View source for Roseola

{{Short description|Human disease caused by human herpesviruses}}
{{Distinguish|2=|text=either rubeola/[[measles]] or [[rubella]], which are also viral diseases with comparable features, or [[rosacea]], a skin condition}}
{{Infobox medical condition (new)
| name            = Roseola
| synonyms        = Exanthema subitum,<ref name=St2014/> roseola infantum,<ref name=St2014/> sixth disease,<ref name=St2014/> baby measles, rose rash of infants, three-day fever
| image           = Roseola on a 21-month-old girl.jpg
| caption         = Roseola rash on the arms and legs of a 21-month-old girl
| field           = [[Infectious disease (medical specialty)|Infectious disease]]
| symptoms        = Fever followed by rash<ref name=St2014/>
| complications   = [[Febrile seizures]]<ref name=St2014/>
| onset           = Before the age of 3, usually somewhere at age 2<ref name=St2014/>
| duration        = Few days<ref name=CDC2017/>
| types           =
| causes          = ''[[Human herpesvirus 6]]'' (HHV-6) or ''[[human herpesvirus 7]]'' (HHV-7)<ref name=St2014/>
| risks           =
| diagnosis       = Typically based on symptoms<ref name=St2014/>
| differential    = [[Measles]], [[rubella]], [[scarlet fever]]<ref name=St2014/>
| prevention      =
| treatment       = [[Supportive care]]<ref name=St2014/>
| medication      =
| prognosis       = Generally good<ref name=St2014/>
| frequency       =
| deaths          =
}}
<!-- Definition and symptoms -->
'''Roseola''', also known as '''sixth disease''', is an [[infectious disease]] caused by certain types of [[Herpesviridae#Human herpesvirus types|human herpes viruses]].<ref name=CDC2017>{{cite journal|last1=Campadelli-Fiume|first1=Gabriella|title=Human Herpesvirus 6: An Emerging Pathogen|journal=Emerging Infectious Diseases|volume=5|issue=3|pages=353–366|language=en-us|doi=10.3201/eid0503.990306|pmid=10341172|pmc=2640789|year=1999}}</ref> Most infections occur before the age of three.<ref name=St2014>{{cite journal|last1=Stone|first1=RC|last2=Micali|first2=GA|last3=Schwartz|first3=RA|title=Roseola infantum and its causal human herpesviruses.|journal=International Journal of Dermatology|date=April 2014|volume=53|issue=4|pages=397–403|doi=10.1111/ijd.12310|pmid=24673253|s2cid=2652000}}</ref> Symptoms vary from absent to the classic presentation of a fever of rapid onset followed by a rash.<ref name=St2014/><ref name=CDC2017/> The fever generally lasts for three to five days, while the rash is generally pink and lasts for less than three days.<ref name=St2014/> Complications may include [[febrile seizures]], with serious complications being rare.<ref name=St2014/><ref name=CDC2017/>

<!-- Cause and diagnosis -->
It is caused by ''[[human herpesvirus 6]]'' (HHV-6A, '''HHV-6B''') or ''[[human herpesvirus 7]]'' (HHV-7).<ref name=St2014/> Spread is usually through the [[saliva]] of those who are otherwise healthy.<ref name=St2014/><ref name=CDC2017/> However, it may also spread from the mother to the baby during pregnancy.<ref name=St2014/> Diagnosis is typically based on symptoms and does not need to be confirmed with blood tests (PCR or antigen).<ref name=St2014/> Low numbers of [[white blood cell]]s may also be present.<ref name=St2014/>

<!-- Treatment and epidemiology -->
Treatment includes sufficient fluids and medications to treat the fever.<ref name=St2014/> Nearly all people are infected at some point.<ref name=CDC2017/> Males and females are affected equally often.<ref name=St2014/> The disease may reactivate in those with a [[immunocompromised|weakened immune system]] and may result in significant health problems.<ref name=CDC2017/>

The disease was first described in 1910 while the causal virus was isolated in 1988.<ref name="St2014" /> The name "sixth disease" comes from its place on the standard list of [[Exanthem|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 [[Fifth disease|erythema infectiosum]] (fifth).<ref>{{Citation|last1=Feder|first1=Henry M.|title=Classic Viral Exanthems|date=2008|url=https://www.cambridge.org/core/books/clinical-infectious-disease/classic-viral-exanthems/3CF0D1C1D493C8F6E34E9A72CB0BF56C|work=Clinical Infectious Disease|pages=135–140|editor-last=Schlossberg|editor-first=David|place=Cambridge|publisher=Cambridge University Press|doi=10.1017/cbo9780511722240.020|isbn=978-0-511-72224-0|access-date=2022-01-04|last2=Grant-Kels|first2=Jane M.|url-access=subscription}}</ref>

