VIRAL EXANTHEMS

VIRAL EXANTHEMS

21 Nov 2013Danize Buemio

Mary April Chan

MEASLES

Measles• Etiology– Measles virus– Single-stranded lipid enveloped

RNA virus– Family Paramyxoviridae, genus

Morbilivirus– 6 major structural proteins• Hemagglutinin (H) protein • Fusion (F) protein – antibodies limit

proliferation

Measles

• Transmission– Contact with large droplets or small droplet

aerosols in which virus is suspended– Entry into respiratory tract or conjunctivae– Approx. 90% of exposed individuals develop

measles– Face-fece contact is not necessary– Viable virus may be suspended in the air up to 1

hour

Measles• Pathology– Necrosis of the respiratory tract

epithelium with lymphocytic infiltrate– Small vessel vasculitis on the skin and

oral mucosa– Histological findings

• Rash reveals intracellular edema and dyskeratosis

• Epidermal syncytial giant cells with up to 26 nuclei

• Lymphoid hyperplasia• Fusion of infected cells multinucleated

giant cells– Warthin-Finkeldey giant cells:

pathognomonic for measles, up to 100 nuclei

Measles

Incubation Period

Prodromal Illness

Exanthematous Phase Recovery

Measles

Incubation Period

Prodromal Illness


• Incubation period: 8-12 days• Virus migrates to regional lymph nodes• Primary viremia disseminates the virus to the

reticuloendothelial system• Secondary viremia spreads virus to body surfaces

Measles

Incubation Period

Prodromal Illness


• Prodromal Phase: mild fever, Conjunctivitis with photophobia, Coryza, Cough• Enanthem: Koplik spots pathognomonic

– Appears 1-4 days before rash• Symptoms increase in intensity for 2-4 days until 1st day of the rash• Epithelial necrosis • Giant cell formation• Viral shedding• Viral replication

Measles

Incubation Period

Prodromal Illness


• Exanthem: maculopapular rash begins around forehead (hairline), behind the ears, upper neck torso extremities

• Antibody production viral replication and symptoms subside, rash fades over 7 days desquamation

• Infection of CD4 T cells suppresion of immune response

Inapparent Measles Infection

• Subclinical form of measles• Individuals with passively acquired antibody– Infants, recepients of blood products

• Rash may be indistinct, brief or absent• Do not shed measles virus or transmit

infection

Atypical measles

• Original formalin-inactivated measles vaccine• More severe form• High onset of fever and headache• Maculopapular rash on the extremities petechial and

purpuric– Progress in centripetal direction

• Frequently complicated by pneumonia and pleural effusion

• Circulating immune complexes due to abnormal response to vaccine

Diagnostics

• CBC– Reduction in WBC count– Decrease in lymphocytes > neutrophils– ESR and C-protein normal

• Serologic confirmation: IgM and IgG– IgM: appears 1-2 days after onset of rash, remains

detectable for ~1month– IgG: 4-fold rise In specimens take 2-4 weeks later

• Viral isolation and PCR

Differential Diagnoses

• Rubella• Adenoviruses• Epstein-Barr virus• Kawasaki Disease – presents with

thrombocytosis, lacks Koplik spots and severe cough

• Drug eruptions

Treatment• Supportive• Goals of therapy:– Hydration, oxygenation, comfort

• ORS, IV fluids• Airway humidification and supplemental O2• Ventilatory support for croup or pneumonia• Antipyretics• Prophylactic antimicrobial tx is NOT indicated• Antiviral therapy is NOT effective in otherwise normal

patients

Treatment

• Measles in immunocompromised is highly lethal– Ribavarin with or without intravenous gamma

globulin

Treatment

• Vitamin A– Measles lowers serum retinol– Higher morbidity and mortality

Complications

• Morbidity and mortality are greatest in <5 years and >20 years

• Crowding – larger inoculum dose• Severe malnutrition – suboptimal immune

response• Measles in immunocompromised

Complications

• Dehydration– Fever, diarrhea, vomiting

• Known to suppress PPD skin test responsiveness– May have an increased rate of PTB activation

