Intervention Pityriasis Rosea

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Interventions for pityriasis rosea (Review)

Chuh AAT, Dofitas BL, Comisel G, Reveiz L, Sharma V, Garner SE, Chu FKM

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published inThe Cochrane Library2009, Issue 3

http://www.thecochranelibrary.com

Interventions for pityriasis rosea (Review)

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
http://www.thecochranelibrary.com/http://www.thecochranelibrary.com/


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T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

5OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

20DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Glycyrrhizin vs Procaine, Outcome 1 Good or excellent rash improvement as rated by a medical

practitioner (disappearance of symptoms and rash). . . . . . . . . . . . . . . . . . . . . . 21

Analysis 2.1. Comparison 2 Erythromycin vs Placebo, Outcome 1 Mean reduction in itch score. . . . . . . . 22Analysis 2.2. Comparison 2 Erythromycin vs Placebo, Outcome 2 Excellent rash improvement (cure) as rated by the

medical practitioner at 2 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Analysis 2.3. Comparison 2 Erythromycin vs Placebo, Outcome 3 Minor adverse events (gastrointestinal upset and

nausea). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Analysis 3.1. Comparison 3 Dexchlorpheniramine vs Betamethasone, Outcome 1 Number of participants with resolution

of itch, as reported by participant. . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Analysis 3.2. Comparison 3 Dexchlorpheniramine vs Betamethasone, Outcome 2 Number of participants with good or

excellent rash improvement as rated by a medical practitioner. . . . . . . . . . . . . . . . . . 24

Analysis 4.1. Comparison 4 Betamethasone vs Betamethasone + Dexchlorpheniramine, Outcome 1 Number of participants

with resolution of itch, as reported by participant. . . . . . . . . . . . . . . . . . . . . . 24

Analysis 4.2. Comparison 4 Betamethasone vs Betamethasone + Dexchlorpheniramine, Outcome 2 Number of participants

with good or excellent rash improvement as rated by a medical practitioner. . . . . . . . . . . . . 25

Analysis 5.1. Comparison 5 Dexchlorpheniramine vs Betamethasone + Dexchlorpheniramine, Outcome 1 Number ofparticipants with resolution of itch, as reported by participant. . . . . . . . . . . . . . . . . . 25

Analysis 5.2. Comparison 5 Dexchlorpheniramine vs Betamethasone + Dexchlorpheniramine, Outcome 2 Number of

participants with good or excellent rash improvement as rated by the medical practitioner. . . . . . . . 26

26ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

29APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

32WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

34INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iInterventions for pityriasis rosea (Review)



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[Intervention Review]

Interventions for pityriasis rosea

Antonio AT Chuh1

, Belen L Dofitas2

, Gabriela Comisel3

, Ludovic Reveiz4

, Vidya Sharma5

, Sarah E Garner6

, Fergus KM Chu7

1Department of Community and Family Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong. 2Section of

Dermatology, Department of Medicine, St Lukes Medical Center, Quezon City, Philippines. 3Famiy Medical Office, Romanian Family

Doctors Collegium, Craiova, Romania. 4 Research Institute, Sanitas Foundation, Bogot, Colombia. 5Department of Pediatrics, The

Childrens Mercy Hospital and Clinics, Kansas City, USA. 6Appraisals Team, National Institute for Clinical Excellence, London, UK.7Messrs. Gary Lau & Partners, Hong Kong, Hong Kong

Contact address: Antonio AT Chuh, Department of Community and Family Medicine, The Chinese University of Hong Kong, Shop

B5, Ning Yeung Terrace, 78 Bonham Road, Ground Floor, The Mid-Levels Hong Kong, Hong Kong. [email protected].

Editorial group:Cochrane Skin Group.

Publication status and date: Edited (no change to conclusions), published in Issue 3, 2009.

Review content assessed as up-to-date: 20 February 2007.

Citation: Chuh AAT, Dofitas BL, Comisel G, Reveiz L, Sharma V, Garner SE, Chu FKM. Interventions for pityriasis rosea.CochraneDatabase of Systematic Reviews2007, Issue 2. Art. No.: CD005068. DOI: 10.1002/14651858.CD005068.pub2.


A B S T R A C T

Background

Pityriasis rosea is a scaly rash that mainly affects young adults. It can be very itchy but most people recover within 2 to 12 weeks.

Objectives

To assess the effects of interventions for pityriasis rosea.

Search methods

We searched the Cochrane Skin Group Specialised Register (December 2004), the Cochrane Central Register of Controlled Clinical

Trials inThe Cochrane Library(Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1976 to January 2005), LILACS (1982to January 2005), BIOSIS Preview (1980 to June 2002), and ongoing trials databases. We scanned bibliographies of published studies,

abstracts from dermatology conference proceedings, corresponded with trialists and contacted the pharmaceutical industry.

Selection criteria

Randomised controlled trials evaluating interventions for pityriasis rosea.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. We contacted study authors to retrieve missing data.

Main results

Three trials involving 148 people were included. One poor quality trial (23 people), compared intravenous glycyrrhizin and intravenous

procaine. It found no significant difference between the two interventions for treating symptoms and rash.

One fair quality trial (85 people), compared the oral antihistamine dexchlorpheniramine (4 mg), the oral steroid betamethasone (500

mcg), and a combination of betamethasone (250 mcg) and dexchlorpheniramine (2 mg). It found no significant difference in itch

resolution at two weeks, as rated by the participants, between dexchlorpheniramine and betamethasone, and the combination of

1Interventions for pityriasis rosea (Review)

mailto:[email protected]:[email protected]


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pattern over the body and limbs. Pityriasis (meaning bran-like),

indicates that there are scales in the skin lesions (Percival 1932).

Rosea means rose-like and describes the typical colour of the rash

(Percival 1932), although the colour varies to a wide extent in

different races (Ahmed 1986).

A characteristic of PR is the apparently programmed course ofevents. Many peoplewill discoverone plaque, usually on thetrunk,

several days before the generalised eruption. This initial lesion is

known as the herald patch (Figure 1). However, the herald patch

may not be identifiable in many people and thus its absence does

not necessarily exclude a diagnosis of PR.

Figure 1. Classical pityriasis rosea. The largest lesion is the herald patch. The other lesions are the

secondary eruption. This person did not have any itch.

This figure was previously published by us in Journal of the European Academy of Dermatology and

Venereology (2003; 17: 101-3), and is reproduced here with the kind permission of Ms Zoe Ellams, Permissions

Co-ordinator, Blackwell Publishing.

The subsequent generalised eruption is known as the secondary

eruption. It usually occurs on the trunk and extends to the upper

arms and upper thighs. In some people, the forearms and legs can

be involved. Involvement of the face is rare but has been reported

(Klauder 1924;Vollum 1973). The palms of the hands and soles

of the feet are usually unaffected.

More plaques will keep on appearing in the first two to six weeks.




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All lesions will then disappear spontaneously without treatment.

The entire disease duration is usually between 2 and 12 weeks, but

may last for as long as 5 months ( Nelson 2000). After recovery,

some darkeningor lighteningof theaffectedskin(but notscarring)

might however remain for months (Truhan 1984).

