DOI: 10.1111/j.1468-3083.2010.03676.

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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 dened as being the aetiology of PR. Objective The aim of this study was to compare a low dose (400 mg ve 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 ve 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 rst, second, third and fourth week of treatment. Although the decrease in scaling was higher in the acyclovir group at the end of the rst, second and third week of treatment, there was no statistical signicance 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

Conict of interest
None declared.

Introduction
Pityriasis rosea (PR) is a common self-limited inammatory skin disease.1 It has been shown that PR may be associated with the reactivation of human herpes virus 7 (HHV-7) and sometimes human herpes virus 6 (HHV-6).15 Although many patients need no treatment 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 ve times daily for 1 week) may be effective in the treatment of PR and reduces the time of lesion clearing.6 Importantly, this trial was neither randomized nor blind, and so our purpose was to compare the efcacy of low dose acyclovir (400 mg ve times daily for 1 week) (2 g day) with follow-up for the treatment of PR in a randomized investigator-blind protocol.

Materials and methods

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.

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Study design

The study employed a randomized, comparative, investigatorblind 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 ve times a day (2 g day) for 1 week] or control group (followup). The used medications were not revealed to their physicians. The patients instructed to eat the medication ve 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 treatment and weekly for 1 month. All lesions were photographed using a canon digital camera (S21S) with 5 mega pixel resolution every week, and any change in scaling and erythema was recorded.
Statistical analysis

Table 2 Percentage of patients who showed scaling reduction in lesions

Studied group Acyclovir group Follow-up group 1st week 64.3 26.9 2nd week 100 65.4 3rd week 100 92.3 4th week 100 80.1

The sample size was calculated after checking relevant, related published articles.6 The number of cutaneous lesions and reduction 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 signicant.

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 1060 years), and the mean duration of the disease before treatment was 18.25 days. At the beginning of the study, treatment groups were not signicantly different with respect to age, number of lesions and malefemale ratio. Twentyeight patients in the acyclovir group and 26 patients in follow-up group were evaluated for efcacy. 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 rst 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

the week two (P = 0.000). All 28 patients in acyclovir group (100%) and 17 patients in follow-up group (65.4%) showed scaling 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 gures 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 erythema 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 signicantly superior to follow-up with respect to the erythema after 4 weeks treatment. With respect to scaling, although there was no signicant difference between two groups by week 4 but in the rst 3 weeks of treatment signicantly, acyclovir was superior to follow-up in reduction in scaling.

Discussion
Recent studies have showed a probable aetiological role for HHV6 and HHV-7 or both in PR.47 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 ve times daily for a week. After 14 days of treatment, 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 rst week from onset and in 19.7 days in the patients treated later.6 Notably, this trial was neither randomized nor blind, but in this study we randomized 64 patients with PR to receive either lower dose acyclovir (400 mg ve times daily for 1 week) (2 g day) or no treatment, because this lower dose has less side-effects and expense. Additionally, acyclovir 800 mg ve times a day is standard treatment for varicellazoster,11 but recommended dosage of acyclovir for treatment of herpes viruses such as HSV infection is less than varicella-zoster virus.12

Table 1 Percentage of patients who showed erythema reduction in lesions

Studied group Acyclovir group Follow-up group 1st week 46.4 15.4 2nd week 78.5 27 3rd week 92.8 34.5 4th week 92.8 61.5

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Rassai et al.

In our study, patients were observed for changes in scaling and erythema of their lesions. At the end of the second week in acyclovir 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 gures were 34.5% and 80.1%, respectively. Acyclovir was signicantly superior to follow-up in scaling and erythema reduction by week two. Our results showed that acyclovir was signicantly 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 signicant difference between two groups by week four (P = 0.135) but in the rst 3 weeks of treatment signicantly acyclovir was superior to follow-up in reduction in scaling (P = 0.015). The advice of acyclovir as a treatment for PR for the rst time was described by Drago et al.6 The randomized investigatorblinded trail with lower dosage of acyclovir carried out in this study, even though not exactly in line with the previous study by Drago6, conrms 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 effectivity of acyclovir, we suggest to our colleagues to consider this treatment when facing a patient suffering from this conundrum, at least in extensive lesions or having pruritus cases.

References
1 Drago F, Ranieri E, Malaguti F, Losi E, Rebora A. Human herpes virus 7 and pityriasis rosea. Lancet 1997; 349: 13671368. 2 Watanabe T, Kawamura T, Jacob SE et al. Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6. J Invest Dermatol 2002; 119: 793797. 3 Broccolo F, Drago F, Careddu AM et al. Additional evidence that pityriasis rosea is associated with reactivation of HHV-6 and HHV-7. J Invest Dermatol 2005; 124: 12341240. 4 Drago F, Malaguti F, Ranieri E, Losi E, Rebora A. Human herpes viruslike particles in pityriasis rosea lesions: an electron microscopy study. J Cutan Pathol 2002; 29: 359361. 5 Kosuge H, Tanaka-Taya K, Miyoshi H et al. Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea. Br J Dermatol 2000; 143: 795798. 6 Drago F, Vecchio F, Rebora A. Use of high dose acyclovir in pityriasis rosea. J Am Acad Dermatol 2006; 54: 8285. 7 Drago F, Broccolo F, Rebora A. Pityriasis rosea: an update with a critical appraisal of its possible herpesviral etiology. J Am Acad Dermatol 2009; 61: 303318. 8 Drago F, Ranieri E, Malaguti F, Battifoglio ML, Losi E, Rebora A. Human herpesvirus 7 in patients with pityriasis rosea. Electron microscopy investigations and polymerase chain reaction in mononuclear cells, plasma and skin. Dermatology 1997; 195: 374378. 9 Burns WH, Sandford GR. Susceptibility of human herpesvirus-6 to antivirals in vitro. J Infect Dis 1990; 162: 634637. 10 Yoshida M, Yamada M, Tsukazaki T et al. Comparison of antiviral compounds against human herpesvirus 6 and 7. Antiviral Res 1998; 40: 7384. 11 Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A metaanalysis. Arch Intern Med 1997; 157: 909912. 12 de Ruiter A, Thin RN. Genital herpes. A guide to pharmacological therapy. Drugs 1994; 47: 297304.

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