F. Drago, MD and A. Rebora, MD
Department of Endocrinological and Medical Sciences, Section of Dermatology, University of Genoa, Genoa, Italy
Pityriasis rosea is a common skin disorder in children and young adults. It is a self-limiting disease with symptoms that are typically mild and tolerable. Consequently, the best treatment remains the one followed so far by generations of dermatologists: reassuring the patient and letting the condition go away on its own. However, there are times when treatment is recommended. In this paper, we review the available treatments for this skin disease.
erythroderma; pityriasis rosea; pruritus
Discussing the treatment of pityriasis rosea (PR) with patients can be a frustrating experience. As a self-limiting disease, the best treatment regime is to reassure the patient and let the condition resolve on its own. In our experience, pruritus, when it occurs, is always mild and tolerable. Those complaining of severe pruritus have usually been “treated” either within their family, by a pharmacist, or by an inexperienced physician. For such cases, and for those who have received corticosteroids,1 the eruption may tend to turn into erythroderma.
A recent Cochrane collaboration paper reviewed the literature on the different types of treatment used.2 There is inadequate evidence for the efficacy of all topical medications (i.e., emollients, antihistamines, and corticosteroids). Other agents that have not been found to be significantly active include sunlight, artificial UV therapy, systemic antihistamines and corticosteroids, antiviral agents, and intravenous glycyrrhizin. There is some evidence that oral erythromycin may shorten the course of the rash and alleviate pruritus, and a recent publication reported a 73% cure rate, although 12% of the patients experienced gastrointestinal disturbances.3 In this paper we will discuss new and existing evidence that maintain some significance today.
The erythromycin issue has been raised very recently. In a placebo-controlled study of 184 patients who were comparable in sex, age, and mean duration of disease at the time they attended the clinic, adult patients were treated with 200mg of erythromycin 4 times daily and children were given 20-40mg/kg daily in 4 divided doses. Controls were given a placebo (an emollient cream) that was not identical in appearance. Subjects were seen for follow-up visits at weeks 2, 4, 6, and 8 following the start of treatment. No significant difference between the 2 treatment groups were found at weeks 4, 6, and 8.3
In a double-blind, placebo-controlled clinical study, 90 patients, who were comparable with regard to age at presentation, sex, and average duration of disease at the time of reporting to the clinic, were alternatively treated for 14 days with erythromycin in divided doses or assigned to the placebo group. All patients were followed for 6 weeks. Complete response was observed in 33 patients (73.33%) in the treatment group and none in the placebo group.4 However, it should be noted that of the studies mentioned in the Cochrane collaboration paper above,2 this study was excluded because of the lack of randomization.
Clarithromycin was studied in 52 patients presenting with a PR rash of 7 days duration or less. Patients were started on oral clarithromycin 250mg twice daily for 2 weeks. In 50 patients, the lesions regressed by the end of week 1, mostly cleared by the end of week 2, and completely disappeared by the end of week 4. In 2 patients, the condition resolved after 6 weeks.5
Azithromycin was studied in 49 children in order to explore its fewer adverse effects and greater biological half-life, while still having a spectrum of antimicrobial activity. Its activity is very similar to erythromycin. Patients were randomly assigned to azithromycin (12mg/kg/day, up to a maximum of 500mg/day) for 5 days or to a similar-appearing placebo. Rates of cure and partial resolution were similar in the azithromycin and placebo groups.6
Beta-guanine analogues, e.g., 9-(2-hydroxyethoxymethyl) guanine or acyclovir, have low activity on human
herpesvirus-6 (HHV-6) and -7 (HHV-7). The in vitro median effective concentration (EC50) values of acyclovir are approximately 6-8mg/mL for HHV-6A, 16-24mg/mL for HHV-6B, and 121-128mg/mL for HHV-7. In addition, the sensitivity of HHV-7 is different from HHV-6.7 Nonetheless, considering the association of PR with HHV-6 and -7,8 acyclovir 400mg every 4 hours for 5 days has been tried in a single patient with almost total resolution of PR and non-recurrence of the rash in 6 days.9 However, this patient had a persistent form of PR, and lesions had been exacerbated by repeated UVB exposures over 1 week. In 2006, we studied the effect of acyclovir in 87 consecutive patients who were treated for 1 week with either oral acyclovir (800mg 5 times daily) or placebo. In all patients, the time of lesion clearing and the number of new lesions appearing during treatment were recorded. On the 14th day of treatment, 79% of treated
patients fully regressed compared with 4% of patients in the placebo group. The lesions cleared in 18.5 days for treated patients and in 37.9 days for the placebo group.
