Roseola

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

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

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

The disease was first described in 1910 while the causal virus was isolated in 1988.[2] 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]

## Contents

* 1 Signs and symptoms
* 1.1 Fever
* 1.2 Rash
* 1.3 Other symptoms
* 2 Cause
* 2.1 Spread
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 Prognosis
* 7 Epidemiology
* 8 History
* 9 Names
* 10 Research
* 11 See also
* 12 References
* 13 External links

## 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] 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. The rash sometimes presents 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][8][9]

### 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][10] 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 postoccipital lymphadenopathy can also be seen, but this generally presents 2–4 days after the onset of the febrile phase.[6][11]

In rare cases, HHV-6 can become active in an adult previously infected during childhood and can show signs of mononucleosis.[12]

## 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, under which Cytomegalovirus is also classified.[6] HHV-6 has been further classified into HHV-6A and HHV-6B, two distinct viruses that share 88% of the same DNA makeup, with HHV-6B the most common cause of roseola.[4][13]

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 shedding the 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 the management of the disease.[6] An exception is in people who are immunocompromised in whom serologic tests with viral identification can be used to confirm the diagnosis.[8]

Roseola should be differentiated based on symptoms from other similar-appearing illnesses, such as rubella, measles, fifth disease, scarlet fever, and drug reactions.[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 prevention method. Those exposed or infected have been shown to shed the virus for the rest of their lives.[14] No current guidelines exist regarding children staying home or away from child care when infected.[14]

## Treatment

Most cases of HHV-6 infection improve on their own.[15] 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 the resolution of the infection.[5]

If encephalitis occurs in immunocompromised children, ganciclovir or foscarnet have inconsistently shown usefulness in treatment.[16] 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 or long-term effects.[4][5]

## Epidemiology

Between the two human herpesvirus 6 types, HHV-6B has been detected much more frequently in hosts.[13] HHV-6B has been shown to affect about 90% of children before the age of 3.[17] Out of these, 20% develop symptoms of roseola, also known as exanthem subitum.[17]

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 ages 6 months and 12 months who have a fever, twenty percent of these are due to HHV-6.[6]

Many children 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.[18]

## 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  | Adamdemet, אדמדמת, אביבית (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)[19] | "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.[20]

## See also

* Fifth disease

## References

1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Campadelli-Fiume, Gabriella (1999). "Human Herpesvirus 6: An Emerging Pathogen" (in en-us). Emerging Infectious Diseases 5 (3): 353–366. doi:10.3201/eid0503.990306. PMID 10341172.
2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 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.
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, https://www.cambridge.org/core/books/clinical-infectious-disease/classic-viral-exanthems/3CF0D1C1D493C8F6E34E9A72CB0BF56C, retrieved 2022-01-04
4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 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. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 Cherry, James D. (2019). "Roseola Infantum (Exanthem Subitum)". Feigin and Cherry's Textbook of Pediatric Infectious Diseases. Elsevier. pp. 559–561. ISBN 978-0-323-37692-1.
6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 "Human Herpesvirus 6 (Including Roseola) and 7 | Red Book® 2018 | Red Book Online | AAP Point-of-Care-Solutions". https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640111&bookid=2205.
7. ↑ Roseola – Topic Overview , webmd.com
8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 American Academy of Pediatrics textbook of pediatric care (2nd ed.). Elk Grove Village, IL: American Academy of Pediatrics. 2017. ISBN 978-1-61002-047-3. OCLC 952123506.
9. ↑ Measles Rash , webmd.com
10. ↑ Zerr, Danielle M.; Meier, Amalia S.; Selke, Stacy S.; Frenkel, Lisa M.; Huang, Meei-Li; Wald, Anna; Rhoads, Margaret P.; Nguy, Long et al. (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.
11. ↑ 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.
12. ↑ 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.
13. ↑ 13.0 13.1 Strausbaugh, Larry J.; Caserta, Mary T.; Mock, David J.; Dewhurst, Stephen (2001-09-15). "Human Herpesvirus 6" (in en). Clinical Infectious Diseases 33 (6): 829–833. doi:10.1086/322691. ISSN 1058-4838. PMID 11512088.
14. ↑ 14.0 14.1 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.
15. ↑ 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. PMID 25462439.
16. ↑ 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. PMID 27538995.
17. ↑ 17.0 17.1 "HHV-6 & Rash/Roseola | HHV-6 Foundation | HHV-6 Disease Information for Patients, Clinicians, and Researchers | Apply for a Grant". https://hhv-6foundation.org/associated-conditions/hhv-6-rash-roseola.
18. ↑ John Zahorsky. Roseola Infantum. Journal of the American Medical Association. Oct 18, 1913 pages 1446-1450
19. ↑ Nylander, Gro (2009) "Lille venn, hva nå?"
20. ↑ 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. PMID 29557362.

