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Fifth disease

Last updated: November 23, 2020

Summary

Erythema infectiosum (fifth disease) is one of the clinical syndromes caused by human parvovirus B19 infection. The virus is transmitted by respiratory droplets and primarily affects children between the ages of five and fifteen. Erythema infectiosum begins with a mild febrile illness followed two to five days later by a maculopapular rash that is especially noticeable on the cheeks (i.e., "slapped‑cheek" rash) and may be pruritic. Once the rash has appeared, the infected individual is no longer contagious and usually feels well again. Erythema infectiosum is self‑limited, and the rash usually resolves within seven to ten days, but may be recurrent over several weeks. Whereas adult infection is characterized much more by arthritic symptoms and less by a rash, parvovirus B19 infection also manifests with joint symptoms in a minority of children. There is no specific vaccine or treatment for parvovirus B19 infection, though symptomatic treatment for arthralgias or pruritus can be used. Previous parvovirus B19 infection results in lifelong immunity against the virus. Because of its ability to infect erythrocyte progenitor cells, parvovirus B19 can cause transient anemia in infected patients, as well as complications such as a transient aplastic crisis in patients with chronic hemolytic diseases (e.g., sickle cell disease), and chronic pure red cell aplasia in the immunocompromised. Infection with parvovirus B19 (one of the TORCH congenital infections) during pregnancy may also have serious consequences for the fetus.

Epidemiology

  • Peak incidence: 5–15 years
  • Prevalence of seropositivity
    • ∼ 10% in preschool children
    • ∼ 70% in adults

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathogen

Route of transmission

  • Main route: aerosol
  • Other routes:
    • Hematogenous transmission
    • Transplacental transmission: In seronegative pregnant women, transmission to the unborn fetus may occur (in up to 30% of cases).

References:[4][5][6]

Pathophysiology

Clinical features

Disease course

Clinical symptoms

  • Mild cold‑like symptoms
  • Exanthem: 2–5 days following the onset of cold‑like symptoms
    • Initial diffuse redness of the face with perioral sparing (slapped‑cheek rash)
    • Spread of exanthem to the extremities and trunk
      • Initially confluent and maculopapular; adopts a lace‑like, reticular appearance over time as it clears.
      • Associated with mild pruritus (in ∼ 50% of cases)
      • Fades after ∼ 7–10 days; can be recurrent over several weeks (becoming more pronounced after exposure to sunlight or heat)
    • Third phase with rash that varies with exposure to sun or heat and resolves spontaneously after several weeks.

Parvovirus B19-associated arthritis

  • Epidemiology: : affects < 10% of children and up to 60% of adults ( > ) infected with parvovirus B19
  • Clinical findings
    • Arthralgia with symmetrical, nondestructive polyarthritis, particularly in the joints of the fingers, hand, knee, and ankle
    • Usually resolves after 3–4 weeks
  • Complications: In some cases, persistent arthritis may develop (see “Complications” below).

References:[1][11][12][13][14][15]

Diagnostics

The diagnostic approach for parvovirus B19 infection varies by patient group. However, all groups may be affected by transient normocytic anemia with a low reticulocyte count because of the ability of the virus to infect erythrocyte progenitor cells.

Immunocompetent children

  • Erythema infectiosum is typically a clinical diagnosis (i.e., slapped‑cheek or lace‑like appearance of rash) in children.

Immunocompetent adults

  • Lab tests only if the diagnosis is unclear
  • Antibody testing
    • IgM antibody
      • Appears within ∼ 10 days of initial exposure, indicating acute illness
      • Remains positive for 2–3 months
    • IgG antibody
      • Appears approx. 2 weeks following infection
      • Remains positive for life
  • Differentiating between parvovirus B19‑associated arthritis and acute rheumatoid arthritis may require additional tests (see diagnostics section of rheumatoid arthritis)

Patients with transient aplastic crisis and immunocompromised patients

Pregnant women

References:[3][11][13]

Differential diagnoses

References:[11]

The differential diagnoses listed here are not exhaustive.

Treatment

References:[3][16]

Complications

References:[17][18][19]

We list the most important complications. The selection is not exhaustive.