The rash is not painful, but about 50% of people with PR willexperience itching of moderate to severe intensity (Bjornberg

1962) (Figure 2). Most people who have had an episode of PR

will not have another attack throughout their lifetime (Bjornberg

1962;Chuang 1982).

Figure 2. The urticarial variant of pityriasis rosea. The lesions were intensely itchy.

This figure was previously published by us in Journal of the European Academy of Dermatology and

Venereology (2005; 19: 120-6), and is reproduced here with the kind permission of Ms Zoe Ellams, Permissions

Co-ordinator, Blackwell Publishing.

Pityriasis rosea is a relatively common condition. We analysed data

from 9 studies (Vollum 1973;Jacyk 1980;de Souza 1984;Ahmed

1986; Olumide 1987; Cheong 1989; Harman 1998; Nanda 1999;

Tay 1999) and found that out of every 1000 people seen by der-

matologists, about 7 are diagnosed with PR. One study ( Chuang

1982) reported that for every 100,000 people in the community,

about 170 will have PR in any one year.

Most people with PR are between 10 and 35 years of age (Truhan

1984). Girls and women are more likely to have PR; the overall




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male to female ratio is about 1:1.4. The data on seasonal variation

in the occurrence of PR is conflicting. However, it is known that

cases of PR tend to occur in clusters (Messenger 1982; Chuh

2003a,Chuh 2005c).

TerminologyPR is also known by the following names: pityriasis rosea of Gib-

ert, pityriasis rosea of Vidal, pityriasis circinata et marginata, and

pityriasis maculata et circinata (Percival 1932).

Causes

The cause of PR is unknown. Three major facts suggest that PR is

caused by an infectious agent. The first is that the disease course,

as mentioned above, is programmed. This programmed course of

events is similar to the course of some viral rashes such as measles

or chicken pox. The second is that most people who have suffered

from the eruption will not have another attack throughout their

lifetime. This suggests that PR is caused by an infectious agent. Ifa person has had an attack, they will developimmunity against the

infectious agent, and therefore be free from further attacks. The

third fact is that some cases of PR tend to cluster, suggesting that

it is potentially infectious.

Researchers have searched for the infectious agent for generations

to no avail. Recently the focus has been on the roles of two viruses

- human herpesvirus 6 and human herpesvirus 7. Different in-

vestigators have however reported conflicting results. There are

positive reports (Drago 1997a; Drago 1997b; Watanabe 1999;

Watanabe 2002,Vag 2003;Vag 2004;Broccolo 2005) support-

ing the role of one or both of these viruses as well as many nega-

tive reports (Kempf 1999;Yasukawa 1999;Yoshida 1999;Kosuge

2000;Offidani 2000;Chuh 2001;Wong 2001;Karabulut 2002;Yildirim 2004). The role of these viruses in causing PR is con-

troversial at the present. PR has recently been reported not to be

associated with human herpesvirus 8 infection (Chuh 2006).

Some drugs produce a skin rash as a side-effect, which canresemble

pityriasis rosea. However, these rashes are different in nature from

PR (Chuh 2003b).

Impact

About 50% of all people with PR have itching of moderate to severe

intensity (Bjornberg 1962). The quality of life of people with PR

is significantly affected (Chuh 2003c;Chuh 2005a). Parents of

children with PR also have significant anxieties about the cause,

nature, and possible infectivity of the eruption (Chuh 2003c).

ManypeoplewithPR are likelyto consult a primary care physician,

but primary care physicians have been reported significantly to

under diagnose this disease (Pariser 1987). If people consult a

primary care physician and a precise diagnosis of PR is not given,

they can become anxious about the nature of the eruption and its

prognosis.

Description of the intervention

Currently both topical and systemic treatments are used to treat

pityriasis rosea. Topical treatments mainly comprise emollients

and topical corticosteroids. Systemic treatments include medica-

tionsfor symptomatic control such as oral antihistamines, sunlight

and artificial ultraviolet radiation (usually as narrow-band ultravi-olet-B), systemic corticosteroids, and oral antibiotics. The use of

antiviral agents, like acyclovir, has also been reported (Castanedo

2003).

Why it is important to do this review

The current use of some treatments for pityriasis rosea is based

on anecdotal experience only. Conflicting results have also been

reported for some treatments. For example, oral corticosteroids

have been reported to be of benefit to people with very extensive

PR (Tay 1999). On the other hand, there are reports of PR get-

ting worse when treated with systemic corticosteroids (Leonforte

1981).

The use of some treatments may also be related to inadequate

understanding of the present controversies about the cause of PR.

Forexample,the association of humanherpesvirus 7 infectionwith

PR is still controversial. Even if human herpesvirus 7 infection is

the true cause of pityriasis rosea, acyclovir would be a poor choice

for antiviral therapy since it has little to no action against human

herpesvirus 7 in laboratory conditions (Zhang 1999). Its action

depends on the enzyme thymidine kinase and human herpesvirus

7 does not possess the gene coding for this enzyme.

Pityriasis rosea is an essentially a self limiting disease and the rash

mostlydisappears at 2 to 12 weeks,with or without treatment. The

benefits associated with the use of any active intervention should

therefore outweigh any potential adverse effects. Adverse effects

may be short-term (such as stomach upsets caused by antibiotics)

or long-term (such as the risk of skin cancer caused by ultraviolet

radiation, or the effects of systemic corticosteroids on bones). The

use of antibiotics and antivirals may theoretically induce resistance

to bacteria and viruses, thus affecting not only the individual but

also the community as a whole.

Manyquestions areunanswered in the treatment of pityriasis rosea.

It is unknown whether many of the available treatments can mod-

ify the disease course, relieve the itch, or improve the quality of

life. A systematic review will help determine: the most effective

therapies; when and for whom they should be used; the duration

of treatment; possible risks and side effects; and the level of treat-ment acceptability. The review will also enable an assessment of

the level and quality of the evidence that is currently available,

and identify areas of uncertainty or gaps in knowledge that require

further research.

O B J E C T I V E S




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To assess the effects of interventions used in the management of

pityriasis rosea.

M E T H O D S

Criteria for considering studies for this review

Types of studies

All randomised controlled trials that evaluate the effectiveness of

interventions for pityriasis rosea.

Types of participants

Any individual who has been diagnosed with pityriasis rosea by a

medical practitioner.

Types of interventions

(1) Topical therapy

Emollients

Antihistamine creams or ointments

Corticosteroid creams or ointments

(2) Light therapy

Sunlight

Artificial ultraviolet light therapy

(3) Systemic therapy

Oral antihistamines

Oral corticosteroids

Oral antibiotics

Oral antiviral agents

The interventions can be either single therapy, or combination

therapy. The comparators can be no treatment, placebo, vehicle

only, another active compound, or placebo radiation treatment.

Types of outcome measures

Timing of outcome assessment

We chose 2 weeks as people without any active treatment usually

have spontaneous recovery in between 2 and 12 weeks. If there

is any improvement after two weeks with active treatment, it is

difficult to differentiate whether the improvement is due to spon-

taneous recovery from the disease or due to the treatment.

Primary outcomes

(i) The proportion of participants with good or excellent rash

improvement within two weeks, as rated by the participant.

(ii) The proportion of participants with resolution of itch within

two weeks, as rated by the participant.

(iii) Reduction in itch score within two weeks, as rated by theparticipant.

