COMMON VIRAL EXANTHEMAS (MEASLES, CHICKENPOX & RUBELLA)

Dr SARIKA GUPTA (MD,PhD),Assistant Professor

Measles-Etiology

An acute viral disease Highly contagious Measles virus is a single-stranded, lipid-

enveloped RNA virus in the family Paramyxoviridae and genus Morbillivirus

Humans are the only host of measles virus Maintenance of >90% immunity through

vaccination- NO OUTBREAKS

Measles-Pathogenesis

Necrosis of the respiratory tract epithelium & an accompanying lymphocytic infiltrate

Small vessel vasculitis on the skin & on the oral mucous membranes

Warthin-Finkeldey giant cells: pathognomonic for measles, formed by fusion of infected cells, with up to 100 nuclei and intracytoplasmic and intranuclear inclusions

Measles virus also infects CD4+ T cells, resulting in suppression of the Th1 immune response

Measles-Pathogenesis

4 phases:

Incubation period

Prodromal illness

Exanthematous phase

Recovery

Measles-Pathogenesis

Measles-Transmission

Through the respiratory tract or conjunctivae Following contact with large droplets or small-

droplet aerosols in which the virus is suspended Patients are infectious from 3-4 days before to

up to 4-6 days after the onset of rash

Measles-Clinical Features

High fever, an enanthem, cough, coryza, conjunctivitis & a prominent exanthem

Incubation period: 8-12 days Prodromal phase: mild fever, conjunctivitis with

photophobia, coryza, a prominent cough & KOPLIK’S SPOTS

Koplik spots: enanthem & the pathognomonic sign of measles

Appear 1 to 4 days prior to the onset of the rash Discrete red lesions with bluish white spots in the

center on the inner aspects of the cheeks at the level of the premolars

Measles-Clinical Features

Koplick’s spots: spread

to involve the lips,

hard palate & gingiva They also may occur

in conjunctival folds

Measles-Clinical Features

Temperature rises abruptly as rash appears & may reach upto 40OC

Measles rash: generalized, maculopapular, erythematous, confluent

The rash begins on the face around

the hairline & behind the ears It then spreads downward

to the neck, trunk, arms, legs

& feet over next 24-48 hours

Measles-Clinical Features

The rash fades over about 7 days in the same progression as it evolved

Leaves a fine, browny, branny desquamation of skin

Severity of disease: related to the extent & confluence of rash

Rash: may be absent in immunocompromised children

Hemorrhagic measles (black measles): bleeding from mouth, nose or bowels

Measles-Clinical Features

Diarrhoea: more common in malnourished & small children

Severe cases: generalized lymphadenopathy including cervical & mesenteric lymph nodes

Mild splenomegaly

Measles-Diagnosis

Almost always based on clinical and epidemiologic findings (history of contact)

Fever of at least 3 days with at least one of three C (cough, coryza, conjuctivitis)

Decreased total white blood cell count, with relative lymphocytosis

Measles-Diagnosis

IgM antibody in serum: appears 1-2 days after the onset of the rash & remains detectable for about 1 mo

Demonstration of a fourfold rise in IgG antibodies in acute & convalescent specimens collected 2-4 wk later

Viral isolation from blood, urine or respiratory secretions by culture or rt-PCR

Measles-Differential Diagnosis

Rubella-rashes & fever are less striking Roseola infantum (exanthem subitum)- rash

appear as the fever disappears Echovirus Coxsachie Adenovirus Infectious mononucleosis Scarlet fever-diffuse fleshy papular rash with

“goose flesh” texture

Measles-Differential Diagnosis

Meningococcemia-rashes are similar but NO conjuctivitis & cough

Kawasaki disease- no cough, elevations of neutrophils and acute-phase reactants; the characteristic thrombocytosis

Drug fever

Measles-Complications

Due to the pathogenic effects of the virus on the respiratory tract & immune system

Risk factors for complications Children <5 years of age & adults >20 years of

age Severe malnutrition Vitamin A deficiency Immunocompromised persons

Measles-Complications

Pneumonia- giant cell pneumonia (direct viral infection) or superimposed bacterial infection (Streptococcus pneumoniae, Haemophilus influenzae & Staphylococcus aureus)

Croup, tracheitis or bronchiolitis Acute otitis media Sinusitis and mastoiditis Retropharyngeal abscess Activation of pulmonary tuberculoses

Measles-Complications

Diarrhea & vomiting Appendicitis- obstruction of the appendiceal

lumen by lymphoid hyperplasia Febrile seizures Encephalitis- 1-3/1,000 cases of measles;

postinfectious, immunologically mediated process, not due to a direct viral effect

Measles-Complications

Measles encephalitis in immunocompromised patients-from direct damage to the brain by the virus

Thrombocytopenia Myocarditis Bacteremia, cellulitis & toxic shock syndrome Measles during pregnancy-high maternal

morbidity, fetal wastage & stillbirths & congenital malformations in 3% of live born infants

