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

4. 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

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

6. Measles-Pathogenesis
Incubation period: measles virus migrates to regional lymph nodes primary viremia-disseminates 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

7. 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

8. 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

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

10. 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 hours

11. 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

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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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)

23. 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 months of age

24. 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

25. 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%

26. 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

27. 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  wk, 11% at 13-14 wk & 24% at 15-16 wk
After 16 wk of gestation: defects uncommon

28. Rubella-Clinical Features
POSTNATAL INFECTION
Incubation period: 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

29. 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

30. 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

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

32. 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

33. 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

34. 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

35. 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%)

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. Chickenpox-Clinical Fetures
Prodromal symptoms: fever (moderate), malaise, anorexia, headache & occasionally mild abdominal pain, 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

43. 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

44. Chickenpox-Clinical Fetures
The average number of varicella lesions is about 300 ( )
Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks in some children
Severe scarring is unusual unless the lesions were secondarily infected

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

46. 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

47. 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

48. 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

49. 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

50. 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

51. 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

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

53. 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)