Reduction in itch score within two weeks, as rated by the partic-

ipant has been added to the primary outcome measures because

we decided that it is equally as important as the proportion of

participants with resolution of itch within two weeks, as rated by

the participant.

Secondary outcomes

(iv) The proportion of participants with good or excellent rash

improvementwithin two weeks,as ratedby a medical practitioner.

(v) Improvement in quality of life as rated by the participant by

the use of questionnaires or other methods.(vi) Serious adverse events, i.e. serious enough to require with-

drawal of the treatment.

(vii) Minor participant reported adverse eventsnot requiring with-

drawal of the treatment.

Search methods for identification of studies

Language

No language restrictions were imposed and translations were

sought where necessary.

Electronic searches

We searched the Cochrane Skin Group Specialised Register in

December 2004 using the following terms:

pityriasis and (rosea or Gibert or Vidal or circinata or marginata

or maculata)

We searched the Cochrane Central Register of Controlled Clinical

Trials (CENTRAL) from The Cochrane Library(Issue 4, 2004)using the search strategy inAppendix 1.

We searched MEDLINE (from 1966 to January week 2, 2005)

using the search strategy inAppendix 2.

We searched EMBASE (from 1976 to January week 2, 2005) using

the search strategy inAppendix 3.

We searched LILACS (from 1982 to January 2005) using the

search strategy inAppendix 4.

We searched BIOSIS Preview (from 1980 to January 2005), We

searched this using the search strategy inAppendix 5.

We searched the metaRegister of Controlled Trials, the UK NHS

Trusts Clinical Trials Register and Clinicaltrials.gov for ongoing




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trials on www.controlled-trials.com using the search strategy in

Appendix 6.

Searching other resources

References from published studies

We looked at the bibliographies of the included and excluded

studies and scanned for possible references to RCTs.

Unpublished literature

The pharmaceutical industry was contacted in an attempt to ob-

tain unpublished trial data. Electronic addresses of leading re-

searchers possibly involved in this field were searched for, in elec-

tronic databases, to obtain additional published and unpublished

trials. We wrote to those trial authors to try to locate trials. No

RCTs were obtained.

Conference proceedings

The abstracts from major dermatology conference proceedings

were scanned for further RCTs. The CAB Abstracts database was

searched using the following text words in Ovid:

Pityriasis rosea, Pityriasis vidal, Pityriasis circinata, Pityriasis and

marginata. There were no further attempts to locate abstracts.

Adverse effects

We searched PubMed for adverse effects using the strategy in

Appendix 7.The articles usually described reports of medications that can pro-

duce Pityriasis rosea like reactions and were not related with

medicament toxicity when treating PR.

Data collection and analysis

General

Where there was uncertainty, trial authors were contacted for clar-

ification. A consumer (FC) was involved throughout the review

process to ensure the readability of the final review.

Other aspects of quality

Themethods of diagnosiswere slightly differentfor thethree trials.

Although it was not explicitly stated in all three studies whether

the diagnoses of pityriasis rosea were made by dermatologists, all

three studies were conducted in dermatology departments. We

thus believe that all three studies incur a high degree of certainty

that the participants had PR. All three trials did not specifically

exclude drug-induced PR.

All three trials documented baseline assessment of the participants

for age, sex, and duration of pityriasis rosea. All three trials had

some documentation of the distribution and extent of eruption.

The trial byLazaro-Medina 1996 documented the presence or

absence of itch at baseline. The trial byVillaramadocumented theseverity of itch with a visual analogue scale. The trial byZhu 1992

did not document the presence or severity of itch at baseline.

The objectives and outcome measures were clearly defined for the

studies byLazaro-Medina 1996 and Villarama. In the study by

Zhu 1992, the disappearance of symptoms and rash were assessed

together. Symptoms were not specified as itch. The authors had

to assume that the symptoms were limited to itch only.

The drug doses and duration of treatment were clearly defined in

the studies byLazaro-Medina 1996andVillarama. In the study

byZhu 1992, the drug doses were clearly defined. How the dura-

tion of treatment was decided was unclear. All three trials did not

comprehensively document the use of previous medications afterthe appearance of rash, but before consultation.

Overall, we believe that the methodological quality is poor for the

study byZhu 1992, fair for the study byLazaro-Medina 1996,

and good for the study byVillarama.

Selection of studies

Two authors (BD, LR) checked the titles and abstracts identified

from the searches. If it was clear that the study did not refer to

a randomised controlled trial on PR, it was excluded. Quasi-ran-

domised trials, whereallocation was by non-random methods such

as alternation, or was based on characteristics such as date of birth,

name or case number, were excluded. Two authors (BD, LR) inde-pendently assessed each study to determinewhether it met the pre-

defined selection criteria, any differences being resolved through

discussion with the review team. There was no blinding of the

reviewer as to the origin, or conclusions of the article for eligibility

assessment, data extraction or quality assessment. Excluded stud-

ies were listed in the Characteristics of Excluded Studies Table and

reasons for exclusion given.

Data extraction and management

Two authors (GC and BD) independently performed data extrac-

tion and a third team member (VS) resolved the differences. Any

missing data was obtained from the trial authors where possible. A

data collection form was developed and piloted in order to sum-

marise the trials. One author (LR) checked and entered the data.

Assessment of risk of bias in included studies

Assessment of methodological quality




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The quality assessment included an evaluation of the following

components for each included study, since there is some evidence

that these are associated with biased estimates of treatment effect

(Juni 2001):

(a) the method of generation of the randomisation sequence;

(b) the method of allocation concealment - it was considered ad-equate if the assignment cannot be foreseen;

(c) who was blinded / not blinded (participants, clinicians, out-

come assessors);

(d) how many participants were lost to follow up in each arm and

whether participants were analysed in the groups to which they

were originally randomised (intention-to-treat).

In addition the quality assessment also included:

(e) degree of certainty that the participants have PR; e.g. whether

the diagnoses were made by primary care physicians or dermatol-

ogists;

(f) whether participants with drug-induced PR-like rashes were

excluded;

(g) baseline assessment of the participants for age, sex, durationand severity of PR;

(h) aims, interventions (including drugdoses anddurationof treat-

ment) and outcome measures clearly defined.

We recorded the information in a Table of Quality Criteria (Table

1) and a description of the quality of each study was given based

on a summary of the above components. We used the results of

the methodological quality assessment as the basis for sensitivity

analysis and not as exclusion criteria.

Data synthesis

For studies with a similar type of intervention andcomparator, e.g.

oral erythromycin versus placebo, we performed a meta-analysisto calculate a weighted treatment effect across trials using a ran-

dom effects model. Where it was not possible to perform a meta-

analysis, we summarised the data for each trial. Data are presented

as risk ratios (RR) with 95% confidence intervals, and as numbers

need to treat (NNT) for dichotomous outcomes.

The participant rated global assessments of rash and itch improve-

ment were the primary outcome measures if available. If they were

not available, the medical practitioner global rating wasused. Both

measures were taken into account where both were available. No

attempt was made to combine these measures as theyare often not

well-correlated. There exists evidence that, before treatment, rash

severity in PR as rated by the medical practitioner is not correlated

with effects on quality of life as rated by the participant (Chuh2005a).

Non-randomised controlled studies were listed but not discussed

further.

