Doctor123.org

Roseola

- Rash (exanthem subitum) (1) - Rose-pink macules and/or papules that blanch - First appears on the trunk then peripherally - May occur up to 3 days after fever resolves (1) - Fades within 2 days - Occurs in approximately 20% of patients in the United States (1)

- Other laboratory findings (1) - Decreased total leukocytes, lymphocytes, and neutrophils - Elevated transaminases - Thrombocytopenia

para>A disease of infants and very young children (4) ‚

EPIDEMIOLOGY

  • Predominant ageHHV-6Infants and very young children (<2 years old) (5)Peak age infection 6 to 9 months, rarely congenital or perinatal infection (1)95% of children have been infected with HHV-6 by 2 years of life.HHV-7Later childhoodMean age of infection 26 months>90% population with HHV-7 by 10 years (1)
  • Predominant sex: male = female (1)
  • No seasonal variance

Incidence

Common " ”accounts for 20% ED visits for febrile illness among children 6 to 8 months (6) ‚

Prevalence

  • Peak prevalence is between 9 and 21 months (5).
  • Nearly 100% population carrying HHV-6 by 3 years (1)
  • Approximately 20% patients with primary HHV-6 have roseola (6).

ETIOLOGY AND PATHOPHYSIOLOGY

  • HHV-6 and HHV-7 (4)
  • Majority of cases (60 " “74%) due to HHV-6HHV-6B > HHV-6A (4)HHV-6A seen in children in AfricaHHV-6 binds to CD46 receptors on all nucleated cells (4).
  • Primary infection typically through respiratory droplets or saliva
  • Congenital infection/vertical transmission occurs in 1% of cases (1).Transplacental transmissionChromosomal integration (clinical significance unknown)
  • Lifelong latent or persistent asymptomatic infection occurs after primary infection (1).80 " “90% population intermittently sheds HHV-6/HHV-7 in saliva (4).Patients are viremic from 2 days prior to fever until defervescence and onset of rash.HHV-6 latency is also implicated in CSF (6).

Genetics

HHV-6 is integrated into the chromosomes of 0.2 " “3.0% of the population. This leads to vertical transmission of the virus. Clinical significance of this is unknown (1). ‚

RISK FACTORS

  • Female gender (5)
  • Having older siblings (5)
  • At-risk adults: immunocompromised (7)Renal, liver, other solid organ, and bone marrow transplant (BMT) (5)HHV-6 reactivation can occur in 1st week posttransplant (7). HHV-6 viremia occurs in 30 " “45% of BMT within the first several weeks after transplantation (6).Usually asymptomatic (6)Up to 82% of HHV-6 reactivation/reinfection in solid organ transplant (7)
  • Nonrisk factors (5)Child care attendanceMethod of deliveryBreastfeeding (HHV does not appear to pass through breast milk)Maternal ageSeason

DIAGNOSIS

HISTORY

  • 3 to 5 days abrupt fever 102.2 " “104.0 ‚ °F (39 " “40 ‚ °C) not associated with a rash (1)
  • The child may be fussy during this prodrome (1,6).
  • Sudden drop of fever associated with appearance of rash (1)Rash on trunk then spreads centrifugally mainly to neck, possibly also to peripheral extremities, and face.
  • Diarrhea (5)
  • Mild upper respiratory symptoms (5)
  • Rhinorrhea (5)
  • Febrile seizure occurs in 13% of cases (1).

PHYSICAL EXAM

  • Rash (exanthem subitum) (1)Rose-pink macules and/or papules that blanchFirst appears on the trunk then peripherallyMay occur up to 3 days after fever resolves (1)Fades within 2 daysOccurs in approximately 20% of patients in the United States (1)
  • Mild inflammation of tympanic membrane, pharynx, and/or conjunctiva (1,6)
  • Ulcers on soft palate and uvula (Nagayama spots) (1)
  • Cervical lymphadenopathy (1)
  • Periorbital edema (4)

DIFFERENTIAL DIAGNOSIS

  • Enterovirus infection (8)
  • Adenovirus infection (1)
  • Epstein-Barr virus
  • Fifth disease " ”parvovirus B19 (8)
  • Rubella (8)
  • Scarlet fever (8)
  • Drug eruption (1)
  • Measles (1)

DIAGNOSTIC TESTS & INTERPRETATION

  • Primarily a clinical diagnosis not requiring laboratory or radiologic testing (1)
  • Tests often cannot differentiate latent or active disease (9).
  • Specific diagnosis only necessary in severe cases, unclear diagnosis where more serious disease needs to be ruled out, or if considering antiviral therapy (1).

