doi: 10.1111/1346-8138.

15153 Journal of Dermatology 2019;

: 1–4

CONCISE COMMUNICATION
Case of chickenpox in which varicella zoster virus genotype
E was identified for the first time in Japan
Gyohei EGAWA,1 Kiyofumi EGAWA,2 Kenji KABASHIMA1
1
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, 2Amakusa Dermatology and Internal Medicine
Clinic, Kamiamakusa, Japan

ABSTRACT
Varicella zoster virus (VZV) is now classified into seven genotypes, and type J (clade 2) is known as an exclusively
prevalent genotype in Japan. Here, we describe an adult Japanese patient who was suffering from chickenpox
caused by VZV type E, the most prevalent genotype in Western Europe. Because the eruptions were distributed
over the trunk and limbs and the patient had a high titer of immunoglobulin G against VZV, we diagnosed this
case as secondary VZV infection. To investigate the current prevalence of VZV genotypes in Japan, we examined
the genotype of VZV in an additional 49 Japanese varicella/zoster patients who visited our hospital during 2018–
2019. We found that VZV type E was still an exceptionally rare genotype (1/50) in Japan. Because foreign nationals
living in Japan who carry VZV genotypes other than type J are increasing in number, secondary chickenpox may
increase in Japan in the near future, as well as in the USA where multiple VZV genotypes are distributed.

Key words: chickenpox, herpes zoster, reinfection, varicella, varicella zoster virus.

INTRODUCTION
Varicella zoster virus (VZV) is one of eight herpesviruses
known to cause human infection and is widely distributed
throughout the community. In Japan, the VZV antibody posi-
tivity in children (aged 3–4 years) and adults (aged ≥20 years)
is 37.3% and 95.2%, respectively.1 VZV is an etiologic patho-
gen of two clinically distinct forms: varicella (chickenpox) and
herpes zoster (shingles). Primary infection of VZV causes
chickenpox, which is characterized by a vesicular rash of the
entire body. After the primary infection, VZV establishes life-
long latency, mainly in the dorsal root ganglia and trigeminal
ganglion. Endogenous reactivation of latent VZV causes her-
pes zoster, which usually occurs in a restricted dermatomal
distribution.
Chickenpox usually occurs in childhood and its skin eruption
is generally mild, but VZV acquired in adulthood may result in
serious complications, sometimes even life-threatening.2 Some
case reports of chickenpox in the elderly have been
reported,3–5 although it is considered to be rare because VZV
seroconversion generally occurs by early adulthood. The clini-
cal manifestation is rather mild in the elderly, similar to that in
childhood, and of note, it occurs even in the VZV-seropositive
population.5
Varicella zoster virus is divided into three genogroups: E,
European; M, mosaic; and J, Japanese type.6,7 Using single
nucleotide polymorphisms (SNP) from open reading frame
(ORF) 21 and 22 of the VZV genome that are highly polymor-
phic, up to seven stable genotypes are now identified (E1, E2,
M1–M4 and J). At the international nomenclature meeting in
2008, the seven following clades were established: clade 1,
E1; clade 2, J; clade 3, E2; clade 4, M2; clade 5, M1; clade
6, M4; and clade 7, M3.8 The VZV type E group (clades 1 and
3) is the most prevalent genotype in Western Europe and the
area settled by Europeans. On the other hand, type J (clade
2) has been found almost exclusively in Japan, and VZV type
E has yet never been reported in Japan.7 A live, attenuated
varicella vaccine (Oka strain) has been used worldwide and
this strain was derived from VZV type J. Previous reports
showed that the Oka strain is sometimes a cause of chicken-
pox and herpes zoster, especially in immunocompromised
hosts.9,10
Here, we describe for the first time a case of chickenpox in
a Japanese adult, which was caused by VZV type E. In addi-
tion, to investigate the current prevalence of VZV genotypes in
Japan, we examined the genotype of VZV in an additional 49
Japanese varicella/zoster patients who visited our hospital dur-
ing 2018–2019, which showed that all patients studied har-
bored VZV type J.
CASE REPORT
A 54-year-old Japanese woman who was suffering from leg
ulcers complicated by leg cellulitis was admitted to our

Correspondence: Gyohei Egawa, M.D., Ph.D., Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho,
Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Email: gyohei@kuhp.kyoto-u.ac.jp
Received 29 July 2019; accepted 23 October 2019.