R E S U L T S

Description of studies

See: Characteristicsof included studies; Characteristicsof excluded

studies.

Results of the searchWe found 16 studies. The studies investigated various topical

treatments(Yamashita 1988), ultraviolet therapy (Merchant 1974;

Arndt 1983; Chen 1994; Leenutaphong 1995; Valkova 2004),and

systemic treatments (Roxas; Gutowski 1950; Kalbarczyk 1957;

Salin1957; Grobe 1984; Zhu1992; Lazaro-Medina1996 ; Sharma

2000;Villarama;Karpouzis 2003).

Included studies

Three randomised trials (Villarama; Zhu 1992; Lazaro-Medina

1996)mettheinclusioncriteria.Onestudy(Lazaro-Medina 1996)

was published but not identified in any of the electronic databases,

conference proceedings, or references. One author (BD) identi-fied this article by hand-searching. One study (Villarama) was un-

published. The same author (BD) identified this article by direct

correspondence with the trialists. The data from one study (Zhu

1992) was extracted from an abstract in Chinese. We translated

the abstract into English. We failed to obtain full text of the study

from the trialists, despite repeated attempts. Futher details of each

included study are given in theCharacteristics of included studies

table.

All three trials were performed in dermatology departments, in

hospital settings. The age and sex distributions were similar in the

three studies. As the three included studies investigated different

interventions and different outcome measures, pooling of data for

analysis was not feasible.In a parallel-group study byLazaro-Medina 1996, 85 participants

with pityriasis rosea were recruited. The mean age of participants

was 22.1 years: 38 were men and 47 were women. The inter-

ventions investigated were the oral antihistamine dexchlorpheni-

ramine and the oral corticosteroid betamethasone. The partici-

pants were randomised to receive one of three combinations of

the interventions: (1) oral dexchlorpheniramine tablet 4 mg twice

daily for two weeks, then once daily for another two weeks (27

participants); (2) oral betamethasone tablet (500 mcg) twice daily

for two weeks, then daily for another two weeks (31 participants),

and (3) oral betamethasone (250 mcg) - dexchlorpheniramine (2

mg) combination tablet twice daily for two weeks, then once daily

for another two weeks (27 participants). The participants were

followed up for 12 weeks. Assessment was done on day 3, then

weekly for 4 weeks, then every 4 weeks until week 12. The major

outcome measures were the proportionof participants with resolu-

tion of itch, as rated by the participants (a primary outcome mea-

sure), and the proportion of participants with good or excellent

rash improvement as rated by the medical practitioner (reported

as increase or decrease in the number of lesions) (a secondary out-




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come measure). Other outcome measures included adverse effects

of the treatment. Ultimately, 25 (93%), 29 (94%), and 17 (63%)

participants in the 3 groups completed the trial.

In the trial byVillarama, 40 participants with pityriasis rosea were

recruited to investigate the effectiveness of the oral antibiotic ery-

thromycin. There were 18 men and 22 women and the meanage of the participants was 25.9 years. The participants were ran-

domised to receive either one oral erythromycin capsule 250 mg

(as erythromycin stearate) every six hours for two weeks (20 par-

ticipants), or one oral placebo (flour) capsule of the same appear-

ance, weight, and packaging every six hours for two weeks (20

participants). The participants were assessed weekly for six weeks.

The major outcome measures were the mean decrease in itch as

assessed by the participants using visual analogue scale (a primary

outcome measure), and the proportion of participants with good

or excellent rash improvement as rated by a medical practitioner

(a secondary outcome measure). Other outcome measures were

adverse effects of the treatment. Ultimately, 17 (85%) participants

in the treatment group and 17 (85%) participants in the placebogroup completed the trial.

In the trial byZhu 1992, 23 participants with PR with mean age

of 27.2 years were recruited. There were 15 men and 8 women.

The study investigated glycyrrhizin, which is the active ingredient

of liquorice root, and has been used for many medical conditions

including peptic ulcer and cough. The anaesthetic procaine was

used in the study as a placebo. The participants were randomised

into two groups. The first group (12 participants) was given (80

ml) glycyrrhizin and (500 ml)10% glucose solution intravenously

for 5 to 11 days. The second group (11 participants) were given

300 to 600 mg procaine and (500 ml) 10% glucose solution for 10

to 20 days. The participants were followed for 10 to 20 days. The

interval of follow-up was not explicitly stated. The main outcomemeasure was the proportion of participants with good or excellent

rash improvement as rated by the medical practitioner (reported

as disappearance of symptoms and rash), a secondary outcome

measure. All participants in both groups completed the trial.

Excluded studies

We excluded 13 out of the 16 studies because there was no

randomisation. Four studies on artificial ultraviolet therapy (

Merchant 1974;Arndt 1983; Leenutaphong 1995; Valkova 2004)

were bilateral comparison studies. In two studies (Arndt 1983;

Leenutaphong 1995), therightsidesof allparticipants were treated

with ultraviolet-B, while the left sides of all participants were

shielded (Arndt 1983) or given placebo ultraviolet-A treatment

(Leenutaphong 1995). In the study byValkova 2004, two groups

of participants were recruited. The first group of participants re-

ceived ultraviolet-B to their right sides and placebo ultraviolet-

A to their left sides. The second group received ultraviolet-B to

their whole bodies. In the study byMerchant 1974, one side of all

participants was treated with ultraviolet light while the other side

was untreated. In two studies comparing oral erythromycin and

placebo (Roxas,Sharma 2000), participants were alternately as-

signed to treatment and control groups. See Table Characteristics

of excluded studies for full list of excluded studies.

Risk of bias in included studies

A table of quality components for each study is provided inTable

1

Allocation

The trial byLazaro-Medina 1996used a randomised table pro-

vided by a statistician for the generation of the randomisation

sequence. We consider this adequate. The methods of alloca-

tion concealment were, however, unclear. The trial byVillarama

used a computer-generated table of random numbers. The trialists

adopted a third party approach in allocation concealment. Four

separate trialists conducted the following four tasks: (1) assessingthe participants for inclusion or exclusion, (2) randomising the

participants into Treatment A and Treatment B, (3) assigning oral

erythromycin and placebo to either Treatment A and Treatment B,

and (4) dispensing test medications to participants. Selection bias

was thus minimised in this study, and we consider such adequate.

No information was given in theZhu 1992study on the method

of generation of the randomisation sequence. Whether allocation

was concealed or not was not reported. We consider such unclear.

Blinding

In the study byLazaro-Medina 1996, the outcome assessors, par-

ticipants and clinicians were blinded after allocation and whenassessing outcomes. The method of blinding was not stated.

Whether the analyses were performed by a person having no

knowledge of the allocation was not stated. We consider such

unclear. In the study byVillarama, after randomisation and al-

location, the outcome assessors, participants and clinicians were

blinded when assessing rash resolution and when assessing itch

improvement. A trialist who was not involved in randomisation

and allocation concealment conducted the clinical evaluation. An

independent statistician being blinded regarding the identities of

treatment groups performed data analyses. Performance bias and

detection bias were thus minimised in this study, and we consider

such adequate. Whether trialists and participants were blinded af-

ter allocation and when assessing outcomes was not stated in the

trial byZhu 1992. We consider such unclear.

