Continuing Education Activity

Roseola infantum, also known as exanthema subitum or sixth disease, is a common viral illness of early childhood caused primarily by human herpesvirus 6 and less frequently by human herpesvirus 7. The condition predominantly affects infants aged 6 to 12 months, with most cases occurring in those younger than 2. Clinical presentation is characterized by the abrupt onset of high fever, often exceeding 104 °F (40 °C), lasting several days, followed by rapid defervescence and the appearance of a nonpruritic, pink, papular rash that begins on the trunk and spreads to the neck and extremities. Febrile seizures occur in a subset of patients during the febrile phase. Diagnosis is clinical, and the illness is typically self-limited in immunocompetent children. Although human herpesvirus 6 establishes lifelong latency, significant morbidity is uncommon except in immunocompromised populations, in whom severe or atypical disease may occur.

Participants in this course enhance their competence in recognizing the characteristic clinical course of roseola infantum, differentiating it from other causes of febrile illness and childhood exanthems, and providing appropriate supportive management. Clinicians develop skills in counseling caregivers regarding fever management, seizure risk, and the benign natural history of the disease. The activity emphasizes the value of interprofessional collaboration among clinicians, nurses, and allied health professionals to ensure accurate assessment, symptom control, caregiver education, and timely escalation of care for high-risk patients. Effective team-based care supports patient safety, reduces unnecessary diagnostic testing, and improves outcomes for children affected by roseola infantum.

Objectives:

• Evaluate infants with prolonged fever, immunocompromised status, or atypical rash patterns for alternative diagnoses or complications.
• Assess infants with suspected roseola infantum to determine when additional diagnostic evaluation or referral is warranted.
• Determine when laboratory testing or imaging is unnecessary versus when atypical features justify additional evaluation.
• Implement evidence-based management strategies for roseola in collaboration with the interprofessional care team, including nurses, pharmacists, and dietitians, to ensure effective fever control, provide consistent caregiver counseling, and minimize unnecessary interventions for patients with roseola.

Introduction

Roseola infantum, also known as exanthema subitum or sixth disease, is a common childhood illness worldwide caused by infection with human herpesvirus 6 (HHV-6) or, less often, human herpesvirus 7 (HHV-7) (see Image. Roseola Infantum Rash). This condition typically affects children aged 6 to 12 months; 90% of cases occur in infants younger than 2 years, and it accounts for 10% to 45% of febrile illnesses in infants. Patients typically present with a sudden-onset fever up to 104 °F (40 °C) that lasts 3 to 5 days, followed by the sudden appearance of a non-pruritic exanthem as the fever subsides. The rash appears on the trunk and then spreads to the neck and extremities.

The term "sixth disease" originated from the historical classification of childhood exanthems, in which pediatricians in the late 19th and early 20th centuries systematically distinguished and numbered common febrile exanthems. This numerical system allowed physicians to organize and communicate about pediatric exanthems before their etiologies were understood.[1] Roseola infantum was first identified as a distinct clinical syndrome by American pediatrician John Zahorsky in 1913, establishing it as the sixth disease in this sequential system (JAMA 1913;61:1446–1450). Zahorsky used the term "exanthem subitum," meaning "sudden rash," to describe the characteristic pattern of high fever followed by the rapid appearance of a pink, papular rash upon defervescence. 

In most cases, roseola is a benign, self-limited infection diagnosed through history and distinctive physical exam findings. Treatment is limited to symptom relief, and the outlook is typically favorable, although atypical cases and complications can occur. Failure to recognize roseola can cause unnecessary parental anxiety, inappropriate diagnostic testing, unnecessary interventions, and inefficient use of healthcare resources.[2] This article reviews the clinical evaluation, diagnosis, and management of roseola, highlights atypical presentations and potential complications, and emphasizes the role of interprofessional collaboration in optimizing care for affected children.