Complications• Pneumonia – most common cause of death

– Giant cell pneumonia caused by virus– Superimposed bacterial infection– Final pathway: bronchiolitis obliterans– Croup, tracheitis

• Otitis Media – most common complication• Sinusitis, mastoiditis, retropharygeal abscess• Encephalitis

– Postinfectious immunologically mediated process– Seizures (56%), lethargy (45%), coma (28%), irritability (26%)– CSF: lymphocytic pleocytosis, elevated protein– Approx 15% death, 20-40% mental retardation, deafness, motor disabilities

• Hemorrhagic or “black measles”: hemorrhagic skin eruption, fatal• Myocarditis: rare• Subacute Sclerosing Paraencephalitis (SSPE)

Subacute Sclerosing Paraencephalitis (SSPE)

• Rare disease• Results from a persistent infection with an

altered measles virus harbored in CNS for years• After 7-10 years, virus regains virulence and

attacks cells in CNS that offered the virus protection

• Inflammation and cell death neurodegenerative process


• Age of onset: <1 to <30 years• Usually in children in adolescents• Measles at an early age favors SSPE development• Males affected twice as often as females• Defective measles virus• Defective or immature immune system• Immature virus able to reside within neural cells

for long periods


• Symptoms begin 7-13 years after primary measles infection• 1st stage: Subtle changes in behavior

– Irritability, reduced attention span, temper outbursts– Fever, headache, signs of encephalitis are absent

• 2nd stage: massive myoclonus– Extension of inflammatory process to deeper brain structures

including basal ganglia• 3rd stage: choreoathetosis, immobility, dystonia, lead pipe

rigidity– Sensorium deteriorates: dementia stupor coma– involuntary movements disappear

• 4th stage– Loss of centers supporting breathing, heart rate, BP– Death

Mumps• Etiology– Mumps virus– Single-stranded pleomorphic RNA

virus– Family Paramyxoviridae, Genus

Rubulavirus– Encapsulated in a lipoprotein

envelope– 7 structural proteins

• Hemagglutin-neuraminidase (HN)• Fusion (F)

– Humans are the only natural host

Mumps

• Transmission– Spread from person-person via respiratory

droplets– Virus appears in saliva 7 days before and 7 days

after the onset of parotid swelling– Period of maximum infectiousness: 1-2 days

before to 5 days after parotid swelling

Mumps• Pathology– Targets the salivary glands, CNS,

pancreas, testes– Thyroid, ovaries, heart, kidneys,

liver, joint synovia– Initial viral replication in the

upper respiratory tract– Spread to adjacent lymph nodes

target tissues– Necrosis of infected cells – Salivary gland ducts are lined with

necrotic epithelium, interstitium lined with lymphocytes

Mumps

Incubation Period

Prodromal Illness


• Incubation Period: 12-25 days, usu. 16-18

Mumps

Incubation Period

Prodromal Illness Parotitis Recovery

• Prodrome: 1-2 days • Fever, headache, vomiting, achiness

Mumps

Incubation Period


• Parotid swelling appears• May be unilateral initially, but becomes

bilateral 70%• Peaks in 3 days, subsides over 7 days • Submandibular glands may also be involved

Mumps

• Parotid gland is tender• May be preceeded by ear

pain• Angle of jaw is obscured• Earlobe lifted upward and

outward• Sour or acidic food may

enhance pain• Morbiliform rash is rarely

seen

Mumps

Incubation Period


• Fever resolves in 3-5 days along with other systemic symptoms

Diagnostics

• History of exposure to mumps infection• Clinical findings• Elevated amylase level• Relative lymphocytosis• Serologic testing– Increase in mumps IgG, IgM– IgG may cross react with antibodies to parainfluenza virus