Incomplete outcome data

Follow-up and exclusions




12/36

Two (7%), two (6%), and ten (37%) participants were lost to fol-

low up in the three arms in the study byLazaro-Medina 1996.

No reason was given by the trialists for the large number of par-

ticipants who dropped out in the third arm. Intention-to-treat

analyses were not performed: participants who did not complete

four weeks of treatment were not included in the analysis. Three(15%) participants werelost in each armof the study byVillarama

because they did not follow up after the first week of treatment.

The evaluable participants were analysed in the groups to which

they were originally randomised. There was no loss to follow up

in the trial byZhu 1992.

Selective reporting

There was no selective reporting of outcomes, time points, sub-

groups or analyses in all three trials.

Other potential sources of bias

Other aspects of quality

Themethods of diagnosiswere slightly differentfor thethree trials.

Although it was not explicitly stated in all three studies whether

the diagnoses of pityriasis rosea were made by dermatologists, all

three studies were conducted in dermatology departments. We

thus believe that all three studies incur a high degree of certainty

that the participants had PR. All three trials did not specifically

exclude drug-induced PR.

All three trials documented baseline assessment of the participants

for age, sex, and duration of pityriasis rosea. All three trials hadsome documentation of the distribution and extent of eruption.

The trial byLazaro-Medina 1996 documented the presence or

absence of itch at baseline. The trial byVillaramadocumented the

severity of itch with a visual analogue scale. The trial byZhu 1992

did not document the presence or severity of itch at baseline.

The objectives and outcome measures were clearly defined for the

studies byLazaro-Medina 1996andVillarama. In the study by

Zhu 1992, the disappearance of symptoms and rash were assessed

together. Symptoms were not specified as itch. The authors had

to assume that the symptoms were limited to itch only.

The drug doses and duration of treatment were clearly defined in

the studies byLazaro-Medina 1996and Villarama. In the studybyZhu 1992, the drug doses were clearly defined. How the dura-

tion of treatment was decided was unclear. All three trials did not

comprehensively document the use of previous medications after

the appearance of rash, but before consultation.

Overall, we believe that the methodological quality is poor for the

study byZhu 1992, fair for the study byLazaro-Medina 1996,

and good for the study byVillarama.

Effects of interventions

Primary outcome measures

(i) The proportion of participants with good or excellent

rash improvement within two weeks, as rated by the

participant

None of the studies measured this outcome.

(ii) The proportion of participants with resolution of itch

within two weeks, as rated by the participant (1 study)

One trial (Lazaro-Medina 1996) measured this outcome. The pro-

portion of participants with resolution of itch, as rated by the par-

ticipants, was compared between (1) oral dexchlorpheniramine (4

mg) (Analysis 3.1), (2) oral betamethasone (500 mcg) (Analysis

4.1), and (3) combination of oral betamethasone (250 mcg) andoral dexchlorpheniramine (2 mg) (Analysis 5.1). There was no

statistically significant difference between the three groups of par-

ticipants after two weeks.

(iii) Reduction in itch score within two weeks, as rated by

the participant (1 study; comparison 02.03)

The trial byVillaramameasured the mean reduction in itch score

(using a visual analogue scale) after two weeks of treatment. Ery-

thromycin significantly reduced the itch scores (P value less than

0.0027) showing a difference of 3.95 points(95% CI 3.37to 4.53)

compared with placebo. This result was from 17 participants on

erythromycin and 17 participants on placebo; no information wasavailable on 3 participants in each group.

Secondary outcome measures

(iv) The proportion of participants with good or excellent

rash improvement within two weeks, as rated by the

medical practitioner (3 studies)

All three trials measured this outcome. For the trial by Lazaro-

Medina 1996, there was no significant difference in the propor-

tion of participants with good or excellent rash improvement, as

rated by the medical practitioner, between oral dexchlorpheni-

ramine (4 mg ) and oral betamethasone (500 mcg) at two weeks

(RR 0.66, 95% CI 0.42 to 1.06; Analysis 3.2). 500 mcg of oral

betamethasone was significantly better than the combination of

oral betamethasone (250 mcg) and dexchlorpheniramine (2 mg)

in clearing the rash at two weeks (21/29; 1/17; RR 12.31, 95% CI

1.81 to 83.52; Analysis 4.2). Oral dexchlorpheniramine (4 mg)

was significantly better than the combination of oral betametha-

sone (250 mcg) and oral dexchlorpheniramine (2 mg) in clearing




13/36

the rash at two weeks (12/25 vs 1/17; RR 8.16, 95% CI 1.17 to

57.05;Analysis 5.2).

The study byVillaramareported that 13 out of 17 (76.5%) partic-

ipantson oral erythromycinwho completedthe study, and 1 outof

17 (5.9%) participants on oral placebo who completed the study,

achieved excellent rash improvement (reported as complete cure)in two weeks (RR 13.00; 95% CI 1.91 to 88.64; Analysis 2.2).

The NNT was 1.42 meaning that for approximately every two

participants treated with 250 mg of erythromycin every six hours

for two weeks, one participant would achieve complete clearing of

the rash within two weeks.

The trial byZhu 1992reported that 10 days after commencement

of treatment, 12 out of 12 (100.0%) participants on intravenous

glycyrrhizin and glucose, and 8 out of 11 participants (72.7%) on

intravenous procaine and glucose, achieved good or excellent rash

improvement (reported as disappearance of symptoms and rash,

or disappearance or obvious relief of symptoms, or disappearance

of rash by more than 70%). The trialists defined the disappearance

of symptoms and rash as cure. Taking this outcome measurealone, they reported that 11 out of 12 (91.7%) participants on

intravenous glycyrrhizin and glucose and 3 out of 11 (27.3%)

participants on intravenous procaine and glucose achieved cure

(RR 1.38, 95% CI 0.96 to 1.97;Analysis 1.1). The size of the trial

is too small for definite conclusions to be drawn.

(v) Improvement in quality of life within two weeks, as rated

by the participant by questionnaires or other methods

None of the trials measured this outcome.

(vi) Serious adverse events, i.e. serious enough to require

withdrawal of the treatment (2 studies)

Two of the trials (Villarama;Lazaro-Medina 1996) measured this

outcome. Neither reported any serious adverse event.

(vii) Minor participant reported adverse events not requiring

withdrawal of the treatment (2 studies)

Two of the trials measured this outcome. The trial byLazaro-

Medina 1996reported no minor adverse event in any of the three

intervention groups. The trial byVillarama reported three par-

ticipants with gastrointestinal upset and nausea. Two participants

were in the oral erythromycin group and one was in the oral

placebo group (RR 2.00, 95% CI 0.20 to 20.04; Analysis 2.3).

The effects were mild and tolerable for all three participants, with

no drop-out and no need for treatment with an antacid. These

side effects are common for erythromycin.

The study byZhu 1992did not quantitatively measure adverse

events. The trialists reported qualitatively that adverse effects were

less frequent and less severe for glycyrrhizin than for procaine.

D I S C U S S I O N

Pityriasis rosea was first accurately described by the French derma-

tologist Camille Melchior Gibert in 1860. Many trials have been

conducted to identify its cause, however, the number of controlled

trials on its treatment is small.

