DOI: 10.1111/j.1468-3083.2010.03676.

x JEADV

ORIGINAL ARTICLE

Low dose of acyclovir may be an effective treatment

against pityriasis rosea: a random investigator-blind
clinical trial on 64 patients
S Rassai, A Feily,* N Sina, SA Abtahian
Dermatology Department, Jondishapur University of Medical sciences, Ahvaz, Iran
*Correspondence: A Feily. E-mail: dr.feily@yahoo.com

Abstract
Background Pityriasis rosea (PR) is a papulosquamous disease with an unknown aetiology, but recently the role of
two herpes viruses human herpes virus 6 and human herpes virus 7 was defined as being the aetiology of PR.
Objective The aim of this study was to compare a low dose (400 mg five times a day for a week) anti-viral agent,
acyclovir, with follow-up protocol for the treatment of PR.
Methods A randomized, investigator-blind, prospective, 4-week study was designed. Sixty-four patients with PR
presenting at the outpatient clinic were randomly allocated to acyclovir (400 mg five times a day for 1 week) or
follow-up group. Fifty-four of them completed the period of study and their clinical responses such as improvement
rate of erythema, and scaling and occurrence of complications were evaluated by two dermatologists using weekly
photographic records.
Results Statistically, acyclovir was more effective than follow-up in reducing erythema at the end of the first,
second, third and fourth week of treatment. Although the decrease in scaling was higher in the acyclovir group at
the end of the first, second and third week of treatment, there was no statistical significance between two groups at
the end of fourth week of treatment in the both groups.
Conclusions According to our study, acyclovir may be more effective than follow-up in reducing erythema and
shortening of duration of PR even in lower doses than was applied in previous studies. So given the safety of
acyclovir, we suggest to our colleagues to consider this treatment when facing a patient suffering from this
conundrum, at least in extensive or having pruritus ones.
Received: 25 November 2009; Accepted: 25 February 2010

Keywords
acyclovir, duration, erythema, pityriasis rosea, scaling

Conflict of interest
None declared.

Introduction Materials and methods

Pityriasis rosea (PR) is a common self-limited inflammatory skin dis-
ease.1 It has been shown that PR may be associated with the reactiva-
tion of human herpes virus 7 (HHV-7) and sometimes human
herpes virus 6 (HHV-6).1–5 Although many patients need no treat-
ment except education about the disease course and reassurance,
some patients need treatment because of their extensive lesions or
having pruritus.6 Recently, Drago et al. demonstrated that high-dose
acyclovir (800 mg five times daily for 1 week) may be effective in the
treatment of PR and reduces the time of lesion clearing.6 Impor-
tantly, this trial was neither randomized nor blind, and so our pur-
pose was to compare the efficacy of low dose acyclovir (400 mg five
times daily for 1 week) (2 g ⁄ day) with follow-up for the treatment
of PR in a randomized investigator-blind protocol.
The study was conducted at the outpatient clinic of Dermatology,
Department of Jondishapur University of medical sciences, Ahvaz,
Iran between October 2006 and February 2007. The eligible
patients had to meet the following criteria: (i) clinical diagnosis of
PR; (ii) ages between 12 and 60 years; (iii) <1 month from the
onset of PR; and (iv) no systemic or topical treatment for the
existing or any other condition.
Exclusion criteria included: (i) pregnant and breast feeding
women; (ii) a known hypersensitivity to acyclovir; and (iii) any
serious systemic diseases.
The study was approved by ethics Committee of Faculty of
Medicine before the trial started, and all patients gave written
informed consent.