© 2019 Japanese Dermatological Association 1

G. Egawa et al.

hospital. At the age of 38 years, she had been diagnosed with
cutaneous polyarteritis nodosa and had been administrated
10–40 mg oral prednisolone daily for over 10 years. At the day
of admission, she had been given 15 mg oral prednisolone
daily and was administrated antibiotics i.v. At the 14th day
after admission, small (1–2-mm diameter) vesicles surrounded
by erythema had developed on her trunk and limbs (Fig. 1a–e).
She complained of no pruritus or pain. No fever or neuralgia
was observed during the course. She noticed no obvious
opportunity of having been in contact with varicella/herpes
zoster patients beforehand and had no recent history of travel
abroad. The Tzanck test from the vesicles was positive and
histological examination showed the presence of an intraepi-
dermal vesicle containing ballooned, acantholytic keratinocytes
with intranuclear inclusion bodies (Fig. 1f,g). Based on these
clinical and histological observations, she was diagnosed with
chickenpox and was prescribed a p.o. dose of 3000 mg
valacyclovir daily. Vesicles became crusts within 1 week and
then disappeared.
Antibody titers against VZV were examined at the day of the
vesicle formation. She had a high titer of immunoglobulin (Ig)G
(128.0) and a low titer of IgM (1.38) against VZV, suggesting
that this case was not the primary VZV infection. To examine
the genotype of causative VZV, one of the vesicles was punc-
tured, and the vesicular content was directly subjected to poly-
merase chain reaction (PCR) using specific primers for ORF 22
of VZV (forward, 50 -GGGTTTTGTATGAGCGTTGG-30 ; reverse,
50 -CCCCCGAGGTTCGTAATATC-30 ). We examined the DNA
sequence of PCR products and identified that the genotype of
VZV in this case was type E (Fig. 2).
Because VZV type E had never been reported in Japan thus
far, we investigated the current prevalence of VZV genotypes
in Japan. We examined the genotype of VZV in an additional
49 Japanese varicella/zoster patients (aged 10–96 years, four

(a) (b)

(c) (d) (e)

(f) (g)

Figure 1. Small vesicles on the (a) neck, (b) trunk, (c) back, (d) thigh and (e) forearm. Arrows represent the vesicles. The right panel
in (b) is a higher magnification of the vesicles. (f,g) Histology of the vesicles. Inset in (f) is magnified in (g) (bars, 100 lm).

2 © 2019 Japanese Dermatological Association

 Chickenpox by VZV type E in Japan

(a)

(b)

Figure 2. (a) Single nucleotide polymorphism (SNP) variations in open reading frame 22 in different varicella zoster virus (VZV) genotypes.
(b) DNA sequences of our case (patient) and the control subject of VZV type J (Ctrl). Yellow represents the position of SNP variations.

chickenpox and 46 herpes zoster patients) who visited our DISCUSSION

hospital during 2018–2019. All subjects other than the case
Here, we described a case of chickenpox in late adulthood.
reported here were identified as type J (Table 1), suggesting
The clinical manifestation was mild and indistinguishable from
that VZV type E is still an exceptionally rare genotype in Japan.
that of general chickenpox in childhood. For this case, we
To distinguish the wild-type VZV J strain from the Oka strain,
needed to exclude the possibility of disseminated herpes zos-
we performed a PCR restriction fragment length polymorphism
ter, because she already had a high titer of IgG against VZV at
assay using specific primers for ORF 62 of VZV (forward,
the onset of the eruption, but we diagnosed this case as chick-
50 -AGGTTGGCAAACGCAGTC-30 ; reverse, 50 -ATTACTGTC-
enpox, namely the secondary VZV infection, because she did
GACCCGAGACC-30 ) together with the restriction enzyme SmaI
not have eruptions in a dermatomal distribution and she com-
as described previously.11 We found that all of the type J sub-
plained of no neuralgia suggestive of zoster sine herpete.
jects examined in this study were of wild type (Table 1).
A previous study showed that secondary varicella infection is
more common than generally thought in the USA: among 9947
Table 1. Varicella zoster virus genotypes of Japanese
chickenpox patients, 684 (6.8%) experienced repeated infec-
varicella/zoster patients
tions.12 Our patient was a prednisolone-treated immunocompro-
J mised host, but no case of repeated chickenpox with pre-
existing immunocompromising condition has been reported,
Wild type Oka E1/E2 M1 M2 Total
suggesting that the immunosuppression is not a prerequisite for
Varicella 3 0 1 0 0 4 repeated VZV infection. Secondary infection does not tend to be
Herpes zoster 46 0 0 0 0 46
more severe than the first/single infection, especially among
Total 49 0 1 0 0 50
individuals younger than 9 years; but it gets more severe in early

© 2019 Japanese Dermatological Association 3

G. Egawa et al.
adulthood,13 and may become milder again in the elderly, as
reported here and previously.5 The secondary chickenpox may
tend to occur among the late adulthood or older population
when the incidence of herpes zoster increases, because the
immunity against VZV can be attenuated at those ages.
The VZV type J-derived vaccine strain (Oka) has been used
worldwide and it immunizes against all genotypes of VZV, sug-
gesting that anti-VZV antibodies can cross-react among different
genotypes. However, even though individuals have already been
immunized with some VZV genotypes, they may retain the sus-
ceptibility to the infections of VZV even at lower levels than before
the immunization, especially to the other genotypes of VZV.
Because VZV type E has never been identified, meaning VZV
type E is extremely rare, if existent, in Japan (Table 1), it is highly
possible that the primary and secondary VZV infection in our
case was caused by VZV with distinct genotypes, namely the
primary infection was caused by VZV type J and the secondary
infection by VZV type E. We should note that the genotypic
prevalence of VZV may be different among primary chickenpox
patients in children, or between urban and provincial areas. Fur-
ther study is necessary to clarify these points.
In summary, this is the first case report identifying VZV type E
in Japan. In the USA where multiple genotypes of VZV are dis-
tributed, secondary infection is known to increase. Because for-
eign nationals living in Japan who carry VZV genotypes other
than type J are increasing, the infection of such VZV genotypes
may increase in Japan. In accordance with that, secondary
infection of VZV may also increase in Japan in the near future.
ACKNOWLEDGMENT: We thank H. Doi for her technical
assistance.
CONFLICT OF INTEREST: None declared.
4 © 2019 Japanese Dermatological Association
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