• Isolation of the virus in cell culture, PCR, immunofluorescence

Treatment

• No specific antiviral therapy is available for mumps

• Pain control• Adequate hydration• Antipyretics for fever

Complications• Encephalitis, meningitis, meningoencephalitis

– Usually manifests 5 days after parotid swelling– Infants, young children: fever, malaise, lethargy– Older children: headache, meningeal signs

• Pancreatitis– Epigastric pain, vomiting

• Orchitis– 2nd to parotitis as a common finding– After puberty, occurs 30-40%– High fever, chills, pain and swelling of testes

• Oophoritis– Uncommon in postpubertal females– Severe pain

Prognosis

• Excellent• Some fatal cases of encephalitis were reported

Prevention

• 2 dose MMR vaccine– MMR1: 12-15 mos– MMR2: 4-6 years

ROSEOLA

Roseola Infantum• Exanthem subitum or Sixth disease • Mild febrile exanthematous illness• Occurs almost exclusively during infancy• >95% occur in children younger than 3, peak at 6-15 mos• Etiology

– Human herpesvirus (HHV) types 6 and 7– Genus: Roseolovirus– Subfamily: Betaherpesvirinae

• Transmission– Droplet– From saliva of healthy persons, enters host through oral, nasal or conjunctival

mucosa

Roseola Infantum

• Prodrome– Usually asymptomatic– Mild URTI signs: minimal rhinorrhea, slight

pharyngeal inflammation, mild conjunctival redness

– Mild cervical or occipital lymphadenoathy– Mild palpebral edema

Roseola Infantum

• High fever (average: 39C), lasts for 3-5 days• Rhinorrhea, sore throat, abdominal pain, vomiting,

diarrhea• Nagayama spots: ulcers at uvulopalatoglossal junction• Rash appears within 12-24 hours of fever lysis– Rose-colored, discrete, 2-5mm, slightly raised lesions on

trunk neck face proximal ext– Usu. Non-pruritic, no vesicles or pustules– Fades after 1-3 days

Clinical Manifestation

Abrupt onset of high fever with fussiness

Rash: faint pink or rose-colored, nonpruritic, 2- to 3-mm morbilliform

rash

Diagnostics

• Clinical presentation• Serology• Virus culture• PCR

Treatment

• Supportive therapy• HHV-6 inhibit by ganciclovir, cidofovir, foscarnet

(but not acyclovir) • HHV-7 inhibited by cidovir and foscarnet• No approved treatment• Treatment is warranted for immunocompromised

children with severe disease– Gangciclovir, cidofovir for 2-3 weeks

RUBELLA

Rubella

• German measles• Three-day measles

• Rash similar to that of mild rubeola or scarlet fever

• Enlargement and tenderness of the postoccipital, retroauricular, and posterior cervical lymph nodes

• Rubella in early pregnancy may cause the congenital rubella syndrome

Etiology

• RNA virus• Genus Rubivirus• Family Togaviridae

Epidemiology

• Humans are the only natural host of rubella virus

• Distributed worldwide, affects both sexes equally

• Spread by:– Oral droplet– Transplacentally to the fetus

Epidemiology

• Peak incidence: 5-14 years of age• In closed populations, such as institutions and

military barracks, almost 100% of susceptible individuals may become infected.

• In family settings, 50-60% of susceptible family members acquire the disease.

Epidemiology

• Virus is shed in nasopharyngeal secretions, blood, feces, and urine

• Virus is present in the nasopharynx 7 days before exanthem, and 7-8 days after its disappearance

• Subclinical disease is also infectious

Pathogenesis

• Not well understood• Virus can be found from both infected and

uninfected areas of the skin– Immune processes may be important

Pathogenesis

• Primary maternal infection during the 1st trimester: greatest risk of congenital defects

• <11th wk AOG: 90% • End of trimester: 10-20%• >16th wk AOG: low risk for congenital defects• Overall risk for first trimester infection: 70%

Clinical Manifestations

• Incubation period: 14-21 days• Prodromal phase of mild catarrhal symptoms

is shorter than that of measles


• Retroauricular, posterior cervical, and postoccipital lymphadenopathy– Most characteristic

