Journal of the Egyptian

Dermatologic Society:

Women's

Accepted June 15, 2009

Abstract

January 2011 - Volume 8 - Issue 1 - p 21

24

Evaluation of pityriasis rosea associated

with human herpesviruses 6 and 7

Background: Pityriasis rosea (PR) is

suspected to have an infectious etiology,
either viral or bacterial. Although the exact
etiology of PR is yet to be identified,
speculations exist that the disease is viral in
origin, which could be certain strains of the
human herpes virus (HHV).

Mohammed, Yasser F.a; Balaha, Aadel A.b;

Rashed, Mohammedb

Objective: To evaluate HHV-6 and HHV-7

as etiological factors for PR.

doi:
10.1097/01.EWX.0000392820.13832.b7
Original Articles

Article Outline
Author Information

aDepartment of Dermatology, Venereology

and Andrology

bDepartment of Clinical Pathology, Faculty

of Medicine, Al-Azhar University, Cairo,
Egypt

Correspondence to Yasser F. Mohammed,

MD, Department of Dermatology &
Venereology, Al-Azhar University, Cairo,
Egypt Tel: +2 010 4547144; fax: +2 022
5104146; e-mail: yaserclinic@yahoo.com

Received March 2, 2009

Patients and Methods: Plasma samples from

24 patients with PR and from an equal, agematched and sex-matched healthy control
group were tested for the presence of HHV-6
and HHV-7-specific DNA sequences in
plasma and peripheral blood mononuclear
cells (PBMCs) using nested PCR.

Results: HHV-6 and HHV-7 DNA were

detected in both plasma (33 and 54%,
respectively) and PBMCs (50 and 75%,
respectively) of patients with PR more than
in controls (0% for both in plasma and 16.66
and 33%, respectively, in PBMCs) with
more statistical significance for HHV-7.

Conclusion: This study provides further

evidence for HHV-6 and HHV-7 as
etiological factors in pityriasis rosea, and

detecting HHV-7 DNA in biopsy specimens

from skin lesions is recommended.
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Introduction

Pityriasis rosea (PR) is an ancestral illness,

described for the first time by GIBERT in
1860 [1]. It is a common, acute,
inflammatory, self limited papulosquamous
skin disorder that usually lasts for 48
weeks. It is suspected to have an infectious
etiology [2,3], either viral [4,5] or bacterial
[6]. Although its cause is uncertain and the
exact etiology of PR is yet to be identified,
speculations exist that the disease is viral in
origin, however recent evidence is still
inconclusive [6]. PR typically presents with
a large herald patch followed by truncal
crops of ovoid lesions [7]. Clinical
presentation,
immunologic,
light
microscopic, and electron microscopic
studies suggest a viral etiology for PR [8,9].
Several clinical features have suggested a
viral cause, including occasional association
of prodromal symptoms, clustering in
families or communities and an increased
incidence in patients with decreased
immunity such as in pregnant or bonemarrow transplantation patients [10].
Moreover, a viral etiology has been
suggested for PR on the basis of
immunological and histological data. The
superficial dermis contains aggregates of
CD4+ helper T cells in perivascular
locations and increased numbers of
Langerhans cells. It has been postulated that
immunoglobulin
M
antibodies
to
keratinocytes cause the secondary form of

the eruption [11]. The viral origin could be

certain strains of the human herpes virus
[HHV (HHV-6 or HHV-7)] [2]. An
association between HHV-7 and PR was
initially reported in 1997 [11] but remains
controversial [12]. It has been reported that
HHV-7 was present in cell-free plasma,
peripheral
blood
mononuclear
cells
(PBMCs), and lesional skin from all 12
patients with PR examined [9]. Virions with
electron microscopic features of HHVs were
detected in the supernatant of co-cultured
mononuclear cells from patients with acute
PR [13]. Owing to their morphology and to
PCR studies, the study ascribed them to
HHV-7. However, six studies using PCR and
immunohistochemical analyses of tissue
samples to detect HHV-7 DNA sequences
and antigens have provided inconclusive
evidence of a causal relationship between
HHV-7 and PR [11]. Although the role of
HHV-7 in PR has been implicated, its
primary or recurrent infection is still in
question [14]. HHV-6 and HHV-7 belong to
the genus Roseolavirus within the subfamily
Betaherpesvirinae. These ubiquitous viruses
may cause primary or chronic persistent
infection or remain in a state of latency for
many years, until a decrease in the
immunologic state of the host leads to
reactivation of infection. Several diseases
have been linked with HHV-6 and HHV-7.
In the dermatological arena, a definite
association has been proven only for HHV-6
and exanthema subitum (roseola infantum),
whereas the role of HHV-7 in the
pathogenesis of PR remains a matter of
debate [15,16].

Therefore, the aim of this study was to

evaluate HHV-6 and HHV-7 as etiological
factors for PR.
Back to Top | Article Outline
Patients and methods

Plasma samples from 24 patients with PR

attending the outpatient clinics for
dermatology at Al-Azhar university
hospitals (EL-Hussein and Bab-Elshaaria)
and an equal, age-matched and sex-matched
healthy control group were tested from
20072008. Complete history taking and
clinical examination were carried out for all
participants. We investigated the presence of
HHV-6-specific and HHV-7-specific DNA
sequences in plasma and PBMCs using
nested PCR. Plasma samples were
suspended in K-buffer and DNA was
extracted with phenol and chloroform.
PBMC were isolated from blood by density
gradient centrifugation over Ficoll-Paque
(Amersham/Pharmacia
Biotech,
Baie
D'Urf, Quebec, Canada) according to the
manufacturer's instructions. We used
specific primers (OPERON technologies
Inc., Germany), fHV-7S/HV-8A external
sences, and HV-10S/HV11A internal sences
for HHV-6 and HHV-7 DNA sequences to
amplify a 264-bp HHV-7 DNA that was
located between basepairs 83998 and 84261
of the published sequences. Nested PCR was
carried out according to Jackson et al. [17].
Products were analyzed by electrophoresis
on 2% agarose gel.
Back to Top | Article Outline
Statistical analysis

