definition of Roseola Infantum , cause ,clinical features,differential diagnosis ,

1. Prof.Saad S Al Ani Senior Pedaitric Consultant Head of pedaitric Department Khorfakkan Hospital Sharjah ,UAE Roseola infantum

2. Roseola is a mild febrile, exanthematous illness occurring almost exclusively during infancy Roseola Infantum ( exanthem subitum , or sixth disease ) More than 95% of roseola cases occur in children younger than 3 yr, with a peak at 6-15 mo of age Roseola infantum Prof. Saad S Al Ani

3. Roseola Infantum (cont.) ( exanthem subitum , or sixth disease ) Transplacental antibodies likely protect most infants until 6 mo of age. Infants with classic roseola exhibit a unique constellation of findings displayed over a short period of time Roseola infantum Prof. Saad S Al Ani

4. Etiology Human herpesvirus 6 (HHV-6) is the etiologic agent for most cases of and human herpesvirus 7 (HHV-7) is in some cases of roseola HHV-6 and HHV-7 belong to the β-herpesvirus subfamily of herpesviruses

5. Etiology (cont.) The principal target cells for HHV-6 and HHV-7 infection in vivo are CD4 T cells HHV-6 can also infect other cells, including : CD8 (suppressor) T cells , natural killer T cells , δγ T cells , glial cells , epithelial cells , monocytes , megakaryocytes , and endothelial cells

6. Roseola infantum Prof. Saad S Al Ani Epidemiology Primary HHV-6 infection occurs early in life . More than 90% of newborn infants are HHV-6 seropositive , reflecting transplacental transfer of maternal antibodies.

7. Epidemiology (cont.) By 4-6 mo of age , the prevalence drops significantly (0-60 %). By 12 mo of age , 60-90% of children possess antibodies to HHV-6,

8. Roseola infantum Prof. Saad S Al Ani Epidemiology (cont.) By 3-5 yr , 80-100% of children are seropositive . Peak acquisition of primary HHV-6 infection , from 6-15 mo of age, corresponds with peak acquisition of roseola.

9. Roseola infantum Prof. Saad S Al Ani Epidemiology (cont.) Less than half of HHV-6 infections in U.S. infants are clinically recognizable as roseola , Primary infection with HHV-7 occurs slightly later than HHV-6 infection, with 45-75% of children infected by 2 yr of age and 90% by 7-10 yr of age whereas 80% of Japanese infants with primary HHV-6 infection develop roseola.

10. Epidemiology (cont.) Roseola can develop in children year-round A higher incidence during spring and fall months

11. Epidemiology (cont.) Children with roseola rarely report contact with other affected children Outbreaks are uncommon .

12. The incubation period averages 10 days (range of 5-15 days ). Epidemiology (cont.) Sex , race , and geography , do not play an important role in acquisition of roseola.

13. Pathogenesis Virus is probably acquired from the saliva of healthy persons and enters the host through the oral , nasal , or conjunctival mucosa . Cellular receptors for both viruses have been identified: * HHV-6 uses the CD46 receptor * HHV-7 uses the CD4 receptor Both viruses may evade the immune system through downregulation of the major histocompatibility complex (MHC) type I response

14. Clinical Manifestations Infants with classic roseola exhibit a unique constellation of findings displayed over a short period of time . The prodromal period is usually asymptomatic but may include mild upper respiratory tract signs , among them: * minimal rhinorrhea*slight pharyngeal inflammation* mild conjunctival redness .

15. Clinical Manifestations (Cont.) Mild cervical or, less frequently, occipital lymphadenopathy may be noted Some children may have mild palpebral edema

16. Clinical Manifestations (Cont.) Physical findings during the prodromal stage may simply reflect an accompanying respiratory viral infection . Clinical illness is generally heralded by high temperature usually ranging from 37.9 to 40°C (101-106°F), with an average of 39°C (103°F).

17. Clinical Manifestations (Cont.) Some children may become irritable and anorexic during the febrile stage, but most behave normally despite high temperatures. Seizures may occur in 5-10% of children with roseola during this febrile period. Infrequent complaints include: * rhinorrhea*sore throat* abdominal pain, vomiting, and diarrhea .

18. Clinical Manifestations (Cont.) In Asian countries, ulcers at the uvulopalatoglossal junction ( Nagayama spots ) are common in infants with roseola. Fever persists for 3-5 days , and then typically resolves rather abruptly ("crisis"). A rash appears within 12-24 hr of fever resolution

19. Clinical signs associated with primary HHV-6 infection and the proportion of children with primary HHV-6 infection manifesting each sign as documented by both viremia and seroconversion in 335 children studied in Rochester, NY.

20. In patients with primary HHV-6 infection, the mean total white blood cell (WBC) and lymphocyte counts are shown by day of illness in relation to the average course of fever Pruksananonda P, Hall C, Insel R, et al. Primary human herpesvirus 6 infection in young children. N Engl J Med 1992;326:1445–1450.)

21. Exanthems associated with roseola

22. The rash In many cases, the rash develops during defervescence or within a few hours of fever resolution . The rash of roseola is rose colored and is fairly distinctive

23. The rash (cont.) it may be confused with exanthems resulting from rubella , measles , or erythema infectiosum The roseola rash begins as discrete , small (2-5 mm), slightly raised pink lesions on the trunk and usually spreads to the neck , face , and proximal extremities

24. The rash (cont.) The rash is not usually pruritic , and no vesicles or pustules develop Lesions typically remain discrete but occasionally may become almost confluent After 1-3 days , the rash fades

25. Subtle differences in clinical presentation In roseola associated with HHV-7 Subtle differences in clinical presentation compared with HHV-6 cases include : 1. Slightly older age 2. Lower mean temperature 3. Shorter duration of fever These differences are insufficient to clinically distinguish HHV-6- from HHV-7-associated roseola

27. LABORATORY FINDINGS (cont.) The cerebrospinal fluid from rare cases of HHV-6-associated meningoencephalitis and encephalitis is characterized by: * mild pleocytosis with predominance of mononuclear cells * normal glucose * normal to slightly elevated protein . The cerebrospinal fluid in children with HHV-6-associated febrile seizures typically is normal

28. DIFFERENTIAL DIAGNOSIS 1.Rubella 2.Measles 3.roseola-like illnesses i.e. Enteroviruses 4.Scarlet fever 5.Drug hypersensitivity

29. Treatment The generally benign nature of roseola precludes consideration of antiviral therapy Children with neurologic complications of roseola or immunocompromised children with severe HHV-6 or HHV-7 infection may address the need for specific antiviral therapy Children in the febrile, pre-eruptive phase of roseola usually are quite comfortable and require little supportive therapy

31. Prognosis The prognosis for the great majority of children with roseola is excellent, with no obvious sequelae Damage resulting from direct viral invasion of the brain, liver, and other organs has been demonstrated for HHV-6 Deaths directly attributable to HHV-6 have been reported in normal as well as immunocompromised patients in whom encephalitis , hepatitis , pneumonitis , disseminated disease , or hemophagocytosis syndrome developed.