Initial Tests (lab, imaging)

  • HHV-6 and HHV-7 by PCR (1,7)Serum, whole blood, CSF, or salivaBecoming more widely available
  • HHV-6 IgM immunofluorescence (1)Diagnostic for acute infectionSpike seen in 1st week of illness
  • HHV-6 IgG immunofluorescence (1)Check at diagnosis and then 2 weeks later.Use with IgM to show primary infection.Negative initial test and rise on follow-up suggests primary infection.
  • Viral culture (7)Rarely doneNo clinical use (very time consuming)
  • Other laboratory findings (1)Decreased total leukocytes, lymphocytes, and neutrophilsElevated transaminasesThrombocytopenia

Diagnostic Procedures/Other

  • Urine culture: to rule out UTI as source of fever (2)
  • Chest x-ray (CXR): if a child has respiratory symptoms

TREATMENT

No treatment necessary, resolves without sequelae (1)[C]. ‚

GENERAL MEASURES

  • Symptomatic relief including antipyretics (1)[C]
  • Hydration (1)[C]

MEDICATION

First Line

  • No specific first-line treatment in immunocompetent hosts beyond supportive measures (4)[C]Antivirals are not recommended in immunocompetent.
  • No approved antiviral treatment in immunocompromised (4).
  • Second-line IV ganciclovir, cidofovir, foscarnet tested in vitro studies in stem cell transplant patientsHHV-6B susceptible: ganciclovir and foscarnet (7)[C]HHV-6A and HHV-7 are more resistant to ganciclovir (7).
  • Antivirals suggested in individual cases of encephalitis (associated with reactivation of HHV-6) (7)
  • In bone marrow and stem cell transplant recipients receiving immunosuppression, ganciclovir prophylaxis is effective in preventing reactivation of HHV-6 (10)[B].

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • During febrile prodrome, monitor for dehydration.
  • None after typical rash appears and fever resolves
  • Mean duration of illness is 6 days (6).
  • If febrile seizures occur, they will cease after fever subsides and will not likely recur (6).
  • Symptomatic reactivation in immunocompromised (1)

DIET

Encourage fluids. ‚

PATIENT EDUCATION

  • Parental reassurance that this is usually a benign, self-limited disease (1).
  • There is no specific recommended period of exclusion from out-of-home care for affected children.
  • Patient is viremic a few days prior to fever until time of defervescence and rash onset.

PROGNOSIS

  • Course: acute, complete recovery without sequelae (1)
  • Reactivation in immunocompromised patients is common (6).

COMPLICATIONS

  • Febrile seizures13% patients with roseola (1,6)Accounts for ¢ … “; of primary seizures in children <2 years old (1)
  • Medication hypersensitivity syndromes (drug reaction with eosinophilia and systemic symptoms) (4)
  • Reactivation can occur in transplant patients, HIV-1 infection, and other immunocompromised individuals (6).
  • Meningoencephalitis occurs in immunocompetent and in immunosuppressed patients (6). Poor association with multiple sclerosis (6)
  • Pityriasis rosea (1)
  • Possible association with progressive multifocal leukoencephalopathy (6)

REFERENCES

11 Stone ‚ RC, Micali ‚ GA, Schwartz ‚ RA. Roseola infantum and its causal human herpesviruses. Int J Dermatol. 2014;53(4):397 " “403.22 Watkins ‚ J. Diagnosing rashes, part 4: generalized rashes with fever. Practice Nursing. 2013;24:335 " “340.33 Ely ‚ JW, Seabury Stone ‚ M. The generalized rash: part I. Differential diagnosis. Am Fam Physician. 2010;81(6):726 " “734.44 Wolz ‚ MM, Sciallis ‚ GF, Pittelkow ‚ MR. Human herpesrviruses 6, 7, and 8 from a dermatologic perspective. Mayo Clin Proc. 2012;87(10):1004 " “1014.55 Zerr ‚ DM, Meier ‚ AS, Selke ‚ SS, et al. A population-based study of primary human herpesvirus 6 infection. N Engl J Med. 2005;352(8):768 " “776.66 Caserta ‚ MT, Mock ‚ DJ, Dewhurst ‚ S. Human herpesrvirus 6. Clin Infect Dis. 2001;33(6):829 " “833.77 Le ‚ J, Gantt ‚ S. Human herpesvirus 6, 7 and 8 in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):128 " “137.88 Ely ‚ JW, Seabury Stone ‚ M. The generalized rash: part II. Diagnostic approach. Am Fam Physician. 2010;81(6):735 " “739.99 Dreyfus ‚ DH. Herpesviruses and the microbiome. J Allergy Clin Immunol. 2013;132(6):1278 " “1286.1010 Tokimasa ‚ S, Hara ‚ J, Osugi ‚ Y, et al. Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell transplantation. Bone Marrow Transplant. 2002;29(7):595 " “598.