Etiology

In 1986, the Japanese virologist Koichi Yamanishi identified HHV-6 as the causative agent of roseola by isolating the virus from the peripheral blood lymphocytes of patients with exanthem subitum, more than 7 decades after Zahorsky's original publication.[3][4] While contemporary texts mainly refer to the disease as "roseola infantum" or "exanthem subitum," the historical label "sixth disease" remains a recognized term in pediatric and infectious disease literature. Roseola is primarily caused by human herpesvirus 6B (HHV-6B) and, less commonly, by HHV-7, both members of the family Herpesviridae. HHV-6 and HHV-7 belong to the betaherpesvirinae subfamily, which is characterized by slow replication, lifelong latency, and reactivation, particularly in immunocompromised individuals. HHV-6 and HHV-7 are closely related to human cytomegalovirus.[5] 

HHVs-6 and -7 have linear, double-stranded DNA genomes flanked by direct terminal repeats containing reiterated hexanucleotide sequences. These repeats are believed to contribute to their shared ability to integrate into host chromosomes and establish latency.[6] Transmission of roseola occurs through viral shedding in the saliva of caregivers or other close contacts.[2] HHV-6 can be detected in saliva during primary infection and intermittently thereafter, allowing transmission from asymptomatic carriers (often parents or older siblings) to susceptible infants and young children. 

Epidemiology

HHV-6 infection is common worldwide, with seroprevalence rates exceeding 90% in most populations by early childhood.[3] In the United States, the virus has been identified as the cause of illness in 10% to 45% of febrile infants. A 2005 population-based study reported that 40% of children acquire HHV-6 infection by 12 months of age and 77% by 24 months, with higher rates in girls and in children with older siblings. Infection shows seasonal peaks in spring and fall, and transmission occurs primarily through saliva, likely via respiratory droplets.[7]

Serologic studies confirm that HHV-6 is ubiquitous, with most children infected by age 3.[8] Primary infection peaks between 6 and 11 months, and approximately 75% of cases occur in children aged 6 to 17 months, with a median age of acquisition of 9 months.[9] This age distribution likely reflects waning maternal antibody protection and increasing social exposure as infants become more mobile. The virus spreads efficiently among young children, likely via shared objects, saliva, or respiratory droplets. Both healthy and immunocompromised individuals can shed the virus, thereby allowing asymptomatic carriers to serve as reservoirs for ongoing transmission.[8]

Pathophysiology

During primary infection, HHV-6 mainly replicates in leukocytes and salivary glands, resulting in high viral loads in saliva that facilitate transmission. The virus also replicates effectively in CD4+ T cells, with an incubation period of approximately 9 to 10 days.[5] Early viral replication occurs in the respiratory tract, followed by viremia involving peripheral blood mononuclear cells; HHV-6 can be isolated from these cells during the first 3 days of fever, with detection decreasing afterward. This viremic phase corresponds with the sudden onset of high fever typical of roseola infantum. As the immune system mounts an antibody response, viremia declines, fever subsides, and the rash appears—indicating immune-driven rather than direct viral effects. Immunoglobulin G titers usually increase fourfold during recovery.[10] 

After the acute phase, HHV-6 remains in a latent state in mononuclear cells for life, with viral DNA detectable months after infection.[10] Persistent infection has been found in both salivary glands and brain tissue.[11] Additionally, HHV-6 can integrate into host chromosomes, resulting in chromosomally integrated HHV-6 (ci-HHV-6), a unique trait among human herpesviruses that may influence viral persistence and reactivation patterns.[7][8]

Neurologic symptoms, including febrile seizures, may result from several mechanisms. Elevated levels of matrix metalloproteinase-9 and its inhibitor,  tissue inhibitor of metalloproteinases-1, have been linked to blood–brain barrier dysfunction in infected infants, possibly contributing to seizure activity.[12] In some cases, HHV-6 has been shown to invade the central nervous system early in the course of the illness.[13] Both HHV-6B and HHV-7 have been associated with febrile status epilepticus, underscoring their potential effects on the developing nervous system. 