ª 2010 The Authors

JEADV 2011, 25, 24–26 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
Pityriasis rosea and acyclovir
Study design
The study employed a randomized, comparative, investigator-
blind design. Randomization was performed by using a simple
random table, and the patients were randomly allocated to one
of the two arms of the study: study group [acyclovir 400 mg
five times a day (2 g ⁄ day) for 1 week] or control group (follow-
up). The used medications were not revealed to their physicians.
The patients instructed to eat the medication five times a day
for 1 week and were prohibited to use any other drug during
the study. Each patient was examined at the beginning of treat-
ment and weekly for 1 month. All lesions were photographed
using a canon digital camera (S21S) with 5 mega pixel resolu-
tion every week, and any change in scaling and erythema was
recorded.
Statistical analysis
The sample size was calculated after checking relevant, related
published articles.6 The number of cutaneous lesions and reduc-
tion in erythema and scaling in acyclovir group was compared
with those of the follow-up group. The test between groups was
carried out using the t-test. A P-value of <0.05 was required for a
result to be considered statistically significant.
Results
After 4-week course of treatment, 54 out of 64 patients who
referred to our clinic completed the study. The patients’ mean age
was 27.12 years (range 10–60 years), and the mean duration of the
disease before treatment was 18.25 days. At the beginning of the
study, treatment groups were not significantly different with
respect to age, number of lesions and male–female ratio. Twenty-
eight patients in the acyclovir group and 26 patients in follow-up
group were evaluated for efficacy.
All patients showed herald patch, most on the abdomen (37%)
and least on the chest and arms (14.8%), respectively (Table 2).
Thirty-six patients (66.7% of all) reported a history of common
cold during the month before PR. The results of the physical
examination and a comparison between photos taken of patients
were as follows:
At the end of the first week, thirteen patients in acyclovir group
(46.4%) and four patients in follow-up group (15.4%) showed
reduction in erythema (P = 0.014). Eighteen patients in acyclovir
group (64.3%) and seven patients in follow-up group (26.9%)
showed reduction in scaling (P = 0.006) (Tables 1 and 2).
Twenty-two patients in acyclovir group (78.5%) and seven
patients in follow-up group (27%) showed erythema reduction by
Table 1 Percentage of patients who showed erythema reduc-
tion in lesions
Studied group 1st week 2nd week 3rd week 4th week
Acyclovir group 46.4 78.5 92.8 92.8
Follow-up group 15.4 27 34.5 61.5
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Table 2 Percentage of patients who showed scaling reduction
in lesions
Studied group 1st week 2nd week 3rd week 4th week
Acyclovir group 64.3 100 100 100
Follow-up group 26.9 65.4 92.3 80.1
the week two (P = 0.000). All 28 patients in acyclovir group
(100%) and 17 patients in follow-up group (65.4%) showed scal-
ing reduction in this week (P = 0.001) (Tables 1 and 2).
At the end of the third week, in acyclovir group, 26 patients
(92.8%) showed erythema reduction and 28 patients (100%)
showed scaling reduction, but in the follow-up group, these figures
were nine (24.5%) (P = 0.000) and 21 (80.1%) (P = 0.015),
respectively (Tables 1 and 2).
At the end of the fourth week, in acyclovir group, 26 patients
(92.8%) and in follow-up group 16 patients (61.5%) showed ery-
thema reduction (P = 0.006). All patients in acyclovir group
(100%) and 24 patients in follow-up group (92.3%) experienced
reduction in scaling by week 4 (P = 0.135) (Tables 1 and 2). There
was no side-effect in both groups during the trial.
Acyclovir was significantly superior to follow-up with respect to
the erythema after 4 weeks treatment. With respect to scaling,
although there was no significant difference between two groups
by week 4 but in the first 3 weeks of treatment significantly,
acyclovir was superior to follow-up in reduction in scaling.
Discussion
Recent studies have showed a probable aetiological role for HHV-
6 and HHV-7 or both in PR.4–7 The detection of HHV-7 and
HHV-6 DNA or both in peripheral mononuclear cells, tissues and
in cell-free plasma of PR patients corresponding to active viral
replication supports a causal relationship.8
So it is possible that an effective treatment against these viruses
may help in reduction of severity of this disease.6
Acyclovir in high doses is effective against HHV-6 and HHV-7
in vitro. This drug has much less side-effects than other effective
anti-viral drugs such as gancyclovir, foscarnet and pencyclovir.9,10
Drago et al. conducted a similar study on 87 patients with PR
to consecutively received acyclovir or follow-up. Acyclovir was
given 800 mg five times daily for a week. After 14 days of treat-
ment, 79% of the treated patients fully regressed compared with
4% of the follow-up group. Clearance was achieved in 17.2 days
in patients treated in first week from onset and in 19.7 days in
the patients treated later.6 Notably, this trial was neither ran-
domized nor blind, but in this study we randomized 64 patients
with PR to receive either lower dose acyclovir (400 mg five
times daily for 1 week) (2 g ⁄ day) or no treatment, because this
lower dose has less side-effects and expense. Additionally, acyclo-
vir 800 mg five times a day is standard treatment for varicella-
zoster,11 but recommended dosage of acyclovir for treatment of
herpes viruses such as HSV infection is less than varicella-zoster
virus.12
ª 2010 The Authors
26
In our study, patients were observed for changes in scaling and
erythema of their lesions. At the end of the second week in acyclo-
vir group, 78.5% of the patients showed erythema reduction and
100% of them experienced scaling reduction, whereas in the
follow-up group, at the end of second week, these figures were
34.5% and 80.1%, respectively. Acyclovir was significantly superior
to follow-up in scaling and erythema reduction by week two.
Our results showed that acyclovir was significantly superior to
follow-up with respect to the erythema after 4 weeks treatment
(P = 0.006) interestingly with respect to scaling although there
was no significant difference between two groups by week four
(P = 0.135) but in the first 3 weeks of treatment significantly
acyclovir was superior to follow-up in reduction in scaling
(P = 0.015).
The advice of acyclovir as a treatment for PR for the first time
was described by Drago et al.6 The randomized investigator-
blinded trail with lower dosage of acyclovir carried out in this
study, even though not exactly in line with the previous study by
Drago6, confirms the results of the latter study. Thus our trial for
the second time demonstrated the favorable clinical response of
patients with PR to acyclovir.
In conclusion, we think that acyclovir can be regarded as a new
therapeutic option in the treatment of PR even in lower doses than
was applied in the previous study. So given the safety and effectiv-
ity of acyclovir, we suggest to our colleagues to consider this treat-
ment when facing a patient suffering from this conundrum, at
least in extensive lesions or having pruritus cases.
JEADV 2011, 25, 24–26 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology
Rassai et al.
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ª 2010 The Authors