==Signs and symptoms==

=== Fever ===
Symptoms begin with a three to six-day febrile illness.<ref name=":2" /><ref name=":3">{{Cite book|last=Cherry|first=James D.|title=Feigin and Cherry's Textbook of Pediatric Infectious Diseases|year=2019|isbn=978-0-323-37692-1|pages=559–561|chapter=Roseola Infantum (Exanthem Subitum)|publisher=Elsevier }}</ref> During this time, temperatures can peak above 40&nbsp;°C and children can experience increased irritability with general malaise.<ref name=":3" /> Many children in the febrile phase feel well, engaged, and alert. For these patients, fever is usually diagnosed incidentally.<ref name=":3" />

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 seizure]]s which can precipitate [[status epilepticus]] due to the sudden rise in body temperature.<ref name=":4">{{Cite web|url=https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640111&bookid=2205|title=Human Herpesvirus 6 (Including Roseola) and 7 {{!}} Red Book® 2018 {{!}} Red Book Online {{!}} AAP Point-of-Care-Solutions|website=redbook.solutions.aap.org|access-date=2020-04-22}}</ref>

=== Rash ===
Once the [[febrile]] phase subsides, a rash develops. The rash sometimes presents one or two days after the fever resolves.<ref name=":3" /> The rash is classically described as an [[erythematous]] [[morbilliform]] [[exanthem]]<ref name=":2" /> and presents as a distribution of soft pink, discrete, and slightly raised lesions each with a 2-5mm diameter.<ref name=":2" /><ref name=":3" /><ref name=":4" /> 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.<ref name=":2" /> Usually, peeling and itching are not characteristic of this rash.<ref name=":3" /> This phase can last anywhere from several hours to 2 days.<ref name=":2" /><ref name=":3" /><ref name=":4" /><ref>[http://www.webmd.com/skin-problems-and-treatments/tc/roseola-topic-overview ''Roseola – Topic Overview''] {{webarchive|url=https://web.archive.org/web/20080727031317/http://www.webmd.com/skin-problems-and-treatments/tc/roseola-topic-overview|date=2008-07-27}}, webmd.com</ref><ref name=":5" /><ref>[https://kdl.ru/patient/blog/kori-kak-ne-zaboleti''Measles Rash''] {{webarchive|url=https://web.archive.org/web/20080727031317/https://kdl.ru/patient/blog/kori-kak-ne-zaboleti }}, webmd.com</ref>

=== Other symptoms ===
A small percentage of children acquire HHV-6 with few signs or symptoms of the disease.<ref name=":5" /> Children with HHV-6 infection can also present with myringitis (inflammation of the tympanic membranes),<ref name=":2" /> upper respiratory symptoms,<ref name=":4" /><ref>{{Cite journal|last1=Zerr|first1=Danielle M.|last2=Meier|first2=Amalia S.|last3=Selke|first3=Stacy S.|last4=Frenkel|first4=Lisa M.|last5=Huang|first5=Meei-Li|last6=Wald|first6=Anna|last7=Rhoads|first7=Margaret P.|last8=Nguy|first8=Long|last9=Bornemann|first9=Rena|last10=Morrow|first10=Rhoda Ashley|last11=Corey|first11=Lawrence|date=2005-02-24|title=A Population-Based Study of Primary Human Herpesvirus 6 Infection|journal=New England Journal of Medicine|volume=352|issue=8|pages=768–776|doi=10.1056/NEJMoa042207|issn=0028-4793|pmid=15728809|doi-access=free}}</ref> diarrhea, and a bulging fontanelle.<ref name=":4" /> In addition, children can experience pharyngitis with lymphoid hyperplasia seen on the soft palate and swelling of the eyelids.<ref name=":3" /> These symptoms usually present during the febrile phase of roseola.<ref name=":4" /> Cervical and postoccipital [[lymphadenopathy]] can also be seen, but this generally presents 2–4 days after the onset of the febrile phase.<ref name=":4" /><ref>{{Cite journal|last1=Asano|first1=Y.|last2=Yoshikawa|first2=T.|last3=Suga|first3=S.|last4=Kobayashi|first4=I.|last5=Nakashima|first5=T.|last6=Yazaki|first6=T.|last7=Kajita|first7=Y.|last8=Ozaki|first8=T.|date=January 1994|title=Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum)|journal=Pediatrics|volume=93|issue=1|pages=104–108|doi=10.1542/peds.93.1.104 |issn=0031-4005|pmid=8265302|s2cid=23785433 }}</ref>