History and Physical

Children with roseola often appear relatively well despite high fever, appearing alert and playful.[2]  Some may exhibit nonspecific symptoms such as irritability, malaise, anorexia, cough, or other upper respiratory tract symptoms. Gastrointestinal symptoms, including diarrhea, may also occur. Caregivers may report conjunctivitis or transient orbital edema during the febrile phase. Additional symptoms reported in the history include poor appetite, decreased oral intake, and sleepiness.

Many infants have no focal physical findings other than fever during the early phase of illness. When present, significant clinical signs include conjunctivitis, orbital edema, lymphadenopathy, tympanic membrane inflammation, and, in some infants, a bulging fontanelle. Uvulopalatoglossal (Nagayama) spots—erythematous papules on the soft palate and uvula—are present in approximately two-thirds of affected children.[7]

Following defervescence, typically between days 3 and 5, the characteristic roseola exanthem appears. Consisting of discrete rose-pink macules and maculopapules measuring 2 to 5 mm, this rash sometimes surrounds a pale halo. The rash begins on the trunk and spreads to the neck and proximal extremities, with minimal or no involvement of the face. The eruption is blanching, nonpruritic, and short-lived, generally lasting only 1 to 2 days.[3] Classic descriptions note its rubella-like or measles-like appearance, central-to-peripheral spread, and sparing of the palms and soles.[14] The rash resolves without desquamation or sequelae.[3] Notably, only 23% to 31% of children with primary HHV-6 infection develop the typical rash, and many present with fever alone or nonspecific symptoms without an exanthem.[9]

Evaluation

The diagnosis of roseola infantum is primarily clinical; it relies on recognizing the characteristic sequence of high fever followed by the rapid appearance of a truncal maculopapular exanthem upon defervescence.[15] Routine diagnostic testing is not necessary for otherwise healthy children with a classic presentation. When performed, laboratory studies may reveal early leukopenia, sometimes followed by a transient rise in the white blood cell count that returns to normal within 7 to 10 days.

A retrospective study published in Japan in 2013 reported that about 13% of children with roseola showed sterile pyuria during their illness. This finding can complicate the assessment of febrile infants, potentially leading to a misdiagnosis of urinary tract infection and unnecessary antibiotic treatment.[16] When patients with roseola have febrile seizures, a thorough neurological evaluation is recommended. For febrile infants aged 8 to 60 days who do not yet exhibit the characteristic rash, assessment should follow age-specific fever protocols to rule out serious bacterial infections before diagnosing roseola.[17]

Diagnostic evaluation is usually reserved for children with unusual symptoms or high fevers without an obvious source, as well as for immunocompromised patients who appear ill. Confirmatory results include: serology showing seroconversion or a fourfold increase in HHV-6–specific IgG titers (observed in about 75% of cases diagnosed clinically), HHV-6 polymerase chain reaction from blood or other body fluids to detect active infection, and viral culture from peripheral blood mononuclear cells, which has the highest yield within the first 3 days of fever when viremia peaks.[10][18][19][20] However, for most children with typical roseola, laboratory testing rarely influences management and is unnecessary.

Treatment / Management

Treatment of roseola infantum is supportive, as the illness is mild and self-limited, typically resolving without long-term sequelae. No antiviral therapy is indicated for uncomplicated disease in immunocompetent children, and no vaccine is currently available for prevention. Good hand hygiene is vital to minimize transmission. Management focuses on symptomatic relief. Caregivers should treat fever with antipyretics such as acetaminophen or ibuprofen, and ensure adequate hydration and rest. The high fever generally resolves within 3 to 4 days. Because the exanthem is typically nonpruritic, no specific therapy for the rash is necessary.[3]