ADDITIONAL READING

  • Ablashi ‚ DV, Devin ‚ CL, Yoshikawa ‚ T, et al. Review part 3: human herpesvirus-6 in multiple non-neurological diseases. J Med Virol. 2010;82(11):1903 " “1910.
  • Caselli ‚ E, Di Luca ‚ D. Molecular biology and clinical associations of Roseoloviruses human herpesvirus 6 and human herpesvirus 7. New Microbiol. 2007;30(3):173 " “187.
  • Dockrell ‚ DH, Smith ‚ TF, Paya ‚ CV. Human herpesvirus 6. Mayo Clin Proc. 1999;74(2):163 " “170.
  • Dyer ‚ JA. Childhood viral exanthems. Pediatr Ann. 2007;36(1):21 " “29.
  • Evans ‚ CM, Kudesia ‚ G, McKendrick ‚ M. Management of herpesvirus infections. Int J Antimicrob Agents. 2013;42(2):119 " “128.
  • F ƒ ¶lster-Holst ‚ R, Kreth ‚ HW. Viral exanthems in childhood " ”infectious (direct) exanthems. Part 1: classic exanthems. J Dtsch Dermatol Ges. 2009;7(4):309 " “316.
  • Huang ‚ CT, Lin ‚ LH. Differentiating roseola infantum with pyuria from urinary tract infection. Pediatr Int. 2013;55(2):214 " “218.
  • Leach ‚ CT. Human herpesvirus-6 and -7 infections in children: agents of roseola and other syndromes. Curr Opin Pediatr. 2000;12(3):269 " “274.
  • Lowry ‚ M. Roseola infantum. Pract Nurse. 2013;43:40 " “42.
  • Stoeckle ‚ MY. The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease. Annu Rev Med. 2000;51:423 " “430.
  • Vianna ‚ RA, de Oliveira ‚ SA, Camacho ‚ LA, et al. Role of human herpesvirus 6 infection in young Brazilian children with rash illnesses. Pediatr Infect Dis J. 2008;27(6):533 " “537.

CODES

ICD10

  • B08.20 Exanthema subitum [sixth disease], unspecified
  • B08.21 Exanthema subitum [sixth disease] due to human herpesvirus 6
  • B08.22 Exanthema subitum [sixth disease] due to human herpesvirus 7
  • B09 Unsp viral infection with skin and mucous membrane lesions

ICD9

  • 058.10 Roseola infantum, unspecified
  • 058.11 Roseola infantum due to human herpesvirus 6
  • 058.12 Roseola infantum due to human herpesvirus 7
  • 057.8 Other specified viral exanthemata

SNOMED

  • 54385001 Exanthema subitum
  • 402902002 Roseola infantum (HHV 6)
  • 402903007 Roseola infantum (HHV 7)
  • 402419007 Roseolar erythema

CLINICAL PEARLS

  • Roseola infection should be suspected if an infant or young child presents with a high temperature without other clinical findings.
  • As the fever abates, a macular rash will be seen on the trunk, with eventual spread to the face and extremities in 20% of patients.
  • Roseola is a clinical diagnosis, and laboratory testing is not necessary for most children with classic presentation.
  • For atypical presentations, complications, and immunocompromised hosts, several laboratory tools are available, including serologic testing for antibody, viral PCR testing, and viral culture.
  • Infection is typically self-limiting and without sequelae.
  • Usually only symptomatic treatment is needed.
  • Consider prophylaxis in patients undergoing bone marrow or stem cell transplant and receiving immunosuppressive therapy.