In rare cases, HHV-6 can become active in an adult previously infected during childhood and can show signs of [[Infectious mononucleosis|mononucleosis]].<ref name="pmid10774474">{{cite journal |author=Stoeckle MY |title=The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease |journal=Annu. Rev. Med. |volume=51 |pages=423–30 |year=2000 |pmid=10774474 |doi=10.1146/annurev.med.51.1.423 }}</ref>

==Cause==
[[File:Hhv-6 (1).jpg|thumb|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]].<ref name=":4" /> These viruses are of the [[Herpesviridae]] family and the ''[[Betaherpesvirinae]]'' subfamily, under which [[Cytomegalovirus]] is also classified.<ref name=":4" /> 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.<ref name=":2">{{Cite journal|last1=Arango|first1=Carlos A.|last2=Jones|first2=Ross|date=October 2017|title=8 viral exanthems of childhood|journal=The Journal of Family Practice|volume=66|issue=10|pages=598–606|issn=1533-7294|pmid=28991936}}</ref><ref name=":0">{{Cite journal|last1=Strausbaugh|first1=Larry J.|last2=Caserta|first2=Mary T.|last3=Mock|first3=David J.|last4=Dewhurst|first4=Stephen|date=2001-09-15|title=Human Herpesvirus 6|journal=Clinical Infectious Diseases|language=en|volume=33|issue=6|pages=829–833|doi=10.1086/322691|pmid=11512088|issn=1058-4838|doi-access=free}}</ref>

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.<ref name=":4" />

=== Spread ===
After exposure to roseola, the causative virus becomes latent in its host but is still present in saliva, skin, and lungs.<ref name=":4" /> HHV-6 is thought to be transmitted from previously exposed or infected adults to young children by shedding the virus through saliva.<ref name=":5">{{Cite book|title=American Academy of Pediatrics textbook of pediatric care|editor-last1=McInerny|editor-first1=Thomas K.|editor-last2=Adam|editor-first2=Henry M.|editor-last3=Campbell|editor-first3=Deborah E.|editor-last4=Foy|editor-first4=Jane Meschan|editor-last5=Kamat|editor-first5=Deepak M. |date=2017 |isbn=978-1-61002-047-3|edition=2nd|location=Elk Grove Village, IL|publisher=American Academy of Pediatrics|oclc=952123506}}</ref> Even so, most cases of roseola are transmitted without known exposure.<ref name=":3" />

== Diagnosis ==
The diagnosis of roseola is made clinically based on the presence of the two phases: fever and rash.<ref name=":3" /> Laboratory testing is seldom used as the results do not alter the management of the disease.<ref name=":4" /> An exception is in people who are immunocompromised in whom [[serologic test]]s with viral identification can be used to confirm the diagnosis.<ref name=":5" />

Roseola should be differentiated based on symptoms from other similar-appearing illnesses, such as [[rubella]], [[measles]], [[fifth disease]], [[scarlet fever]], and drug reactions.<ref name=":5" />

==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.<ref name=":3" /> 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.<ref name=":6" /> No current guidelines exist regarding children staying home or away from child care when infected.<ref name=":6">{{Cite journal|last1=Richardson|first1=M.|last2=Elliman|first2=D.|last3=Maguire|first3=H.|last4=Simpson|first4=J.|last5=Nicoll|first5=A.|date=April 2001|title=Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools|journal=The Pediatric Infectious Disease Journal|volume=20|issue=4|pages=380–391|doi=10.1097/00006454-200104000-00004|issn=0891-3668|pmid=11332662|s2cid=7700827}}</ref>

==Treatment==
Most cases of HHV-6 infection improve on their own.<ref>{{cite journal|last1=Tesini|first1=BL|last2=Epstein|first2=LG|last3=Caserta|first3=MT|title=Clinical impact of primary infection with roseoloviruses.|journal=Current Opinion in Virology|date=December 2014|volume=9|pages=91–6|pmid=25462439|doi=10.1016/j.coviro.2014.09.013|pmc=4267952}}</ref> 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 seizure]]s.<ref name=":4" /><ref name=":5" /> In the case of febrile seizures, medical advice should be sought, and treatment aggressively pursued.<ref name=":3" /> Antiepileptic drugs are not recommended for patients who develop seizures from roseola.<ref name=":2" /> 

Once children have entered the rash phase, reassurance is important as this indicates the resolution of the infection.<ref name=":3" />

