Roseola

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Roseola is a disease of infants. It is characterized by an abrupt rise in body temperature to as high as 40°C (104°F) followed by a rapid drop to normal within the next 2–4 days which coincides with the appearance of an erythematous maculopapular skin rash that persists for 1–3 days. It is typically a benign disease which resolves without sequelae. Roseola disease is caused by Human herpes virus 6 (HHV6). HHV-6A and HHV-6B are two distinct species of HHV-6.

For the first time, Zahorsky of St. Louis in 1910 described a febrile exanthem occurring in infants which he termed roseola. Human herpes virus 6 was first identified in 1986.

There is no established classification system for roseola.

Roseola has two phases, the febrile and the rash (maculopapular) phase. During the first phase, HHV6 replicates in salivary glands and is secreted as primary source of infection. After complete resolution of the febrile phase, due to the latency of the virus in the lymphocytes and monocytes, the rash phase begins. A more serious form of HHV 6 is seen in older children, immunocompromised adults and organ transplant patients.

Roseola is caused by Human herpes virus 6, a member of the Herpesvirales order, Herpesviridae family, Betaherpesvirinae subfamily, and Roseolovirus genus. Herpesviruses have a unique four-layered structure: a core containing the large, double-stranded DNA genome is enclosed by an icosapentahedral capsid which is composed of capsomers. The capsid is surrounded by an amorphous protein coat called the tegument. It is encased in a glycoprotein-bearing lipid bilayer envelope.

Roseola must be differentiated from other diseases that cause fever and rash, such as Rubella (german measles), Rubeola (measles), hand foot and mouth disease caused by coxsackie virus, erythema infectiosum caused by parvovirus B19, scarlet fever and even drug allergy.

There is no accurate data for the prevalence or incidence of roseola. This is because the disease is a self limiting disease and it is under reported in most cases. Roseola is an illness of young children, with a peak prevalence between 7 and 13 months. Ninety percent of cases occur in children younger than two years. Roseola occurs equally in boys and girls. It occurs throughout the year, although outbreaks may occur in groups according to season 

The common risk factors in the development of roseola includes infancy (younger 2 years), immunosuppression, and organ transplantation.

According to the USPSTF, there is insufficient evidence to recommend routine screening for roseola.

The symptoms of roseola usually starts in the first 2 years of life of an infant. If roseola, left untreated, it will resolve by itself. In rare cases, febrile seizures, encephalitis, aseptic meningitis, thrombocytopenic purpura, bone marrow failure and pneumonitis. The overall prognosis of roseola is very good.

The hallmark of roseola is a non pruritic macular or maculopapular rash. A positive history of a high fever of 40ºC (104ºF) that lasts for 3 to 5 days.

Physical examination findings in a patient with roseola will depend on the presenting phase (febrile or rash). Vital signs are affected in the febrile phase and stabilize in the rash phase. Conversely, in the rash phase, vital signs become normal while skin appearance is affected.

The diagnosis of roseola is made clinically. However, in atypical cases, the diagnosis can be made by both serologic and direct detection of HHV6 virus in the saliva of the patient. Expected results of diagnostic studies include antigen detection, PCR, and immunofluorescence.

There are no electrocardiogram findings associated with roseola.

There are no chest x ray findings associated with roseola.

There are no MRI findings associated with roseola.

There are no echocardiography or ultrasound findings associated with roseola.

There are no other imaging findings associated with roseola.

There are no other diagnostic studies associated with roseola.

There is no treatment for roseola; it is a self limiting disease that resolves on its own without any medical intervention but antipyretics can be used as a supportive therapy in cases of high fever.[1]

Surgical intervention is not recommended for the management of roseola.

There is no established method of prevention of roseola. However, standard sanitary procedures such as hand washing can help prevent the spread of the HHV 6 virus.

There are no secondary preventive measures available for roseola.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

For the first time, Zahorsky of St. Louis in 1910 described a febrile exanthem occurring in infants which he termed roseola. Human herpes virus 6 was first identified in 1986.

• For the first time, Zahorsky of St. Louis in 1910 described a febrile exanthem occurring in infants which he termed roseola.
• In 1986, Human herpes virus 6 (HHV6), the main causative agent of roseola disease was first isolated from patients who were diagnosed with HIV AIDS or a lymphoproliferative disorder from the peripheral blood leukocytes. ^[1]
• The two different variants of HHV 6 discovered by Frenkel, Ablashi and Aubin are variant A and Variant B HHV 6 strains.^[2][3][4]
• HHV 6A has been found to be more associated with the development of roseola.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

There is no established classification system for roseola.

