Viral%20infection%20of%20the%20skin%20

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Viral infection of the skin mucous membrane

• Dr Mohammed Arif
• Associate professor
• Consultant virologist
• Head of the virology unit, college of medicine
  KKUH

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Viral infection of the skin mucous membrane

• Viral diseases associated with maculopapular
  rash.
• Viral disease associated with vesicular rash.
• Human warts.

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Viral diseases associated with maculopapular rash

• Measles.
• Rubella (German measles),
• Erythema infectiosum (slapped cheek or fifth
  disease).
• Exanthem subitum (roseola infantum or sixth
  disease).

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Measles

• Viral etiology measles virus.
• Family paramyxoviridae,
• Enveloped, with two glycoprotein spikes.
• Hemagglutinine spikes are the main neutralizing
  Ag.
• Also mediate adsorption of the virus to the host
  cell surface.

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Structure classification (cont.)

• The F-glycoprotein, mediate penetration of the
  virus to the host cell by fusion process and
  mediate fusion of infected cells together to form
  multinucleated giant cell (syncytium formation).
• The viral genome is SS-RNA, with negative
  polarity.
• Virion contains the enzyme transcriptase.
• One antigenic serotype.

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Measles

• Transmission by inhalation of respiratory
  droplets.
• IP 10 14 days.
• Target group children.

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Pathogenesis

• After entry, the virus replicates in the
  epithelial cells of the URT.
• The virus spreads by blood to the lymphoid
  tissues and replicates there.
• The virus then spreads by blood and infects the
  endothelial cells of the blood vessels.
• The cytotoxic T-cells attack virus infected
  vascular endothelial cells. And this will lead to
  the development of the maculopapular rash.

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Clinical features

• Prodromal Fever, cough, mild conjunctivitis,
  nasal discharge. Lasting1-3 days.
• Kopliks spots small, red papules with white
  central dot, appear on the side of the cheek,
  their number 5 or 6, remain for a day or two.
  They are diagnostic for measles.
• Rash maculopapular rash, first appear on the
  face then spread downward over the trunk and
  extremities.

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Clinical features (cot,)

• The rash is red, become confluent, last 4 or 5
  days, then disappears leaving brownish
  discoloration of the skin and fine desquamation.
• Recovery is usual.

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Complications

• Common complications croup, bronchitis , otitis
  media.
• Rare complications post-infectious
  encephalomyelitis, Sub acute sclerosing pan
  encephalitis (SSPE) giant cell pneumonia.

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Clinical features of measles
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Post infectious encephalomyelitis

• Rare complication of measles.
• Develops few days of the main illness.
• Symptoms are fever, headache, vomiting,
  drowsiness, mental confusion, lack of
  coordination, convulsions.
• Survivors are left with permanent neurological
  sequalae.
• It is an auto immune disease, in whish the immune
  system attacks neurons.

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SSPE

• Late and rare complication of measles.
• Due to reactivation of latent measles virus in
  the brain.
• Develops several years after measles attack.
• The disease is characterized by personality
  changes, memory defect, impairment of vision
  speech and cognition, lack of coordination,
  blindness, convulsion, coma death.
• No effective treatment.

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SSPE

• Diagnosis is based on the clinical features,
  characteristic EEG and high level of measles Ab
  in the CSF.

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Giant cell pneumonia

• Rare complication.
• Seen in the immunocompromised children.
• Due to direct virus invasion of the lungs.

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Prevention

• Live attenuated vaccine (MMR).
• Contains live attenuated measles, mumps and
  rubella virus strains.
• Administered in one dose.
• Protection good immunity.
• Contraindications should not be given to
  pregnant women and immunocompromized.

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Treatment lab. diagnosis

• Treatment there is no specific anti viral drug
  therapy.
• Lab. Diagnosis By detection of IgM-Ab to
  measles virus.

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Rubella (German measles)

• Viral etiology Rubella virus.
• Family Togaviridae.
• Genus Rubivirus.
• The virus is enveloped, pleomorphic with helical
  nucleocapsid.
• The viral genome is SS-RNA with positive polarity.