References

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  2. Bua G, Manaresi E, Bonvicini F, Gallinella G. Parvovirus B19 replication and expression in differentiating erythroid progenitor cells. PLoS ONE. 2016; 11 (2): p.e0148547. doi: 10.1371/journal.pone.0148547 . | Open in Read by QxMD
  3. Brown KE, Anderson SM, Young NS. Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science. 1993; 262 (5130): p.114-7.
  4. Bachelier K, Biehl S, Schwarz V, et al. Parvovirus B19-induced vascular damage in the heart is associated with elevated circulating endothelial microparticles. PLoS ONE. 2017; 12 (5): p.e0176311. doi: 10.1371/journal.pone.0176311 . | Open in Read by QxMD
  5. Dyrsen ME, Iwenofu OH, Nuovo G, Magro CM. Parvovirus B19-associated catastrophic endothelialitis with a Degos-like presentation. J Cutan Pathol. 2008; 35 : p.20-25. doi: 10.1111/j.1600-0560.2007.00974.x . | Open in Read by QxMD
  6. Agabegi SS, Agabegi ED. Step-Up To Medicine. Wolters Kluwer Health ; 2015
  7. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education ; 2015
  8. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education ; 2014
  9. Jordan JA. Clinical Manifestations and Diagnosis of Parvovirus B19 Infection. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-parvovirus-b19-infection.Last updated: March 14, 2017. Accessed: March 19, 2017.
  10. Zellmann GL. Erythema Infectiosum. Erythema Infectiosum. New York, NY: WebMD. http://emedicine.medscape.com/article/1132078-overview#a5. Updated: June 2, 2016. Accessed: March 19, 2017.
  11. Jordan JA. Microbiology, epidemiology, and pathogenesis of parvovirus B19 infection. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/microbiology-epidemiology-and-pathogenesis-of-parvovirus-b19-infection?source=search_result&search=epidemiology+of+parvo&selectedTitle=1~150.Last updated: December 15, 2014. Accessed: March 19, 2017.
  12. Le T, Bhushan V, Sochat M, Petersen M, Micevic G, Kallianos K. First Aid for the USMLE Step 1 2014. McGraw-Hill Medical ; 2014
  13. Goodwin TM, Montoro MN, Muderspach L, Paulson R, Roy S. Management of Common Problems in Obstetrics and Gynecology. John Wiley & Sons ; 2010
  14. Lamont RF, Sobel JD, Vaisbuch E, et al. Parvovirus B19 infection in human pregnancy. BJOG. 2010; 118 (2): p.175-186. doi: 10.1111/j.1471-0528.2010.02749.x . | Open in Read by QxMD
  15. Sabella C, Goldfarb J. Parvovirus B19 Infections. Am Fam Physician. 1999; 60 (5): p.1455-1460.
  16. Servey JT, Reamy BV, Hodge J. Clinical Presentations of Parvovirus B19 Infection. Am Fam Physician. 2007; 75 (3): p.373-376.
  17. Aslan B, Serin MS, Aslan G et al. . Detection of parvovirus B19 in synovial fluids of patients with osteoarthritis. Diagn Microbiol Infect Dis. 2007; 60 (4): p.381-5. doi: 10.1016/j.diagmicrobio.2007.11.003 . | Open in Read by QxMD
  18. Heegaard ED, Brown KE. Human Parvovirus B19. Clin Microbiol Rev. 2002; 15 (3): p.485-505. doi: 10.1128/cmr.15.3.485-505.2002 . | Open in Read by QxMD
  19. Khouqeer RA. Viral Arthritis. Viral Arthritis. New York, NY: WebMD. http://emedicine.medscape.com/article/335692-overview. Updated: January 26, 2017. Accessed: March 19, 2017.
  20. Goljan EF. Rapid Review Pathology. Elsevier Saunders ; 2013
  21. Schrier SL, Mentzer WC, Rosmarin AG. Aplastic Anemia: Pathogenesis; Clinical Manifestations; and Diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/aplastic-anemia-pathogenesis-clinical-manifestations-and-diagnosis?source=search_result&search=aplastic%20anemia&selectedTitle=1~150#H23.Last updated: September 8, 2016. Accessed: February 8, 2017.
  22. Maakaron JE. Sickle Cell Anemia. In: Besa EC, Sickle Cell Anemia. New York, NY: WebMD. http://emedicine.medscape.com/article/205926. Updated: October 3, 2016. Accessed: March 19, 2017.
  23. Parvovirus B19 and Fifth Disease - About Parvovirus B19. https://www.cdc.gov/parvovirusb19/about-parvovirus.html. Updated: November 2, 2015. Accessed: March 19, 2017.
  24. Parvovirus B19 and Fifth Disease - Fifth Disease. https://www.cdc.gov/parvovirusb19/fifth-disease.html. Updated: November 2, 2015. Accessed: March 19, 2017.