Febrile seizures are the most common complication of roseola and should be managed according to standard pediatric seizure protocols. Seizure control does not alter the underlying course of the viral infection. Antiviral therapy may be considered for severe HHV-6– or HHV-7–related disease in immunocompromised individuals, especially when accurate virologic testing confirms active infection or reactivation. Care for these patients differs significantly from the supportive care approach used for immunocompetent children, as immunocompromised individuals face a much higher likelihood of critical complications. Children with hematologic malignancies, those undergoing stem cell or organ transplants, and those with HIV are at increased risk for severe roseola caused by either primary infection or reactivation. In cases where serious disease is suspected or confirmed, early empiric antiviral therapy with ganciclovir or foscarnet may be initiated while diagnostic tests are ongoing.[6][21]

Differential Diagnosis

The differential diagnosis for a pediatric individual presenting with signs and symptoms of roseola includes several other viral exanthems and important bacterial infections that demand prompt recognition.[22] Measles presents with a prodrome of fever and the "3 Cs"—cough, coryza, and conjunctivitis—followed by a cephalocaudal maculopapular rash and pathognomonic Koplik spots.[23] Rubella typically presents with a mild, short-lived rash, generalized lymphadenopathy, and minimal fever; up to half of infections remain asymptomatic.[24] Both measles and rubella are rare in fully immunized children.

Enteroviral exanthems, such as Coxsackievirus A6, can cause atypical hand-foot-mouth disease with widespread vesiculobullous lesions.[25] Adenovirus may mimic bacterial sepsis, presenting with fever, respiratory or gastrointestinal symptoms, and conjunctivitis, with seasonal peaks occurring from late winter to early summer.[5] Parvovirus B19 causes a biphasic illness characterized by a "slapped-cheek" or "gloves-and-socks" rash as immunoglobulin M antibodies develop.[8] Scarlet fever should be considered when a finely papular erythematous rash appears alongside streptococcal pharyngitis.[26] The most critical "not to miss" diagnoses are meningococcemia and Kawasaki disease. Patients with meningococcemia present with petechiae, purpura, and hemodynamic instability and require urgent cultures and PCR testing.[27] Kawasaki disease is diagnosed based on fever lasting 5 or more days, along with mucocutaneous and extremity findings, supported by elevated inflammatory markers and thrombocytosis.[28] 

Prognosis

The prognosis for roseola infantum is excellent in immunocompetent children, as the illness is self-limiting and full recovery is typical with little risk of long-term effects; only a small percentage require hospitalization. After the acute phase resolves, children return to their normal health without lasting effects. Although the virus establishes lifelong latency, as is common with herpesviruses, this does not affect the short-term outlook of the initial illness.[3]

In contrast, the prognosis is considerably poorer in immunocompromised pediatric individuals, where reactivation of HHV-6 or HHV-7 can lead to critical and potentially life-threatening complications, including multiorgan failure and neurological damage involving the limbic system, brain stem, and hippocampus.[21][29] The most severe complication is post-transplantation limbic encephalitis linked to HHV-6B reactivation, which has a high risk of morbidity and death. Unlike immunocompetent children, recovery in immunocompromised individuals may be slow and incomplete, with persistent neurological problems or fatal outcomes possible when roseoloviruses reactivate after transplantation.[30]

Complications

Complications of primary HHV-6 infection vary widely, although most are rare. The most common complication is febrile seizures, which occur in about 10% to 15% of children during the high fever phase.[7] Reported incidence varies by setting: in a prospective, population-based cohort of 81 children with clearly defined primary HHV-6 infection, none experienced seizures.

In contrast, emergency department–based studies—reflecting sicker populations—have reported seizures in up to 13% of patients.[31] More severe neurological involvement, including febrile status epilepticus, has also been associated with primary HHV-6B and HHV-7 infections.[2] Beyond neurological issues, a broad spectrum of rare complications has been reported, primarily in case reports or small series in which HHV-6 DNA was detected in affected tissues or bodily fluids. These include myocarditis, rhabdomyolysis, thrombocytopenia, Guillain-Barré syndrome, hepatitis, leukopenia, aseptic meningitis, mononucleosis-like illness with pancytopenia and elevated liver enzymes, bilateral eyelid swelling (Hoagland sign), bronchopneumonia, bulging fontanelle, and diarrhea.[32]