• Evident at least 24 hours before the onset of rashes

• May last up to 1 week


• Exanthem begins on the face and spreads quickly

Discrete maculopapules present in large numbers + Large areas of flushing

Pinpoint appearance over the trunk,

resembling scarlet fever + mild itching

Eruption + Minimal desquamation

24 HOURS 2ND DAY 3RD DAY


• Forchheimer spots– Discrete rose-colored

spots on the soft palate that may coalesce into a red blush and extend over the fauses


• Pharyngeal mucosa and conjunctivae are slightly inflamed

• No photophobia (in contrast to rubeola)• Fever is low grade or absent and usually lasts

only for 3 days• Polyarthritis may occur with arthralgia, swelling,

tenderness, and effusion but usually without any residuum

• NOT common: headache, malaise, anorexia

Differential Diagnosis

Roseola infantum (exanthem subitum) Higher feverAppearance of rash at the end of febrile episode

Infectious mononucleosis Associated with generalized lymphadenopathyCharacteristic atyopical lymphocytosis

Enteroviral infections Accompanied by gastrointestinal or respiratory manifestations in the absence of lymphadenopathy

Drug rashes History of drug intakeNo lymphadenopathy

Diagnosis

• Clinical• Objective findings:– Enlarged spleen– Normal or slightly reduced WBC count– Thrombocytopenia (rare)

• Confirmed by serology or virus culture

Diagnosis

• Rubella virus can be cultured from the nasopharynx and blood.

• It is detected by the ability of rubella-infected African green monkey kidney (AGMK) cells to resist challenge with enterovirus.

Diagnosis

• Hemagglutination-inhibition (HI) antibody • Latex agglutination • enzyme immunoassay• passive hemagglutination, and • fluorescent immunoassay

Diagnosis

• Immunoglobulin (Ig) M antibodies – detectable in the first few days of illness– Also useful for the diagnosis of congenital rubella

syndrome. • Seroconversion, or a fourfold increase in IgG

titer, is diagnostic.

Treatment

• Supportive treatment• No specific antiviral therapy• Antipyretics for fever

Prognosis

• Excellent.• Infection usually confers permanent immunity,

although reinfection may occur.

Complications

• Encephalitis– Occurs in about 1 in 6,000 cases– Overall mortality rate of 20%– Symptoms usually resolve within 1-3 wk without

neurologic sequelae• Thrombocytopenic purpura occurs at an

overall rate of 1 in 3,000 cases.

Complications

• The most important consequence of rubella in a pregnant woman is congenital rubella syndrome.

• Progressive rubella panencephalitis is a persistent, slowly progressive rubella infection of the central nervous system

Congenital Rubella Syndrome

• Intrauterine growth retardation: most common manifestations

• Common findings:– Cataracts– Myocarditis and structural

cardiac defects– Blueberry muffin skin

lesions– Sensorineural hearing loss– Meningoencephalitis


• Diagnosis:– Rubella-specific IgM antibody in the neonatal

serum, or by culturing rubella virus from the infant (nasopharynx, urine, or tissues)

– Isolating the virus from amniotic fluid or by identification of rubella-specific IgM in cord blood.


• Prognosis– Better for infants with fewer stigmata of the

syndrome, presumably those who were initially infected later in gestation.

– Only 30% of infants with encephalitis appear to escape residual neuromotor deficitis, including an autistic syndrome

Reinfection

• The incidence of reinfection– 3-10% on exposure to wild virus among those with

a history of previous rubella – 14-18% among those immunized with the RA 27/3

vaccine. • May lead only to an IgG booster response, to

both an IgM and IgG response, or to clinical rubella.