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Rubella

• Transmission By inhalation of respiratory
  droplets.
• IP 14 21 days.
• Target group children.

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Pathogenesis

• After entry, the virus replicates in the
  epithelial cells lining the URT and invades
  sub-epithelial tissue.
• The virus spreads by the blood stream to lymphoid
  tissues, followed by viremia.
• The virus infects the endothelial cells of blood
  vessels in the skin, leading to the development
  of the maculopapular rash.
• Virus-Ab complexes are thought to play a role in
  the development of the rash.

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Clinical features

• Prodromal Fever, cough, nasal discharge, mild
  conjunctivitis.
• Rash Maculopapular rash, first appears on the
  face then spreads downwards to trunk and limbs.
• The rash is red, discrete, usually fades after 48
  hr.
• In nearly 50 of all infections there is no rash
  at all.
• Rubella is characterized by enlargement of the
  post-auricular and sub-occipital lymph nodes.

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Complications

• Mild arthritis in adult females.
• Post infectious encephalomyelitis.
• Thrombocytopenic purpura.

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Clinical features of rubella
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Prevention , treatment lab Diagnosis.

• Vaccine Live attenuated vaccine (MMR).
• Treatment There is no specific viral therapy.
• Lab. Diagnosis By detection of IgM-Ab rubella
  virus.

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Congenital rubella

• Infection occur in uitro before rupture of the
  fetal membrane.
• The fetus is infected transplacentally.
• Rubella virus has no cytocidal effect on the
  fetal cells,
• The virus establishes persistent infection in the
  fetal cells. It interferes with cell division
  resulting in malformations in the heart, eyes and
  hearing organs.

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Congenital rubella

• Congenital rubella occurs when non-immune
  pregnant women acquires the virus in the first
  trimester of pregnancy.
• The main congenital defects are eye
  abnormalities, congenital heart diseases,
  deafness mental retardation.
• Affected infants have also hepatosplenomegaly,
  thrombocytopenic purpura, low birth weight,
  jaundice and anemia.

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Congenital rubella

• Infected infants shed the virus into throat and
  urine for several months AFTER BIRTH and can
  infect susceptible individuals.

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Prevention lab. Diagnosis.

• Prevention By immunization of all children at
  age of 15-months with the MMR vaccine.
• Lab Diagnosis By detection of IgM-Ab to rubella
  virus in the infant serum.

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Slapped cheek, Erythema infectiosum, Fifth
disease.

• Viral etiology Human parvovirus B-19.
• Family Parvoviridae.
• Small. Unenveloped, icosahedral, ss-DNA.
• One antigenic type.
• IP 4-10 days.
• Transmission By inhalation of respiratory
  droplets.
• Target group children.

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Pathogenesis

• The virus infects two types of cells
• The endothelial cells of the blood vessels in the
  skin.
• And the red blood cells precursors (erythroplast)
  in the bone marrow, which account for aplastic
  anemia.
• Immunocomlexes may attribute to the development
  of the rash and arthritis.

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Clinical features

• The disease starts with fever, sneezing and
  coughing.
• Followed by the development of the maculopapular
  rash.
• The rash is red, confluent, fine, most intense on
  the cheek.
• The rash may appear on the trunk and limbs.
• Lesions fades from the center leaving the
  periphery red, developing characteristic
  reticular or lace like pattern.

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Clinical features

• There is mild generalized lymphadenopathy.
• Arthralgia with swelling and pain in the joints
  are seen in women.
• Recovery is complete.

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Clinical features of slapped cheek
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Complications

• Aplastic anemia, characterized by absence of
  regeneration of RBC seen in the
  immunocompromized.
• Aplastic crisis, sudden and temporary
  disappearance of erythroplasts from the bone
  marrow, seen in patients with hemolytic anemia.

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Prevention, treatment lab. diagnosis

• Prevention. There is no vaccine available yet.
• Treatment. There is no specific antiviral drug
  therapy.
• Lab, diagnosis. By detection of Ig-M antibody.