However, these findings do not always correlate with viral load.[3][33] Encephalitis is uncommon in immunocompetent children but is much more frequent in immunocompromised individuals. In those who are immunosuppressed—such as transplant recipients—reactivation of HHV-6 or HHV-7 can lead to serious complications like encephalitis, limbic system injury, and multiorgan failure, with neurological recovery often slow and sometimes incomplete.[21] Despite these potential complications, the disease course in immunocompetent children is mostly benign: in a population-based study, 93% were symptomatic, and 38% saw a physician, yet all recovered fully without treatment.[31]

Deterrence and Patient Education

Because roseola primarily spreads through saliva and respiratory droplets, caregivers should receive practical guidance on reducing transmission. This includes regular handwashing—especially after wiping a child's nose, before feeding, and after diaper changes—and avoiding sharing cups, utensils, pacifiers, or washcloths. Strict isolation isn't necessary, but limiting close contact while the child has a fever is prudent, as most transmission occurs before the rash appears.

Clinicians should reassure families that roseola is common, harmless, and self-limited in healthy children. Fevers typically resolve within 3 to 4 days. The rash that follows indicates recovery and requires no treatment, and most children quickly return to normal activities. Education should also highlight warning signs requiring medical evaluation, such as febrile seizures, fever lasting more than 4 days, fever returning after defervescence, poor feeding or dehydration, excessive lethargy or irritability, or any signs suggestive of meningitis.

While preventing primary infection isn't practical—given the near-universal presence of HHV-6 and HHV-7—clinicians should be especially vigilant in immunocompromised children, as viral reactivation can cause severe neurologic or multisystem illness. In such cases, institutional protocols might include routine monitoring for viremia and prompt evaluation of new neurologic symptoms. Since no vaccine is available for roseola, prevention depends on good hygiene and clear education about benign versus concerning symptoms.

Enhancing Healthcare Team Outcomes

Effective management of roseola relies on coordinated interprofessional care to ensure accurate diagnosis, avoid unnecessary testing or treatment, and provide clear caregiver education. Physicians and advanced practitioners play a vital role in distinguishing roseola from other febrile illnesses, spotting red flags, and advising caregivers about the condition's usually benign, self-limited nature. Nurses reinforce anticipatory guidance, including fever management, hydration, and when to seek care—especially for febrile seizures. Pharmacists support safe use and dosing of antipyretics, helping to prevent medication errors in infants and toddlers.

Clear communication among team members maintains consistent messaging, reduces caregiver anxiety, and minimizes the inappropriate use of antibiotics or antivirals. In higher-risk settings, such as when caring for immunocompromised children, coordinated surveillance and early detection of potential complications enhance patient safety and outcomes. Interprofessional collaboration improves patient-centered results by reassuring caregivers, promoting prevention through hygiene education, and enabling prompt escalation of care for children with atypical or severe roseola.

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References

1.

Koch WC. Fifth (human parvovirus) and sixth (herpesvirus 6) diseases. Curr Opin Infect Dis. 2001 Jun;14(3):343-56. [PubMed: 11964854]

2.

Leung AK, Lam JM, Barankin B, Leong KF, Hon KL. Roseola Infantum: An Updated Review. Curr Pediatr Rev. 2024;20(2):119-128. [PubMed: 36411550]

3.

Stone RC, Micali GA, Schwartz RA. Roseola infantum and its causal human herpesviruses. Int J Dermatol. 2014 Apr;53(4):397-403. [PubMed: 24673253]

4.

Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet. 1988 May 14;1(8594):1065-7. [PubMed: 2896909]

5.

De Bolle L, Naesens L, De Clercq E. Update on human herpesvirus 6 biology, clinical features, and therapy. Clin Microbiol Rev. 2005 Jan;18(1):217-45. [PMC free article: PMC544175] [PubMed: 15653828]

6.