Clearance was achieved in 17.2 days in patients treated in the first week from onset and in 19.7 days in the patients treated later. On the 7th day, there were significantly fewer new lesions in patients treated in the first week than in those treated later. The trial, however, was neither randomized nor double-blinded. Objectivity was nonetheless achieved by counting the lesions. It is likely that the efficacy of acyclovir is high when the virus is in replication, i.e., in the first week from onset. Unfortunately, dermatologists very rarely see patients just after the onset of the disease, as the patients usually seek the specialist’s advice only after trying familiar remedies.10 However, 1 case has been published reporting the occurrence of PR during acyclovir treatment.11
After its introduction in 1974,12 phototherapy has not acquired many supporters for treating PR. Recently, however, interest has again been raised. In a bilateral comparison study that was also excluded from the Cochrane collaboration paper because it was not randomized, Leenutaphong et al.13 treated 17 patients 5 times/week with unilateral UVB phototherapy. One joule of UVA was used as a “placebo” on the untreated side. After 10 daily erythemogenic exposures of UVB, the severity decrease was greater on the affected side than on the placebo side in 15 of 17 patients. The overall reduction of the severity score was significantly different after the third treatment. However, during the follow-up period, the 2 sides were indistinguishable with regard to severity score and pruritus. The duration of disease was not related to the success of UVB phototherapy. In another study excluded by the Cochrane collaboration paper, Valkova et al. studied 101 patients of various ages and phototypes in whom PR had lasted between 7 and 25 days. The irradiation sessions were held in a conventional UV cabin (Waldmann 7001 K). One group was treated with an initial 80% minimal erythema dose that was progressively increased according to the degree of the preceding erythema. The right half of the body was irradiated with UVB, and UVA (1 J/cm2) was given as a placebo to the left half of the body. A second group was given UVB irradiation on the whole body with an initial dose determined by the patient’s phototype. The procedures were held 4 times weekly. UVA irradiation had no effect on the course of the disease, but total clearing of the rash was observed after UVB phototherapy. Irritation of the rash was observed in 7% of cases. Interestingly, the duration of the disease and the duration of UVB therapy were related. The number of procedures necessary for total recovery can be calculated according to the following equation: Number of procedures = 4.34 + [0.05 × duration of the disease (in days)].14
There are peculiar conditions, however, in which a systemic treatment could be initiated. In children, pruritus may be common and intense, necessitating treatment, e.g., in a recent survey in Burkina-Faso, only 55.5% of school children were left untreated.15 In suberythrodermic forms, oral methylprednisolone (16mg/day) can be safely prescribed. During pregnancy, especially for widespread forms, in the absence of an antiviral drug effective on HHV-6/-7, high doses of acyclovir may prevent miscarriage or premature births.16 In pregnancy, acyclovir efficacy and safety needs to be confirmed.
Only rarely does PR need to be treated. Often, topical remedies induce pruritus. Systemic treatment with oral methylprednisolone can be advocated when pruritus is difficult to manage, lesions are widespread, and erythroderma may supervene. Even in such cases caution is needed, however, for the possible exacerbation of PR lesions.
- Leonforte IF. Pityriasis rosea: exacerbation with corticosteroid treatment. Dermatologica 163(6):480-1 (1981).
- Chuh AA, Dofitas BL, Comisel GG, et al. Interventions for pityriasis rosea. Cochrane Database Syst Rev 2:CD005068 (2007).
- Rasi A, Tajziehchi L, Savabi-Nasab S. Oral erythromycin is ineffective in the treatment of pityriasis rosea. J Drugs Dermatol 7(1):35-8 (2008 Jan).
- Sharma PK, Yadav TP, Gautam RK, et al. Erythromycin in pityriasis rosea: a double-blind, placebo-controlled clinical trial. J Am Acad Dermatol 42(2 Pt 1):241-4 (2000 Feb).
- Bukhari IA. Oral erythromycin is ineffective in the treatment of pityriasis rosea. J Drugs Dermatol 7(7):625 (2008 Jul).
- Amer A, Fischer H. Azithromycin does not cure pityriasis rosea. Pediatrics 117(5):1702-5 (2006 May).
- Yoshida M, Yamada M, Tsukazaki T, et al. Comparison of antiviral compounds against human herpesvirus 6 and 7. Antiviral Res 40(1-2): 73–84 (1998 Dec).
- Broccolo F, Drago F, Careddu AM, et al. Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7. J Invest Dermatol 124(6):1234-40 (2005 Jun).
- Castanedo-Cazares JP, Lepe V, Moncada B. Antivirals for pityriasis rosea. Photodermatol Photoimmunol Photomed 20(2):110 (2004 Apr).
- Drago F, Vecchio F, Rebora A. Use of high-dose acyclovir in pityriasis rosea. J Am Acad Dermatol 54(1):82-5 (2006 Jan).
- Laxman M. Pityriasis rosea occurring during acyclovir therapy. Indian J Dermatol Venereol Leprol 73(3):200-1 (2007 May-Jun).
- Merchant M, Hammond R. Controlled study of ultraviolet light for pityriasis rosea. Cutis 14:548–9 (1974).
- Leenutaphong V, Jiamton S. UVB phototherapy for pityriasis rosea: a bilateral comparison study. J Am Acad Dermatol 33(6):996–9 (1995 Dec).
- Valkova S, Trashlieva M, Christova P. UVB phototherapy for pityriasis rosea. J Eur Acad Dermatol Venereol 18(1):111-2 (2004 Jan).
- Traore A, Korsaga-Some N, Niamba P, et al. [Pityriasis rosea in secondary schools in Ouagadougou, Burkina Faso] Ann Dermatol Venereol 128(5):605-9 (2001 May).
- Drago F, Broccolo F, Zaccaria E, et al. Pregnancy outcome in patients with pityriasis rosea. J Am Acad Dermatol 58(5 Suppl 1):S78-83 (2008 May).