Diagnostic criteria are a concern in RCTs and other forms of re-

search on pityriasis rosea. Only three trials met the inclusion crite-

riafor this reviewand each used differentdiagnostic criteria.While

one trial (Lazaro-Medina 1996) included participants with atypi-

cal features, another study (Villarama) explicitly excluded partici-

pants with atypical features. The third study (Zhu 1992) did not

mention whether people with atypical rash were included. This

discrepancy does not allow results of the trials to be directly com-

pared with one another.

The trial byVillaramaadopted clearly stated diagnostic criteria,

but theyhave not been validated. Many participants with so-called

typical pityriasis rosea can have some atypical features. The dis-

tinction between typical and atypical PR is never a straightforward

task (Chuh 2005b). The use of validated diagnostic criteria might

standardise the inclusionof participants in future clinical trialsand

allow the results to be compared. The results can then be more

validly applied in clinical practice.

Lesional biopsy for histopathology was performed for all partici-

pants in the study byLazaro-Medina 1996. Lesional histopatho-

logical changes in pityriasis rosea are non-specific, and can be used

to substantiate the diagnosis and exclude important differential

diagnoses. For participants with a typical PR eruption, we do not

think that it is necessary to carry out invasive lesional biopsy. In-

sisting on lesional biopsy for all participants might also lead to a

lower recruitment rate in RCTs and other types of research for PR,thus causing a potential threat to external validity.

Pityriasis rosea is a self-limiting condition. Spontaneous resolu-

tion is very likely between 2 and 12 weeks. As there exists no uni-

versally accepted method of active intervention, we believe that

the standard comparator should be placebo. TheLazaro-Medina

1996study did not use a placebo and compared three active in-

terventions. Although some of the comparisons were statistically

more effective than others at certain time points, it is impossi-

ble to determine the clinical importance of these as there was no

comparison with natural progress. Any improvements beyond 2

weeks cannot be directly attributed to treatment as spontaneous

remission is likely at 2 to 12 weeks. We therefore did not evaluatefor outcome measures beyond two weeks.

In pityriasis rosea there is no correlation between the extensive-

ness of the rash, the severity of itch, and effects on the quality of

life (Chuh 2005a). Some people with extensive rash might not be

experiencing any itch at all. As PR rarely involves the face, treat-

ment given with the aim of hastening the resolution of rash might

not have any material benefit . None of the studies investigated




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the impact of treatment on the quality of life. The study byZhu

1992even lumped symptoms (itch) and signs (rash) together and

evaluated them as a single outcome measurement.

The mechanisms of action for oral erythromycin, oral betametha-

sone, and oral dexchlorpheniramine are unknown. Apart from its

effectsas an antibiotic, erythromycin (one of a group of antibioticsknown as macrolides) also exerts anti-inflammatory and modu-

lating effects on the immune system (Labro 1998). Its efficacy

therefore does not necessarily support bacterial infection(s) or ex-

clude viral infection(s) from being the cause of pityriasis rosea.

The corticosteroid, oral betamethasone also exerts anti-inflamma-

tory actions. Its effect in PR might be related to inflammation

and autoimmunity being possible components in the immuno-

logical pathology of pityriasis rosea (Chuh 2003d). Oral dexchlor-

pheniramine is a sedative histamine-1 antagonist, and as such it

exerts non-specific anti-itching effects. The mechanism for its ef-

ficacy, if any, on rash resolution in pityriasis rosea is unknown.

It is known that viral rashes may be associated with atopy and

hyper-immunoglobulinaemia E states (Ricci 2003). Whether thisis related to the action of oral dexchlorpheniramine in pityriasis

rosea is unknown.

A U T H O R S C O N C L U S I O N S

Implications for practice

Present treatments for PR are largely empirical and many different

types of treatment are used. There is inadequate evidence for the

efficacy of topical emollients, topical antihistamines, topical cor-

ticosteroids, sunlight, artificial ultraviolet therapy, systemic anti-

histamines, systemic corticosteroids, systemic antiviral agents, andintravenous glycyrrhizin in PR. Although oral betamethasone (4

mg) and oral dexchlorpheniramine (500 mcg) were both found

to be significantly better for rash clearance than the combination

of oral betamethasone (250 mcg) and oral dexchlorpheniramine

(2 mg) in the early weeks of the trial byLazaro-Medina 1996,

all three interventions were not compared with placebo. Sponta-

neous remission cannot be excluded. There were also inadequacies

of study design. Further investigations need to be performed to

ascertain the benefit of these interventions in PR.

There is some evidence that oral erythromycin at a dose of 250

mg every 6 hours for 2 weeks is effective in hastening the rash

resolution and reducing the itch in PR. However it should be

noted that these results are from a single study by Villarma with a

relatively small number of individuals included. Publication bias

and internal bias are still possible. The potential benefit from oral

erythromycin must be weighed against the potential for adverse

effects. In the study byVillarama, only 2 (12%) out of 17 people

with PR treated with erythromycin reported gastrointestinal reac-

tions. This contrasts significantly with incidences of gastrointesti-

nal side effects of 25.0% (Sato 1975) and 51.4% (Carter 1987) in

studies using oral erythromycin to treat other diseases. Our expe-

rience with oral erythromycin also suggests that more than 12%

develop gastrointestinal side effects.

PR is a self-limiting condition and spontaneous recovery is ex-

pected in 2 to 12 weeks without active treatment. It is unusual

for the face to be affected and many people with PR do not itchat all. The severity of itch and effects on quality of life are not

correlated with the extent of the rash. When choosing treatment

options the severity of itch, the extent and distribution of the rash,

and potential adverse effects of the treatment all need to be taken

into consideration.

Implications for research

The absence of evidence of efficacy for many treatments in pityr-

iasis rosea does not necessarily imply that they are not effective.

We recommend more research to investigate efficacy of these treat-

ments, particularly oral erythromycin or other macrolide antibi-

otics. Macrolides should especially be investigated as they haveanti-inflammatory and immuno-modulating effects in addition

to their antibiotic (antibacterial) actions (Labro 1998). We also

recommend randomised controlled trials to investigate the treat-

ments for PR that are commonly used by dermatologists. For ex-

ample, topical corticosteroids versus placebo, or emollients versus

placebo for people with pityriasis rosea who are symptomatic. The

results of these studies may also shed light on the cause of PR.

We advocate that further research should be conducted to validate

a setof diagnostic criteriafor PR.Future clinical trialson PR might

then adopt such validated diagnostic criteria so that the results

can be directly and validly compared with one another. We believe

that consent for lesional biopsy for histopathology should not be

mandatory as an inclusion criteria for enrolment in trials.

As there is no universally accepted active intervention for PR, we

suggest that future clinical trials for PR should include placebo as

a control, rather than merely comparing several potentially active

interventions against one another. The time frame for assessing

outcomes should preferably be within two weeks, as spontaneous

remission cannot be excluded after two weeks. If the time frame

for assessing outcomes is beyond two weeks, the study should be

powerful enough to compare treatment versus placebo in order

to demonstrate meaningful reductions in average time course to

resolution of rash or symptoms.

We advocate that apart from baseline assessment of extensiveness

of therash.The baseline assessment of symptoms (mainly itch) and

effects on quality of life should be well documented in any future

clinical trials on pityriasis rosea. We also advocate that validated

quality of life indexes should be adopted as measures of outcome.

