontaneous remission
Verruca plantaris
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HPV type 1, 2, 4, 27
Appear at pressure points on the ball of the foot
Frequently several lesions are seen
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Mosaic wart
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May be confused with callous, no black dots
Myrmecia type- occurs as smooth surfaced,
deep, often inflamed and tender papules or
plaques- may be confused with mucinous cyst
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Myrmecial wart
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Cause by HPV 1
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Verrucae plantares
Photo after the
shaving of the
hyperkeratotic
surface
HPV-60
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Ridged wart
Persistence of
dermatoglyphics
This type also causes
plantar verrucous
cysts
Treatment
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Depends on the type of wart and the age
of the patient
Allow 2-3 months of therapy
Do not abandon any treatment too quickly
TX-flat warts
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Frequently undergo spontaneous
remission
Cryotherapy
Topical salicylic acid preparations
topical tretinoin
5-FU
anthralin
TX-common warts
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Two basic approaches
Destruction and Induction of local immune
reactions
Cryotherapy, salicylic acid preparations,
canthrone, bleomycin, surgical ablation,
laser, high dose cimetidine, heat
treatment, isotretinoin, hypnotic
suggestion, DNCB
TX-plantar warts
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Salicylic acid preparations
Cryotherapy
Cantharadin
Bleomycin, laser, and DNCB
Intralesional candida antigen
Genital warts
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The most common sexually transmitted
disease
Lifetime risk in sexually active young
adults may be as high as 80%
A large portion of genital HPV is either
subclinical or latent
Infection is closely linked with cancer of
the cervix, glans penis, anus,
vulvovaginal area, and periungal skin
Transition zones of cervix and anus
Cofactors for progression to cancer
with HPV
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HPV type (16 and 18)
Location of infection
Cigarette smoking
Uncircumcised status
Immunosuppressed status
Genital warts
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More than 30 HPV types are associated
with genital warts
Those producing benign lesions- low
risk
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Those associated with cancer- high risk
or oncogenic type
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Most common are HPV-6 and HPV-11
most common HPV-16 and HPV-18
Virtually all condylomata are caused by
types –6 and –11
Condylomata acuminata
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Appear as lobulated papules that are
frequently multifocal
Intraurethral condylomata may present
with terminal hematuria, altered urinary
stream, or urethral bleeding
Numerous genital warts may appear
during pregnancy
Other sexually transmitted disease may
be present
Bowenoid papulosis and HPVinduced genital dysplasias
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Characterized by flat, often
hyperpigmented papules
Singly or in multiples
HPV-16 may behave similar to other
genital warts
May progress to invasive SCC
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Bowenoid papulosis
of the anus positive
for high-risk HPV
in a homosexual
male
Erythroplasia of Queyrat.
A well
demarcated velvety plaque of the prepuce
positive for high-risk HPV
Giant condyloma acuminatum
(Buschke-Löwenstein tumor)
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A rare, aggressive wart-like growth that
is a verrucous carcinoma
HPV-6
Most often occurs on the glans penis or
prepuce of an uncircumcised male
May invade deeply, and uncommonly
metastases
Complete surgical excision
 Buschke-
Löwenstein
Tumor
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Cauliflower-like
deeply infiltrating
giant condyloma
acuminata
Diagnosis of genital warts
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Inspection
Acetowhitening may help in the
differentiation of certain genital papules
Bowenoid papulosis may require Bx
Treatment of genital warts
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Recurrence is frequent
Not proven to reduce transmission to
sexual partners nor to prevent
progression to dysplasia or cancer
Subclinical of the external genitalia
should not be sought or treated
Bleeding genital warts may increase the
sexual transmission of HIV and hepatitis
B and C
Treatment of genital warts
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Podophyllin 4-8 hrs, weekly application
Purified podophyllotoxin 0.5% sln
