This document discusses several viral infections that cause skin rashes and lesions. It provides details on measles, rubella, slapped cheek disease (erythema infectiosum), and roseola infantum. It describes the causative viruses, transmission, clinical features of the acute infection and potential complications. It also discusses viral diseases that cause vesicular lesions, focusing on herpes simplex virus types 1 and 2, varicella zoster virus, and their ability to establish latency in host neurons.

1. Viral infection of the skin & mucous membrane
Dr Mohammed Arif
Associate professor
Consultant virologist
Head of the virology unit, college of medicine & KKUH

2. Viral infection of the skin & mucous membrane
 Viral diseases associated with maculopapular rash.
 Viral disease associated with vesicular rash.
 Human warts.

3. Viral diseases associated with maculopapular
rash
 Measles.
 Rubella (German measles),
 Erythema infectiosum (slapped cheek or fifth disease).
 Exanthem subitum (roseola infantum or sixth disease).

4. 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.

5. 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.

6. Measles
 Transmission : by inhalation of respiratory droplets.
 IP : 10 – 14 days.
 Target group : children.

7. 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.

8. 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.

9. 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.

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

11. Clinical features of measles

12. 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.

13. 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.

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

15. Giant cell pneumonia
 Rare complication.
 Seen in the immunocompromised children.
 Due to direct virus invasion of the lungs.

16. 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.

17. Treatment & lab. diagnosis
 Treatment: there is no specific anti viral drug therapy.
 Lab. Diagnosis : By detection of IgM-Ab to measles
virus.

18. 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.

19. Rubella
 Transmission :By inhalation of respiratory droplets.
 IP : 14 – 21 days.
 Target group : children.

20. 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.

21. 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.

22. Complications
 Mild arthritis in adult females.
 Post infectious encephalomyelitis.
 Thrombocytopenic purpura.

23. Clinical features of rubella

24. 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.

25. 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.

26. 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.

27. Congenital rubella
 Infected infants shed the virus into throat and urine for
several months AFTER BIRTH and can infect
susceptible individuals.

28. 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.

29. 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.

30. 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.

31. 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.

32. Clinical features
 There is mild generalized lymphadenopathy.
 Arthralgia with swelling and pain in the joints are seen
in women.
 Recovery is complete.

33. Clinical features of slapped cheek

34. 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.

35. 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.

36. 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).

37. 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.

38. 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.

39. Viral diseases associated with vesicular rash
 HSV-1 infection.
 HSV-2 infection.
 Varicella (chickenpox).
 Zoster.
 Herpangina.
 Hand-foot & mouth disease.

40. 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.

41. 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).

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

43. 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.

44. 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.

45. 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.

46. 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.

47. Transmission
 By direct contact with herpes lesions.
 By saliva.

48. 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.

49. Gingivostomatitis

50. Clinical features
2- Herpetic whitlow:
 Vesicles and ulcers appear on the tips of the fingers.
 Affects nurses and dentist.

51. 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.

52. 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.

53. 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.

54. 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.

55. Herpes labialis

56. HSV-2
Types of infections:
 Primary infection
--- Genital herpes.
--- Neonatal herpes.
 Recurrent infection
--- Genital herpes.

57. 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.

58. 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.

59. 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.

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

61. 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.

62. 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.

63. 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.

64. 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.

65. 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.

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

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

68. 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.

69. 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.

70. 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.

71. 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.

72. Complications
 Post-infectious encephalomyelitis.
 Pneumonia in adults.
 Hepatitis.
 Myocarditis.

73. Clinical features of varicella

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

75. Lab. diagnosis
 Detection of Ig-M antibody.
 Scraping from the base of the vesicles.

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

77. 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.

78. 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.

79. 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.

80. 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.

81. 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.

82. Zoster

83. Complications
 Meningitis.
 Encephalitis.
 Myelitis.
 Disseminated zoster in the immunocompromized.

84. 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.