Fifth and sixth diseases: More than a fever and a rash

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Applied Evidence

Fifth and sixth diseases: More than a fever and a rash

J Fam Pract. 2014 October;63(10):E1-E5

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References

1. Kliegman RM, Stanton BMD, St. Geme J, et al. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier/Saunders; 2011.

2. Tuckerman JG, Brown T, Cohen BJ. Erythema infectiosum in a village primary school: clinical and virological studies. J R Coll Gen Pract. 1986;36:267-270.

3. Ramsay M, Reacher M, O’Flynn C, et al. Causes of morbilliform rash in a highly immunised English population. Arch Dis Child. 2002;87:202-206.

4. Anderson LJ. Role of parvovirus B19 in human disease. Pediatr Infect Dis J. 1987;6:711-718.

5. Smith PT, Landry ML, Carey H, et al. Papular-purpuric gloves and socks syndrome associated with acute parvovirus B19 infection: case report and review. Clin Infect Dis. 1998;27:164-168.

6. Tello-Winniczuk N, Diaz-Jouanen E, Diaz-Borjón A. Parvovirus B19-associated arthritis: report on a community outbreak. J Clin Rheumatol. 2011;17:449-450.

7. Molina KM, Garcia X, Denfield SW, et al. Parvovirus B19 myocarditis causes significant morbidity and mortality in children. Pediatr Cardiol. 2013;34:390-397.

8. Jensen IP, Thorsen P, Jeune B, et al. An epidemic of parvovirus B19 in a population of 3,596 pregnant women: a study of sociodemographic and medical risk factors. BJOG. 2000;107:637-643.

9. Lassen J, Jensen AK, Bager P, et al. Parvovirus B19 infection in the first trimester of pregnancy and risk of fetal loss: a population-based case-control study. Am J Epidemiol. 2012;176:803-807.

10. Enders M, Weidner A, Zoellner I, et al. Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn. 2004;24:513-518.

11. Heegaard ED, Brown KE. Human parvovirus B19. Clin Microbiol Rev. 2002;15:485-505.

12. American College of Obstetrics and Gynecologists. ACOG practice bulletin. Perinatal viral and parasitic infections. Number 20, September 2000. (Replaces educational bulletin number 177, February 1993). Int J Gynaecol Obstet. 2002;76:95-107.

13. Harger JH, Adler SP, Koch WC, et al. Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms. Obstet Gynecol. 1998;91:413-420.

14. Zerr DM, Meier AS, Selke SS, et al. A population-based study of primary human herpesvirus 6 infection. N Engl J Med. 2005;352:768-776.

15. Hall CB, Caserta MT, Schnabel KC, et al. Congenital infections with human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7). J Pediatr. 2004;145:472-477.

16. Richardson M, Elliman D, Maguire H, et al. Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and pre-schools. Pediatr Infect Dis J. 2001;20:380-391.

17. Gewurz BE, Marty FM, Baden LR, et al. Human herpesvirus 6 encephalitis. Curr Infect Dis Rep. 2008;10:292-299.

18. Howell KB, Tiedemann K, Haeusler G, et al. Symptomatic generalized epilepsy after HHV6 posttransplant acute limbic encephalitis in children. Epilepsia. 2012;53:e122-e126.

19. Nicolson GL, Gan R, Nicolson NL, et al. Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders. J Neurosci Res. 2007;85:1143-1148.

20. De Bolle L, Naesens L, De Clercq E. Update on human herpesvirus 6 biology, clinical features, and therapy. Clin Microbiol Rev. 2005;18:217-245.

21. Baillargeon J, Piper J, Leach CT. Epidemiology of human herpesvirus 6 (HHV-6) infection in pregnant and nonpregnant women. J Clin Virol. 2000;16:149-157.

22. Levy JA, Ferro F, Greenspan D, et al. Frequent isolation of HHV-6 from saliva and high seroprevalence of the virus in the population. Lancet. 1990;335:1047-1050.

