The Topic of This Month Vol.19 No.3(No.217)

Erythema infectiosum

Erythema infectiosum (EI), also called the fifth disease, is a contagious exanthematous disease affecting mainly children. Erythema developing on the cheek and multiformic erythema then developing on the superior and inferior limbs coalesce gradually, resulting in such characteristic erythema that is expressed as lacy, mesh-like, or ring form.

The etiological agent of this disease was proposed to be human parvovirus B19 (B19) by the group of the British Public Health Laboratory Service in 1983 (CDSC, CDR, 83/23). The causal relation between B19 and EI has been confirmed by the subsequent investigations. As the etiological agent has been verified, it has also been found that there are many cases of atypical exanthema and asymptomatic cases around EI patients, and that there are varieties of clinical manifestations and blood-borne infection may occur, although droplet infection is most common in EI.

The National Epidemiological Surveillance of Infectious Diseases (NESID) has been collecting reports on EI from sentinel clinics since July 1981. Before that, there used to be small-scale epidemics in spring toward early summer in 10-year periods, and nation-wide epidemics were confirmed in 1980. The recent epidemics have been in five-year periods as shown in Fig. 1 and less seasonal. The age distribution of cases found in NESID disclosed the largest number of cases of 5-9 years old, followed by those of 1-4 years old (Fig. 2). Since this surveillance collects information primarily from pediatric sentinels, incidence of adult cases is not known; however IASR has reported outbreaks among adults due to nosocomial infection in nurse school students and nurses (see IASR, Vol. 12, No. 7, 1991 and Vol. 18, No. 12, 1997).

Isolation of B19 virus is difficult and development of diagnostic reagents has been delayed. Recently, however, antibody diagnostic reagents making use of B19 particle antigen expressed by recombinant DNA techniques have been developed also in this country. The prevalence of age-specific IgG antibody among healthy individuals found with the reagents in 1993 is shown in Fig. 3. The age group of 0-4 years gave prevalence as low as about 10%, that of 5-14 years about 60%, that of 15-29 years gave a slightly lower prevalence, and that of over 30 years again higher prevalence, and the higher was the age, the higher was the antibody prevalence. There was no significant difference in the antibody prevalence between males and females (Matsunaga et al., J. Japan. Assoc. Infect. Dis., 69, 1371, 1995).

EI was first reported as atypical rubella (1889) and later established an independent disease entity. The epidemic periods of rubella and EI have often been overlapped. Fig. 4 compares the trend of reports on rubella with that on EI (Fig. 1) disclosed by NESID. Both, showing similar incidence patterns, give peaks in 1987 and 1992. No clinical misdiagnosis could be made in typical EI cases, but differentiation of atypical EI cases from rubella-like rash may be difficult. It was stated that about half of the patients diagnosed as rubella were actually B19 infection in a serological survey conducted in UK (CDSC, CDR, Vol. 3, No. 28). Recently, B19 antibody diagnostic reagent kits have been available, which has accomplished simplification of serological survey. It is, therefore, expected that differential diagnosis of the two diseases will depend more on the laboratory diagnosis.

EI is a typical B19 infection with favorable prognosis, whereas B19 infection is not restricted merely to EI. If a hemolytic anemia patient is infected with B19, severe aplastic crisis will develop. Besides, acute arthritis, thrombocytopenia, granulocytopenia, virus-associated hemophagocytic syndrome/hemophagocytic syndrome (VAHS/HPS), and persistent infection among immunocompromised hosts have been recognized.

One of the matters to be attended concerning B19 infection is such fetal abnormality as hydrops fetalis due to infection of pregnant women. It has been reported in UK that the frequency of B19 infection among pregnant women was about 1/400, about 9% of which caused fetal deaths (CDSC, CDR, Vol. 4, Review No. 9 and see IASR, Vol. 15, No. 9, 1994). Anomalies of stillborn infants have been reported, but no congenital anomalies of liveborn infants have been found. According to the reports in this country, the frequency of hydrops fetalis in an EI epidemic year in Fukuoka City was about two per 1,000 child births, and many of them died (see p. 52 of this issue). Unlike rubella infection among pregnant women, the risk of congenital anomalies may be small; but it is important to grasp the condition of the fetus by ultrasound scanning and to ensure performing virological diagnosis.

B19 virus particles, being as small as 18-26 nm in diameter, are difficult to remove by filtration, resistant to organic solvents or detergents, and highly heat stable because of the lack of envelopes (lipid membrane). Since B19 DNA may occasionally be detected in plasma derivatives, the possibility of B19 infection from their administration could not be denied. Such warnings as "the postadministration course should carefully be watched", "in patients of hemolytic or blood-loss anemia and those in immunodeficiency or immunosuppressed condition, fever, sudden onset of anemia, and continuous or prolonged anemia may sometimes develop", "pregnant women or women anticipating pregnancy may be administered only when the benefit exceeds the risk after due consideration of the risk-and-benefit balance of the treatment" have been added to the instructions for use of plasma derivatives (Information on Adverse Reactions to Drugs, the Ministry of Health and Welfare, No. 141, January 1997 and see p. 52 of this issue). As for immunoglobulin products, it is possible that the antibodies contained in the products have neutralized the infectivity; however, as there are no data firmly supporting this, the restrictions for their use have been changed in line with other plasma derivatives.

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