Prevention

• Rubella vaccine is derived from the RA 27/3 strain of rubella virus

• Induces antibody in more than 99% of seronegative recipients and has protective efficacy in more than 90%

• Vaccine virus may be shed from the nasopharynx in low titers for as long as 18-25 days after vaccination

Prevention

• MMR– 1st: recommended at 12-15 mo of age. – 2nd: recommended routinely at 4-6 yr of age but may

be administered at any time during childhood provided at least 4 wk have elapsed since the first dose.

• Pregnant women should not be given live rubella virus vaccine and should avoid becoming pregnant for 3 mo after they have been vaccinated

Prevention

• Symptoms that may follow rubella immunization include – Fever (5-15%), – Rash (5%), – Lymphadenopathy, and– Arthralgias and arthritis

Postexposure prophylaxis

• Nonpregnant susceptible contacts of persons with rubella should be vaccinated– does not prevent infection but ensures protection

for future rubella exposures• All pregnant women, regardless of

immunization history, should make every effort to avoid exposure to rubella.

ERYTHEMA INFECTIOSUM

Parvovirus B19

• Erythema infectiosum• Fifth disease

Etiology

• Parvovirus B19 – Genus Erythrovirus – Family Parvoviridae

• Only Parvovirus pathogenic in humans• Composed of an icosahedral protein capsid without

an envelope that contains single-stranded DNA• It is relatively heat- and solvent-resistant. • Replicate in mitotically-active cells– require host cell factors present in late S phase to replicate

Epidemiology

• Most prevalent in school-aged children– 70% of cases occurring between 5 and 15 yr of age

• Transmission:– respiratory route (large droplet)

• Other mode:– Blood and blood products– Fomite

Pathogenesis

• Erythroid cell line– Primary target– Specifically erythroid precursors near the pronormoblast

stage• Viral infection produces lysis of these cells– progressive depletion and a transient arrest of erythropoiesis

• Erythrocyte P blood group antigen serves as a cellular receptor for the virus. – Found in Endothelial cells, placenta, and fetal myocardial cells

also possess this antigen

Pathogenesis

Biphasic illness

7-11 daysViremia,

nasopharyngeal viral shedding, drop in reticulocyte count

Fever, malaise, rhinorrhea

17-18 days

Rash associated with arthralgia

Pathogenesis

• B19 is associated with nonimmune fetal hydrops and stillbirth in women experiencing a primary infection

• Not teratogenic


• Most common manifestation: erythema infectiosum

• Benign self-limited exanthematous• Incubation period: 4-28 days (ave: 16-17 days)


• Low-grade fever• Headache• Symptoms of mild URTI• Hallmark: characteristic

rash


• Spares palms and soles• Prominent on extensor surfaces• Afebrile and NOT ill-appearing

Erythematous facial flushing – “slapped

cheek”

Spreads to trunk and proximal extremities as

diffuse macular erythema

Central clearing of macular lesions – “lacy, reticulated”


• Papular-purpuric "gloves and socks" syndrome (PPGSS)– Fever– Pruritus– Painful edema and erythema localized to the distal

extremities in a distinct glove and sock distribution– Acral petechiae and oral lesions

Diagnosis

• Clinical• Serologic tests– B19-specific IgM: persists for 6-8 wk– Anti-B19 IgG: marker of past infection/immunity– Anti-B19 IgM: best marker of recent/acute

infection – seroconversion of anti-B19 IgG antibodies can also

be used to confirm recent infection

Diagnosis

• Cannot be isolated by culture– PCR or nucleic acid hybridization are necessary


• Rubella• Measles• Enteroviral infections• Drug reactions• Juvenile rheumatoid arthritis• SLE

Treatment

• No specific antiviral therapy• Administration of IVIG may give only a

temporary remission, and periodic re-infusions may be required.

Complications

• Arthralgia or arthritis– May persist after the rash

• Thrombocytic purpura• Aseptic meningitis• Virus-associated hemophagocytic syndrome

Prevention

• Children with erythema infectiosum are not likely to be infectious at presentation because the rash and arthropathy represent immune-mediated, postinfectious phenomena.