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Fetal infection

• Congenital infection due to parvovirus B-19
  occurs when non immune pregnant women acquire the
  virus in the first half of pregnancy.
• Intrauterine infection can lead to severe anemia,
  massive edema, congestive heart failure and fetal
  death (hydrops fetalis).

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Exanthem subitum, Roseola infantum,Sixth disease

• Caused by human herpes virus type-6.
• Family herpesviridae.
• Enveloped, icosahedral, with ds-DNA genome.
• IP 10-14 days.
• Transmission By inhalation of respiratory
  droplets,
• Target group Children.

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Clinical features.

• The disease starts with fever for 3-5 days. As
  the fever subsides a discrete maculopapular rash
  appears first on the trunk then spreads to face
  and limps.
• There is a mild generalized lymphadenopathy.
• Recovery is complete.
• Complications Rare, thrombocytopenia,
  encephalitis.
• Prevention There is no vaccine available yet.
• Treatment there is no specific anti-viral drug
  therapy.

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Viral diseases associated with vesicular rash

• HSV-1 infection.
• HSV-2 infection.
• Varicella (chickenpox).
• Zoster.
• Herpangina.
• Hand-foot mouth disease.

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Family Herpesviridae.

• All herpes viruses are morphologically identical
  and have the same structure.
• They consist of outer envelope and internal
  nucleocapsid.
• The capsid is icosahedral with 162-capsomeres.
• The viral genome is linear ds-DNA.

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Herpesviruses

• There are eight human herpes viruses.
• Herpes simplex virus type-1 (HSV-1).
• Herpes simplex virus type-2 (HSV-2).
• Varicella zoster virus (VZV).
• Cytomegalovirus (CMV).
• Epstein-Bar virus (EBV).
• Human herpes virus type 6 (HHV-6).
• Human herpes virus type 7 (HHV-7).
• Human herpes virus type 8 (HHV-8).

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Classification

• Three subfamilies.
• Alfa herpesvirinae, HSV-1, HSV-2, VZV.
• Beta herpesvirinae, CMV, HHV-6, HHV-7.
• Gamma herpesvirinae, EBV, HHV-8.

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Latency

• The most important characteristic of herpes
  viruses is latency.
• After resolution of primary infection, the virus
  remains latent inside the human body for life.
• HSV-1, remains latent in the trigeminal ganglion.
• HSV-2, remains latent in the sacral ganglion.
• VZV, remains latent in the dorsal root ganglion.

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Types of HSV-1 infection

• 1--- Primary HSV-1 infection
• Mostly inapparent, if there is a clinical
  manifestation, it takes the form of
• Gingivostomatitis.
• Pharyngotonsilitis.
• Herpetic whitlow.
• Keratoconjunctivitis.
• Encephalitis.
• Disseminated infection in the immunocompromised.

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Types of HSV-1 infection

• 2--- Recurrent infection
• Due to reactivation of latent virus in the
  trigeminal ganglion. Two types of recurrent
  infections
• Herpes labialis.
• Keratitis.

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Pathogenesis

• After entry ,the virus replicates locally in the
  skin at the site of entry.
• Typical herpes lesions are developed.
• The virus migrates up the neurons to the
  trigeminal ganglion and remain latent.
• When the virus is reactivated, it travels through
  neurons to the same site where primary infection
  occurred.

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Transmission

• By direct contact with herpes lesions.
• By saliva.

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Clinical features

• 1- Gingivostomatitis
• Occurs primarily in children.
• The disease is characterized by
• Fever, localized pain, vesicles develop on
  the buccal mucosa and gums, vesicles ruptures to
  form ulcers.
• The disease is self limiting, recovery is usual.
• The virus remains latent in the trigeminal
  ganglion.
• The disease usually lasts for 5-12 days.

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Gingivostomatitis

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Clinical features

• 2- Herpetic whitlow
• Vesicles and ulcers appear on the tips of the
  fingers.
• Affects nurses and dentist.

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Clinical features

• 3- Kerato conjunctivitis
• Primary infection can involve both conjunctivitis
  and cornea.
• Incase of conjunctivitis, there is localized
  pain, edema, preauricular adenopathy,
  lacrimation, vesicles and ulcers appear on the
  conjunctiva.