Agut H, Bonnafous P, Gautheret-Dejean A. Laboratory and clinical aspects of human herpesvirus 6 infections. Clin Microbiol Rev. 2015 Apr;28(2):313-35. [PMC free article: PMC4402955] [PubMed: 25762531]

7.

Tesini BL, Epstein LG, Caserta MT. Clinical impact of primary infection with roseoloviruses. Curr Opin Virol. 2014 Dec;9:91-6. [PMC free article: PMC4267952] [PubMed: 25462439]

8.

Miller JM, Binnicker MJ, Campbell S, Carroll KC, Chapin KC, Gonzalez MD, Harrington A, Jerris RC, Kehl SC, Leal SM, Patel R, Pritt BS, Richter SS, Robinson-Dunn B, Snyder JW, Telford S, Theel ES, Thomson RB, Weinstein MP, Yao JD. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clin Infect Dis. 2024 Mar 05; [PubMed: 38442248]

9.

Vianna RA, de Oliveira SA, Camacho LA, Knowles W, Brown D, Pereira AC, Velarde LG, Siqueira MM. Role of human herpesvirus 6 infection in young Brazilian children with rash illnesses. Pediatr Infect Dis J. 2008 Jun;27(6):533-7. [PubMed: 18449066]

10.

Pruksananonda P, Hall CB, Insel RA, McIntyre K, Pellett PE, Long CE, Schnabel KC, Pincus PH, Stamey FR, Dambaugh TR. Primary human herpesvirus 6 infection in young children. N Engl J Med. 1992 May 28;326(22):1445-50. [PubMed: 1315416]

11.

Abdel Massih RC, Razonable RR. Human herpesvirus 6 infections after liver transplantation. World J Gastroenterol. 2009 Jun 07;15(21):2561-9. [PMC free article: PMC2691485] [PubMed: 19496184]

12.

Kittaka S, Hasegawa S, Ito Y, Ohbuchi N, Suzuki E, Kawano S, Aoki Y, Nakatsuka K, Kudo K, Wakiguchi H, Kajimoto M, Matsushige T, Ichiyama T. Serum levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in human herpesvirus-6-infected infants with or without febrile seizures. J Infect Chemother. 2014 Nov;20(11):716-21. [PubMed: 25156011]

13.

Bronisz E, Kurkowska-Jastrzębska I. Matrix Metalloproteinase 9 in Epilepsy: The Role of Neuroinflammation in Seizure Development. Mediators Inflamm. 2016;2016:7369020. [PMC free article: PMC5220508] [PubMed: 28104930]

14.

Asano Y, Nakashima T, Yoshikawa T, Suga S, Yazaki T. Severity of human herpesvirus-6 viremia and clinical findings in infants with exanthem subitum. J Pediatr. 1991 Jun;118(6):891-5. [PubMed: 1645770]

15.

Allmon A, Deane K, Martin KL. Common Skin Rashes in Children. Am Fam Physician. 2015 Aug 01;92(3):211-6. [PubMed: 26280141]

16.

Huang CT, Lin LH. Differentiating roseola infantum with pyuria from urinary tract infection. Pediatr Int. 2013 Apr;55(2):214-8. [PubMed: 23190314]

17.

Pantell RH, Roberts KB, Adams WG, Dreyer BP, Kuppermann N, O'Leary ST, Okechukwu K, Woods CR., SUBCOMMITTEE ON FEBRILE INFANTS. Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics. 2021 Aug;148(2) [PubMed: 34281996]

18.

Linnavuori K, Peltola H, Hovi T. Serology versus clinical signs or symptoms and main laboratory findings in the diagnosis of exanthema subitum (roseola infantum). Pediatrics. 1992 Jan;89(1):103-6. [PubMed: 1309393]

19.

Aktürk H, Bağci MS, Yiğit MH, Khalilova F, Ünlügedik Ö, Asarcikli F. Roseola Infantum During the COVID-19 Pandemic. J Pediatr Hematol Oncol. 2022 Jan 01;44(1):e296-e298. [PubMed: 33828033]

20.

