Viral infection of the skin mucous membrane Dr

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

Viral infection of the skin & mucous membrane Viral diseases associated with maculopapular rash. l Viral disease associated with vesicular rash. l Human warts. l Macules : flat, red spots. l Papules : slightly raised spot from the skin, but do not contain fluids. l The virus is not shed from the lesions of the maculopapular rash. l

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

Measles l l l 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.

Structure & classification (cont. ) l l l The F-glycoproteins, 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). Helical nucleocapsid. The viral genome is SS-RNA, with negative polarity. Virion contains the enzyme transcriptase. One antigenic serotype.

Measles virus

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

Pathogenesis After entry, the virus replicates in the epithelial cells of the URT. l The virus then invades the sub-epithelial tissues and reaches the lymphatic system and the blood stream. l The virus then spreads by blood and infects the endothelial cells of the blood vessels. l The cytotoxic T-cells attack virus infected vascular endothelial cells. And this will lead to the development of the maculopapular rash. l

Clinical features Prodromal : Fever, cough, mild conjunctivitis, nasal discharge. Lasting 1 -3 days. l Koplik's 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. l Rash : maculopapular rash, first appear on the face then spread downward over the trunk and extremities. l

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. l Recovery is usual. l

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

Koplik’s spots

Clinical features of measles

Measles

Post infectious encephalomyelitis l l l 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.

SSPE l l l Late and rare complication of measles. Due to reactivation of mutant measles virus, latent 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.

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

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

Prevention l l l 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.

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

Rubella (German measles) l l l Viral etiology: Rubella virus. Family : Togaviridae. Genus : Rubivirus. The virus is enveloped, pleomorphic with icosahedral nucleocapsid. The viral genome is SS-RNA with positive polarity.

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

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

Clinical features l l l 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 postauricular and sub-occipital lymph nodes.

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

Clinical features of rubella

Rubella

Prevention , treatment & lab Diagnosis. Vaccine : Live attenuated vaccine (MMR). l Treatment : There is no specific viral therapy. l Lab. Diagnosis : By detection of Ig. M-Ab rubella virus. l

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

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

Congenital rubella l Infected infants shed the virus into throat and urine for several months and can infect susceptible individuals.

Prevention & lab. Diagnosis. l Prevention : By immunization of all children at age of 15 -months with the MMR vaccine. l Lab Diagnosis : By detection of Ig. M-Ab to rubella virus in the infant serum.

Slapped cheek, Erythema infectiosum, Fifth disease. l l l l 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.

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

Clinical features l l l 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.

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

Clinical features of slapped cheek

Slapped cheek.

Complications l Aplastic anemia, absence of regeneration of blood cells , seen in the immunocompromized. Transient aplastic crisis, sudden and temporary disappearance of erythroblasts from the bone marrow, seen in patients with hemolytic anemia. l The bone marrow does not manufacture RBC ( bone marrow suppression ). l

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

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

Exanthem subitum, Roseola infantum, Sixth disease l l l 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.

Clinical features. l l l 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.

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

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

Typical structure of herpes viruses

Herpesviruses l l l l l 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).

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

Latency l l l 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.

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

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. l Keratitis. l

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

Latency in HSV-1 ( trigeminal ganglion).

HSV-1 Latency

Transmission By direct contact with herpes lesions. l By saliva. l

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

Gingivostomatitis

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

Herpetic whitlow

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

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

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

Herpes encephalitis

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

Herpes labialis

Gingivostomatitis

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

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

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

Pathogenesis l l l 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.

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

Primary genital herpes l l l 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.

Genital herpes

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

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. l

Neonatal herpes

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

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

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

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

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

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

Clinical features l l l l 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.

Complications Post-infectious encephalomyelitis. l Pneumonia in adults. l Hepatitis. l Myocarditis. l

Clinical features of varicella

Varicella

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

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

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

Congenital varicella Very rare. l Most pregnant women have immunity to varicella, due to previous exposure. l 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. l

Neonatal varicella l 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. l If the mother acquired varicella within 7 -days of delivery, the neonate is likely to develop severe disease.

Zoster (shingles) Zoster is localized unilateral vesicular rash. l It is a disease of elderly. l It is due to reactivation of VZV, which is latent in the dorsal root ganglion. l

Zoster

Types of zoster 1 - Thoracic zoster. l 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. l 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.

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

Zoster

zoster

Complications Meningitis. l Encephalitis. l Myelitis. l Disseminated zoster in the immunocompromized. l

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