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Clinical features

• Keratitis
• Corneal infection varies from superficial that
  heal without damage to one affecting deeper parts
  of the eye.
• Severe ulceration of the cornea may lead to
  blindness, usually unilateral.
• Symptoms include severe eye pain, photophobia,
  blurred vision and intense lacrimation.

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Clinical features

• 4- Encephalitis
• A rare manifestation of primary HSV-1 infection.
• The virus invades directly the brain.
• Usually vesicles are not present on the body
  surface.
• The temporal lobes are primarily involved.
• The main symptoms are fever, severe headache,
  drowsiness, metal confusion, lack of
  coordination, convulsions.
• Herpes encephalitis is usually caused by HSV-1 .
• Mortality rate is high, survivors are left with
  permanent neurological sequalae.

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Recurrent infections

• 1- Herpes labiales (cold sores)
• Usually milder disease, with short duration.
• Few vesicles usually appear around the lips.
• 2- Keratitis
• Repeated ulceration of the cornea may lead to
  blindness.

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Herpes labialis

• 
  

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HSV-2

• Types of infections
• Primary infection
• --- Genital
  herpes.
• --- Neonatal
  herpes.
• Recurrent infection
• --- Genital
  herpes.

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Genital herpes

• Both HSV-1 HSV-2 can cause genital herpes.
• About 90 of genital herpes are caused by HSV-2
  and only 10 by HSV-1.
• The signs and symptoms are similar in both cases.

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Transmission

• Sexually, by direct skin contact with herpetic
  lesions, vesicle fluid and vaginal secretions.
• From infected mother to neonate (neonatal herpes)
  mainly perinatally (during labor and delivery).
• HSV-2 infects sexually active adults, especially
  those with multiple sexual partners.

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Pathogenesis

• HSV-2 enters the body through the mucous membrane
  of the genitalia or through abraded or
  traumatized skin.
• After entry, the virus replicate at the portal of
  entry.
• After resolution of primary infection, the virus
  travels along the neurons to the sacral ganglion
  and remain latent for life.
• The latent virus may reactivated under certain
  stimuli and recurrent herpetic infection occurs.
• When the virus is reactivated, it travel backs
  from the sacral ganglion through nerve axons to
  the same site of primary infection.

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Pathogenesis

• The virus remains latent in an episomal form
  (plasmid).
• During latency, no viral genes are expressed,

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Primary genital herpes

• Primary infection is usually asymptomatic.
• Symptomatic infection is characterized by
  localized pain, erythema, edema, inguinal lymph
  adenopathy, development of localized vesicular
  rash, vesicles ruptures to form ulcers.
• Herpetic lesions appear on the external genitalia
  of males and females.
• Lesions also appear inside vagina, urethra and
  cervix.
• After resolution of primary infection, the virus
  travels from the genitalia via neurons to the
  sacral ganglion where it remains latent.

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Neonatal herpes

• Rare condition and often fatal to the neonate.
• It occurs when the mother is shedding the virus
  in the birth canal at the time of delivery.
• The neonate acquires the virus during the passage
  in the birth canal.
• Since the neonate is not immune to HSV-2, the
  virus spread to many organs such as lungs, liver
  and the CNS.

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Neonatal herpes

• Neonatal herpes may take the form of
• 1- Generalized infection the virus disseminates
  through the neonatal organs and often fatal.
• The clinical features include hepatomegaly,
  thrombocytopenia, pneumonia and encephalitis.
• 2- Encephalitis due to direct invasion of the
  brain, the mortality rate is high.
• 3- Cutaneous lesions confined to the skin.
  Prognosis is good.

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Recurrent infections

• Recurrent genital herpes is usually mild and last
  for few days.
• Usually few vesicles develop on the external
  genitalia,with mild local symptoms such as pain
  and itching.
• Lesions usually lasts 2-5 days.
• The reactivated virus travels back from the
  sacral ganglion through neurons to the genital
  areas.

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Lab. diagnosis

• Isolation of the virus in tissue culture,
  followed by identification of the virus.
• Scraping from the base of the vesicles, direct
  IF.
• Detection of Ig-M antibody to HSV-2.
• Detection of the viral-DNA, using PCR. This
  method is limited to life threatening conditions,
  such as encephalitis.