Keshavarz M, Ghasemi S, Arjeini Y, Namdari H, Maleki H, Mousavi N, Mokhtari-Azad T, Rezaei F. Frequency evaluation and molecular characterization of HHV-6 and HHV-7 among children under 5 years with fever and skin rash. J Med Virol. 2023 Mar;95(3):e28608. [PubMed: 36815506]

21.

Ongrádi J, Ablashi DV, Yoshikawa T, Stercz B, Ogata M. Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals. J Neurovirol. 2017 Feb;23(1):1-19. [PMC free article: PMC5329081] [PubMed: 27538995]

22.

Muzumdar S, Rothe MJ, Grant-Kels JM. The rash with maculopapules and fever in children. Clin Dermatol. 2019 Mar-Apr;37(2):119-128. [PubMed: 30981292]

23.

Strebel PM, Orenstein WA. Measles. N Engl J Med. 2019 Jul 25;381(4):349-357. [PubMed: 31184814]

24.

Winter AK, Moss WJ. Rubella. Lancet. 2022 Apr 02;399(10332):1336-1346. [PubMed: 35367004]

25.

Yasuda M, Shoji K, Tomita K, Uchida Y, Uematsu S, Yoshida K, Kono N, Funatsu M, Miyairi I. Clinical and Laboratory Diagnosis of Exanthems Among Japanese Children Younger Than 6 Years Old in the Post-Measles-Rubella Vaccine Era. Pediatr Infect Dis J. 2024 Feb 01;43(2):e44-e48. [PubMed: 37963264]

26.

Wessels MR. Clinical practice. Streptococcal pharyngitis. N Engl J Med. 2011 Feb 17;364(7):648-55. [PubMed: 21323542]

27.

van de Beek D, Brouwer MC, Koedel U, Wall EC. Community-acquired bacterial meningitis. Lancet. 2021 Sep 25;398(10306):1171-1183. [PubMed: 34303412]

28.

Jone PN, Tremoulet A, Choueiter N, Dominguez SR, Harahsheh AS, Mitani Y, Zimmerman M, Lin MT, Friedman KG., American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; and Council on Clinical Cardiology. Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association. Circulation. 2024 Dec 03;150(23):e481-e500. [PubMed: 39534969]

29.

Stoeckle MY. The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease. Annu Rev Med. 2000;51:423-30. [PubMed: 10774474]

30.

Hill JA, Zerr DM. Roseoloviruses in transplant recipients: clinical consequences and prospects for treatment and prevention trials. Curr Opin Virol. 2014 Dec;9:53-60. [PMC free article: PMC4570620] [PubMed: 25285614]

31.

Zerr DM, Meier AS, Selke SS, Frenkel LM, Huang ML, Wald A, Rhoads MP, Nguy L, Bornemann R, Morrow RA, Corey L. A population-based study of primary human herpesvirus 6 infection. N Engl J Med. 2005 Feb 24;352(8):768-76. [PubMed: 15728809]

32.

Mizuno S, Horiba K, Nakahashi T, Atsumi Y, Takahara T, Hashino M, Ito Y, Kamimura K. A 1-year-old boy presenting with roseola accompanied by bilateral eyelid oedema and acute infectious mononucleosis syndrome caused by human herpesuvirus-6B: A case report. Int J Infect Dis. 2026 Feb;163:108213. [PubMed: 41248707]

33.

Huang LM, Lee CY, Chen JY, Lee PI, Chen JM, Hsu CY, Kuo T. Roseola infantum caused by human herpesvirus-6: report of 7 cases with emphasis on complications. J Formos Med Assoc. 1991 Jun;90(6):579-82. [PubMed: 1681005]

Disclosure: Tessa Mullins declares no relevant financial relationships with ineligible companies.

Disclosure: Sharon Daley declares no relevant financial relationships with ineligible companies.

Disclosure: Karthik Krishnamurthy declares no relevant financial relationships with ineligible companies.