There is no established classification system for roseola.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Roseola has two phases, the febrile and the rash (maculopapular) phase. During the first phase, HHV6 replicates in salivary glands and is secreted as primary source of infection. After completes resolution of the febrile phase, due to the latency of the virus in the lymphocytes and monocytes, the rash phase begins.

Roseola has two phases:

1. The febrile phase
2. The rash phase

• HHV 6 virus is replicated in the salivary glands and secreted in saliva in the primary infection.^[1]
• Intrauterine transmission was suggested by polymerase chain reaction (PCR) positivity of uncultured cord blood mononuclear cells.^[2]

• CNS invasion is believed to occur in rare cases accounting for some of the CNS manifestations such as febrile seizures.^[3]

• In the second phase of the disease, the HHV 6 virus is found to remain latent in lymphocytes and monocytes and found in low levels in some tissues. CD4 positive T cells have been found to support the growth of roseola.^[1][4]

• Infection of the CD134 cells has been shown in some studies to be responsible for the reactivation of HHV 6 from latency in vitro.
• The human herpes virus infects the T cells, monocytes–macrophages, epithelial cells, and central nervous system cells resulting in a lifelong latency or persistence of virus at multiple sites. HHV-6 exists in a true state of viral latency in monocytes and macrophages.^[4]
• HHV-6 has tropism towards CD4 T cells and replicates in the T cells inducing a lifelong latent infection in humans.

Chromosomal integration of HHV-6A and HHV-6B is responsible for transmission of infection from the parents to the newborn and is observed in 1% of the population.

A more serious form of HHV 6 is seen in older children, immunocompromised adults and organ transplant patients.

There are no gross pathologic findings associated with roseola.

There are no microscopic findings associated with roseola.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Roseola may be caused by either Human herpes virus 6A, 6B and 7 (HHV6A, HHV6B and HHV 7). The most common cause is HHV6B. Other causes include enteroviruses (Coxsackie A and B, echoviruses), adenoviruses and parainfluenza viruses.

• Roseola may be caused by Human herpes virus 6A, 6B and 7 (HHV6A, HHV6B and HHV 7). Other causes include enteroviruses (Coxsackie A and B, echoviruses), adenoviruses and parainfluenza viruses.^[1]
• Roseola belongs to the Roseolovirus genus of the Betaherpesviridnae subfamily.
• HHV-6B causes exanthema subitum.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Roseola must be differentiated from other diseases that cause fever and rash, such as Rubella (german measles), Rubeola (measles), hand foot and mouth disease caused by coxakie virus, erythema infectiosum caused by parvovirus B19, scarlet fever and even drug allergy.

Roseola, also known as Exanthem subitum must be differentiated from all other childhood diseases that cause rash, and fever. The following table summarizes the differential diagnosis for roseola.^{[1][2][3][4][5][6][7][8]}

Differential Diagnosis of fever and rash.