Researchers should be alerted to the fact that many people with

PR have little or no itch in the first place. A diagnostic label in

Latin may be given but the condition may not bother the person

at all. The potential adverse effects of any intervention should be




15/36


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C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Lazaro-Medina 1996

Methods Parallel group

Duration of trial: 12 weeks

Interval of assessment: Day 3, then weekly for 4 weeks, then every 4 weeks until week 12

Unit of randomisation: Whole person

Unit of analysis: Whole person

Participants Inclusion Criteria

a) diagnosticClinical diagnosis of pityriasis rosea

b) severity of condition

Not stated

c) duration of condition

Not stated

d) other

Man or woman of any age, no history of oral steroids, antihistamine, or combination of the two within

the week prior to consultation, no history of topical steroid use during the week prior to consult, negative

potassium hydroxide smear on skin scrapings

Exclusion criteria

Participant with a history of intake of oral steroids, antihistamine or combination of the two within the

week prior to consult, history of topical steroid use a week prior to consult, positive KOH, no consent

for biopsy

Interventions Intervention 1:DexchlorpheniramineTablet 4 mg2 times per day for 2 weeks,then once a day for another

2 weeks

Intervention 2: Betamethasone Tablet 500 mcg, 2 times per day for 2 weeks, then once a day for another

2 weeks

Intervention 3: Betamethasone 250 mcg + dexchlorpheniramine 2 mg, tablets 2 times per day for 2 weeks,

then once a day for another 2 weeks

Outcomes Primary outcome measures

ii) The proportion of participants with resolution of itch, as rated by the participant

Secondary outcome measures

iv) The proportion of participants with good or excellent rash improvement as rated by a medical practi-

tioner (reported as increase or decrease in the number of lesions).vi) Serious adverse events, i.e. serious enough to require withdrawal of the treatment.

vii) Minor participant-reported adverse events not requiring withdrawal of the treatment

Others

1. The proportion of participants with hypopigmentation and hyperpigmentation (assessed by the inves-

tigators).

2. The proportion of participants with recurrence (assessed by whom not stated)




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Lazaro-Medina 1996 (Continued)

Notes

Risk of bias

Item Authors judgement Description

Allocation concealment? Unclear B - Unclear

Villarama


Duration of trial: 6 weeks

Interval of assessment: weekly

Unit of randomisation: whole person

Unit of analysis: whole person

Participants Inclusion criteria

a) diagnostic

Clinical diagnosis. Based on (1) history of acute onset of skin lesions, (2) characteristic morphology of

plaques including collarette scaling and erythema, (3) characteristic distribution


Not stated


Not stated

Exclusion criteria

Past history of signs/symptoms of other skin disorders such as psoriasis, leprosy, pityriasis lichenoides

chronica, cutaneous drug reactions, syphilis, fungal infections or contact dermatitis. Oral or intravenous

medications 1 week priorto consultation. Topical Corticosteroids applied at anytime during the condition.History of hypersensitivity to erythromycin, gastrointestinal ulcers, or hepatic disease Atypical variants

of pityriasis rosea (localised pityriasis rosea, inverse pityriasis rosea, papular pityriasis rosea). Pregnant/

lactating women. Children less than 12 years of age (due to unavailable placebo in syrup preparation)

Interventions Intervention 1. Erythromycin (as erythromycin stearate) Capsule 250 mg, 1 capsule orally every 6 hours

for 2 weeks

Intervention 2

Placebo (flour) Capsule (physical appearance, weight and external packaging identical as Intervention 1)

. 1 capsule orally every 6 hours for 2 weeks

Outcomes Primary outcome measures

iii) Reduction in itch (assessed by participants using visual analogue scale)

Secondary outcome measuresiv) The proportion of participants with good or excellent rash improvement as rated by a medical practi-

tioner.

vi) Serious adverse events, i.e. serious enough to require withdrawal of the treatment.

vii) Minor participant-reported adverse events not requiring withdrawal of the treatment

Notes




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Villarama (Continued)

Risk of bias


Allocation concealment? Yes A - Adequate

Zhu 1992


Duration of trial: 20 days

Interval of assessment: Daily (not explicitly stated; implied based on report of results)

Unit of randomisation: Whole person

Unit of analysis: Whole person

Participants Inclusion criteria a) diagnostic

Not stated


Not stated


Not stated

Exclusion criteria

Not stated

Interventions Intervention 1: Glycyrrhizin Intravenous solution 80 ml glycyrrhizin + 500 ml 10% glucose solution once

daily for 10 times = one treatment cycle

Intervention 2: Procaine Intravenous solution 300-600 mg procaine + 500 ml 10% glucose solution once

daily for 10 times = one treatment cycle

Outcomes Secondary outcome measure

iv) The proportion of participants with good or excellent rash improvement as rated by a medical practi-

tioner (reported as disappearance of symptoms and rash)

Notes

Risk of bias


Allocation concealment? Unclear B - Unclear




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Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Arndt 1983 According to the report, Treatments were given to the right side of the body only; the left side was draped

and shielded (paragraph 3, page 381). There is no randomisation

Chen 1994 There is no mention of randomisation.

Grobe 1984 There is no mention of randomisation.

Gutowski 1950 There is no mention of randomisation.

Kalbarczyk 1957 There is no mention of randomisation.

Karpouzis 2003 There is no mention of randomisation.

Leenutaphong 1995 According to the report, UVB irradiation was given to the right side of the body only; the left side was draped

and shielded. Later, 1J of UVA irradiation was given to the left side as a placebo. (paragraph 2, page 997).

There is no randomisation

Merchant 1974 According to the report, Sixty-six patients presented to the Madigan Army Medical Center Dermatology

Clinic with pityriasis rosea were treated with ultraviolet light. One-half of their anterior and one-half of their

posterior trunk was treated with ultraviolet light. The other half was used as an untreated control. There is

no mention of randomisation

Roxas According to the report, 36 patients were alternatively assigned to study and control groups. This is pseudo-

randomisation

Salin 1957 There is no mention of randomisation.

Sharma 2000 According to the report,Patients were allocated by alternate assignment to either thetreatment or the placebo

group (paragraph 2, page 242). This is pseudo-randomisation

Valkova 2004 According to the report, The irradiation sessions were held in a conventional UV cabin (Waldmann 7001K)

. Two groups of patients were formed. The first one comprised 24 (23.8%) people. The initial dose of the

irradiation was 80% minimal erythema dose (MED). It was increased according to the degree of the preceding

erythema. Only the right half of the body was irradiated with UVB. UVA (1 J/cm2) was given as a placebo

to the left half of the body. The second group consisted of 77 (76.2%) patients. The UVB irradiation was

applied to the whole body. The initial UVB dose was determined according to the phototype. There is no

mention of randomisation

Yamashita 1988 There is no mention of randomisation.