Aldara, 3 alternate days per week
TCA (safe in pregnancy)
Cryotherapy (also safe in pregnancy)
Electrofulgeration or electrocauterization
CO2 laser
PDT (ALA 6-10 h prior to blue light)
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Any surgical method that generates a
smoke plume is potentially infectious to
the surgeon
5-FU 5% cream, esp. bowenoid papulosis
Systemic and intralesional interferon alfa
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CDC no longer recommends
Genital warts in children
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Children can acquire genital warts
through vertical transmission
perinatally, digital inoculation or
autoinoculation, fomite or social
nonsexual contact, or through sexual
abuse
HPV typing has demonstrated that most
warts in the genital area of children are
“genital” HPV type
And most children with them have
family members with them as well
Genital warts in children
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Finding of a nongenital type does not
exclude abuse
The risk for sexual abuse is highest for
children older than 3 yrs of age
Case-by-case management
Should screen for other STDs
Podophyllotoxin, imiquimod, light
cryotherapy
Recurrent respiratory (laryngeal)
papillomatosis
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HPV associated papillomas may occur throughout
the respiratory tract, from the nose to the lungs
Bimodal distribution- children under 5 and after
15
Affected young children were born to mothers
with genital condylomata and present with
hoarseness
HPV-6 HPV-11
Carcinoma that is often fatal develops in 14%
Heck’s disease
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Linked to HPV-13
AKA focal epithelia
hyperplasia
Small white to pinkish
papules occur diffusely in
the oral cavity
Common in Native
Americans, Greenland,
and Turkey
Epidermodysplasia verruciformis
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A rare inherited disorder characterized by
widespread HPV infection and cutaneous
SCCs
Most commonly inherited as and AR trait
HPV-3, HPV-10 and many other “unique”
types
Pathogenesis is unknown
Presents in childhood and continues
throughout life
Epidermodysplasia verruciformis
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Skin lesions include flat, wartlike lesions of the
dorsal hands, extremities, and face
SCCs develop in 30-60% of pts, most often on
sun exposed areas,-5,-8,-47
Actinic background
Surgery, radiation is contraindicated
Patients cannot be sensitized to topical
immunosensitizers.
Strict sun avoidance
EV histology
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Cells of the upper epidermis have a
characterisitic clear, smoky or light blue
pale cytoplasm and a central pyknotic
nucleus
Characterized by Rapini as “bubbly bluish
cytoplasm” in keratinocytes
May have hyperchromatic, pleomorphic
cells
EV histology
Warts in immunosuppressed
patients
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Predisposing conditions include organ
transplantation, immunosuppressive medication,
congenital immunodeficiency diseases,
lymphoma and HIV infection
By 5 yrs posttransplant 90% of pts have warts
Regular dermatologic examinations
Standard methods of treatment, efficacy is
reduced
Warts at angle of mouth bilaterally is a
characteristic and often unique manifestation of
HPV infection in AIDS
RETROVIRUSES
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Contain RNA which is converted by a
virally coded reverse transcriptase to
DNA in the host cell
The target cell population is primarily
CD4+ lymphocytes
Transmission by sexual intercourse,
blood products/intravenous drug use,
and from mother to child during
childbirth or breastfeeding
HTLV-1
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Endemic in Japan, subSaharan Africa and
southeastern US
Responsible for several clinical syndromes
1% will develop adult T-cell leukemialymphoma
Four forms: smoldering, chronic, acute, and
lymphomatous, usually progressing in that
order
Skin lesions in ATLL include erythematous
papules or nodules
HTLV-1
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Infected patients may develop various
forms of dermatitis mimicking other skin
diseases
Infective dermatitis, children present with
a chronic eczema of the scalp, axilla,
groin, external auditory canal,
retroauricular area, eyelid margins,
paranasal areas and neck
Chronic nasal discharge
Cultures positive for S. aureus
Human Immunodeficiency Virus
(HIV, HTLV III)
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Cutaneous manifestations are prominent
Affecting up to 90% of HIV-infected persons
Many have multiple skin lesions of different
types
Skin lesions can be classified into three broad
categories: infections, inflammatory
dermatoses, and neoplasms
Skin lesions tend to appear at a specific stage of