Measles-SSPE

Fatal degenerative disease of central nervous system

Chronic complication of measles Result from a persistent infection with an altered

measles virus that is harbored intracellularly in the CNS for several years

Usually after 7-10 year the virus apparently regains virulence & attacks the cells in the CNS

Change in personality, gradual onset of mental deterioration & myoclonus

Measles vaccination protects against SSPE

Measles-Treatment

SUPPORTIVE Maintenance of hydration, oxygenation & comfort Antipyretics-comfort and fever control Vitamin A supplementation-reduced morbidity

and mortality from measles Single dose of 200,000 IU orally for children

≥1 yr of age (100,000 IU for children 6 mo–1 yr of age and 50,000 IU for infants <6 mo of age)

Measles-Prevention

Isolation- from 7 days after exposure to 4-6 days after the onset of rash

Vaccine or immunoglobulin- vaccine is effective in prevention or modification of measles only if given within 72 hr of exposure. Immune globulin may be given up to 6 days after exposure to prevent or modify infection.

Immune globulin-for susceptible household contacts younger than 6 months of age, pregnant women & immunocompromised persons

Immunization during an outbreak-immunize infant as young as 6 months of age; additional dose at 12-15 months of age

Rubella

Rubella (German measles or 3-day measles) Mild exanthematous disease of infants & children Major clinical significance- fetal damage as part of

the congenital rubella syndrome Etiology: Rubella virus; RNA virus of genus

Rubivirus under family Togaviridae Humans are the only known host

Rubella-Epidemiology

Transmission-through oral droplet or transplacental route

Virus is shed in nasopharyngeal secretions 7 days before exanthem & upto 7-8 days after its disappearance

Rubella susceptibility among women of child bearing age in India- 4%-43%

Rubella-Pathogenesis

Infection virus replication in the respiratory epithelium spreads to regional lymph nodes

viremia viral shedding from the nasopharynx Cellular & tissue damage in the infected fetus:

tissue necrosis, reduced cellular multiplication time, chromosomal breaks & production of a protein inhibitor causing mitotic arrests

Most distinctive feature of congenital rubella: chronicity

Ongoing tissue damage and reactivation

Rubella

Risk factor for severe congenital defects: stage of gestation at the time of infection

Maternal infection during the 1st 8 wk of gestation: most severe & widespread defects

Risk for congenital defects: 90% for maternal infection before 11 wk of gestation, 33% at 11-12 wk, 11% at 13-14 wk & 24% at 15-16 wk

After 16 wk of gestation: defects uncommon

Rubella-Clinical Features

POSTNATAL INFECTION Incubation period: 14-21 days Prodrome: low-grade fever, sore throat, red eyes

with or without eye pain, headache, malaise, anorexia & lymphadenopathy (suboccipital, postauricular & anterior cervical lymph nodes)

Rash: begins on the face & neck as small, irregular pink macules that coalesce & it spreads centrifugally to involve the torso & extremities, where it tends to occur as discrete macules

Rubella-Clinical Features

Rash: fades from the face as it extends to the rest of the body so that the whole body may not be involved at any 1 time

The duration of the rash is generally 3 days & it resolves without desquamation

Rubella-Clinical Features

About the time of onset of the rash, examination of the oropharynx- reveal tiny, rose-colored lesions (Forchheimer spots) or petechial hemorrhages on the soft palate

Subclinical infections are common (25-40%) Polyarthritis or arthralgia-common in adult

females Lab findings: Leukopenia, neutropenia & mild

thrombocytopenia

Rubella-Differential Diagnosis

Mild form of measles Scarlet fever Roseola infantum Enteroviral infections Drug fever Infectoius mononucleosis Erythema infectiosum

Rubella-Diagnosis

Supportive history of exposure or consistent clinical findings

Rubella specific IgM enzyme immunosorbent assay (4-72 days)

Fourfold rise in IgG in sequential sera Rubella virus culture from nasopharynx & blood by

tissue culture system or PCR WHO definition of PROBABLE infection: fever,

maculopapular rash, lymphadenopathy or arthralgia/arthritis

WHO definition of CONFORMED infection: probable case with IgM positivity within 28 days of onset of rash

Rubella-Complications

Postinfectious thrombocytopenia  Arthritis- classically involves the small joints of the

hands Encephalitis-a postinfectious syndrome following

acute rubella & a rare progressive panencephalitis manifesting as a neurodegenerative disorder years following rubella

Guillain-Barré syndrome, peripheral neuritis Myocarditis

Congenital Rubella Syndrome

Result of in utero fetal infection Classical CRS triad: cataract, sensorineural

hearing loss & congenital heart disease

Clinical manifestations: Intrauterine growth restriction, postnatal mental &

motor retardation Bilateral/unilateral cataract, salt-and-pepper

retinopathy, microphthalmia Nerve deafness Meningoencephalitis at birth

Congenital Rubella Syndrome

Patent ductus arteriosus, pulmonary artery stenosis, VSD & ASD, myocarditis

Hepatitis Dermal erythropoiesis (blueberry muffin

lesions) Thrombocytopenic purpura Anemia Hepatosplenomegaly Microcephaly Interstitial pneumonitis Delayed manifestations: Diabetes mellitus