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D A T A A N D A N A L Y S E S

Comparison 1. Glycyrrhizin vs Procaine

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Good or excellent rash

improvement as rated by

a medical practitioner

(disappearance of symptoms

and rash)

1 Risk Ratio (M-H, Random, 95% CI) Totals not selected

Comparison 2. Erythromycin vs Placebo


studies

No. of


1 Mean reduction in itch score 1 Mean Difference (IV, Random, 95% CI) Totals not selected

2 Excellent rash improvement

(cure) as rated by the medical

practitioner at 2 weeks


3 Minor adverse events

(gastrointestinal upset and

nausea)


Comparison 3. Dexchlorpheniramine vs Betamethasone


studies

No. of


1 Number of participants with

resolution of itch, as reportedby participant


2 Number of participants

with good or excellent rash

improvement as rated by a

medical practitioner





23/36

Comparison 4. Betamethasone vs Betamethasone + Dexchlorpheniramine


studies

No. of



resolution of itch, as reported

by participant




improvement as rated by a



Comparison 5. Dexchlorpheniramine vs Betamethasone + Dexchlorpheniramine


studies

No. of



resolution of itch, as reported

by participant




improvement as rated by the



Analysis 1.1. Comparison 1 Glycyrrhizin vs Procaine, Outcome 1 Good or excellent rash improvement as

rated by a medical practitioner (disappearance of symptoms and rash).

Review: Interventions for pityriasis rosea

Comparison: 1 Glycyrrhizin vs Procaine

Outcome: 1 Good or excellent rash improvement as rated by a medical practitioner (disappearance of symptoms and rash)

Study or subgroup Glycyrrhizin Procaine Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Zhu 1992 12/12 8/11 1.36 [ 0.93, 1.98 ]

0.1 0.2 0.5 1 2 5 10

Favours procaine Favours glycyrhizin




24/36

Analysis 2.1. Comparison 2 Erythromycin vs Placebo, Outcome 1 Mean reduction in itch score.


Comparison: 2 Erythromycin vs Placebo

Outcome: 1 Mean reduction in itch score

Study or subgroup Erythromycin PlaceboMean

DifferenceMean

Difference

N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI

Villarama 17 5.71 (0.7) 17 1.76 (0.99) 3.95 [ 3.37, 4.53 ]

-10 -5 0 5 10

Favours placebo Favours erythromycin

Analysis 2.2. Comparison 2 Erythromycin vs Placebo, Outcome 2 Excellent rash improvement (cure) as

rated by the medical practitioner at 2 weeks.



Outcome: 2 Excellent rash improvement (cure) as rated by the medical practitioner at 2 weeks

Study or subgroup Erythromycin Placebo Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Villarama 13/17 1/17 13.00 [ 1.91, 88.64 ]

0.1 0.2 0.5 1 2 5 10

Favours placebo Favours erythromycin




25/36

Analysis 2.3. Comparison 2 Erythromycin vs Placebo, Outcome 3 Minor adverse events (gastrointestinal

upset and nausea).



Outcome: 3 Minor adverse events (gastrointestinal upset and nausea)

Study or subgroup Erythromycin Placebo Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Villarama 2/17 1/17 2.00 [ 0.20, 20.04 ]

0.1 0.2 0.5 1 2 5 10

Favours erythromycin Favours placebo

Analysis 3.1. Comparison 3 Dexchlorpheniramine vs Betamethasone, Outcome 1 Number of participants

with resolution of itch, as reported by participant.


Comparison: 3 Dexchlorpheniramine vs Betamethasone

Outcome: 1 Number of participants with resolution of itch, as reported by participant

Study or subgroup Dexchlorpheniramine Betamethasone Risk Ratio Risk Ratio

n/N n/NM-H,Random,95%CI

M-H,Random,95%CI

Lazaro-Medina 1996 11/25 14/29 0.91 [ 0.51, 1.63 ]

0.1 0.2 0.5 1 2 5 10

Favours betameth Favours dexchlor




26/36

Analysis 3.2. Comparison 3 Dexchlorpheniramine vs Betamethasone, Outcome 2 Number of participants

with good or excellent rash improvement as rated by a medical practitioner.


Comparison: 3 Dexchlorpheniramine vs Betamethasone

Outcome: 2 Number of participants with good or excellent rash improvement as rated by a medical practitioner

Study or subgroup Dexchlorpheniramine Betamethasone Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Lazaro-Medina 1996 12/25 21/29 0.66 [ 0.42, 1.06 ]

0.1 0.2 0.5 1 2 5 10

Favours betameth Favours dexchlor

Analysis 4.1. Comparison 4 Betamethasone vs Betamethasone + Dexchlorpheniramine, Outcome 1

Number of participants with resolution of itch, as reported by participant.


Comparison: 4 Betamethasone vs Betamethasone + Dexchlorpheniramine


Study or subgroup Betamethasone Betameth+dexchlor Risk Ratio Risk Ratio


M-H,Random,95%CI

Lazaro-Medina 1996 14/29 9/17 0.91 [ 0.51, 1.64 ]

0.1 0.2 0.5 1 2 5 10

Favours betameth+dex Favours betameth




27/36

Analysis 4.2. Comparison 4 Betamethasone vs Betamethasone + Dexchlorpheniramine, Outcome 2

Number of participants with good or excellent rash improvement as rated by a medical practitioner.


Comparison: 4 Betamethasone vs Betamethasone + Dexchlorpheniramine

Outcome: 2 Number of participants with good or excellent rash improvement as rated by a medical practitioner

Study or subgroup Betamethasone Betameth+dexchlor Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Lazaro-Medina 1996 21/29 1/17 12.31 [ 1.81, 83.52 ]

0.1 0.2 0.5 1 2 5 10

Favours betameth+dex Favours betameth

Analysis 5.1. Comparison 5 Dexchlorpheniramine vs Betamethasone + Dexchlorpheniramine, Outcome 1

Number of participants with resolution of itch, as reported by participant.


Comparison: 5 Dexchlorpheniramine vs Betamethasone + Dexchlorpheniramine


Study or subgroup Dexchlorpheniramine Betamethasone+Dex Risk Ratio Risk Ratio


M-H,Random,95%CI

Lazaro-Medina 1996 11/25 9/17 0.83 [ 0.44, 1.56 ]

0.1 0.2 0.5 1 2 5 10

Favours betameth+dex Favours dex




28/36

Analysis 5.2. Comparison 5 Dexchlorpheniramine vs Betamethasone + Dexchlorpheniramine, Outcome 2

Number of participants with good or excellent rash improvement as rated by the medical practitioner.


Comparison: 5 Dexchlorpheniramine vs Betamethasone + Dexchlorpheniramine

Outcome: 2 Number of participants with good or excellent rash improvement as rated by the medical practitioner

Study or subgroup Dexchlorpheniramine Betamethasone+Dex Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Lazaro-Medina 1996 12/25 1/17 8.16 [ 1.17, 57.05 ]

0.1 0.2 0.5 1 2 5 10

Favours betameth+dex Favours dex

A D D I T I O N A L T A B L E S

Table 1. Quality components

Study Randomi-

sation se-

quence

Alloca-

tion con-

cealment

Blinding Loss to

follow-up

Diagnosis

certainty

Drug-in-

duced PR

Baseline

assess-

ment

Aims, in-

terven-

tions clear

Useofpre-

vi-

ous medi-

cation

Lazaro-

Medina

Ade-

quate: ran-

domisedtable pro-

vided by

statistician

Unclear:

method

not speci-fied

Unclear Data is ad-

equate.

Two (7%), two (6%)

, and 10

(37%) pa-

tients were

lost to fol-

low up

at week 4

in thethree

arms in

Intervention Pityriasis Rosea

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