disease, making them useful markers
Human Immunodeficiency Virus
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Seborrheic dermatitis , pruritis ani,
psoriasis, Reiter’s syndrome, atopic
dermatitis, herpes zoster, acne rosacea,
oral hairy leukoplakia, onychomycosis,
warts, recurrent S. aureus folliculitis and
mucocutaneous candidiasis- helper T-cell
counts 200-500
Human Immunodeficiency Virus
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With counts < 200, pt defined as AIDS
Opportunistic infections: chronic herpes
simplex, MC, bacillary angiomatosis,
systemic fungal infections and
mycobacterial infections
Hyperreactive skin is also seen:
eosinophilic folliculitis, GA, drug
reactions, enhanced reactions to insect
bites, photodermatitis
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Eosinophilic
folliculitis (right)
Bacillary
angiomatosis
(below)
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T-cell count < 50 = advanced AIDS
Unusual presentations of opportunistic
infection
HAART, highly active antiretroviral therapy,
is typically associated with resolution of
cutaneous complications
About half of HIV patients respond
Immune reconstitution assoc with HAART
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Eosinophilic folliculitis, drug eruptions, HPV,
tattoo and foreign body granulomas, and
sarcoidosis may exacerbate during this period
Secondary to sudden improvement of immune
system
Primary HIV infection
(Acute seroconversion
syndrome)
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An acute illness develops several weeks after
infection
Clinical syndrome resembles Ebstein-Barr
infection
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Fever, sore throat, cervical adenopathy, rash, and
oral and genital and rectal ulceration
Dysphagia may be prominent
Papular eruption of discrete, slightly scaly,
oval lesions of the upper trunk resembling PR
HIV-Associated pruritus
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Not caused by HIV disease itself but related to
its associated inflammatory dermatoses
“papular pruritic eruption”- a wastebasket
diagnosis
Follicular eruptions are more common
Eosinophilic folliculitis is the most common
pruritic follicular eruption, helper T-cell <200
Urticarial follicular papules on the upper trunk,
face, scalp, and neck
90% of lesions occur above the nipple line
HIV-Associated pruritus
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Disease waxes and wanes and may
spontaneously clear, only to flare
unpredictably
Peripheral eosinophilia may be present
Topical steroids and antihistamines
Phototherapy or itraconazole
isotretinoin
HIV-Associated Neoplasia
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Kaposi’s sarcoma
Superficial BCC
SCC
Genital HPV-induced SCC
Extranodal B-cell and T-cell lymphoma
BCC’s behave in the same manner, receive
standard management
HIV-Associated Neoplasia
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SCC’s, standard management, excision is
recommended
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15% recurrence rate with ED&C unacceptable
SCC in sun-exposed skin can be very
aggressive
Genital SCC, associated with “high-risk”
HPV types (-16, -18)
Extranodal B-cell and T-cell
lymphoma
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Associated with advanced
immunosuppression of AIDS
Present as violaceous or plum-colored
papules, nodules or tumors
MF can also be seen in patients with HIV
infection
Melanoma with HIV
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Occasionally seen in HIV patients
Prognosis is unknown
It has been suggested that the risk of metastasis
is increased
Patients have same risk factors as other
melanoma patients
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Multiple nevi, fair skin type, prior sunburn
Many fair skinned individuals with HIV complain of
new onset atypical moles (analogous to organ
transplant patients).
AIDS and Kaposi’s Sarcoma
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HHV-8
Patients with AIDS present with
symmetrical widespread lesions, that
are often numerous
Any mucocutaneous surface may be
involved
Favors hard palate, trunk, penis, lower
legs and soles
DX by biopsy
Red-violet papules on the palate
in addition to oral candidiasis
AIDS and Kaposi’s Sarcoma
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Treatment depends on the extent and
aggressiveness of the disease
Effective HAART after about 6 months is
associated with involution of KS lesions
Initial treatment for fewer than 50 lesions
Intralesional vinblastine
Cryotherapy
Irradiation therapy
AIDS and Kaposi’s Sarcoma
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Systemic therapy in aggressive disease
Interferon alfa
Vinca alkaloids
Bleomycin
Liposomal doxyrubicin
Taxol may be used for treatment failures