Common Viral Exanthemas (Measles, Chickenpox & Rubella)

1. Common Viral Exanthemas (Measles, Chickenpox & Rubella) Dr SARIKA GUPTA (MD,PhD),Assistant Professor

2. 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

3. 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

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

5. Measles-Pathogenesis

6. 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

7. 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

8. Measles-Clinical Features • Koplick’s spots: spread to involve the lips, hard palate & gingiva • They also may occur in conjunctival folds

9. 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

10. 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

11. Measles-Clinical Features • Diarrhoea: more common in malnourished & small children • Severe cases: generalized lymphadenopathy including cervical & mesenteric lymph nodes • Mild splenomegaly

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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)

22. 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

23. 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

24. 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%

25. 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

26. 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 wkof gestation, 33% at 11-12 wk, 11% at 13-14 wk &24% at 15-16 wk • After 16 wk of gestation: defects uncommon

27. 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

28. 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

29. 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

30. Rubella-Differential Diagnosis • Mild form of measles • Scarlet fever • Roseola infantum • Enteroviral infections • Drug fever • Infectoius mononucleosis • Erythema infectiosum

31. 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

32. 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

33. 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

34. 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%)

35. 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

36. 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

37. 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

38. 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

39. Chickenpox-Pathogenesis

40. 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

41. 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

42. 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

43. 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

44. Chickenpox-Differential Diagnosis Vesicular rashes caused by • Herpes simplex virus • Enterovirus • Rickettsial pox • S. aureus • Drug reactions • Contact dermatitis • Insect bites

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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