(20%), thyroid dysfunction (5%)

Rubella-Treatment

No specific treatment available for either acquired rubella or CRS

Supportive treatment- antipyretics and analgesics Intravenous immunoglobulin or

corticosteroids-for severe, nonremitting thrombocytopenia

Hearing screening- important, early intervention improve outcomes

Rubella-Treatment

Management of exposed pregnant women Rubella antibody status is tested immediately

result positive mother is immune no further action

Rubella antibody status negative repeat samples after 1-2 weeks negative 1st specimen & positive test result in either the 2nd or 3rd specimen seroconversion suggesting recent infection termination of pregnancy

Rubella-Treatment

Management of congenital rubella syndrome Children with CRS may excrete the virus in

respiratory secretions up to 1 yr of age Isolation & contact precautions maintained unless

repeated cultures of urine and pharyngeal secretions have negative results

Isolation at home my be required for 1 year Care of CRS infants require multidisciplinary team Prognosis poor PREVENTION by IMMUNIZATION

Chickenpox (Varicella)

Varicella is an acute febrile rash illness Caused by VZV which is a neurotropic human α-

herpesvirus Secondary attack rate: 90% Transmission: by airborne spread or through direct

contact with skin lesions Varicella results from inoculation of the virus onto

the mucosa of the upper respiratory tract & tonsillar lymphoid tissue

Chickenpox-Pathogenesis

Chickenpox (Varicella)

Transportation of virus in a retrograde manner through sensory axons to the dorsal root ganglia throughout the spinal cord establishment of virus latent infection in the neurons subsequent reactivation 

herpes zoster, a vesicular rash that usually is dermatomal in distribution

Chickenpox-Clinical Fetures

Prodromal symptoms: fever (moderate), malaise, anorexia, headache & occasionally mild abdominal pain, 24-48 hours before the rash appears

These symptoms resolve within 2-4 days after the onset of the rash

Varicella rash often appear first on the scalp, face, or trunk

The initial exanthem consists of intensely pruritic erythematous macules that evolve through the papular stage to form clear, fluid-filled vesicles

Clouding & umbilication of the lesions begin in 24-48 hr

Chickenpox-Clinical Fetures

While the initial lesions are crusting, new crops form on the trunk & then the extremities

The simultaneous presence of lesions in various stages of evolution is characteristic of varicella

The distribution of the rash is predominantly central or centripetal

Pearl on a rose patel

Chickenpox-Clinical Fetures

The average number of varicella lesions is about 300 (10-1500)

Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks in some children

Severe scarring is unusual unless the lesions were secondarily infected

Chickenpox-Differential Diagnosis

Vesicular rashes caused by Herpes simplex virus Enterovirus Rickettsial pox S. aureus Drug reactions Contact dermatitis Insect bites

Chickenpox-Diagnosis

CLINICAL Leukopenia during the 1st 72 hours after onset of

rash; followed by a relative & absolute lymphocytosis

Elevated hepatic enzymes Specific diagnosis of VZV infection: needed in

immunocompromised children

Chickenpox-Complictions

Mild thrombocytopenia, petechiae (common); purpura, hemorrhagic vesicles, hematuria & gastrointestinal bleeding (rare)

Cerebellar ataxia, encephalitis, Guillian-Barre syndrome, transverse myelitis

Pneumonia Nephritis, nephrotic syndrome, hemolytic-uremic

syndrome Arthritis Myocarditis, pericarditis Pancreatitis

Chickenpox-Complictions

Orchitis Secondary bacterial infections of the skin (group A

streptococci & S. aureus): impetigo, cellulitis, lymphadenitis & subcutaneous abscesses; varicella gangrenosa- more invasive skin infections

Congenital Varicella Syndrome

In infants born to women who have varicella before 20 wk of gestation

Characterized by Cicatricial skin scarring in a zoster-like distribution,

limb hypoplasia Neurologic abnormalities: microcephaly, cortical

atrophy, seizures & mental retardation Eye abnormalities: chorioretinitis, microphthalmia &

cataracts Renal abnormalities: hydroureter & hydronephrosis Autonomic nervous system abnormalities: neurogenic

bladder, swallowing dysfunction & aspiration pneumonia

Chickenpox-Complictions

If a baby is born <4 days after onset of maternal varicella or upto 2 days before the onset: high risk for severe varicella & a high mortality rate

Chickenpox-Treatment

Supportive treatment for fever & itching

Indications for acyclovir in children: Malignancies BMT Chmotherapy or high dose steroid treatment HIV infection Severe vaicella Chronic skin disease Long term salicylate therapy Chlidren >12 years

Treatment should be initiated within 24 hr of the onset of rash

Chickenpox-Treatment

Foscarnet is the only drug for the treatment of acyclovir-resistant VZV infections (in children infected with HIV)

Chickenpox-Prevention

Since persons with chickenpox are infectious for 1-2 days before the onset of rash isolation only reduces the spread

Individual protection NECESSARY (vaccine)