If [[encephalitis]] occurs in [[immunocompromised]] children, [[ganciclovir]] or [[foscarnet]] have inconsistently shown usefulness in treatment.<ref>{{cite journal|last1=Ongrádi|first1=J|last2=Ablashi|first2=DV|last3=Yoshikawa|first3=T|last4=Stercz|first4=B|last5=Ogata|first5=M|title=Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals.|journal=Journal of NeuroVirology|date=February 2017|volume=23|issue=1|pages=1–19|pmid=27538995|doi=10.1007/s13365-016-0473-0|pmc=5329081}}</ref> Treatment of children who are immunocompromised centers around decreasing their levels of immunosuppression as much as possible.<ref name=":5" />

== Prognosis ==
Children infected with roseola generally have a good prognosis. Most recover without intervention or long-term effects.<ref name=":2" /><ref name=":3" />

== Epidemiology ==
Between the two human herpesvirus 6 types, HHV-6B has been detected much more frequently in hosts.<ref name=":0" /> HHV-6B has been shown to affect about 90% of children before the age of 3.<ref name=":1">{{Cite web|url=https://hhv-6foundation.org/associated-conditions/hhv-6-rash-roseola|title=HHV-6 & Rash/Roseola {{!}} HHV-6 Foundation {{!}} HHV-6 Disease Information for Patients, Clinicians, and Researchers {{!}} Apply for a Grant|website=hhv-6foundation.org|access-date=2020-04-22|archive-date=2020-05-12|archive-url=https://web.archive.org/web/20200512214421/https://hhv-6foundation.org/associated-conditions/hhv-6-rash-roseola|url-status=dead}}</ref> Out of these, 20% develop symptoms of roseola, also known as exanthem subitum.<ref name=":1" />

Roseola affects girls and boys equally worldwide year-round.<ref name=":3" /> Roseola typically affects children between six months and two years of age, with peak prevalence in children between 7 and 13 months old.<ref name=":3" /><ref name=":4" /> This correlates with the decrease in maternal antibodies, thus virus protection, that occurs at the age of 6 months.<ref name=":4" /> 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.<ref name=":4" />

Many children exposed and infected can present without symptoms, which makes determining the incidence within the population difficult.<ref name=":3" />

==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.<ref>John Zahorsky. Roseola Infantum. Journal of the American Medical Association. Oct 18, 1913 pages 1446-1450</ref>

==Names==
{{More citations needed section|date=November 2017}}

{| class="wikitable"
|-
|'''Country'''
|'''Local name (language)'''
|'''Translated name'''
|-
|Belgium
|Driedagenkoorts (Dutch)<br />Zesde ziekte (Dutch)<br />Roséole (French)
|"three-day fever"<br />"sixth disease"<br />-
|-
|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)<br />Hatodik betegség (Hungarian)
|"three-day fever"<br />"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)<ref>Nylander, Gro (2009) "Lille venn, hva nå?"</ref>
|"fourth disease"
|-
|Philippines
|Tigdas Hangin (Tagalog)
|"wind measles"
|-
|Poland
|Gorączka trzydniowa (Polish)
|"Three-day fever"
|-
|Romanian
|Roseola<br />eruptia subita
|Roseola
|-
|Russia
|Розеола (Russian)<br />шестая болезнь (Russian)
|Roseola<br />"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<br />Sjätte sjukan (Swedish)
|"three-day fever"<br />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 disease]]s.<ref>{{cite journal |last1=Hogestyn |first1=JM |last2=Mock |first2=DJ |last3=Mayer-Proschel |first3=M |title=Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology. |journal=Neural Regeneration Research |date=February 2018 |volume=13 |issue=2 |pages=211–221 |doi=10.4103/1673-5374.226380 |pmid=29557362|pmc=5879884 |doi-access=free }}</ref>

== See also ==
* [[Fifth disease]]

==References==
{{Reflist}}

== External links ==
{{Medical resources
| DiseasesDB      = 5857
| ICD10           = {{ICD10|B|08|2|b|00}}
| ICD9            = {{ICD9|057.8}}
| ICDO            =
| OMIM            =
| MedlinePlus     = 000968
| eMedicineSubj   = emerg
| eMedicineTopic  = 400
| eMedicine_mult  = {{eMedicine2|derm|378}} {{eMedicine2|ped|998}}
| MeshID          = D005077
| SNOMED CT       = 240559001
}}
* {{DermNet|viral/roseola}}
{{Viral cutaneous conditions}}
{{Numbered Diseases of Childhood}}

{{DEFAULTSORT:Exanthema Subitum}}
[[Category:Virus-related cutaneous conditions]]
[[Category:Pediatrics]]
[[Category:Wikipedia medicine articles ready to translate]]