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