Roseola

Roseola, also known as sixth disease, is an infectious disease caused by certain types of human herpes viruses.[2] Most infections occur before the age of three.[1] Symptoms vary from absent to the classic presentation of a fever of rapid onset followed by a rash.[1][2] The fever generally lasts for three to five days, while the rash is generally pink and lasts for less than three days.[1] Complications may include febrile seizures, with serious complications being rare.[1][2]

Roseola
Other namesExanthema subitum,[1] roseola infantum,[1] sixth disease,[1] baby measles, rose rash of infants, three-day fever
Roseola on a 21-month-old girl
SpecialtyInfectious disease
SymptomsFever followed by rash[1]
ComplicationsFebrile seizures[1]
Usual onsetBefore the age of three[1]
DurationFew days[2]
CausesHuman herpesvirus 6 (HHV-6) or human herpesvirus 7 (HHV-7)[1]
Diagnostic methodTypically based on symptoms[1]
Differential diagnosisMeasles, rubella, scarlet fever[1]
TreatmentSupportive care[1]
PrognosisGenerally good[1]

It is caused by human herpesvirus 6 (HHV-6A, HHV-6B) or human herpesvirus 7 (HHV-7).[1] Spread is usually through the saliva of those who are otherwise healthy.[1][2] However, it may also spread from the mother to baby during pregnancy.[1] Diagnosis is typically based on symptoms and does not need to be confirmed with blood tests (PCR or antigen).[1] Low numbers of white blood cells may also be present.[1]

Treatment includes sufficient fluids and medications to treat the fever.[1] Nearly all people are infected at some point in time.[2] Males and females are affected equally often.[1] The disease may reactivate in those with a weakened immune system and may result in significant health problems.[2]

The disease was first described in 1910 while the causal virus was determined in 1988.[1] The name "sixth disease" comes from its place on the standard list of rash-causing childhood diseases, which also includes measles (first), scarlet fever (second), rubella (third), Dukes' disease (fourth, but is no longer widely accepted as distinct from scarlet fever), and erythema infectiosum (fifth).[3]

Signs and symptoms

Fever

Symptoms begin with a three to six day febrile illness.[4][5] During this time, temperatures can peak above 40 °C and children can experience increased irritability with general malaise.[5] However, many children in the febrile phase feel well, engaged, and alert. For these patients, fever is usually diagnosed incidentally.[5]

The most common complication (10-15% of children between 6 and 18 months) and most common cause of hospitalization in children with primary infection of HHV-6B is febrile seizures which can precipitate status epilepticus due to the sudden rise in body temperature.[6]

Rash

Once the febrile phase subsides, a rash develops. In some cases, the rash can present after one or two days after the fever resolves.[5] The rash is classically described as an erythematous morbilliform exanthem[4] and presents as a distribution of soft pink, discrete, and slightly raised lesions each with a 2-5mm diameter.[4][5][6] It classically begins on the trunk (torso) and spreads outward to the neck, extremities, and face. This pattern is referred to as a centrifugal spread.[4] Usually, peeling and itching are not characteristic of this rash.[5] This phase can last anywhere from several hours to 2 days.[4][5][6][7]

Other symptoms

A small percentage of children acquire HHV-6 with few signs or symptoms of the disease.[8] Children with HHV-6 infection can also present with myringitis (inflammation of the tympanic membranes),[4] upper respiratory symptoms,[6][9] diarrhea, and a bulging fontanelle.[6] In addition, children can experience pharyngitis with lymphoid hyperplasia seen on the soft palate and swelling of the eyelids.[5] These symptoms usually present during the febrile phase of roseola.[6] Cervical and postocciptal lymphadenopathy can also be seen, but this generally presents 2–4 days after the onset of the febrile phase.[6][10]

In rare cases, HHV-6 can become active in an adult previously infected during childhood and can show signs of mononucleosis.[11]

Cause

Electron micrograph of HHV-6

There are nine known human herpesviruses. Of these, roseola has been linked to two: human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), which are sometimes referred to collectively as Roseolovirus.[6] These viruses are of the Herpesviridae family and the Betaherpesvirinae subfamily, underwhich Cytomegalovirus is also classified.[6] HHV-6 has been further classified into HHV-6A and HHV-6B, two distinct viruses which share 88% of the same DNA makeup, with HHV-6B the most common cause of roseola.[4][12]

After infection, these viruses enter a latent phase. Roseola caused by HHV-7 has been linked to the ability of HHV-7 infection to reactivate latent HHV-6.[6]

Spread

After exposure to roseola, the causative virus becomes latent in its host but is still present in saliva, skin, and lungs.[6] HHV-6 is thought to be transmitted from previously exposed or infected adults to young children by the shedding of virus through saliva.[8] Even so, most cases of roseola are transmitted without known exposure.[5]

Diagnosis

The diagnosis of roseola is made clinically based on the presence of the two phases: fever and rash.[5] Laboratory testing is seldom used as the results do not alter management of the disease.[6] An exception is in people who are immunocompromised in who serologic tests with viral identification can be used to confirm the diagnosis.[8]

