COMMON VIRAL EXANTHEMAS MEASLES CHICKENPOX RUBELLA Dr SARIKA

COMMON VIRAL EXANTHEMAS (MEASLES, CHICKENPOX & RUBELLA) Dr SARIKA GUPTA (MD, Ph. D), Assistant Professor

Measles-Etiology

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 CD 4+ T cells, resulting in suppression of the Th 1 immune response

Measles-Pathogenesis 4 phases: Incubation period Prodromal illness Exanthematous phase Recovery

Measles-Pathogenesis Incubation period: measles virus migrates to regional lymph nodes primary viremiadisseminates the virus to the reticuloendothelial system secondary viremia spreads virus to body surfaces The prodromal illness begins after the secondary viremia; associated with epithelial necrosis, giant cell formation & virus shedding With onset of the rash, antibody production begins & viral replication & symptoms begin to subside

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 40 OC 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 Ig. M 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 Ig. G 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 patientsfrom 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 q q q 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 1 st 8 wk of gestation: most severe & widespread defects Risk for congenital defects: 90% for maternal infection before 11 wk of gestation, 33% at 1112 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 Ig. M enzyme immunosorbent assay (4 -72 days) Fourfold rise in Ig. G 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 Ig. M 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 1 st specimen & positive test result in either the 2 nd or 3 rd 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 αherpesvirus 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 Incubation period (10 -21 days): replication in the local lymphoid tissue primary viremia-disseminates the virus to the reticuloendothelial system secondary viremia spreads virus to body surfaces leading to widespread cutaneous lesions During the late incubation period-VZV transported back to the mucosa of the upper respiratory tract & oropharynx, permitting spread to susceptible contacts 1 -2 days before the appearance of rash Host immune responses limit viral replication and facilitate recovery from infection Immunocompromised child-continued viral replication -disseminated infection

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 1 st 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)