All statistical analyses were conducted using

SPSS statistical software, version 12 (Cherry
Hill, New Jersey, USA). The 2 test was
conducted to analyze the relations between
variables. Statistical significance was
assumed if P value was less than or equal to
0.05.
Back to Top | Article Outline
Results

The age of patients with PR ranged from 6

to 62 years and from 5 to 57 years for
controls. The mean age was 29.8611.77
years for patients with PR and 25.3311.69
years for controls. The mean duration of the
disease was 16.2815.74 days. The mean
duration of the disease was calculated as
11.679.85 days for patients with positive
HHV-7 and 18.1317.05 days for the
patients with negative HHV-7, and there was
no statistically significant difference in
either of the groups. In addition, the mean
duration of the disease was calculated as
10.768.69 days for patients with positive
HHV-6 and 16.1115.22 days for patients
with negative HHV-6, and again there was
no statistically significant difference in
either of the groups. HHV-6 and HHV-7
DNA were detected in 33% and in 54% of
PR plasma, respectively, but not in controls;
statistical significance was more for HHV-7
(P value was <0.05 and <0.01, respectively)
(Table 1 and Fig. 1). HHV-6 and HHV-7
DNA levels in PBMCs were higher in
patients with PR than in controls (50 and
75% for patients versus 16.66 and 33% in

controls, respectively, and P value again was

more statistically significant for HHV-7,
being <0.05 and <0.01, respectively) (Table
2 and Fig. 2).

Table 1

pathogenetic association of HHV-7 with this

exanthematic skin disease. Nevertheless, the
role of HHV-7 in various skin diseases and
the clinical manifestations of reactivation of
HHV-7 infection still have to be defined
[19]. For all this dilemma, we proceeded in
this study.

Image Tools
Table 2
Image Tools
Figure 1
Image Tools

This study used nested PCR to investigate

the presence of HHV-6 and HHV-7 DNA in
patients with PR. It enhances the sensitivity
and specificity of PCR amplification. Nested
PCR is 1000 times more sensitive than 50
cycles of standard PCR. It also avoids falsepositive signals as a result of jumping PCR
[17].

Figure 2
Image Tools
Back to Top | Article Outline
Discussion

Pityriasis rosea is a common, acute,

inflammatory papulosquamous skin disease
with unknown etiology. Clinical and
experimental findings indicate an infectious
etiology of PR. Various infectious agents
including viruses have been proposed as
causative agents and their presence in PR
samples has been extensively investigated.
None of the known viruses could, so far, be
conclusively associated with PR [3]. The
possible relationship of HHV 7 with PR has
been extensively studied [18]. Contradictory
findings have been reported by various
investigators [3]. Kempf [19] mentioned that
there is not enough evidence for a

In this study, HHV-6 and HHV-7 DNA

showed statistically significant increase in
both PR plasma and PBMCs of patients than
in those of controls with more statistical
significance for HHV-7. This is in
agreement with the results obtained by
Watanabe et al. [4]. Poljacki et al. [20]
concluded that the presence of DNA
sequences of HHV-7 in mononuclear cells of
peripheral blood, skin, and plasma of
patients with PR points to possible
connection between this illness and HHV-7
infection. Unlike the results of this study,
Kosuge et al. [2] found no difference in the
prevalence of HHV-6 or HHV-7 in PBMCs
between patients with PR and controls. In
addition, Karabulut et al. [8] did not find a
statistically significant difference for the
presence of HHV-7 DNA sequence between
patients with PR and controls and concluded
that their results failed to support a possible

role for HHV-7 in the pathogenesis of PR.

Kempf et al. [21] concluded that the low
detection rate of HHV-7 DNA sequences
and antigens argues strongly against a
causative role for HHV-7 in the
pathogenesis of PR. It was found that HHV6 is present in a high proportion of the
healthy population [22] and that almost all
adults are infected with HHV-7 in early
childhood [23]. It was proposed that PR is a
clinical presentation of HHV-7 reactivation
[9] and HHV-7 infection itself may
reactivate HHV-6 [24].

Conclusion

This study provides further evidence of the

etiology of HHV-6 and HHV-7 for some
patients with PR, with a more stronger
association between HHV-7 infection and
PR. Detecting HHV-7 DNA in biopsy
specimens
from
skin
lesions
is
recommended.

There is no conflict of interest.

Back to Top | Article Outline

Kosuge et al. [2] tried to resolve the great

controversy in the aforementioned relation
between HHV-6 and HHV-7 and PR and
concluded that HHV-7 and HHV-6 may play
a part in some patients with PR, but that
other causative agents may exist and that
further analyses are needed to determine the
causative agents of PR. An impressive
conclusion by Drago et al. [14] was that
HHV-7 does not infect epidermal cells, but
can be detected in the infiltrating
lymphocytes of skin eruptions, in which it
induces an altered mediator production that
might be responsible for the general and
local symptoms.

Finally, a therapeutic response supporting

the role of HHV-6 and HHV-7 in PR was
noticed. Drago et al. [7] observed
surprisingly strong clinical effects, that is,
speed resolution and shorten the course of
PR [7].
Back to Top | Article Outline

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Keywords:

herpes virus 6; herpes virus 7; nested

polymerase chain reaction; pityriasis rosea

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2011 Egyptian Women's Dermatologic
Society