Roseola should be differentiated from other similar-appearing illnesses, such as rubella, measles, fifth disease, scarlet fever, and drug reactions. This differentiation may be determined based on symptoms.[8]

Prevention

Many viruses can cause Roseola and are shed by carriers without symptoms. Because of this and the fact that most children with the disease are not seriously ill, there is no particular method of prevention.[5] Proper hygienic measures, like regular handwashing, can be implemented as a routine method of prevention. Those who have been exposed or infected have been shown to shed the virus for the rest of their lives.[13] Because of this, there are no current guidelines regarding children staying home or away from child-care when infected.[13]

Treatment

Most cases of HHV-6 infection improve on their own.[14] Because of this, supportive care is the mainstay treatment. The febrile phase can be managed using acetaminophen to control fever and prevent spikes in temperature which can lead to febrile seizures.[6][8] In the case of febrile seizures, medical advice should be sought, and treatment aggressively pursued.[5] Antiepileptic drugs are not recommended for patients who develop seizures from Roseola.[4] Once children have entered the rash phase, reassurance is important as this indicates resolution of the infection.[5]

If encephalitis occurs in immunocompromised children, ganciclovir or foscarnet have inconsistently shown usefulness in treatment.[15] Treatment of children who are immunocompromised centers around decreasing their levels of immunosuppression as much as possible.[8]

Prognosis

Children infected with roseola generally have a good prognosis. Most recover without intervention and without long-term effects.[4][5]

Epidemiology

Between the two types of human herpesvirus 6, HHV-6B has been detected much more frequently in hosts.[12] HHV-6B has been shown to affect about 90% of children before the age of 3.[16] Out of these, 20% develop symptoms of roseola, also known as exanthem subitum.[16]

Roseola affects girls and boys equally worldwide year-round.[5] Roseola typically affects children between six months and two years of age, with peak prevalence in children between 7 and 13 months old.[5][6] This correlates with the decrease in maternal antibodies, thus virus protection, that occurs at the age of 6 months.[6] Out of all emergency department visits for children between the ages of 6 months and 12 months who have fever, twenty percent of these are due to HHV-6.[6]

Many children who have been exposed and infected can present without symptoms, which makes determining the incidence within the population difficult.[5]

History

John Zahorsky MD wrote extensively on this disease in the early 20th century, his first formal presentation was to the St Louis Pediatric society in 1909 where he described 15 young children with the illness. In a JAMA article published on Oct 18, 1913 he noted that "the name 'Roseola infantilis' had an important place in the medical terminology of writers on skin diseases" but that descriptions of the disease by previous writers tended to confuse it with many other diseases that produce febrile rashes. In this JAMA article Zahorsky reports on 29 more children with Roseola and notes that the only condition that should seriously be considered in the differential diagnosis is German Measles (rubella) but notes that the fever of rubella only lasts a few hours whereas the prodromal fever of Roseola lasts three to five days and disappears with the formation of a morbilliform rash.[17]

Names

Country Local name (language) Translated name
Belgium Driedagenkoorts (Dutch)
Zesde ziekte (Dutch)
Roséole (French)
"three-day fever"
"sixth disease"
-
China (PRC) 急疹 (Mandarin) jí zhěn (pinyin) "fast rash"
Czech republic Šestá nemoc (Czech) "sixth disease"
Denmark Tredagesfeber (Danish) "three day fever"
Estonia Roseool, kolme päeva palavik Roseola/three day fever
Finland Vauvarokko (Finnish) "baby measles"
France Roséole "Roseola"
Germany Drei-Tage-Fieber (German) "three-day fever"
Greece Αιφνίδιο εξάνθημα (Greek) "sudden rash"
Hungary Háromnapos láz (Hungarian)
Hatodik betegség (Hungarian)
"three-day fever"
"sixth disease"
Iceland Mislingabróðir (Icelandic) "measles' brother"
Israel Tifrachat vrooda תפרחת ורודה (Hebrew) "rose/pink rash"
Italy Sesta malattia (Italian) "sixth disease"
Japan 突発性発疹 (Japanese) toppatsuseihosshin "fast/sudden rash"
Korea (South) 돌발진 (Korean) Dolbaljin "fast/sudden rash"
Malaysia Campak halus (Malay) "small/tiny measles"
Netherlands Zesde ziekte (Dutch) "sixth disease"
Norway Fjerde barnesykdom (Norwegian)[18] "fourth disease"
Philippines Tigdas Hangin (Tagalog) "wind measles"
Poland Gorączka trzydniowa (Polish) "three-day fever"
Romanian Roseola
eruptia subita
Roseola
Russia Розеола (Russian)
шестая болезнь (Russian)
Roseola
"sixth disease"
Singapore Jiǎ má 假麻 (Chinese) "false measles"
Slovakia Šiesta (detská) choroba (Slovak) "sixth disease"
Slovenia Šesta bolezen (Slovenian) "sixth disease"
South Africa Roseola (English) "Roseola"
Sweden Tredagarsfeber
Sjätte sjukan (Swedish)
"three-day fever"
Sixth disease
Taiwan Méiguī zhěn 玫瑰疹 (Chinese) "rose rash"
Turkey Altıncı hastalık (Turkish) "sixth disease"
Vietnam Sốt phát ban (Vietnamese) "baby rash"