Treat supportively

No specific treatment exists for parvovirus B19 infection. Management is supportive and the infection is usually mild and self-limiting. A nonsteroidal anti-inflammatory agent may be sufficient for associated arthritis; if needed, a low-dose oral corticosteroid can be used without prolonging the viral illness.⁶ Refer for hematologic consultation any immunocompromised patient with confirmed parvovirus who develops a hematologic complication, which may require intravenous immunoglobulin treatment or, in severe cases, bone marrow transplantation.

Clinical recommendations

Parvovirus B19 is communicable only during the nonspecific prodromal period—the 4 to 21 days of incubation in which the patient seems to have a common cold, with coryza, sore throat, and headache. With the appearance of the “slapped cheek” rash (an immune-mediated, postinfectious sequela), a child with erythema infectiosum is no longer infectious. At this stage, exclusion from school or child care is unnecessary.¹

Perform serologic testing to determine immunity for all pregnant women with documented exposure to parvovirus B19.¹² Retest women who are initially nonimmune after 3 to 4 weeks. Patients who seroconvert should undergo serial ultrasounds for 10 weeks to evaluate for hydrops fetalis or growth restriction. Repeat testing is unwarranted for those who do not seroconvert. There is no evidence to suggest that seronegative pregnant women should avoid work environments during endemic periods of infection.¹³

Sixth disease

Human herpesvirus 6 (HHV-6) causes sixth disease, also known as roseola infantum or exanthem subitum. Ninety percent of children have been infected by 2 years of age, with peak incidence occurring between 9 and 21 months of age.¹⁴ HHV-6 is most likely transmitted via the saliva of healthy individuals and enters the body via a mucosal surface. One percent of HHV-6 infection is acquired congenitally without known sequelae, similar to the transmission rate of cytomegalovirus.¹⁵

Clinical presentation:  Only 20% may exhibit a rash 

After an incubation period of 10 to 15 days, sixth disease is characterized by a prodrome of mild rhinorrhea, sore throat, and conjunctival redness, followed by a high fever (100.4°F to 104°F).¹⁶ Cervical, postauricular, or occipital lymphadenopathy usually develops. Other symptoms are usually absent but may include abdominal pain, vomiting, or diarrhea. After 3 to 5 days, the fever abates and the rash of roseola may begin—if at all— as tiny, erythematous, raised papules on the trunk that spread to the neck and extremities (FIGURE 2), lasting 1 to 3 days. Interestingly, while 93% of those infected are symptomatic (fevers, fussiness, rhinorrhea), only 20% of those infected exhibit the rash of roseola.¹ Nagayama spots (ulcers at the uvulopalatoglassal junction) can be seen in Asian infants.

Complications. Fifteen percent of infected children have febrile seizures.¹ Based on several case reports, HHV-6 infection has been associated with meningoencephalitis, acute disseminated demyelination, hepatitis, and myocarditis.¹⁷ It is unknown whether seizures increase the risk of these complications. Long-term sequelae from these manifestations of HHV-6 infection include developmental disorders and autism-spectrum disorders.^18,19

Treat supportively

Patients with primary HHV-6 infection usually require antipyretics and frequent hydration. Reserve antivirals such as ganciclovir, foscarnet, and cidofovir for immunocompromised patients or those with HHV-6 encephalitis.²⁰

Clinical recommendations

Most patients infected with HHV-6 have fever and rhinorrhea,  and are fussy. Only 20% exhibit the rash of roseola. Treat seizures associated with HHV-6 infection as you would any other febrile seizure, giving an antiepileptic (diazepam, lorazepam, or midazolam) if the seizure lasts >5 minutes. Risk of seizure recurrence with HHV-6 is equivalent to that seen with other causes of febrile seizure.¹

Because of the ubiquitous prevalence of HHV-6 infection, there are no effective preventive measures. Little is known about the effect of HHV-6 exposure during pregnancy because most pregnant mothers are immune to the virus.²¹ Exclusion from school or child care is not recommended because of the prolonged shedding of the virus.^16,22

CORRESPONDENCE
Jason S. O’Grady, MD, Department of Family Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; ogrady.jason@mayo.edu

ACKNOWLEDGEMENT
The author thanks Anne Mounsey, MD, Department of Family Medicine, University of North Carolina at Chapel Hill, for her invaluable assistance in editing this manuscript.