Disease	Cause	Typical Age	Prodrome	Fever	Duration of the rash (days)	Workup	Treatment
Roseola Infantum (exanthem subitum)	Human herpes virus type 6	6 months to 2 years	None	High	1-2; it follows defervescence	Discrete erythematous macules, rarely involves face, begins as fever ends	Lymphadenopathy, irritability
Measles	Paramyxovirus Measles virus	1 to 20 years	2-4 days of cough, conjunctivitis, and coryza	High	5 – 6	Erythematous, irregular size, maculopapular; starts on temples and behind ears; progresses down from face; fades to brownish	Koplik’s spots: C blue-white papules (salt grains) on bright red mucosa opposite premolar teeth
Rubella	Togavirus	7 months to 29 years	0 – 4 days; mild malaise, fever; absent in children	Low grade	1 – 3	Discrete, rose-pink, diffuse, maculopapular; progresses downward from face, may change quickly	Arthralgia (usually in adults), tender posterior cervical and suboccipital lymphadenopathy, malaise, petechiae on soft palate
Erythema Infectiosum (Fifth Disease)	Human parvovirus type B19	5 – 10 years	None, usually in children, may occur in adults	None to low-grade	2 – 4	Starts as “slapped cheek”, maculopapular; progresses to reticular (lacy) pattern; can recur with environmental changes such as sunlight exposure	Arthralgia/arthritis in adults, adenopathy
Infectious Mononucleosis	Epstein-Barr Virus	10 – 30 years	2 – 5 days of malaise and fatigue	Low to high	2 – 7	Trunk and proximal extremities. Rash common if Ampicillin given	Pharyngitis, lymphadenopathy, splenomegaly, malaise
Kawasaki disease	Unknown	< 5 years	3 days of abrupt fever	High; fever of 5 days is a diagnostic criteria	5 – 7	Erythematous, morbilliform, maculopapular or scarlatiniform, central distribution; erythematous, indurated palms and soles	Acute: dry, fissured and injected lips, strawberry tongue; irritability; cervical lymphadenopathy; conjunctival injection; peripheral edema; Subacute: finger-tip desquamation; Complications: arthritis, carditis
Scarlet Fever	ß-hemolytic streptococci	> 2 years	0 – 6 day, marked	Low to high	2 – 7	Scarlet “sunburn” with punctate papules “sandpaper”, circumoral pallor, increased intensity in skin folds, blanches stars face/head, upper trunk and progresses downward	Sore throat, exudative tonsillitis, vomiting, abdominal pain, lmphadenopathy, white then red strawberry tongue
Enterovirus	Echovirus Coxsackie virus	Mainly childhood	0 – 1 day fever and myalias	Low to high	1 – 5	Fine, pink, always affects face; variant is Boston exanthem (large ~ 1 cm, discrete maculopapules)	Sore throat, headache, malaise, no lymphadenopathy, gastroenteritis
Dengue Fever	Flavivirus Dengue virus types 1 – 4		None	High	1 – 5	Generalized maculopapular rash after defervescence; spares palms and soles	Headache, myalgia, abdominal pain, pharyngitis, vomiting
Drug induced rash	Many	Any	Possible due to underlying illness	Possible	Varies	Typically diffuse but may be concentrated in diaper area, typically no progression, erythema multiform rash can progress over a few days	Possibly due to underlying illness or complications
Pharyngoconjunctival Fever	Adenovirus types 2, 3, 4, 7, 7a	< 5 years		Low to high	3 – 5	Starts on face and spreads down to trunk and extremities	Sore throat, conjunctivitis, headache, anorexia

Table adapted from CDC Pinkbook.^[9]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

There is no accurate data for the prevalence or incidence of roseola. This is because the disease is a self limiting disease and it is under reported in most cases. Roseola is an illness of young children, with a peak prevalence between 7 and 13 months. Ninety percent of cases occur in children younger than two years. Roseola occurs equally in boys and girls. It occurs throughout the year, although outbreaks may occur in groups according to season .

• There is no accurate data for the prevalence or incidence of roseola.
• More than 90% of adult populations in developed countries are seropositive for HHV 6.

Roseola commonly affects young children between the ages of 7 and 13 months.^[1]

• Males and females are affected equally by roseola.^[2]

• There is no racial predilection for roseola.

• HHV6 infection is nearly universal accounting for 10-45% of febrile illness in infants.

• There is a strong association of HHV 6A in Zambian children when compared to rest of the world.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

The common risk factors in the development of roseola includes infancy (younger 2 years), immunosuppression, and organ transplantation.

Risk factors predisposing to roseola infection include:

• Infancy: primary infection usually occurs in children less than 2 years of age
• Immunosuppression in adults with solid organ transplants and patients with HIV infection are at a higher risk of developing complications such as encephalitis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

According to the USPSTF, there is insufficient evidence to recommend routine screening for roseola.

According to the USPSTF, there is insufficient evidence to recommend routine screening for roseola.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

The symptoms of roseola usually starts in the first 2 years of life of an infant. If roseola is left untreated, it will resolve by itself. In rare cases, febrile seizures, encephalitis, aseptic meningitis, thrombocytopenic purpura, bone marrow failure and pneumonitis. The overall prognosis of roseola is very good.

• The symptoms of roseola usually start in the first 2 years of life of an infant. It starts as a high fever 40ºC (104ºF) which lasts for 3 to 5 days, as the fever abates, the child develops a non pruritic blanching papular or maculopapular rash that starts on the neck and progresses downward.^[1]
• Roseola is a self limiting disease; if left untreated, it resolves without any sequelae.

Roseola is usually benign and self limited. However patients with HIV or immunosuppressed patients may experience reactivation of the virus and signs and symptoms such as:^[1]

• Seizures ( generally related to fever)
• Aseptic meningitis
• Encephalitis
• Thrombocytopenic purpura
• Bone marrow failure
• Pneumonitis

The prognosis of roseola is good even without treatment. It is a self limiting disease, most children recover without any sequelae.^[2][3]