Research

HHV-6 has been tentatively linked with neurodegenerative diseases.[19]

See also

  • Fifth disease

References

  1. Stone, RC; Micali, GA; Schwartz, RA (April 2014). "Roseola infantum and its causal human herpesviruses". International Journal of Dermatology. 53 (4): 397–403. doi:10.1111/ijd.12310. PMID 24673253. S2CID 2652000.
  2. Campadelli-Fiume, Gabriella (1999). "Human Herpesvirus 6: An Emerging Pathogen". Emerging Infectious Diseases. 5 (3): 353–366. doi:10.3201/eid0503.990306. PMC 2640789. PMID 10341172.
  3. Feder, Henry M.; Grant-Kels, Jane M. (2008), Schlossberg, David (ed.), "Classic Viral Exanthems", Clinical Infectious Disease, Cambridge: Cambridge University Press, pp. 135–140, doi:10.1017/cbo9780511722240.020, ISBN 978-0-511-72224-0, retrieved 2022-01-04
  4. Arango, Carlos A.; Jones, Ross (October 2017). "8 viral exanthems of childhood". The Journal of Family Practice. 66 (10): 598–606. ISSN 1533-7294. PMID 28991936.
  5. Cherry, James D. (2019). "Roseola Infantum (Exanthem Subitum)". Feigin and Cherry's Textbook of Pediatric Infectious Diseases. pp. 559–561. ISBN 978-0-323-37692-1.
  6. "Human Herpesvirus 6 (Including Roseola) and 7 | Red Book® 2018 | Red Book Online | AAP Point-of-Care-Solutions". redbook.solutions.aap.org. Retrieved 2020-04-22.
  7. Roseola – Topic Overview Archived 2008-07-27 at the Wayback Machine, webmd.com
  8. American Academy of Pediatrics textbook of pediatric care. McInerny, Thomas K.,, American Academy of Pediatrics. (2nd ed.). [Elk Grove Village, IL]. ISBN 978-1-61002-047-3. OCLC 952123506.{{cite book}}: CS1 maint: others (link)
  9. Zerr, Danielle M.; Meier, Amalia S.; Selke, Stacy S.; Frenkel, Lisa M.; Huang, Meei-Li; Wald, Anna; Rhoads, Margaret P.; Nguy, Long; Bornemann, Rena; Morrow, Rhoda Ashley; Corey, Lawrence (2005-02-24). "A Population-Based Study of Primary Human Herpesvirus 6 Infection". New England Journal of Medicine. 352 (8): 768–776. doi:10.1056/NEJMoa042207. ISSN 0028-4793. PMID 15728809.
  10. Asano, Y.; Yoshikawa, T.; Suga, S.; Kobayashi, I.; Nakashima, T.; Yazaki, T.; Kajita, Y.; Ozaki, T. (January 1994). "Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum)". Pediatrics. 93 (1): 104–108. doi:10.1542/peds.93.1.104. ISSN 0031-4005. PMID 8265302. S2CID 23785433.
  11. Stoeckle MY (2000). "The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease". Annu. Rev. Med. 51: 423–30. doi:10.1146/annurev.med.51.1.423. PMID 10774474.
  12. Strausbaugh, Larry J.; Caserta, Mary T.; Mock, David J.; Dewhurst, Stephen (2001-09-15). "Human Herpesvirus 6". Clinical Infectious Diseases. 33 (6): 829–833. doi:10.1086/322691. ISSN 1058-4838. PMID 11512088.
  13. Richardson, M.; Elliman, D.; Maguire, H.; Simpson, J.; Nicoll, A. (April 2001). "Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools". The Pediatric Infectious Disease Journal. 20 (4): 380–391. doi:10.1097/00006454-200104000-00004. ISSN 0891-3668. PMID 11332662. S2CID 7700827.
  14. Tesini, BL; Epstein, LG; Caserta, MT (December 2014). "Clinical impact of primary infection with roseoloviruses". Current Opinion in Virology. 9: 91–6. doi:10.1016/j.coviro.2014.09.013. PMC 4267952. PMID 25462439.
  15. Ongrádi, J; Ablashi, DV; Yoshikawa, T; Stercz, B; Ogata, M (February 2017). "Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals". Journal of NeuroVirology. 23 (1): 1–19. doi:10.1007/s13365-016-0473-0. PMC 5329081. PMID 27538995.
  16. "HHV-6 & Rash/Roseola | HHV-6 Foundation | HHV-6 Disease Information for Patients, Clinicians, and Researchers | Apply for a Grant". hhv-6foundation.org. Retrieved 2020-04-22.
  17. John Zahorsky. Roseola Infantum. Journal of the American Medical Association. Oct 18, 1913 pages 1446-1450
  18. Nylander, Gro (2009) "Lille venn, hva nå?"
  19. Hogestyn, JM; Mock, DJ; Mayer-Proschel, M (February 2018). "Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology". Neural Regeneration Research. 13 (2): 211–221. doi:10.4103/1673-5374.226380. PMC 5879884. PMID 29557362.
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