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Prevention

• There is no vaccine is available yet for HSV-2.
• Prevention measures, by practicing safer sex
  (having one sexual partner).

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Treatment

• Acyclovir, 400mg thrice daily for 10-days.
• Famciclovir, 250 mg thrice daily for 5-days.
• Valaciclovir, 1g, twice daily for 10-days.

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The link between HSV-2 and cervical cancer

• Recent study shows that
• HSV-2 infects the tissue of the cervix, causing
  ulcerating lesions.
• Therefore, it serves as initiator co-factor for
  human papilloma viruses which progress it to
  cervical cancer.
• HSV-2 makes it easier to HPV to get deeper into
  the cervical tissue.

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Varicella (chickenpox)

• Caused by varicella-zoster virus (VZV).
• The virus is transmitted by inhalation of
  respiratory droplets and by direct contact with
  the skin lesions.
• Varicalla is a common childhood disease.
• Varicella is the primary illness.
• Zoster is the recurrent form of the disease.

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Pathogenesis

• After entry, the virus replicates in the
  epithelial cells of the URT.
• The virus spread by blood stream to the skin,
  where the typical vesicular rash occurs.

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Clinical features

• IP 14-21 days.
• The disease starts with, fever, malaise, cough,
  headache, generalized vesicular rash.
• The rash first appears on the trunk, then spreads
  to face and limbs.
• The rash appears in successive waves.
• Lesions progress from macules to papules to
  vesicles.
• Vesicles ruptures to form ulcers.
• The illness usually lasts for 4-7 days.

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Complications

• Post-infectious encephalomyelitis.
• Pneumonia in adults.
• Hepatitis.
• Myocarditis.

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Clinical features of varicella

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Vaccine

• Live attenuated vaccine is available.
• Administered in one dose.
• Recommended for children 1-12 years, teenagers
  and adult who have not the diseases.

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Lab. diagnosis

• Detection of Ig-M antibody.
• Scraping from the base of the vesicles.

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Treatment

• No anti-viral drug therapy is necessary for
  immunocompetent children.
• Severe cases of chickenpox is treated with
  acyclovir.

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Congenital varicella

• Very rare.
• Most pregnant women have immunity to varicella,
  due to previous exposure.
• Varicella in the first half of pregnancy is
  associated with fetal abnormalities include
• --- limb hypoplasia, muscular atrophy,
  optical atrophy, chorioretinitis, mental
  retardation and skin lesions.

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Neonatal varicella

• If the mother acquired varicella more than 7-days
  before delivery, then the disease in the neonate
  is usually mild. The disease is modified by the
  passively acquired maternal antibody.
• If the mother acquired varicella within 7-days of
  delivery, the neonate is likely to develop severe
  disease.

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Zoster (shingles)

• Zoster is localized vesicular rash.
• It is a disease of elderly.
• It is due to reactivation of VZV, which is latent
  in the dorsal root ganglion.

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Types of zoster

• 1- Thoracic zoster.
• Reactivation of virus latent in the dorsal root
  ganglion, results in a segmental rash, extends
  from the mid of the back in a horizontal strip,
  round the side of the chest.
• 2- Ophthalmic zoster.
• Reactivation of virus latent in the trigeminal
  ganglion results in a localized vesicular rash
  that involves the scalp, forehead, eye lids and
  may be cornea.

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Types of zoster

• 3- Ramsay Hunt syndrome.
• Localized vesicular rash appears on the tympanic
  membrane and the external auditory canal.
• Often there is a facial nerve palsy.

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Zoster

• 
  

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Complications

• Meningitis.
• Encephalitis.
• Myelitis.
• Disseminated zoster in the immunocompromized.

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Treatment

• Acyclovir (zovirax), 800 mg,orally, five times
  daily for 5 to 7 days.
• Famciclovir (Famvir), 500 mg, orally, three times
  daily for seven days.
• Valacyclovir (valtrex), 1000 mg. orally, three
  times daily, for seven days.