## External links

Classification|

* ICD-10: B08.2
* ICD-9-CM: 057.8
* MeSH: D005077
* DiseasesDB: 5857
* SNOMED CT: 240559001

|

External resources|

* MedlinePlus: 000968
* eMedicine: emerg/400 derm/378 ped/998

* DermNet viral/roseola

* v
* t
* e

Infectious skin disease: Viral cutaneous conditions, including viral exanthema (B00–B09, 050–059)

| DNA virus|

| Herpesviridae|

| Alpha|

| HSV|

* Herpes simplex
* Herpetic whitlow
* Herpes gladiatorum
* Herpes simplex keratitis
* Herpetic sycosis
* Neonatal herpes simplex
* Herpes genitalis
* Herpes labialis
* Eczema herpeticum
* Herpetiform esophagitis

|

Herpes B virus|

* B virus infection

VZV|

* Chickenpox
* Herpes zoster
* Herpes zoster oticus
* Ophthalmic zoster
* Disseminated herpes zoster
* Zoster-associated pain
* Modified varicella-like syndrome

Beta|

* Human herpesvirus 6/Roseolovirus
* Exanthema subitum
* Roseola vaccinia
* Cytomegalic inclusion disease

Gamma|

* KSHV
* Kaposi's sarcoma

Poxviridae|

| Ortho|

* Variola
* Smallpox
* Alastrim
* MoxV
* Monkeypox
* CPXV
* Cowpox
* VV
* Vaccinia
* Generalized vaccinia
* Eczema vaccinatum
* Progressive vaccinia
* Buffalopox

|

Para|

* Farmyard pox: Milker's nodule
* Bovine papular stomatitis
* Pseudocowpox
* Orf
* Sealpox

Other|

* Yatapoxvirus: Tanapox
* Yaba monkey tumor virus
* MCV
* Molluscum contagiosum

Papillomaviridae|

| HPV|

* Wart/plantar wart
* Heck's disease
* Genital wart
* giant
* Laryngeal papillomatosis
* Butcher's wart
* Bowenoid papulosis
* Epidermodysplasia verruciformis
* Verruca plana
* Pigmented wart
* Verrucae palmares et plantares

|

* BPV
* Equine sarcoid

Parvoviridae|

* Parvovirus B19
* Erythema infectiosum
* Reticulocytopenia
* Papular purpuric gloves and socks syndrome

Polyomaviridae|

* Merkel cell polyomavirus
* Merkel cell carcinoma

RNA virus|

| Paramyxoviridae|

* MeV
* Measles

|

Togaviridae|

* Rubella virus
* Rubella
* Congenital rubella syndrome ("German measles" )
* Alphavirus infection
* Chikungunya fever

Picornaviridae|

* CAV
* Hand, foot, and mouth disease
* Herpangina
* FMDV
* Foot-and-mouth disease
* Boston exanthem disease

Ungrouped|

* Asymmetric periflexural exanthem of childhood
* Post-vaccination follicular eruption
* Lipschütz ulcer
* Eruptive pseudoangiomatosis
* Viral-associated trichodysplasia
* Gianotti–Crosti syndrome

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