• No vaccine• No data to support post-exposure prophylaxis

VARICELLA

Varicella-Zoster

• Primary– Varicella (chickenpox)– Establishment of lifelong latent infection of

sensory ganglion neurons• Reactivation – herpes zoster (shingles)

Etiology

• Neurotropic human herpesvirus • Double-stranded DNA genomes

Epidemiology

• Within households, transmission to susceptible individuals occurs at a rate of 65-86%;

• More casual contact is associated with lower attack rates among susceptible children

Epidemiology

• Contagious period: – From 24-48 hr BEFORE the rash appears – Until 3-7 days after onset of rash (crusted vesicles)

• Susceptible children may also acquire varicella after close, direct contact with adults or children who have herpes zoster.

Epidemiology

• Lifetime risk for herpes zoster is 10-15%• 75% of cases occurring after 45 yr of age

Pathogenesis

• Transmission:– Respiratory secretions (airborne)– Fluid of skin lesions (direct contact)

Pathogenesis

• Incubation period: 10-21 days– Virus replicates in the respiratory tract followed by

a brief subclinical viremia– During the late incubation period, virus is

transported back to respiratory mucosal sites facilitating transmission even before appearance of rash

• Second viremic phase: Widespread cutaneous lesions

Pathogenesis

• VZV establishes latent infection in sensory ganglia cells in all individuals who experience primary infection.

• Subsequent reactivation: herpes zoster– a vesicular rash that usually is dermatomal– necrotic changes may be produced in the

associated ganglia


• Acute febrile rash illness• Variable severity but usually self-limited• Herpes zoster, uncommon in children, causes

localized cutaneous symptoms


• Illness usually begins 14-16 days after exposure


• Fever, malaise, anorexia, headache, and occasionally mild abdominal pain may occur 24-48 hr before the rash appears.

• Fever and other systemic symptoms persist during the first 2-4 days after the onset of the rash.


• Lesions appear first on the scalp, face, trunk

• Characteristic: lesions in various stages

Initial: pruritic erythematous

macules

Papular stage: clear, fluid-

filled vesicles

Clouding and umbilication


• Distribution: central or centripetal– As opposed to smallpox where rashes are

prominent on the face and distal extremities


• Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks in some children, but severe scarring is unusual unless the lesions were secondarily infected


• Includes vesicular rashes caused by other infectious agents– herpes simplex virus– enterovirus, or – Staphylococcus aureus;

• Drug reactions• Contact dermatitis• Insect bites.

Diagnosis

• Leukopenia is typical during the first 72 hours; it is followed by a relative and absolute lymphocytosis. Results of liver function tests are also usually (75%) mildly elevated

Diagnosis

• VZV can be identified quickly by direct fluorescence assay (DFA) of cells from cutaneous lesions, which is widely available, and by polymerase chain reaction (PCR) amplification testing. Although multinucleated giant cells can be detected with nonspecific stains (Tzanck smear), they have poor sensitivity and do not differentiate VZV and herpes simplex virus infections.

Diagnosis

• Infectious virus may be recovered using tissue culture methods; newer methods have decreased time needed for culture from 7-10 days to 3-4 days. VZV immunoglobulin G (IgG) antibodies can be detected by several methods and a 4-fold rise in IgG antibodies is also confirmatory of acute infection. VZV IgG antibody tests can also be valuable to determine the immune status of individuals whose clinical history of varicella is unknown or equivocal.

Treatment

• Antiviral treatment modifies the course of both varicella and herpes zoster.

• Acyclovir• Foscarnet for acyclovir-resistant VZV

Treatment

• Oral therapy with acyclovir (20 mg/kg/dose; maximum: 800 mg/dose) given as 4 doses per day for 5 days should be used to treat uncomplicated varicella

• To be most effective, treatment should be initiated as early as possible, preferably within 24 hr of the onset of the exanthem.

Complications

• Bacterial super-infection• Pneumonia• Encephalitis• Bleeding disorders• Congenital infection• Life-threatening perinatal infection

VIRAL EXANTHEMS

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